Miracle-dz/UniFAR-FTUs huggingface dataset:
A Three-Dimensional Organoid Model of Primary Breast Cancer to Investigate the Effects of Oncolytic Virotherapy

Background: Although several oncolytic viruses have already been tested in early-stage clinical studies of breast cancer, there is still an urgent need to develop patient-derived experimental systems that mimic the response of breast cancer to oncolytic agents in preparation of testing different oncolytic viruses in clinical trials. We addressed this need by developing a protocol to study the effects of oncolytic viruses in stable organoid cell cultures derived from breast cancer tissue. Methods: We used an established three-dimensional organoid model derived from tissue of 10 patients with primary breast cancer. We developed an experimental protocol for infecting organoid cultures with oncolytic viruses and compared the oncolytic effects of a measles vaccine virus (MeV) and a vaccinia virus (GLV) genetically engineered to express either green fluorescent protein (MeV-GFP) and red fluorescent protein (GLV-0b347), respectively, or a suicide gene encoding a fusion of cytosine deaminase with uracil phosphoribosyltransferase (MeV-SCD and GLV-1h94, respectively), thereby enabling enzymatic conversion of the prodrug 5-fluorocytosine (5-FC) into cytotoxic compounds 5-fluorouracil (5-FU) and 5-fluorouridine monophosphate (5-FUMP). Results: The method demonstrated that all oncolytic viruses significantly inhibited cell viability in organoid cultures derived from breast cancer tissue. The oncolytic effects of the oncolytic viruses expressing suicide genes (MeV-SCD and GLV-1h94) were further enhanced by virus-triggered conversion of the prodrug 5-FC to toxic 5-FU and toxic 5-FUMP. Conclusions: We were able to develop a protocol to assess the effects of two different types of oncolytic viruses in stable organoid cell cultures derived from breast cancer tissue. The greatest oncolytic effects were observed when the oncolytic viruses were engineered to express a suicide gene (MeV-SCD and GLV-1h94) in the presence of the prodrug 5-FC. The model therefore provides a promising in vitro method to help further testing and engineering of new generations of virotherapeutic vectors for in vivo use.
DIC Score Combined With CLIF-C OF Score Is More Effective in Predicting Prognosis in Patients With Hepatitis B Virus Acute-on-Chronic Liver Failure

Coagulation and fibrinolysis disorders are major prognostic factors in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients. Here, we aimed to clarify the role of disseminated intravascular coagulation (DIC) scores in predicting HBV-ACLF patient prognosis. We assessed the DIC score from HBV-ACLF patients at Huashan Hospital in Shanghai, China from June 2013 to May 2021 and evaluated it in relation to short-term mortality, clinical course, and infection. A novel prognostic scoring model was proposed based on DIC scores. A total of 163 transplant-free HBV-ACLF patients were enrolled. DIC scores were higher in non-survivors than survivors (6 vs. 4, P = 0.000) and were independently associated with short-term mortality [hazard ratio (HR): 1.397, 95% confidence interval (95% CI): 1.040–1.875, P = 0.026]. DIC scores were associated with ACLF grade, clinical course, and infection. Moreover, they were correlated with model for end-stage liver disease (MELD) scores (r = 0.521, P < 0.001). The area under the receiver operating curve (auROC) of CLIF-C OF-DICs [a novel prognostic score based on age, DIC score, and Chronic liver failure-consortium organ function score (CLIF-C OFs)] for 90-day mortality was 0.936, which was higher than six other generic prognostic scoring models. These results were confirmed in a validation cohort (n = 82). In conclusion, elevated DIC score is associated with poor prognosis in HBV-ACLF patients, and can be used jointly with CLIF-C OFs to improve the accuracy of prognosis prediction.
Alterations in the Gut Microbiota and Their Metabolites in Colorectal Cancer: Recent Progress and Future Prospects

Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality worldwide. The etiology and pathogenesis of CRC remain unclear. A growing body of evidence suggests dysbiosis of gut bacteria can contribute to the occurrence and development of CRC by generating harmful metabolites and changing host physiological processes. Metabolomics, a systems biology method, will systematically study the changes in metabolites in the physiological processes of the body, eventually playing a significant role in the detection of metabolic biomarkers and improving disease diagnosis and treatment. Metabolomics, in particular, has been highly beneficial in tracking microbially derived metabolites, which has substantially advanced our comprehension of host-microbiota metabolic interactions in CRC. This paper has briefly compiled recent research progress of the alterations of intestinal flora and its metabolites associated with CRC and the application of association analysis of metabolomics and gut microbiome in the diagnosis, prevention, and treatment of CRC; furthermore, we discuss the prospects for the problems and development direction of this association analysis in the study of CRC. Gut microbiota and their metabolites influence the progression and causation of CRC, and the association analysis of metabolomics and gut microbiome will provide novel strategies for the prevention, diagnosis, and therapy of CRC.
Influence of Emerging Technologies on the Utilization of Plant Proteins

Protein from plant sources is claimed alternatives to animal sources in the human diet. Suitable protein sources need high protein digestibility and amino acid bioavailability. In terms of protein functionality and food applications, they also need high-quality attributes, such as solubility, gelling, water- and oil-holding capacities, emulsifying, and foaming. Thermal processing can improve the nutritional quality of plants with some disadvantages, like reducing the assimilation of micronutrients (vitamins and minerals). Emerging technologies—such as ultrasound, high-pressure, ohmic heating, microwave, pulsed electric field, cold plasma, and enzymatic processes—can overcome those disadvantages. Recent studies demonstrate their enormous potential to improve protein techno-functional properties, protein quality, and decrease protein allergenicity. However, the literature lacks a broader evaluation, including protein digestibility, industrial-scale optimization, and exploring applications to these alternative protein sources.
The Impact of Breathing Hypoxic Gas and Oxygen on Pulmonary Hemodynamics in Patients With Pulmonary Hypertension

Background Pure oxygen breathing (hyperoxia) may improve hemodynamics in patients with pulmonary hypertension (PH) and allows to calculate right-to-left shunt fraction (Qs/Qt), whereas breathing normobaric hypoxia may accelerate hypoxic pulmonary vasoconstriction (HPV). This study investigates how hyperoxia and hypoxia affect mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) in patients with PH and whether Qs/Qt influences the changes of mPAP and PVR. Study Design and Methods Adults with pulmonary arterial or chronic thromboembolic PH (PAH/CTEPH) underwent repetitive hemodynamic and blood gas measurements during right heart catheterization (RHC) under normoxia [fractions of inspiratory oxygen (FiO2) 0.21], hypoxia (FiO2 0.15), and hyperoxia (FiO2 1.0) for at least 10 min. Results We included 149 patients (79/70 PAH/CTEPH, 59% women, mean ± SD 60 ± 17 years). Multivariable regressions (mean change, CI) showed that hypoxia did not affect mPAP and cardiac index, but increased PVR [0.4 (0.1–0.7) WU, p = 0.021] due to decreased pulmonary artery wedge pressure [−0.54 (−0.92 to −0.162), p = 0.005]. Hyperoxia significantly decreased mPAP [−4.4 (−5.5 to −3.3) mmHg, p < 0.001] and PVR [−0.4 (−0.7 to −0.1) WU, p = 0.006] compared with normoxia. The Qs/Qt (14 ± 6%) was >10 in 75% of subjects but changes of mPAP and PVR under hyperoxia and hypoxia were independent of Qs/Qt. Conclusion Acute exposure to hypoxia did not relevantly alter pulmonary hemodynamics indicating a blunted HPV-response in PH. In contrast, hyperoxia remarkably reduced mPAP and PVR, indicating a preserved vasodilator response to oxygen and possibly supporting the oxygen therapy in patients with PH. A high proportion of patients with PH showed increased Qs/Qt, which, however, was not associated with changes in pulmonary hemodynamics in response to changes in FiO2.
The Elastin Receptor Complex: An Emerging Therapeutic Target Against Age-Related Vascular Diseases

The incidence of cardiovascular diseases is increasing worldwide with the growing aging of the population. Biological aging has major influence on the vascular tree and is associated with critical changes in the morphology and function of the arterial wall together with an extensive remodeling of the vascular extracellular matrix. Elastic fibers fragmentation and release of elastin degradation products, also known as elastin-derived peptides (EDPs), are typical hallmarks of aged conduit arteries. Along with the direct consequences of elastin fragmentation on the mechanical properties of arteries, the release of EDPs has been shown to modulate the development and/or progression of diverse vascular and metabolic diseases including atherosclerosis, thrombosis, type 2 diabetes and nonalcoholic steatohepatitis. Most of the biological effects mediated by these bioactive peptides are due to a peculiar membrane receptor called elastin receptor complex (ERC). This heterotrimeric receptor contains a peripheral protein called elastin-binding protein, the protective protein/cathepsin A, and a transmembrane sialidase, the neuraminidase-1 (NEU1). In this review, after an introductive part on the consequences of aging on the vasculature and the release of EDPs, we describe the composition of the ERC, the signaling pathways triggered by this receptor, and the current pharmacological strategies targeting ERC activation. Finally, we present and discuss new regulatory functions that have emerged over the last few years for the ERC through desialylation of membrane glycoproteins by NEU1, and its potential implication in receptor transactivation.
Type 1 Diabetes Patients With Different Residual Beta-Cell Function but Similar Age, HBA1c, and Cardiorespiratory Fitness Have Differing Exercise-Induced Angiogenic Cell Mobilisation

Background Many individuals with type 1 diabetes retain residual beta-cell function. Sustained endogenous insulin and C-peptide secretion is associated with reduced diabetes related complications, but underlying mechanisms remain unclear. Lower circulating numbers of endothelial and hematopoietic progenitor cells (EPCs and HPCs), and the inability to increase the count of these cells in response to exercise, are also associated with increased diabetes complications and cardiovascular disease. It is unknown whether residual beta-cell function influences HPCs and EPCs. Thus, this study examined the influence of residual beta-cell function in type 1 diabetes upon exercise-induced changes in haematopoietic (HPCs) and endothelial progenitor cells (EPCs). Methods Participants with undetectable stimulated C-peptide (n=11; Cpepund), 10 high C-peptide (Cpephigh; >200 pmol/L), and 11 non-diabetes controls took part in this observational exercise study, completing 45 minutes of intensive walking at 60% V ˙ O 2 p e a k . Clinically significant HPCs (CD34+) and EPCs (CD34+VEGFR2+) phenotypes for predicting future adverse cardiovascular outcomes, and subsequent cell surface expression of chemokine receptor 4 (CXCR4) and 7 (CXCR7), were enumerated at rest and immediately post-exercise by flow cytometry. Results Exercise increased HPCs and EPCs phenotypes similarly in the Cpephigh and control groups (+34-121% across phenotypes, p<0.04); but Cpepund group did not significantly increase from rest, even after controlling for diabetes duration. Strikingly, the post-exercise Cpepund counts were still lower than Cpephigh at rest. Conclusions Residual beta-cell function is associated with an intact exercise-induced HPCs and EPCs mobilisation. As key characteristics (age, fitness, HbA1c) were similar between groups, the mechanisms underpinning the absent mobilisation within those with negative C-peptide, and the vascular implications, require further investigation.
Analysis of Digital Voltage-Mode Controlled Buck Converter with Dual-Edge Constant on-Time Modulation

To improve the accuracy of output regulation in a switching converter with constant on-time( COT) modulation,dual-edge constant-on time( DCOT) modulation scheme for the switching converter in continuous conduction mode was proposed,based on the characteristics of COT modulation and dual-edge pulse-width modulation. The principle of digital voltage-mode controlled Buck converter with DCOT modulation was introduced. Moreover,its steady-state and transient performances were analyzed and compared with those of digital voltage-mode controlled Buck converter with COT modulation. The results show that digital voltage-mode controlled Buck converter with DCOT modulation improves output-regulation accuracy by 50% of peak-to-peak value of output voltage ripple and reduces the transient regulation time by one switching cycle. Finally, the simulation and experimental results validate the correctness of the theoretical analysis.
Polysialic Acid in the Immune System

Polysialic acid (polySia) is a highly regulated polymer of sialic acid (Sia) with such potent biophysical characteristics that when expressed drastically influences the interaction properties of cells. Although much of what is known of polySia in mammals has been elucidated from the study of its role in the central nervous system (CNS), polySia is also expressed in other tissues, including the immune system where it presents dynamic changes during differentiation, maturation, and activation of different types of immune cells of the innate and adaptive response, being involved in key regulatory mechanisms. At least six polySia protein carriers (CCR7, ESL-1, NCAM, NRP2, ST8Sia 2, and ST8Sia 4) are expressed in different types of immune cells, but there is still much to be explored in regard not only to the regulatory mechanisms that determine their expression and the structure of polySia chains but also to the identification of the cis- and trans- ligands of polySia that establish signaling networks. This review summarizes the current knowledge on polySia in the immune system, addressing its biosynthesis, its tools for identification and structural characterization, and its functional roles and therapeutic implications.
No Support for the Neolithic Plant Invasion Hypothesis: Invasive Species From Eurasia Do Not Perform Better Under Agropastoral Disturbance in Early Life Stages Than Invaders From Other Continents

Pre-adaptation to disturbance is an important driver of biological invasions in human-altered ecosystems. Agropastoralism is one of the oldest forms of landscape management. It surged 12,000 years ago in Western Asia and it was then imported to Europe starting 8,000 years ago. The Neolithic Plant Invasion hypothesis suggests that Eurasian plants succeed at invading agroecosystems worldwide thanks to their adaptation to agropastoralism, which derives from these species’ long co-evolution with such practice. Plant species from Western Asia are predicted to have the highest degree of adaptation to agropastoralism, since they have co-evolved with such practice for several millennia more than European plants, and non-Eurasian species should be poorly adapted due to their relatively short exposure. However, this Eurocentric perspective largely ignores that several other cultures around the world independently developed and implemented agropastoralism through history, which challenges this hypothesized superior adaptation of Eurasian species. Here, we tested whether the early-life performance of invasive plants under disturbance depends on their geographical origin and the associated assumed exposure time to agropastoralism. We selected 30 species divided into three groups: exposure long, native to Western Asia; exposure medium, native to Central Europe; exposure short, native to America. Three soil disturbance treatments (control/compaction/tilling) combined with two space occupancy levels (available/occupied) were applied to monospecific experimental units (n = 900), each containing 50 seeds. We predicted that Eurasian species would benefit more from disturbance in terms of germination and seedling performance than species with shorter assumed exposure to agropastoralism, and that this effect would be stronger when space is occupied. Contrary to these expectations, all species groups profited equally from disturbance, while non-Eurasian species were most hampered by space occupancy. For germination success and speed, exposure long species had higher values than exposure short species, regardless of the disturbance treatment. These results do not support that Eurasian species possess a higher adaptation to agropastoralism, but rather that non-Eurasian species can cope just as well with the associated disturbances. We discuss how future experiments that address the complex relationships between species interactions, plant life-phases and the quality of disturbance can help to understand the role of land-use history in plant invasion success.
Luteinizing Hormone Suppression by Progestin-Primed Ovarian Stimulation Is Associated With Higher Implantation Rate for Patients With Polycystic Ovary Syndrome Who Underwent in vitro Fertilization/Intracytoplasmic Sperm Injection Cycles: Comparing With Short Protocol

Background Many studies have demonstrated the positive clinical value of progestin-primed ovarian stimulation (PPOS) in patients with polycystic ovary syndrome (PCOS) who underwent assisted reproductive technology. However, the underlying factors contributing to this phenomenon remain unclear. We conducted a retrospective observational study to compare the clinical outcomes of women with PCOS who underwent PPOS or the short protocol to identify possible factors that influence the outcome. Methods This study included 304 patients who underwent PPOS and 152 patients who underwent short protocol from April 2014 to July 2019 after propensity-score matching. Human menopausal gonadotropin (hMG) dose, hormone profile, embryo development, and clinical outcomes of frozen-thawed embryo transfer (FET) cycles were compared. The primary outcome measure was the implantation rate. Logistic regression was performed to identify contributing factors, and receiver operating characteristic curve analysis was used to calculate the cutoff of luteinizing hormone (LH) difference ratio in clinical outcomes. Results Compared with the short protocol, PPOS resulted in a higher implantation rate (43.4% vs. 31.9%, P < 0.05), clinical pregnancy rate (61.8% vs. 47.4%, P < 0.05), and live birth rate (48.4% vs. 36.8%, P < 0.05). Similar fertilization, cleavage, and valid embryo rate per oocyte retrieved between groups were observed. The LH difference ratio was positively associated with implantation rate [P = 0.027, odds ratio (OR) = 1.861, 95% CI: 1.074–3.226]. The relationship between the LH difference ratio with clinical outcomes was confirmed by receiver operating characteristic curve analysis and comparisons among patients grouped by the LH difference ratio. Conclusion The implantation rate was associated with the LH difference ratio during ovary stimulation in patients with PCOS. Our results provide the explanation why PPOS shows the positive clinical outcomes for patients with PCOS.
Mutations of CX46/CX50 and Cataract Development

Cataract is a common disease in the aging population. Gap junction has been considered a central component in maintaining homeostasis for preventing cataract formation. Gap junction channels consist of connexin proteins with more than 20 members. Three genes including GJA1, GJA3, and GJA8, that encode protein Cx43 (connexin43), Cx46 (connexin46), and Cx50 (connexin50), respectively, have been identified in human and rodent lens. Cx46 together with Cx50 have been detected in lens fiber cells with high expression, whereas Cx43 is mainly expressed in lens epithelial cells. Disrupted expression of the two connexin proteins Cx46 and Cx50 is directly related to the development of severe cataract in human and mice. In this review article, we describe the main role of Cx46 and Cx50 connexin proteins in the lens and the relationship between mutations of Cx46 or Cx50 and hereditary cataracts. Furthermore, the latest progress in the fundamental research of lens connexin and the mechanism of cataract formation caused by lens connexin dysfunction are summarized. Overall, targeting connexin could be a novel approach for the treatment of cataract.
Freshwater Microbial Eukaryotic Core Communities, Open-Water and Under-Ice Specialists in Southern Victoria Island Lakes (Ekaluktutiak, NU, Canada)

Across much of the Arctic, lakes and ponds dominate the landscape. Starting in late September, the lakes are covered in ice, with ice persisting well into June or early July. In summer, the lakes are highly productive, supporting waterfowl and fish populations. However, little is known about the diversity and ecology of microscopic life in the lakes that influence biogeochemical cycles and contribute to ecosystem services. Even less is known about the prevalence of species that are characteristic of the seasons or whether some species persist year-round under both ice cover and summer open-water conditions. To begin to address these knowledge gaps, we sampled 10 morphometrically diverse lakes in the region of Ekaluktutiak (Cambridge Bay), on southern Victoria Island (NU, Canada). We focused on Greiner Lake, the lakes connected to it, isolated ponds, and two nearby larger lakes outside the Greiner watershed. The largest lakes sampled were Tahiryuaq (Ferguson Lake) and the nearby Spawning Lake, which support commercial sea-run Arctic char (Salvelinus alpinus) fisheries. Samples for nucleic acids were collected from the lakes along with limnological metadata. Microbial eukaryotes were identified with high-throughput amplicon sequencing targeting the V4 region of the 18S rRNA gene. Ciliates, dinoflagellates, chrysophytes, and cryptophytes dominated the lake assemblages. A Bray–Curtis dissimilarity matrix separated communities into under-ice and open-water clusters, with additional separation by superficial lake area. In all, 133 operational taxonomic units (OTUs) occurred either in all under-ice or all open-water samples and were considered “core” microbial species or ecotypes. These were further characterized as seasonal indicators. Ten of the OTUs were characteristic of all lakes and all seasons sampled. Eight of these were cryptophytes, suggesting diverse functional capacity within the lineage. The core open-water indicators were mostly chrysophytes, with a few ciliates and uncharacterized Cercozoa, suggesting that summer communities are mixotrophic with contributions by heterotrophic taxa. The core under-ice indicators included a dozen ciliates along with chrysophytes, cryptomonads, and dinoflagellates, indicating a more heterotrophic community augmented by mixotrophic taxa in winter.