Miracle-dz/UniFAR-FTUs huggingface dataset:
The Development of Arthropod Segmentation Across the Embryonic/Post-embryonic Divide – An Evolutionary Perspective

In many arthropods, the appearance of new segments and their differentiation are not completed by the end of embryogenesis but continue, in different form and degree, well after hatching, in some cases up to the last post-embryonic molt. Focusing on the segmentation process currently described as post-embryonic segment addition (or, anamorphosis), we revise here the current knowledge and discuss it in an evolutionary framework which involves data from fossils, comparative morphology of extant taxa and gene expression. We advise that for a better understanding of the developmental changes underlying the evolution of arthropod segmentation, some key concepts should be applied in a critical way. These include the notion of the segment as a body block and the idea that hatching represents a well-defined divide, shared by all arthropods, between two contrasting developmental phases, embryonic vs. post-embryonic. This eventually reveals the complexity of the developmental processes occurring across hatching, which can evolve in different directions and with a different pace, creating the observed vagueness of the embryonic/post-embryonic divide.
A Novel Signature Constructed by RNA-Binding Protein Coding Genes to Improve Overall Survival Prediction of Glioma Patients

RNA binding proteins (RBPs) have been reported to be involved in cancer malignancy but related functions in glioma have been less studied. Herein, we screened 14 prognostic RBP genes and constructed a risk signature to predict the prognosis of glioma patients. Univariate Cox regression was used to identify overall survival (OS)-related RBP genes. Prognostic RBP genes were screened and used to establish the RBP-signature using the least absolute shrinkage and selection operator (Lasso) method in The Cancer Genome Atlas (TCGA) cohort. The 14 RBP genes signature showed robust and stable prognostic value in the TCGA training (n = 562) cohort and in three independent validation cohorts (Chinese Glioma Genome Atlas [CGGA]seq1, CGGAseq2, and GSE16011 datasets comprising 303, 619, and 250 glioma patients, respectively). Risk scores were calculated for each patient and high-risk gliomas were defined by the median risk score in each cohort. Survival analysis in subgroups of glioma patients showed that the RBP-signature retained its prognostic value in low-grade gliomas (LGGs) and glioblastomas (GBM)s. Univariate and multivariate Cox regression analysis in each dataset and the meta cohort revealed that the RBP-signature stratification could efficiently recognize high-risk gliomas [Hazard Ratio (HR):3.662, 95% confidence interval (CI): 3.187–4.208, p < 0.001] and was an independent prognostic factor for OS (HR:1.594, 95% CI: 1.244–2.043, p < 0.001). Biological process and KEGG pathway analysis revealed the RBP gene signature was associated with immune cell activation, the p53 signaling pathway, and the PI3K-Akt signaling pathway and so on. Moreover, a nomogram model was constructed for clinical application of the RBP-signature, which showed stable predictive ability. In summary, the RBP-signature could be a robust indicator for prognostic evaluation and identifying high-risk glioma patients.
Involvement of Circulating Exosomal MicroRNAs in Jian-Pi-Yi-Shen Formula Protection Against Adenine-Induced Chronic Kidney Disease

Jian-Pi-Yi-Shen formula (JPYSF) is a traditional Chinese medicine (TCM) formula used in clinic to treat chronic kidney disease (CKD) for decades. However, the mechanisms of JPYSF in treating CKD have not been fully elucidated. The aim of the present study was to test the renoprotective effect of JPYSF on CKD rat model and investigate the potential mechanism from the perspective of serum exosomal microRNAs (miRNAs). CKD rat model was induced by feeding Sprague-Dawley rats a diet containing 0.75% w/w adenine for four weeks. The rats in the treatment group were given 10.89 g/kg JPYSF by gavage every day, starting from the 3rd week of the adenine-containing diet for six weeks. Serum biochemistry and histopathology were used to evaluate the renoprotective effects of JPYSF. Serum exosomes were isolated by ExoQuick-TC PLUS exosomes extraction kit and were identified by transmission electron microscopy, nanoparticle tracking analysis, and western blot. Exosomal miRNAs profiling was analyzed by small RNA sequencing. The results showed that JPYSF treatment significantly lowered serum creatinine and blood urea nitrogen levels and alleviated renal pathological injury in CKD rats. Furthermore, serum exosomes were successfully isolated and identified. Small RNA sequencing revealed that 4 exosomal miRNAs (miR-192-5p, miR-194-5p, miR-802-5p, and miR-143-3p) were significantly downregulated in the CKD group and were markedly upregulated after JPYSF treatment. At last, miR-192-5p was identified as the most relevant miRNA for CKD diagnosis and JPYSF treatment. In conclusion, JPYSF protects kidney from adenine-induced CKD, which may be associated with modulation of exosomal miRNAs.
Base and Prime Editing Technologies for Blood Disorders

Nuclease-based genome editing strategies hold great promise for the treatment of blood disorders. However, a major drawback of these approaches is the generation of potentially harmful double strand breaks (DSBs). Base editing is a CRISPR-Cas9-based genome editing technology that allows the introduction of point mutations in the DNA without generating DSBs. Two major classes of base editors have been developed: cytidine base editors or CBEs allowing C>T conversions and adenine base editors or ABEs allowing A>G conversions. The scope of base editing tools has been extensively broadened, allowing higher efficiency, specificity, accessibility to previously inaccessible genetic loci and multiplexing, while maintaining a low rate of Insertions and Deletions (InDels). Base editing is a promising therapeutic strategy for genetic diseases caused by point mutations, such as many blood disorders and might be more effective than approaches based on homology-directed repair, which is moderately efficient in hematopoietic stem cells, the target cell population of many gene therapy approaches. In this review, we describe the development and evolution of the base editing system and its potential to correct blood disorders. We also discuss challenges of base editing approaches–including the delivery of base editors and the off-target events–and the advantages and disadvantages of base editing compared to classical genome editing strategies. Finally, we summarize the recent technologies that have further expanded the potential to correct genetic mutations, such as the novel base editing system allowing base transversions and the more versatile prime editing strategy.
Cytokine Signature Induced by SARS-CoV-2 Spike Protein in a Mouse Model

Although COVID-19 has become a major challenge to global health, there are currently no efficacious agents for effective treatment. Cytokine storm syndrome (CSS) can lead to acute respiratory distress syndrome (ARDS), which contributes to most COVID-19 mortalities. Research points to interleukin 6 (IL-6) as a crucial signature of the cytokine storm, and the clinical use of the IL-6 inhibitor tocilizumab shows potential for treatment of COVID-19 patient. In this study, we challenged wild-type and adenovirus-5/human angiotensin-converting enzyme 2-expressing BALB/c mice with a combination of polyinosinic-polycytidylic acid and recombinant SARS-CoV-2 spike-extracellular domain protein. High levels of TNF-α and nearly 100 times increased IL-6 were detected at 6 h, but disappeared by 24 h in bronchoalveolar lavage fluid (BALF) following immunostimulant challenge. Lung injury observed by histopathologic changes and magnetic resonance imaging at 24 h indicated that increased TNF-α and IL-6 may initiate CSS in the lung, resulting in the continual production of inflammatory cytokines. We hypothesize that TNF-α and IL-6 may contribute to the occurrence of CSS in COVID-19. We also investigated multiple monoclonal antibodies (mAbs) and inhibitors for neutralizing the pro-inflammatory phenotype of COVID-19: mAbs against IL-1α, IL-6, TNF-α, and granulocyte-macrophage colony-stimulating factor (GM-CSF), and inhibitors of p38 and JAK partially relieved CSS; mAbs against IL-6, TNF-α, and GM-CSF, and inhibitors of p38, extracellular signal-regulated kinase, and myeloperoxidase somewhat reduced neutrophilic alveolitis in the lung. This novel murine model opens a biologically safe, time-saving avenue for clarifying the mechanism of CSS/ARDS in COVID-19 and developing new therapeutic drugs.
A Selective α7 Nicotinic Acetylcholine Receptor Agonist, PNU-282987, Attenuates ILC2s Activation and Alternaria-Induced Airway Inflammation

Background The anti-inflammatory effect of an α7nAChR agonist, PNU-282987, has previously been explored in the context of inflammatory disease. However, the effects of PNU-282987 on type 2 innate lymphoid cells (ILC2s)-mediated allergic airway inflammation has not yet been established. Aims To determine the effects of PNU-282987 on the function of ILC2s in the context of IL-33– or Alternaria Alternata (AA)– induced airway inflammation. Methods PNU-282987 was administered to mice that received recombinant IL-33 or AA intranasal challenges. Lung histological analysis and flow cytometry were performed to determine airway inflammation and the infiltration and activation of ILC2s. The previously published α7nAChR agonist GTS-21 was employed as a comparable reagent. ILC2s were isolated from murine lung tissue and cultured in vitro in the presence of IL-33, IL-2, and IL-7 with/without either PNU-282987 or GTS-21. The expression of the transcription factors GATA3, IKK, and NF-κB were also determined. Results PNU-282987 and GTS-21 significantly reduced goblet cell hyperplasia in the airway, eosinophil infiltration, and ILC2s numbers in BALF, following IL-33 or AA challenge. In vitro IL-33 stimulation of isolated lung ILC2s showed a reduction of GATA3 and Ki67 in response to PNU-282987 or GTS-21 treatments. There was a significant reduction in IKK and NF-κB phosphorylation in the PNU-282987–treated group when compared to the GTS-21–treated ILC2s. Conclusion PNU-282987 inhibits ILC2-associated airway inflammation, where its effects were comparable to that of GTS-21.
Editorial: The Role of Saliva in Arthropod-Host-Pathogen Relationships

1 Laboratory of Bacteriology, Tick-Pathogen Transmission Unit, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Hamilton, MT, United States, 2 Laboratory of Malaria and Vector Research, Molecular Entomology Unit, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Rockville, MD, United States, 3 Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan, 4 Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, 5 Faculdade de Veterinária, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Large-Scale Counting and Localization of Pineapple Inflorescence Through Deep Density-Estimation

Natural flowering affects fruit development and quality, and impacts the harvest of specialty plants like pineapple. Pineapple growers use chemicals to induce flowering so that most plants within a field produce fruit of high quality that is ready to harvest at the same time. Since pineapple is hand-harvested, the ability to harvest all of the fruit of a field in a single pass is critical to reduce field losses, costs, and waste, and to maximize efficiency. Traditionally, due to high planting densities, pineapple growers have been limited to gathering crop intelligence through manual inspection around the edges of the field, giving them only a limited view of their crop's status. Through the advances in remote sensing and computer vision, we can enable the regular inspection of the field and automated inflorescence counting enabling growers to optimize their management practices. Our work uses a deep learning-based density estimation approach to count the number of flowering pineapple plants in a field with a test MAE of 11.5 and MAPD of 6.37%. Notably, the computational complexity of this method does not depend on the number of plants present and therefore efficiently scale to easily detect over a 1.6 million flowering plants in a field. We further embed this approach in an active learning framework for continual learning and model improvement.
Combination of Polydopamine Coating and Plasma Pretreatment to Improve Bond Ability Between PEEK and Primary Teeth

Preformed crowns are preferred to reduce the failure risk of restoration of primary teeth, but some drawback of conventional material is still a main barrier for their clinical use. Polyether etherketone (PEEK), a tooth colored, high-performance thermoplastic polymer, has been recognized as a promising alternative to manufacture the restoration of primary teeth. However, the hydrophobic surface and low surface energy of PEEK make it hard to establish a strong and durable adhesion. In this study, we have evaluated a modification method of polydopamine (PDA) coating with plasma pretreatment for the PEEK films by physical and chemical characterization, bonding properties, and biocompatibility. The surface properties of PEEK were well-characterized by scanning electron microscope (SEM) and X-ray photoelectron spectroscopy (XPS). The adhesive strength of the PEEK films was greatly improved without significant reduction of the proliferation rate of human gingival fibroblast cells in MTT and Live/Dead assays. Therefore, PDA coating with plasma pretreatment may give a new solution for effective clinical application of PEEK in primary performed crowns.
A Study Protocol for a Parallel-Designed Trial Evaluating the Impact of Plant-Based Diets in Comparison to Animal-Based Diets on Health Status and Prevention of Non-communicable Diseases—The Nutritional Evaluation (NuEva) Study

Background and Aims: Currently, there is a continuing upward trend for plant-based lifestyles in Germany and Europe. The implementation of vegetarian and vegan lifestyles is characterized by omitting defined food groups such as fish, meat, sausage (vegetarians), or dairy products and honey (vegans). This carries the risk of an undersupply of valuable nutrients. The NuEva study is designed to examine this hypothesis and to evaluate the impact of plant-based diets on health status and disease risk. Methods: The NuEva study is a parallel-designed trial with at least 55 participants for each diet (vegetarian, vegan, flexitarian [rare meat/sausage consumption, once or twice per week]), and participants who consume a traditional Western diet as the control group. In the screening period critical nutrients are identified for the studied diets by analysis of a broad spectrum of nutrients in the human samples (fatty acids, vitamins, minerals, trace elements, nutrient metabolites). Results: Based on the data from the screening period, defined menu plans, ensuring an adequate nutrient intake in accordance with the nutritional guidelines are prepared for each group. The plans are adapted and personalized to individual energy requirements based on the basal metabolic rate and physical activity level. The compliance with the NuEva concept and their impact on nutrient status and cardiovascular risk factors are validated during the intervention period of the NuEva study over 1 year. To investigate the impact of the studied diets on the microbiome, feces samples are collected at the beginning and after the 12 months intervention period (follow up: 12 months). Conclusion: The NuEva study is designed to investigate the impact of common diets on health and disease status, with focus on prevention of cardiovascular diseases. In addition, the effectiveness of the prepared nutritional coaching strategy, ensuring optimal nutrient intake in accordance with the guidelines, is validated during the intervention period of the NuEva study. Clinical Trial Registration: Registered under ClinicalTrials.gov Identifier no. NCT03582020.
Marine Oil Snow, a Microbial Perspective

Under certain conditions, dispersed crude oil in the sea combines with organisms, organic matter, and minerals to form marine oil snow (MOS), thereby contributing to the sinking of oil to the seafloor. Marine microbes are the main players in MOS formation, particularly via the production of extracellular polymeric substances. Distinct groups of microbes also consume the majority of the hydrocarbons during descent, leading to enrichment of the less bioavailable hydrocarbons and asphaltenes in the residue. Here we discuss the dynamics of microbial communities in MOS together with their impacts on MOS evolution. We explore the effects of dispersant application on MOS formation, and consider ways in which laboratory experiments investigating MOS formation can be more representative of the situation in the marine environment, which in turn will improve our understanding of the contribution of MOS to the fate of spilled oil.
Clinical and MRI Differences Between Patients With Subacute Combined Degeneration of the Spinal Cord Related vs. Unrelated to Recreational Nitrous Oxide Use: A Retrospective Study

Objective: To explore the clinical and imaging characteristics of subacute combined degeneration of the spinal cord (SCD) related to recreational nitrous oxide (N2O) use. Methods: Clinical and imaging data were retrospectively collected from patients with SCD related to recreational N2O use who were diagnosed and treated at Shengjing Hospital of China Medical University from January 2016 to June 2020. The clinical and imaging features of patients with recreational N2O-related SCD were compared with those of patients with N2O-unrelated SCD, who were diagnosed and treated during the same period of time. Results: The study enrolled 50 patients (male/female: 22/28, age: 21.4 ± 4.7 years) with N2O-related SCD and 48 patients (male/female: 27/21, age: 62.0 ± 11.4 years) with SCD unrelated to N2O use. The most common signs/symptoms of the patients in both groups were limb numbness and weakness and unsteady gait, but the incidence of limb weakness, unsteady gait, disorders of urination and defecation, anorexia, reduced deep sensation in lower limbs, ataxia, and positive Babinski sign were lower in the N2O-related SCD group than those in the N2O-unrelated SCD group (P < 0.05). The functional disability rating score of patients in the N2O-related SCD group (median: 3, IQR: 2–5) was also significantly lower than the score in the N2O-unrelated SCD group (median: 5, IQR: 4–7) (P < 0.05). The serum vitamin B12 level was significantly lower in the N2O-unrelated SCD group (median: 96 pg/mL, IQR: 50–170 pg/mL) than the level in the N2O-related SCD group (median: 218 pg/mL, IQR:121–350 pg/mL) (P < 0.05), while both groups had similarly increased levels of homocysteine (P > 0.05). Compared with the N2O-unrelated SCD patients, more patients with N2O-related SCD had abnormal spinal magnetic resonance imaging (MRI) scans (80.0 vs. 64.2%). The patients with N2O-related SCD also had wider spinal lesions on sagittal MRI (5.3 ± 0.8 mm vs. 4.2 ± 1.0 mm), fewer spinal segments with lesions (median: 5, IQR: 4–6 segments vs. median: 6, IQR: 5–7.5 segments), and a higher incidence of the inverted V sign on axial MRI (72.0 vs. 31.2%) (all P < 0.05). Conclusion: The recreational use of N2O has become an important cause of SCD in young patients. Compared with the N2O-unrelated SCD patients, the N2O-related SCD patients had less severe clinical presentations, less obvious decrease in serum VB12 levels, and more obvious MRI changes.
Successful HCV Therapy Reduces Liver Disease Severity and Inflammation Biomarkers in HIV/HCV-Coinfected Patients With Advanced Cirrhosis: A Cohort Study

Background: Eradication of hepatitis C virus (HCV) promotes an improvement in liver disease and the deactivation of the immune system. Here, we aimed to evaluate the changes in liver disease scores and plasma biomarkers following HCV clearance with direct-acting antivirals (DAAs) in HIV-infected patients with advanced HCV-related cirrhosis. Methods: We performed an observational study of 50 patients with advanced cirrhosis who received DAAs therapy. Variables were assessed at baseline and 48 weeks after HCV treatment completion. Epidemiological and clinical data were collected through an online form. Liver stiffness measurement (LSM), hepatic venous pressure gradient (HVPG), and Child-Pugh-Turcotte (CTP) were evaluated by physicians. Plasma biomarkers were measured by multiplex immunoassay. Results: We found significant decreases in severity scores of liver disease [LSM (q-value < 0.001), HVPG (q-value = 0.011), and CTP (q-value = 0.045)] and plasma biomarkers [LBP (q-value < 0.001), IP-10 (q-value < 0.001), IL-8 (q-value < 0.001), IL-18 (q-value < 0.001), IL-1RA (q-value = 0.013), OPG (q-value < 0.001), sVCAM-1 (q-value < 0.001), sICAM-1 (q-value < 0.001), PAI-1 (q-value = 0.001), and VEGF-A (q-value = 0.006)]. We also found a significant direct association between the change in LSM values and the change in values of LBP (q-value < 0.001), IP-10 (q-value < 0.001), MCP-1 (q-value = 0.008), IL-8 (q-value < 0.001), IL-18 (q-value < 0.001), OPG (q-value = 0.004), sVCAM-1 (q-value < 0.001), sICAM-1 (q-value < 0.001), and PAI-1 (q-value = 0.002). For CTP values, we found significant positive associations with IP-10 (q-value = 0.010), IL-6 (q-value = 0.010), IL-1RA (q-value = 0.033), and sICAM-1 (q-value = 0.010). Conclusion: The HCV eradication with all-oral DAAs in HIV/HCV-coinfected patients with advanced cirrhosis promoted an improvement in the severity of advanced cirrhosis and plasma biomarkers (inflammation, coagulopathy, and angiogenesis). The decrease in plasma biomarkers was mainly related to the reduction in LSM values.