Miracle-dz/UniFAR-FTUs huggingface dataset:
Co-Microencapsulation of Anthocyanins from Black Currant Extract and Lactic Acid Bacteria in Biopolymeric Matrices

Anthocyanins from black currant extract and lactic acid bacteria were co-microencapsulated using a gastro-intestinal-resistant biocomposite of whey protein isolate, inulin, and chitosan, with an encapsulation efficiency of 95.46% ± 1.30% and 87.38% ± 0.48%, respectively. The applied freeze-drying allowed a dark purple stable powder to be obtained, with a satisfactory content of phytochemicals and 11 log colony forming units (CFU)/g dry weight of powder (DW). Confocal laser microscopy displayed a complex system, with several large formations and smaller aggregates inside, consisting of biologically active compounds, lactic acid bacteria cells, and biopolymers. The powder showed good storage stability, with no significant changes in phytochemicals and viable cells over 3 months. An antioxidant activity of 63.64 ± 0.75 mMol Trolox/g DW and an inhibitory effect on α-amylase and α-glucosidase of 87.10% ± 2.08% and 36.96% ± 3.98%, respectively, highlighted the potential biological activities of the co-microencapsulated powder. Significantly, the in vitro digestibility profile showed remarkable protection in the gastric environment, with controlled release in the intestinal simulated environment. The powder was tested by addition into a complex food matrix (yogurt), and the results showed satisfactory stability of biologically active compounds when stored for 21 d at 4 °C. The obtained results confirm the important role of microencapsulation in ensuring a high degree of protection, thus allowing new approaches in developing food ingredients and nutraceuticals, with enhanced functionalities.
NIV Is not Adequate for High Intensity Endurance Exercise in COPD

Noninvasive ventilation (NIV) during exercise has been suggested to sustain higher training intensity but the type of NIV interface, patient-ventilator asynchronies (PVA) or technological limitation of the ventilator may interfere with exercise. We assessed whether these parameters affect endurance exercise capacity in severe COPD patients. In total, 21 patients with severe COPD not eligible to home NIV performed three constant workload tests. The first test was carried out on spontaneous breathing (SB) and the following ones with NIV and a nasal or oronasal mask in a randomized order. PVA and indicators of ventilator performance were assessed through a comprehensive analysis of the flow pressure tracing raw data from the ventilator. The time limit was significantly reduced with both masks (406 s (197–666), 240 s (131–385) and 189 s (115–545), p < 0.01 for tests in SB, with oronasal and nasal mask, respectively). There were few PVA with an oronasal mask (median: 3.4% (1.7–5.2)) but the ventilator reached its maximal generating capacity (median flowmax: 208.0 L/s (189.5–224.8) while inspiratory pressure dropped throughout exercise (from 10.1 (9.4–11.4) to 8.8 cmH2O (8.6–10.8), p < 0.01). PVA were more frequent with nasal mask (median: 12.8% (3.2–31.6), p < 0.01). Particularly, the proportion of patients with ineffective efforts > 10% was significantly higher with nasal interface (0% versus 33.3%, p < 0.01). NIV did not effectively improve endurance capacity in COPD patients not acclimated to home NIV. This was due to a technological limitation of the ventilator for the oronasal mask and the consequence either of an insufficient pressure support or a technological limitation for the nasal mask.
Epstein–Barr Virus-Induced Post-Transplant Lymphoproliferative Disorder of the Central Nervous System Successfully Treated with Chemo-Immunotherapy

Aplastic anemia is a rare blood disease characterized by the destruction of the hematopoietic stem cells (HSC) in the bone marrow that, in the majority of cases, is caused by an autoimmune reaction. Patients with aplastic anemia are treated with immunosuppressive drugs and some of them, especially younger individuals with a donor available, can be successfully treated with hematopoietic stem cell transplantation (HSCT). We report here a rare case of post-transplant lymphoproliferative disorder (PTLD) associated with Epstein–Barr virus (EBV) reactivation in a 30-year-old female patient who underwent allogeneic HSCT for severe aplastic anemia. The PTLD, which was diagnosed 230 days after transplantation, was localized exclusively in the central nervous system (specifically in the choroid plexus) and manifested with obvious signs of intracranial hypertension. After receiving three cycles of high dose methotrexate (HD-MTX) combined with rituximab, the patient achieved a complete clinical recovery with normalization of blood cell counts, no evidence of EBV reactivation, and no associated neurotoxicity.
The anticancer effects of 7-Methoxyheptaphylline against the human retinoblastoma cells are facilitated via S-phase cell cycle arrest, mitochondrial apoptosis and inhibition of Wnt/β-catenin signalling pathway.

PURPOSE The main purpose of the current study was to evaluate the anticancer action of 7-Methoxyheptaphylline in Y-79 human retinoblastoma cells along with evaluating its effects on cellular apoptosis, cell cycle phase distribution and Wnt/β-catenin signalling pathway. METHODS The retinoblastoma cell line RbY-79 was used in this study. Cell viability was assessed by WTS-1 assay while apoptotic studies were carried out by DAPI, acridine orange (AO)/ethidium bromide (EB), annexin V + propidium iodide (PI) staining using fluorescence microscopy and flow cytometry. Effects on cell cycle progression were studied using Annexin V/PI staining in combination with flow cytometry. Western blot assay was used to examine the effects on Bax, Bcl-2 and proteins associated with Wnt/β-catenin signalling pathway. RESULTS The results indicated that 7-Methoxyheptaphylline suppressed the viability of the Y-79 cells concentration-dependently with IC50 value of 15.5 μM. The percentage of the DAPI-positive cells showed a significant upsurge reminiscent of the apoptosis in the Y-79 retinoblastoma cells. 7-Methoxyheptaphylline also caused considerable nuclear fragmentation of the Y-79 retinoblastoma cells, representative of apoptosis. The apoptosis percentage increased significantly as the dose of the 7-Methoxyheptaphylline increased from 0 to 12, 24 and 48 µM. The molecule caused upregulation of Bax and downregulation of Bcl-2 in Y-79 retinoblastoma cells. 7-Methoxyheptaphylline also caused S-phase cell cycle arrest with concomitant concentration-dependent decline in the expression levels of cyclin A, E and D1. It was also seen that increasing doses of 7-Methoxyheptaphylline led to a dose-dependent decline in the expression levels of wnt-13a and β-catenin. CONCLUSIONS In conclusion, it is believed that the molecule may prove to be a promising anticancer agent for the treatment of retinoblastoma.
Two cases of successful recanalization for acute cerebral artery embolism during perioperative period of radiofrequency ablation for atrial fibrillation

To explore the strategy of acute cerebral artery embolism after radiofrequency catheter ablation (RFA) for atrial fibrillation (AF). Reporting two cases with acute cerebral infarction after RFA for AF. Two patients were both with AF, and intracardiac thrombus was excluded through transesophageal echocardiogram (TEE) before procedure. Approach of ablation: circumferential pulmonary vein ablation in left atrium to isolate pulmonary vein plus linear ablation in the top and bottom of left atrium (BOX procedure). They both received Dabigatran Etexilate 110 mg twice daily, starting 6 hr after ablation. Symptoms of major stroke appeared 30 hr after ablation in Case 1. Occlusion was detected in M1 segment of the left middle cerebral artery by MRI 2 hr after symptoms onset. Intravenous thrombolysis was given immediately. In Case 2, the patient presented symptoms of major stroke 34 hr after ablation and occlusion in the basilar artery was confirmed by MRI 4.5 hr after symptoms onset. Although it was beyond the thrombolysis time window, mechanical thrombectomy was taken 7 hr after the symptoms onset. The culprit artery was successfully revascularized in both cases. In Case 1, NIHSS score was reduced from 8 (before thrombolysis) to 0 (24 hr after thrombolysis). In Case 2, NIHSS score decreased from 18 (before embolectomy) to 3 (24 hr after embolectomy). Both of the patients live a normal life without brain function impairment and hemorrhage until the last follow‐up. Timely recanalization could attained a good cure effect when acute stoke was happened after RFA for AF.
Targeting Autophagy Augments Berberine-Mediated Cell Death in Human Hepatoma Cells Harboring Hepatitis C Virus RNA

Hepatocellular carcinoma (HCC), including hepatitis C virus (HCV)-induced HCC, is a deadly disease highly refractory to chemotherapy, thus requiring the continuous identification of novel treatment strategies. Berberine (BBR) has been previously reported to inhibit hepatoma cell growth, but the main type of cell death elicited by BBR, and whether the alkaloid can inhibit hepatoma cells carrying HCV genomes, is unclear. Herein, we show that BBR treatment induced a biphasic cell death irrespective of the presence of HCV subgenomic replicon RNA, first triggering apoptosis that then progressed to necrosis between 24 and 48 h post-treatment. Furthermore, BBR treatment potentiated the HCV replicon-induced reactive oxygen species (ROS) production, inhibition of which with an antioxidant attenuated the cell death that was elicited by BBR in these cells. Moreover, BBR dampened the autophagic response in HCV RNA-positive or negative hepatoma cells, and pharmacological inhibition of autophagy conversely augmented the BBR-induced cell death. Finally, BBR inhibited the growth of Huh-7 cells that were persistently infected with the full-length genome HCV particles, and concomitant pharmacological inhibition of autophagy potentiated the killing of these cells by BBR. Our findings suggest that combining BBR with the inhibition of autophagy could be an attractive treatment strategy against HCC, irrespective of the presence of the HCV genome.
An optimized method for the extraction of ancient eukaryote DNA from marine sediments

Marine sedimentary ancient DNA (sedaDNA) provides a powerful means to reconstruct marine palaeo‐communities across the food web. However, currently there are few optimized sedaDNA extraction protocols available to maximize the yield of small DNA fragments typical of ancient DNA (aDNA) across a broad diversity of eukaryotes. We compared seven combinations of sedaDNA extraction treatments and sequencing library preparations using marine sediments collected at a water depth of 104 m off Maria Island, Tasmania, in 2018. These seven methods contrasted frozen versus refrigerated sediment, bead‐beating induced cell lysis versus ethylenediaminetetraacetic acid (EDTA) incubation, DNA binding in silica spin columns versus in silica‐solution, diluted versus undiluted DNA in shotgun library preparations to test potential inhibition issues during amplification steps, and size‐selection of low molecular‐weight (LMW) DNA to increase the extraction efficiency of sedaDNA. Maximum efficiency was obtained from frozen sediments subjected to a combination of EDTA incubation and bead‐beating, DNA binding in silica‐solution, and undiluted DNA in shotgun libraries, across 45 marine eukaryotic taxa. We present an optimized extraction protocol integrating these steps, with an optional post‐library LMW size‐selection step to retain DNA fragments of ≤500 base pairs. We also describe a stringent bioinformatic filtering approach for metagenomic data and provide a comprehensive list of contaminants as a reference for future sedaDNA studies. The new extraction and data‐processing protocol should improve quantitative paleo‐monitoring of eukaryotes from marine sediments, as well as other studies relying on the detection of highly fragmented and degraded eukaryote DNA in sediments.
Atg3 promotes Atg8 lipidation via altering lipid diffusion and rearrangement

Atg3‐catalyzed transferring of Atg8 to phosphatidylethanolamine (PE) in the phagophore membrane is essential for autophagy. Previous studies have demonstrated that this process requires Atg3 to interact with the phagophore membrane via its N‐terminal amphipathic helix. In this study, by using combined biochemical and biophysical approaches, our data showed that in addition to binding to the membranes, Atg3 attenuates lipid diffusion and enriches lipid molecules with smaller headgroup. Our data suggest that Atg3 promotes Atg8 lipidation via altering lipid diffusion and rearrangement.
Generation and characterization of Six2 conditional mice

Heterozygous deletion of Six2, which encodes a member of sine oculis homeobox family transcription factors, has recently been associated with the frontonasal dysplasia syndrome FND4. Previous studies showed that Six2 is expressed in multiple tissues during craniofacial development in mice, including embryonic head mesoderm, postmigratory frontonasal neural crest cells, and epithelial and mesenchymal cells of the developing palate and nasal structures. Whereas Six2 −/− mice exhibited cranial base defects but did not recapitulate frontonasal phenotypes of FND4 patients, Six1 −/‐Six2 −/− double mutant mice showed severe craniofacial defects including midline facial clefting. The complex phenotypes of FND4 patients and of Six1 −/‐Six2 −/− mutant mice indicate that Six2 plays crucial roles in distinct cell types at multiple stages of craniofacial morphogenesis. Here we report generation of mice carrying insertions of a pair of loxP sites flanking exon‐1 of the Six2 gene (Six2 f allele) using CRISPR/Cas9‐mediated genome editing. We show that the Six2 f allele functions normally and is effectively inactivated by Cre‐mediated recombination in vivo. Furthermore, we show that Six2 f/f;Wnt1‐Cre mice recapitulated cranial base defects but not neonatal lethality of Six2 −/− mice. These results indicate that Six2 f/f mice enable systematic investigation of cell type‐ and stage‐specific Six2 function in development and disease.
The Emerging Role of the RBM20 and PTBP1 Ribonucleoproteins in Heart Development and Cardiovascular Diseases

Alternative splicing is a regulatory mechanism essential for cell differentiation and tissue organization. More than 90% of human genes are regulated by alternative splicing events, which participate in cell fate determination. The general mechanisms of splicing events are well known, whereas only recently have deep-sequencing, high throughput analyses and animal models provided novel information on the network of functionally coordinated, tissue-specific, alternatively spliced exons. Heart development and cardiac tissue differentiation require thoroughly regulated splicing events. The ribonucleoprotein RBM20 is a key regulator of the alternative splicing events required for functional and structural heart properties, such as the expression of TTN isoforms. Recently, the polypyrimidine tract-binding protein PTBP1 has been demonstrated to participate with RBM20 in regulating splicing events. In this review, we summarize the updated knowledge relative to RBM20 and PTBP1 structure and molecular function; their role in alternative splicing mechanisms involved in the heart development and function; RBM20 mutations associated with idiopathic dilated cardiovascular disease (DCM); and the consequences of RBM20-altered expression or dysfunction. Furthermore, we discuss the possible application of targeting RBM20 in new approaches in heart therapies.
Bioassay-Guided Isolation, Metabolic Profiling, and Docking Studies of Hyaluronidase Inhibitors from Ravenala madagascariensis

Hyaluronidase enzyme (HAase) has a role in the dissolution or disintegration of hyaluronic acid (HA) and in maintaining the heathy state of skin. Bioassay-guided fractionation of Ravenala madagascariensis (Sonn.) organ extracts (leaf, flower, stem, and root) testing for hyaluronidase inhibition was performed followed by metabolic profiling using LC–HRMS. Additionally, a hyaluronidase docking study was achieved using Molecular Operating Environment (MOE). Results showed that the crude hydroalcoholic (70% EtOH) extract of the leaves as well as its n-butanol (n-BuOH) partition showed higher HAase activity with 64.3% inhibition. Metabolic analysis of R. madagascariensis resulted in the identification of 19 phenolic compounds ranging from different chemical classes (flavone glycosides, flavonol glycosides, and flavanol aglycones). Bioassay-guided purification of the leaf n-BuOH partition led to the isolation of seven compounds that were identified as narcissin, rutin, epiafzelechin, epicatechin, isorhamnetin 7-O-glucoside, kaempferol, and isorhamnetin-7-O-rutinoside. The docking study showed that narcissin, rutin, and quercetin 3-O-glucoside all interact with HAase through hydrogen bonding with the Asp111, Gln271, and/or Glu113 residues. Our results highlight Ravenala madagascariensis and its flavonoids as promising hyaluronidase inhibitors in natural cosmetology preparations for skin care.
Robust CAPTCHA Image Generation Enhanced with Adversarial Example Methods

SUMMARY Malicious attackers on the Internet use automated attack programs to disrupt the use of services via mass spamming, unnecessary bulletin boarding, and account creation. Completely automated public turing test to tell computers and humans apart (CAPTCHA) is used as a security solution to prevent such automated attacks. CAPTCHA is a system that determines whether the user is a machine or a person by providing distorted letters, voices, and images that only humans can understand. However, new attack techniques such as optical character recognition (OCR) and deep neural networks (DNN) have been used to bypass CAPTCHA. In this paper, we propose a method to generate CAPTCHA images by using the fast-gradient sign method (FGSM), iterative FGSM (I-FGSM), and the DeepFool method. We used the CAPTCHA image provided by python as the dataset and Tensorﬂow as the machine learning library. The experimental results show that the CAPTCHA image generated via FGSM, I-FGSM, and DeepFool methods exhibits a 0% recognition rate with (cid:2) = 0 . 15 for FGSM, a 0% recognition rate with α = 0 . 1 with 50 iterations for I-FGSM, and a 45% recognition rate with 150 iterations for the DeepFool method.
Lysosomal Exocytosis, Exosome Release and Secretory Autophagy: The Autophagic- and Endo-Lysosomal Systems Go Extracellular

Beyond the consolidated role in degrading and recycling cellular waste, the autophagic- and endo-lysosomal systems play a crucial role in extracellular release pathways. Lysosomal exocytosis is a process leading to the secretion of lysosomal content upon lysosome fusion with plasma membrane and is an important mechanism of cellular clearance, necessary to maintain cell fitness. Exosomes are a class of extracellular vesicles originating from the inward budding of the membrane of late endosomes, which may not fuse with lysosomes but be released extracellularly upon exocytosis. In addition to garbage disposal tools, they are now considered a cell-to-cell communication mechanism. Autophagy is a cellular process leading to sequestration of cytosolic cargoes for their degradation within lysosomes. However, the autophagic machinery is also involved in unconventional protein secretion and autophagy-dependent secretion, which are fundamental mechanisms for toxic protein disposal, immune signalling and pathogen surveillance. These cellular processes underline the crosstalk between the autophagic and the endosomal system and indicate an intersection between degradative and secretory functions. Further, they suggest that the molecular mechanisms underlying fusion, either with lysosomes or plasma membrane, are key determinants to maintain cell homeostasis upon stressing stimuli. When they fail, the accumulation of undigested substrates leads to pathological consequences, as indicated by the involvement of autophagic and lysosomal alteration in human diseases, namely lysosomal storage disorders, age-related neurodegenerative diseases and cancer. In this paper, we reviewed the current knowledge on the functional role of extracellular release pathways involving lysosomes and the autophagic- and endo-lysosomal systems, evaluating their implication in health and disease.
Temperature and Emissivity Inversion Accuracy of Spectral Parameter Changes and Noise of Hyperspectral Thermal Infrared Imaging Spectrometers

The emergence of hyperspectral thermal infrared imaging spectrometers makes it possible to retrieve both the land surface temperature (LST) and the land surface emissivity (LSE) simultaneously. However, few articles focus on the problem of how the instrument’s spectral parameters and instrument noise level affect the LST and LSE inversion errors. In terms of instrument development, this article simulated three groups of hyperspectral thermal infrared data with three common spectral parameters and each group of data includes tens of millions of simulated radiances of 1525 emissivity curves with 17 center wavelength shift ratios, 6 full width at half maximum (FWHM) change ratios and 6 noise equivalent differential temperatures (NEDTs) under 15 atmospheric conditions with 6 object temperatures, inverted them by two temperature and emissivity separation methods (ISSTES and ARTEMISS), and analyzed quantitatively the effects of the spectral parameters change and noise of an instrument on the LST and LSE inversion errors. The results show that: (1) center wavelength shifts and noise affect the inversion errors strongly, while FWHM changes affect them weakly; (2) the LST and LSE inversion errors increase with the center wavelength shift ratio in a quadratic function and increase with FWHM change ratio slowly and linearly for both the inversion methods, however they increase with NEDT in an S-curve for ISSTES while they increase with NEDT slightly and linearly for ARTEMISS. During the design and development of a hyperspectral thermal infrared instrument, it is highly recommended to keep the potential center wavelength shift within 1 band and keep NEDT within 0.1K (corresponding LST error < 1K and LSE error < 0.015) for normal applications and within 0.03K (corresponding LST error < 0.5K and LSE error < 0.01) for better application effect and level.