Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel myeloma patient-derived xenograft models unveil the potency of anlotinib to overcome bortezomib resistance

Multiple myeloma (MM) remains a common hematologic malignancy with a 10-year survival rate below 50%, which is largely due to disease relapse and resistance. The lack of a simple and practical approach to establish myeloma patient-derived xenograft (PDX) hampers translational myeloma research. Here, we successfully developed myeloma PDXs by subcutaneous inoculation of primary mononuclear cells from MM patients following series tumor tissue transplantations. Newly established myeloma PDXs retained essential cellular features of MM and recapitulated their original drug sensitivities as seen in the clinic. Notably, anlotinib therapy significantly suppressed the growth of myeloma PDXs even in bortezomib-resistant model. Anlotinib treatments polarized tumor-associated macrophages from an M2- to an M1-like phenotype, decreased tumor vascular function, and accelerated cell apoptosis in myeloma PDXs. Our preclinical work not only unveiled the potency of anlotinib to overcome bortezomib resistance, but also provided a more practical way to establish MM PDX to facilitate myeloma research.
Intermediate filaments: Integration of cell mechanical properties during migration

Cell migration is a vital and dynamic process required for the development of multicellular organisms and for immune system responses, tissue renewal and wound healing in adults. It also contributes to a variety of human diseases such as cancers, autoimmune diseases, chronic inflammation and fibrosis. The cytoskeleton, which includes actin microfilaments, microtubules, and intermediate filaments (IFs), is responsible for the maintenance of animal cell shape and structural integrity. Each cytoskeletal network contributes its unique properties to dynamic cell behaviour, such as cell polarization, membrane protrusion, cell adhesion and contraction. Hence, cell migration requires the dynamic orchestration of all cytoskeleton components. Among these, IFs have emerged as a molecular scaffold with unique mechanical features and a key player in the cell resilience to mechanical stresses during migration through complex 3D environment. Moreover, accumulating evidence illustrates the participation of IFs in signalling cascades and cytoskeletal crosstalk. Teaming up with actin and microtubules, IFs contribute to the active generation of forces required for cell adhesion and mesenchymal migration and invasion. Here we summarize and discuss how IFs integrate mechanical properties and signalling functions to control cell migration in a wide spectrum of physiological and pathological situations.
Exploring strain diversity of dominant human skin bacterial species using single-cell genome sequencing

To understand the role of the skin commensal bacterial community in skin health and the spread of pathogens, it is crucial to identify genetic differences in the bacterial strains corresponding to human individuals. A culture-independent genomics approach is an effective tool for obtaining massive high-quality bacterial genomes. Here we present a single-cell genome sequencing to obtain comprehensive whole-genome sequences of uncultured skin bacteria from skin swabs. We recovered 281 high-quality (HQ) and 244 medium-quality single-amplified genomes (SAGs) of multiple skin bacterial species from eight individuals, including cohabiting group. Single-cell sequencing outperformed in the genome recovery from the same skin swabs, showing 10-fold non-redundant strain genomes compared to the shotgun metagenomic sequencing and binning approach. We then focused on the abundant skin bacteria and identified intra-species diversity, especially in 47 Moraxella osloensis derived HQ SAGs, characterizing the strain-level heterogeneity at mobile genetic element profiles, including plasmids and prophages. Even between the cohabiting individual hosts, they have unique skin bacterial strains in the same species, which shows microdiversity in each host. Genetic and functional differences between skin bacterial strains are predictive of in vivo competition to adapt bacterial genome to utilize the sparse nutrients available on the skin or produce molecules that inhibit the colonization of other microbes or alter their behavior. Thus, single-cell sequencing provides a large number of genomes of higher resolution and quality than conventional metagenomic analysis and helps explore the skin commensal bacteria at the strain level, linking taxonomic and functional information.
Real-time mental stress detection using multimodality expressions with a deep learning framework

Mental stress is becoming increasingly widespread and gradually severe in modern society, threatening people’s physical and mental health. To avoid the adverse effects of stress on people, it is imperative to detect stress in time. Many studies have demonstrated the effectiveness of using objective indicators to detect stress. Over the past few years, a growing number of researchers have been trying to use deep learning technology to detect stress. However, these works usually use single-modality for stress detection and rarely combine stress-related information from multimodality. In this paper, a real-time deep learning framework is proposed to fuse ECG, voice, and facial expressions for acute stress detection. The framework extracts the stress-related information of the corresponding input through ResNet50 and I3D with the temporal attention module (TAM), where TAM can highlight the distinguishing temporal representation for facial expressions about stress. The matrix eigenvector-based approach is then used to fuse the multimodality information about stress. To validate the effectiveness of the framework, a well-established psychological experiment, the Montreal imaging stress task (MIST), was applied in this work. We collected multimodality data from 20 participants during MIST. The results demonstrate that the framework can combine stress-related information from multimodality to achieve 85.1% accuracy in distinguishing acute stress. It can serve as a tool for computer-aided stress detection.
Buffalo long non-coding RNA gene11007 promotes myoblasts proliferation

Buffalo meat is of good quality because it is lean and tender, and could bring significant cardiovascular benefits. The underlying difference in muscle development and meat quality is a complex and precisely orchestrated process which has been demonstrated to be regulated by long non-coding RNAs (lncRNAs). However, the regulatory role of lncRNAs in the growth and development of buffalo skeletal muscle is still unclear. In this study, the Ribo-Zero RNA-Seq method was used to explore the lncRNA expression profiles of buffalo myoblasts during the proliferation and differentiation phases. A specific set of 9,978 lncRNAs was found. By comparing the expression profiles of lncRNAs, it was found that there were 1,576 differentially expressed lncRNAs (DELs) during buffalo myoblast differentiation. Twelve DELs were chosen and subsequently verified in eight different buffalo tissues during fetal and adult stages by using qPCR. Gene11007 was found to be one of the most down-regulated lncRNAs during buffalo myoblasts differentiation and it was subsequently characterized. EdU, CCK-8, qPCR and western blotting assays showed that gene11007 promoted the proliferation of buffalo myoblasts but it had no effect on cell differentiation. Our research may enrich the genome annotations of buffalo and provide a new molecular target for the in-depth understanding of the regulation of lncRNAs in skeletal muscle.
Influencing factors for effective teaching evaluation of massively open online courses in the COVID-19 epidemics: An exploratory study based on grounded theory

Many factors affect the teaching of massively open online courses (MOOCs). In this study, to explore the factors that influence the effective teaching of MOOCs, a large number of relevant studies are analyzed. Based on grounded theory, semi-structured interviews were conducted with 30 students and teachers who used MOOCs for online teaching. The interview data were subjected to four research processes –open coding, axial coding, selective coding, and saturation testing– to explore the factors influencing MOOCs’ effective teaching and the interactions between them. The results demonstrate that: (1) Effective teachers, effective tuition, effective communication, active online learning, social support guarantees, and online course design have important positive effects on effective teaching, while only certain online learning behaviors will seriously affect the teaching effectiveness of MOOC, resulting in negative effects. (2) Effective communication is essential for effective teaching in MOOCs; effective teachers are the leading factor, thus teachers should take the initiative to study and understand the students to understand their various learning needs and difficulties. (3) Reasonable and effective classroom teaching design is key to improving MOOCs’ teaching efficiency. (4) E-learning is respected, cared for, and valued by society, including cognition, emotion, and learning platform support from family, school, teachers, and classmates, and has an important impact on students’ motivation and the effects of online learning. The results of this study further clarify factors influencing effective teaching of MOOCs, thus helping to enrich and supplement the theory of effective teaching and evaluation and providing theoretical guidance for teachers to effectively implement MOOC teaching.
Exendin-4 alleviates β-Amyloid peptide toxicity via DAF-16 in a Caenorhabditis elegans model of Alzheimer's disease

Epidemiological analyses indicate that type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer's disease (AD). They share common pathophysiological mechanisms. Thus, it has been increasingly suggested that several anti-T2DM drugs may have therapeutic potential in AD. Exendin-4, as a glucagon-like peptide-1 (GLP-1) receptor agonist, is an approved drug used to treat T2DM. In this research, the neuroprotective effect of Exendin-4 was investigated for the first time using transgenic Caenorhabditis elegans. Our results demonstrated that Exendin-4 attenuated the amyloid-β (1-42) (Aβ1-42) toxicity via multiple mechanisms, such as depressing its expression on protein and mRNA and reducing Aβ (1-42) accumulation. Exendin-4 at 0.5 mg/ml had been shown to extend life by 34.39% in CL4176 and delay the onset of paralysis in CL4176 and CL2006 which were increased by 8.18 and 8.02%, respectively. With the treatment of Exendin-4, the nuclear translocation of DAF-16 in the transgenic nematode TJ356 was enhanced. Superoxide dismutase-3 (SOD-3), as a downstream target gene regulated by DAF-16, was upregulated on mRNA level and activity. The reactive oxygen species (ROS) level was decreased. In contrast, we observed that the ability of Exendin-4 to regulate SOD was decreased in CL4176 worms with the DAF-16 gene silenced. The activity of SOD and the mRNA level of sod-3 were downregulated by 30.45 and 43.13%, respectively. Taken together, Exendin-4 attenuated Aβ (1-42) toxicity in the C. elegans model of AD via decreasing the expression and the accumulation of Aβ (1-42). Exendin-4 exhibited the ability of antioxidant stress through DAF-16. With continuous research, Exendin-4 would become a potential therapeutic strategy for treating AD.
Gut microbiota in women with gestational diabetes mellitus has potential impact on metabolism in pregnant mice and their offspring

Studies have shown that gestational diabetes mellitus (GDM) is closely related to abnormalities in the gut microbiota, and the offspring of these women have an increased risk of diabetes. There is no direct evidence of whether bacteria in women with GDM colonize the intestinal tract of offspring and cause hyperglycemia. In this fecal microbiota transplantation (FMT), pregnant mouse model study, two groups of germ-free (GF) mice after FMT showed different colonization patterns of gut microbiota and phenotype. Compared with the control group (healthy-FMT), we found in the GDM-FMT group as a lower relative abundance of Akkermansia and Faecalibacterium; a lower content of short-chain fatty acids and naringenin in feces; an elevated blood glucose; an inflammatory factor expression (TNF-α, CXCL-15, and IL-6), and a hepatic fat deposition. In addition, the influence of the gut microbiota continued in offspring. The gut microbiota of the offspring of GDM-FMT mice was still different from that of the control group as a lower relative abundance of Akkermansia and Parvibacter; and a higher relative abundance of bacteria such as Oscillibacter, Romboutsia, and Harryflintia. In addition, the offspring of GDM-FMT mice had higher body weight and blood glucose levels than the control offspring.
Medical image registration utilizing tissue P systems

The tissue P system (TPS) possesses intrinsic attributes of parallel execution in comprehensive data and instruction space, which provides fast convergence during the transition from local to global optima. Method- In this study, we have proposed and built a TPSysIR framework using the TPS for image registration that optimizes upon the mutual information (MI) similarity metric to find a global solution. Result- The model was tested on single- and multimodal brain MRI scans and other prominent optimization-based image registration techniques. Conclusion- Results show that, among all methods, TPSysIR provides better MI values with minimum deviation in a range of experiment setups conducted iteratively.
Intramuscular coherence during challenging walking in incomplete spinal cord injury: Reduced high-frequency coherence reflects impaired supra-spinal control

Individuals regaining reliable day-to-day walking function after incomplete spinal cord injury (iSCI) report persisting unsteadiness when confronted with walking challenges. However, quantifiable measures of walking capacity lack the sensitivity to reveal underlying impairments of supra-spinal locomotor control. This study investigates the relationship between intramuscular coherence and corticospinal dynamic balance control during a visually guided Target walking treadmill task. In thirteen individuals with iSCI and 24 controls, intramuscular coherence and cumulant densities were estimated from pairs of Tibialis anterior surface EMG recordings during normal treadmill walking and a Target walking task. The approximate center of mass was calculated from pelvis markers. Spearman rank correlations were performed to evaluate the relationship between intramuscular coherence, clinical parameters, and center of mass parameters. In controls, we found that the Target walking task results in increased high-frequency (21–44 Hz) intramuscular coherence, which negatively related to changes in the center of mass movement, whereas this modulation was largely reduced in individuals with iSCI. The impaired modulation of high-frequency intramuscular coherence during the Target walking task correlated with neurophysiological and functional readouts, such as motor-evoked potential amplitude and outdoor mobility score, as well as center of mass trajectory length. The Target walking effect, the difference between Target and Normal walking intramuscular coherence, was significantly higher in controls than in individuals with iSCI [F(1.0,35.0) = 13.042, p < 0.001]. Intramuscular coherence obtained during challenging walking in individuals with iSCI may provide information on corticospinal gait control. The relationships between biomechanics, clinical scores, and neurophysiology suggest that intramuscular coherence assessed during challenging tasks may be meaningful for understanding impaired supra-spinal control in individuals with iSCI.
Anterior cingulate cortex and its projections to the ventral tegmental area regulate opioid withdrawal, the formation of opioid context associations and context-induced drug seeking

Clinical evidence suggests that there are correlations between activity within the anterior cingulate cortex (ACC) following re-exposure to drug-associated contexts and drug craving. However, there are limited data contributing to our understanding of ACC function at the cellular level during re-exposure to drug-context associations as well as whether the ACC is directly related to context-induced drug seeking. Here, we addressed this issue by employing our novel behavioral procedure capable of measuring the formation of drug-context associations as well as context-induced drug-seeking behavior in male mice (8–12 weeks of age) that orally self-administered oxycodone. We found that mice escalated oxycodone intake during the long-access training sessions and that conditioning with oxycodone was sufficient to evoke conditioned place preference (CPP) and drug-seeking behaviors. Additionally, we found that thick-tufted, but not thin-tufted pyramidal neurons (PyNs) in the ACC as well as ventral tegmental area (VTA)-projecting ACC neurons had increased intrinsic membrane excitability in mice that self-administered oxycodone compared to controls. Moreover, we found that global inhibition of the ACC or inhibition of VTA-projecting ACC neurons was sufficient to significantly reduce oxycodone-induced CPP, drug seeking, and spontaneous opioid withdrawal. These results demonstrate a direct role of ACC activity in mediating context-induced opioid seeking among other behaviors, including withdrawal, that are associated with the DSM-V criteria of opioid use disorder.
Copper-containing nanoparticles: Mechanism of antimicrobial effect and application in dentistry-a narrative review

Copper has been used as an antimicrobial agent long time ago. Nowadays, copper-containing nanoparticles (NPs) with antimicrobial properties have been widely used in all aspects of our daily life. Copper-containing NPs may also be incorporated or coated on the surface of dental materials to inhibit oral pathogenic microorganisms. This review aims to detail copper-containing NPs’ antimicrobial mechanism, cytotoxic effect and their application in dentistry.
Editorial: Cellular dormancy—State determination and plasticity

Most cells in the adult human body are non-dividing. Among these dormant cells, many are postmitotic and permanently out of the cell cycle (e.g., terminally differentiated and senescent cells), while a small sub-population, namely quiescent cells (such as adult stem and progenitor cells), can re-enter the cell cycle and divide in response to physiological cues. The balance between cell proliferation and dormancy plays critical roles in tissue homeostasis, repair, regeneration, and development. Pathological changes in cellular dormancy can lead to a wide range of hyperor hypo-proliferation diseases, including cancer, fibrosis, autoimmunity, anemia, and aging. Cellular dormancy exhibits significant heterogeneity and plasticity. Like sleep that has shallow and deep stages, dormancy appears to have different depths that are inversely correlated with the likelihood of cell cycle re-entry upon stimulation (Coller et al., 2006; Rodgers et al., 2014; Kwon et al., 2017). We lack a fundamental understanding of what determines and shapes cellular dormancy states: What cellular activities control dormancy entry, maintenance, and exit? What physiological signals regulate cell dormancy in different tissues and organs? Can we manipulate dormant states to improve human health, e.g., against aging and cancer? This Research Topic includes original research and review articles that address the fascinating and complex states of cell dormancy in both human and model organisms. Three broad themes are collectively addressed: OPEN ACCESS
Predicting and mitigating fatigue effects due to sleep deprivation: A review

The deleterious effects of insufficient sleep have been well-established in the literature and can lead to a wide range of adverse health outcomes. Some of the most replicated findings demonstrate significant declines in cognitive functions such as vigilance and executive attention, psychomotor and cognitive speed, and working memory. Consequently, these decrements often lead individuals who are in a fatigued state to engage in substandard performance on everyday tasks. In the interest of curtailing these effects, prior work has attempted to identify mechanisms that predict fatigue onset and develop techniques to mitigate its negative consequences. Nonetheless, these results are often confounded by variables such as an individual’s resistance to fatigue, sleep history, and unclear distinctions about whether certain performance decrements are present due to fatigue or due to other confounding factors. Similar areas of research have provided approaches to produce models for the prediction of cognitive performance decrements due to fatigue through the use of multi-modal recording and analysis of fatigue-related responses. Namely, gathering and combining response information from multiple sources (i.e., physiological and behavioral) at multiple timescales may provide a more comprehensive representation of what constitutes fatigue onset in the individual. Therefore, the purpose of this review is to discuss the relevant literature on the topic of fatigue-related performance effects with a special emphasis on a variety of physiological and behavioral response variables that have shown to be sensitive to changes in fatigue. Furthermore, an increasing reliance on sleep loss, meant to assist in meeting the demands of modern society, has led to an upsurge in the relevance of identifying dependable countermeasures for fatigued states. As such, we will also review methods for the mitigation of performance effects due to fatigue and discuss their usefulness in regulating these effects. In sum, this review aims to inspire future work that will create opportunities to detect fatigue and mitigate its effects prior to the onset of cognitive impairments.