Miracle-dz/UniFAR-FTUs huggingface dataset:
Paeoniflorin Protects against ANIT-Induced Cholestatic Liver Injury in Rats via the Activation of SIRT1-FXR Signaling Pathway

Paeoniflorin (PF), a water-soluble monoterpene glycoside, is initially isolated from the dried roots of Paeonia lactiflora Pall. , which has effects on ameliorating cholestasis in our previous study. However, comprehensive approaches for understanding the protective effects and mechanisms underlying cholestatic liver injury from the regulating of bile acid metabolism have not been sufficiently elucidated. This study was aimed to explore the effectiveness as well as potential mechanism of PF on alpha-naphthylisothiocyanate (ANIT)-induced cholestatic liver injury. Rats with cholestasis induced by ANIT was used to evaluate the protective effects and mechanism of PF by regulating SIRT1/FXR and NF-κB/NLRP3 signaling pathway. Rats were intragastrically administrated with ANIT to establish cholestatic liver injury model. Serum levels of ALT, AST, TBA, TBIL, ALP, γ-GT and ALB in rats were detected. The histopathology of the liver of rats was analyzed in vivo. The relative mRNA expression and protein expression levels of IL-18, IL-1β, TNF-α, HO-1, Nrf2, TLR4, NLRP3, Caspase-1, ASC, NF-κB, FXR, and SIRT1 in liver of rats were investigated. The results showed that the serum indexes and the liver histopathology were significantly improved by PF. The overexpression of IL-18, IL-1β, TNF-α, NLRP3, ASC, and Caspase-1 in liver was markedly reduced by PF. Furthermore, PF dramatically increased the mRNA and protein expressions of SIRT1, FXR, HO-1, and Nrf2, but decreased NF-κB p65 and TLR4 levels in liver of rats. Taken together, the protective effects of PF on cholestatic liver injury were possibly related to the activation of the SIRT1/FXR and inhibition of NF-κB/NLRP3 inflammasome signaling pathway. These findings might provide a potential protection for cholestatic liver injury.
Increased Angiogenin Expression Correlates With Radiation Resistance and Predicts Poor Survival for Patients With Nasopharyngeal Carcinoma

Background: Despite the development of such multiple therapeutic approaches, approximately 20% patients experience recurrence. Identification of molecular markers for stratifying the different risks of tumour recurrence and progression is considered imperative. Methods: We used a RayBio Human Cytokine Antibody Array that simultaneously detected the levels of 297 proteins and profiled the conditioned medium of HONE1 cells and the radioresistant NPC cells HONE1-IR. We found Angiogenin(ANG) expression to be significantly increased in HONE1-IR and HONE1-IR cells exposed to 4-Gy X-ray radiation. Results: We investigated the expression of ANG in NPC tissues and explored its prognostic significance in patients with NPC. We found that ANG expression was increased in recurrent NPC tissues. Elevated expression of ANG induced radio-resistance in NPC cells, in addition to being significantly associated with shorter PFS, OS, and LRFS in patients with NPC. Multivariate analysis results revealed that ANG was an independent prognostic factor that predicted PFS, OS, and LRFS. Furthermore, a nomogram model was generated to predict OS in terms of ANG expression. Conclusion: Our results found the radioresistant function of ANG and proved the clinical prognostic significance of ANG, and the results could help predict radio-sensitivity and stratify high-risk patients or tumour recurrence.
Neuropathology in the North American sudden unexpected death in epilepsy registry

Abstract Sudden unexpected death in epilepsy is the leading category of epilepsy-related death and the underlying mechanisms are incompletely understood. Risk factors can include a recent history and high frequency of generalized tonic-clonic seizures, which can depress brain activity postictally, impairing respiration, arousal and protective reflexes. Neuropathological findings in sudden unexpected death in epilepsy cases parallel those in other epilepsy patients, with no implication of novel structures or mechanisms in seizure-related deaths. Few large studies have comprehensively reviewed whole brain examination of such patients. We evaluated 92 North American Sudden unexpected death in epilepsy Registry cases with whole brain neuropathological examination by board-certified neuropathologists blinded to the adjudicated cause of death, with an average of 16 brain regions examined per case. The 92 cases included 61 sudden unexpected death in epilepsy (40 definite, 9 definite plus, 6 probable, 6 possible) and 31 people with epilepsy controls who died from other causes. The mean age at death was 34.4 years and 65.2% (60/92) were male. The average age of death was younger for sudden unexpected death in epilepsy cases than for epilepsy controls (30.0 versus 39.6 years; P = 0.006), and there was no difference in sex distribution respectively (67.3% male versus 64.5%, P = 0.8). Among sudden unexpected death in epilepsy cases, earlier age of epilepsy onset positively correlated with a younger age at death (P = 0.0005) and negatively correlated with epilepsy duration (P = 0.001). Neuropathological findings were identified in 83.7% of the cases in our cohort. The most common findings were dentate gyrus dysgenesis (sudden unexpected death in epilepsy 50.9%, epilepsy controls 54.8%) and focal cortical dysplasia (FCD) (sudden unexpected death in epilepsy 41.8%, epilepsy controls 29.0%). The neuropathological findings in sudden unexpected death in epilepsy paralleled those in epilepsy controls, including the frequency of total neuropathological findings as well as the specific findings in the dentate gyrus, findings pertaining to neurodevelopment (e.g. FCD, heterotopias) and findings in the brainstem (e.g. medullary arcuate or olivary dysgenesis). Thus, like prior studies, we found no neuropathological findings that were more common in sudden unexpected death in epilepsy cases. Future neuropathological studies evaluating larger sudden unexpected death in epilepsy and control cohorts would benefit from inclusion of different epilepsy syndromes with detailed phenotypic information, consensus among pathologists particularly for more subjective findings where observations can be inconsistent, and molecular approaches to identify markers of sudden unexpected death in epilepsy risk or pathogenesis.
Regional Expression of npy mRNA Paralogs in the Brain of Atlantic Salmon (Salmo salar, L.) and Response to Fasting

Neuropeptide Y (NPY) is known as a potent orexigenic signal in vertebrates, but its role in Atlantic salmon has not yet been fully established. In this study, we identified three npy paralogs, named npya1, npya2, and npyb, in the Atlantic salmon genome. In silico analysis revealed that these genes are well conserved across the vertebrate’s lineage and the mature peptide sequences shared at least 77% of identity with the human homolog. We analyzed mRNA expression of npy paralogs in eight brain regions of Atlantic salmon post-smolt, and the effect of 4 days of fasting on the npy expression level. Results show that npya1 was the most abundant paralog, and was predominantly expressed in the telencephalon, followed by the midbrain and olfactory bulb. npya2 mRNA was highly abundant in hypothalamus and midbrain, while npyb was found to be highest expressed in the telencephalon, with low mRNA expression levels detected in all the other brain regions. 4 days of fasting resulted in a significant (p < 0.05) decrease of npya1 mRNA expression in the olfactory bulb, increased npya2 mRNA expression in the midbrain and decreased npyb mRNA expression in the pituitary. In the hypothalamus, the vertebrate appetite center, expression of the npy paralogs was not significantly affected by feeding status. However, we observed a trend of increased npya2 mRNA expression (p = 0.099) following 4 days of fasting. Altogether, our findings provide a solid basis for further research on appetite and energy metabolism in Atlantic salmon.
A Prehepatectomy Circulating Exosomal microRNA Signature Predicts the Prognosis and Adjuvant Chemotherapeutic Benefits in Colorectal Liver Metastasis

Simple Summary Exosomal miRNAs are associated with colorectal cancer liver metastasis (CRLM)-related biological behavior and prognosis. However, an exosomal miRNA signature predicting postoperative survival and the value of adjuvant chemotherapy for CRLM remains elusive. Using miRNA sequencing and the LASSO model, we constructed an miRNA signature comprising four exosomes. The signature showed a good predictive performance for patient outcome and the advantage of adjuvant chemotherapy after hepatectomy in two institutions’ training and validation cohorts. In addition, we found that the four miRNAs could target signaling molecules playing crucial roles in colorectal cancer metastasis, vesicle-related processing, and T cell activation. Furthermore, the exosomal miRNA score also increased with the decreasing Immunoscore. We believe that our signature can predict the prognosis and guide adjuvant chemotherapy decisions after liver metastasectomy in CRLM patients, further improving the predictive performance of the current CRLM predictive model system. Abstract Background: The clinical risk score (CRS) for prediction and treatment decision in colorectal liver metastasis (CRLM) is important, but imprecise. Exosomal miRNAs play critical roles in CRLM-related biological behavior. However, an exosomal miRNA score system for predicting posthepatectomy survival and the adjuvant chemotherapy benefit of CRLM remains elusive. Methods: miRNA sequencing was used to identify differentially expressed miRNAs, and the LASSO model was used to select miRNAs to construct the intent model. The predictive performance of the model was evaluated by the area under the ROC curve (AUC) in the training, internal validation, and external validation cohorts. Results: Sixteen differentially expressed exosomal miRNAs were identified, and four miRNAs were selected for model construction. Our model performed well in predicting prognosis with five-year AUCs of 0.70 (95% CI: 0.59–0.81), 0.70 (0.61–0.81), and 0.72 (057–0.86) in the training, internal, and external validation cohorts, respectively. miRNA classifier high-risk patients had better survival benefit from adjuvant chemotherapy regardless of CRS. All four miRNAs target signaling molecules play crucial roles in colorectal cancer metastasis, vesicle-related processing, and T cell activation. It also negatively correlated with the liver metastasis Immunoscore. Conclusion: We developed a circulating exosomal miRNA signature that can predict the prognosis and guide adjuvant chemotherapy decisions after hepatectomy in CRLM.
Preclinical and clinical progress for HDAC as a putative target for epigenetic remodeling and functionality of immune cells

Genetic changes are difficult to reverse; thus, epigenetic aberrations, including changes in DNA methylation, histone modifications, and noncoding RNAs, with potential reversibility, have attracted attention as pharmaceutical targets. The current paradigm is that histone deacetylases (HDACs) regulate gene expression via deacetylation of histone and nonhistone proteins or by forming corepressor complexes with transcription factors. The emergence of epigenetic tools related to HDACs can be used as diagnostic and therapeutic markers. HDAC inhibitors that block specific or a series of HDACs have proven to be a powerful therapeutic treatment for immune-related diseases. Here, we summarize the various roles of HDACs and HDAC inhibitors in the development and function of innate and adaptive immune cells and their implications for various diseases and therapies.
Genome-Wide Association Study of Waterlogging Tolerance in Barley (Hordeum vulgare L.) Under Controlled Field Conditions

Waterlogging is one of the main abiotic stresses severely reducing barley grain yield. Barley breeding programs focusing on waterlogging tolerance require an understanding of genetic loci and alleles in the current germplasm. In this study, 247 worldwide spring barley genotypes grown under controlled field conditions were genotyped with 35,926 SNPs with minor allele frequency (MAF) > 0.05. Significant phenotypic variation in each trait, including biomass, spikes per plant, grains per plant, kernel weight per plant, plant height and chlorophyll content, was observed. A genome-wide association study (GWAS) based on linkage disequilibrium (LD) for waterlogging tolerance was conducted. Population structure analysis divided the population into three subgroups. A mixed linkage model using both population structure and kinship matrix (Q+K) was performed. We identified 17 genomic regions containing 51 significant waterlogging-tolerance-associated markers for waterlogging tolerance response, accounting for 5.8–11.5% of the phenotypic variation, with a majority of them localized on chromosomes 1H, 2H, 4H, and 5H. Six novel QTL were identified and eight potential candidate genes mediating responses to abiotic stresses were located at QTL associated with waterlogging tolerance. To our awareness, this is the first GWAS for waterlogging tolerance in a worldwide barley collection under controlled field conditions. The marker-trait associations could be used in the marker-assisted selection of waterlogging tolerance and will facilitate barley breeding.
Scoring System Based on RNA Modification Writer-Related Genes to Predict Overall Survival and Therapeutic Response in Bladder Cancer

Introduction It’s widely reported the “writer” enzymes mediated RNA adenosine modifications which is known as a crucial mechanism of epigenetic regulation in development of tumor and the immunologic response in many kinds of cancers. However, the potential roles of these writer genes in the progression of bladder cancer (BLCA) remain unclear. Materials and Methods We comprehensively described the alterations of 26 RNA modification writer genes in BLCA from the genetic and transcriptional fields and identified writer-related genes from four independent datasets. Utilizing least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression, we constructed a ten writer-related gene signature. After that, we confirmed the predictive and prognostic value of this signature on another six independent datasets and established a nomogram to forecast the overall survival (OS) and mortality odds of BLCA patients clinically. Results The writer-related genes signature showed good performance in predicting the OS for BLCA patients. Moreover, the writer-related gene signature was related to EMT-related pathways and immune characteristics. Furthermore, the immune cell infiltration levels of CD8 T cells, cytotoxic cells, M1/2 macrophage cells and tumor mutation burden might be able to predict which patients will benefit from immunotherapy. This could also be reflected by the writer-related gene signature. Conclusions This signature might play an important role in precision individualized immunotherapy. The present work highlights the crucial clinical implications of RNA modifications and may help developing individualized therapeutic strategies for patients with BLCA.
General Techno-Economic Analysis of CO2 Electrolysis Systems

The electrochemical reduction of carbon dioxide (CO2) has received significant attention in academic research, although the techno-economic prospects of the technology for the large-scale production of chemicals are unclear. In this work, we briefly reviewed the current state-of-the-art CO2 reduction figures of merit, and performed an economic analysis to calculate the end-of-life net present value (NPV) of a generalized CO2 electrolyzer system for the production of 100 tons/day of various CO2 reduction products. Under current techno-economic conditions, carbon monoxide and formic acid were the only economically viable products with NPVs of $13.5 million and $39.4 million, respectively. However, higher-order alcohols such as ethanol and n-propanol could be highly promising under future conditions if reasonable electrocatalytic performance benchmarks are achieved (e.g. 300mA/cm2 and 0.5V overpotential at 70% faradaic efficiency). Herein, we established performance targets such that if these targets are ach.
Cardioprotective Roles of Endothelial Progenitor Cell-Derived Exosomes

With the globally increasing prevalence, cardiovascular diseases (CVDs) have become the leading cause of mortality. The transplantation of endothelial progenitor cells (EPCs) holds a great promise due to their potential for vasculogenesis, angiogenesis, and protective cytokine release, whose mechanisms are essential for CVD therapies. In reality, many investigations have attributed the therapeutic effects of EPC transplantation to the secretion of paracrine factors rather than the differentiation function. Of note, previous studies have suggested that EPCs could also release exosomes (diameter range of 30–150 nm), which carry various lipids and proteins and are abundant in microRNAs. The EPC-derived exosomes (EPC-EXs) were reported to act on the heart and blood vessels and were implicated in anti-inflammation, anti-oxidation, anti-apoptosis, the inhibition of endothelial-to-mesenchymal transition (EndMT), and cardiac fibrosis, as well as anti-vascular remodeling and angiogenesis, which were considered as protective effects against CVDs. In this review, we summarize the current knowledge on using EPC-EXs as therapeutic agents and provide a detailed description of their identified mechanisms of action to promote the prognosis of CVDs. Graphical Abstract EPC-EXs: The hallmarks and pleiotropic functions. EPC-EXs are extracellular vesicles generated by EPCs and they carry lipids, proteins, nucleic acids, metabolites, and some EPC markers. They mediate intercellular communication and affect various aspects of cell biology.
Transient Eyelid Edema Following COVID-19 Vaccination

vaccination. However, there are proposed immunologic mechanisms for adverse vaccine-related events, including complement system activation and molecular mimicry. In normal immunology, the complement system within tear film is an important part of the closed eye’s immunological defense, and its activation results in an increase in cytokine inflammatory mediators. It has been suggested that complement mediators in the tear film are the result of the leakage of plasma. Studies have demonstrated that the complement system has a critical role in the pathogenicity of COVID-19. In our patients, it is possible that the COVID-19 vaccine caused complement activation that increased complement mediators within the plasma and tear film, resulting in eyelid edema. Alternatively, the COVID 19 vaccine may trigger a specific immune response pathway through molecular mimicry. There are a number of SARS-CoV-2 proteins that exhibit cross reactivity with human proteins and could result in autoimmunity. However, it is not plausible that an adaptive cross-reactive immune response to SARS-CoV-2 spike protein receptor-binding domain could be manifest as soon as 1 day after administration of mRNA encoding it. It has also been suggested that antibodies to the spike glycoprotein of the mRNA vaccines can elicit an acute autoimmune response. Specific stimuli that initiate reactivation of autoimmune responses in diseases such as thyroid eye disease have not been identified, and it has been suggested that molecular mimicry has a role in the development of such diseases. We hypothesize that the patients’ eyelid edema is the result of a reactivation of an autoimmune response that is triggered by the mRNA vaccine. These 3 cases may represent a relatively uncommon reaction related to the vaccine that was either self-limited or resolved with minimal treatment. In similar cases, appropriate workup should be performed to rule out masquerading entities, but it may assist the clinician to appreciate this potentially selflimited, vaccine-related entity in the appropriate context. To our knowledge, this is the first report of unilateral, spontaneous eyelid edema following vaccination with the Pfizer COVID 19 mRNA vaccine. It is important for the ophthalmologic and medical community to be aware that such ocular reactions do occur *Ocular Center, Heredia; †Macula, Vitreous and Retina Associates of Costa Rica, San Jose, Costa Rica; and ‡Illinois Eye and Ear Infirmary, University of Illinois, Chicago, Illinois, U.S.A.
Understanding the Impact of the Psychological Cognitive Process on Student Learning Satisfaction: Combination of the Social Cognitive Career Theory and SOR Model

In higher education, student learning satisfaction is a significant predictor of learning that indicates the commitment students have to their learning and future academic achievement. The study combines the social cognitive career theory (SCCT) and the stimulus-organism-response (SOR) model to explore the psychological cognition and attitudes derived from students during their learning, discusses the pattern of student learning satisfaction enhancement from the aspect of process, and further understands the relationships among social support systems, interaction relationships, self-efficacy, generic skills, and learning satisfaction. In this study, 800 valid copies of questionnaires were collected from 12 universities through purposive sampling, and the structural model was analyzed by partial least squares structural equation modeling (PLS-SEM). The results showed that the relationships among all the constructs were positive and showed a significant effect; furthermore, the research results showed that self-efficacy and student generic skills had a significantly indirect effect in the model—specifically, a mediating effect. Finally, corresponding theoretical and practical implications were put forward based on the research results.
Altered Regional Homogeneity and Functional Connectivity during Microlesion Period after Deep Brain Stimulation in Parkinson's Disease

Background Patients with Parkinson's disease (PD) undergoing deep brain electrode implantation experience a temporary improvement in motor symptoms before the electrical stimulation begins. We usually call this the microlesion effect (MLE), but the mechanism behind it is not clear. Purpose This study aimed to assess the alterations in brain functions at the regional and whole-brain levels, using regional homogeneity (ReHo) and functional connectivity (FC), during the postoperative microlesion period after deep brain stimulation (DBS) in PD patients. Method Resting-state functional MRI data were collected from 27 PD patients before and after the first day of DBS and 12 healthy controls (HCs) in this study. The ReHo in combination with FC analysis was used to investigate the alterations of regional brain activity in all the subjects. Results There were increased ReHo in the basal ganglia-thalamocortical circuit (left supplementary motor area and bilateral paracentral lobule), whereas decreased ReHo in the default mode network (DMN) (left angular gyrus, bilateral precuneus), prefrontal cortex (bilateral middle frontal gyrus), and the cerebello-thalamocortical (CTC) circuit (Cerebellum_crus2/1_L) after DBS. In addition, we also found abnormal FC in the lingual gyrus, cerebellum, and DMN. Conclusion Microlesion of the thalamus caused by electrode implantation can alter the activity of the basal ganglia-thalamocortical circuit, prefrontal cortex, DMN, and CTC circuit and induce abnormal FC in the lingual gyrus, cerebellum, prefrontal cortex, and DMN among PD patients. The findings of this study contribute to the understanding of the mechanism of MLE.