Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic and Phenotypic Characterization of the Novel Metallo-β-Lactamase NDM-29 From Escherichia coli

Objectives: The New Delhi metallo-β-lactamase (NDM) can hydrolyze almost all clinically available β-lactam antibiotics and has widely spread all over the world. NDM-29, a novel carbapenemase, was discovered in an Escherichia coli (19NC225) isolated from a patient with biliary tract infection in 2019 in China. Methods: Conjugation, transformation, cloning test, fitness cost, PacBio Sequel, and Illumina sequencing were performed to analyze the genetic and phenotypic characterization of blaNDM–29. Results: The susceptibility testing results showed 19NC225 was resistant to cephalosporins, carbapenems, combinations of β-lactam and β-lactamase inhibitors, and levofloxacin. Conjugation and transformation were performed to verify the transferability of NDM-29-encoding plasmid, and cloning test was conducted to prove the function of blaNDM–29 to increase carbapenem resistance. Furthermore, fitness cost test confirmed that the presence of NDM-29 exerts no survival pressure on bacteria. PacBio Sequel and Illumina sequencing were performed to analyze the genetic characterization of 19NC225, which contains two plasmids (pNC225-TEM1B and pNC225-NDM-29). pNC225-NDM-29, exhibiting 99.96% identity and 100% coverage with pNDM-BTR (an IncN1 plasmid from an E. coli in urine specimen from Beijing in 2013), showed responsibility for the multidrug-resistant (MDR) phenotype. Compared with blaNDM–1, blaNDM–29, located on pNC225-NDM-29, carries a G388A (D130N) mutation. The region harboring blaNDM–29 is located in an ISKpn19-based transposon, and two Tn6292 remnants are symmetrically located upstream and downstream of the transposon. The sequence results also indicated several important virulence genes. Conclusion: The findings of the novel carbapenemase NDM-29 could pose a threat to the control of antimicrobial resistance and arouse attention about the mutation of bacteria.
Crosstalk Between SMPDL3b and NADPH Oxidases Mediates Radiation-Induced Damage of Renal Podocytes

Patients undergoing radiotherapy (RT) for various tumors localized in the abdomen or pelvis often suffer from radiation nephrotoxicity as collateral damage. Renal podocytes are vulnerable targets for ionizing radiation and contribute to radiation-induced nephropathies. Our prior work previously highlighted the importance of the lipid-modifying enzyme sphingomyelinase acid phosphodiesterase like 3b (SMPDL3b) in modulating the radiation response in podocytes and glomerular endothelial cells. Hereby, we investigated the interplay between SMPDL3b and oxidative stress in mediating radiation injury in podocytes. We demonstrated that the overexpression of SMPDL3b in cultured podocytes (OE) reduced superoxide anion generation and NADPH oxidase activity compared to wild-type cells (WT) post-irradiation. Furthermore, OE podocytes showed downregulated levels of NOX1 and NOX4 after RT. On the other hand, treatment with the NOX inhibitor GKT improved WTs' survival post-RT and restored SMPDL3b to basal levels. in vivo, the administration of GKT restored glomerular morphology and decreased proteinuria in 26-weeks irradiated mice. Taken together, these results suggest a novel role for NOX-derived reactive oxygen species (ROS) upstream of SMPDL3b in modulating the response of renal podocytes to radiation.
Regeneration in Stentor coeruleus

We often think about regeneration in terms of replacing missing structures, such as organs or tissues, with new structures generated via cell proliferation and differentiation. But at a smaller scale, single cells, themselves, are capable of regenerating when part of the cell has been removed. A classic model organism that facilitates the study of cellular regeneration in the giant ciliate Stentor coeruleus. These cells, which can grow to more than a millimeter in size, have the ability to survive after extensive wounding of their surface, and are able to regenerate missing structures. Even a small piece of a cell can regenerate a whole cell with normal geometry, in a matter of hours. Such regeneration requires cells to be able to trigger organelle biogenesis in response to loss of structures. But subcellular regeneration also relies on intracellular mechanisms to create and maintain global patterning within the cell. These mechanisms are not understood, but at a conceptual level they involve processes that resemble those seen in animal development and regeneration. Here we discuss single-celled regeneration in Stentor from the viewpoint of standard regeneration paradigms in animals. For example, there is evidence that regeneration of the oral apparatus in Stentor follows a sender-receiver model similar to crustacean eyestalk regeneration. By drawing these analogies, we find that many of the concepts already known from the study of animal-scale regeneration and development can be applied to the study of regeneration at the cellular level, such as the concepts of determination, induction, mosaic vs. regulative development, and epimorphosis vs. morphallaxis. We propose that the similarities may go beyond analogy, and that some aspects of animal development and regeneration may have evolved by exploiting pre-existing subcellular developmental strategies from unicellular ancestors.
Medicinal Plants in Traditional Herbal Wines and Liquors in the East of Spain and the Balearic Islands

Homemade herbal preparations from the East of Spain are the witness of traditional medicine inherited from the ancient complex formulas of herbal teas and medicinal wines. In this study, we document the use of traditional alcoholic beverages, identify their ingredients, almost exclusively botanical, record the local medicinal uses of these mixtures, and discuss patterns of distribution of this knowledge in regions of eastern Spain, the Balearic Islands and Andorra. We determine marker species and relevant patterns of herbal formulas in the different regions of the territory. Homemade liquors and liqueurs are consumed for their digestive and tonic-restorative properties but they also play in some cases an important social role. The elderly remember other medicinal uses such as aperitif, emmenagogue, or antidiarrheal, for some of the most popular preparations. The herbal liqueur formulas include predominantly Lamiaceae, Asteraceae, Rosaceae, Rutaceae, and Apiaceae species. Herbs (58%), fruits (28%), and mixtures of both (12%) are ingredients of liquors and wines, being the aerial parts the most frequent in terms of species (30%) and records (49%). Dictamnus hispanicus, Santolina villosa, Salvia blancoana subsp. mariolensis, Rosmarinus officinalis, Thymus vulgaris, and Clinopodium serpyllifolium subsp. fruticosum are the species most frequently used. Others species used to a lesser extent as Polygonatum odoratum, Thymus moroderi, and Saxifraga longifolia are restricted to locally homemade preparations because their collection and uses require special knowledge of the rare or endemic flora. Sustainability of these practices is strongly limited by the overall loss of local traditional knowledge and by the limited availability of most of the wild species; some of them are endangered or threatened mainly by the loss of their natural habitats. Cultivation and domestication are a promising alternative to collecting from wild populations. The cultivation of Thymus moroderi in the province of Alicante and Polygonatum odoratum in the province of Teruel are good examples. There is a notable decrease in the complexity of the formulas registered throughout the nearly 15 years of the study. This is interpreted as a consequence of a loss of knowledge, less accessibility to wild resources, and changes in traditions and preferences.
Functional–Structural Plant Modeling Highlights How Diversity in Leaf Dimensions and Tillering Capability Could Promote the Efficiency of Wheat Cultivar Mixtures

Increasing the cultivated diversity has been identified as a major leverage for the agroecological transition as it can help improve the resilience of low input cropping systems. For wheat, which is the most cultivated crop worldwide in terms of harvested area, the use of cultivar mixtures is spreading in several countries, but studies have seldom focused on establishing mixing rules based on plant architecture. Yet, the aerial architecture of plants and the overall canopy structure are critical for field performance as they greatly influence light interception, plant interactions and yield. The very high number of trait combinations in wheat mixtures makes it difficult to conduct experimentations on this issue, which is why a modeling approach appears to be an appropriate solution. In this study, we used WALTer, a functional structural plant model (FSPM), to simulate wheat cultivar mixtures and try to better understand how differences between cultivars in key traits of the aerial architecture influence mixture performance. We simulated balanced binary mixtures of cultivars differing for different critical plant traits: final height, leaf dimensions, leaf insertion angle and tillering capability. Our study highlights the impact of the leaf dimensions and the tillering capability on the performance of the simulated mixtures, which suggests that traits impacting the plants' leaf area index (LAI) have more influence on the performance of the stand than traits impacting the arrangement of the leaves. Our results show that the performance of mixtures is very variable depending on the values of the explored architectural traits. In particular, the best performances were achieved by mixing cultivars with different leaf dimensions and different tillering capability, which is in agreement with numerous studies linking the diversity of functional traits in plant communities to their productivity. However, some of the worst performances were also achieved by mixing varieties differing in their aerial architecture, which suggests that diversity is not a sufficient criterion to design efficient mixtures. Overall, these results highlight the importance of simulation-based explorations for establishing assembly rules to design efficient mixtures.
Comparison of the Efficacy of Melasma Treatments: A Network Meta-Analysis of Randomized Controlled Trials

Background: Melasma is an acquired pigmentation disorder with challenges in treatment because of its refractory nature and high risk of recurrence. Objectives: This study aimed to compare the efficacy and side effects of 14 common therapies for melasma using a systematic review and network meta-analysis (NMA). Methods: The PubMed, Embase, and Cochrane Library databases were searched till December 2020 using the melasma area and severity index as a therapeutic index. A total of 59 randomized controlled trials (RCTs) met the inclusion criteria and were selected. Results: The ranking of relative efficacy compared with placebo in descending order was Q-switched Nd:Yag 1,064-nm laser (QSND), intense pulsed light, ablative fractional laser (AFL), triple combined cream (TCC), topical vitamin C, oral tranexamic acid (oTA), peeling, azelaic acid, microneedles (MNs), topical tranexamic acid (tTA), tretinoin, picosecond laser, hydroquinone (HQ), and non-AFL. Moreover, QSND was more effective than HQ and tTA against melasma. The ranking of percentage (%) of side effects in ascending order for each of 14 therapies with more than 80 participants was tretinoin (10.1%), oTA (17.6%), HQ (18.2%), AFL (20.0%), QSND (21.5%), TCC (25.7%), tTA (36.75%), peeling (38.0%), and MN (52.3%). Taking both efficacy and safety into consideration, TCC was found to be the most favorable selection among the topical drugs for melasma. QSND and AFL were still the best ways to treat melasma among photoelectric devices. oTA as system administration was a promising way recommended for melasma. Among 31 studies, 87% (27/31) studies showed that the efficacy of combination therapies is superior to that of single therapy. The quality of evidence in this study was generally high because of nearly 50% of split-face RCTs. Conclusions: Based on the published studies, this NMA indicated that QSND, AFL, TCC, and oTA would be the preferred ways to treat melasma for dermatologists. However, more attention should be paid to the efficacy and safety simultaneously during the clinical application. Most of the results were in line with those of the previous studies, but a large number of RCTs should be included for validation or update. Systematic Review Registration: identifier: CRD42021239203.
Pan-Genome of the Genus Streptomyces and Prioritization of Biosynthetic Gene Clusters With Potential to Produce Antibiotic Compounds

Species of the genus Streptomyces are known for their ability to produce multiple secondary metabolites; their genomes have been extensively explored to discover new bioactive compounds. The richness of genomic data currently available allows filtering for high quality genomes, which in turn permits reliable comparative genomics studies and an improved prediction of biosynthetic gene clusters (BGCs) through genome mining approaches. In this work, we used 121 genome sequences of the genus Streptomyces in a comparative genomics study with the aim of estimating the genomic diversity by protein domains content, sequence similarity of proteins and conservation of Intergenic Regions (IGRs). We also searched for BGCs but prioritizing those with potential antibiotic activity. Our analysis revealed that the pan-genome of the genus Streptomyces is clearly open, with a high quantity of unique gene families across the different species and that the IGRs are rarely conserved. We also described the phylogenetic relationships of the analyzed genomes using multiple markers, obtaining a trustworthy tree whose relationships were further validated by Average Nucleotide Identity (ANI) calculations. Finally, 33 biosynthetic gene clusters were detected to have potential antibiotic activity and a predicted mode of action, which might serve up as a guide to formulation of related experimental studies.
Physical Activity and Risks of Cardiovascular Diseases: A Mendelian Randomization Study

Background: Although some observational studies have shown that physical activity may have a positive relationship with cardiovascular diseases, the causal effect remains uncertain. We conducted a Mendelian randomization (MR) study to identify the potential causal effect between physical activity and cardiovascular diseases. Methods: Summary statistics of genome-wide association studies on four physical activity phenotypes and cardiovascular diseases were utilized. MR analysis was performed using inverse-variance weighted (IVW) and multivariable MR. Multiple sensitivity analysis was further conducted to identify the robustness of our results. Results: Genetically predicted self-reported vigorous physical activity (VPA) was significantly associated with lower risk of myocardial infarction (IVW OR: 0.24, 95% CI: 0.08–0.68, p-value: 0.007). Additionally, the causal effect of VPA with myocardial infarction was robust after adjusting for several cardiovascular risk factors through using the multivariable MR. There were no apparent causal associations between physical activity with other cardiovascular diseases. Results were consistent with the sensitivity analysis. Conclusion: The present study supports a protective role of self-reported vigorous physical activity in the initiation of myocardial infarction and highlights the importance of activity levels of physical activity. Further studies are required to elucidate the potential biological pathways of physical activity with cardiovascular diseases.
How Do Anchors' Characteristics Influence Consumers' Behavioural Intention in Livestream Shopping? A Moderated Chain-Mediation Explanatory Model

Livestream shopping has become the focus of current marketing practises, while theoretical research on it is still in initial stages. Thus, from the para-social interaction (PSI) theory perspective, this study draws on cognitive–affective system theory as an analytical framework to explore internal mechanisms of how anchors' characteristics influence consumer behavioural intentions in livestream shopping while considering the characteristics of consumer online interaction propensity. We conducted a survey questionnaire with a sample of 355 consumers who experienced livestream shopping and used structural equation modelling to assess their behavioural intentions. Our results reveal that anchors' physical attractiveness, social attractiveness, and professional ability influence consumers' intentions to follow the authors' suggestions and recommend anchors to others during live streams. PSI and affective trust in anchors are the chain-mediation mechanisms. Furthermore, consumers' online interaction propensity positively moderates the influence of anchors' characteristics on PSI and plays a moderating role on the whole chain mediation. However, this only affects anchors' physical attractiveness and social attractiveness while exert no effect on anchors' professional ability. This study advances the theoretical research on livestream shopping and provides practical inspiration for managers to develop more targeted livestream marketing strategies.
Health Effects Associated With Pre- and Perinatal Exposure to Arsenic

Inorganic arsenic is a well-established human carcinogen, able to induce genetic and epigenetic alterations. More than 200 million people worldwide are exposed to arsenic concentrations in drinking water exceeding the recommended WHO threshold (10μg/l). Additionally, chronic exposure to levels below this threshold is known to result in long-term health effects in humans. The arsenic-related health effects in humans are associated with its biotransformation process, whereby the resulting metabolites can induce molecular damage that accumulates over time. The effects derived from these alterations include genomic instability associated with oxidative damage, alteration of gene expression (including coding and non-coding RNAs), global and localized epigenetic reprogramming, and histone posttranslational modifications. These alterations directly affect molecular pathways involved in the onset and progression of many conditions that can arise even decades after the exposure occurs. Importantly, arsenic metabolites generated during its biotransformation can also pass through the placental barrier, resulting in fetal exposure to this carcinogen at similar levels to those of the mother. As such, more immediate effects of the arsenic-induced molecular damage can be observed as detrimental effects on fetal development, pregnancy, and birth outcomes. In this review, we focus on the genetic and epigenetic damage associated with exposure to low levels of arsenic, particularly those affecting early developmental stages. We also present how these alterations occurring during early life can impact the development of certain diseases in adult life.
A Substrate-Mimicking Basement Membrane Drives the Organization of Human Mesenchymal Stromal Cells and Endothelial Cells Into Perivascular Niche-Like Structures

Extracellular matrix-derived products (e.g. Matrigel) are widely used for in vitro cell cultures both as two-dimensional (2D) substrates and as three-dimensional (3D) encapsulation gels because of their ability to control cell phenotypes through biospecific cues. However, batch-to-batch variations, poor stability, cumbersome handling, and the relatively high costs strictly limit their use. Recently, a new substrate known as PhenoDrive-Y has been used as 2D coating of tissue culture plastic showing to direct the bone marrow mesenchymal stromal cells (MSCs) toward the formation of 3D spheroids. When organized into 3D spheroids, the MSCs expressed levels of pluripotency markers and of paracrine angiogenic activity higher than those of the MSCs adhering as fibroblast-like colonies on tissue culture plastic. The formation of the spheroids was attributed to the properties of this biomaterial that resemble the main features of the basement membrane by mimicking the mesh structure of collagen IV and by presenting the cells with orderly spaced laminin bioligands. In this study, PhenoDrive-Y was compared to Matrigel for its ability to drive the formation of perivascular stem cell niche-like structures in 2D co-culture conditions of human endothelial cells and adult bone marrow MSCs. Morphological analyses demonstrated that, when compared to Matrigel, PhenoDrive-Y led endothelial cells to sprout into a more consolidated tubular network and that the MSCs nestled as compact spheroids above the anastomotic areas of this network resemble more closely the histological features of the perivascular stem cell niche. A study of the expressions of relevant markers led to the identification of the pathways linking the PhenoDrive-Y biomimicking properties to the acquired histological features, demonstrating the enhanced levels of stemness, renewal potential, predisposition to migration, and paracrine activities of the MSCs.
Respiratory Motion-Registered Isotropic Whole-Heart T2 Mapping in Patients With Acute Non-ischemic Myocardial Injury

Background: T2 mapping is a magnetic resonance imaging technique that can be used to detect myocardial edema and inflammation. However, the focal nature of myocardial inflammation may render conventional 2D approaches suboptimal and make whole-heart isotropic 3D mapping desirable. While self-navigated 3D radial T2 mapping has been demonstrated to work well at a magnetic field strength of 3T, it results in too noisy maps at 1.5T. We therefore implemented a novel respiratory motion-resolved compressed-sensing reconstruction in order to improve the 3D T2 mapping precision and accuracy at 1.5T, and tested this in a heterogeneous patient cohort. Materials and Methods: Nine healthy volunteers and 25 consecutive patients with suspected acute non-ischemic myocardial injury (sarcoidosis, n = 19; systemic sclerosis, n = 2; acute graft rejection, n = 2, and myocarditis, n = 2) were included. The free-breathing T2 maps were acquired as three ECG-triggered T2-prepared 3D radial volumes. A respiratory motion-resolved reconstruction was followed by image registration of the respiratory states and pixel-wise T2 mapping. The resulting 3D maps were compared to routine 2D T2 maps. The T2 values of segments with and without late gadolinium enhancement (LGE) were compared in patients. Results: In the healthy volunteers, the myocardial T2 values obtained with the 2D and 3D techniques were similar (45.8 ± 1.8 vs. 46.8 ± 2.9 ms, respectively; P = 0.33). Conversely, in patients, T2 values did differ between 2D (46.7 ± 3.6 ms) and 3D techniques (50.1 ± 4.2 ms, P = 0.004). Moreover, with the 2D technique, T2 values of the LGE-positive segments were similar to those of the LGE-negative segments (T2LGE−= 46.2 ± 3.7 vs. T2LGE+ = 47.6 ± 4.1 ms; P = 0.49), whereas the 3D technique did show a significant difference (T2LGE− = 49.3 ± 6.7 vs. T2LGE+ = 52.6 ± 8.7 ms, P = 0.006). Conclusion: Respiratory motion-registered 3D radial imaging at 1.5T led to accurate isotropic 3D whole-heart T2 maps, both in the healthy volunteers and in a small patient cohort with suspected non-ischemic myocardial injury. Significantly higher T2 values were found in patients as compared to controls in 3D but not in 2D, suggestive of the technique's potential to increase the sensitivity of CMR at earlier stages of disease. Further study will be needed to demonstrate its accuracy.