Promising Research Approaches Research Articles

Intracellular and extracellular untargeted metabolomics reveal the effect of acute uranium exposure in HK-2 cells

Uranium exposure poses a serious threat to the health of occupational populations and the public. Although metabolomics is a promising research approach to study the toxicological mechanisms of uranium exposure, in vitro studies using human cells are scarce. Applying cultured cell metabolomics, we exhaustively analyzed the intracellular and extracellular differential metabolites upon uranium exposure and characterized the possible biological effects of uranium exposure on human kidney cells. Uranium exposure significantly induced disturbance in the amino acid biosynthesis and linoleic acid metabolism of the cells. Cells exposed to uranium produce excessive amounts of arachidonic acid, which has the potential to cause oxidative stress and damage cells. The results provide new evidence for an oxidative stress mechanism of uranium-induced renal cell injury. Cell metabolomics has proven to be a useful diagnostic tool to study the molecular mechanisms of uranium poisoning.

De microanalyse van online en gemedieerde interactie: ‘digitale conversatieanalyse’

The microanalysis of online and mediated interaction: ‘digital conversation analysis’ The immense increase of digital communication in all spheres of human life has led to a need for qualitative research approaches to study this development. This article sets out the contours of a qualitative micro-analytical approach to online and digitally mediated communication called ‘digital conversation analysis’. It describes its emergence, explains its relation to Conversation Analysis (CA) and Discursive Psychology and outlines its main characteristics. Digital CA is illustrated by providing an analytical example of sharing news in WhatsApp interactions between friends. Despite several challenges, digital CA may be a promising research approach that can be applied in various academic disciplines.

Direct Conversion to Achieve Glial Cell Fates: Oligodendrocytes and Schwann Cells.

Glia have been known for its pivotal roles in physiological and pathological conditions in the nervous system. To study glial biology, multiple approaches have been applied to utilize glial cells for research, including stem cell-based technologies. Human glial cells differentiated from pluripotent stem cells are now available, allowing us to study the structural and functional roles of glia in the nervous system, although the efficiency is still low. Direct conversion is an advanced strategy governing fate conversion of diverse cell types directly into the desired lineage. This novel strategy stands as a promising approach for preliminary research and regenerative medicine. Direct conversion employs genetic and environmental cues to change cell fate to that with the required functional cell properties while retaining maturity-related molecular features. As an alternative method, it is now possible to obtain a variety of mature cell populations that could not be obtained using conventional differentiation methods. This review summarizes current achievements in obtaining glia, particularly oligodendrocytes and Schwann cells.

Recent developments of Madhuca indica (Mahua) oil-based polymers: A mini review

Nowadays, the use of non-edible vegetable oils as the raw material for polymer development is growing in interest because of the scarcity and high demand for crude oil and also because of its eco-friendly approach. The utilization of non-edible oil to synthesize the applicable polymers reduces the usage of petrochemicals. To eliminate the reliance on petrochemicals, it is important to search for and extract alternate and domestic non-edible oils suitable for the synthesis of polymeric materials. This is now a promising research approach. The outstanding feature of indigenous, non-edible Madhuca indica oil (MO) is its chemical structure, with unsaturated sites and esters that are considerable ingredient polyols for the development of polymers. This review discusses the origin, structure and extraction of MO and systematically focuses on the recently developed polymers using oil as a renewable source of polyols. We have briefly reviewed MO-based polymeric materials such as alkyd resins like pentaalkyds for scratch resistance, glycerol alkyds for fly-ash coating, pentalkyd LC resins for display coating applications and epoxies of MO for biological coating materials. Also, the important polyurethanes in the pathways of MO-based fatty amide are transformed into the polyetherimide polyols through a step-growth reaction with bisphenol-A or bisphenol derivatives, which again react with isocyanates to produce MO-based PU for excellent adhesion and coating applications. Another type of waterborne polyurethane is made from polyesteramides. These PU coatings are used in the paint and pigment industries. We reviewed their synthesis and widespread use in coatings and composites.

Resource approach in diagnostics of pedagogical workers of educational organizations of Russia

Introduction. The introduction of a new model of professional development of education workers in Russia involves the technology of an individual development route developed on the basis of previously identified professional deficits. However, approaches to identifying deficits do not yet serve as a proper source of such routes, since they state the facts of subject or methodological difficulties of teachers in isolation from the context of the teacher's professional activity. As a possible solution to the current situation, it is proposed to approach the diagnosis of pedagogical workers in the logic of the resource approach, when a particular shortage of a pedagogical worker is interpreted in two aspects: as a consequence of the scarcity of other resources of an educational organization, for example, managerial or methodological, and as a cause of gaps in educational achievements of students. Materials and methods. The study was conducted on the material of a freely available regional report on the results of diagnostics of professional competencies of teachers. The key method is document analysis. The subject of the study were: the conclusions made in the report on the degree of reflection in diagnostic materials of the purpose and objectives of diagnostics; the structure and purpose of diagnostic data; the typology of tasks used to identify professional deficits of teachers; commentary on the methods of processing primary information. Results. The following costs of working with data based on the results of diagnostics of pedagogical workers of educational organizations are revealed: the predominance of stating facts over their comprehension; the lack of contextual assessment of the stated data; limitations in the use of data; the undetected connection of teacher deficits with the gaps of the students themselves. It is concluded that the work with data on teachers is built in the pledge of conditions, and not in the pledge of resources. That is, the data only indicate the existing level of pedagogical conditions, but do not explain the potential of professional skills of teachers, their resource capacity. Conclusion. The use of a resource approach in working with data on teachers requires updating the structure of analytical data, mandatory inclusion of contextual information; more attention to the analysis of the relationship between teacher deficits and student deficits. We consider promising further research approaches to the analysis of the results of diagnostics of professional competencies of teachers. We consider the resource approach proposed by us as one of the possible, but not exhaustive, arsenal of analytical practices that allow using data on teachers to manage the quality of general education.

Urinary metabolomics study of vancomycin-associated nephrotoxicity based on ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry.

Drug-induced nephrotoxicity is widespread and seriously affects human health. Vancomycin is a classical glycopeptide antibiotic. Vancomycin is widely used for severe infections caused by Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus but its obvious nephrotoxicity affects the safety of its clinical application. However, the etiology of vancomycin induced kidney injury is not well understood. This study aimed to explore the potential mechanism of vancomycin-induced nephrotoxicity in rats. Vancomycin (400mgkg-1) was used to establish kidney injury models in rats. A metabonomic approach was employed using ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) to delineate metabolic alterations. As a result, 15, 22, and 37 biomarkers were identified in urine samples from the treatment group compared to the control model on D2, D4, and D7, respectively. Changes in the levels of these metabolites indicated that amino acid metabolism and energy metabolism were disturbed in rats with vancomycin-associated nephrotoxicity. This study revealed the kidney effect of vancomycin, which may provide novel and promising research approaches to vancomycin-induced renal toxicity.

First Things First: How to Elicit the Initial Program Theory for a Realist Evaluation of Complex Integrated Care Programs.

The complexity of integrated care and the need for transferable evaluation insights ask for a suitable evaluation paradigm. Realist evaluation (RE), underpinned by the philosophy of critical realism, is a theory-driven approach that addresses what works, how, for whom, and in what circumstances. The current study illustrates the process needed for RE's first step: eliciting the initial program theory (IPT). The TARGET program, a Dutch primary care initiative to facilitate more integrated care for chronically ill patients, i.e., care that is efficient,tailored,and holistic, was taken as a real-world case. An RE approach informed the phased IPT elicitation: (1) identifying an abstract theory framework; (2) formulating the preliminary IPT, building on the abstract theory and informed by previous scientific studies that underpin TARGET; and (3) refining the preliminary IPT, informed by RE expert interviews (n = 7). An RE heuristic tool, specifying the interplay between intervention-context-actors-mechanisms-outcomes (ICAMO) and retroductive reasoning, was applied to synthesize the underlying theory of individual TARGET components into TARGET's IPT. Separate but related IPTs were identified for the two main types of actors involved in TARGET: primary care professionals (PCPs) and patients. For both actors, two sorts of mechanisms are assumed to be activated by TARGET, which-via instrumental outcomes-contribute to long-term quadruple aim targets. The first is confidence to enhance PCPs' person-centered conversational skills and to increase patients' active engagement in TARGET. The second is mutual trust, between PCPs and patients and between PCPs and their network partners. A supportive context is assumed crucial for activating these mechanisms-for example, sufficient resources to invest in integrated care. Although the IPT elicitation process is time intensive and requires a mind shift, it facilitates a deeper insight into program functioning than accommodated by the prevailing experimental designs in integrated care. Furthermore, the design of a realist-informed evaluation process can be informed by the IPT.

Supranuclear gaze disorders – How do I approach them?

Progressive Supranuclear Palsy (PSP) is a rapidly progressive neurodegenerative tauopathy. It is a rare neurodegenerative condition characterised by a range of motor and cognitive symptoms. Unfortunately, despite several promising pharmacological research approaches, including reducing levels of the toxic tau protein or alleviating the loss of tau function, there is currently no approved disease-modifying treatment option for this condition. To aid in the development of such treatments, there is a real need for the development of objective clinical tools for the support of diagnosis and for monitoring disease progression.

Online measures of looking and learning in infancy.

Infants in laboratory settings look longer at events that violate their expectations, learn better about objects that behave unexpectedly, and match utterances to the objects that likely elicited them. The paradigms revealing these behaviors have become cornerstones of research on preverbal cognition. However, little is known about whether these canonical behaviors are observed outside laboratory settings. Here, we describe a series of online protocols that replicate classic laboratory findings, detailing our methods throughout. In Experiment 1a, 15-month-old infants (N=24) looked longer at an online support event culminating in an Unexpected outcome (i.e., appearing to defy gravity) than an Expected outcome. Infants did not, however, show the same success with an online solidity event. In Experiment 1b, 15-month-old infants (N=24) showed surprise-induced learning following online events-they were better able to learn a novel object's label when the object had behaved unexpectedly compared to when it behaved expectedly. Finally, in Experiment 2, 16-month-old infants (N=20) who heard a valenced utterance ("Yum!") showed preferential looking to the object most likely to have generated that utterance. Together, these results suggest that, with some adjustments, online testing is a feasible and promising approach for infant cognition research.

Abstract P305: Patient-specific Ipsc-derived Cardiomyocytes Reveal Abnormal Regulation Of Fgf16 In A Familial Atrial Septal Defect

Aims: Congenital heart disease (CHD) frequently occurs in newborns due to abnormal formation of the heart or major blood vessels. Mutations in the GATA4 gene, which encodes GATA binding protein 4, are responsible for atrial septal defect (ASD), a common CHD. This study aims to gain insights into the molecular mechanisms of CHD using human induced pluripotent stem cells (iPSCs) from a family cohort with ASD. Methods and Results: Patient-specific iPSCs possess the same genetic information as the donor and can differentiate into various cell types from all three germ layers in vitro , thus presenting a promising approach for disease modeling and molecular mechanism research. Here, we generated a patient-specific iPSC line (iPSC-G4 T280M ) from a family cohort carrying a hereditary ASD mutation in GATA4 gene (T280M), as well as a human embryonic stem cell line (ESC-G4 T280M ) carrying the isogenic T280M mutation using the CRISPR/Cas9 genome editing method. The GATA4-mutant iPSCs and ESCs were then differentiated into cardiomyocytes (CMs) to model GATA4 mutation-associated ASD. We observed an obvious defect in cell proliferation in cardiomyocytes derived from both GATA4 T280M -mutant iPSCs (iPSC-G4 T280M -CMs) and ESCs (ESC-G4 T280M -CMs), while the impaired proliferation ability of iPSC-G4 T280M -CMs could be restored by gene correction. Integrated analysis of RNA-Seq and ChIP-Seq data indicated that FGF16 is a direct target of wild-type GATA4. However, the T280M mutation obstructed GATA4 occupancy at the FGF16 promoter region, leading to impaired activation of FGF16 transcription. Overexpression of FGF16 in GATA4-mutant cardiomyocytes rescued the cell proliferation defect. The direct relationship between GATA4 T280M and ASD was demonstrated in a human iPSC model for the first time. Conclusions: In summary, our study revealed the molecular mechanism of the GATA4 T280M mutation in ASD. Understanding the roles of the GATA4-FGF16 axis in iPSC-CMs will shed light on heart development and provide novel insights for the treatment of ASD and other CHD disorders.

In vitro osteogenic activities of sulfated derivative of polysaccharide extracted from Tamarindus indica L.

Osteoporosis, one of the most serious public health concerns caused by an imbalance between bone resorption and bone formation, has a major impact on the population. Therefore, finding the effective osteogenic compounds for the treatment of osteoporosis is a promising research approach. In our study, tamarind (Tamarindus indica L.) seed polysaccharide (TSP) extracted from tamarind seed was subjected to synthesize its sulfate derivatives. The 1H NMR, FT-IR, SEM, monosaccharide compositions and elemental analysis data revealed that tamarind seed polysaccharide sulfate (TSPS) was successfully prepared. As the result, TSPS showed potent effects on inducing osteoblast differentiation via increasing alkaline phosphatase (ALP) activity up to 20% after 10days and bone mineralization approximately 58% after four weeks at concentration of 20μg/mL, whereas no statistically increase for both ALP activity and bone mineralization was observed in TSP treatment. Furthermore, TSPS enhanced expression of several marker genes in bone formation. Overall, the obtained data provided novelty on osteogenic compounds originated from TSP of T.indica, as well as scientific fundamentals on drug development and bone tissue engineering for the treatment of osteoporosis and other bone-related diseases.

Geographic object-based image analysis and artificial neural networks for digital soil mapping

The use of techniques to calibrate soil prediction models based on legacy maps is restricted to areas where conventional survey and soil mapping were performed. It is necessary to seek alternatives to calibrate soil predictive models without a legacy soil map. The problem is the difficulty to delineate polygons of soil classes based on soil sampling points. This paper presents a novel digital soil mapping strategy using only georeferenced points of soil profiles to delineate detailed polygons of soil classes by the Geographic Object-Based Image Analysis (GEOBIA) approach and Artificial Neural Networks (ANN) models. The main objective was to evaluate the integration of the GEOBIA approach at different segmentation levels with ANN’s models and sampling points to produce a digital soil map of the Vale dos Vinhedos region, in Rio Grande do Sul, Brazil. From a Digital Terrain Model, 10 predictive variables were extracted. From the RapidEye remote sensing image the following spectral variables were extracted: Normalized Difference Vegetation Index and Normalized Difference Water Index. A new set of variables was produced using principal component analysis after standardization of the original variables. The multiresolution segmentation algorithm was used to create image objects at different segmentation levels. Four segmentation levels were tested with scale parameter (SP) 1, 2, 5 and 10; and the Cheesboard segmentation (CS) was used to transform the original pixels into polygons. Information on types of soil was obtained from 163 georeferenced soil profiles. Five ANN’s structures were implemented: four for the segmented data (SP01, SP02, SP05 and SP10) and one for the per-pixel approach (CS); 16 repetitions of each ANN were performed. With the best models for each segmentation level, extrapolations of soil classes were performed for the entire study area and validated with a detailed legacy soil map. The per-pixel approach model obtained the worst result. The best result in the extrapolation of soil types found was with the object-based approach (SP1). In our understanding, the scientific community can profit from the proposed methodology particularly when it only has georeferenced points of soil classes and not a legacy map, i.e., immediately after a field survey without the need for photointerpretation for delineation of the soil mapping units. The use of GEOBIA for digital mapping of soil classes seems to be a promising approach for future research.

Urinary proteome profiling for children with autism using data-independent acquisition proteomics.

BackgroundAutism is a complex neurodevelopmental disorder. Objective and reliable biomarkers are crucial for the clinical diagnosis of autism. Urine can accumulate early changes of the whole body and is a sensitive source for disease biomarkers.MethodsThe data-independent acquisition (DIA) strategy was used to identify differential proteins in the urinary proteome between autistic and non-autistic children aged 3–7 years. Receiver operating characteristic (ROC) curves were developed to evaluate the diagnostic performance of differential proteins.ResultsA total of 118 differential proteins were identified in the urine between autistic and non-autistic children, of which 18 proteins were reported to be related to autism. Randomized grouping statistical analysis indicated that 91.5% of the differential proteins were reliable. Functional analysis revealed that some differential proteins were associated with axonal guidance signaling, endocannabinoid developing neuron pathway, synaptic long-term depression, agrin interactions at neuromuscular junction, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signaling and synaptogenesis signaling pathway. The combination of cadherin-related family member 5 (CDHR5) and vacuolar protein sorting-associated protein 4B (VPS4B) showed the best discriminative performance between autistic and non-autistic children with an area under the curve (AUC) value of 0.987.ConclusionsThe urinary proteome could distinguish between autistic children and non-autistic children. This study will provide a promising approach for future biomarker research of neuropsychiatric disorders.

Implementation of the Social Component of Higher Education: Bottom-up Approach

Pedagogical strategies for the implementation of the social content of higher education should be exercised through the application of the bottom-up approach. The bottom-up approach is aimed at ensuring proper development of the student’s personality. This approach is based on the subject-specific (academic achievements) and generic (leadership, management skills and focus on personal and professional development) competencies. The purpose of this study was to investigate the range of tools as well as the effectiveness of the bottom-up approach to the implementation of the social component of higher education through perspective development and the emphasis on students’ leadership and management skills. The study is of an empirical nature and the research component is based on the formative experimental methodology. Fifteen students of the Faculty of Primary Education participated in the experimental part of the study. They were involved in the specific bottom-up approach to educational environment organization and were evaluated accordingly by a jury. The two-year implementation period of the bottom-up approach to the implementation of the social content of higher education took place through customized projects of personal and professional development. The average socialization readiness level within the group was 78.2 (out of 100 max.), with 13.3% of students showing an average socialization readiness level, and 86.7% of students achieving a good level. The results confirmed the effectiveness of the principal notions of the study. The task of adapting the content of higher education in order to achieve a positive momentum of students’ socialization readiness was successfully completed. The most promising approach for future research is finding out the advisability and effectiveness of expanding the range of participants of the projects of personal and professional self-development and leadership with the preservation of the essence and identified values of the bottom-up approach.

Home food environment and associations with weight and diet among U.S. adults: a cross-sectional study

BackgroundThe home provides the physical and social context for the majority of eating behaviors for U.S. adults. This study describes eleven dimensions of the home food environment among a national sample of U.S. adults and identifies which are associated with diet quality and overweight/obesity.MethodsA national sample of U.S. adults ages 18 to 75 was recruited from an online survey panel. Respondents (n = 4942) reported on foods available in the home, including 1) fruit and vegetables, 2) salty snacks/sweets, 3) less healthy beverages, as well as 4) food placement, 5) shopping practices for fruits and vegetables, 6) food preparation, 7) portion control methods, 8) family meals from restaurants, 9) family household practices around TV and eating, 10) presence of a TV in the dining area, and 11) ownership of a scale. Self-reported height and weight, fruit and vegetable intake, and percent calories from fat were also assessed.ResultsMean household size was 2.6, 32.7% had children in the home, and 23.1% lived alone. The majority were White (67.7%), with 12.3% Black and 14.3% Hispanic. Mean age was 44.4 and 48.3% were men. In multivariable models, seven features of the home food environment were associated with meeting the recommended fruit and vegetable intake guidelines, with food placement, meal preparation, frequency of shopping for fruit, and a greater variety of fruits and vegetables available in the home most strongly associated. Eight of 11 features were associated with percent energy from fat, including restaurant food for family meals, salty snacks and sweets availability, less healthy beverages availability, food placement, meal preparation, frequency of shopping for fruit, family eating with the TV on, and having a TV in the dining area. More diverse fruit and vegetable availability was associated with lower odds of overweight/obesity, and more frequent family eating while watching TV was associated with increased odds of overweight/obesity.ConclusionTargeting these dimensions of the home food environment may be a promising approach for future intervention research.

Advance on alkaloids of<italic> Lycium</italic> genus

<p indent=0mm>Natural products derived from medicinal and edible plants, such as polysaccharides, polyphenols, flavonoids, and alkaloids, are a valuable source of potential drug candidates and have attracted interest for their rich structural motifs and diverse physiological activities. Therefore, the discovery of new natural products with unique structures and potential bioactivity from esculent resources has emerged as a promising approach for drug research. In the Solanaceae family, plants of the genus <italic>Lycium</italic> are relatively abundant, containing about 80 species of plants. Of these, seven species and three varieties are found in China where <italic>L</italic>. <italic>barbarum</italic> L., <italic>L</italic>. <italic>chinense</italic> Mill., and <italic>L</italic>. <italic>ruthenicum</italic> Murr. are most common. Among them, <italic>L</italic>. <italic>barbarum</italic> L. and <italic>L</italic>. <italic>ruthenicum</italic> Murr are also major medicinal and edible plant resources in Northwest China. “Gou Qi Zi”, also known as Goji or Goji berry, are fruit from <italic>L</italic>.<italic> barbarum </italic>L., which has been used as a valuable traditional Chinese herbal medicine and functional food for <sc>2500 years.</sc> The earliest recorded mention of these berries is found in the oracle bone script (Jiaguwen) of the Shang Dynasty (1600−1040 BE). Goji berries and Cortex Lycii, which is derived from the root bark of <italic>L</italic>.<italic> chinense</italic> and <italic>L</italic>.<italic> barbarum</italic>, have many pharmacological functions, such as hypoglycemic, hypolipidemic, immuno-modulatory, antioxidant, anti-aging, neuroprotective, and anti-Alzheimer’s disease properties. Medical and pharmaceutical knowledge regarding <italic>L</italic>.<italic> barbarum</italic> has been recorded and summarized in Shennong’s Root and Herbal Classic (Shennong bencao jing) and isolated products are highly desired medicines and contribute to longevity. Li Shizhen also summarized the health and tonic effects of Goji berries in the Compendium of Materia Medica. Many researchers have focused significant attention on the <italic>Lycium </italic>genus in recent years and various chemical components have been isolated. Phytochemical studies have revealed that the genus<italic> Lycium</italic> possesses an abundance of secondary metabolites, such as glycerogalactolipids, phenylpropanoids, coumarins, lignans, flavonoids, amides, alkaloids, anthraquinones, organic acids, terpenoids, sterols, steroids and other small molecules and trace elements. Of these, the alkaloids are considered to be one of the main active ingredients. The aim of this review is to focus on identification and biological activity of alkaloids derived from a variety of species in <italic>Lycium </italic>genus. Up to 2021, at least 124 alkaloids, including 42 amide alkaloids, 31 spermine alkaloids, 17 nortropane alkaloids, 16 pyrrole alkaloids, 4 piperidine alkaloids, 5 imidazole alkaloids, 3 quinoline alkaloids, 3 indole alkaloids, and 3 other alkaloids were reported from different species in the <italic>Lycium </italic>genus. These can be found in diverse plant structures, such as fruits, root bark, leaves, seeds, or flowers. This review lays a solid foundation for better understanding of pharmacological activities of <italic>Lycium-</italic>derived compounds and is systematically summarized on the basis of phytochemical studies. This information provides reference values that should facilitate further investigation on additional pharmacological properties and add to the development and utilization of the<italic> Lycium</italic>.

Patient-specific iPSC-derived cardiomyocytes reveal abnormal regulation of FGF16 in a familial atrial septal defect.

Congenital heart disease (CHD) frequently occurs in newborns due to abnormal formation of the heart or major blood vessels. Mutations in the GATA4 gene, which encodes GATA binding protein 4, are responsible for atrial septal defect (ASD), a common CHD. This study aims to gain insights into the molecular mechanisms of CHD using human-induced pluripotent stem cells (iPSCs) from a family cohort with ASD. Patient-specific iPSCs possess the same genetic information as the donor and can differentiate into various cell types from all three germ layers in vitro, thus presenting a promising approach for disease modelling and molecular mechanism research. Here, we generated a patient-specific iPSC line (iPSC-G4T280M) from a family cohort carrying a hereditary ASD mutation in GATA4 gene (T280M), as well as a human embryonic stem cell line (ESC-G4T280M) carrying the isogenic T280M mutation using the CRISPR/Cas9 genome editing method. The GATA4-mutant iPSCs and ESCs were then differentiated into cardiomyocytes (CMs) to model GATA4 mutation-associated ASD. We observed an obvious defect in cell proliferation in cardiomyocytes derived from both GATA4T280M-mutant iPSCs (iPSC-G4T280M-CMs) and ESCs (ESC-G4T280M-CMs), while the impaired proliferation ability of iPSC-G4T280M-CMs could be restored by gene correction. Integrated analysis of RNA-Seq and ChIP-Seq data indicated that FGF16 is a direct target of wild-type GATA4. However, the T280M mutation obstructed GATA4 occupancy at the FGF16 promoter region, leading to impaired activation of FGF16 transcription. Overexpression of FGF16 in GATA4-mutant cardiomyocytes rescued the cell proliferation defect. The direct relationship between GATA4T280M and ASD was demonstrated in a human iPSC model for the first time. In summary, our study revealed the molecular mechanism of the GATA4T280M mutation in ASD. Understanding the roles of the GATA4-FGF16 axis in iPSC-CMs will shed light on heart development and provide novel insights for the treatment of ASD and other CHD disorders.

Graphdiyne‐Stabilized Silver Nanoparticles as an Efficient Electrocatalyst for CO2 Reduction

Electrochemical CO2 reduction reaction (e‐CO2RR) into high‐value chemicals is a promising approach for sustainable energy research, but there remains a great challenge to develop efficient and stable catalysts. Herein, in situ synthesized uniform Ag nanoparticles (AgNPs) directly growing on the surface of 2D graphdiyne (GDY) for selectively reducing CO2 to CO with high efficiency and stability are reported. Due to the special electronic distribution of GDY, it not only serves as a template for the growth of AgNPs to prevent its aggregation, but also increases active sites and transformation of electrons through the intimate interaction between phase interface to enhance their cooperative catalytic effect, which highly improves the electrocatalytic performance of the nanocomposite. Through investigations, it is found that the Ag/GDY/CC nanocomposite electrochemically reduces CO2 to CO with Faraday efficiency up to 92.1% and current density of 25.74 mA/cm2 at the potential of −1.3 V versus reversible hydrogen electrode (RHE). Meanwhile, during catalysis, the Ag/GDY/CC composite maintains excellent stability with a high current density of ≈26 mA/cm2 (threefold higher than that of Ag/CC), unchanged for over 24 h. To the best knowledge, herein, the first experimental study of an efficient CO2 reduction electrocatalyst based on GDY is represented.

Preparation of nanoemulsion of Cinnamomum zeylanicum oil and evaluation of its larvicidal activity against a main malaria vector Anopheles stephensi.

There is a growing need to use green and efficient larvicidal as alternatives for conventional chemicals in vector control programs. Nanotechnology has provided a promising approach for research and development of new larvicides. Larvicidal potential of a nanoemulsion of Cinnamomum zeylanicum essential oil reports against Anopheles stephensi. The nanoemulsion of was formulated in various ratios comprising of C. zeylanicum oil, tween 80, span 20 and water by stirrer. It was characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). All components of C. zeylanicum essential oil were identified by GC-MS analysis. The larvicidal potential of the oil and its nanoformulation were evaluated against larvae of An. stephensi. The stability and durability of nanoemulsion was observed over a period of time. Sixty one components in the oil were identified, cinnamaldehyde (56.803%) was the main component. The LC90 and LC50 values of C. zeylanicum essential oil were calculated as 49ppm and 37ppm, respectively. The nanoemulsion droplets were found spherical in shape. It was able to kill 100% of larvae in up to 3days. It was stable after dilution and increased its larvicidal activity up to 32% compared with the essential oil. A novel larvicide based on nanotechnology introduced. This experiment clearly showed increasing larvicidal activity and residual effect of the nanoformulation in comparison with the bulk essential oil. It could be concluded that this nanoemulsion may be considered as safe larvicide and should be subject of more research in this field.

Correlational selection in the age of genomics.

Ecologists and evolutionary biologists are well aware that natural and sexual selection do not operate on traits in isolation, but instead act on combinations of traits. This long-recognized and pervasive phenomenon is known as multivariate selection, or-in the particular case where it favours correlations between interacting traits-correlational selection. Despite broad acknowledgement of correlational selection, the relevant theory has often been overlooked in genomic research. Here, we discuss theory and empirical findings from ecological, quantitative genetic and genomic research, linking key insights from different fields. Correlational selection can operate on both discrete trait combinations and quantitative characters, with profound implications for genomic architecture, linkage, pleiotropy, evolvability, modularity, phenotypic integration and phenotypic plasticity. We synthesize current knowledge and discuss promising research approaches that will enable us to understand how correlational selection shapes genomic architecture, thereby linking quantitative genetic approaches with emerging genomic methods. We suggest that research on correlational selection has great potential to integrate multiple fields in evolutionary biology, including developmental and functional biology, ecology, quantitative genetics, phenotypic polymorphisms, hybrid zones and speciation processes.