Miracle-dz/UniFAR-FTUs huggingface dataset:
Determination of Post-Harvest Biochemical Composition, Enzymatic Activities, and Oxidative Browning in 14 Apple Cultivars

Phenolic compounds in fruit provide human health benefits, and they contribute to color, taste, and the preservation of post-harvest fruit quality. Phenolic compounds also serve as modifiers of enzymatic activity, whether inhibition or stimulation. Polyphenol oxidases (PPO) and peroxidases (POD) use phenolic compounds as substrates in oxidative browning. Apple browning leads to flesh color, taste, texture, and flavor degradation, representing a drawback for the variety and its’ market appraisal. This study was conducted to investigate the process of browning in 14 apple cultivars throughout post-harvest at three-time points: immediately (T0), one hour (T1), and 24 h (T2) after apples were cut in half. Color parameters L* (lightness), a* (red/green), b* (yellow/blue) were measured, and chroma (ΔC*) and color (ΔE) were calculated to quantify differences between T0₋T1 and T1₋T2 on the fruit surface. Enzymatic activity (PPO, POD) and phenolic composition were also quantified for each cultivar. ‘Granny Smith’ and ‘Cripps Pink’ browned minimally. In contrast, ‘Fiesta’ and ‘Mondial Gala’ browned severely, reporting high enzymatic activity and quantified phenolic concentration (QPC). Phenolic compound polymerization appears to play a significant role in enzymatic inhibition. ‘Topaz’ does not fit the high QPC, PPO, and browning formula, suggesting alternative pathways that contribute to apple browning.
Neuroradiologic Phenotyping of Galactosemia: From the Neonatal Form to the Chronic Stage

SUMMARY: Galactosemia is a rare genetic condition caused by mutation of enzymes involved in galactose and glucose metabolism. The varying clinical spectrum reflects the genetic complexity of this entity manifesting as acute neonatal toxicity syndrome, requiring prompt diagnosis and treatment, to more insidious clinical scenarios as observed in the subacute and chronic presentations. The current literature predominantly focuses on the long-standing sequelae of this disease. The purpose of this multicenter clinical report comprising 17 patients with galactosemia is to highlight the MR imaging patterns encompassing the whole spectrum of galactosemia, emphasizing the 3 main clinical subtypes: 1) acute neonatal presentation, with predominant white matter edema; 2) subacute clinical onset with a new finding called the “double cap sign”; and 3) a chronic phase of the disease with heterogeneous imaging findings. The knowledge of these different patterns together with MR spectroscopy and the clinical presentation may help in prioritizing galactosemia over other neonatal metabolic diseases and prevent possible complications.
Efficacy and Safety of a New Botulinum Toxin (HU-014) Versus Existing Onabotulinumtoxin A in Subjects With Moderate to Severe Glabellar Lines.

BACKGROUND Recently, the safety of a new botulinum toxin (HU-014) was confirmed through animal experiments. The evaluation of the efficacy and safety of this newly introduced botulinum toxin is required considering the risk of adverse events (AEs) and need for standardization before its universal use. OBJECTIVE The aim of this multicenter, double-blind, randomized, parallel, active-controlled phase III clinical trial was to investigate the noninferiority of HU-014 versus existing onabotulinumtoxin A for the treatment of moderate to severe glabellar lines. METHODS In total, 267 subjects were randomized to either the test (HU-014) or control (onabotulinumtoxin A) group. At the baseline and at weeks 4, 8, 12, and 16, investigator's live assessment, independent photographic assessment, subjects' improvement assessment, subjects' satisfaction assessment, and safety assessment were performed. RESULTS At week 4, the response rate was 90.15% and 92.31% in the test and control groups, respectively, as per investigator's live assessment while frowning, without a significant difference. Both groups also showed no significant differences in response rates in the other assessments. In addition, no serious AEs were reported. CONCLUSION HU-014 was noninferior to existing onabotulinumtoxin A in the treatment of glabellar lines at a 1:1 dose ratio, and both products were well tolerated.
Beneficial Effects of Akkermansia muciniphila Are Not Associated with Major Changes in the Circulating Endocannabinoidome but Linked to Higher Mono-Palmitoyl-Glycerol Levels as New PPARα Agonists

Akkermansia muciniphila is considered as one of the next-generation beneficial bacteria in the context of obesity and associated metabolic disorders. Although a first proof-of-concept of its beneficial effects has been established in the context of metabolic syndrome in humans, mechanisms are not yet fully understood. This study aimed at deciphering whether the bacterium exerts its beneficial properties through the modulation of the endocannabinoidome (eCBome). Circulating levels of 25 endogenous endocannabinoid-related lipids were quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in the plasma of overweight or obese individuals before and after a 3 months intervention consisting of the daily ingestion of either alive or pasteurized A. muciniphila. Results from multivariate analyses suggested that the beneficial effects of A. muciniphila were not linked to an overall modification of the eCBome. However, subsequent univariate analysis showed that the decrease in 1-Palmitoyl-glycerol (1-PG) and 2-Palmitoyl-glycerol (2-PG), two eCBome lipids, observed in the placebo group was significantly counteracted by the alive bacterium, and to a lower extent by the pasteurized form. We also discovered that 1- and 2-PG are endogenous activators of peroxisome proliferator-activated receptor alpha (PPARα). We hypothesize that PPARα activation by mono-palmitoyl-glycerols may underlie part of the beneficial metabolic effects induced by A. muciniphila in human metabolic syndrome.
The predictive value of diabetic retinopathy on subsequent diabetic nephropathy in patients with type 2 diabetes: a systematic review and meta-analysis of prospective studies

Abstract This systematic review and meta-analysis aimed to assess the predictive value of diabetic retinopathy (DR) on further diabetic nephropathy (DN) risk in patients with type 2 diabetes (T2D) based on the prospective cohort studies. PubMed, Embase, and the Cochrane Library were systematically searched for eligible prospective cohort studies through March 2020. The predictive value of DR was assessed using sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC) through the bivariate generalized linear mixed model and the random-effects model. Ten prospective cohort studies recruited 635 patients with T2D. The pooled sensitivity and specificity of DR for predicted DN were noted to be 0.64 (95% CI, 0.54–0.73) and 0.77 (95% CI, 0.60–0.88), respectively. The pooled PLR and NLR of DR for predicted DN were 2.72 (95% CI, 1.42–5.19) and 0.47 (95% CI, 0.33–0.67), respectively. The summary DOR for the relationship between DR and subsequent DN for T2D patients was 5.53 (95% CI, 2.00–15.30), and the AUC of DR for predicted DN was 0.73 (95% CI, 0.69–0.77). This study found significant associations between DR and subsequent DN risk for patients with T2D. Moreover, the predictive value of DR on subsequent DN risk was relatively lower.
Interactions of Viral Proteins from Pathogenic and Low or Non-Pathogenic Orthohantaviruses with Human Type I Interferon Signaling

Rodent-borne orthohantaviruses are asymptomatic in their natural reservoir, but they can cause severe diseases in humans. Although an exacerbated immune response relates to hantaviral pathologies, orthohantaviruses have to antagonize the antiviral interferon (IFN) response to successfully propagate in infected cells. We studied interactions of structural and nonstructural (NSs) proteins of pathogenic Puumala (PUUV), low-pathogenic Tula (TULV), and non-pathogenic Prospect Hill (PHV) viruses, with human type I and III IFN (IFN-I and IFN-III) pathways. The NSs proteins of all three viruses inhibited the RIG-I-activated IFNβ promoter, while only the glycoprotein precursor (GPC) of PUUV, or its cleavage product Gn/Gc, and the nucleocapsid (N) of TULV inhibited it. Moreover, the GPC of both PUUV and TULV antagonized the promoter of IFN-stimulated responsive elements (ISRE). Different viral proteins could thus contribute to inhibition of IFNβ response in a viral context. While PUUV and TULV strains replicated similarly, whether expressing entire or truncated NSs proteins, only PUUV encoding a wild type NSs protein led to late IFN expression and activation of IFN-stimulated genes (ISG). This, together with the identification of particular domains of NSs proteins and different biological processes that are associated with cellular proteins in complex with NSs proteins, suggested that the activation of IFN-I is probably not the only antiviral pathway to be counteracted by orthohantaviruses and that NSs proteins could have multiple inhibitory functions.
MGMT expression in pituitary corticotroph adenomas and its relationship to clinical, pathological, and ultrastructural parameters in patients with Cushing's disease.

INTRODUCTION Transsphenoidal surgery is the treatment of choice in Cushing's disease (CD), although even late recurrences occur in some patients. Low expression of O-6-methylguanine-DNA methyltransferase (MGMT) has been linked to a high risk of relapse in pituitary tumours, but the evidence for corticotroph adenomas is limited. Therefore, we investigated whether MGMT expression was associated with CD remission or clinicopathological markers of tumour aggressiveness among patients with corticotroph adenomas. MATERIAL AND METHODS We included 72 consecutive patients (83% female, mean age ±SD: 44.15 ±15.15 years) with CD, who underwent transsphenoidal adenomectomy between 2012 and 2018. The invasiveness of corticotroph tumours was assessed based on the Knosp scale. Immunohistochemistry was used to analyse MGMT expression as well as the proliferation markers (Ki-67, p53, mitotic index). Electron microscopy was used to categorise tumours into densely or sparsely granulated. Early biochemical remission was evaluated in all patients 6 months after pituitary surgery. RESULTS Early remission was observed in 47 (65%) patients 6 months after surgery. MGMT expression was > 75% in half of all tumours, < 25% in 14 tumours, and 25-50% or 50-75% in 11 tumours. Lower MGMT expression was associated with a larger tumour diameter (p = 0.001), higher adrenocorticotropic hormone (ACTH) concentration (p = 0.002), higher p53 expression (p = 0.026), and higher frequency of sparsely granulated corticotroph adenomas (p = 0.009). Low MGMT expression was significantly related to lower frequency of early clinical remission (p = 0.005). CONCLUSIONS MGMT predicted the outcomes of transsphenoidal surgery for CD. Pituitary corticotroph adenomas with low MGMT expression may be associated with increased invasiveness and poorer prognosis.
The NFκB Antagonist CDGSH Iron-Sulfur Domain 2 Is a Promising Target for the Treatment of Neurodegenerative Diseases

Proinflammatory response and mitochondrial dysfunction are related to the pathogenesis of neurodegenerative diseases (NDs). Nuclear factor κB (NFκB) activation has been shown to exaggerate proinflammation and mitochondrial dysfunction, which underlies NDs. CDGSH iron-sulfur domain 2 (CISD2) has been shown to be associated with peroxisome proliferator-activated receptor-β (PPAR-β) to compete for NFκB and antagonize the two aforementioned NFκB-provoked pathogeneses. Therefore, CISD2-based strategies hold promise in the treatment of NDs. CISD2 protein belongs to the human NEET protein family and is encoded by the CISD2 gene (located at 4q24 in humans). In CISD2, the [2Fe-2S] cluster, through coordinates of 3-cysteine-1-histidine on the CDGSH domain, acts as a homeostasis regulator under environmental stress through the transfer of electrons or iron-sulfur clusters. Here, we have summarized the features of CISD2 in genetics and clinics, briefly outlined the role of CISD2 as a key physiological regulator, and presented modalities to increase CISD2 activity, including biomedical engineering or pharmacological management. Strategies to increase CISD2 activity can be beneficial for the prevention of inflammation and mitochondrial dysfunction, and thus, they can be applied in the management of NDs.
Physical Interaction between HPV16E7 and the Actin-Binding Protein Gelsolin Regulates Epithelial-Mesenchymal Transition via HIPPO-YAP Axis

Simple Summary Human papilloma viruses cause benign or malignant hyper-proliferative lesions in cervical, anogenital and oropharyngeal tissues. Our previous studies revealed that HPV16 E7 alters actin cytoskeleton mainly by binding to and inhibiting Gelsolin. We suggest that the physical interaction E7/Gelsolin in HPV positive tumor cell, and the resulting epithelial to mesenchymal transition process, induce HIPPO signaling cascade by promoting YAP inactivation and favoring HPV-induced cell transformation, cancer motility and aggressiveness. The results of this study provide new insights into the oncogenic transformation mechanisms elicited by HPV in the infected cells and may suggest a repertoire of targets for therapeutic purposes. Abstract Human papillomavirus 16 (HPV16) exhibits a strong oncogenic potential mainly in cervical, anogenital and oropharyngeal cancers. The E6 and E7 viral oncoproteins, acting via specific interactions with host cellular targets, are required for cell transformation and maintenance of the transformed phenotype as well. We previously demonstrated that HPV16E7 interacts with the actin-binding protein gelsolin, involved in cytoskeletal F-actin dynamics. Herein, we provide evidence that the E7/gelsolin interaction promotes the cytoskeleton rearrangement leading to epithelial-mesenchymal transition-linked morphological and transcriptional changes. E7-mediated cytoskeletal actin remodeling induces the HIPPO pathway by promoting the cytoplasmic retention of inactive P-YAP. These results suggest that YAP could play a role in the “de-differentiation” process underlying the acquisition of a more aggressive phenotype in HPV16-transformed cells. A deeper comprehension of the multifaceted mechanisms elicited by the HPV infection is vital for providing novel strategies to block the biological and clinical features of virus-related cancers.
ABT-751 Induces Multiple Anticancer Effects in Urinary Bladder Urothelial Carcinoma-Derived Cells: Highlighting the Induction of Cytostasis through the Inhibition of SKP2 at Both Transcriptional and Post-Translational Levels

The objective was to investigate the anti-cancer effects and underlying molecular mechanisms of cytostasis which were activated by an anti-microtubule drug, ABT-751, in two urinary bladder urothelial carcinoma (UBUC)-derived cell lines, BFTC905 and J82, with distinct genetic backgrounds. A series of in vitro assays demonstrated that ABT-751 induced G2/M cell cycle arrest, decreased cell number in the S phase of the cell cycle and suppressed colony formation/independent cell growth, accompanied with alterations of the protein levels of several cell cycle regulators. In addition, ABT-751 treatment significantly hurdled cell migration and invasion along with the regulation of epithelial–mesenchymal transition-related proteins. ABT-751 triggered autophagy and apoptosis, downregulated the mechanistic target of rapamycin kinase (MTOR) and upregulated several pro-apoptotic proteins that are involved in extrinsic and intrinsic apoptotic pathways. Inhibition of autophagosome and autolysosome enhanced apoptosis was also observed. Through the inhibition of the NFκB signaling pathway, ABT-751 suppressed S-phase kinase associated protein 2 (SKP2) transcription and subsequent translation by downregulation of active/phospho-AKT serine/threonine kinase 1 (AKT1), component of inhibitor of nuclear factor kappa B kinase complex (CHUK), NFKB inhibitor alpha (NFKBIA), nuclear RELA proto-oncogene, NFκB subunit (RELA) and maintained a strong interaction between NFKBIA and RELA to prevent RELA nuclear translocation for SKP2 transcription. ABT-751 downregulated stable/phospho-SKP2 including pSKP2(S64) and pSKP2(S72), which targeted cyclin-dependent kinase inhibitors for degradation through the inactivation of AKT. Our results suggested that ABT-751 may act as an anti-cancer drug by inhibiting cell migration, invasion yet inducing cell cycle arrest, autophagy and apoptosis in distinct UBUC-derived cells. Particularly, the upstream molecular mechanism of its anticancer effects was identified as ABT-751-induced cytostasis through the inhibition of SKP2 at both transcriptional and post-translational levels to stabilize cyclin dependent kinase inhibitor 1A (CDKN1A) and CDKN1B proteins.
Flavonoid Glycosides in Brassica Species Respond to UV-B Depending on Exposure Time and Adaptation Time

Recently, there have been efforts to use ultraviolet-B radiation (UV-B) as a biotechnological tool in greenhouses. Leafy Brassica species are mainly considered for their ability to synthesize glucosinolates and are valued as baby salads. They also have a remarkable concentration of chemically diverse flavonoid glycosides. In this study, the effect of short-term UV-B radiation at the end of the production cycle was investigated without affecting plant growth. The aim was to verify which exposure and adaptation time was suitable and needs to be further investigated to use UV as a biotechnological tool in greenhouse production of Brassica species. It is possible to modify the flavonoid glycoside profile of leafy Brassica species by increasing compounds that appear to have potentially high antioxidant activity. Exemplarily, the present experiment shows that kaempferol glycosides may be preferred over quercetin glycosides in response to UV-B in Brassica rapa ssp. chinensis, for example, whereas other species appear to prefer quercetin glycosides over kaempferol glycosides, such as Brassica oleracea var. sabellica or Brassica carinata. However, the response to short-term UV-B treatment is species-specific and conclusions on exposure and adaptation time cannot be unified but must be drawn separately for each species.
MicroRNA-Mediated Gene Regulatory Mechanisms in Mammalian Female Reproductive Health

Mammalian reproductive health affects the entire reproductive cycle starting with the ovarian function through implantation and fetal growth. Various environmental and physiological factors contribute to disturbed reproductive health status leading to infertility problems in mammalian species. In the last couple of decades a significant number of studies have been conducted to investigate the transcriptome of reproductive tissues and organs in relation to the various reproductive health issues including endometritis, polycystic ovarian syndrome (PCOS), intrauterine growth restriction (IUGR), preeclampsia, and various age-associated reproductive disorders. Among others, the post-transcriptional regulation of genes by small noncoding miRNAs contributes to the observed transcriptome dysregulation associated with reproductive pathophysiological conditions. MicroRNAs as a class of non-coding RNAs are also known to be involved in various pathophysiological conditions either in cellular cytoplasm or they can be released to the extracellular fluid via membrane-bounded extracellular vesicles and proteins. The present review summarizes the cellular and extracellular miRNAs and their association with the etiology of major reproductive pathologies including PCOS, endometritis, IUGR and age-associated disorders in various mammalian species.
Genomic signatures of selection in bats surviving white‐nose syndrome

Rapid evolution of advantageous traits following abrupt environmental change can help populations recover from demographic decline. However, for many introduced diseases affecting longer‐lived, slower reproducing hosts, mortality is likely to outpace the acquisition of adaptive de novo mutations. Adaptive alleles must therefore be selected from standing genetic variation, a process that leaves few detectable genomic signatures. Here, we present whole genome evidence for selection in bat populations that are recovering from white‐nose syndrome (WNS). We collected samples both during and after a WNS‐induced mass mortality event in two little brown bat populations that are beginning to show signs of recovery and found signatures of soft sweeps from standing genetic variation at multiple loci throughout the genome. We identified one locus putatively under selection in a gene associated with the immune system. Multiple loci putatively under selection were located within genes previously linked to host response to WNS as well as to changes in metabolism during hibernation. Results from two additional populations suggested that loci under selection may differ somewhat among populations. Through these findings, we suggest that WNS‐induced selection may contribute to genetic resistance in this slowly reproducing species threatened with extinction.
Depressive symptoms among patients with lung cancer: Elucidating the roles of shame, guilt, and self-compassion

The link between smoking and lung cancer predisposes patients to feeling shame and guilt, which increases risk for depression. To test the hypothesis shame would have a stronger association with depressive symptoms than guilt, a hierarchical regression was conducted. Three regressions were run to examine the associations of self-compassion with shame, guilt, and depressive symptoms. The best model to explain depressive symptoms included shame, but not guilt. Greater self-compassion was associated with less shame and fewer depressive symptoms, but not guilt. Results point to interventions targeting shame via enhancing self-compassion among patients with lung cancer and histories of smoking.