Biological Characteristics Research Articles

ОТ ПОЛИГОНА К КАРБОНОВОЙ ФЕРМЕ: БИЗНЕС-МОДЕЛЬ

In the context of the climate agenda, a systematic presentation of the scientific, methodological and educational tasks of the carbon landfill is given, the «carbon theme» is designated and the subprocesses (main, accompanying, providing and managerial) of the carbon sequestration process implemented on carbon farm plantations as a potential business-process are highlighted. Based on a comparison of well-known approaches to business modeling of entrepreneurial activity, a research hypothesis was formulated and the interpretation, composition of elements of the carbon farm business model, its value proposition were clarified, and the uniqueness of the final product (services for the absorption and sequestration of carbon by «air-plant-soil» ecosystems) was noted. The distinctive characteristics of the dynamic, complex, sensitive and multifactorial natural process of decarbonization as the basis of the operating cycle are substantiated. It is shown that biological features of the business process generate various risks, this does not guarantee sustainable profit generation. A three-link value chain and a business-model mind-map are proposed, which can serve as a working tool for planning, monitoring, diagnostics and critical analysis of the commercialization of an ecosystem service in the context of the emerging sequestration (decarbonization) industry. The scientific novelty of the work consists in adapting the management template «business-model» proven by the practice of industrial enterprises in relation to the new ecosystem service «decarbonization», which is a natural result of the transformation of carbon polygons into carbon farms as business entities.

Classifying Neuronal Cell Types Based on Shared Electrophysiological Information from Humans and Mice.

The brain is an intricate system that controls a variety of functions. It consists of a vast number of cells that exhibit diverse characteristics. To understand brain function in health and disease, it is crucial to classify neurons accurately. Recent advancements in machine learning have provided a way to classify neurons based on their electrophysiological activity. This paper presents a deep-learning framework that classifies neurons solely on this basis. The framework uses data from the Allen Cell Types database, which contains a survey of biological features derived from single-cell recordings from mice and humans. The shared information from both sources is used to classify neurons into their broad types with the help of a joint model. An accurate domain-adaptive model, integrating electrophysiological data from both mice and humans, is implemented. Furthermore, data from mouse neurons, which also includes labels of transgenic mouse lines, is further classified into subtypes using an interpretable neural network model. The framework provides state-of-the-art results in terms of accuracy and precision while also providing explanations for the predictions.

ОТ ПОЛИГОНА К КАРБОНОВОЙ ФЕРМЕ: БИЗНЕС-МОДЕЛЬ

In the context of the climate agenda, a systematic presentation of the scientific, methodological and educational tasks of the carbon landfill is given, the «carbon theme» is designated and the subprocesses (main, accompanying, providing and managerial) of the carbon sequestration process implemented on carbon farm plantations as a potential business-process are highlighted. Based on a comparison of well-known approaches to business modeling of entrepreneurial activity, a research hypothesis was formulated and the interpretation, composition of elements of the carbon farm business model, its value proposition were clarified, and the uniqueness of the final product (services for the absorption and sequestration of carbon by «air-plant-soil» ecosystems) was noted. The distinctive characteristics of the dynamic, complex, sensitive and multifactorial natural process of decarbonization as the basis of the operating cycle are substantiated. It is shown that biological features of the business process generate various risks, this does not guarantee sustainable profit generation. A three-link value chain and a business-model mind-map are proposed, which can serve as a working tool for planning, monitoring, diagnostics and critical analysis of the commercialization of an ecosystem service in the context of the emerging sequestration (decarbonization) industry. The scientific novelty of the work consists in adapting the management template «business-model» proven by the practice of industrial enterprises in relation to the new ecosystem service «decarbonization», which is a natural result of the transformation of carbon polygons into carbon farms as business entities.

Deciphering glutamine metabolism patterns for malignancy and tumor microenvironment in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer characterized by metabolic reprogramming. Glutamine metabolism is pivotal in metabolic reprogramming, contributing to the significant heterogeneity observed in ccRCC. Consequently, developing prognostic markers associated with glutamine metabolism could enhance personalized treatment strategies for ccRCC patients. This study obtained RNA sequencing and clinical data from 763 ccRCC cases sourced from multiple databases. Consensus clustering of 74 glutamine metabolism related genes (GMRGs)- profiles stratified the patients into three clusters, each of which exhibited distinct prognosis, tumor microenvironment, and biological characteristics. Then, six genes (SMTNL2, MIOX, TMEM27, SLC16A12, HRH2, and SAA1) were identified by machine-learning algorithms to develop a predictive signature related to glutamine metabolism, termed as GMRScore. The GMRScore showed significant differences in clinical prognosis, expression profile of immune checkpoints, abundance of immune cells, and immunotherapy response of ccRCC patients. Besides, the nomogram incorporating the GMRScore and clinical features showed strong predictive performance in prognosis of ccRCC patients. ALDH18A1, one of the GRMGs, exhibited elevated expression level in ccRCC and was related to markedly poorer prognosis in the integrated cohort, validated by proteomic profiling of 232 ccRCC samples from Fudan University Shanghai Cancer Center (FUSCC). Conducting western blotting, CCK-8, transwell, and flow cytometry assays, we found the knockdown of ALDH18A1 in ccRCC significantly promoted apoptosis and inhibited proliferation, invasion, and epithelial-mesenchymal transition (EMT) in two human ccRCC cell lines (786-O and 769-P). In conclusion, we developed a glutamine metabolism-related prognostic signature in ccRCC, which is tightly linked to the tumor immune microenvironment and immunotherapy response, potentially facilitating precision therapy for ccRCC patients. Additionally, this study revealed the key role of ALDH18A1 in promoting ccRCC progression for the first time.

New advances of NG2-expressing cell subset in marrow mesenchymal stem cells as novel therapeutic tools for liver fibrosis/cirrhosis

BackgroundBone marrow-derived mesenchymal stem cell (BMMSC)-based therapy has become a major focus for treating liver fibrosis/cirrhosis. However, although these cell therapies promote the treatment of this disease, the heterogeneity of BMMSCs, which causes insufficient efficacy during clinical trials, has not been addressed. In this study, we describe a novel Percoll–Plate–Wait procedure (PPWP) for the isolation of an active cell subset from BMMSC cultures that was characterized by the expression of neuroglial antigen 2 (NG2/BMMSCs).MethodsBy using the key method of PPWP and other classical biological techniques we compared NG2/BMMSCs with parental BMMSCs in biological and functional characteristics within a well-defined diethylnitrosamine (DEN)-induced liver fibrosis/cirrhosis injury male C57BL/6 mouse model also in a culture system. Of note, the pathological alterations in the model is quite similar to humans’.ResultsThe NG2/BMMSCs revealed more advantages compared to parentalBMMSCs. They exhibited greater proliferation potential than parental BMMSCs, as indicated by Ki-67 immunofluorescence (IF) staining. Moreover, higher expression of SSEA-3 (a marker specific for embryonic stem cells) was detected in NG2/BMMSCs than in parental BMMSCs, which suggested that the “stemness” of NG2/BMMSCs was greater than that of parental BMMSCs. In vivo studies revealed that an injection of NG2/BMMSCs into mice with ongoing DEN-induced liver fibrotic/cirrhotic injury enhanced repair and functional recovery to a greater extent than in mice treated with parental BMMSCs. These effects were associated with the ability of NG2/BMMSCs to differentiate into bile duct cells (BDCs). In particular, we discovered for the first time that NG2/BMMSCs exhibit unique characteristics that differ from those of parental BMMSCs in terms of producing liver sinusoidal endothelial cells (LSECs) to reconstruct injured blood vessels and sinusoidal structures in the diseased livers, which are important for initiating hepatocyte regeneration. This unique potential may also suggest that NG2/BMMSCs could be an novel off-liver progenitor of LSECs. Ex vivo studies revealed that the NG2/BMMSCs exhibited a similar trend to that of their in vivo in terms of functional differentiation responding to the DEN-diseased injured liver cues. Additionally, the obvious core role of NG2/BMMSCs in supporting the functions of BMMSCs in bile duct repair and BDC-mediated hepatocyte regeneration might also be a novel finding.ConclusionsOverall, the PPWP-isolated NG2/BMMSCs could be a novel effective cell subset with increased purity to serve as a new therapeutic tool for enhancing treatment efficacy of BMMSCs and special seed cell source (BDCs, LSECs) also for bioliver engineering.

The Development of a Fluorescent Microsatellite Marker Assay for the Pitaya Canker Pathogen (Neoscytalidium dimidiatum)

Pitaya canker, caused by Neoscytalidium dimidiatum, is a destructive disease that significantly threatens the safety of the pitaya industry. The authors of previous studies have mainly focused on its biological characteristics and chemical control. However, there are no molecular markers available thus far that can be used for the population genetics study of this pathogen. In the present study, a draft genome of N. dimidiatum with a total length of 41.46 MB was assembled in which 9863 coding genes were predicted and annotated. In particular, the microsatellite sequences in the draft genome were investigated. To improve the successful screening rate of potentially polymorphic microsatellite makers, another five N. dimidiatum isolates were resequenced and assembled. A total of eight pairs of polymorphic microsatellite primers were screened out based on the polymorphic microsatellite loci after investigating the sequencing and resequencing assemblies of the six isolates. A total of thirteen representative isolates sampled from different pitaya plantations were genotyped in order to validate the polymorphism of the resulting eight markers. The results indicated that these markers were able to distinguish the isolates well. Lastly, a neighbor-joining tree of 35 isolates, sampled from different pitaya plantations located in different regions, was constructed according to the genotypes of the eight molecular markers. The developed tree indicated that these molecular markers had sufficient genotyping capabilities for our test panel of isolates. In summary, we developed a set of polymorphic microsatellite markers in the following study that can effectively genotype and distinguish N. dimidiatum isolates and be utilized in the population genetics study of N. dimidiatum.

The Identification of Kabatiella zeae as a Causal Agent of Northern Anthracnose of Sorghum in China and Estimation of Host Resistance.

Sorghum northern anthracnose is a leaf disease affecting sorghum, which results in plant death and substantial yield loss. This study aimed to effectively understand the disease, clarify its biological characteristics, and evaluate the resistance of germplasm resources. A field sample was collected to isolate and purify the pathogen. The pathogen, identified as Kabatiella zeae Narita et Hiratsuka using both morphological and molecular techniques, was further confirmed as the causative agent of northern anthracnose of sorghum following Robert Koch's principles. The results revealed the optimal culture temperature to be 25 °C, preferred dark culture conditions, and the best growth on potato glucose agar medium with sucrose and L-leucine as the optimal carbon and nitrogen sources, respectively. A total of 138 sorghum germplasm resources were inoculated and evaluated using the isolated pathogen, with 20 lines (14.49%) exhibiting high resistance, 18 lines (13.04%) showing disease resistance, 27 lines (19.57%) demonstrating medium resistance, 37 lines (26.81%) being susceptible, and 36 lines (26.09%) classified as highly susceptible. The indoor fungicide screening was conducted through pathogen medium application, and enilconazole, pyraclostrobin, methylthiophanate, and flusilazole were screened for the best fungicide inhibition with a 100% inhibition rate compared with the control. This study provides reference for field pharmaceutical control in sorghum production.

Single-cell transcriptome analysis reveals two subtypes of tumor cells of sclerosing pneumocytoma with distinct molecular features and clinical implications

Pulmonary sclerosing pneumocytoma (PSP) is a rare, distinctive benign lung adenoma of pneumocyte origin. Despite its rarity, the tumor's unique cellular morphology has sparked ongoing debates regarding the origin of its constituent cells. This study aimed to elucidate the molecular features of PSP tumor cells and enhance our understanding of the cellular processes contributing to PSP formation and biological behavior. Tissue samples from PSP and corresponding normal lung tissues (n = 4) were collected. We employed single-cell RNA sequencing and microarray-based spatial transcriptomic analyses to identify cell types and investigate their transcriptomes, with a focus on transcription factors, enriched gene expression, and single-cell trajectory evaluations. Our analysis identified two types of tumor cells: mesenchymal epithelial dual phenotype cells (MEDPs) and a distinct subpopulation of type II alveolar epithelial cells exhibiting characteristics slightly reminiscent of type I alveolar epithelial cells (AT2Cs), corresponding to histological round stromal cells and surface cuboidal cells, respectively. MEDPs displayed weak alveolar epithelial differentiation but strong collagen production capabilities, as indicated by the expression of both TTF-1 and vimentin. These cells played a pivotal role in forming the solid and sclerotic areas of PSP. Moreover, MEDPs exhibited a pronounced propensity for epithelial-mesenchymal transition, suggesting a greater potential for metastasis compared to AT2Cs. The capillary endothelial cells of PSP displayed notable diversity. Overall, this study provides, for the first time, a comprehensive mapping of the single-cell transcriptome profile of PSP. Our findings delineate two distinct subtypes of tumor cells, MEDPs and AT2Cs, each with its own biological characteristics and spatial distribution. A deeper understanding of these cell types promises insights into the histology and biological behaviors of this rare tumor.

The Development of a Fluorescent Microsatellite Marker Assay for the Pitaya Canker Pathogen (Neoscytalidium dimidiatum)

Pitaya canker, caused by Neoscytalidium dimidiatum, is a destructive disease that significantly threatens the safety of the pitaya industry. The authors of previous studies have mainly focused on its biological characteristics and chemical control. However, there are no molecular markers available thus far that can be used for the population genetics study of this pathogen. In the present study, a draft genome of N. dimidiatum with a total length of 41.46 MB was assembled in which 9863 coding genes were predicted and annotated. In particular, the microsatellite sequences in the draft genome were investigated. To improve the successful screening rate of potentially polymorphic microsatellite makers, another five N. dimidiatum isolates were resequenced and assembled. A total of eight pairs of polymorphic microsatellite primers were screened out based on the polymorphic microsatellite loci after investigating the sequencing and resequencing assemblies of the six isolates. A total of thirteen representative isolates sampled from different pitaya plantations were genotyped in order to validate the polymorphism of the resulting eight markers. The results indicated that these markers were able to distinguish the isolates well. Lastly, a neighbor-joining tree of 35 isolates, sampled from different pitaya plantations located in different regions, was constructed according to the genotypes of the eight molecular markers. The developed tree indicated that these molecular markers had sufficient genotyping capabilities for our test panel of isolates. In summary, we developed a set of polymorphic microsatellite markers in the following study that can effectively genotype and distinguish N. dimidiatum isolates and be utilized in the population genetics study of N. dimidiatum.

Acute Toxicity of Malathion, Permethrin, and Roundup on the Tropical Freshwater Shrimp Xiphocaris elongata (Guérin-Méneville, 1855)

Urban and agricultural runoffs can transport contaminants and pesticides into freshwater ecosystems, particularly in the developing tropics. For instance, organophosphate and pyrethroids pesticides, such as Roundup, Malathion, and Permethrin, have been found in tropical streams. The uncontrolled application of these pesticides has become a growing concern due to their adverse effects on various non-targeted organisms. Unfortunately, most studies have focused on a few selected model species, ignoring the effects on other non-target organisms, which may play an important role in tropical lotic ecosystems. In addition, the biological characteristics of aquatic crustaceans, including their morphology, physiology, and behavior, make them susceptible to toxic chemicals. For this reason, this study used the widely distributed freshwater shrimp Xiphocaris elongata as a model organism to determine the acute toxicity of Permethrin, Malathion, and Roundup. Our results show that the proportion of mortality of X. elongata in each concentration group became progressively higher as the concentration of exposure increased. We also found that the synthetic pyrethroid Permethrin was the most toxic pesticide tested, with a median lethal concentration (LC50) value for 96 h of 3.96 × 10−6 µg·L−1, followed by organophosphate Malathion (8.87 µg·L−1) and Roundup (748.92 µg·L−1). Experiments with this freshwater shrimp showed a good control performance and reproducibility for the tested pesticides. This study demonstrated that X. elongata is a suitable test organism that can be a representative bioindicator of pesticide toxicity in tropical streams.

Soil Giant Phage: Genome and Biological Characteristics of Sinorhizobium Jumbo Phage.

This paper presents the first in-depth research on the biological and genomic properties of lytic rhizobiophage AP-J-162 isolated from the soils of the mountainous region of Dagestan (North Caucasus), which belongs to the centers of origin of cultivated plants, according to Vavilov N.I. The rhizobiophage host strains are nitrogen-fixing bacteria of the genus Sinorhizobium spp., symbionts of leguminous forage grasses. The phage particles have a myovirus virion structure. The genome of rhizobiophage AP-J-162 is double-stranded DNA of 471.5 kb in length; 711 ORFs are annotated and 41 types of tRNAs are detected. The closest phylogenetic relative of phage AP-J-162 is Agrobacterium phage Atu-ph07, but no rhizobiophages are known. The replicative machinery, capsid, and baseplate proteins of phage AP-J-162 are structurally similar to those of Escherichia phage T4, but there is no similarity between their tail protein subunits. Amino acid sequence analysis shows that 339 of the ORFs encode hypothetical or functionally relevant products, while the remaining 304 ORFs are unique. Additionally, 153 ORFs are similar to those of Atu_ph07, with one-third of the ORFs encoding different enzymes. The biological properties and genomic characteristics of phage AP-J-162 distinguish it as a unique model for exploring phage-microbe interactions with nitrogen-fixing symbiotic microorganisms.

The Pattern of Anemia in Pediatric Solid Tumors Prior to and after Chemotherapy- A Retrospective Cohort Study.

Solid pediatric tumors refer to cancers that affect children and adoles-cents, and they present unique challenges due to their distinct biological characteristics and their vulnerability to young patients. This study aims to shed light on addressing anemia and the causes of anemia in patients with solid pediatric tumors. This retrospective cohort comprised 200 healthy children as controls and 235 patients with solid tumors. The study was conducted at first Affiliated Hospital of Zhengzhou University between January 2020 and June 2023. We evaluated different parameters of blood components in controls and patients with solid tumors such as medulloblastoma, neuroblastoma, rhabdomyosarcoma, germ cell tumors, hepatoblastoma and nephroblastoma before and patients with only these tumors 3 weeks after the first cycle of chemotherapy. Further, we evaluated the relationship between serum ferritin and the weight of patients and assessed the relationship be-tween anemia and metastasis to the bone marrow in patients with neuroblastoma and hepatoblas-toma. We observed various combinations of derangements in blood parameters such as hemo-globin, red blood cells, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscu-lar hemoglobin concentration, hematocrit, red cell distribution width, white blood cells, and plate-let in medulloblastoma, neuroblastoma, rhabdomyosarcoma, germ cell tumors, hepatoblastoma and nephroblastoma before and 3 weeks after first cycle of chemotherapy. We found a significant correlation between serum ferritin levels and weight in neuroblastoma patients who are ≤ 2 years (p = 0.022). Involvement of tumor cells in bone marrow correlates with decreased Hb levels in both neuroblastoma (CI = 93.21-106.68, p = 0.001) and hepatoblastoma (CI = 113.36-121.00, p = 0.001). Anemia may manifest as an early symptom in neuroblastoma, hepatoblastoma, and nephroblastoma. Also, anemia may be worse in patients with neuroblastoma and hepatoblastoma after chemotherapy and might warrant anemia therapy.

Acute Toxicity of Malathion, Permethrin, and Roundup on the Tropical Freshwater Shrimp Xiphocaris elongata (Guérin-Méneville, 1855)

Urban and agricultural runoffs can transport contaminants and pesticides into freshwater ecosystems, particularly in the developing tropics. For instance, organophosphate and pyrethroids pesticides, such as Roundup, Malathion, and Permethrin, have been found in tropical streams. The uncontrolled application of these pesticides has become a growing concern due to their adverse effects on various non-targeted organisms. Unfortunately, most studies have focused on a few selected model species, ignoring the effects on other non-target organisms, which may play an important role in tropical lotic ecosystems. In addition, the biological characteristics of aquatic crustaceans, including their morphology, physiology, and behavior, make them susceptible to toxic chemicals. For this reason, this study used the widely distributed freshwater shrimp Xiphocaris elongata as a model organism to determine the acute toxicity of Permethrin, Malathion, and Roundup. Our results show that the proportion of mortality of X. elongata in each concentration group became progressively higher as the concentration of exposure increased. We also found that the synthetic pyrethroid Permethrin was the most toxic pesticide tested, with a median lethal concentration (LC50) value for 96 h of 3.96 × 10−6 µg·L−1, followed by organophosphate Malathion (8.87 µg·L−1) and Roundup (748.92 µg·L−1). Experiments with this freshwater shrimp showed a good control performance and reproducibility for the tested pesticides. This study demonstrated that X. elongata is a suitable test organism that can be a representative bioindicator of pesticide toxicity in tropical streams.

The biological characteristics and infection dynamics of a novel H3N2 canine influenza virus genotype in beagles

BackgroundThe canine influenza virus (CIV) outbreak has garnered considerable attention as it poses a significant threat to dog health. During the H3N2 CIV evolution in beagles, the virus formed a new clade after 2019 and gradually became more adaptable to other mammals. Therefore, successfully elucidating the biological characteristics and constructing a canine influenza infection model is required for CIV characterization.MethodsWe performed genetic analyses to examine the biological characteristics and infection dynamics of CIV.ResultsThe genotype of our H3N2 CIV strain (from 2019 in Shanghai) belonged to the 5.1 clade, which is now prevalent in China. Using MDCK cells, we investigated viral cytopathic effects. Virus size and morphology were observed using transmission electron microscopy. Beagles were also infected with 104, 105, and 106 50% egg-infectious doses (EID50). When compared with the other groups, the 106 EID50 group showed the most obvious clinical symptoms, the highest virus titers, and typical lung pathological changes. Our results suggested that the other two treatments caused mild clinical manifestations and pathological changes. Subsequently, CIV distribution in the 106 EID50 group was detected by hematoxylin and eosin (H&E) and immunofluorescence (IF) staining, which indicated that CIV primarily infected the lungs.ConclusionsThe framework established in this study will guide further CIV prevention strategies.

Genome-wide characterization of drought-responsive long non-coding RNAs in sorghum (Sorghum bicolor)

Drought stress strongly affects crop yield. Although knowledge of long non-coding RNAs (lncRNAs) has been updated continuously and rapidly, information about lncRNAs in drought resistance regulation is extremely limited in sorghum. Here, lncRNA-sequencing was performed with seedlings of a sorghum cultivar (Jinza29) under three water control treatments to investigate the mechanism of lncRNAs responsible for drought resistance in sorghum. A total of 377 differentially expressed lncRNAs (DElncRNAs) were identified. We also predicted 4322 and 2827 transcripts as potential cis-target and trans-target genes for drought-responsive lncRNAs, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that those target genes exhibited marked enrichment into “oxidoreductase activity”, “signal transducer activity”, “DNA repair”, “photosynthesis”, “glutathione metabolism”, and “phenylpropanoid biosynthesis” and other terms associated with abiotic stress resistance. Moreover, several lncRNAs were estimated to modulate the expression of other genes related to stress response and photosynthetic carbon metabolism. Additionally, we found 107 DElncRNAs that might be candidate target mimics for 56 miRNAs. LncRNAs play important roles in drought adaptation of sorghum through interacting with protein-encoding genes. The obtained results provided novel insights into the biological characteristics of lncRNAs and offered potential regulatory factors for genetically enhancing drought resistance in sorghum.

Integrative multi-omics analyses identify molecular subtypes of head and neck squamous cell carcinoma with distinct therapeutic vulnerabilities.

Substantial heterogeneity in molecular features, patient prognoses, and therapeutic responses in head and neck squamous cell carcinomas (HNSCC) highlights the urgent need to develop molecular classifications that reliably and accurately reflect tumor behavior and inform personalized therapy. Here, we leveraged the similarity network fusion bioinformatics approach to jointly analyze multi-omics datasets spanning copy number variations, somatic mutations, DNA methylation, and transcriptomic profiling and derived a prognostic classification system for HNSCC. The integrative model consistently identified three subgroups (IMC1-3) with specific genomic features, biological characteristics, and clinical outcomes across multiple independent cohorts. The IMC1 subgroup included proliferative, immune-activated tumors and exhibited a more favorable prognosis. The IMC2 subtype harbored activated EGFR signaling and an inflamed tumor microenvironment with cancer-associated fibroblast/vascular infiltrations. Alternatively, the IMC3 group featured highly aberrant metabolic activities and impaired immune infiltration and recruiting. Pharmacogenomics analyses from in silico predictions and from patient-derived xenograft model data unveiled subtype-specific therapeutic vulnerabilities including sensitivity to cisplatin and immunotherapy in IMC1 and EGFR inhibitors (EGFRi) in IMC2, which was experimentally validated in patient-derived organoid models. Two signatures for prognosis and EGFRi sensitivity were developed via machine learning. Together, this integrative multi-omics clustering for HNSCC improves current understanding of tumor heterogeneity and facilitates patient stratification and therapeutic development tailored to molecular vulnerabilities.

Upper gastrointestinal bleeding on veno-arterial extracorporeal membrane oxygenation support

IntroductionPatients on veno-arterial extracorporeal membrane oxygenation (V-A ECMO) support are at a high risk of hemorrhagic complications, including upper gastrointestinal bleeding (UGIB). The objective of this study was to evaluate the incidence and impact of this complication in V-A ECMO patients.Materials and methodsA retrospective single-center study (2013–2017) was conducted on V-A ECMO patients, excluding those who died within 24 h. All patients with suspected UGIB underwent esophagogastroduodenoscopy (EGD) and were analyzed and compared to the remainder of the cohort, from the initiation of ECMO until 5 days after explantation.ResultsA total of 150 V-A ECMO cases (65 after cardiac surgery and 85 due to medical etiology) were included. 90% of the patients received prophylactic proton pump inhibitor therapy and enteral nutrition. Thirty-one patients underwent EGD for suspected UGIB, with 16 confirmed cases of UGIB. The incidence was 10.7%, with a median occurrence at 10 [7–17] days. There were no significant differences in clinical or biological characteristics on the day of EGD. However, patients with UGIB had significant increases in packed red blood cells and fresh frozen plasma needs, mechanical ventilation duration and V-A ECMO duration, as well as in length of intensive care unit and hospital stays. There was no significant difference in mortality. The only independent risk factor of UGIB was a history of peptic ulcer (OR = 7.32; 95% CI [1.07–50.01], p = 0.042).ConclusionUGIB occurred in at least 1 out of 10 cases of V-A ECMO patients, with significant consequences on healthcare resources. Enteral nutrition and proton pump inhibitor prophylaxis did not appear to protect V-A ECMO patients. Further studies should assess their real benefits in these patients with high risk of hemorrhage.

Pangenome graph layout by Path-Guided Stochastic Gradient Descent.

The increasing availability of complete genomes demands for models to study genomic variability within entire populations. Pangenome graphs capture the full genomic similarity and diversity between multiple genomes. In order to understand them, we need to see them. For visualization, we need a human-readable graph layout: a graph embedding in low (e.g. two) dimensional depictions. Due to a pangenome graph's potential excessive size, this is a significant challenge. In response, we introduce a novel graph layout algorithm: the Path-Guided Stochastic Gradient Descent (PG-SGD). PG-SGD uses the genomes, represented in the pangenome graph as paths, as an embedded positional system to sample genomic distances between pairs of nodes. This avoids the quadratic cost seen in previous versions of graph drawing by SGD. We show that our implementation efficiently computes the low-dimensional layouts of gigabase-scale pangenome graphs, unveiling their biological features. We integrated PG-SGD in ODGI which is released as free software under the MIT open source license. Source code is available at https://github.com/pangenome/odgi.

Stem Cell-Based Acellular Therapy: Insight into Biogenesis, Bioengineering and Therapeutic Applications of Exosomes

The vast regenerative potential of stem cells has laid the foundation for stem cell-based therapies. However, certain challenges limit the application of cell-based therapies. The therapeutic use of cell-free therapy can avoid limitations associated with cell-based therapies. Acellular stem cell-based therapies rely on the use of biological factors released by stem cells, including growth factors and extracellular vesicles such as exosomes. Due to their comparable regenerative potential, acellular therapies may provide a feasible and scalable alternative to stem cell-based therapies. Exosomes are small vesicles secreted by various types of cells, including stem cells. Exosomes contain parent cell-derived nucleic acids, proteins, lipids, and other bioactive molecules. They play an important role in intra-cellular communication and influence the biological characteristics of cells. Exosomes inherit the properties of their parent cells; therefore, stem cell-derived exosomes are of particular interest for applications of regenerative medicine. In comparison to stem cell-based therapy, exosome therapy offers several benefits, such as easy transport and storage, no risk of immunological rejection, and few ethical dilemmas. Unlike stem cells, exosomes can be lyophilized and stored off-the-shelf, making acellular therapies standardized and more accessible while reducing overall treatment costs. Exosome-based acellular treatments are therefore readily available for applications in patients at the time of care. The current review discusses the use of exosomes as an acellular therapy. The review explores the molecular mechanism of exosome biogenesis, various methods for exosome isolation, and characterization. In addition, the latest advancements in bioengineering techniques to enhance exosome potential for acellular therapies have been discussed. The challenges in the use of exosomes as well as their diverse applications for the diagnosis and treatment of diseases have been reviewed in detail.

O-130 The spatial conformational features of blastocysts can serve as a new basis for selection

Abstract Study question Can spatial conformational features become a new basis for blastocyst selection? Summary answer The spatial conformational features of blastocysts can be associated with clinical outcomes, which is a new basis for blastocyst selection. What is known already At present, the quality evaluation of blastocysts is two-dimensional, and there are relatively few evaluation indicators. There are now methods for exploring three-dimensional reconstruction of blastocysts, including fluorescence staining to obtain three-dimensional structures or artificial rotation to obtain images and restore three-dimensional conformations. However, one drawback of these methods is that they are far from true clinical applications. There are no reports on the reconstruction techniques that can be used in clinical blastocyst selection techniques, and there are no reports on the spatial conformational features related to them. Study design, size, duration This study included 2,141 frozen thaw single blastocyst transfer cycles at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from 2020 to 2021. Simultaneously collect multi-focal plane (11) image data for each blastocyst (EmbryoScope+). The inclusion criteria for patients are those under 40 years old, with an endometrial thickness of 7-16mm, and a history of embryo transfer failure of less than or equal to 1 time. Participants/materials, setting, methods This study iteratively interpolated the 11 focal planes using a multi focal plane generation network model. The contour and spatial information of blastocyst TE and ICM were obtained through deep-learning and segmentation networks. Texture information was extracted using depth estimation and image fusion and mapped to a 3D model to obtain a complete blastocyst spatial model. Then calculate a series of new spatial conformational features of the blastocyst and analyze their correlation with clinical outcomes. Main results and the role of chance We validated the model using the fluorescence reconstruction of human blastocysts as the gold standard (key indicator accuracy>90%). The obtained spatial conformational parameters of blastocysts include: Blastocyst: overall volume (BOV), cystic cavity volume (BCV), surface area (BSA); ICM: volume (IV), surface area (ISA), spatial aspect ratio (ISAr), surface sphericity (ISS), relative distance from ICM to TE (IRD), contact area with TE (ICA); TE cells: number (TN), density (TD), distribution difference (TDD), TE cell roundness (TR), circumference (TC), area (TA) and variance, TE cell aspect ratio (TMM) and variance. The BOV, BCV, and BSA of the blastocyst were positively correlated with clinical pregnancy rate (CPR). The quartile results showed significant differences in CPR when the values were >179 wμm3, 165 wμm3, and 25.8 wμm2, respectively. In terms of ICM, there was no significant difference in CPR among the IV, ISA, IRD, and ICA. However, we found ISAr and ISS had higher CPR in the range of 0.715-0.912 and 0.920-0.943, respectively. In terms of TE, TN is positively correlated with CPR. TD, TDD, TR were not significantly associated with CPR. The pleasing finding is that TC, TA, TMM, and their variances are significantly correlated with CPR. Limitations, reasons for caution The overall quality of blastocysts is relatively good, which is related to the priority thawing of the best blastocysts. Some blastocysts may appear partially out of view, leading to data unavailability and potentially affecting 3D reconstruction. Further exploration and discovery are needed for the spatial conformational features of blastocysts. Wider implications of the findings This work provides a 3D reconstruction system for blastocysts that is closer to clinical applications and discovers new spatial features that are related to clinical outcomes. This enables the study of more dimensional biological characteristics of blastocysts, and our research further promotes the development of embryo reconstruction technology. Trial registration number not applicable