Identification and genetic validation of leukemia inhibitory factor super-enhancers in acute respiratory distress syndrome and lung cancer.

Super-enhancers play prominent roles in driving robust pathological gene expression, but they are hidden in human genome at noncoding regions, making them difficult to explore. Leukemia inhibitory factor (LIF) is a multifunctional cytokine crucially involved in acute respiratory distress syndrome (ARDS) and lung cancer progression. However, the mechanisms governing LIF regulation in disease contexts remain largely unexplored. In this study, we observed elevated levels of LIF in the bronchoalveolar lavage fluid (BALF) of patients with sepsis-related ARDS compared to those with nonsepsis-related ARDS. Furthermore, both basal and LPS-induced LIF expression were under the control of super-enhancers. Through analysis of H3K27Ac ChIP-seq data, we pinpointed three potential super-enhancers (LIF-SE1, LIF-SE2, and LIF-SE3) located proximal to the LIF gene in cells. Notably, genetic deletion of any of these three super-enhancers using CRISPR-Cas9 technology led to a significant reduction in LIF expression. Moreover, in cells lacking these super-enhancers, both cell growth and invasion capabilities were substantially impaired. Our findings highlight the critical role of three specific super-enhancers in regulating LIF expression and offer new insights into the transcriptional regulation of LIF in ARDS and lung cancer.

Knockdown of KDM5B Leads to DNA Damage and Cell Cycle Arrest in Granulosa Cells via MTF1.

KDM5B is essential for early embryo development, which is under the control of maternal factors in oocytes. Granulosa cells (GCs) play a critical role during oocyte mature. However, the role of KDM5B in GCs remains to be elucidated. In the current study, we found that KDM5B expressed highly in the ovaries and located in goat GCs. Using an RNA sequence, we identified 1353 differentially expressed genes in the KDM5B knockdown GCs, which were mainly enriched in cell cycle, cell division, DNA replication and the cellular oxidative phosphorylation regulation pathway. Moreover, we reported a decrease in the percentage of proliferated cells but an increase in the percentage of apoptotic cells in the KDM5B knockdown GCs. In addition, in the KDM5B knockdown GCs, the percentage of GCs blocked at the S phase was increased compared to the NC group, suggesting a critical role of KDM5B in the cell cycle. Moreover, in the KDM5B knockdown GCs, the reactive oxygen species level, the mitochondrial depolarization ratio, and the expression of intracellular phosphorylated histone H2AX (γH2AX) increased, suggesting that knockdown of KDM5B leads to DNA damage, primarily in the form of DNA double-strand breaks (DSBs). Interestingly, we found a down-regulation of MTF1 in the KDM5B knockdown GCs, and the level of cell proliferation, as well as the cell cycle block in the S phase, was improved. In contrast, in the group with both KDM5B knockdown and MTF1 overexpression, the level of ROS, the expression of γH2AX and the number of DNA DSB sites decreased. Taken together, our results suggest that KDM5B inhibits DNA damage and promotes the cell cycle in GCs, which might occur through the up-regulation of MTF1.

Computer-designed surgical templates improve the extraction of impacted supernumerary teeth in the hard palate.

OBJECTIVES: The surgical procedure of bony impacted supernumerary teeth (SNT) in hard palate is commonly done with poor visualization and uncomfortable posture. This study aims to introduce our primary practice of presurgical evaluation and guiding exodontia of bony impacted supernumerary teeth (SNT) in the hard palate to reduce surgical trauma, duration and uncertainty. STUDY DESIGN: Twelve patients with impacted supernumerary teeth in hard palate were included. Intraoral scan and the three-dimensional (3D) reconstruction of the cone beam computed tomography (CBCT) file was superimposed, and virtual simulation of flap elevation and osteotomy was conducted on the rebuilt 3D model. A couple of surgical templates were designed with surgical planning software Mimics, fabricated by a 3D printer and were used to guide the extraction of the impacted SNT. RESULTS: The surgical templates fitted well to the teeth and operation site. All the impacted SNTs were accurately located and extracted without damaging the adjacent vital anatomical structures. All patients had an uneventful postoperative recovery without infection or sensory disturbance. CONCLUSIONS: The application of 3D printed surgical templates reduced trauma and increased the accuracy and predictability of surgical extraction of bony impacted SNT in hard palate. The results of this study increased the accuracy and predictability of surgical extraction of bony impacted SNT in hard palate, and reduced the surgeon's embarrassment and surgical trauma because of location difficulty.

Screening for proteins related to the biosynthesis of hispidin and its derivatives in Phellinus igniarius using iTRAQ proteomic analysis.

BACKGROUND: Hispidin (HIP) and its derivatives, a class of natural fungal metabolites, possess complex chemical structures with extensive pharmacological activities. Phellinus igniarius, the most common source of HIP, can be used as both medicine and food. However, the biosynthetic pathway of HIP in P. igniarius remains unclear and we have a limited understanding of the regulatory mechanisms related to HIP. In this work, we sought to illustrate a biosynthesis system for hispidin and its derivatives at the protein level. RESULTS: We found that tricetolatone (TL) is a key biosynthetic precursor in the biosynthetic pathway of hispidin and that its addition led to increased production of hispidin and various hispidin derivatives. Based on the changes in the concentrations of precursors and intermediates, key timepoints in the biosynthetic process were identified. We used isobaric tags for relative and absolute quantification (iTRAQ) to study dynamic changes of related proteins in vitro. The 270 differentially expressed proteins were determined by GO enrichment analysis to be primarily related to energy metabolism, oxidative phosphorylation, and environmental stress responses after TL supplementation. The differentially expressed proteins were related to ATP synthase, NAD binding protein, oxidoreductase, and other elements associated with electron transfer and dehydrogenation reactions during the biosynthesis of hispidin and its derivatives. Multiple reaction monitoring (MRM) technology was used to selectively verify the iTRAQ results, leading us to screen 11 proteins that were predicted to be related to the biosynthesis pathways. CONCLUTION: These findings help to clarify the molecular mechanism of biosynthesis of hispidin and its derivatives and may serve as a foundation for future strategies to identify new hispidin derivatives.

Ontological Organization and Bioinformatic Analysis of Adverse Drug Reactions From Package Inserts: Development and Usability Study.

BACKGROUND: Licensed drugs may cause unexpected adverse reactions in patients, resulting in morbidity, risk of mortality, therapy disruptions, and prolonged hospital stays. Officially approved drug package inserts list the adverse reactions identified from randomized controlled clinical trials with high evidence levels and worldwide postmarketing surveillance. Formal representation of the adverse drug reaction (ADR) enclosed in semistructured package inserts will enable deep recognition of side effects and rational drug use, substantially reduce morbidity, and decrease societal costs. OBJECTIVE: This paper aims to present an ontological organization of traceable ADR information extracted from licensed package inserts. In addition, it will provide machine-understandable knowledge for bioinformatics analysis, semantic retrieval, and intelligent clinical applications. METHODS: Based on the essential content of package inserts, a generic ADR ontology model is proposed from two dimensions (and nine subdimensions), covering the ADR information and medication instructions. This is followed by a customized natural language processing method programmed with Python to retrieve the relevant information enclosed in package inserts. After the biocuration and identification of retrieved data from the package insert, an ADR ontology is automatically built for further bioinformatic analysis. RESULTS: We collected 165 package inserts of quinolone drugs from the National Medical Products Administration and other drug databases in China, and built a specialized ADR ontology containing 2879 classes and 15,711 semantic relations. For each quinolone drug, the reported ADR information and medication instructions have been logically represented and formally organized in an ADR ontology. To demonstrate its usage, the source data were further bioinformatically analyzed. For example, the number of drug-ADR triples and major ADRs associated with each active ingredient were recorded. The 10 ADRs most frequently observed among quinolones were identified and categorized based on the 18 categories defined in the proposal. The occurrence frequency, severity, and ADR mitigation method explicitly stated in package inserts were also analyzed, as well as the top 5 specific populations with contraindications for quinolone drugs. CONCLUSIONS: Ontological representation and organization using officially approved information from drug package inserts enables the identification and bioinformatic analysis of adverse reactions caused by a specific drug with regard to predefined ADR ontology classes and semantic relations. The resulting ontology-based ADR knowledge source classifies drug-specific adverse reactions, and supports a better understanding of ADRs and safer prescription of medications.

Diagnostic performance of 18F­DCFPyL PET vs. 68Ga­PSMA PET/CT in patients with suspected prostate cancer: A systemic review and meta­analysis.

In this systematic review and meta-analysis, the diagnostic performance of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/CT was compared with that of 18F-DCFPyL PET for patients with suspected prostate cancer (PCa). Up to September 2023, the PubMed, Embase and Web of Science databases were thoroughly searched for relevant papers. Studies examining the diagnostic performance of 18F-DCFPyL PET and 68Ga-PSMA PET/CT in patients with suspected PCa were included in the present review. The Quality Assessment of Diagnostic Performance Studies-2 tool was used to rate the diagnostic performance of each study. The diagnostic performance of 18F-DCFPyL PET and 68Ga-PSMA PET/CT for primary PCa was examined by 13 studies included, comprising 1,178 patients. The pooled sensitivity and specificity of 18F-DCFPyL PET were 0.92 (95% CI, 0.85-0.96) and 0.59 (95% CI, 0.08-0.96), respectively. For 68Ga-PSMA PET/CT, the pooled sensitivity and specificity were 0.96 (95% CI, 0.88-0.99) and 0.71 (95% CI, 0.57-0.82), respectively. 18F-DCFPyL PET and 68Ga-PSMA PET/CT both had an area under the receiver operating characteristic curve of 0.92 (95% CI, 0.89-0.94). In addition, the Fagan nomogram revealed that the post-test probabilities for 18F-DCFPyL PET and 68Ga-PSMA PET/CT could rise to 69 and 77% when the pre-test probability was set at 50%. In conclusion, a comparable diagnostic performance for patients with suspected PCa was determined for 18F-DCFPyL PET and 68Ga-PSMA PET/CT. However, it is crucial to keep in mind that the findings of the present meta-analysis come from investigations with modest sample sizes. Therefore, more extensive research is required to obtain more solid data.

The association between statin use and diabetic nephropathy in US adults: data from NHANES 2005 - 2018.

Background: A serious consequence of diabetes is diabetic nephropathy (DN), which is commonly treated by statins. Studies evaluating the effects of statin medication have yielded inconsistent results regarding the potential association with diabetic nephropathy. To manage diabetic nephropathy's onset and improve the quality of life of patients, it is imperative to gain a comprehensive understanding of its contributing factors. Data and methods: Our study was conducted using the National Health and Nutrition Examination Survey (NHANES) as well as weighted multivariate logistic regression models to determine the odds ratio (OR) and 95% confidence intervals (95%CI) for diabetic nephropathy. We conducted stratified analyses to examine the impact of statins and the duration of their usage on diabetic nephropathy in different subgroups. A nomogram model and the receiver operating characteristic (ROC) curve were also developed to predict DN risk. Results: Statin use significantly increased the incidence of DN (OR=1.405, 95%CI (1.199,1.647), p<0.001). Individuals who used statins for 5 to 7 years were more likely to develop diabetic nephropathy (OR=1.472, 95%CI (1.057,2.048), p=0.022) compared to those who used statins for 1-3 years (OR=1.334, 95%CI (1.058,1.682), p=0.015) or <1 year (OR=1.266, 95%CI (1.054,1.522), p = 0.012). Simvastatin has a greater incidence of diabetic nephropathy (OR=1.448, 95%CI(1.177, 1.78), P < 0.001). Conclusion: Taking statins long-term increases the risk of DN. Statin use is associated with an increased risk of DN. Caution should be exercised when prescribing atorvastatin and simvastatin for long-term statin therapy.

Enhancing Mesopore Volume and Thermal Insulation of Silica Aerogel via Ambient Pressure Drying-Assisted Foaming Method.

Ambient pressure drying (APD) of silica aerogels has emerged as an attractive method adapting to large-scale production. Spring-back is a unique phenomenon during APD of silica aerogels with volume expansion after its shrinkage under capillary force. We attribute the intense spring-back at elevated drying temperatures to a dense structure formed on the surface and the formation of positive internal pressure. Furthermore, an APD-assisted foaming method with an in situ introduction of NH4HCO3 was proposed. NH4HCO3 decomposing at drying temperatures hastened the emergence of positive pressure, thereby increasing the expansion volume. Compared to the previous method, the porosity of silica aerogel increased from 82.2% to 92.6%, and mesopore volume from 1.79 cm3 g-1 to 4.54 cm3 g-1. By adjusting the amount of the silicon source, silica aerogels prepared by the APD-assisted foaming method generated higher volume expansion and lower thermal conductivity. After calcination to remove undecomposed ammonium salts, the hydrophobic silica aerogel with a density of 0.112 g cm-3 reached a mesopore volume of 5.07 cm3 g-1 and a thermal conductivity of 18.9 mW m-1·K-1. This strategy not only improves the thermal insulation properties, but also offers a significant advancement in tailoring silica aerogels with specific porosity and mesopore volume for various applications.

Cytoplasmic Accumulation of Histones Induced by BET Inhibition Protects Cells from C9orf72 Poly(PR)-Induced Cell Death.

Repeat dipeptides such as poly(proline-arginine) (polyPR) are generated from the hexanucleotide GGGGCC repeat expansions in the C9orf72 gene. These dipeptides are often considered as the genetic cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In the study, fluorescein isothiocyanate (FITC) labeled PR20 is used to investigate PR20-induced cell death. The findings reveal that the cell death induced by PR20 is dependent on its nuclear distribution and can be blocked by a nuclear import inhibitor called importazole. Further investigation reveals that BRD4 inhibitors, such as JQ-1 and I-BET762, restrict cytoplasmic localization of PR20, thereby reducing its cytotoxic effect. Mechanistically, the inhibition of BRD4 leads to an increase in the expression of numerous histones, resulting in the accumulation of histones in the cytoplasm. These cytoplasmic histones associate with PR20 and limit its distribution within the nucleus. Notably, the ectopic expression of histones alone is enough to confer protection to cells treated with PR20. In addition, phenylephrine (PE) induces cellular hypertrophy and cytoplasmic distribution of histone, which also helps protect cells from PR20-induced cell death. The research suggests that temporarily inducing the presence of cytoplasmic histones may alleviate the neurotoxic effects of dipeptide repeat proteins.

A novel lncRNA LOC105613571 binding with BDNF in pituitary promotes gonadotropin secretion by AKT/ERK-mTOR pathway in sheep associated with prolificacy.

The pituitary is a vital endocrine organ for synthesis and secretion of gonadotropic hormones (FSH and LH), and the gonadotropin showed fluctuations in animals with different fecundity. Long non-coding RNAs (lncRNAs) have been identified as regulatory factors for the reproductive process. However, the profiles of lncRNAs and their roles involved in sheep fecundity remains unclear. In this study, we performed RNA-sequencing for the sheep pituitary gland associated with different fecundity, and identified a novel candidate lncRNA LOC105613571 targeting BDNF related to gonadotropin secretion. Our results showed that expression of lncRNA LOC105613571 and BDNF could be significantly upregulated by GnRH stimulation in sheep pituitary cells in vitro. Notably, either lncRNA LOC105613571 or BDNF silencing inhibited cell proliferation while promoted cell apoptosis. Moreover, lncRNA LOC105613571 knockdown could also downregulate gonadotropin secretion via inactivation AKT, ERK and mTOR pathway. In addition, co-treatment with GnRH stimulation and lncRNA LOC105613571 or BDNF knockdown showed the opposite effect on sheep pituitary cells in vitro. In summary, BDNF-binding lncRNA LOC105613571 in sheep regulates pituitary cell proliferation and gonadotropin secretion via the AKT/ERK-mTOR pathway, providing new ideas for the molecular mechanisms of pituitary functions.

SRRM2 may be a potential biomarker and immunotherapy target for multiple myeloma: a real-world study based on flow cytometry detection.

Serine/arginine repetitive matrix 2 (SRRM2) has been implicated in tumorigenesis, cancer development, and drug resistance through aberrant splicing; however, its correlation with multiple myeloma (MM) has not been reported. We investigated the potential of SRRM2 as a biomarker and immunotherapeutic target in MM by examining its expression in MM cells using flow cytometry. Our study included 95 patients with plasma cell disease, including 80 MM cases, and we detected SRRM2 expression on plasma cells and normal blood cells to analyze its relationship with clinical profiles. We found widespread positive expression of SRRM2 on plasma cells with little expression on normal blood cells, and its expression on abnormal plasma cells was higher than that on normal plasma cells. Comparative analysis with clinical data suggests that SRRM2 expression on plasma cells correlates with MM treatment response. MM patients with high SRRM2 expression had higher levels of serum ß2-mg and LDH, ISS staging, and plasma cell infiltration, as well as high-risk mSMART 3.0 stratification and cytogenetic abnormalities, particularly 1q21 amplification. In patients with previous MM, high SRRM2 expression on plasma cells was associated with higher plasma cell infiltration, high-risk mSMART 3.0 risk stratification, cytogenetic abnormalities, more relapses, and fewer autologous stem cell transplant treatments. In summary, SRRM2 may serve as a novel biomarker and immunotherapeutic target for MM. Its expression level on plasma cells can help in risk stratification of MM and monitoring of treatment response.

Filler effects inspired high performance polyurethane elastomer design: segment arrangement control.

Elastomers with high strength and toughness are in great demand. Previous research on elastomers focused mainly on the design of new chemical structures, but their complicated synthesis process and expensive monomers have restricted the practical application of these materials. Inspired by general filler effects, a strategy is proposed to remarkably enhance the mechanical properties of thermoplastic polyurethane (TPU) elastomers by designing the arrangement of hard/soft segments using traditional chemical compositions. By utilizing the synergetic effect of weak hard segments, normal TPU elastomers are upgraded into advanced elastomers. Combining experiments and simulations, it is demonstrated that a suitable sequence length can achieve considerably enhanced strength and toughness by maximizing the relative surface area of hard domains. Mixing the obtained elastomer with an ionic liquid can result in a durable ionogel sensor with balanced mechanical strength and ionic conductivity. This easy-to-implement strategy offers a new dimension for the development of high-performance elastomers.

Ythdf2-mediated STK11 mRNA decay supports myogenesis by inhibiting the AMPK/mTOR pathway.

An emerging research focus is the role of m6A modifications in mediating the post-transcriptional regulation of mRNA during mammalian development. Recent evidence suggests that m6A methyltransferases and demethylases play critical roles in skeletal muscle development. Ythdf2 is a m6A "reader" protein that mediates mRNA degradation in an m6A-dependent manner. However, the specific function of Ythdf2 in skeletal muscle development and the underlying mechanisms remain unclear. Here, we observed that Ythdf2 expression was significantly upregulated during myogenic differentiation, whereas Ythdf2 knockdown markedly inhibited myoblast proliferation and differentiation. Combined analysis of high-throughput sequencing, Co-IP, and RIP assay revealed that Ythdf2 could bind to m6A sites in STK11 mRNA and form an Ago2 silencing complex to promote its degradation, thereby regulating its expression and consequently, the AMPK/mTOR pathway. Furthermore, STK11 downregulation partially rescued Ythdf2 knockdown-induced impairment of proliferation and myogenic differentiation by inhibiting the AMPK/mTOR pathway. Collectively, our results indicate that Ythdf2 mediates the decay of STK11 mRNA, an AMPK activator, in an Ago2 system-dependent manner, thereby driving skeletal myogenesis by suppressing the AMPK/mTOR pathway. These findings further enhance our understanding of the molecular mechanisms underlying RNA methylation in the regulation of myogenesis and provide valuable insights for conducting in-depth studies on myogenesis.

Empowering standardization of cancer vaccines through ontology: enhanced modeling and data analysis.

BACKGROUND: The exploration of cancer vaccines has yielded a multitude of studies, resulting in a diverse collection of information. The heterogeneity of cancer vaccine data significantly impedes effective integration and analysis. While CanVaxKB serves as a pioneering database for over 670 manually annotated cancer vaccines, it is important to distinguish that a database, on its own, does not offer the structured relationships and standardized definitions found in an ontology. Recognizing this, we expanded the Vaccine Ontology (VO) to include those cancer vaccines present in CanVaxKB that were not initially covered, enhancing VO's capacity to systematically define and interrelate cancer vaccines. RESULTS: An ontology design pattern (ODP) was first developed and applied to semantically represent various cancer vaccines, capturing their associated entities and relations. By applying the ODP, we generated a cancer vaccine template in a tabular format and converted it into the RDF/OWL format for generation of cancer vaccine terms in the VO. '12MP vaccine' was used as an example of cancer vaccines to demonstrate the application of the ODP. VO also reuses reference ontology terms to represent entities such as cancer diseases and vaccine hosts. Description Logic (DL) and SPARQL query scripts were developed and used to query for cancer vaccines based on different vaccine's features and to demonstrate the versatility of the VO representation. Additionally, ontological modeling was applied to illustrate cancer vaccine related concepts and studies for in-depth cancer vaccine analysis. A cancer vaccine-specific VO view, referred to as "CVO," was generated, and it contains 928 classes including 704 cancer vaccines. The CVO OWL file is publicly available on: http://purl.obolibrary.org/obo/vo/cvo.owl , for sharing and applications. CONCLUSION: To facilitate the standardization, integration, and analysis of cancer vaccine data, we expanded the Vaccine Ontology (VO) to systematically model and represent cancer vaccines. We also developed a pipeline to automate the inclusion of cancer vaccines and associated terms in the VO. This not only enriches the data's standardization and integration, but also leverages ontological modeling to deepen the analysis of cancer vaccine information, maximizing benefits for researchers and clinicians. AVAILABILITY: The VO-cancer GitHub website is: https://github.com/vaccineontology/VO/tree/master/CVO .

CanVaxKB: a web-based cancer vaccine knowledgebase.

Cancer vaccines have been increasingly studied and developed to prevent or treat various types of cancers. To systematically survey and analyze different reported cancer vaccines, we developed CanVaxKB (https://violinet.org/canvaxkb), the first web-based cancer vaccine knowledgebase that compiles over 670 therapeutic or preventive cancer vaccines that have been experimentally verified to be effective at various stages. Vaccine construction and host response data are also included. These cancer vaccines are developed against various cancer types such as melanoma, hematological cancer, and prostate cancer. CanVaxKB has stored 263 genes or proteins that serve as cancer vaccine antigen genes, which we have collectively termed 'canvaxgens'. Top three mostly used canvaxgens are PMEL, MLANA and CTAG1B, often targeting multiple cancer types. A total of 193 canvaxgens are also reported in cancer-related ONGene, Network of Cancer Genes and/or Sanger Cancer Gene Consensus databases. Enriched functional annotations and clusters of canvaxgens were identified and analyzed. User-friendly web interfaces are searchable for querying and comparing cancer vaccines. CanVaxKB cancer vaccines are also semantically represented by the community-based Vaccine Ontology to support data exchange. Overall, CanVaxKB is a timely and vital cancer vaccine source that facilitates efficient collection and analysis, further helping researchers and physicians to better understand cancer mechanisms.

Preparation of Titania-Silica Composite Aerogel at Atmospheric Pressure and Its Catalytic Performance in the Synthesis of Poly (Butylene Succinate).

Titanates are widely used in the synthesis of polyesters, such as Poly (butylene succinate) (PBS), due to their excellent catalytic activity for polycondensation. However, the hydrolysis sensitivity of titanate and side reactions at high temperatures restrict the further improvement of the molecular weight of polyesters and lead to the high content of end carboxyl group content in the products. In this work, we prepared titania-silica composite aerogels with resistance to hydrolysis and large specific surface area, which were further explored as an efficient catalyst for polycondensation reactions. A series of titania-silica composite aerogel catalysts for PBS polycondensation were successfully prepared by the sol-gel method. The influence of a Ti/Si ratio on the surface morphology and structure of the aerogels was examined. Titania-silica composite aerogel exhibits the surface characteristics of high specific surface area and high Lewis acid content. The specific surface area of titania-silica composite aerogels can reach 524.59 m2/g, and the Lewis acid content on the surface can reach 370.29 µmol/g. Furthermore, the catalytic performance for the polycondensation reaction of PBS was investigated. The intrinsic viscosity of PBS synthesized by catalysis with the composite catalyst with a Ti/Si ratio of 9/1 reaches 1.74 dL/g, with the Mn of 7.72 × 104 g/mol. The hydrolysis resistance stability of the titania-silica composite aerogel is greatly improved compared with traditional tetrabutyl titanate (TBT), and the end carboxyl group content of PBS is effectively reduced to lower than 30 mol/ton.

CircUBE3A promotes myoblasts proliferation and differentiation by sponging miR-28-5p to enhance expression.

circRNAs have been found to be involved in the regulatory network of skeletal muscle development in studies. However, their precise functions and regulatory mechanisms remain unknown. The expression patterns and alterations of circRNAs in the longissimus dorsi muscle of two major developmental stages of goats (D75 fetus and D1 kid) were studied using high-throughput sequencing technology and bioinformatics tools in this study. In kid skeletal muscles, 831 differently expressed circRNAs were found, comprising 486 up-regulated circRNAs and 345 down-regulated circRNAs. In skeletal muscle, we focused on the highly expressed and variably expressed circUBE3A. CircUBE3A levels were discovered to be much higher in kid skeletal muscle and differentiated myoblasts. Knocking down circUBE3A resulted in a significant increase in cell proliferation and differentiation in goat myoblasts. CircUBE3A specifically binds to and inhibits miR-28-5p, boosting the expression of Hydroxyacyl Coenzyme A Dehydrogenase Beta (HADHB) and contributing to goat myoblast proliferation and differentiation, according to the mechanistic investigation. The above results indicated that circUBE3A could regulate HADHB expression by targeting miR-28-5p, consequently increasing goat myoblast proliferation and differentiation. Our findings offer fresh perspectives on goat breeding and growth regulation, as well as substantial theoretical basis.

Mapping Vaccine Names in Clinical Trials to Vaccine Ontology using Cascaded Fine-Tuned Domain-Specific Language Models.

Background: Vaccines have revolutionized public health by providing protection against infectious diseases. They stimulate the immune system and generate memory cells to defend against targeted diseases. Clinical trials evaluate vaccine performance, including dosage, administration routes, and potential side effects. ClinicalTrials.gov is a valuable repository of clinical trial information, but the vaccine data in them lacks standardization, leading to challenges in automatic concept mapping, vaccine-related knowledge development, evidence-based decision-making, and vaccine surveillance. Results: In this study, we developed a cascaded framework that capitalized on multiple domain knowledge sources, including clinical trials, Unified Medical Language System (UMLS), and the Vaccine Ontology (VO), to enhance the performance of domain-specific language models for automated mapping of VO from clinical trials. The Vaccine Ontology (VO) is a community-based ontology that was developed to promote vaccine data standardization, integration, and computer-assisted reasoning. Our methodology involved extracting and annotating data from various sources. We then performed pre-training on the PubMedBERT model, leading to the development of CTPubMedBERT. Subsequently, we enhanced CTPubMedBERT by incorporating SAPBERT, which was pretrained using the UMLS, resulting in CTPubMedBERT + SAPBERT. Further refinement was accomplished through fine-tuning using the Vaccine Ontology corpus and vaccine data from clinical trials, yielding the CTPubMedBERT + SAPBERT + VO model. Finally, we utilized a collection of pre-trained models, along with the weighted rule-based ensemble approach, to normalize the vaccine corpus and improve the accuracy of the process. The ranking process in concept normalization involves prioritizing and ordering potential concepts to identify the most suitable match for a given context. We conducted a ranking of the Top 10 concepts, and our experimental results demonstrate that our proposed cascaded framework consistently outperformed existing effective baselines on vaccine mapping, achieving 71.8% on top 1 candidate's accuracy and 90.0% on top 10 candidate's accuracy. Conclusion: This study provides a detailed insight into a cascaded framework of fine-tuned domain-specific language models improving mapping of VO from clinical trials. By effectively leveraging domain-specific information and applying weighted rule-based ensembles of different pre-trained BERT models, our framework can significantly enhance the mapping of VO from clinical trials.

Simplified flow cytometry scoring for diagnosis and prognosis of myelodysplastic symptom.

A flow cytometric score (FCM-score) to diagnose myelodysplastic syndromes (MDS) was proposed in 2012 that used four parameters to distinguish low-grade MDS from non-clonal cytopenias. This study was carried out to further simplify the method for better clinical application. Combinations of antibodies CD34, CD19, CD33 and CD45 were analyzed for the four parameters. Compared with the published method that used low side scatter (SSC) and CD45 expression to separate B lymphocyte progenitor cells and myeloblasts, our method (MFCM-Score) used CD19 and CD33 to separate B lymphocyte progenitor cells and myeloblasts within the CD34+CD45dimm population. Subjects were analyzed and compared using the two schemes. In addition, the relationships between the MFCM-Score and the Revised International Prognostic Scoring System (IPSS-R) for MDS were analyzed. There was no significant difference between the MFCM-score and FCM-score in the diagnosis of MDS (P > 0.05); MFCM-score had a positive correlation with the IPSS-R prognosis classification for MDS (Spearman r = 0.848, P < 0.001). All parameters in the MFCM-score were positively correlated to the IPSS-R grades in MDS (P < 0.01). Our work demonstrates that the FCM score using four parameters is simple and practical for screening MDS patients and the MFCM-score could be used to evaluate the risk of MDS patients.

A new 2H-benzindazole compound from Alternaria alternata Shm-1, an endophytic fungus isolated from the fresh wild fruit of Phellinus igniarius.

Endophytic fungi have been shown in recent years to produce a series of bioactive secondary metabolites. Several endophytic fungi were isolated from the fresh wild body of Phellinus igniarius, and initially evaluated for their antimicrobial activity. Among which, Shm-1 extract showed moderate inhibitory activity against Clavibacter michiganense and the fungus was identified to be Alternaria alternata Shm-1 through the comparison of morphological characteristics and the sequence of the rDNA ITS with those of other Alternaria species. A new 2H-benzindazole derivative, alterindazolin A (1), has been isolated from cultures of the endophyte Alternaria alternata Shm-1. Its structure was characterized as 1-benzyl-5-p-hydroxy-phenyloxygen-benz[e]indazole by spectroscopic data analysis including 1D NMR, 2D NMR and MS spectrum.