Miracle-dz/UniFAR-FTUs huggingface dataset:
Design, synthesis, molecular modeling, and bioactivity evaluation of 1,10-phenanthroline and prodigiosin (Ps) derivatives and their Copper(I) complexes against mTOR and HDAC enzymes as highly potent and effective new anticancer therapeutic drugs

Breast cancer is the second type of cancer with a high probability of brain metastasis and has always been one of the main problems of breast cancer research due to the lack of effective treatment methods. Demand for developing an effective drug against breast cancer brain metastasis and finding molecular mechanisms that play a role in effective treatment are gradually increasing. However, there is no effective anticancer therapeutic drug or treatment method specific to breast cancer, in particular, for patients with a high risk of brain metastases. It is known that mTOR and HDAC enzymes play essential roles in the development of breast cancer brain metastasis. Therefore, it is vital to develop some new drugs and conduct studies toward the inhibition of these enzymes that might be a possible solution to treat breast cancer brain metastasis. In this study, a series of 1,10-phenanthroline and Prodigiosin derivatives consisting of their copper(I) complexes have been synthesized and characterized. Their biological activities were tested in vitro on six different cell lines (including the normal cell line). To obtain additional parallel validations of the experimental data, some in silico modeling studies were carried out with mTOR and HDAC1 enzymes, which are very crucial drug targets, to discover novel and potent drugs for breast cancer and related brain metastases disease. Graphical Abstract
Measuring embodied conceptualizations of pitch in singing performances: Insights from an OpenPose study

People conceptualize auditory pitch as vertical space: low and high pitch correspond to low and high space, respectively. The strength of this cross-modal correspondence, however, seems to vary across different cultural contexts and a debate on the different factors underlying this variation is currently taking place. According to one hypothesis, pitch mappings are semantically mediated. For instance, the use of conventional metaphors such as “falling” or “rising” melodies strengthens a pitch-height mapping to the detriment of other possible mappings (e.g., pitch as bright/dark color or small/big size). Hence, entrenched pitch terms shape specific conceptualizations. The deterministic role of language is called into question by the hypothesis that different pitch mappings share a less constraining conceptual basis. As such, conceptual primitives may be concretized ad hoc into specific domains so that more local variation is possible. This claim is supported, for instance, by the finding that musicians use language-congruent (conventional) and language-incongruent (ad hoc) mappings interchangeably. The present paper substantiates this observation by investigating the head movements of musically trained and untrained speakers of Dutch in a melody reproduction task, as embodied instantiations of a vertical conceptualization of pitch. The OpenPose algorithm was used to track the movement trajectories in detail. The results show that untrained participants systematically made language-congruent movements, while trained participants showed more diverse behaviors, including language-incongruent movements. The difference between the two groups could not be attributed to the level of accuracy in the singing performances. In sum, this study argues for a joint consideration of more entrenched (e.g., linguistic metaphors) and more context-dependent (e.g., musical training and task) factors in accounting for variability in pitch representations.
2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside ameliorates bleomycin-induced pulmonary fibrosis via regulating pro-fibrotic signaling pathways

2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-Glucoside (THSG) is the main active ingredient extracted from Polygonum multiflorum Thunb. (PMT), which has been reported to possess extensive pharmacological properties. Nevertheless, the exact role of THSG in pulmonary fibrosis has not been demonstrated yet. The main purpose of this study was to investigate the protective effect of THSG against bleomycin (BLM)-induced lung fibrosis in a murine model, and explore the underlying mechanisms of THSG in transforming growth factor-beta 1 (TGF-β1)-induced fibrogenesis using MRC-5 human lung fibroblast cells. We found that THSG significantly attenuated lung injury by reducing fibrosis and extracellular matrix deposition. THSG treatment significantly downregulated the expression levels of TGF-β1, fibronectin, α-SMA, CTGF, and TGFBR2, however, upregulated the expression levels of antioxidants (SOD-1 and catalase) and LC3B in the lungs of BLM-treated mice. THSG treatment decreased the expression levels of fibronectin, α-SMA, and CTGF in TGF-β1-stimulated MRC-5 cells. Conversely, THSG increased the expression levels of SOD-1 and catalase. Furthermore, treatment of THSG profoundly reduced the TGF-β1-induced generation of reactive oxygen species (ROS). In addition, THSG restored TGF-β1-induced impaired autophagy, accompany by increasing the protein levels of LC3B-II and Beclin 1. Mechanism study indicated that THSG significantly reduced TGF-β1-induced increase of TGFBR2 expression and phosphorylation of Smad2/3, Akt, mTOR, and ERK1/2 in MRC-5 cells. These findings suggest that THSG may be considered as an anti-fibrotic drug for the treatment of pulmonary fibrosis.
Social isolation in adults with cancer: An evolutionary concept analysis

Background In extant literature, the concept of social isolation has been explored primarily in the context of older adults. However, people with cancer may also experience social isolation, and there is a need for increased clarity regarding this phenomenon in this population. Objective To conceptualize social isolation in adult cancer care. Methods PubMed, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure, Wanfang Data, and the Chinese Biomedical Literature Database were systematically searched using the key terms “cancer,” “social isolation,” “social alienation,” and “social exclusion” for studies (from the earliest date available to June 2022). The main disciplines involved were psychology, nursing, medicine, and public health. Rodgers’ evolutionary concept analysis was employed to clarify the antecedents, attributes, and consequences of social isolation in adults with cancer. Results A total of 60 eligible articles were reviewed entirely and the main findings were categorized into antecedents, attributes, and consequences. The antecedents of social isolation were classified into six categories: cancer-related physiological changes, cognitive beliefs, psychological wellbeing, unsatisfactory social supports or relationships, restrictions associated with receiving treatments, and social-level barriers. Attributes were characterized according to behavior or social avoidance and negative affective experiences, while consequences were attributed to low therapeutic compliance, poor health conditions and mental health problems, and low quality of life. White’s heuristic model is a potential theoretical context applicable to social isolation in adults with cancer. Conclusion This concept analysis provides a basis for developing multidimensional assessment tools and measures to alleviate social isolation in adults with cancer, a complex and varied phenomenon. However, while this review contributes to the current knowledge on social isolation in people with cancer, studies should further investigate the relationships among attributes associated with social isolation.
Trends of myopia development among primary and junior school students in the post-COVID-19 epidemic period

Purpose To investigate the trends of myopia among primary and junior school students in the post-COVID-19 epidemic period. Method A prospective of cross-sectional study using spot photoscreenings in 123,538 children among primary and junior school students from 2019 to 2021 was conducted to evaluate the development of myopia in Xuzhou, China in the post-COVID-19 epidemic period. Equivalent refraction and the prevalence of myopia were recorded. Results The spherical equivalent refraction of myopia decreased across all grades except grade 1 (0.23 ± 0.56 D in 2019, 0.24 ± 0.63 D in 2020) from 2019 to 2020. However, refraction exhibited a hyperopic shift in 2021 compared to 2020 for grades 1–5 (no significant decreased for grade 4). The prevalence of myopia in all grades increased in 2020 compared to 2019, and the most dramatic changes were observed from grades 2–5 and grades 7–8 (P < 0.05). The changes in myopia prevalence in grades 1–4 were mild, and the reduction in myopia for Grade 5 is significant from 2020 to 2021. Nevertheless, students in grades 6 and 9 exhibited the greatest growth in myopia prevalence (P < 0.01). All grades had higher myopia prevalence in 2021 compared with 2019, except grade 1 (P = 0.25). The prevalence of myopia in girls was higher compared with boys, and the urban myopia prevalence was higher than in rural areas over the 3 years except in 2019 (P = 0.18). Conclusions The prevalence of myopia increased during the COVID-19 epidemic. However, the spherical equivalent refraction of lower grade children drifted to hyperopia and the trends of myopia development remained stable in the post-COVID-19 epidemic period. We should be more concerned about the prevalence of myopia in graduating for the primary or junior grades in the future.
Dysregulation of prefrontal parvalbumin interneurons leads to adult aggression induced by social isolation stress during adolescence

Social isolation during the juvenile stage results in structural and functional impairment of the brain and deviant adult aggression. However, the specific subregions and cell types that underpin this deviant behavior are still largely unknown. Here, we found that adolescent social isolation led to a shortened latency to attack onset and extended the average attack time, accompanied by anxiety-like behavior and deficits in social preference in adult mice. However, when exposed to social isolation during adulthood, the mice did not show these phenotypes. We also found that the structural plasticity of prefrontal pyramidal neurons, including the dendritic complexity and spine ratio, was impaired in mice exposed to adolescent social isolation. The parvalbumin (PV) interneurons in the prefrontal infralimbic cortex (IL) are highly vulnerable to juvenile social isolation and exhibit decreased cell numbers and reduced activation in adulthood. Moreover, chemogenetic inactivation of IL-PV interneurons can mimic juvenile social isolation-induced deviant aggression and social preference. Conversely, artificial activation of IL-PV interneurons significantly attenuated deviant aggression and rescued social preference during adulthood in mice exposed to adolescent social isolation. These findings implicate juvenile social isolation-induced damage to IL-PV interneurons in long-term aggressive behavior in adulthood.
Sensors securing sustainable digital urban logistics—A practitioner’s perspective

The transport of goods, equipment and waste to, from, in and through urban areas (urban logistics) are essential for the economic vitality of the city but at the same time make urban environmental and social targets more difficult to achieve The European Green Deal and the UN Sustainability Goals also challenge the ways of addressing planning and management. At the same time Covid 19 has led to new challenges for urban logistics together with changes in consumer purchasing and travel patterns. Digitalisation offers new ways of collecting data and providing input to planning and modelling of urban logistics that might alleviate these challenges. This article addresses how digitalisation and especially sensors can contribute to new forms of data for analysis and play a role in developing sustainable digital urban logistics measures and plans through data collection and sharing. The research contains empirical insights from a survey and workshop in Norway. The results from the survey show that sensors are the digital solution that practitioners see as most useful for urban transport. This is supported by results from the workshop supporting a sensor scenario. When it comes to the digitalisation process, the practitioners expect that the different levels of government will facilitate digitalisation of urban logistics and most practitioners have the opinion that all levels of government should do more to facilitate new solutions Testing should take place as collaboration between private and public actors. Due to Covid 19 the government level is seen to have an important role for exchange of information and advice, and for giving economic incentives and support, rather than providing law and regulatory changes or the reorganisation of public services. The local level is considered to have an especially important role for digitalisation including data for modelling, planning or public procurement procedures. The article addresses these questions by reference to the partnerships for freight transport in London and Gothenburg. This article adds insights for planning practitioners into how sensors will challenge as well as provide new possibilities, to suggest new paths for planning and modelling urban logistics and an amplified role for freight partnerships.
Exploring the mechanism of immediate analgesic effect of 1-time tuina intervention in minor chronic constriction injury rats using RNA-seq

Previous studies have proved and investigated the mechanism of the analgesic effect of tuina treatment on neuropathic pain. The purpose of this study was to analyze changes in gene expression in the dorsal root ganglia (DRG) and spinal dorsal horn (SDH) after 1-time tuina intervention to investigate the immediate analgesic mechanism by tuina. An improvement in nociceptive behavior in minor chronic constriction injury (CCI) rats after 1-time tuina was observed. 1-time tuina was more effective in the amelioration of thermal hyperalgesia, but no changes were found in the ultrastructure of DRG and SDH. Sixty-five differentially expressed genes (DEGs) modulated by tuina were detected in the DRG and 123 DEGs were detected in the SDH. Potential immediate analgesic mechanisms of tuina were analyzed by the Kyoto Encyclopedia of Genes and Genomes. DEGs were enriched in 75 pathways in DRG, and 107 pathways in SDH. The immediate analgesic mechanism of tuina is related to the calcium signaling pathway, thermogenesis, and regulation of lipolysis in adipocytes.
Overrepresentation of Enterobacteriaceae and Escherichia coli is the major gut microbiome signature in Crohn’s disease and ulcerative colitis; a comprehensive metagenomic analysis of IBDMDB datasets

Objectives A number of converging strands of research suggest that the intestinal Enterobacteriaceae plays a crucial role in the development and progression of inflammatory bowel disease (IBD), however, the changes in the abundance of Enterobacteriaceae species and their related metabolic pathways in Crohn’s disease (CD) and ulcerative colitis (UC) compared to healthy people are not fully explained by comprehensive comparative metagenomics analysis. In the current study, we investigated the alternations of the Enterobacterales population in the gut microbiome of patients with CD and UC compared to healthy subjects. Methods Metagenomic datasets were selected from the Integrative Human Microbiome Project (HMP2) through the Inflammatory Bowel Disease Multi’omics Database (IBDMDB). We performed metagenome-wide association studies on fecal samples from 191 CD patients, 132 UC patients, and 125 healthy controls (HCs). We used the metagenomics dataset to study bacterial community structure, relative abundance, differentially abundant bacteria, functional analysis, and Enterobacteriaceae-related biosynthetic pathways. Results Compared to the gut microbiome of HCs, six Enterobacteriaceae species were significantly elevated in both CD and UC patients, including Escherichia coli, Klebsiella variicola, Klebsiella quasipneumoniae, Klebsiella pneumoniae, Proteus mirabilis, Citrobacter freundii, and Citrobacter youngae, while Klebsiella oxytoca, Morganella morganii, and Citrobacter amalonaticus were uniquely differentially abundant and enriched in the CD cohort. Four species were uniquely differentially abundant and enriched in the UC cohort, including Citrobacter portucalensis, Citrobacter pasteurii, Citrobacter werkmanii, and Proteus hauseri. Our analysis also showed a dramatically increased abundance of E. coli in their intestinal bacterial community. Biosynthetic pathways of aerobactin siderophore, LPS, enterobacterial common antigen, nitrogen metabolism, and sulfur relay systems encoded by E. coli were significantly elevated in the CD samples compared to the HCs. Menaquinol biosynthetic pathways were associated with UC that belonged to K. pneumoniae strains. Conclusions In conclusion, compared with healthy people, the taxonomic and functional composition of intestinal bacteria in CD and UC patients was significantly shifted to Enterobacteriaceae species, mainly E. coli and Klebsiella species.
Principles of Memory

1. Introduction. 2. Systems or Process? 3. Principle 1: The Cue Driven Principle. 4. Principle 2: The Encoding-Retrieval Principle. 5. Principle 3: The Cue Overload Principle. 6: Principle 4: The Reconstruction Principle. 7. Principle 5: The Impurity Principle. 8. Principle 6: The Relative Distinctiveness Principle. 9: Principle 7: The Specificity Principle. 10. Evaluation, Limitations, and Implications. References.
Optimization and demonstration of two types of spring-roll dielectric elastomer actuators for minimally invasive surgery

Resulting from the restricted size of incisions and confined surgical space, the existing rigid and slender minimally invasive surgery (MIS) instruments are inefficient in providing an optimum articulation to handle certain minimally invasive surgery tasks. Thus, developments of novel articulating actuators are of urgent requirement. In this paper, with the aim to enhance the flexibility and maneuverability of surgical instruments in diverse minimally invasive surgery scenarios, two types of spring-roll dielectric elastomer (DE) actuators, namely linear-type and bending-type, are proposed. The actuators’ parameters were optimized and calibrated using a novel step-by-step procedure, based on the characterization and modeling of dielectric elastomer material (VHB 4905). Critical design factors including dimensions of the core spring, the pre-stretch ratio of the dielectric elastomer, and the excitation level of the actuator were identified, while the boundary conditions for the modeling of the actuator were derived from the requirements of minimally invasive surgery applications. The dielectric elastomer actuators’ deformation behavior and force response were analyzed both theoretically and experimentally, and the results from the two approaches were in good agreement. The linear-type actuator could achieve a maximum strain of 29% and a blocking force up to 5.05 N, while the bending-type actuator could achieve angulation over 70° and a blocking force of up to 0.22 N. The proposed actuators are lightweight, compact, and cost-effective, which could provide novel design inspiration for minimally invasive surgery instruments.
Improved two-photon photopolymerisation and optical trapping with aberration-corrected structured light

We demonstrate the effectiveness of phase only aberration corrections of structured light and their application to versatile optical trapping setups. We calculate phase corrections before (ex-situ) and after (in-situ) a high numerical aperture microscope objective using a spatial light modulator (SLM), and investigate how these corrections can be used to improve the efficiency and resolution of micro-structures fabricated through two-photon-photopolymerisation (2PP). We apply a phase retrieval algorithm to correct for distortions in a femtosecond laser that enables the fabrication of 3D structures using as many as 50 simultaneous foci. The inclusion of aberration correction in the fabrication process shows improved confinement of optically trapped particles and more efficient polymerisation while minimising intensity variations at individual foci, which potentially damage the structure during fabrication. We find that phase corrections allow for consistent voxel sizes, increased sharpness, and an expanded effective printing range when using an SLM, while also allowing for closer proximity of individual trap foci, minimising interference effects that hinder fabrication resolution.
Associations between blood-based biomarkers of Alzheimer’s disease with cognition in motoric cognitive risk syndrome: A pilot study using plasma Aβ42 and total tau

Background Motoric cognitive risk (MCR) syndrome is a conceptual construct that combines slow gait speed with subjective cognitive complaints and has been shown to be associated with an increased risk of developing dementia. However, the relationships between the pathology of Alzheimer’s disease (AD) and MCR syndrome remain uncertain. Therefore, the purpose of this study was to determine the levels of plasma AD biomarkers (Aβ42 and total tau) and their relationships with cognition in individuals with MCR. Materials and methods This was a cross-sectional pilot study that enrolled 25 individuals with normal cognition (NC), 27 with MCR, and 16 with AD. Plasma Aβ42 and total tau (t-tau) levels were measured using immunomagnetic reduction (IMR) assays. A comprehensive neuropsychological assessment was also performed. Results The levels of plasma t-tau proteins did not differ significantly between the MCR and AD groups, but that of plasma t-tau was significantly increased in the MCR and AD groups, compared to the NC group. Visuospatial performance was significantly lower in the MCR group than in the NC group. The levels of plasma t-tau correlated significantly with the Montreal Cognitive Assessment (MoCA) and Boston naming test scores in the MCR group. Conclusion In this pilot study, we found significantly increased plasma t-tau proteins in the MCR and AD groups, compared with the NC group. The plasma t-tau levels were also significantly correlated with the cognitive function of older adults with MCR. These results implied that MCR and AD may share similar pathology. However, these findings need further confirmation in longitudinal studies.