Miracle-dz/UniFAR-FTUs huggingface dataset:
An integrated strategy combining metabolomics and machine learning for the evaluation of bioactive markers that differentiate various bile

Animal bile is an important component of natural medicine and is widely used in clinical treatment. However, it is easy to cause mixed applications during processing, resulting in uneven quality, which seriously affects and harms the interests and health of consumers. Bile acids are the major bioactive constituents of bile and contain a variety of isomeric constituents. Although the components are structurally similar, they exhibit different pharmacological activities. Identifying the characteristics of each animal bile is particularly important for processing and reuse. It is necessary to establish an accurate analysis method to distinguish different types of animal bile. We evaluated the biological activity of key feature markers from various animal bile samples. In this study, a strategy combining metabolomics and machine learning was used to compare the bile of three different animals, and four key markers were screened. Quantitative analysis of the key markers showed that the levels of Glycochenodeoxycholic acid (GCDCA) and Taurodeoxycholic acid (TDCA) were highest in pig bile; Glycocholic acid (GCA) and Cholic acid (CA) were the most abundant in bovine and sheep bile, respectively. In addition, four key feature markers significantly inhibited the production of NO in LPS-stimulated RAW264.7 macrophage cells. These findings will contribute to the targeted development of bile in various animals and provide a basis for its rational application. Graphical Abstract
The impact of Otago exercise programme on the prevention of falls in older adult: A systematic review

Objective To improve the quality of life of older adult in their later years, by increasing the physical activity participation of older adult, the occurrence of falls accident scores in older adult can be prevented. This paper comprehensively summarizes the origin, development, participation forms, and fitness effects of the Otago exercise program (OEP). Methods Using PubMed, web of science, CNKI, dimensional spectrum, and other databases, search for research papers from 2005 to April 2021 by using keywords such as Otago project exercise; aged, Fall; Cognitive function, Balance ability, Lower limb strength, Fall efficiency, and so on. PEDro Scale was used to check the quality of the literatures. Results A total of 34 papers were included after searching for kinds of literature related to the subject of this paper and after careful review by researchers. Conclusions Otago exercise programme is beneficial to improve the cognitive function of older adult, enhance their lower limb muscle strength and dynamic and static balance ability, and then improve the gait stability and posture control ability of older adult, which has significant positive benefits for the prevention of falls in older adult. OEP is helpful to improve the falling efficiency of older adult, help older adult overcome the fear of falling, and form a positive emotion of “exercise improves exercise,” to reduce the harm caused by sedentary behavior and the incidence of depression and improve their subjective wellbeing. Although OEP has significant positive effects on improving the health and physical fitness of older adult, preventing falls, and restoring clinical function, the corresponding neural mechanism for preventing falls is not very clear. At the same time, how OEP can be combined with emerging technologies to maximize its benefits needs to be further discussed in the future.
Candidate genes and sequence variants for susceptibility to mycobacterial infection identified by whole-exome sequencing

Inborn errors of immunity are known to influence susceptibility to mycobacterial infections. The aim of this study was to characterize the genetic profile of nine patients with mycobacterial infections (eight with BCGitis and one with disseminated tuberculosis) from the Republic of Moldova using whole-exome sequencing. In total, 12 variants in eight genes known to be associated with Mendelian Susceptibility to Mycobacterial Disease (MSMD) were detected in six out of nine patients examined. In particular, a novel splice site mutation c.373–2A>C in STAT1 gene was found and functionally confirmed in a patient with disseminated tuberculosis. Trio analysis was possible for seven out of nine patients, and resulted in 23 candidate variants in 15 novel genes. Four of these genes - GBP2, HEATR3, PPP1R9B and KDM6A were further prioritized, considering their elevated expression in immune-related tissues. Compound heterozygosity was found in GBP2 in a single patient, comprising a maternally inherited missense variant c.412G>A/p.(Ala138Thr) predicted to be deleterious and a paternally inherited intronic mutation c.1149+14T>C. Functional studies demonstrated that the intronic mutation affects splicing and the level of transcript. Finally, we analyzed pathogenicity of variant combinations in gene pairs and identified five patients with putative oligogenic inheritance. In summary, our study expands the spectrum of genetic variation contributing to susceptibility to mycobacterial infections in children and provides insight into the complex/oligogenic disease-causing mode.
Evaluating anticancer properties of Withaferin A—a potent phytochemical

Withaferin A is a C28 steroidal lactone derived from the plant Withania somnifera, commonly known as Ashwagandha. Withaferin A has received great attention for its anticancer properties noted in cancer cells of various origins. Extracts of Withania somnifera have been used in traditional Ayurvedic and Unani Indian medicine for their various pharmacological benefits. In recent years, Withania somnifera or Ashwagandha extract has become popularized as a health supplement marketed for its stress and anxiety reducing effects. Withaferin A is one of the most studied withanolides extracted from Withania somnifera that has gained great attention for its anticancer, anti-inflammatory, metabolic, and pro-apoptotic effects. Extensive in vivo and in vitro studies have depicted Withaferin A’s interactions with key role players in cancerous activity of the cell to exert its pro-apoptotic effects. Withaferin A interactions with NF-κB, STAT, Hsp90, ER-α, p53, and TGF-β have noted inhibition in cancer cell proliferation and cell cycle arrest in G2/M stage, ultimately leading to apoptosis or cell death. This review highlights pro-apoptotic properties of Withaferin A including generation of reactive oxidative species, Par-4 activation, endoplasmic reticulum stress (ER) induction, and p53 activation. Analysis of Withaferin A’s involvement in various oncogenic pathways leading to malignant neoplasm and its pharmacologic activity in conjunction with various cancer drugs provides promising evidence in therapeutic potential of Withaferin A as a cancer treatment.
Hypothermia reduces glymphatic transportation in traumatic edematous brain assessed by intrathecal dynamic contrast-enhanced MRI

The glymphatic system has recently been shown to clear brain extracellular solutes and can be extensively impaired after traumatic brain injury (TBI). Despite hypothermia being identified as a protective method for the injured brain via minimizing the formation of edema in the animal study, little is known about how hypothermia affects the glymphatic system following TBI. We use dynamic contrast-enhanced MRI (DCE-MRI) following cisterna magna infusion with a low molecular weight contrast agent to track glymphatic transport in male Sprague–Dawley rats following TBI with hypothermia treatment and use diffusion-weighted imaging (DWI) sequence to identify edema after TBI, and further distinguish between vasogenic and cytotoxic edema. We found that hypothermia could attenuate brain edema, as demonstrated by smaller injured lesions and less vasogenic edema in most brain subregions. However, in contrast to reducing cerebral edema, hypothermia exacerbated the reduction of efficiency of glymphatic transportation after TBI. This deterioration of glymphatic drainage was present brain-wide and showed hemispherical asymmetry and regional heterogeneity across the brain, associated with vasogenic edema. Moreover, our data show that glymphatic transport reduction and vasogenic edema are closely related to reducing perivascular aquaporin-4 (AQP4) expression. The suppression of glymphatic transportation might eliminate the benefits of brain edema reduction induced by hypothermia and provide an alternative pathophysiological factor indicating injury to the brain after TBI. Thus, this study poses a novel emphasis on the potential role of hypothermia in managing severe TBI.
A glial perspective on the extracellular matrix and perineuronal net remodeling in the central nervous system

A structural scaffold embedding brain cells and vasculature is known as extracellular matrix (ECM). The physical appearance of ECM in the central nervous system (CNS) ranges from a diffused, homogeneous, amorphous, and nearly omnipresent matrix to highly organized distinct morphologies such as basement membranes and perineuronal nets (PNNs). ECM changes its composition and organization during development, adulthood, aging, and in several CNS pathologies. This spatiotemporal dynamic nature of the ECM and PNNs brings a unique versatility to their functions spanning from neurogenesis, cell migration and differentiation, axonal growth, and pathfinding cues, etc., in the developing brain, to stabilizing synapses, neuromodulation, and being an active partner of tetrapartite synapses in the adult brain. The malleability of ECM and PNNs is governed by both intrinsic and extrinsic factors. Glial cells are among the major extrinsic factors that facilitate the remodeling of ECM and PNN, thereby acting as key regulators of diverse functions of ECM and PNN in health and diseases. In this review, we discuss recent advances in our understanding of PNNs and how glial cells are central to ECM and PNN remodeling in normal and pathological states of the CNS.
Was that my meal? Uncertainty from source sampling period in diet reconstruction based on stable isotopes in a syngnathid fish

Stable isotopes can be used to reconstruct diet in fishes, an approach that is particularly useful in threatened or endangered species where lethal sampling needs to be avoided To apply this method stable isotopes need to be measured both in the consumers and dietary sources As turnover rates may largely differ across tissues, the reconstruction should consider the uncertainty associated with sampling timing for both consumers and dietary sources. The present study investigated for the first time the application of a time lag for the estimation of the trophic position and the dietary regime in the greater pipefish Syngnathus acus (Family Syngnathidae). For that, two isotopic (δ13C and δ15N) data sets from dorsal fin-clipped tissues were used, including values in potential sources sampled (a) concomitantly with consumers (Unshifted approach) or (b) in the season sampled preceding consumer sampling (Shifted approach). The results attained indicate that the trophic position of the species was not affected (< 0.6% change) by shifting when analyzed for the annual dataset (global assessment). However, the trophic level estimated in the shifted treatment was ca. 6% higher than in the unshifted approach when the analysis was performed using a seasonal dataset (seasonal assessment including exclusively specimens collected in summer). Regarding the reconstruction of the dietary regime and in comparison to the unshifted approach, the results attained with shifted sampling revealed a higher preference for amphipods (43.7%), isopods (19.5%) and mysidaceans (12.1%), and a reduction in the reconstructed abundance for harpacticoid copepods (5.1%). These findings were similar to those attained for specimens and food web components collected in the same sampling period (seasonal dataset), both in females and males. This study demonstrates (1) the variability of estimates in the reconstruction of diet regimes depending on the data time shifting applied, and (2) the importance of considering adequate time lags in the assessment for syngnathid fishes.
Potential predictive and therapeutic applications of small extracellular vesicles-derived circPARD3B in osteoarthritis

Background: Heterogeneous phenotypes that display distinct common characteristics of osteoarthritis (OA) are not well defined and will be helpful in identifying more customized therapeutic options for OA. Circular RNAs (circRNAs) have attracted more and more attention due to their role in the progression of OA. Investigating the role of circRNAs in the pathogenesis of OA will contribute to the phenotyping of OA and to individualized treatment. Methods: Small extracellular vesicles (sEV) were isolated from serum samples from patients with OA of different stages and sEV-derived circPARD3B was determined using RT-qPCR analysis. CircPARD3B expression in a stimulated coculture that included OA fibroblast-like synoviocytes (OA-FLS) as well as human dermal microvascular endothelial cells (HDMECs), plus the effects of circPARD3B on the expression of vascular endothelial growth factor (VEGF) long with angiogenic activity, were evaluated in vitro. Based on bioinformatics analysis and luciferase reporter assay (LRA), MiR-326 and sirtuin 1 (SIRT1) were found to be interactive partners of circPARD3B. Mesenchymal stem cells (SMSCs) overexpressing circPARD3B were constructed and SMSCs-derived sEV with overexpressed circPARD3B (OE-circPARD3B-SMSCs-sEV) were obtained to explore the effect of the intervention of circPARD3B combined with SMSCs-sEV-based therapy in vitro and in a OA model induced by collagenase in vivo. Results: Serum sEV-linked circPARD3B was indentified to be significantly decreased in the inflammatory phenotype of OA. Overexpression of circPARD3B was found to inhibit the expression of VEGF, as well as the angiogenesis induced by VEGF in a IL-1β stimulated the co-culture of OA-FLS as well as HDMECs. CircPARD3B is directly bound to miR-326. SIRT1 was considered a novel miR-326 target gene. OE-circPARD3B-SMSCs-sEV significantly reduced VEGF expression in coculture of OA-FLS and HDMECs. Injection of OE-circPARD3B-SMSCs-sEV could also reduce synovial VEGF; additionally, it could further ameliorate OA in the mouse model of OA in vivo. Conclusion: Serum sEV circPARD3B is a potential biomarker that enables the identification of the inflammatory phenotype of patients with OA. Correspondingly, intracellular transfer of circPARD3B through OE-circPARD3B-SMSCs-sEV could postpone disease progression through a functional module regulated angiogenesis of circPARD3B-miR-326-SIRT1, providing a novel therapeutic strategy for OA.
Survival for patients with metastatic colon cancer underwent cytoreductive colectomy in the era of rapid development of anticancer drugs: A real-world analysis based on updated population dataset of 2004–2018

Objective: Metastatic colon cancer (mCC) poses a great threat to the survival of patients suffering from it. In the past decade, many clinical trials have been carried out to improve the prognosis of patients with mCC. Numerous treatments have emerged, and satisfactory efficacy has been demonstrated in randomized phase III trials in highly selective patients with mCC. Our present study aims to investigate whether these therapeutic advances can be reflected to the broader mCC patients who performed cytoreductive colectomy. Method: General and prognostic data for patients diagnosed with mCC who underwent cytoreductive colectomy between 2004–2018 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Survival was analyzed using the Kaplan-Meier method and Cox proportional hazards model. The hazard ratio (HR) and its 95% confidence interval (CI) were used to evaluate the influence of risk factors on prognosis. Results: A total of 26,301 patients diagnosed with mCC treated with cytoreductive colectomy were included in this study. The median overall survival was 19 months (range, 17–23). The good prognosis was associated with patients diagnosed at the most recent year, younger age, non-black race, female, married, without previous history of malignancy, no second malignancy onset, descending/sigmoid/splenic flexure colon tumor, normal CEA levels at diagnosis, low primary tumor burden, T1/T2 stage, N0 stage, single organ metastasis, underwent surgical resection of synchronous distant metastatic lymph nodes or organs, a high number of lymph-node examinations, low positive lymph-node ratio and received adjuvant chemotherapy. The proportion of patients surviving for ≥24 months increased from 37% in 2004 to 44.2% in 2016 (p < 0.001), especially in ≤49 years patients [46.8% in 2004 to 57.8% in 2016 (p < 0.001)]. The percentage of patients who died within 3 months decreased between 2004 and 2018 (from 19.6% to 15.7%; p < 0.001). Conclusion: Over a span of 15 years, the long-term survival has improved in real-world mCC patients who were treated with cytoreductive colectomy, especially among younger patients. However, the median overall survival remains not substantial.
Sourcing cells for in vitro models of human vascular barriers of inflammation

The vascular system plays a critical role in the progression and resolution of inflammation. The contributions of the vascular endothelium to these processes, however, vary with tissue and disease state. Recently, tissue chip models have emerged as promising tools to understand human disease and for the development of personalized medicine approaches. Inclusion of a vascular component within these platforms is critical for properly evaluating most diseases, but many models to date use “generic” endothelial cells, which can preclude the identification of biomedically meaningful pathways and mechanisms. As the knowledge of vascular heterogeneity and immune cell trafficking throughout the body advances, tissue chip models should also advance to incorporate tissue-specific cells where possible. Here, we discuss the known heterogeneity of leukocyte trafficking in vascular beds of some commonly modeled tissues. We comment on the availability of different tissue-specific cell sources for endothelial cells and pericytes, with a focus on stem cell sources for the full realization of personalized medicine. We discuss sources available for the immune cells needed to model inflammatory processes and the findings of tissue chip models that have used the cells to studying transmigration.
Role of digitalization, digital competence, and parental support on performance of sports education in low-income college students

Educational institutions have failed to achieve desired goals due to the lack of technology adoption, and this situation needs researchers’ emphasis. Hence, the current study examines the impact of digitalization and digital competencies among students on the educational performance of low-income college students in China. The article also investigates the moderating impact of parental support at the nexus of digitalization, digital competencies among students, and educational performance in low-income college students in China. The questionnaires were used by the researchers to gather the data from the selected respondents. The article has applied the smart-PLS to check the linkage among understudy constructs and test the hypotheses. The results revealed that digitalization and digital competencies among students positively link educational performance. The results also exposed that parental support significantly moderates digitalization, digital competencies, and educational performance in low-income college students in China. This article helps policymakers develop policies to improve educational performance using technology adoption.
Evaluation of noise regression techniques in resting-state fMRI studies using data of 434 older adults

Subject motion is a well-known confound in resting-state functional MRI (rs-fMRI) and the analysis of functional connectivity. Consequently, several clean-up strategies have been established to minimize the impact of subject motion. Physiological signals in response to cardiac activity and respiration are also known to alter the apparent rs-fMRI connectivity. Comprehensive comparisons of common noise regression techniques showed that the “Independent Component Analysis based strategy for Automatic Removal of Motion Artifacts” (ICA-AROMA) was a preferred pre-processing technique for teenagers and adults. However, motion and physiological noise characteristics may differ substantially for older adults. Here, we present a comprehensive comparison of noise-regression techniques for older adults from a large multi-site clinical trial of exercise and intensive pharmacological vascular risk factor reduction. The Risk Reduction for Alzheimer’s Disease (rrAD) trial included hypertensive older adults (60–84 years old) at elevated risk of developing Alzheimer’s Disease (AD). We compared the performance of censoring, censoring combined with global signal regression, non-aggressive and aggressive ICA-AROMA, as well as the Spatially Organized Component Klassifikator (SOCK) on the rs-fMRI baseline scans from 434 rrAD subjects. All techniques were rated based on network reproducibility, network identifiability, edge activity, spatial smoothness, and loss of temporal degrees of freedom (tDOF). We found that non-aggressive ICA-AROMA did not perform as well as the other four techniques, which performed table with marginal differences, demonstrating the validity of these techniques. Considering reproducibility as the most important factor for longitudinal studies, given low false-positive rates and a better preserved, more cohesive temporal structure, currently aggressive ICA-AROMA is likely the most suitable noise regression technique for rs-fMRI studies of older adults.