Design, synthesis, and preclinical evaluation of 11C/18F-labeled inhibitors for RIPK1 PET imaging.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is a promising target for the diagnosis and treatment of various diseases, especially neurodegenerative disorders. Developing PET imaging probes targeting RIPK1 is beneficial for visualizing the connections between RIPK1 and diseases, as well as for related drug development. In this study, we report the design and synthesis of a series of novel RIPK1 inhibitors. Three potent inhibitors, 7i, 7k, and 8a, with good cell anti-necroptosis potency and physicochemical properties, were identified and selected for PET imaging probe development. Subsequently, three PET imaging radioligands ([11C]7k, [18F]7i, and [18F]8a) were successfully synthesized. In mouse PET imaging studies, all three radioligands showed good brain uptake. Among them, probe [18F]8a exhibited good binding specificity in both in vitro autoradiography and in vivo PET imaging studies. Additionally, [18F]8a demonstrated good in vivo metabolic stability. This work highlights the potential of probe [18F]8a for imaging brain RIPK1 in live animals, laying the groundwork for the future development of RIPK1 PET radioligands.

Effect of Hope Theory combined with active cycle of breathing techniques on pulmonary rehabilitation among COPD patients: A quasi-experiment study.

BACKGROUND: Pulmonary rehabilitation plays a positive role in improving exercise tolerance and reducing readmission rates in patients with chronic obstructive pulmonary disease (COPD), while the adherence of pulmonary rehabilitation in COPD patients is still poor. The active cycle of breathing techniques based on the Hope Theory is a method to enhance patients' confidence in overcoming the disease and improve the intrinsic motivation of exercise through symptom improvement such as cough and sputum evacuation ability. OBJECTIVES: To investigate the effect of Hope Theory education combined with the active cycle of breathing techniques on pulmonary rehabilitation of COPD patients, including exercise adherence, cough and sputum evacuation ability, hope index and exercise self-efficacy. METHODS: The study assigned 70 COPD patients hospitalized into intervention and control groups to receive the active cycle of breathing techniques based on Hope Theory or routine treatment in order of admission. Data for cough and sputum evacuation ability, hope, exercise confidence were collected at baseline and after the program. Exercise adherence was assessed at the end of 1, 4 and 8 week following discharge. RESULTS: The actual number of sample consisted of 65 patients divided into intervention (n = 33) and control (n = 32) groups due to severe complications, explicit refusal, disinterest and loss to follow-up. After two weeks of intervention, exercise adherence of the intervention group were better than those of the control group at the end of 4 and 8 week of discharge (P < 0.05). And there was an improvement in cough and sputum evacuation ability, hope and exercise self-efficacy outcomes in the intervention group, with a statistically significant difference between the two groups (P < 0.05). CONCLUSION: The active cycle of breathing techniques based on Hope Theory education can improve cough and sputum evacuation ability, hope index, exercise self-efficacy, and exercise adherence of COPD patients.

Development and Evaluation of [11C]I-58: A Novel PET Radiotracer Targeting BRD4 BD2 for Advanced Epigenetic Imaging.

The paired bromodomains (BD1 and BD2), located in the bromodomain and extra-terminal (BET) family proteins, perform specific functions in gene transcriptional control and expression. Targeting specific bromodomains with inhibitors holds promise for achieving therapeutic benefits with reduced side effects. However, the comprehension of this target related to the disease is still restricted. Positron emission tomography (PET) imaging is a powerful tool that provides a valuable avenue for exploring the BD2 bromodomain. This investigation introduces a novel radioligand, [11C]I-58, for PET targeting the BET BD2 domain. The synthesis of compound I-58, along with its radiosynthetic process for C11 labeling, is detailed, and the suitability of [11C]I-58 for PET imaging of the BD2 bromodomain is evaluated. Initial PET study findings in mice indicate that [11C]I-58 exhibits suitable biodistribution in peripheral organs and tissues. Additionally, in vitro autoradiography studies and blocking experiments provide compelling evidence supporting the specific binding of [11C]I-58 to the BD2 bromodomain. These results establish [11C]I-58 as a promising instrument for the PET imaging of the BD2 bromodomain. This research not only holds the potential to pave the path for developing PET radioligands precisely targeting the BD2 bromodomain but also adds to a more profound comprehension of the biological mechanisms linked to the BD bromodomain.

Development of Dual Diagnostic-Therapeutic Nanoformulation Effective Against Pancreatic Cancer in Animal Model.

Purpose: Erythrocytes and fibroblasts in the pancreatic cancer tumor microenvironment promote tumor cell growth and invasion by providing nutrients and promoting immunosuppression. Additionally, they form a barrier against the penetration of chemotherapeutic drugs. Therefore, the search for diversified tumor-targeting materials plays an essential role in solving the above problems. Methods: Physicochemical characterization of Graphene fluorescent nanoparticles (GFNPs) and nanomedicines were analyzed by transmission electron microscopy (TEM), elemental analyzers and ultraviolet fluorescence (UV/FL) spectrophotometer. Localization of GFNPs in cell and tissue sections imaged with laser confocal microscope, fluorescence scanner and small animal in vivo imager. Qualitative detection and quantitative detection of GFNPs and GFNPs-GEM were performed using High performance liquid chromatography (HPLC). Results: Based on the 3 nm average dimensions, GFNPs penetrate vascular endothelial cells and smooth muscle cells, achieve up to label 30% tumor cells and 60% cancer-associated fibroblasts (CAFs) cells, and accurately label mature red blood cells in the tumor microenvironment. In orthotopic transplanted pancreatic cancer models, the fluorescence intensity of GFNPs in tumors showed a positive correlation with the cycle size of tumor development. The differential spatial distribution of GFNPs in three typical clinical pancreatic cancer samples demonstrated their diagnostic potential. To mediate the excellent targeting properties of GFNPs, we synthesized a series of nanomedicines using popular chemotherapeutic drugs, in which complex of GFNPs and gemcitabine (GFNPs-GEM) possessed stability in vivo and exhibited effective reduction of tumor volume and fewer side effects. Conclusion: GFNPs with multiple targeting tumor microenvironments in pancreatic cancer possess diagnostic efficiency and therapeutic potential.

Neuroimaging analysis reveals distinct cerebral perfusion responses to fasting-postprandial metabolic switching in Alzheimer's disease patients.

AIMS: Extended fasting-postprandial switch intermitting time has been shown to affect Alzheimer's disease (AD). Few studies have investigated the cerebral perfusion response to fasting-postprandial metabolic switching (FMS) in AD patients. We aimed to evaluate the cerebral perfusion response to FMS in AD patients. METHODS: In total, 30 AD patients, 32 mild cognitive impairment (MCI) patients, and 30 healthy control individuals (HCs) were included in the quantification of cerebral perfusion via cerebral blood flow (CBF). The cerebral perfusion response to FMS was defined as the difference (ΔCBF) between fasting and postprandial CBF. RESULTS: Patients with AD had a regional negative ΔCBF in the anterior temporal lobe, part of the occipital lobe and the parietal lobe under FMS stimulation, whereas HCs had no significant ΔCBF. The AD patients had lower ΔCBF values in the right anterior temporal lobe than the MCI patients and HCs. ΔCBF in the anterior temporal lobe was negatively correlated with cognitive severity and cognitive reserve factors in AD patients. CONCLUSIONS: AD patients exhibited a poor ability to maintain cerebral perfusion homeostasis under FMS stimulation. The anterior temporal lobe is a distinct area that responds to FMS in AD patients and negatively correlates with cognitive function.

Impact research of pain nursing combined with hospice care on quality of life for patients with advanced lung cancer.

This study aims to evaluate the impact of integrating pain nursing with hospice care on the quality of life among patients with advanced lung cancer. This study involving 60 advanced lung cancer patients admitted from January 2022 to January 2023. Participants were randomly assigned to 2 groups: the observation group received a combination of pain nursing and hospice care, while the control group received standard nursing care. The study assessed changes in the numeric rating scale for pain, self-rating anxiety scale (SAS), self-rating depression scale (SDS), cancer fatigue scale (CFS), death attitude, and various quality of life dimensions as measured by the Quality of Life Questionnaire-Core 30. Post-intervention, both groups exhibited reductions in numeric rating scale, SAS, SDS, and CFS scores compared to baseline, with more significant improvements observed in the observation group (P < .05). Additionally, post-intervention scores for death attitude and Quality of Life Questionnaire-Core 30 domains (physical, cognitive, social, role, and emotional functioning, as well as overall health) increased in both groups, with the observation group showing greater improvements than the control group (P < .05). The combination of pain nursing and hospice care significantly reduces pain, anxiety, and depression, decreases cancer-related fatigue, and improves the quality of life and death attitudes in patients with advanced lung cancer, highlighting the benefits of this integrative approach in palliative care settings.

Microtubules and cardiovascular diseases: insights into pathology and therapeutic strategies.

Microtubules, complex cytoskeletal structures composed of tubulin proteins in eukaryotic cells, have garnered recent attention in cardiovascular research. Investigations have focused on the post-translational modifications of tubulin, including acetylation and detyrosination. Perturbations in microtubule homeostasis have been implicated in various pathological processes associated with cardiovascular diseases such as heart failure, ischemic heart disease, and arrhythmias. Thus, elucidating the intricate interplay between microtubule dynamics and cardiovascular pathophysiology is imperative for advancing preventive and therapeutic strategies. Several natural compounds have been identified to potentially modulate microtubules, thereby exerting regulatory effects on cardiovascular diseases. This review synthesizes current literature to delineate the roles of microtubules in cardiovascular diseases and assesses the potential of natural compounds in microtubule-targeted therapies.

Knowledge mapping of ferroptosis in Parkinson's disease: a bibliometric analysis: 2012-2023.

Background: Ferroptosis is a crucial pathogenic mechanism in Parkinson's disease, offering significant potential for pharmacological intervention. Despite its importance, the number of bibliometric analyses examining the relationship between ferroptosis and Parkinson's disease remains limited. This study aims to elucidate the knowledge structure and primary research focuses within this field using various bibliometric tools search. Materials and methods: We conducted a comprehensive literature son ferroptosis in Parkinson's disease using the Web of Science Core Collection database. Bibliometric analyses and visualizations were performed with VOSviewer, examining the geographical and institutional distribution of publications, journal interconnections, and keyword prevalence. Furthermore, CiteSpace was used to visually explore and analyze journal interactions and citation dynamics. The bibliometrix R package facilitated the delineation of collaborative networks across different countries and the construction of visual network representations illustrating relationships among authors, keywords, and journals. Data visualization was further enhanced with Microsoft Office Excel 2021. Results: Recently, there has been a significant increase in publications on ferroptosis, with China emerging as a leading contributor in this research area. Keyword analysis highlights the critical role of ferroptosis in the pathogenesis of Parkinson's disease, identifying GPX4 as a key enzyme mitigating lipid peroxidation. This study also elucidates the connections and distinctions between ferroptosis and other cell death processes such as apoptosis, autophagy, and pyroptosis. Current research primarily focuses on immunotherapy, prognosis, oxidative stress, lipid peroxidation, and the tumor microenvironment. Conclusion: This study provides a comprehensive initial analysis of the research landscape, identifying current focal points and potential future directions for ferroptosis research in Parkinson's disease. The findings leverage a variety of bibliometric methodologies to offer valuable insights into this emerging field.

ß-sitosterol alleviates atherosclerosis by regulating catalase.

The aim of this study is to investigate the main active components of Gegen (Puerariae Lobatae Radix) on atherosclerosis and its mechanism of action. Bioinformatics analysis showed that ß-sitosterol was the most likely active ingredient to mediate the anti-atherosclerotic effects. In vivo experiments showed that ß-sitosterol inhibited plaque formation and platelet activation, and decreased serum total cholesterol (TC) and triglyceride (TG) levels. In vitro experiments showed that ß-sitosterol can inhibit lipid deposition and phenotypic transformation of vascular smooth muscle cells (VSMCs). However, knocking down catalase (CAT), the direct target of ß-sitosterol, not only promoted lipid deposition and phenotypic transformation of VSMCs, but also activated the PI3K/Akt/mTOR pathway, and the mTOR inhibitor (ink-128) can eliminate the effect of CAT knockdown, suggesting that ß-sitosterol may inhibit lipid deposition and phenotypic transformation of VSMCs by activating CAT and silencing the PI3K/Akt/mTOR signaling pathway, thereby alleviating atherosclerosis.

Ionic liquid-functionalized covalent organic frameworks on the surface of silica for online solid-phase extraction.

A covalent organic framework (COF) was gown on porous silica with 1,3,5-tri(4-aminophenyl)benzene and 2,5-divinyl-1,4-phenyldiformaldehyde as monomers, and two ionic liquids were grafted to COF by a click reaction. The materials before and after the modification of ionic liquids were separately packed into solid-phase extraction columns (10 × 4.6 mm, i.d.), which were coupled with liquid chromatography to construct online analysis systems. The extraction mechanisms of polycyclic aromatic hydrocarbons, bisphenols, diphenylalkanes and benzoic acids were investigated on these materials. There were π-π, hydrogen-bond and electrostatic interactions on ionic liquid-functionalized sorbents. After the comparison among these materials, the best sorbent was used, and the analytical method was established and successfully applied to the detection of some estrogens from actual samples. For the analytical method, the detection limit was as low as 0.005 µg L-1, linear range was as wide as 0.017-10.0 µg L-1, and enrichment ratio was as high as 3635. The recoveries in actual samples were 70 %-129 %.

Viability of Whole-Slide Imaging for Intraoperative Touch Imprint Cytological Diagnosis of Axillary Sentinel Lymph Nodes in Breast Cancer Patients.

BACKGROUND: Whole-slide imaging (WSI) is a promising tool in pathology. However, the use of WSI in cytopathology has lagged behind that in histology. We aimed to evaluate the utility of WSI for the intraoperative touch imprint cytological diagnosis of axillary sentinel lymph nodes (SLNs) in breast cancer patients. METHODS: Glass slides from touch imprint cytology of 480 axillary SLNs were scanned using two different WSI scanners. The intra- and interobserver concordance, accuracy, possible reasons for misdiagnosis, scanning time, and review time for three cytopathologists were compared between WSI and light microscopy (LM). RESULTS: A total of 4320 diagnoses were obtained. There was substantial to strong intraobserver concordance when comparing reads among paired LM slides and WSI digital slides (κ coefficient ranged from 0.63 to 0.88, and concordance rates ranged from 94.58% to 98.33%). Substantial to strong interobserver agreement was also observed among the three cytopathologists (κ coefficient ranged from 0.67 to 0.85, and concordance rates ranged from 95.42% to 97.92%). The accuracy of LM was slightly higher (average of 98.06%) than that of WSI (averages of 96.81% and 97.78%). The majority of misdiagnoses were false negative diagnoses due to the following top three causes: few cancer cells, confusing cancer cells with histiocytes, and confusing cancer cells with lymphocytes. CONCLUSIONS: This study is the first to address the feasibility of WSI in touch imprint cytology. The use of WSI for intraoperative touch imprint cytological diagnosis of SLNs is a practical option when experienced staff are not available on-site.

One of the major challenges of masking the bitter taste in medications: an overview of quantitative methods for bitterness.

Objective: The aim of the present study was to carry out a systematic research on bitterness quantification to provide a reference for scholars and pharmaceutical developers to carry out drug taste masking research. Significance: The bitterness of medications poses a significant concern for clinicians and patients. Scientifically measuring the intensity of drug bitterness is pivotal for enhancing drug palatability and broadening their clinical utility. Methods: The current study was carried out by conducting a systematic literature review that identified relevant papers from indexed databases. Numerous studies and research are cited and quoted in this article to summarize the features, strengths, and applicability of quantitative bitterness assessment methods. Results: In our research, we systematically outlined the classification and key advancements in quantitative research methods for assessing drug bitterness, including in vivo quantification techniques such as traditional human taste panel methods, as well as in vitro quantification methods such as electronic tongue analysis. It focused on the quantitative methods and difficulties of bitterness of natural drugs with complex system characteristics and their difficulties in quantification, and proposes possible future research directions. Conclusion: The quantitative methods of bitterness were summarized, which laid an important foundation for the construction of a comprehensive bitterness quantification standard system and the formulation of accurate, efficient and rich taste masking strategies.

Analysis of Lignan Content and Rhizosphere Microbial Diversity of Schisandra chinensis (Turcz.) Baill. Resources.

Genetic and environmental factors influence the growth and quality of medicinal plants. In recent years, rhizosphere microorganisms have also emerged as significant factors affecting the quality of medicinal plants. This study aimed to identify Schisandra resources with high lignan content and analyze the microbial diversity of the rhizosphere soil. High-performance liquid chromatography was used to measure the lignan content in nine Schisandra fruits. High-throughput sequencing was used to analyze the 16S rDNA sequences of rhizosphere bacteria to identify bacterial species diversity. The total lignan content of the nine Schisandra resources ranged from 9.726 mg/g to 14.031 mg/g, with ZJ27 having the highest content and ZJ25 the lowest. Among the six lignan components, Schisandrol A had the highest content, ranging from 5.133 mg/g to 6.345 mg/g, with a significant difference between ZJ25, ZJ27, and other resources (p < 0.05). Schizandrin C had the lowest content, ranging from 0.062 mg/g to 0.419 mg/g, with more significant differences among the resources. A total of 903,933 sequences were obtained from the rhizosphere soil of the nine Schisandra resources, clustered into 10,437 OTUs at a 97% similarity level. The dominant bacterial phyla were Actinobacteriota, Acidobacteriota, Proteobacteria, Chloroflexi, Gemmatimonadota, and Verrucomicrobiota. The dominant bacterial genera were Candidatus_Udaeobacter, Candidatus_Solibacter, RB41, Bradyrhizobium, Gaiella, and Arthrobacter. ZJ27 is the Schisandra resource with the highest lignan content, and the rhizosphere bacteria of Schisandra are rich in diversity. Schisandra B is negatively correlated with Bryobacter, Candidatus_Solibacter, and unnamed genera of Gaiellales.

The Role of m6A Methylation in Tumor Immunity and Immune-Associated Disorder.

N6-methyladenosine (m6A) represents the most prevalent and significant internal modification in mRNA, with its critical role in gene expression regulation and cell fate determination increasingly recognized in recent research. The immune system, essential for defense against infections and maintaining internal stability through interactions with other bodily systems, is significantly influenced by m6A modification. This modification acts as a key post-transcriptional regulator of immune responses, though its effects on different immune cells vary across diseases. This review delineates the impact of m6A modification across major system-related cancers-including those of the respiratory, digestive, endocrine, nervous, urinary reproductive, musculoskeletal system malignancies, as well as acute myeloid leukemia and autoimmune diseases. We explore the pathogenic roles of m6A RNA modifications within the tumor immune microenvironment and the broader immune system, highlighting how RNA modification regulators interact with immune pathways during disease progression. Furthermore, we discuss how the expression patterns of these regulators can influence disease susceptibility to immunotherapy, facilitating the development of diagnostic and prognostic models and pioneering new therapeutic approaches. Overall, this review emphasizes the challenges and prospective directions of m6A-related immune regulation in various systemic diseases throughout the body.

Xanthophyllomyces dendrorhous Is a Safe Dietary Supplement with Potent Antioxidant Defense Enhancing Activity.

Xanthophyllomyces dendrorhous (X. dendrorhous), previously known as Phaffia rhodozyma, is a red yeast that is widely recognized as a rich source of carotenoids, particularly astaxanthin, which exhibits potent antioxidant activity and other health-promoting functions. However, there is currently a lack of research on the safety of consuming X. dendrorhous. To address this, we conducted an acute toxicity study followed by a 90-day subchronic toxicity trial to evaluate the safety of X. dendrorhous and investigate its in vivo antioxidant activity. In the acute toxicity study, Sprague-Dawley rats were administered a maximum of 12 g/kg body weight of X. dendrorhous powder by gavage and survived without any adverse effects for 14 days. In the subsequent subchronic toxicity test, the rats were randomly divided into five groups, each with free access to their diet adulterated with 0% (control), 2.5% (low), 5% (middle), 10% (high), and 20% (extreme high) X. dendrorhous powder. The rats' behavior, body weight, and food intake were monitored during the 90-day experiment. At the end of the experiment, urine, blood, and organs were collected from the rats for biochemical testing. Additionally, the antioxidant activity in rat sera was evaluated. The results of the acute toxicity test demonstrated that the LD50 of X. dendrorhous was greater than 12 g/kg body weight, indicating that the substance was not toxic. Throughout the 90-day period of subchronic toxicity, the triglyceride levels of male rats fed with 10 and 20% X. dendrorhous increased to 1.54 ± 0.17 and 1.55 ± 0.25 mmol/L (P < 0.05), respectively. This may be attributed to the elevated fat content of the diet in the high-dose and extreme high-dose groups, which was 5.5 and 2.5% higher than that in the control, respectively. Additionally, the white pulp in the spleen exhibited an increase, and the number of white blood cells in the extreme high-dose group increased by 2.41 × 109/L (P < 0.05), which may contribute to enhanced immunity. Finally, the body weight, food intake, blood and urine indexes, and histopathological examination results of the organs of the rats did not demonstrate any regular toxic effects. With the adulteration of X. dendrorhous, the activity of GSH-Px in male rats increased by 16-36.32%. The activity of GSH-Px in female rats of the extreme high-dose group increased by 14.70% (P < 0.05). The free radical scavenging ability of ABTS in male rats in the two high-dose groups exhibited an increase of 6.5 and 11.41% (P < 0.05). In contrast, the MDA content of male rats in the extreme high-dose group demonstrated a reduction of 2.73 nmol/mL (P < 0.05). These findings indicate that X. dendrorhous has no toxic effects, can be taken in high doses, and has a beneficial antioxidant effect that may enhance the body's immunity.

Structural basis for difunctional mechanism of m-AMSA against African swine fever virus pP1192R.

The African swine fever virus (ASFV) type II topoisomerase (Topo II), pP1192R, is the only known Topo II expressed by mammalian viruses and is essential for ASFV replication in the host cytoplasm. Herein, we report the structures of pP1192R in various enzymatic stages using both X-ray crystallography and single-particle cryo-electron microscopy. Our data structurally define the pP1192R-modulated DNA topology changes. By presenting the A2+-like metal ion at the pre-cleavage site, the pP1192R-DNA-m-AMSA complex structure provides support for the classical two-metal mechanism in Topo II-mediated DNA cleavage and a better explanation for nucleophile formation. The unique inhibitor selectivity of pP1192R and the difunctional mechanism of pP1192R inhibition by m-AMSA highlight the specificity of viral Topo II in the poison binding site. Altogether, this study provides the information applicable to the development of a pP1192R-targeting anti-ASFV strategy.

The orchestration of cell-cycle reentry and ribosome biogenesis network is critical for cardiac repair.

Rationale: Myocardial infarction (MI) is a severe global clinical condition with widespread prevalence. The adult mammalian heart's limited capacity to generate new cardiomyocytes (CMs) in response to injury remains a primary obstacle in developing effective therapies. Current approaches focus on inducing the proliferation of existing CMs through cell-cycle reentry. However, this method primarily elevates cyclin dependent kinase 6 (CDK6) and DNA content, lacking proper cytokinesis and resulting in the formation of dysfunctional binucleated CMs. Cytokinesis is dependent on ribosome biogenesis (Ribo-bio), a crucial process modulated by nucleolin (Ncl). Our objective was to identify a novel approach that promotes both DNA synthesis and cytokinesis. Methods: Various techniques, including RNA/protein-sequencing analysis, Ribo-Halo, Ribo-disome, flow cytometry, and cardiac-specific tumor-suppressor retinoblastoma-1 (Rb1) knockout mice, were employed to assess the series signaling of proliferation/cell-cycle reentry and Ribo-bio/cytokinesis. Echocardiography, confocal imaging, and histology were utilized to evaluate cardiac function. Results: Analysis revealed significantly elevated levels of Rb1, bur decreased levels of circASXL1 in the hearts of MI mice compared to control mice. Deletion of Rb1 induces solely cell-cycle reentry, while augmenting the Ribo-bio modulator Ncl leads to cytokinesis. Mechanically, bioinformatics and the loss/gain studies uncovered that circASXL1/CDK6/Rb1 regulates cell-cycle reentry. Moreover, Ribo-Halo, Ribo-disome and circRNA pull-down assays demonstrated that circASXL1 promotes cytokinesis through Ncl/Ribo-bio. Importantly, exosomes derived from umbilical cord mesenchymal stem cells (UMSC-Exo) had the ability to enhance cardiac function by facilitating the coordinated signaling of cell-cycle reentry and Ribo-bio/cytokinesis. These effects were attenuated by silencing circASXL1 in UMSC-Exo. Conclusion: The series signaling of circASXL1/CDK6/Rb1/cell-cycle reentry and circASXL1/Ncl/Ribo-bio/cytokinesis plays a crucial role in cardiac repair. UMSC-Exo effectively repairs infarcted myocardium by stimulating CM cell-cycle reentry and cytokinesis in a circASXL1-dependent manner. This study provides innovative therapeutic strategies targeting the circASXL1 signaling network for MI and offering potential avenues for enhanced cardiac repair.

LncRNA HOXA­AS2 promotes the progression of epithelial ovarian cancer via the regulation of miR­372.

Long non-coding RNAs, such as homeobox A cluster antisense RNA2 (HOXA-AS2) are understood to be involved in tumor growth and development of numerous cancers. However, the role of HOXA-AS2 in the progression of human epithelial ovarian cancer (EOC) remains unclear. In the present study, the expression of HOXA-AS2 was found to be upregulated in EOC tissues compared with noncancerous tissues, and to be strongly correlated to an advanced Federation International of Gynecology and Obstetrics grade and poor prognosis. Knockdown of HOXA-AS2 in the EOC cells inhibited cell proliferation, invasion and migration, as well as inducing cell apoptosis. The ENCORI database was used to screen the microRNAs (miRNAs/miRs) that bound to HOXA-AS2, and one was tested using RNA pull-down and luciferase reporter assays. It was demonstrated that HOXA-AS2 functioned through the competing endogenous RNA mechanism to regulate miR-372. It was also demonstrated that the downregulation of miR-372 reversed the inhibitory effects of the knockdown of HOXA-AS2 in EOC cells. These results indicated that HOXA-AS2 promoted EOC progression by regulating the miR-372, which suggests that HOXA-AS2 may be a therapy target for EOC.

A data science roadmap for open science organizations engaged in early-stage drug discovery.

The Structural Genomics Consortium is an international open science research organization with a focus on accelerating early-stage drug discovery, namely hit discovery and optimization. We, as many others, believe that artificial intelligence (AI) is poised to be a main accelerator in the field. The question is then how to best benefit from recent advances in AI and how to generate, format and disseminate data to enable future breakthroughs in AI-guided drug discovery. We present here the recommendations of a working group composed of experts from both the public and private sectors. Robust data management requires precise ontologies and standardized vocabulary while a centralized database architecture across laboratories facilitates data integration into high-value datasets. Lab automation and opening electronic lab notebooks to data mining push the boundaries of data sharing and data modeling. Important considerations for building robust machine-learning models include transparent and reproducible data processing, choosing the most relevant data representation, defining the right training and test sets, and estimating prediction uncertainty. Beyond data-sharing, cloud-based computing can be harnessed to build and disseminate machine-learning models. Important vectors of acceleration for hit and chemical probe discovery will be (1) the real-time integration of experimental data generation and modeling workflows within design-make-test-analyze (DMTA) cycles openly, and at scale and (2) the adoption of a mindset where data scientists and experimentalists work as a unified team, and where data science is incorporated into the experimental design.