Miracle-dz/UniFAR-FTUs huggingface dataset:
Ferroptosis-related gene signature predicts the clinical outcome in pediatric acute myeloid leukemia patients and refines the 2017 ELN classification system

Background: The prognostic roles of ferroptosis-related mRNAs (FG) and lncRNAs (FL) in pediatric acute myeloid leukemia (P-AML) patients remain unclear. Methods: RNA-seq and clinical data of P-AML patients were downloaded from the TARGET project. Cox and LASSO regression analyses were performed to identify FG, FL, and FGL (combination of FG and FL) prognostic models, and their performances were compared. Tumor microenvironment, functional enrichment, mutation landscape, and anticancer drug sensitivity were analyzed. Results: An FGL model of 22 ferroptosis-related signatures was identified as an independent parameter, and it showed performance better than FG, FL, and four additional public prognostic models. The FGL model divided patients in the discovery cohort (N = 145), validation cohort (N = 111), combination cohort (N = 256), and intermediate-risk group (N = 103) defined by the 2017 European LeukemiaNet (ELN) classification system into two groups with distinct survival. The high-risk group was enriched in apoptosis, hypoxia, TNFA signaling via NFKB, reactive oxygen species pathway, oxidative phosphorylation, and p53 pathway and associated with low immunity, while patients in the low-risk group may benefit from anti-TIM3 antibodies. In addition, patients within the FGL high-risk group might benefit from treatment using SB505124_1194 and JAK_8517_1739. Conclusion: Our established FGL model may refine and provide a reference for clinical prognosis judgment and immunotherapies for P-AML patients.
Identifying gene variants underlying the pathogenesis of diabetic retinopathy based on integrated genomic and transcriptomic analysis of clinical extreme phenotypes

Diabetic retinopathy (DR) is a common complication and the leading cause of blindness in patients with type 2 diabetes. DR has been shown to be closely correlated with blood glucose levels and the duration of diabetes. However, the onset and progression of DR also display clinical heterogeneity. We applied whole-exome sequencing and RNA-seq approaches to study the gene mutation and transcription profiles in three groups of diabetic patients with extreme clinical phenotypes in DR onset, timing, and disease progression, aiming to identify genetic variants that may play roles in the pathogenesis of DR. We identified 23 putatively pathogenic genes, and ingenuity pathway analysis of these mutated genes reveals their functional association with glucose metabolism, diabetic complications, neural system activity, and dysregulated immune responses. In addition, ten potentially protective genes were also proposed. These findings shed light on the mechanisms underlying the pathogenesis of DR and may provide potential targets for developing new strategies to combat DR.
Spatial-temporal changes of iron deposition and iron metabolism after traumatic brain injury in mice

Excessive iron released by hemoglobin and necrotic tissues is the predominant factor that aggravates the outcome of traumatic brain injury (TBI). Regulating the levels of iron and its metabolism is a feasible way to alleviate damage due to TBI. However, the spatial-temporal iron metabolism and iron deposition in neurons and glial cells after TBI remains unclear. In our study, male C57BL/6 mice (8–12 weeks old, weighing 20–26 g) were conducted using controlled cortical impact (CCI) models, combined with treatment of iron chelator deferoxamine (DFO), followed by systematical evaluation on iron deposition, cell-specific expression of iron metabolic proteins and ferroptosis in ipsilateral cortex. Herein, ferroptosis manifest by iron overload and lipid peroxidation was noticed in ipsilateral cortex. Furthermore, iron deposition and cell-specific expression of iron metabolic proteins were observed in the ipsilateral cortical neurons at 1–3 days post-injury. However, iron overload was absent in astrocytes, even though they had intense TBI-induced oxidative stress. In addition, iron accumulation in oligodendrocytes was only observed at 7–14 days post-injury, which was in accordance with the corresponding interval of cellular repair. Microglia play significant roles in iron engulfment and metabolism after TBI, and excessive affects the transformation of M1 and M2 subtypes and activation of microglial cells. Our study revealed that TBI led to ferroptosis in ipsilateral cortex, iron deposition and metabolism exhibited cell-type-specific spatial-temporal changes in neurons and glial cells after TBI. The different effects and dynamic changes in iron deposition and iron metabolism in neurons and glial cells are conducive to providing new insights into the iron-metabolic mechanism and strategies for improving the treatment of TBI.
In vitro and in vivo Studies of Soybean Peptides on Milk Production, Rumen Fermentation, Ruminal Bacterial Community, and Blood Parameters in Lactating Dairy Cows

Soybean peptides (SPs), a feed additive derived from soybean, exhibit nutritional function and biological activity in monogastric animals, but limited studies have been conducted in dairy cows. Our experiments were conducted to evaluate the effects of SPs on the nutrient degradability of dry matter (DM), crude protein (CP), neutral detergent fiber (NDF), and acid detergent fiber (ADF) in vitro and milk production, rumen fermentation and bacterial community, and blood parameters of dairy cows. For in vitro experiment, ruminal fluids were collected from three ruminal cannulated Holstein dairy cows. A total of three levels of SPs (0, 0.38, and 1.92 g/kg DM of SPs) were added to the total mixed ration (TMR). Nutrient degradability and fermentation fluid pH were determined at 24 and 48 h using 3.0 g samples of the substrate. Gas production after 48 h was recorded by an automated trace gas recording system using 0.5 g samples of the substrate. The results showed that DM, NDF, ADF (p < 0.01), and CP (p < 0.05) degradabilities were significantly increased at 1.92 g/kg DM of SPs at 24 h, and asymptotic gas production (p = 0.05) was increased at 48 h. For in vivo experiment, 110 lactating Holstein cows (209.7 ± 65.2 DIM; 37.2 ± 6.4 kg/d milk yield) were randomly assigned to 0 (control group, CON) or 50 g/head/day SPs (SP-supplemented group). Yields of milk (p < 0.05), milk protein (p < 0.05), and milk lactose (0.05 < p < 0.10) increased on SPs supplementation; however, the milk fat percentage decreased (p < 0.05). The concentrations of individual volatile fatty acids (VFAs) (p < 0.05) and superoxide dismutase (SOD) (p < 0.01) were also increased. Rumen bacterial diversity in SP-supplemented cows was higher (p < 0.05). The relative abundances of Rikenellaceae_RC9_gut_group, Butyrivibrio, Selenomonas, and Shuttleworthia were significantly increased and that of Coprococcus was decreased (p < 0.05). Our results showed that supplementing 1.92 g/kg DM of SPs could improve the nutrient degradability in vitro and 50 g/head/day of SPs could improve milk production and antioxidant ability of dairy cows. The rumen bacterial diversity was also enhanced by SP supplementation.
Progression of Vision in Chinese School-Aged Children Before and After COVID-19

Objectives: To investigate the changes of vision, including the prevalence of myopia, hyperopia, poor vision, and the spherical equivalent refraction (SER), in school-aged children before and after the pandemic of Coronavirus Disease 2019 (COVID-19). Methods: A school-based vision screening study was performed on children in 133 primary schools in Wuhan. This study was conducted in 4 consecutive years (2018–2021). Results: A total of 468,094 children (936,188 eyes) were recruited, 255,863 (54.7%) were boys. The SER decreased in 2020 compared to other years after the age of 10. A positive myopia shift was found in younger children aged 6 (0.1 D), 7 (0.05D), and 8 (0.03 D) in 2020 compared to 2019. The progression of vision has improved slightly in 2021. Among the students included in the study, 33.7% were myopia. Conclusion: The vision of older children decreased significantly during the COVID-19. After the pandemic, there is still a high risk for them. In the future, the focus on vision prevention and control should move forward to preschool children.
Circulating microRNA: Myocardium-derived prenatal biomarker of ventricular septal defects

Background: Recently, circulating microRNAs (miRNAs) from maternal blood and amniotic fluid have been used as biomarkers for ventricular septal defect (VSD) diagnosis. However, whether circulating miRNAs are associated with fetal myocardium remains unknown. Methods: Dimethadione (DMO) induced a VSD rat model. The miRNA expression profiles of the myocardium, amniotic fluid and maternal serum were analyzed. Differentially expressed microRNAs (DE-microRNAs) were verified by qRT–PCR. The target gene of miR-1-3p was confirmed by dual luciferase reporter assays. Expression of amniotic fluid-derived DE-microRNAs was verified in clinical samples. Results: MiRNAs were differentially expressed in VSD fetal rats and might be involved in cardiomyocyte differentiation and apoptosis. MiR-1-3p, miR-1b and miR-293-5p were downregulated in the myocardium and upregulated in amniotic fluid/maternal serum. The expression of amniotic fluid-derived DE-microRNAs (miR-1-3p, miR-206 and miR-184) was verified in clinical samples. Dual luciferase reporter assays confirmed that miR-1-3p directly targeted SLC8A1/NCX1. Conclusion: MiR-1-3p, miR-1b and miR-293-5p are downregulated in VSD myocardium and upregulated in circulation and may be released into circulation by cardiomyocytes. MiR-1-3p targets SLC8A1/NCX1 and participates in myocardial apoptosis. MiR-1-3p upregulation in circulation is a direct and powerful indicator of fetal VSD and is expected to serve as a prenatal VSD diagnostic marker.
How to facilitate employees’ green behavior? The joint role of green human resource management practice and green transformational leadership

Given the severity of today’s environmental issues, companies are increasingly making green concepts a key component of their operational strategies. As an essential complement to corporate environmental strategy, employees’ green behavior has received attention from all sectors of society. Based on resource conservation theory, this study explores the formation mechanism of employees’ green behaviors in enterprises starting from two green management tools: green human resource management (HRM) practices and green transformational leadership. Through two-stage questionnaire research, 296 sample data points were obtained, and the research hypotheses were tested by using linear regression analysis. The results showed that green HRM practices in enterprises enhance employees’ green mindfulness and thus stimulate their green behaviors and that green transformational leadership and green self-efficacy play a positive moderating role in the above relationship. These results support the applicability of resource conservation theory in green management and suggest that green HRM practices and green transformational leadership can be used together in the process of green management.
Motor cortex outputs evoked by long-duration microstimulation encode synergistic muscle activation patterns not controlled movement trajectories

The effects of intracortical microstimulation (ICMS) parameters on the evoked electromyographic (EMG) responses and resulting limb movement were investigated. In ketamine-anesthetized cats, paw movement kinematics in 3D and EMG activity from 8 to 12 forelimb muscles evoked by ICMS applied to the forelimb area of the cat motor cortex (MCx) were recorded. The EMG responses evoked by ICMS were also compared to those evoked by focal ictal bursts induced by the iontophoretic ejection of the GABAA receptor antagonist bicuculline methochloride (BIC) at the same cortical point. The effects of different initial limb starting positions on movement trajectories resulting from long-duration ICMS were also studied. The ICMS duration did not affect the evoked muscle activation pattern (MAP). Short (50 ms) and long (500 ms) stimulus trains activated the same muscles in the same proportions. MAPs could, however, be modified by gradually increasing the stimulus intensity. MAPs evoked by focal ictal bursts were also highly correlated with those obtained by ICMS at the same cortical point. Varying the initial position of the forelimb did not change the MAPs evoked from a cortical point. Consequently, the evoked movements reached nearly the same final end point and posture, with variability. However, the movement trajectories were quite different depending on the initial limb configuration and starting position of the paw. The evoked movement trajectory was most natural when the forelimb lay pendant ~ perpendicular to the ground (i.e., in equilibrium with the gravitational force). From other starting positions, the movements did not appear natural. These observations demonstrate that while the output of the cortical point evokes a seemingly coordinated limb movement from a rest position, it does not specify a particular movement direction or a controlled trajectory from other initial positions.
The photosensitizer-based therapies enhance the repairing of skin wounds

Wound repair remains a clinical challenge and bacterial infection is a common complication that may significantly delay healing. Therefore, proper and effective wound management is essential. The photosensitizer-based therapies mainly stimulate the photosensitizer to generate reactive oxygen species through appropriate excitation source irradiation, thereby killing pathogenic microorganisms. Moreover, they initiate local immune responses by inducing the recruitment of immune cells as well as the production of proinflammatory cytokines. In addition, these therapies can stimulate the proliferation, migration and differentiation of skin resident cells, and improve the deposition of extracellular matrix; subsequently, they promote the re-epithelialization, angiogenesis, and tissue remodeling. Studies in multiple animal models and human skin wounds have proved that the superior sterilization property and biological effects of photosensitizer-based therapies during different stages of wound repair. In this review, we summarize the recent advances in photosensitizer-based therapies for enhancing tissue regeneration, and suggest more effective therapeutics for patients with skin wounds.
A multi-stakeholder potential game model in active distribution network considering the bounded rationality of small users

The increase in the penetration rate of distributed renewable energy sources has brought unprecedented challenges to the economic and stable operation of the active distribution network (ADN). To improve the operating efficiency and total benefits of the ADN, it is necessary to establish an optimization model considering the stakeholders’ market behavior and the game relationship among them under the market environment. In this paper, a multi-stakeholder potential game model in the ADN considering the bounded rationality of small users is proposed. The game relationships among five stakeholders, including the distributed photovoltaic generation aggregators, the distributed wind power aggregators, the energy storage operators, the large users and the load aggregators, are modeled on an hourly time scale. Existing research has proved that the game equilibrium of the potential game model must exist. Based on the information transfer and the strategy update mode on the social network, a demand response evolutionary game model for small users is established. Moreover, a distributed algorithm is designed to obtain the pure strategy equilibrium. Finally, a case with five stakeholders and 160 small users is used to verify the rationality and feasibility of the proposed model.
Tumor markers and depression scores are predictive of non-suicidal self-injury behaviors among adolescents with depressive disorder: A retrospective study

Background Non-suicidal self-injury (NSSI) is an important risk factor for suicide in adolescents with depressive disorders; therefore, it is important to predict NSSI occurrence as early as possible. Disturbances in biological rhythms are characteristic manifestations of depressive disorders and can lead to immune dysfunction, leading to changes in tumor markers. This study aimed to produce an index that utilizes tumor markers to predict NSSI behaviors among adolescents with depressive disorders. Methods A total of 120 hospitalized adolescent patients with depressive disorders aged 14–24 years were included in this study. Participants were divided into NSSI and non-NSSI groups based on self-reports using the Ottawa Self-Injury Inventory. Demographics, tumor marker concentrations, other peripheral blood indices, Hamilton Depression Rating Scale (HDRS) scores, and Hamilton Anxiety Rating Scale (HAMA) scores were compared between the two groups. Logistic regression analysis was conducted to develop a joint index, and a receiver operating characteristic (ROC) curve was created to predict NSSI behaviors among adolescents with depressive disorders. Results Compared with the non-NSSI group, the NSSI group had significantly higher insight, retardation, insomnia, hopelessness, psychiatric anxiety, total HDRS and HAMA scores, and significantly higher levels of cancer antigen 125 (CA-125), cancer antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA). In addition, a joint index was developed by combining CA-125, CA19-9, CEA, HDRS total score, HAMA total score and age using multiple logistic regression to predict NSSI behaviors. The area under the curve was 0.831, with a sensitivity and specificity of 0.734 and 0.891, respectively. Conclusion A combination of depression score, tumor marker levels, and age can identify NSSI behaviors among adolescents with depressive disorders.
Role of microRNA alternation in the pathogenesis of gouty arthritis

Gouty arthritis is a common inflammatory disease. The condition is triggered by a disorder of uric acid metabolism, which causes urate deposition and gout flares. MicroRNAs are a class of conserved small non-coding RNAs that bind to the 3’ untranslated region (UTR) of mRNA and regulate the expression of a variety of proteins at the post-transcriptional level. In recent years, attention has been focused on the role of miRNAs in various inflammatory diseases, including gouty arthritis. It is thought that miRNAs may regulate immune function and inflammatory responses, thereby influencing the onset and progression of the disease. This article mainly reviewed the roles of miRNAs in the pathogenesis of gouty arthritis and prospected their potential as diagnostic and prognostic relevant biomarkers and as possible therapeutic targets.
A review of granulocyte colony-stimulating factor receptor signaling and regulation with implications for cancer

Granulocyte colony-stimulating factor receptor (GCSFR) is a critical regulator of granulopoiesis. Studies have shown significant upregulation of GCSFR in a variety of cancers and cell types and have recognized GCSFR as a cytokine receptor capable of influencing both myeloid and non-myeloid immune cells, supporting pro-tumoral actions. This systematic review aims to summarize the available literature examining the mechanisms that control GCSFR signaling, regulation, and surface expression with emphasis on how these mechanisms may be dysregulated in cancer. Experiments with different cancer cell lines from breast cancer, bladder cancer, glioma, and neuroblastoma are used to review the biological function and underlying mechanisms of increased GCSFR expression with emphasis on actions related to tumor proliferation, migration, and metastasis, primarily acting through the JAK/STAT pathway. Evidence is also presented that demonstrates a differential physiological response to aberrant GCSFR signal transduction in different organs. The lifecycle of the receptor is also reviewed to support future work defining how this signaling axis becomes dysregulated in malignancies.
Transcriptome-metabolome analysis reveals how sires affect meat quality in hybrid sheep populations

Crossbreeding improves and enhances meat quality and is widely used in sheep production; however, the molecular mechanisms underlying the meat quality of various crossbred sheep remain unknown. In this study, male Southdown, Suffolk and Hu sheep were crossbred with female Hu sheep, and the transcriptomes and metabolomes of the longissimus dorsi muscle of the F1 generation were sequenced to explore how different sire breeds affect meat quality. The results showed that 631 differentially expressed genes and 119 significantly altered metabolites contributed to muscle development characteristics and meat quality-related diversity (P < 0.05). These genes and metabolites were significantly enriched in lipid metabolism pathways, including arachidonic acid metabolism and PPAR signaling. Several candidate genes were associated with muscle growth, such as MYLK3, MYL10, FIGN, MYH8, MYOM3, LMCD1, and FLRT1. Among these, MYH8 and MYL10 participated in regulating muscle growth and development and were correlated with meat quality-related fatty acid levels (|r| > 0.5 and p < 0.05). We selected mRNA from four of these genes to verify the accuracy of the sequencing data via qRT-PCR. Our findings provide further insight into the key genes and metabolites involved in muscle growth and meat quality in hybrid sheep populations.
Distinct alterations of fecal microbiota refer to the efficacy of adalimumab in Crohn’s disease

Background and Aims: Anti-tumor necrosis factor mAb (i.e., adalimumab, ADA) is currently used in the treatment of patients with Crohn’s disease (CD). However, its regulation on fecal microbiota is still not fully understood. Methods: A retrospective analysis was conducted on 115 patients with CD who received treatment with ADA for 12 weeks at the Inflammatory Bowel Disease Center in Shanghai Tenth People’s Hospital and Department of Gastroenterology in Shanghai General Hospital. The Crohn’s disease activity index (CDAI) evaluation was applied to patients before ADA therapy at week 0, 4, 8, and 12. Clinical remission (CR) was defined as the CDAI < 150. All patients underwent ileocolonoscopy or enteroscopy at baseline (week 0) and week 12. Crohn’s Disease Endoscopic Index of Severity (CDEIS) scores were calculated by two experienced physicians to assess endoscopic activity. Mucosal healing (MH) was assigned a CDEIS score between 0 and 3. Fecal samples were collected from eight CD patients at baseline and week 12, and the microbiota was analyzed by using 16S RNA sequencing. Results: At week 12, CR was achieved in 70.6% (72/102) of the patients with active CD. A total of 47.1% (48/102) of the patients with active CD attained MH, among which, 56.6% (30/53) of the patients with mildly active CD (3 ≤ CDEIS <9) and 48.0% (12/25) of the moderately active CD patients (9 ≤ CDEIS <12) attained MH, but only 25.0% (6/24) achieved MH in severely active CD patients (CDEIS ≥12). The efficacy of ADA was not associated with lesion locations (χ 2 = 0.409, p = 0.815). Unexpectedly, we found an increase in protective microbiota at the genus level (e.g., Barnesiella, Anaerostipes, Tyzzerella, Lachnoclostridium, and Lachnospiraceae_unclassified) but a decrease in pathogenic bacteria (Escherichia–Shigella) in fecal samples of the ADA-responsive group (ADA-R) when compared with those in the ADA-nonresponsive group (ADA-NR). Notably, the gene bglX coding β-glucosidase and gph encoding phosphoglycolate phosphatase were enriched in fecal samples of ADA-R. Conversely, the abundance of genes coding ATP-binding cassette (ABC) transporter system proteins was significantly enriched in fecal samples of ADA-NR when compared with that of the ADA-R. Conclusion: This study reveals that ADA markedly improves clinical remission and induces MH in mildly to moderately active CD patients and that distinct changes in the gut microbiota can be used to predict the efficacy of ADA.