Miracle-dz/UniFAR-FTUs huggingface dataset:
A Systematic Way to Infer the Regulation Relations of miRNAs on Target Genes and Critical miRNAs in Cancers

MicroRNAs (miRNAs) are a class of important non-coding RNAs, which play important roles in tumorigenesis and development by targeting oncogenes or tumor suppressor genes. One miRNA can regulate multiple genes, and one gene can be regulated by multiple miRNAs. To promote the clinical application of miRNAs, two fundamental questions should be answered: what's the regulatory mechanism of a miRNA to a gene, and which miRNAs are important for a specific type of cancer. In this study, we propose a miRNA influence capturing (miRNAInf) to decipher regulation relations of miRNAs on target genes and identify critical miRNAs in cancers in a systematic approach. With the pair-wise miRNA/gene expression profiles data, we consider the assigning problem of a miRNA on target genes and determine the regulatory mechanisms by computing the Pearson correlation coefficient between the expression changes of a miRNA and that of its target gene. Furthermore, we compute the relative local influence strength of a miRNA on its target gene. Finally, integrate the local influence strength and target gene's importance to determine the critical miRNAs involved in specific cancer. Results on breast, liver and prostate cancers show that positive regulations are as common as negative regulations. The top-ranked miRNAs show great potential as therapeutic targets driving cancer to a normal state, and they are demonstrated to be closely related to cancers based on biological functional analysis, drug sensitivity/resistance analysis and survival analysis. This study will be helpful for the discovery of critical miRNAs and development of miRNAs-based clinical therapeutics.
Advances of Stem Cell-Laden Hydrogels With Biomimetic Microenvironment for Osteochondral Repair

Osteochondral damage from trauma or osteoarthritis is a general joint disease that can lead to an increased social and economic burden in the modern society. The inefficiency of osteochondral defects is mainly due to the absence of suitable tissue-engineered substrates promoting tissue regeneration and replacing damaged areas. The hydrogels are becoming a promising kind of biomaterials for tissue regeneration. The biomimetic hydrogel microenvironment can be tightly controlled by modulating a number of biophysical and biochemical properties, including matrix mechanics, degradation, microstructure, cell adhesion, and intercellular interactions. In particular, advances in stem cell-laden hydrogels have offered new ideas for the cell therapy and osteochondral repair. Herein, the aim of this review is to underpin the importance of stem cell-laden hydrogels on promoting the development of osteochondral regeneration, especially in the field of manipulation of biomimetic microenvironment and utilization growth factors with various delivery methods.
Ammonium Impacts Methane Oxidation and Methanotrophic Community in Freshwater Sediment

Lacustrine ecosystems are regarded as one of the important natural sources of greenhouse gas methane. Aerobic methane oxidation, carried out by methane-oxidizing bacteria, is a key process regulating methane emission. And ammonium is believed to greatly influence aerobic methane oxidation activity. To date, disagreement exists in the threshold of ammonium effect. Moreover, knowledge about how aerobic methanotrophic community composition and functional gene transcription respond to ammonium is still lacking. In the present study, microcosms with freshwater lake sediment were constructed to explore the effect of ammonium level on aerobic methanotrophs. Methane oxidation potential, and the density, diversity and composition of pmoA gene and its transcripts were examined during 2-week incubation. A negative impact of ammonium on aerobic methane oxidation potential and a positive impact on pmoA gene density were observed only at a very high level of ammonium. However, pmoA gene transcription increased notably at all ammonium levels. The composition of functional pmoA gene and transcripts were also influenced by ammonium. But a great shift was only observed in pmoA transcripts at the highest ammonium level.
Alcohol Craving in Heavy and Occasional Alcohol Drinkers After Cue Exposure in a Virtual Environment: The Role of the Sense of Presence

The development of new technologies, and more specifically the opportunity to immerse participants in virtual controlled environments, provides a new ecological framework for researchers to study complex behaviors. This experiment aimed to compare post-immersion craving in occasional and heavy alcohol drinkers. Twenty-two occasional drinkers and eighteen heavy drinkers were recruited and immersed in a virtual bar, including alcoholic beverages. After the exposure, heavy drinkers reported a significantly higher craving than occasional drinkers. Post-immersion alcohol craving was significantly related to the levels of perceived ecological validity of the virtual environment. Finally, a moderation analysis suggested that the levels of craving more strongly increased with perceived ecological validity in heavy drinkers than in occasional drinkers. Therefore, the perceived ecological validity was an important experimental parameter to study craving in a virtual environment. These results further suggested that virtual reality might be a useful tool for both the scientific study of alcohol addiction and the treatment of alcohol dependence and relapse.
Assistance and Therapy Dogs Are Better Problem Solvers Than Both Trained and Untrained Family Dogs

When faced with unsolvable or difficult situations dogs use different behavioral strategies. If they are motivated to obtain rewards, they either try to solve the problem on their own or tend to interact with a human partner. Based on the observation that in problem situations less successful and less perseverant dogs look more at the humans' face, some authors claim that the use of social strategies is detrimental to attempting an independent solution in dogs. Training may have an effect on dogs' problem-solving performance. We compared the behavior of (1) untrained, (2) trained for recreational purposes, and (3) working dogs: assistance and therapy dogs living in families (N = 90). During the task, dogs had to manipulate an apparatus with food pellets hidden inside. We measured the behaviors oriented toward the apparatus and behaviors directed at the owner/experimenter, and ran a principal component analysis. All measures loaded in one factor representing the use of the social strategy over a more problem-oriented strategy. Untrained dogs obtained the highest social strategy scores, followed by dogs trained for recreational purposes, and assistance and therapy dogs had the lowest scores. We conclude that assistance and therapy dogs' specific training and working experience (i.e., to actively help people) favors their independent and more successful problem-solving performance. General training (mainly obedience and agility in this study) also increases problem-oriented behavior.
Pharmacological Characteristics of Porcine Orexin 2 Receptor and Mutants

Orexin receptors (OXRs) play a critical regulatory role in central control of food intake, maintenance of sleeping states, energy metabolism, and neuroendocrine homeostasis. However, most previous studies have focused on the sleep-promoting functions of OXRs in human beings, while their potential value in enhancing food intake for livestock breeding has not been fully exploited. In this study, we successfully cloned porcine orexin 2 receptor (pOX2R) complementary DNA and constructed four pOX2R mutants (P10S, P11T, V308I, and T401I) by site-directed mutagenesis, and their functional expressions were further confirmed through Western blotting analysis. Pharmacological characteristics of pOX2R and their mutants were further investigated. These results showed that the P10S, P11T, and T401I mutants had decreased cAMP signaling with orexin A, whereas only the P11T mutant decreased under the stimulation of orexin B. Besides, only P10S displayed a decreased calcium release in response to both orexin ligands. Importantly, these mutants exhibited decreased phosphorylation levels of ERK1/2, p38, and CREB to some degree compared with wild-type pOX2R. Collectively, these findings highlight the critical role of these mutations in pOX2R signaling and expand our understanding of molecular and pharmacological characterization of pOX2R.
Real-Ambient Particulate Matter Exposure-Induced Cardiotoxicity in C57/B6 Mice

It is generally accepted that exposure to particulate matter (PM) increases the risk of cardiovascular-related morbidity and mortality, though the exact mechanism behind this has yet to be elucidated. Oxidative stress plays a potentially important role in the mechanism of toxicity, with Nrf2 serving as a major antioxidant gene. In the current study, a Nrf2 knockout mouse model was used in combination with an individual ventilated cage (IVC)-based real-ambient PM exposure system to assess the potential cardiotoxicity induced by real-ambient PM exposure and the potential role of Nrf2 and related signaling in this endpoint. After 6- or 11-weeks exposure to PM, ICP-mass spectrometry was used to assess the metal depositions in the heart tissue following PM exposure. Functional and morphological changes in the hearts were investigated with echocardiography and histopathology, and oxidative stress levels were assessed with a serum malondialdehyde content assay. In the further mechanistic study, an RNA-seq technique was utilized to assess the gene transcription status in the hearts of C57/B6 mice exposed to PM with or without Nrf2 knockout. The expression levels of genes of interest were then further investigated with quantitative real-time PCR and western blotting. The results indicated that PM exposure resulted in significant elevation of sodium, potassium, selenium, and ferrum levels in mouse heart tissue. Meanwhile, significantly altered heart function and morphology were observed. Interestingly, Nrf2 knockout led to abolishment of PM-induced effects in several functional parameters but not the morphological changes. Meanwhile, elevated malondialdehyde content was observed in Nrf2 knockout animals. RNA-seq results revealed thousands of genes altered by PM exposure and/or Nrf2 knockout, and this affected several pathways, such as MAPK, phagosome, calcium signaling, and JAK-STAT. In subsequent molecular studies, enhanced nuclear translocation of Nrf2 was also observed following PM exposure, while the MAPK signaling pathway along with related JAK-STAT and TGF-β1 pathway genes, such as p38MAPK, AKT, TAK1, JAK1, STAT3, GRB2, TGFb1, and SMAD2, were confirmed to be affected by PM exposure and/or Nrf2 knockout. The data suggested that PM may induce cardiotoxicity in C57/B6 mice in which Nrf2 plays both protective and detrimental roles involving cardiac-related pathways, such as MAPK, JAK-STAT, and TGF-β1.
Comparative Effectiveness of Radiofrequency Ablation vs. Surgical Resection for Patients With Solitary Hepatocellular Carcinoma Smaller Than 5 cm

Background: This study aims to compare survival outcome after receiving radiofrequency ablation (RFA) and surgical resection (SR) for solitary hepatocellular carcinoma (HCC) with size large as 5 cm. Methods: The SEER database was queried for patients with HCC tumors who were treated with RFA or SR between 2004 and 2015. Univariate and multivariate Cox analysis was used to assess the influence of potential variables on the patients' outcome. Additionally, propensity score matching (PSM) and multiple imputations (MI) were used as sensitivity analyses. Results: Of 1,985 cases, 934 patients received RFA treatment, while the rest underwent surgical resection. The patients in the RFA group had poorer overall survival (OS) and cancer-specific survival (CSS) than those in the SR group regardless of the tumor size before matching and MI. By using PSM analysis at a 1:1 ratio, 1,302 cases were paired and we have found that SR had a positive impact on OS and CSS of patients with tumors measuring from 3.1 to 5 cm. However, when the tumor size was <3 cm, patients undergoing SR had similar survival benefit with those after RFA. The above results were confirmed after performing PSM analysis at a 1:2 and 1:3 ratio. Conclusion: By applying several effective sensitivity analyses, we demonstrated that OS and CSS were similar between the patients with tumors smaller than 3 cm receiving RFA and SR. But SR may be a superior treatment option with better long-term outcome than RFA in patients with tumor measuring 3.1–5 cm.
Bacterial Community Structure and Predicted Function in Wheat Soil From the North China Plain Are Closely Linked With Soil and Plant Characteristics After Seven Years of Irrigation and Nitrogen Application

The influence of water and nitrogen (N) management on wheat have been investigated, but studies on the impact of long-term interactive water and N management on microbial structure and function are limited. Soil chemical properties and plants determine the soil microbial communities whose functions involved in nutrient cycling may affect plant productivity. There is an urgent need to elucidate the underlying mechanisms to optimize these microbial communities for agricultural sustainability in the winter wheat production area of the North China Plain. We performed high-throughput sequencing and quantitative PCR of the 16S rRNA gene on soil from a 7-year-old stationary field experiment to investigate the response of bacterial communities and function to water and N management. It was observed that water and N management significantly influenced wheat growth, soil properties and bacterial diversity. N application caused a significant decrease in the number of operational taxonomic units (OTUs), and both Richness and Shannon diversity indices, in the absence of irrigation. Irrigation led to an increase in the relative abundance of Planctomycetes, Latescibacteria, Anaerolineae, and Chloroflexia. In addition, most bacterial taxa were correlated with soil and plant properties. Some functions related to carbohydrate transport, transcription, inorganic ion transport and lipid transport were enriched in irrigation treatment, while N enriched predicted functions related to amino acid transport and metabolism, signal transduction, and cell wall/membrane/envelope biogenesis. Understanding the impact of N application and irrigation on the structure and function of soil bacteria is important for developing strategies for sustainable wheat production. Therefore, concurrent irrigation and N application may improve wheat yield and help to maintain those ecosystem functions that are driven by the soil microbial community.
Calcipotriol Inhibits NLRP3 Signal Through YAP1 Activation to Alleviate Cholestatic Liver Injury and Fibrosis

Cholestasis is common in multiple clinical circumstances. The NOD-like receptor protein 3 (NLRP3) inflammasome pathway has been demonstrated to play an important role in liver injury and fibrosis induced by cholestasis. We previously proved that MCC950, a selective NLRP3 inhibitor, alleviates liver fibrosis and injury in experimental liver cholestasis induced by bile-duct ligation (BDL) in mice. Herein, we investigate the role of calcipotriol, a potent vitamin D receptor agonist, in experimental liver cholestasis, test its therapeutic efficacy, and explore its potential protective mechanism. C57BL/6 mice were made to undergo BDL or fed the 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet to establish two classic cholestatic models. Calcipotriol was administered intraperitoneally to these mice daily. Serum makers of liver damage and integrity, liver histological changes, levels of liver pro-fibrotic markers, bile acid synthetases and transporters were measured in vivo. The underlying mechanism by which calcipotriol alleviates cholestatic liver injury and fibrosis was further investigated. The results of the current study demonstrated that calcipotriol supplement significantly alleviate cholestatic liver injury and fibrosis. Moreover, calcipotriol supplement markedly inhibited NLRP3 inflammasome pathway activation to alleviate liver injury and fibrosis in vivo and inhibit hepatic stellate cell (HSC) activation in vitro. In addition, VDR agonist calcipotriol exert inhibitory effect on NLRP3 inflammasome activation through activating yes-associated protein 1 (YAP1). In conclusion, our findings proved that calcipotriol suppressed the NLRP3 signal by activating YAP1 to alleviate liver injury and retard fibrogenesis in cholestasis.
Phagocytosis of Apoptotic Cells in Resolution of Inflammation

Efficient inflammation resolution is important not only for the termination of the inflammatory response but also for the restoration of tissue integrity. An integral process to resolution of inflammation is the phagocytosis of dying cells by macrophages, known as efferocytosis. This function is mediated by a complex and well-orchestrated network of interactions amongst specialized phagocytic receptors, bridging molecules, as well as “find-me” and “eat-me” signals. Efferocytosis serves not only as a waste disposal mechanism (clearance of the apoptotic cells) but also promotes a pro-resolving phenotype in efferocytic macrophages and thereby termination of inflammation. Alterations in cellular metabolism are critical for shaping the phenotype and function of efferocytic macrophages, thus, representing an important determinant of macrophage plasticity. Impaired efferocytosis can result in inflammation-associated pathologies or autoimmunity. The present mini review summarizes current knowledge regarding the mechanisms regulating macrophage efferocytosis during clearance of inflammation.
The Effects of Cold Water Immersion on the Recovery of Drop Jump Performance and Mechanics: A Pilot Study in Under-20 Soccer Players

Cold water immersion (CWI) is a popular method used for enhancing recovery from exercise. However, the efficacy of this approach is inconclusive and studies investigating variables contributing to overall performance are scarce. Additionally, few studies have investigated the recovery of stretch-shortening cycle (SSC) performance after a fatiguing SSC task. The SSC occurs naturally in human locomotion and induces a recovery pattern different from isolated muscle contractions (e.g., pure eccentric exercise). Therefore, the main aim of this study was to investigate the effects of a single CWI on jumping performance and mechanics after exhaustive SSC exercise. On a sledge apparatus, 10 male under-20 soccer players (age 18–20 years) performed five sets of 20 maximal drop jumps (DJ) followed by continuous submaximal rebounding. Subjects were equally randomized into a passive recovery control (CON) or CWI group (10 ± 0.5°C for 20 min). Prior to, upon completion of, and at 24 and 48 h follow-ups, subjects performed maximal DJs recorded with a high-speed video camera. Blood samples were taken and subjective muscle soreness was measured. Rebound jump height was impaired immediately after exercise, although significant only for CWI (CON: −12.4 cm, p = 0.083; CWI: −9.9 cm, p = 0.009). The CWI group demonstrated significant recovery of jump height at 24 h (+6.3 cm, p = 0.031) and 48 h (+8.9 cm, p = 0.002) compared to post-exercise. Ankle joint stiffness was decreased for CWI (−2.1 to −2.5 Nm/°, p = 0.005–0.041). Creatine kinase activity was similarly increased for both groups at 24 and 48 h, while there was also no group effect in muscle soreness (p ≥ 0.056). This pilot study demonstrates the potential for CWI to slightly enhance the recovery of DJ performance. However, this occurred in parallel with reduced ankle joint stiffness, signifying that jumps were performed with less efficiency, which would not be favorable for repeated SSC actions. While this should be confirmed with a larger sample size, this highlights the potential for CWI to be detrimental to the mechanical properties of the ankle joint. Therefore, future recovery intervention studies should concomitantly investigate variables contributing to performance, rather than just overall performance itself.
Changes in Working Conditions and Mental Health Among Intensive Care Physicians Across a Decade

Background: International studies have shown that among physicians working in intensive care, a relatively high level of work load, an elevated risk of developing burnout and reduced mental health are frequent. The implementation of a legislative intervention in Germany with the goal to reduce the working hours of physicians, offered an opportunity to investigate the potential influence of occupational conditions on stress and mental health. The present study investigates working conditions, occupational stress and burnout risk in two samples of German Intensive Care Physicians in 2006 and 2016. The aim was to assess how occupational and private stress factors influenced burnout and Effort-Reward-Imbalance indices over this time-period. Methods: Intensive care physicians were surveyed during the annual conference of their profession in two cross-sectional studies (10-year gap). Data on demographic (occupational, family), medical history, and mental health (burnout and Effort-Reward-Imbalance) were assessed by paper pencil questionnaires. Results: In total, N = 2,085 physicians participated (2006: N = 1,403, 2016: N = 695), with N = 1,840 (2006 = 1,248; 2016 = 592) eligible for propensity score matching comparison. In general, more working hours per week and working days on weekends were associated with an increased effort/reward imbalance and higher burnout scores. From 2006 to 2016, reductions in working hours per week and days worked on weekends were accompanied by improvements in occupational stress (Effort-Reward-Imbalance) and by trend in mental health indices (burnout) after matching for differences in working conditions. Conclusions: The study presents the changes concerning occupational stress factors and mental wellbeing in physicians working in intensive care in 2016 as compared to 2006. These findings may promote the implementation of preventive strategies in the vocational context to protect health and productivity of physicians, especially intensive care physicians.
Cauliflower mosaic virus (CaMV) Biology, Management, and Relevance to GM Plant Detection for Sustainable Organic Agriculture

In today's global market, some organic farmers must meet regulatory requirements to demonstrate that their plants and feedstocks are genetically modified organism (GMO)-free. Many GM plants are engineered to contain a promoter from the plant virus, Cauliflower mosaic virus (CaMV), in order to facilitate expression of an engineered target gene. The relative ubiquity of this CaMV 35S promoter (P35S) in GM constructs means that assays designed to detect GM plants often target the P35S DNA sequence, but these detection assays can yield false-positives from plants that are infected by naturally-occurring CaMV or its relatives within the Caulimoviridae. This review places CaMV infection and these ambiguous GM plant detection assays in context, serving as a resource for industry professionals, regulatory bodies, and researchers at the nexus of organic farming and global commerce. We first briefly introduce GM plants from a regulatory perspective, and then we describe CaMV biology, transmission, and management practices, highlighting the relatively widespread nature of CaMV infection in both GM and non-GM crops within the Brassicaceae and Solanaceae families. Finally, we discuss current knowledge of public food safety related to the consumption of CaMV-infected produce.