Similar Biological Characteristics Research Articles

Philadelphia chromosome-positive or Philadelphia chromosome-like B-cell precursor acute lymphoblastic leukemia with multilineage involvement in pediatric patients: a report of two cases and literature review.

Based on driver mutations and gene expression profiles, the International Consensus Classification currently divided the entity 'Philadelphia chromosome-positive (Ph+) B-cell precursor acute lymphoblastic leukemia (ALL)' into two subtypes: lymphoid-only and multilineage involvement (Ph+ ALL-L and -M, respectively). The similar biological characteristics of Ph-like ALL and Ph+ ALL drove us to assume that Ph-like ALL-M subtypes exist. This report presents two pediatric ALL cases (one Ph+ and one Ph-like) with minimal residual disease negativity established by multicolor flow cytometry but persistent transcript detection by quantitative PCR (qPCR) even after second-line treatment with tyrosine kinase inhibitors combined with blinatumomab immunotherapy. Using droplet digital PCR, BCR::ABL1 or TPM3::PDGFRB transcripts were identified in CD19+ cells as well as in non-CD19+ cells, suggesting the presence of a Ph+ or Ph-like ALL-M subtype originating from hematopoietic stem cells. This report provides information for better characterization, diagnosis, and treatment of these ALL subtypes.

A remarkable new species of the genus Digitivalva Gaedike, 1970 (Lepidoptera, Glyphipterigidae, Acrolepiinae) from Japan

A new species of the genus Digitivalva Gaedike, 1970 from Japan, D. bella Zhang, Yagi & Hirowatari, sp. nov., is described. The host plant of this species is identified as Carpesium divaricatum Sieb. & Zucc. (Asteraceae). Larvae of this species pupate beneath the host tissue; this habit is for the first time reported for the genus Digitivalva in Japan. Adult specimens with male and female genitalia and pupae are illustrated and described in detail. Although the wing markings differ, the new species is considered closely related to D. arnicella (Heyden, 1863) from Europe, with which it shares similar biological and morphological features.

Mesenchymal Stromal/Stem Cells Isolated by Explant Culture Method from Wharton’s Jelly and Subamnion Possess Similar Biological Characteristics

Human umbilical cord (UC) is an attractive source of mesenchymal stromal/stem cells (MSCs) for tissue engineering and regenerative medicine due to its easy availability, non-invasive procedure of collection, and no ethical concerns. The aim of this study was to isolate MSCs from the Wharton’s jelly (WJ) and subamnion (SA) from the same umbilical cord by an optimized explant method, and to compare the morphology, proliferation, and stemness properties of the MSCs from both sources. Cells from the WJ and SA of six umbilical cords were characterized by flow cytometry, differentiation capacity and proliferation assays, immunofluorescence staining, and RT-PCR. The optimized explant method was successfully used to isolate WJ-MSCs and SA-MSCs. The MSCs from both sources showed similar patterns of growth kinetics, adipogenic and osteogenic potential, and the expression of pluripotency markers (OCT4, SOX2, NANOG, and SSEA-4). The current findings support the usage of the optimized explant method to generate a relatively homogenous population of MSCs from Wharton’s jelly and subamnion, which can facilitate the reproducibility of the results from experimental and practical applications of the obtained cells.

Integrative Multiomic Profiling of Triple-Negative Breast Cancer for Identifying Suitable Therapies.

Triple-negative breast cancer (TNBC) is a heterogeneous disease that carries the poorest prognosis of all breast cancers. Although novel TNBC therapies in development are frequently targeted toward tumors carrying a specific genomic, transcriptomic, or protein biomarker, it is poorly understood how these biomarkers are correlated. To better understand the molecular features of TNBC and their correlation with one another, we performed multimodal profiling on a cohort of 95 TNBC. Our approach involved quantifying tumor-infiltrating lymphocytes through hematoxylin and eosin staining, assessing the abundance of retinoblastoma, androgen receptor, and PDL1 proteins through IHC, and carrying out transcriptomic profiling using the NanoString BC360 platform, targeted DNA sequencing on a subset of cases, as well as evaluating associations with overall survival. Levels of RB1 mRNA and RB proteins are better correlated with markers of retinoblastoma functionality than RB1 mutational status. Luminal androgen receptor tumors clustered into two groups with transcriptomes that cluster with either basal or mesenchymal tumors. Tumors classified as PDL1-positive by the presence of immune or tumor cells showed similar biological characteristics. HER2-low TNBC showed no distinct biological phenotype when compared with HER2-zero. The majority of TNBC were classified as basal or HER2-enriched by PAM50, the latter showing significantly improved overall survival. Our study contributes new insights into biomarker utility for identifying suitable TNBC therapies and the intercorrelations between genomic, transcriptomic, protein, and cellular biomarkers. Additionally, our rich data resource can be used by other researchers to explore the interplay between DNA, RNA, and protein biomarkers in TNBC.

Biologic and prognostic significance of HER2-low and ER-low expressions in de novo metastatic breast cancer.

e13170 Background: It is unclear whether ER-low-positive (ER-low) and HER2-low-positive (HER2-low) biomarkers, as new biological subtypes, have different biological and clinicopathological characteristics in de novo metastatic breast cancer (dnMBC). Per ASCO/CAP guidelines, tumors were defined as HER2-low-positive (HER2-low) if they had an HER2 immunohistochemical (IHC) score of 1+ or 2+ with negative in situ hybridization assay and HER2-0 if they had an HER2 IHC score of 0; ER-low refers to the tumor IHC staining of 1%-10%, if the staining is less than 1%, it is defined as ER-0. This study aimed to investigate whether ER-low and HER2-low expressions is associated with clinicopathologic characteristics and prognosis among patients with de novo metastatic breast cancer. The study was approved by the Ethics Committee of Hebei Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine (2017-AF29-058). Methods: Using hospital-based database, we identified patients with dnMBC diagnosed between 2010 and 2017, retrospectively collecting demographic data, tumor characteristics, treatment types, histopathological report and survival data. According to ASCO/CAP guideline recommendations, patient-specific histopathological results were classified, and IHC-based breast cancer markers, mainly including ER-low and HER2-low, were evaluated and analyzed. Median survival time (MST) was estimated by Kaplan-Meier method and log rank test. Univariable and multivariable analyses were performed using the Cox proportional hazard model to identify statistically significant prognostic factors. All statistical analyses were performed using Stata 18.0. Results: A total of 518 patients (median age of 53 years) were included in this study, including 194 patients with HER2-low, 201 patients with HER2-low, 36 patients with ER-low, and 179 patients with ER-0. Expression of HER2-low was significantly more common among ER-positive tumors (excluding the ER-low) compared with HER2-0 tumors (71.1% vs. 62.2%; P < .001). The MST in the HER2-low cohort was longer than that in the HER2-0 cohort (40 vs. 30 months; HR,0.65; 95% CI, 0.52-0.82, p=.0001); while the MST of ER-low cohort was slightly longer than that of the ER-0 cohort (27 vs. 20 months; HR,0.75; 95% CI, 0.51-1.11, p=.231), but there was no statistical difference. Notably, in the metastasis pattern cohort, HER2-low showed a significantly higher MST compared with HER2-0 (P<.001), with a MST of up to 68 months for bone-only metastases. There was no significant difference in MST between ER-low and ER-0 regardless of whether patients received endocrine therapy (P=.135). Conclusions: In the present study, for dnMBC patients, ER-low expression has similar biological and clinical outcome characteristics as ER-0. However, unlike HER2-0, HER2-low expression may predict a survival benefit in bone-only metastases.

Treatment outcomes and survival of patients with breast cancer aged 75 and older: A comparative study using propensity score-adjusted analysis.

e13763 Background: With an aging society, the incidence of breast cancer among elderly patients is expected to rise. We aimed to explore treatment outcomes in breast cancer patients aged 75 and older at our institution. The lack of consensus on whether adjuvant therapy for elderly breast cancer patients should mimic that for younger patients prompted our investigation. Methods: We conducted a comparative study using data from 1553 breast cancer surgery cases (stage 0-3) treated between April 2007 and August 2021. Patients were divided into two groups: those aged 75 and older (n=184) and those aged 74 and younger (n=1369). Variables investigated included mean age, tumor size, stage, and subtype; surgical procedures and adjuvant therapies; overall survival (OS); and OS in the 75 and older group, considering the presence or absence of hormone therapy, and propensity score-adjusted OS. Results: Comparing the group aged 74 and younger with the group aged 75 and older revealed: Mean age: (55.5 years vs. 79.6 years), tumor size: (2.4 cm vs. 2.3 cm), stage (0/1/2/3) (%): (7.3/43.1/44.1/4/6 vs. 7.6/43.4/43.4/5.7), subtype (Luminal A/Luminal B/TN/HER2) (%): (60.0/16.7/11.3/7.9 vs. 63.5/10.7/15.7/5.7). Except for age, no significant differences were observed. Mastectomy (%): 45.9 vs. 50.8, axillary lymph node dissection (%): 33 vs. 22.3, adjuvant therapy (%): 93.2 vs. 65.7, adjuvant hormone therapy (%): 90 vs. 68, adjuvant chemotherapy (%): 68 vs. 14. The group aged 75 and older received significantly less adjuvant hormone therapy and chemotherapy. Kaplan-Meier 10-year OS rates: 90.3% vs. 77.5%, showing a trend toward lower survival in the group aged 75 and older, albeit not statistically significant. No significant differences were found in overall survival rates by subtype. In the group aged 75 and older, hormone therapy was omitted in 44.6% and administered in 55.4%, resulting in a significant difference in 10-year OS rates (63.5% vs. 84.7%). Following propensity score adjustment for age, stage, and subtype, the hormone therapy-free group exhibited a higher 10-year OS rate of 100%, in contrast to 84.7% in the hormone therapy group. Conclusions: Breast cancer cases in patients aged 75 and older show similar biological characteristics to those aged 74 and younger. The absence of adjuvant therapy does not impact OS, even though elderly patients aged 75 and older are less likely to receive adjuvant hormone therapy and chemotherapy.

A Chymotrypsin-Dependent Live-Attenuated Influenza Vaccine Provides Protective Immunity against Homologous and Heterologous Viruses.

Influenza virus is one of the main pathogens causing respiratory diseases in humans. Vaccines are the most effective ways to prevent viral diseases. However, the limited protective efficacy of current influenza vaccines highlights the importance of novel, safe, and effective universal influenza vaccines. With the progress of the COVID-19 pandemic, live-attenuated vaccines delivered through respiratory mucosa have shown robustly protective efficacy. How to obtain a safe and effective live-attenuated vaccine has become a major challenge. Herein, using the influenza virus as a model, we have established a strategy to quickly obtain a live-attenuated vaccine by mutating the cleavage site of the influenza virus. This mutated influenza virus can be specifically cleaved by chymotrypsin. It has similar biological characteristics to the original strain in vitro, but the safety is improved by at least 100 times in mice. It can effectively protect against lethal doses of both homologous H1N1 and heterologous H5N1 viruses post mucosal administration, confirming that the vaccine generated by this strategy has good safety and broad-spectrum protective activities. Therefore, this study can provide valuable insights for the development of attenuated vaccines for respiratory viruses or other viruses with cleavage sites.

Abstract 1155: Symptomatic Low- And High-degree Carotid Stenoses Exhibit Similar Features Of Plaque Instability

Background: Carotid endarterectomy (CEA) for symptomatic carotid stenosis is recommended for patients with the >70% (NASCET) stenosis but not for those with <50%. Since low-degree stenoses may still cause strokes, refined risk stratification is necessary, which could be improved by incorporating biological features of plaque instability. In order to challenge risk-stratification by the degree of stenosis, we compared biological features of carotid plaques from symptomatic patients with <50% stenosis vs. >70% and explored mechanisms behind plaque instability in low-degree stenoses. Methods: CEA specimens were retrieved from symptomatic patients with >70% (n=204) and <50% stenosis (n=34), all part of the Biobank of Karolinska Endarterectomies (BiKE). Patient demographics, plaque morphology from image analyses of preoperative computed tomography angiography (CTA), and RNA-seq analyses of lesions were used for comparisons. Plaque biology was assessed by transcriptomics using principal component analyses (PCA), differential gene expression (DGE)- and gene-set enrichment analyses (GSEA). Immunohistochemistry (IHC) was used to study proteins corresponding to upregulated genes. Results: The demographics of the two groups were statistically similar. They also showed similar plaque morphology with respect to intraplaque hemorrhage (IPH), plaque burden and fibrous cap thickness, whereas calcification was higher in the <50% group and lipid-rich necrotic core higher in the >70% group. PCA analysis indicated poor clustering, while DGE and GSEA identified enrichment of genes and pathways related to tissue hypoxia and angiogenesis in <50% lesions. Corresponding proteins were detected by IHC in neo-vascularized plaque regions. Conclusions: Plaques from symptomatic patients with <50% carotid stenoses exhibit largely similar morphological and biological features as those from >70% stenoses, emphasizing the need for improved stratification of patients for CEA of symptomatic carotid stenosis. However, pathways associating plaque burden, hypoxia and angiogenesis were particularly enriched in low-grade stenosis lesions suggesting mechanisms behind plaque instability and symptoms in patients with both low- and high-degree stenosis.

The role of the "gut microbiota-mitochondria" crosstalk in the pathogenesis of multiple sclerosis.

Multiple Sclerosis (MS) is a neurologic autoimmune disease whose exact pathophysiologic mechanisms remain to be elucidated. Recent studies have shown that the onset and progression of MS are associated with dysbiosis of the gut microbiota. Similarly, a large body of evidence suggests that mitochondrial dysfunction may also have a significant impact on the development of MS. Endosymbiotic theory has found that human mitochondria are microbial in origin and share similar biological characteristics with the gut microbiota. Therefore, gut microbiota and mitochondrial function crosstalk are relevant in the development of MS. However, the relationship between gut microbiota and mitochondrial function in the development of MS is not fully understood. Therefore, by synthesizing previous relevant literature, this paper focuses on the changes in gut microbiota and metabolite composition in the development of MS and the possible mechanisms of the crosstalk between gut microbiota and mitochondrial function in the progression of MS, to provide new therapeutic approaches for the prevention or reduction of MS based on this crosstalk.

Adipose Tissue and Bone Marrow-Derived Mesenchymal Stem Cells are not Really the Same: Investigating the Differences in Their Immunomodulatory, Migratory, and Adhesive Profile.

Mesenchymal stem cells (MSCs) are the most widely used stem cells in regenerative medicine. They can be isolated from multiple sources, most commonly bone marrow and adipose tissue. MSCs derived from different sources show similar molecular and biological characteristics, but there is ongoing debate regarding the best source of MSCs and the potential biological differences between MSCs from different origins. Bone marrow derived-MSCs (BM-MSCs) and adipose tissue-derived MSCs (AD-MSCs) share many molecular and immunomodulatory properties. In this study, we compared the levels of major immunomodulatory, adhesive, and migratory factors in human BM-MSCs and AD-MSCs under normal conditions, which will help determine the suitability and specificity of each type for certain therapeutic applications. WST1 assay and fluorescent assay SUC-LLVY-AMC were used to measure MSC proliferation and 26S proteasome activity, respectively. Western blotting, ELISA Assays, and bright field live imaging were also used. AD-MSCs and BM-MSCs exhibited similar morphology and proliferation rate. A significantly higher 26S proteasome activity was detected in AD-MSCs than in BM-MSCs. Levels of ICAM-1, integrin α5 and integrin α6 were significantly higher in AD-MSCs compared to BM-MSCs, while no significant difference in CXCR4 levels was observed. Expression of IDO and factor H was significantly higher in AD-MSCs, while CTLA-4 and IL-10 levels were higher in BM-MSCs. This indicates that AD-MSCs and BM-MSCs have different immunomodulatory and adhesion profiles. MSCs isolated from different sources may show differences in their biological and immunomodulatory properties, suggesting a potential suitability of certain MSCs type for specific conditions. Also, combination of different MSCs types could help optimize therapeutic outcomes.

Molecular Phenotypes of Acute Respiratory Distress Syndrome in the ROSE Trial Have Differential Outcomes and Gene Expression Patterns That Differ at Baseline and Longitudinally over Time.

Rationale: Two molecular phenotypes have been identified in acute respiratory distress syndrome (ARDS). In the ROSE (Reevaluation of Systemic Early Neuromuscular Blockade) trial of cisatracurium in moderate to severe ARDS, we addressed three unanswered questions: 1) Do the same phenotypes emerge in a more severe ARDS cohort with earlier recruitment; 2) Do phenotypes respond differently to neuromuscular blockade? and 3) What biological pathways most differentiate inflammatory phenotypes?Methods: We performed latent class analysis in ROSE using preenrollment clinical and protein biomarkers. In a subset of patients (n = 134), we sequenced whole-blood RNA using enrollment and Day 2 samples and performed differential gene expression and pathway analyses. Informed by the differential gene expression analysis, we measured additional plasma proteins and evaluated their abundance relative to gene expression amounts.Measurements and Main Results: In ROSE, we identified the hypoinflammatory (60.4%) and hyperinflammatory (39.6%) phenotypes with similar biological and clinical characteristics as prior studies, including higher mortality at Day 90 for the hyperinflammatory phenotype (30.3% vs. 61.6%; P < 0.0001). We observed no treatment interaction between the phenotypes and randomized groups for mortality. The hyperinflammatory phenotype was enriched for genes associated with innate immune response, tissue remodeling, and zinc metabolism at Day 0 and collagen synthesis and neutrophil degranulation at Day 2. Longitudinal changes in gene expression patterns differed dependent on survivorship. For most highly expressed genes, we observed correlations with their corresponding plasma proteins' abundance. However, for the class-defining plasma proteins in the latent class analysis, no correlation was observed with their corresponding genes' expression.Conclusions: The hyperinflammatory and hypoinflammatory phenotypes have different clinical, protein, and dynamic transcriptional characteristics. These findings support the clinical and biological potential of molecular phenotypes to advance precision care in ARDS.

Infection pattern of Echinorhynchus salobrensis (Acanthocephala) in congeneric species of piranha from a Neotropical floodplain region.

Acanthocephalans are obligate endoparasites characterised by the presence of a proboscis with hooks, which are used to adhere and perforate the intestinal wall of their hosts. Individuals of Echinorhynchus salobrensis Machado Filho, 1948 have been reported parasitising the piranhas Serrasalmus maculatus Kner and Serrasalmus marginatus Valenciennes in the upper Paraná River floodplain. Serrasalmus marginatus is considered non-native at this site, and its establishment occurred after the closure of the Itaipu Hydroelectric, which flooded a natural geographic barrier that separated two ecoregions in the Paraná River. Since they are phylogenetically close and have similar biological and ecological characteristics competition for resources caused the non-native species to become dominant over the native one. Considering the specificity of species of Echinorhynchus Zoega, 1776 in serrasalmids, we evaluated the distribution of E. salobrensis along the gastrointestinal tract of S. maculatus and S. marginatus from the upper Paraná River floodplain. All parasites indices of E. salobrensis were higher in the invasive host S. marginatus when compared to the native S. maculatus. There were no significant interaction effects between host species and sex, and host species and/or sex in the presence of the parasite. When we evaluated the effect of E. salobrensis parasitism on the different gut regions and accessory organs, total abundance was significant in the stomach and caecum organs, and in the first and second regions of the intestine. None of the analytical approaches tested showed an effect of the sex of the host or the sex of the parasite on the presence and abundance of the parasite in the gastrointestinal tract. Studies on acanthocephalan parasitism in fish in Brazil focus on fish farm. The fact that two species of selvage carnivorous fish present high rates of acanthocephalan parasitism, added to the fact that most studies with this group are on farmed fish fed with feed, only emphasise the need for continuity in studies of acanthocephalans in the parasitology of aquatic organisms.

High Grade B-Cell Lymphoma with 11q Aberration Is Not a Rare Event in HIV-Associated Lymphoma

High grade B-cell lymphoma with 11q aberration/diffuse large cell lymphoma with 11q aberration (HGBL-11q; previously classified as Burkitt-like lymphoma with 11q aberration, a provisional category in WHO 4-revised) is a relatively new entity recognized by both the WHO-5 and International Consensus Classification (ICC). These lesions show high grade morphology which is often, but not always, similar to Burkitt lymphoma (BL), and a genetic composition that is similar to that of germinal center (GC) derived diffuse large cell lymphoma (DLBCL). While these lymphomas have been described in immunocompetent patients, where they occur usually in children/adolescents and adults under 60 years, they have been only been rarely described in HIV positive patients. In this study we examined the incidence of the 11q aberration in HIV positive lymphomas. Four tissue microarrays (TMA) containing 144 HIV-associated lymphomas (HIV-NHLs; 57 pre-ART; 16 females; median age 44 years) were examined for the 11q aberration by FISH using the ZytoLight SPEC 11q gain/loss Triple Color Probe (ZytoVision GmbH, Fischai1, Germany). The cases were classified morphologically, evaluated for cell of origin (Hans' criteria; immunohistochemistry for CD10, BCL6, MUM1), the presence of Kaposi sarcoma herpesvirus (KSHV; immunohistochemistry for LANA) and the Epstein Barr virus (EBV; in situ hybridization; EBER probe). Clinical data, when available, was obtained from the EMR. Of the 144 cases, 123 (85%) were evaluable by FISH, including 76 DLBCLs, 10 BL, 14 primary effusion lymphoma (PEL)/EC-PEL, 7 plasmablastic lymphomas, 1 marginal zone lymphomas and 15 polymorphic lymphoproliferative lesions. Four abnormal patterns were seen (Table 1) in 39 cases (32%): polysomy (≥ 3 copies of chromosome 11), 11q23q24 amplification (≥10 copies), variant or atypical 11q aberration (11q24 loss only) and classic or typical 11q aberration (11q23 gain and 11q24 loss). Although survival data was available in only a proportion of HIV+ patients with HGBL-11q, these patients showed in general better survival than patients with other chromosome 11 abnormalities (Table 1) and appear to trend to better survivals compared to HIV+ lymphoma patients without the 11q aberration (alive: 11-202 mo; median 73 mo; died 1 - 45 mo; median 6 mo). Our results demonstrate that chromosome 11 abnormalities are not an uncommon finding in HIV positive lymphoproliferative lesions. Furthermore, although previously only rarely described in HIV+ individuals, HIV-associated lymphomas with the classic or variant 11q aberration is not a rare event. As in immunocompetent patients, the HIV-associated high grade B cell lymphomas with 11q aberration are usually of germinal center origin and EBV negative and in at least some patients are associated with a relatively good prognosis. Thus, these findings indicate that HIV-associated high grade B cell lymphomas with 11q aberration exhibit similar biologic features as those arising in immunocompetent individuals.

Detection and Quantification of Bacteriophages in Wastewater Samples by Culture and Molecular Methods.

Bacteriophages are promising tools for the detection of fecal pollution in water bodies and particularly for viral pathogen risk assessment. Having similar morphological and biological characteristics, bacteriophages are perfect surrogates for the study of the fate and transport of enteric viruses, generally better than any other group of indicators.Different groups of bacteriophages, such as somatic coliphages, F-specific RNA bacteriophages, and bacteriophages infecting selected strains of Bacteroides, have been comprehensively tested as indicators of fecal pollution. Somatic coliphages and F-specific RNA bacteriophages can be used as indicators of general fecal contamination, whereas Bacteroides phages can be used to detect a particular fecal source, for instance, human, bovine, porcine, or poultry fecal contamination.Feasible and cost-effective protocols standardized by the International Standardization Organization and the United States Environmental Protection Agency for the detection of infectious bacteriophages belonging to these three groups are available. Molecular methods for the detection of some particular phages have also been developed. Here we introduce those methods for the detection, enumeration, and isolation of bacteriophages in wastewater samples.

Single-cell transcriptomic atlas throughout anti-BCMA CAR-T therapy in patients with multiple myeloma.

The emergence of chimeric antigen receptor (CAR)-T therapy targeting B cell maturation antigen (BCMA) has improved the prognosis of patients with multiple myeloma (MM); however, the majority of patients eventually experience relapse. In this study, employing the latest single-cell RNA sequencing technology, we examined 24 bone marrow or peripheral blood samples collected throughout the course of anti-BCMA CAR-T therapy, analyzing a total of 59,725 bone marrow cells and 72,479 peripheral blood cells. Our findings reveal that tumor cells in relapsed patient exhibit higher expression levels of HSP90B1 and HSPA5, and demonstrate significantly enriched pathways regarding endoplasmic reticulum stress and unfolded protein response. In the analysis of T cells, we observed that patient with impaired effector function and increased expression of immune checkpoints in endogenous T cell are more susceptible to relapse. Notably, T cells from both the bone marrow microenvironment and peripheral blood share highly similar biological characteristics. Overall, this study provides a comprehensive atlas of endogenous immune cells, particularly in the relatively long term, after CAR-T therapy. It offers clinical evidence for a deeper understanding of the internal environment post CAR-T treatment and for identifying mechanisms underlying relapse.

Informative community structure revealed using Arabidopsis time series transcriptome data via partitioned local depth

Abstract Transcriptome studies that provide temporal information about transcript abundance facilitate identification of gene regulatory networks (GRNs). Inferring GRNs from time series data using computational modeling remains a central challenge in systems biology. Commonly employed clustering algorithms identify modules of like-responding genes but do not provide information on how these modules are interconnected. These methods also require users to specify parameters such as cluster number and size, adding complexity to the analysis. To address these challenges, we used a recently developed algorithm, partitioned local depth (PaLD), to generate cohesive networks for 4 time series transcriptome datasets (3 hormone and 1 abiotic stress dataset) from the model plant Arabidopsis thaliana. PaLD provided a cohesive network representation of the data, revealing networks with distinct structures and varying numbers of connections between transcripts. We utilized the networks to make predictions about GRNs by examining local neighborhoods of transcripts with highly similar temporal responses. We also partitioned the networks into groups of like-responding transcripts and identified enriched functional and regulatory features in them. Comparison of groups to clusters generated by commonly used approaches indicated that these methods identified modules of transcripts that have similar temporal and biological features, but also identified unique groups, suggesting that a PaLD-based approach (supplemented with a community detection algorithm) can complement existing methods. These results revealed that PaLD could sort like-responding transcripts into biologically meaningful neighborhoods and groups while requiring minimal user input and producing cohesive network structure, offering an additional tool to the systems biology community to predict GRNs.

Inhibitory effects on bovine babesial infection by iron chelator, 1-(N-acetyl-6-aminohexyl)− 3-hydroxy-2-methylpyridin-4-one (CM1), and antimalarial drugs

BackgroundBabesiosis is an infectious disease caused by protozoa of the apicomplexan phylum, genus Babesia. It is a malaria-like parasitic disease that can be transmitted via tick bites. The apicomplexan phylum of eukaryotic microbial parasites has had detrimental impacts on human and veterinary medicine. There are only a few drugs currently available to treat this disease; however, parasitic strains that are resistant to these commercial drugs are increasing in numbers. Plasmodium and Babesia are closely related as they share similar biological features including mechanisms for host cell invasion and metabolism. Therefore, antimalarial drugs may be useful in the treatment of Babesia infections. In addition to antimalarials, iron chelators also inhibit parasite growth. In this study, we aimed to evaluate the in vitro inhibitory efficacy of iron chelator and different antimalarials in the treatment of Babesia bovis. MethodsCytotoxicity of antimalarial drugs; pyrimethamine, artefenomel, chloroquine, primaquine, dihydroarthemisinine, and the iron chelator, 1-(N-acetyl-6-aminohexyl)− 3-hydroxy-2 methylpyridin-4-one (CM1), were evaluated against Madin Darby Bovine Kidney (MDBK) cells and compared to diminazene aceturate, which is the currently available drug for animal babesiosis using an MTT solution. Afterwards, an evaluation of the in vitro growth-inhibitory effects of antimalarial drug concentrations was performed and monitored using a flow cytometer. Half maximal inhibitory concentrations (IC50) of each antimalarial and iron chelator were determined and compared to the antibabesial drug, diminazine aceturate, by interpolation using a curve-fitting technique. Subsequently, the effect of the drug combination was assessed by constructing an isobologram. Values of the sum of fractional inhibitions at 50% inhibition were then estimated. ResultsResults indicate that all drugs tested could safely inhibit babesia parasite growth, as high as 2500 μM were non-toxic to mammalian cells. Although no drugs inhibited B. bovis more effectively than diminazine aceturate in this experiment, in vitro growth inhibition results with IC50 values of pyrimethamine 6.25 ± 2.59 μM, artefenomel 2.56 ± 0.67 μM, chloroquine 2.14 ± 0.76 μM, primaquine 22.61 ± 6.72 μM, dihydroarthemisinine 4.65 ± 0.22 μM, 1-(N-acetyl-6-aminohexyl)− 3-hydroxy-2 methylpyridin-4-one (CM1) 9.73 ± 1.90 μM, and diminazine aceturate 0.42 ± 0.01 μM, confirm that all drugs could inhibit B. bovis and could be used as alternative treatments for bovine babesial infection. Furthermore, the efficacy of a combination of the iron chelator, CM1, in combination with artefenomel dihydroarthemisinin or chloroquine, and artefenomel in combination with the iron chelator, CM1, dihydroarthemisinin or chloroquine, exhibited synergism against B. bovis in vitro. ConclusionOur evaluation of the inhibitory efficacy of the iron chelator CM1, antimalarial drugs, and a combination of these drugs against B. bovis could be potentially useful in the development and discovery of a novel drug for the treatment of B. bovis in the future.

MCSNet+: Enhanced Convolutional Neural Network for Detection and Classification of Tribolium and Sitophilus Sibling Species in Actual Wheat Storage Environments.

Insect pests like Tribolium and Sitophilus siblings are major threats to grain storage and processing, causing quality and quantity losses that endanger food security. These closely related species, having very similar morphological and biological characteristics, often exhibit variations in biology and pesticide resistance, complicating control efforts. Accurate pest species identification is essential for effective control, but workplace safety in the grain bin associated with grain deterioration, clumping, fumigator hazards, and air quality create challenges. Therefore, there is a pressing need for an online automated detection system. In this work, we enriched the stored-grain pest sibling image dataset, which includes 25,032 annotated Tribolium samples of two species and five geographical strains from real warehouse and another 1774 from the lab. As previously demonstrated on the Sitophilus family, Convolutional Neural Networks demonstrate distinct advantages over other model architectures in detecting Tribolium. Our CNN model, MCSNet+, integrates Soft-NMS for better recall in dense object detection, a Position-Sensitive Prediction Model to handle translation issues, and anchor parameter fine-tuning for improved matching and speed. This approach significantly enhances mean Average Precision (mAP) for Sitophilus and Tribolium, reaching a minimum of 92.67 ± 1.74% and 94.27 ± 1.02%, respectively. Moreover, MCSNet+ exhibits significant improvements in prediction speed, advancing from 0.055 s/img to 0.133 s/img, and elevates the recognition rates of moving insect sibling species in real wheat storage and visible light, rising from 2.32% to 2.53%. The detection performance of the model on laboratory-captured images surpasses that of real storage facilities, with better results for Tribolium compared to Sitophilus. Although inter-strain variances are less pronounced, the model achieves acceptable detection results across different Tribolium geographical strains, with a minimum recognition rate of 82.64 ± 1.27%. In real-time monitoring videos of grain storage facilities with wheat backgrounds, the enhanced deep learning model based on Convolutional Neural Networks successfully detects and identifies closely related stored-grain pest images. This achievement provides a viable solution for establishing an online pest management system in real storage facilities.

Major considerations of the biological mechanisms of bone regeneration through mesenchymal stem cells, exosomes, and microRNAs in the scenario of bucco-maxillo-facial surgery: a systematic review

Introduction: In the context of bucco-maxillo facial surgery, the development of biomaterials for use in clinical dentistry in recent years has represented a powerful therapeutic instrument in the correction of bone defects. Adult tissue stem cells (mesenchymal stem cells) mediate homeostasis and regeneration of tissues and organs. Growing evidence suggests that metabolism during quiescence, activation, and differentiation may vary between tissues, integrating signaling cues and metabolic inputs with the release of exosomes and microRNAs as important metabolic messengers. Objective: It was to carry out a systematic review to present the main considerations and scientific evidence of the cellular and molecular mechanisms of bone formation or regeneration through mesenchymal stem cells, exosomes, and microRNAs in the scenario of bucco-maxillo-facial surgery with bone graft or biomaterials. Methods: The systematic review rules of the PRISMA Platform were followed. The search was carried out from March to May 2023 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases, with articles dated 2001 (gold standard) through 2022. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed accordingly, according to the Cochrane instrument. Results and Conclusion: A total of 145 articles were found, 45 articles were evaluated and 34 were included and developed in this systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 30 studies with a high risk of bias and 15 studies that did not meet GRADE. The greater potential of guided bone regeneration was associated with the graft material due to the higher grade of vital bone and the lower percentage of residual graft particles. Inorganic bovine bone and porcine bone minerals combined with autogenous maxillary cortical bone showed similar biological and radiological characteristics in terms of biomaterial resorption, osteoconduction, and osteogenesis when used for maxillary sinus floor augmentation. In this regard, three fundamental parameters in bone tissue engineering that determine the capacity for osteoinduction were evidenced, such as the presence of soluble osteoinductive signals, the viability of undifferentiated mesenchymal stem cells, having the ability to differentiate into bone-forming cells and production of adequate extracellular matrix. The exosomes that contain proteins, mRNAs, microRNAs, and DNAs stand out. Exosomes change the biochemical characteristics of recipient cells through the delivery of biomolecules and play a role in cell communication. Evidence suggests that exosomes derived from mesenchymal stem cells exhibit functions similar to mesenchymal stem cells with low immunogenicity and without tumorization.

Stem cell sources from human biological waste material: a role for the umbilical cord and dental pulp stem cells for regenerative medicine.

Stem cell research with biological waste material is an area that holds promise to revolutionize treatment modalities and clinical practice. The interest in surgical remnants is increasing with time as research on human embryonic stem cells remains controversial due to legal and ethical issues. Perhaps, these restrictions are the motivation for the use of alternative mesenchymal stem cell (MSC) sources in the regenerative field. Stem cells (SCs) of Umbilical Cord (UC) and Dental Pulp (DP) have almost similar biological characteristics to other MSCs and can differentiate into a number of cell lineages with enormous potential future prospects. A concise critical observation of UC-MSCs and DP-MSCs is presented here reviewing articles from the last two decades along with other stem cell sources from different biological waste materials.