bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of fishery management parameters for major prey fish species in the lower reaches of the Songhua River
Authors: Lu Wanqiao , Li Peilun , Ma Bo , Huo Tangbin , Yin Zengqiang , Tang Fujiang , Wang Jilong
Published: June 2023

The stability of the ecosystem directly affects the water quality and safety, fishery production, and people’s quality of life along the route. In this study, extensive biological information on five dominant species of prey fish, includingHemiculter leucisculus(Basilewsky, 1855),Acheilognathus macropterus(Bleeker),Rhodeus sericeus(Pallas,1776),Pseudorasbora parva(Temminck & Schlegel, 1846), andSqualidus argentatus(Sauvage & Dabry de Thiersant, 1874), was collected in the lower reaches of the Songhua River, and the population parameters and variation rules of these fish were evaluated. The results showed that at present, the fish resources in the lower reaches of the Songhua River were in an overexploited state. Although the growth rate of prey fish was accelerating, their growth potential was decreasing. In addition to the homogeneous structure of the fish community, it was increasingly evident that a high proportion of small-sized fish were present in the fish community. In addition, the growth length coefficients of the five prey fish species were all greater than 0.2, indicating that the prey fish were growing at a faster rate, and the range of the growth performance indicators were 3.49 ~ 4.37. Our data also demonstrated that the exploitation rates ofHemiculter leucisculusandSqualidus argentatuswere both greater than 0.5, and the exploitation rates of all species were higher thanEmaxexcept forPseudorasbora parva. Finally, based on the above results, the mesh size of all nets should be controlled above 45 mm to ensure the size of the main prey fish populations in the lower reaches of the Songhua River. In summary, these results provided variation rules and growth of prey fish resources in the lower reaches of the Songhua River. At the same time, the distribution of major commercial or endangered baiting grounds in the lower reaches of the Songhua River was determined, which was beneficial to the balance and integrity of the ecosystem.
Long distance dispersal and oceanographic fronts shape the connectivity of the keystone sponge Phakellia ventilabrum in the deep northeast Atlantic
Authors: Taboada Sergi , Whiting Connie , Wang Shuangqiang , Ríos Pilar , Davies Andrew J. , Mienis Furu , Kenchington Ellen , Cárdenas Paco , Cranston Alex , Koutsouveli Vasiliki , Cristobo Javier , Rapp Hans Tore , Drewery Jim , Baldó Francisco , Morrow Christine , Picton Bernard , Xavier Joana R. , Arias Maria Belén , Leiva Carlos , Riesgo Ana
Published: June 2023

Little is known about dispersal in deep-sea ecosystems, especially for sponges, which are abundant ecosystem engineers. Understanding patterns of gene flow in deep-sea sponges is essential, especially in areas where rising pressure from anthropogenic activities makes difficult to combine management and conservation. Here, we combined population genomics and oceanographic modelling to understand how Northeast Atlantic populations (Cantabrian Sea to Norway) of the deep-sea sponge Phakellia ventilabrum are connected. The analysis comprised ddRADseq derived SNP datasets of 166 individuals collected from 57 sampling stations from 17 different areas, including two Marine Protected Areas, one Special Area of Conservation and other areas with different levels of protection. The 4,017 neutral SNPs used indicated high connectivity and panmixis amongst the majority of areas (Ireland to Norway), spanning ca. 2,500-km at depths of 99–900 m. This was likely due to the presence of strong ocean currents allowing long-distance larval transport, as supported by our migration analysis and by 3D particle tracking modelling. On the contrary, the Cantabrian Sea and Roscoff (France) samples, the southernmost areas in our study, appeared disconnected from the remaining areas, probably due to prevailing current circulation patterns and topographic features, which might be acting as barriers for gene flow. Despite this major genetic break, our results suggest that all protected areas studied are well-connected with each other. Interestingly, analysis of SNPs under selection replicated results obtained for neutral SNPs. The relatively low genetic diversity observed along the study area, though, highlights the potential fragility of this species to changing climates, which might compromise resilience to future threats.
Modeling the effects of large-scale interior headland restoration on tidal hydrodynamics and salinity transport in an open coast, marine-dominant estuary
Authors: Passeri Davina L. , Jenkins Robert L. , Poisson Autumn , Bilskie Matthew V. , Bacopoulos Peter
Published: June 2023

The effects of large-scale interior headland restoration on tidal hydrodynamics and salinity transport in an open coast, marine dominant estuary (Grand Bay, Alabama, U.S.A) are investigated using a two-dimensional model, the Discontinuous-Galerkin Shallow Water Equations Model (DG-SWEM). Three restoration alternatives are simulated for present-day conditions, as well as under 0.5 m of sea level rise (SLR). Model results show that the restoration alternatives have no impact on tidal range within the estuary but change maximum tidal velocities by ±5 cm/s in the present-day scenarios and by ±7 cm/s in the scenarios with 0.5 m of SLR. Differences in average salinity concentrations for simulated tropical and frontal seasons show increases and decreases on the order of 2 pss in the embayments surrounding the restoration alternatives; differences were larger (on the order of ±4 pss) for the scenarios with 0.5 m of SLR. There were minimal changes in average salinity outside of the estuary and no changes offshore. The size and position of the alternatives played a role in the salinity response as a result of changing the estuarine shoreline geometry and affecting the fetch within the bay. SLR was more impactful in increasing exposure to low salinity values (i.e., less than 5 pss) than the presence of the restoration alternatives. Overall, the modeled results indicate that these large-scale restoration actions have limited and localized impacts on the hydrodynamics and salinity patterns in this open coast estuary. The results also demonstrate the nonlinear response of salinity to SLR, with increases and decreases in the maximum, mean and minimum daily salinity concentrations from present-day conditions. This nonlinear response was a result of changes in the directions of the residual currents, which affected salinity transport.
Endoglin and squamous cell carcinomas
Authors: Hakuno Sarah K. , Janson Stefanus G. T. , Trietsch Marjolijn D. , de Graaf Manon , de Jonge-Muller Eveline , Crobach Stijn , Harryvan Tom J. , Boonstra Jurjen J. , Dinjens Winand N. M. , Slingerland Marije , Hawinkels Lukas J. A. C.
Published: June 2023

Despite the fact that the role of endoglin on endothelial cells has been extensively described, its expression and biological role on (epithelial) cancer cells is still debatable. Especially its function on squamous cell carcinoma (SCC) cells is largely unknown. Therefore, we investigated SCC endoglin expression and function in three types of SCCs; head and neck (HNSCC), esophageal (ESCC) and vulvar (VSCC) cancers. Endoglin expression was evaluated in tumor specimens and 14 patient-derived cell lines. Next to being expressed on angiogenic endothelial cells, endoglin is selectively expressed by individual SCC cells in tumor nests. Patient derived HNSCC, ESCC and VSCC cell lines express varying levels of endoglin with high interpatient variation. To assess the function of endoglin in signaling of TGF-β ligands, endoglin was overexpressed or knocked out or the signaling was blocked using TRC105, an endoglin neutralizing antibody. The endoglin ligand BMP-9 induced strong phosphorylation of SMAD1 independent of expression of the type-I receptor ALK1. Interestingly, we observed that endoglin overexpression leads to strongly increased soluble endoglin levels, which in turn decreases BMP-9 signaling. On the functional level, endoglin, both in a ligand dependent and independent manner, did not influence proliferation or migration of the SCC cells. In conclusion, these data show endoglin expression on individual cells in the tumor nests in SCCs and a role for (soluble) endoglin in paracrine signaling, without directly affecting proliferation or migration in an autocrine manner.
A novel method of assessing balance and postural sway in patients with hypermobile Ehlers-Danlos syndrome
Authors: Whitmore Miguel , Barker Brittany , Chudej Katie , Goines Ciarra , Kester Jenna , Campbell Hannah , Jeffcoat Anna , Castleberry Brynn , Lowder Thomas William
Published: June 2023

Patients with hypermobile Ehlers-Danlos syndrome (hEDS) frequently suffer from poor balance and proprioception and are at an increased risk for falls. Here we present a means of assessing a variety of balance and postural conditions in a fast and non-invasive manner. The equipment required is commercially available and requires limited personnel. Patients can be repeatedly tested to determine balance and postural differences as a result of disease progression and aging, or a reversal following balance/exercise interventions.
Utilization of—Omic technologies in cold climate hydrocarbon bioremediation: a text-mining approach
Authors: Abdullah Kristopher , Wilkins Daniel , Ferrari Belinda C.
Published: June 2023

Hydrocarbon spills in cold climates are a prominent and enduring form of anthropogenic contamination. Bioremediation is one of a suite of remediation tools that has emerged as a cost-effective strategy for transforming these contaminants in soil, ideally into less harmful products. However, little is understood about the molecular mechanisms driving these complex, microbially mediated processes. The emergence of −omic technologies has led to a revolution within the sphere of environmental microbiology allowing for the identification and study of so called ‘unculturable’ organisms. In the last decade, −omic technologies have emerged as a powerful tool in filling this gap in our knowledge on the interactions between these organisms and their environment in vivo. Here, we utilize the text mining software Vosviewer to process meta-data and visualize key trends relating to cold climate bioremediation projects. The results of text mining of the literature revealed a shift over time from optimizing bioremediation experiments on the macro/community level to, in more recent years focusing on individual organisms of interest, interactions within the microbiome and the investigation of novel metabolic degradation pathways. This shift in research focus was made possible in large part by the rise of omics studies allowing research to focus not only what organisms/metabolic pathways are present but those which are functional. However, all is not harmonious, as the development of downstream analytical methods and associated processing tools have outpaced sample preparation methods, especially when dealing with the unique challenges posed when analyzing soil-based samples.
Promising bioactive metabolites of mangrove inhabitant Streptomyces tauricus and prostate cancer PC3 cell inhibition by antimicrobial peptides
Authors: Karthik Yalpi , Kalyani Manjula Ishwara , Krishnappa Srinivasa , Ramakrishna Krishnaveni , Sayed Samy M. , Aharthy Ohud Muslat , Alhelaify Seham Sater , Mushtaq Muntazir
Published: June 2023

Streptomyces is a group of microbes known for antibiotic production and has contributed to more than 70% of present commercially available antibiotics. These antibiotics are important in the management, protection, and treatment of chronic illnesses. In the present study, the isolated S. tauricus strain from mangrove soil in Mangalore, India (GenBank accession number: MW785875) was subjected for differential cultural characterization, phenotype involving brown pigmentation, filamentous mycelia, and ash-colored spore production was observed using field emission scanning electron microscopy (FESEM) analysis revealing filamentous mycelia possessing a straight spore chain. Spores were visualized as elongated, rod-shaped, smooth surfaces with curved edges. After optimized growth conditions for S. tauricus on starch-casein agar medium, the GC/MS analysis of S. tauricus intracellular extract detected bioactive compounds reported for pharmacological applications. Analyzed using the NIST library, most of the bioactive compounds identified in intracellular extract had molecular weights of less than 1 kDa. On the PC3 cell line, the Sephadex G-10 partially purified eluted peak protein fraction demonstrated significant anticancer activity. The LCMS analysis revealed the presence of Tryprostatin B, Fumonisin B1, Microcystin LR, and Surfactin C with molecular weights below 1 kDa. This study found that small molecular weight microbial compounds are more effective in a variety of biological applications.
Tripartite interactions comprising yeast-endobacteria systems in the gut of vector mosquitoes
Authors: Cappelli Alessia , Damiani Claudia , Capone Aida , Bozic Jovana , Mensah Priscilla , Clementi Emanuela , Spaccapelo Roberta , Favia Guido , Ricci Irene
Published: June 2023

It is shown that bacteria use yeast as a niche for survival in stressful conditions, therefore yeasts may act as temporary or permanent bacterial reservoirs. Endobacteria colonise the fungal vacuole of various osmotolerant yeasts which survive and multiply in sugar-rich sources such as plant nectars. Nectar-associated yeasts are present even in the digestive system of insects and often establish mutualistic symbioses with both hosts. Research on insect microbial symbioses is increasing but bacterial-fungal interactions are yet unexplored. Here, we have focused on the endobacteria ofWickerhamomyces anomalus(formerlyPichia anomalaandCandida pelliculosa), an osmotolerant yeast associated with sugar sources and the insect gut.Symbiotic strains ofW. anomalusinfluence larval development and contribute digestive processes in adults, in addition to exerting wide antimicrobial properties for host defence in diverse insects including mosquitoes. Antiplasmodial effects ofW. anomalushave been shown in the gut of the female malaria vector mosquitoAnopheles stephensi. This discovery highlights the potential of utilizing yeast as a promising tool for symbiotic control of mosquito-borne diseases. In the present study, we have carried out a large Next Generation Sequencing (NGS) metagenomics analysis includingW. anomalusstrains associated with vector mosquitoesAnopheles,AedesandCulex, which has highlighted wide and heterogeneous EB communities in yeast. Furthermore, we have disclosed a Matryoshka-like association in the gut ofA stephensithat comprises different EB in the strain ofW. anomalus WaF17.12. Our investigations started with the localization of fast-moving bacteria-like bodies within the yeast vacuole ofWaF17.12. Additional microscopy analyses have validated the presence of alive intravacuolar bacteria and 16S rDNA libraries fromWaF17.12 have identified a few bacterial targets. Some of these EB have been isolated and tested for lytic properties and capability to re-infect the yeast cell. Moreover, a selective competence to enter yeast cell has been shown comparing different bacteria. We suggested possible tripartite interactions among EB,W. anomalusand the host, opening new knowledge on the vector biology.
Nine new species of black lichenicolous fungi from the genus Cladophialophora (Chaetothyriales) from two different climatic zones of China
Authors: Chang Runlei , Wang Yichen , Liu Yanyu , Wang Yiran , Li Shiguo , Zhao Guoyan , Zhang Susu , Dai Meixue , Zheng Xiaoxiao , Bose Tanay , Si Hongli
Published: June 2023

Lichenicolous fungi are parasites of lichens. Many of these fungi are referred to as “black fungi”. A diversity of these black fungi include species that are pathogenic to humans and plants. A majority of black fungi reside in the phylum Ascomycota within the sub-classes Chaetothyriomycetidae and Dothideomycetidae. To explore the diversity of lichenicolous “black fungi” associated with lichens in China, we conducted several field surveys in the Inner Mongolia Autonomous Region and Yunnan Province between 2019 and 2020. We recovered 1,587 fungal isolates from the lichens collected during these surveys. During the preliminary identification of these isolates using the complete internal transcribed spacer (ITS), partial large subunit of nuclear ribosomal RNA gene (LSU), and small subunit of nuclear ribosomal RNA gene (SSU), we identified 15 fungal isolates from the genus Cladophialophora. However, these isolates had low sequence similarities with all known species from the genus. Therefore, we amplified additional gene regions, such as, translation elongation factor (TEF) and partial β-tubulin gene (TUB), and constructed a multi-gene phylogeny using maximum likelihood, maximum parsimony, and Bayesian inference. In our datasets, we included type sequences where available for all Cladophialophora species. Phylogenetic analyses revealed that none of the 15 isolates belonged to any of the previously described species in the genus. Therefore, using both morphological and molecular data, we classified these 15 isolates as nine new species within the genus Cladophialophora: C. flavoparmeliae, C. guttulate, C. heterodermiae, C. holosericea, C. lichenis, C. moniliformis, C. mongoliae, C. olivacea, and C. yunnanensis. The outcome from this study shows that lichens are an important refugia for black lichenicolous fungi, such as those from Chaetothyriales.
Denitrification contributes to N2O emission in paddy soils
Authors: Xiang Hua , Hong Yiguo , Wu Jiapeng , Wang Yu , Ye Fei , Ye Jiaqi , Lu Jing , Long Aimin
Published: June 2023

Denitrification is vital to nitrogen removal and N2O release in ecosystems; in this regard, paddy soils exhibit strong denitrifying ability. However, the underlying mechanism of N2O emission from denitrification in paddy soils is yet to be elucidated. In this study, the potential N2O emission rate, enzymatic activity for N2O production and reduction, gene abundance, and community composition during denitrification were investigated using the 15N isotope tracer technique combined with slurry incubation, enzymatic activity detection, quantitative polymerase chain reaction (qPCR), and metagenomic sequencing. Results of incubation experiments showed that the average potential N2O emission rates were 0.51 ± 0.20 μmol⋅N⋅kg–1⋅h–1, which constituted 2.16 ± 0.85% of the denitrification end-products. The enzymatic activity for N2O production was 2.77–8.94 times than that for N2O reduction, indicating an imbalance between N2O production and reduction. The gene abundance ratio of nir to nosZ from qPCR results further supported the imbalance. Results of metagenomic analysis showed that, although Proteobacteria was the common phylum for denitrification genes, other dominant community compositions varied for different denitrification genes. Gammaproteobacteria and other phyla containing the norB gene without nosZ genes, including Actinobacteria, Planctomycetes, Desulfobacterota, Cyanobacteria, Acidobacteria, Bacteroidetes, and Myxococcus, may contribute to N2O emission from paddy soils. Our results suggest that denitrification is highly modular, with different microbial communities collaborating to complete the denitrification process, thus resulting in an emission estimation of 13.67 ± 5.44 g N2O⋅m–2⋅yr–1 in surface paddy soils.
Excessively increased thalamocortical connectivity and poor initial antiseizure medication response in epilepsy patients
Authors: Zhong Jiyuan , Tan Ge , Wang Haijiao , Chen Yangmei
Published: June 2023

Objectives

The network mechanism underlying the initial response to antiseizure medication in epilepsy has not been revealed yet. Given the central role of the thalamus in the brain network, we conducted a case-control study to investigate the association between thalamic connectivity and medication response.

Methods

We recruited 39 patients with newly diagnosed and medication-naïve epilepsy of genetic or unknown etiology, including 26 with a good response (GR group) and 13 with a poor response (PR group), and 26 matched healthy participants (control group). We measured the gray matter density (GMD) and the amplitude of low-frequency fluctuation (ALFF) of bilateral thalami. We then set each thalamus as the seed region of interest (ROI) to calculate voxel-wise functional connectivity (FC) and assessed ROI-wise effective connectivity (EC) between the thalamus and targeted regions.

Results

We found no significant difference between groups in the GMD or ALFF of bilateral thalami. However, we observed that the FC values of several circuits connecting the left thalamus and the cortical areas, including the bilateral Rolandic operculum, the left insula, the left postcentral gyrus, the left supramarginal gyrus, and the left superior temporal gyrus, differed among groups (False Discovery Rate correction, P < 0.05), with a higher value in the PR group than in the GR group and/or the control group (Bonferroni correction, P < 0.05). Similarly, both the outflow and the inflow EC in each thalamocortical circuit were higher in the PR group than in the GR group and the control group, although these differences did not remain statistically significant after applying the Bonferroni correction (P < 0.05). The FC showed a positive correlation with the corresponding outflow and inflow ECs for each circuit.

Conclusion

Our finding suggested that patients with stronger thalamocortical connectivity, potentially driven by both thalamic outflowing and inflowing information, may be more likely to respond poorly to initial antiseizure medication.
Cerebellum and hippocampus abnormalities in patients with insomnia comorbid depression: a study on cerebral blood perfusion and functional connectivity
Authors: Xu Minghe , Wang Qian , Li Bo , Qian Shaowen , Wang Shuang , Wang Yu , Chen Chunlian , Liu Zhe , Ji Yuqing , Liu Kai , Xin Kuolin , Niu Yujun
Published: June 2023

Chronic insomnia disorder and major depressive disorder are highly-occurred mental diseases with extensive social harm. The comorbidity of these two diseases is commonly seen in clinical practice, but the mechanism remains unclear. To observe the characteristics of cerebral blood perfusion and functional connectivity in patients, so as to explore the potential pathogenesis and biological imaging markers, thereby improving the understanding of their comorbidity mechanism. 44 patients with chronic insomnia disorder comorbid major depressive disorder and 43 healthy controls were recruited in this study. The severity of insomnia and depression were assessed by questionnaire. The cerebral blood perfusion and functional connectivity values of participants were obtained to, analyze their correlation with questionnaire scores. The cerebral blood flow in cerebellum, vermis, right hippocampus, left parahippocampal gyrus of patients were reduced, which was negatively related to the severity of insomnia or depression. The connectivities of left cerebellum-right putamen and right hippocampus-left inferior frontal gyrus were increased, showing positive correlations with the severity of insomnia and depression. Decreased connectivities of left cerebellum-left fusiform gyrus, left cerebellum-left occipital lobe, right hippocampus-right paracentral lobule, right hippocampus-right precentral gyrus were partially associated with insomnia or depression. The connectivity of right hippocampus-left inferior frontal gyrus may mediate between insomnia and depression. Insomnia and depression can cause changes in cerebral blood flow and brain function. Changes in the cerebellar and hippocampal regions are the result of insomnia and depression. They reflect abnormalities in sleep and emotion regulation. That may be involved in the pathogenesis of comorbidity.
Seed nutritional quality in lentil (Lens culinaris) under different moisture regimes
Authors: Bansal Ruchi , Bana Ram Swaroop , Dikshit Harsh K. , Srivastava Harshita , Priya Swati , Kumar Sunil , Aski Muraleedhar S. , Kumari N. K. Prasanna , Gupta Sanjeev , Kumar Shiv
Published: June 2023

The world’s most challenging environmental issue is climate change. Agricultural productivity and nutritional quality are both substantially threatened by extreme and unpredicted climate events. To develop climate resilient cultivars, stress tolerance along with the grain quality needs to be prioritized. Present study was planned to assess the effect of water limitation on seed quality in lentil, a cool season legume crop. A pot experiment was carried out with 20 diverse lentil genotypes grown under normal (80% field capacity) and limited (25% field capacity) soil moisture. Seed protein, Fe, Zn, phytate, protein and yield were recorded in both the conditions. Seed yield and weight were reduced by 38.9 and 12.1%, respectively, in response to stress. Seed protein, Fe, Zn, its availability as well as antioxidant properties also reduced considerably, while genotype dependent variation was noted with respect to seed size traits. Positive correlation was observed between seed yield and antioxidant activity, seed weight and Zn content and availability in stress. Based on principal component analysis and clustering, IG129185, IC559845, IC599829, IC282863, IC361417, IG334, IC560037, P8114 and L5126 were promising genotypes for seed size, Fe and protein content, while, FLIP-96-51, P3211 and IC398019 were promising for yield, Zn and antioxidant capacity. Identified lentil genotypes can be utilized as trait donors for quality improvement in lentil breeding.
Rac and Cdc42 inhibitors reduce macrophage function in breast cancer preclinical models
Authors: Torres-Sanchez Anamaris , Rivera-Robles Michael , Castillo-Pichardo Linette , Martínez-Ferrer Magaly , Dorta-Estremera Stephanie M. , Dharmawardhane Suranganie
Published: June 2023

Background

Metastatic disease lacks effective treatments and remains the primary cause of mortality from epithelial cancers, especially breast cancer. The metastatic cascade involves cancer cell migration and invasion and modulation of the tumor microenvironment (TME). A viable anti-metastasis strategy is to simultaneously target the migration of cancer cells and the tumor-infiltrating immunosuppressive inflammatory cells such as activated macrophages, neutrophils, and myeloid-derived suppressor cells (MDSC). The Rho GTPases Rac and Cdc42 are ideal molecular targets that regulate both cancer cell and immune cell migration, as well as their crosstalk signaling at the TME. Therefore, we tested the hypothesis that Rac and Cdc42 inhibitors target immunosuppressive immune cells, in addition to cancer cells. Our published data demonstrate that the Vav/Rac inhibitor EHop-016 and the Rac/Cdc42 guanine nucleotide association inhibitor MBQ-167 reduce mammary tumor growth and prevent breast cancer metastasis from pre-clinical mouse models without toxic effects.

Methods

The potential of Rac/Cdc42 inhibitors EHop-016 and MBQ-167 to target macrophages was tested in human and mouse macrophage cell lines via activity assays, MTT assays, wound healing, ELISA assays, and phagocytosis assays. Immunofluorescence, immunohistochemistry, and flow cytometry were used to identify myeloid cell subsets from tumors and spleens of mice following EHop-016 or MBQ-167 treatment.

Results

EHop-016 and MBQ-167 inhibited Rac and Cdc42 activation, actin cytoskeletal extensions, migration, and phagocytosis without affecting macrophage cell viability. Rac/Cdc42 inhibitors also reduced tumor- infiltrating macrophages and neutrophils in tumors of mice treated with EHop-016, and macrophages and MDSCs from spleens and tumors of mice with breast cancer, including activated macrophages and monocytes, following MBQ-167 treatment. Mice with breast tumors treated with EHop-016 significantly decreased the proinflammatory cytokine Interleukin-6 (IL-6) from plasma and the TME. This was confirmed from splenocytes treated with lipopolysaccharide (LPS) where EHop-016 or MBQ-167 reduced IL-6 secretion in response to LPS.

Conclusion

Rac/Cdc42 inhibition induces an antitumor environment via inhibition of both metastatic cancer cells and immunosuppressive myeloid cells in the TME.
Breast cancer: miRNAs monitoring chemoresistance and systemic therapy
Authors: Singh Shivam , Saini Heena , Sharma Ashok , Gupta Subhash , Huddar V. G. , Tripathi Richa
Published: June 2023

With a high mortality rate that accounts for millions of cancer-related deaths each year, breast cancer is the second most common malignancy in women. Chemotherapy has significant potential in the prevention and spreading of breast cancer; however, drug resistance often hinders therapy in breast cancer patients. The identification and the use of novel molecular biomarkers, which can predict response to chemotherapy, might lead to tailoring breast cancer treatment. In this context, accumulating research has reported microRNAs (miRNAs) as potential biomarkers for early cancer detection, and are conducive to designing a more specific treatment plan by helping analyze drug resistance and sensitivity in breast cancer treatment. In this review, miRNAs are discussed in two alternative ways-as tumor suppressors to be used in miRNA replacement therapy to reduce oncogenesis and as oncomirs to lessen the translation of the target miRNA. Different miRNAs like miR-638, miR-17, miR-20b, miR-342, miR-484, miR-21, miR-24, miR-27, miR-23 and miR-200 are involved in the regulation of chemoresistance through diverse genetic targets. For instance, tumor-suppressing miRNAs like miR-342, miR-16, miR-214, and miR-128 and tumor-promoting miRNAs like miR101 and miR-106-25 cluster regulate the cell cycle, apoptosis, epithelial to mesenchymal transition and other pathways to impart breast cancer drug resistance. Hence, in this review, we have discussed the significance of miRNA biomarkers that could assist in providing novel therapeutic targets to overcome potential chemotherapy resistance to systemic therapy and further facilitate the design of tailored therapy for enhanced efficacy against breast cancer.
Emerging diversity in extracellular vesicles and their roles in cancer
Authors: Sohal Ikjot S. , Kasinski Andrea L.
Published: June 2023

Extracellular vesicles have undergone a paradigm shift from being considered as ‘waste bags’ to being central mediators of cell-to-cell signaling in homeostasis and several pathologies including cancer. Their ubiquitous nature, ability to cross biological barriers, and dynamic regulation during changes in pathophysiological state of an individual not only makes them excellent biomarkers but also critical mediators of cancer progression. This review highlights the heterogeneity in extracellular vesicles by discussing emerging subtypes, such as migrasomes, mitovesicles, and exophers, as well as evolving components of extracellular vesicles such as the surface protein corona. The review provides a comprehensive overview of our current understanding of the role of extracellular vesicles during different stages of cancer including cancer initiation, metabolic reprogramming, extracellular matrix remodeling, angiogenesis, immune modulation, therapy resistance, and metastasis, and highlights gaps in our current knowledge of extracellular vesicle biology in cancer. We further provide a perspective on extracellular vesicle-based cancer therapeutics and challenges associated with bringing them to the clinic.
Traditional Chinese medicine inhibits PD-1/PD-L1 axis to sensitize cancer immunotherapy: a literature review
Authors: Zheng Huilan , Wang Gang , Liu Ming , Cheng Hongbin
Published: June 2023

The Programmed death-1 (PD-1) and its programmed death-ligand 1 (PD-L1) comprise the PD-1/PD-L1 axis and maintain tumor immune evasion. Cancer immunotherapy based on anti-PD-1/PD-L1 antibodies is the most promising anti-tumor treatment available but is currently facing the thorny problem of unsatisfactory outcomes. Traditional Chinese Medicine (TCM), with its rich heritage of Chinese medicine monomers, herbal formulas, and physical therapies like acupuncture, moxibustion, and catgut implantation, is a multi-component and multi-target system of medicine known for enhancing immunity and preventing the spread of disease. TCM is often used as an adjuvant therapy for cancer in clinical practices, and recent studies have demonstrated the synergistic effects of combining TCM with cancer immunotherapy. In this review, we examined the PD-1/PD-L1 axis and its role in tumor immune escape while exploring how TCM therapies can modulate the PD-1/PD-L1 axis to improve the efficacy of cancer immunotherapy. Our findings suggest that TCM therapy can enhance cancer immunotherapy by reducing the expression of PD-1 and PD-L1, regulating T-cell function, improving the tumor immune microenvironment, and regulating intestinal flora. We hope this review may serve as a valuable resource for future studies on the sensitization of immune checkpoint inhibitors (ICIs) therapy.
The complexity of DNA damage by radiation follows a Gamma distribution: insights from the Microdosimetric Gamma Model
Authors: Bertolet Alejandro , Chamseddine Ibrahim , Paganetti Harald , Schuemann Jan
Published: June 2023

Introduction

DNA damage is the main predictor of response to radiation therapy for cancer. Its Q8 quantification and characterization are paramount for treatment optimization, particularly in advanced modalities such as proton and alpha-targeted therapy.

Methods

We present a novel approach called the Microdosimetric Gamma Model (MGM) to address this important issue. The MGM uses the theory of microdosimetry, specifically the mean energy imparted to small sites, as a predictor of DNA damage properties. MGM provides the number of DNA damage sites and their complexity, which were determined using Monte Carlo simulations with the TOPAS-nBio toolkit for monoenergetic protons and alpha particles. Complexity was used together with a illustrative and simplistic repair model to depict the differences between high and low LET radiations.

Results

DNA damage complexity distributions were were found to follow a Gamma distribution for all monoenergetic particles studied. The MGM functions allowed to predict number of DNA damage sites and their complexity for particles not simulated with microdosimetric measurements (yF) in the range of those studied.

Discussion

Compared to current methods, MGM allows for the characterization of DNA damage induced by beams composed of multi-energy components distributed over any time configuration and spatial distribution. The output can be plugged into ad hoc repair models that can predict cell killing, protein recruitment at repair sites, chromosome aberrations, and other biological effects, as opposed to current models solely focusing on cell survival. These features are particularly important in targeted alpha-therapy, for which biological effects remain largely uncertain. The MGM provides a flexible framework to study the energy, time, and spatial aspects of ionizing radiation and offers an excellent tool for studying and optimizing the biological effects of these radiotherapy modalities.
Metagenomics analysis of the neonatal intestinal resistome
Authors: Leo Stefano , Cetiner Omer F. , Pittet Laure F. , Messina Nicole L. , Jakob William , Falquet Laurent , Curtis Nigel , Zimmermann Petra
Published: June 2023

Introduction

The intestinal microbiome forms a major reservoir for antibiotic resistance genes (ARGs). Little is known about the neonatal intestinal resistome.

Objective

The objective of this study was to investigate the intestinal resistome and factors that influence the abundance of ARGs in a large cohort of neonates.

Methods

Shotgun metagenomics was used to analyse the resistome in stool samples collected at 1 week of age from 390 healthy, term-born neonates who did not receive antibiotics.

Results

Overall, 913 ARGs belonging to 27 classes were identified. The most abundant ARGs were those conferring resistance to tetracyclines, quaternary ammonium compounds, and macrolide-lincosamide-streptogramin-B. Phylogenetic composition was strongly associated with the resistome composition. Other factors that were associated with the abundance of ARGs were delivery mode, gestational age, birth weight, feeding method, and antibiotics in the last trimester of pregnancy. Sex, ethnicity, probiotic use during pregnancy, and intrapartum antibiotics had little effect on the abundance of ARGs.

Conclusion

Even in the absence of direct antibiotic exposure, the neonatal intestine harbours a high abundance and a variety of ARGs.
Elevated serum polyclonal immunoglobulin free light chains in patients with severe asthma
Authors: Basile Umberto , Santini Giuseppe , Napodano Cecilia , Macis Giuseppe , Pocino Krizia , Gulli Francesca , Malerba Mario , Bush Andrew , Adcock Ian M. , Montuschi Paolo
Published: June 2023

Background: Inflammation plays a pivotal role in the pathophysiology of asthma. Free light chains (FLC) can cause inflammation by mast cell antigen-activation. Serum immunoglobulin (Ig) FLC κ, but not λ, were shown elevated in adult males with asthma. We sought to investigate if serum Ig FLC concentrations are affected by asthma severity and their relationships with inflammatory outcomes.

Methods: By using immunoassays, we measured serum κ and λ Ig FLCs in 24 severe persistent asthma patients, 15 patients with moderate persistent asthma, 15 steroid-naïve mild persistent asthma patients and 20 healthy control subjects in a cross-sectional observational study. Total and specific serum IgE concentrations, fractional exhaled nitric oxide (FENO), lung function, peripheral blood eosinophils and neutrophils, and C reactive protein (CRP) were also measured.

Results: Serum κ FLC concentrations were elevated in severe asthma patients compared mild asthma patients (p < 0.05) and healthy subjects (p < 0.05). Serum λ FLCs were higher in severe asthma patients than in healthy subjects (p < 0.05) and correlated with blood eosinophil counts (percentage, κ: r = 0.51, p = 2.9678−6; λ: r = 0.42, p = 1.7377−4; absolute values, κ: r = 0.45, p = 6.1284−5; λ: r = 0.38, p = 7.8261−4), but not with total or specific serum IgE. In severe asthma patients, serum Ig FLC correlated with serum CRP (κ: r = 0.33; p = 0.003; λ: r = 0.38, p = 8.8305−4) and blood neutrophil cell counts (percentage, κ: r = 0.31; p = 0.008; λ: r = 0.29, p = 0.01; absolute values, κ: r = 0.40; p = 3.9176−4; λ: r = 0.40, p = 4.5479−4), were elevated in subjects with blood eosinophilia (≥300 cells/µL) (n = 13) compared with non-eosinophilic subjects (n = 10) (κ: 19.2 ± 1.2 mg/L versus 12.1 ± 1.3 mg/L, p < 0.001; λ: 27.2 ± 2.6 mg/L versus 16.8 ± 2.5 mg/L, p < 0.01), but were similar in atopic (n = 15) versus nonatopic subjects (n = 9) (κ: p = 0.20; λ: p = 0.80). Serum FLC were negatively correlated with lung function tests, including forced expiratory volume in one second (FEV1) (κ: r = −0.33; p = 0.0034; λ: r = −0.33; p = 0.0035), and FEV1/forced vital capacity ratio (κ: r = −0.33; p = 0.0034; λ: r = −0.33; p = 0.0036).

Conclusion: Serum Ig FLCs are elevated in severe asthma adults and might represent new surrogate markers of inflammation. The pathophysiological implications of these findings require further research. This study was approved by the ethics committee of the University Hospital Agostino Gemelli Foundation and Catholic University of the Sacred Heart (approval number P/1034/CE2012).
A flavonoid-rich fraction of Euphorbia peplus attenuates hyperglycemia, insulin resistance, and oxidative stress in a type 2 diabetes rat model
Authors: Alruhaimi Reem S. , Mostafa-Hedeab Gomaa , Abduh Maisa Siddiq , Bin-Ammar Albandari , Hassanein Emad H. M. , Kamel Emadeldin M. , Mahmoud Ayman M.
Published: June 2023

Background: Type 2 diabetes (T2D) is a metabolic disorder characterized by insulin resistance (IR) and hyperglycemia. Plants are valuable sources of therapeutic agents for the management of T2D. Euphorbia peplus has been widely used as a traditional medicine for the treatment of various diseases, but its beneficial role in T2D has not been fully explored.

Methods: The anti-diabetic efficacy of E. peplus extract (EPE) was studied using rats with T2D induced by high-fat diet (HFD) and streptozotocin (STZ). The diabetic rats received 100, 200, and 400 mg/kg EPE for 4 weeks.

Results: Phytochemical fractionation of the aerial parts of E. peplus led to the isolation of seven known flavonoids. Rats with T2D exhibited IR, impaired glucose tolerance, decreased liver hexokinase and glycogen, and upregulated glycogen phosphorylase, glucose-6-phosphatase (G-6-Pase), and fructose-1,6-bisphosphatase (F-1,6-BPase). Treatment with 100, 200, and 400 mg/kg EPE for 4 weeks ameliorated hyperglycemia, IR, liver glycogen, and the activities of carbohydrate-metabolizing enzymes. EPE attenuated dyslipidemia, serum transaminases, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and liver lipid accumulation, nuclear factor (NF)-κB p65, and lipid peroxidation, nitric oxide and enhanced antioxidants. All EPE doses upregulated serum adiponectin and liver peroxisome proliferator-activated receptor γ (PPARγ) in HFD/STZ-induced rats. The isolated flavonoids showed in silico binding affinity toward hexokinase, NF-κB, and PPARγ.

Conclusion:E. peplus is rich in flavonoids, and its extract ameliorated IR, hyperglycemia, dyslipidemia, inflammation and redox imbalance, and upregulated adiponectin and PPARγ in rats with T2D.
Age-related transversal changes in craniofacial sutures of the anterior viscerocranium in growing rats
Authors: Gorucu-Coskuner Hande , Al-Yassary Mustafa , Billiaert Kelly , Kiliaridis Stavros , Antonarakis Gregory S.
Published: June 2023

Objective: To evaluate the dimensional changes that occur in the internasal and nasopremaxillary sutures, and related transverse craniofacial dimensions, of rats from 4 to 38-weeks of age.

Methods: Four groups of twelve male Wistar rats were sacrificed at different ages [4-weeks (immature), 16-weeks (adolescent), 26-weeks (young adult), 38-weeks (adult)]. The rats were scanned with a high-resolution micro-computed tomography imaging device with 90 µm voxel size and 45 mm × 45 mm field of view (FOV) to obtain images of the viscreocranium, and with 10 µm voxel size and 5 mm × 5 mm FOV to obtain images of the internasal and left nasopremaxillary sutures. The nasal bone width, transverse width between the nasopremaxillary sutures and interzygomatic width were measured as craniofacial measurements. The endocranial, ectocranial and mean suture widths (cross-sectional area between endocranial and ectocranial borders/suture height), and suture height were measured at 5 frontal planes with 1.2 mm intervals. Outcomes were compared at different ages, and correlation coefficients were used to assess the relationship between craniofacial and suture changes.

Results: All transverse craniofacial dimensions increased significantly from 4–16 weeks of age (p < 0.001). After 16-weeks of age, the only significant increase was observed in interzygomatic width (p = 0.02), between 26 and 38 weeks. In both the internasal and nasopremaxillary sutures, the endocranial suture mean widths decreased from 4–16 weeks (p < 0.001 and p = 0.002, respectively), but did not show any significant change after 16-weeks of age. The ectocranial internasal suture width decreased from 4–16 weeks (p < 0.001), increased until 26-weeks (p = 0.035), and subsequently decreased (p < 0.001). The nasopremaxillary suture widths decreased from 4–38 weeks to varying degrees in different frontal planes. Except for the internasal ectocranial suture width, all suture measurements were found highly and negatively correlated with the transverse craniofacial dimensions. The height of the sutures increased with time, with the most significant changes occurring between 4 and 16 weeks of age (p < 0.001).

Conclusion: Although the internasal and nasopremaxillary endocranial suture widths nearly reach their final widths during adolescence, the changes in the ectocranial and mean suture widths continue into early adulthood. These results may serve as a reference for future studies aiming to evaluate the effects of functional demands on suture development and dimensional changes of the viscerocranium.
The use of tensiomyography in older adults: a systematic review
Authors: Pus Katarina , Paravlic Armin H. , Šimunič Boštjan
Published: June 2023

Introduction: Aging of skeletal muscles results in a cascade of events negatively affecting muscle mass, strength, and function, leading to reduced mobility, increased risk of falls, disability, and loss of independence. To date, different methods are used to assess muscle mechanical function, tensiomyography (TMG) being one of them. The aim of this review was twofold: to summarize the evidence-based usefulness of tensiomyography in older adults and to establish reference values for the main tensiomyography parameters in older adults.

Methods: The PubMed, Web of Science, SPORTDiscus, and tensiomyography databases were searched from inception until 25 December 2022. Studies investigating older adults (aged 60+ years) that reported tensiomyography-derived parameters such as contraction time (Tc) and/or maximal displacement (Dm) were included. Methodological quality was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.

Results: In total, eight studies satisfied the inclusion criteria. Tensiomyography has been used on different groups of older adults, including asymptomatic, master athletes, patients with peripheral arterial disease, and patients with end-stage knee osteoarthritis with a mean age of 71.5 ± 5.38 (55.7% male subjects). The most evaluated were leg muscles such as vastus lateralis (VL), gastrocnemius medialis (GM), and biceps femoris (BF). The present review demonstrates that tensiomyography is used to assess neuromuscular function in asymptomatic and diseased older adults. When compared to asymptomatic individuals, power master athletes, knee osteoarthritis patients, and patients diagnosed with peripheral arterial disease have the shortest Tc in BF, VL, and GM muscles, respectively. On the other hand, endurance master athletes showed the longest Tc in all three evaluated muscles. Less mobile, nursing-home residents showed higher Dm in VL and BF, while lower Dm in GM than the asymptomatic group. The knee osteoarthritis group showed the largest Dm in BF and VL while having the smallest Dm in GM.

Conclusion: Tensiomyography can serve as a valuable tool for assessing neuromuscular function in older adults. The method is sensitive to muscle composition, architecture, and (pre) atrophic changes of the skeletal muscles and might be responsive to muscle quality changes in aging and diseased populations.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=402345, identifier CRD42023402345.
Metabolic profiling and expression analysis of key genetic factors in the biosynthetic pathways of antioxidant metabolites in mungbean sprouts
Authors: Kim Byeong Cheol , Lim Insu , Ha Jungmin
Published: June 2023

Mungbeans (Vigna radiata L.), a major legume crop in Asia, contain higher amounts of functional substances than other legumes, such as catechin, chlorogenic acid, and vitexin. Germination can improve the nutritional value of legume seeds. Here, 20 functional substances were profiled in germinated mungbeans and the expression levels of the transcripts of key enzymes in targeted secondary metabolite biosynthetic pathways were identified. VC1973A, a reference mungbean elite cultivar, had the highest amount of gallic acid (99.93 ± 0.13 mg/100 g DW) but showed lower contents of most metabolites than the other genotypes. Wild mungbeans contained a large amount of isoflavones compared with cultivated genotypes, especially for daidzin, genistin and glycitin. The expression of key genes involved in biosynthetic pathways had significant positive or negative correlations with the target secondary metabolite contents. The results indicate that functional substance contents are regulated at the transcriptional level, which can be applied to improve the nutritional value of mungbean sprouts in molecular breeding or genetic engineering, and wild mungbeans are a useful resource to improve the quality of mungbean sprouts.