Substantiation of Parameters and Operating Modes for the Bunch Planting Device of the Pneumatic Seeder

Abstract The purpose of this work is to develop a dosing system that provides high-quality bunch planting of watermelon seeds with a given seeding rate and their uniform distribution over the plant nutrition area. It is important to know how many seeds it is needed in the bunch in order to provide the required number of plants in a certain plant nutrition area. The method to achieve this goal is to determine the optimal operating modes for the seeding device, in which the dosing system would supply the seed to the bunch without gaps, searching for dependencies that can determine the required number of the sown seeds in the bunch, taking into account their germination and the number of plants specified by agrotechnical conditions in every bunch. Based on the obtained dependencies, determining the probability of bunches with various numbers of plants, while sowing four seeds in the seedbed with maximum field germination, the design of experimental seed discs is proposed, allowing bunch planting and germination due to easy destruction of the soil crust. At the same time, optimal use of the nutritional area for plants, and, consequently, an increase in the yield of the sown crops is ensured. Experimental seed discs with a group arrangement of suction holes (four cells each) will provide bunch planting of watermelon seeds in accordance with agrotechnical requirements

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Carborane-Containing Folic Acid bis-Amides: Synthesis and In Vitro Evaluation of Novel Promising Agents for Boron Delivery to Tumour Cells

The design of highly selective low-toxic, low-molecular weight agents for boron delivery to tumour cells is of decisive importance for the development of boron neutron capture therapy (BNCT), a modern efficient combined method for cancer treatment. In this work, we developed a simple method for the preparation of new closo- and nido-carborane-containing folic acid bis-amides containing 18–20 boron atoms per molecule. Folic acid derivatives containing nido-carborane residues were characterised by high water solubility, low cytotoxicity, and demonstrated a good ability to deliver boron to tumour cells in in vitro experiments (up to 7.0 µg B/106 cells in the case of U87 MG human glioblastoma cells). The results obtained demonstrate the high potential of folic acid–nido-carborane conjugates as boron delivery agents to tumour cells for application in BNCT

The Toll-Like Receptor 5 Agonist Entolimod Mitigates Lethal Acute Radiation Syndrome in Non-Human Primates.

There are currently no approved medical radiation countermeasures (MRC) to reduce the lethality of high-dose total body ionizing irradiation expected in nuclear emergencies. An ideal MRC would be effective even when administered well after radiation exposure and would counteract the effects of irradiation on the hematopoietic system and gastrointestinal tract that contribute to its lethality. Entolimod is a Toll-like receptor 5 agonist with demonstrated radioprotective/mitigative activity in rodents and radioprotective activity in non-human primates. Here, we report data from several exploratory studies conducted in lethally irradiated non-human primates (rhesus macaques) treated with a single intramuscular injection of entolimod (in the absence of intensive individualized supportive care) administered in a mitigative regimen, 1-48 hours after irradiation. Following exposure to LD50-70/40 of radiation, injection of efficacious doses of entolimod administered as late as 25 hours thereafter reduced the risk of mortality 2-3-fold, providing a statistically significant (P<0.01) absolute survival advantage of 40-60% compared to vehicle treatment. Similar magnitude of survival improvement was also achieved with drug delivered 48 hours after irradiation. Improved survival was accompanied by predominantly significant (P<0.05) effects of entolimod administration on accelerated morphological recovery of hematopoietic and immune system organs, decreased severity and duration of thrombocytopenia, anemia and neutropenia, and increased clonogenic potential of the bone marrow compared to control irradiated animals. Entolimod treatment also led to reduced apoptosis and accelerated crypt regeneration in the gastrointestinal tract. Together, these data indicate that entolimod is a highly promising potential life-saving treatment for victims of radiation disasters

HK3 overexpression associated with epithelial-mesenchymal transition in colorectal cancer

Abstract Background Colorectal cancer (CRC) is a common cancer worldwide. The main cause of death in CRC includes tumor progression and metastasis. At molecular level, these processes may be triggered by epithelial-mesenchymal transition (EMT) and necessitates specific alterations in cell metabolism. Although several EMT-related metabolic changes have been described in CRC, the mechanism is still poorly understood. Results Using CrossHub software, we analyzed RNA-Seq expression profile data of CRC derived from The Cancer Genome Atlas (TCGA) project. Correlation analysis between the change in the expression of genes involved in glycolysis and EMT was performed. We obtained the set of genes with significant correlation coefficients, which included 21 EMT-related genes and a single glycolytic gene, HK3. The mRNA level of these genes was measured in 78 paired colorectal cancer samples by quantitative polymerase chain reaction (qPCR). Upregulation of HK3 and deregulation of 11 genes (COL1A1, TWIST1, NFATC1, GLIPR2, SFPR1, FLNA, GREM1, SFRP2, ZEB2, SPP1, and RARRES1) involved in EMT were found. The results of correlation study showed that the expression of HK3 demonstrated a strong correlation with 7 of the 21 examined genes (ZEB2, GREM1, TGFB3, TGFB1, SNAI2, TWIST1, and COL1A1) in CRC. Conclusions Upregulation of HK3 is associated with EMT in CRC and may be a crucial metabolic adaptation for rapid proliferation, survival, and metastases of CRC cells

Histological evaluation of hematopoietic/lymphoid organs from NHPs that survived to day 40 after 6.5 Gy TBI and vehicle or entolimod treatment (study Rs-06)

<p>^A Scoring was performed based on a 5-grade scale developed for each organ: 0 –total aplasia; 1 –pronounced atrophy, 2 –moderate atrophy, 3 –slight atrophy, close to normal morphology; 4 –normal morphology. Scoring criteria for individual organs are described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135388#pone.0135388.s008" target="_blank">S1 Methods</a>.</p><p>^B Student’s t-test vs. vehicle, 2-tailed.</p><p>Histological evaluation of hematopoietic/lymphoid organs from NHPs that survived to day 40 after 6.5 Gy TBI and vehicle or entolimod treatment (study Rs-06)</p

Effect of entolimod treatment on G-CSF and IL-6 levels in peripheral blood of irradiated NHPs.

<p><b>A, B</b>: Effect of different entolimod doses administered 1 h after LD_50/40 TBI (6.75 Gy; study Rs-09; N = 18). <b>C, D</b>: Effect of different entolimod doses administered 25 h after LD_50/40 TBI (6.75 Gy; study Rs-14; N = 10). <b>E, F</b>: Comparison of dose-dependence of background-adjusted Area Under the Curve (AUC_0-24) values for G-CSF and IL-6 after entolimod treatment given 1 h versus 25 h after LD_50/40 TBI (with dashed log-linear regression lines). Error bars represent standard errors.</p

Enhanced morphological recovery of hematopoietic and lymphoid organs in NHPs treated with entolimod post-irradiation.

<p>NHPs were treated with a single injection of 40 μg/kg entolimod 16, 25 or 48 hours after LD_75/40 total body irradiation (TBI). Tissue morphology was assessed 40 days post-irradiation and compared to that in control NHPs treated with vehicle 16 hours after LD_75/40 TBI. Representative histological images (hematoxylin-eosin staining) of sternum bone marrow sections, thymuses, spleens and mesenteric lymph nodes of animals that survived to study termination on Day 40 post-TBI (study Rs-06) are shown. Scale bars: 100 μm for bone marrow, 200 μm for thymus, spleen, and lymph node.</p

Mean nadir values of neutrophils, platelets and hemoglobin in peripheral blood following total body irradiation and vehicle or entolimod treatment.

<p>^A P-value by Student's t-test (two-tailed) for comparisons vs. vehicle groups within individual studies or in pooled group analysis</p><p>^B Source I: Sichuan Atomic Energy Institute, cylindrical bundle of Co60 rods</p><p>^C Source II: Sichuan Atomic Energy Institute, vertical array of Co60 rods</p><p>^D Vehicle-treated animals from studies Rs-03, Rs-06, Rs-09, and Rs-14</p><p>^E Entolimod-treated animals from studies Rs-06 and Rs-14</p><p>Mean nadir values of neutrophils, platelets and hemoglobin in peripheral blood following total body irradiation and vehicle or entolimod treatment.</p

Schematic presentation of mechanism(s) underlying anti-acute radiation syndrome (ARS) effects of entolimod.

<p>Entolimod binding to Toll-like receptor 5 (TLR5) initiates a cascade of events, all merging at attenuation of major pathological processes—leading causes of death in ARS: damage to hematopoietic (HP) and gastrointestinal (GI) systems resulting in bleeding and sepsis. The immediate TLR5-dependent effectors include anti-oxidants (e.g., SOD2), anti-apoptotic factors (both NF-κB-dependent (i.e., IAP and Bcl family members [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135388#pone.0135388.ref067" target="_blank">67</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135388#pone.0135388.ref070" target="_blank">70</a>]), and NF-κB-independent (i.e., PI3K/AKT, MKP7 and STAT3 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135388#pone.0135388.ref054" target="_blank">54</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135388#pone.0135388.ref071" target="_blank">71</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135388#pone.0135388.ref073" target="_blank">73</a>]), hematopoietic cytokines (e.g., G-CSF and IL-6 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135388#pone.0135388.ref049" target="_blank">49</a>]), anti-infective factors [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135388#pone.0135388.ref054" target="_blank">54</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135388#pone.0135388.ref090" target="_blank">90</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135388#pone.0135388.ref095" target="_blank">95</a>] and processes (e.g., neutrophil mobilization). In addition, stimulation of TLR5 is expected to inhibit radiation-induced aseptic inflammation involved in secondary tissue damage [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135388#pone.0135388.ref064" target="_blank">64</a>] e.g. via induction of an anti-inflammatory cytokine IL-10, IL-1β antagonist (IL-1βa) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135388#pone.0135388.ref076" target="_blank">76</a>] and stimulation of mesenchymal stem cells (MSC) known to express TLR5 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135388#pone.0135388.ref077" target="_blank">77</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135388#pone.0135388.ref078" target="_blank">78</a>] and to have anti-inflammatory properties [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135388#pone.0135388.ref079" target="_blank">79</a>]. Together with fibroblasts that can be induced to proliferate via TLR5 stimulation [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135388#pone.0135388.ref104" target="_blank">104</a>], MSC may also contribute to wound-healing processes [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135388#pone.0135388.ref079" target="_blank">79</a>]. Dashed lines show all molecular connections downstream of TLR5 that are not directly established for entolimod, but are extrapolated from published data on TLR5-dependent effects of flagellin.</p