Miracle-dz/UniFAR-FTUs huggingface dataset:
Combination of Irreversible Electroporation and STING Agonist for Effective Cancer Immunotherapy

Simple Summary This study deals with a new strategy for effective cancer immunotherapy using a combination of electrical ablation and immune adjuvant, a stimulator of interferon genes (STING) agonist. The combination treatment significantly improved the cancer treatment effect by converting the immunosuppressive tumor microenvironment (TME) to an immunogenic TME. The combination of interventional oncology and immuno-oncology is expected to contribute to the treatment of various difficult-to-treat tumors. Abstract Recently, cancer immunotherapy has received attention as a viable solution for the treatment of refractory tumors. However, it still has clinical limitations in its treatment efficacy due to inter-patient tumor heterogeneity and immunosuppressive tumor microenvironment (TME). In this study, we demonstrated the triggering of anti-cancer immune responses by a combination of irreversible electroporation (IRE) and a stimulator of interferon genes (STING) agonist. Optimal electrical conditions inducing damage-associated molecular patterns (DAMPs) by immunogenic cell death (ICD) were determined through in vitro 2D and 3D cell experiments. In the in vivo syngeneic lung cancer model, the combination of IRE and STING agonists demonstrated significant tumor growth inhibition. We believe that the combination strategy of IRE and STING agonists has potential for effective cancer immunotherapy.
Use of COST networking tools to achieve the objectives of a COST Action, enhance its impact, and maximize the benefits of its Members – challenges and lessons learnt in COST Action TU1208

Scientists and experts participating in COST Actions can benefit from a wide range of COST networking tools. Meetings, workshops, conferences and training schools can be organized. Shortterm scientific missions (STSM) can be funded: these are exchange visits where an Action Member spends five days up to six months abroad, in a host institution; the aim of STSMs is to foster collaboration between institutions and sharing of new techniques that may not be available in a participant’s home institution. COST also funds dissemination and communication of Action’s outcomes within research communities and beyond. Finally, conference grants for early-career researchers from Inclusiveness Target Countries (ITC) aim at helping participants from ITC to attend international science and technology related conferences that are not organised by COST Actions.
Temperature effects on the potential window of water and acetonitrile and heterogeneous electron transfer rates of outer sphere redox probes

This thesis examines the effects of temperature on the electrochemistry of an aqueous solvent, HNO3, and a non aqueous solvent, acetonitrile and their respective analytes. It has been demonstrated previously that lowering the temperature of a solvent expands the available potential window in which to perform electrochemical experiments. The working window of an aqueous solvent is limited by the electrolysis of water. Cyclic voltammetry was utilized to examine the temperature effects on the rates of the oxidation and reduction of the solvent as well as the effects on the redox species in solution. The redox species experienced decreased peak splitting with lower temperatures, and the diffusion constants and rate constants were lowered as the temperature decreased. It was determined that the solvent window of the HNO3 solution was extended in experiments conducted at lower temperatures. The voltage window went from 2.349 V at 25 ◦C to 2.671 V at 5 ◦C using a glassy carbon working electrode. No significant improvement in the voltage window of acetonitrile was seen at lower temperatures. Rate constants for the oxidation and reduction of water were lowered and the voltage window of nitric acid expanded.
International Journal of Stem Cell Research and Transplantation (IJST) 2328-3548 Obtaining Mesenchymal Stem Cells From Adipose Tissue Of Murin Origin: Experimental Study

Study. Int J Stem Cell Res Transplant . 2(5), 1-5. (ISCT) proposed a set Abstract The aim of this study was to isolate and characterize rat Adipose Derived Mesenchymal Stem Cells (AD-MSCs) in order to evaluate their proliferative potential and their ability to differentiate in different cell types. AD-MSCs and Derived Mesenchymal Stem Cells (BM-MSCs) have the same characteristics in terms of plasticity. The advantage of adipose tissue is that it is an easier accessible source and it offers a large amount of MSCs by less invasive surgical tecniques. MSCs were obtained from subcutaneous adipose tissue of Wistar rats. First of all microbiological controls were made to exclude the presence of bacteria or fungi in the tissue. Adipose tissue was mechanically and enzimatically fragmented and stomal cell fraction was seeded in adherent culture flasks in DMEM 20% FBS. After 48h the medium was replaced. Cells were characterized by evaluating: 1)their ability to adhere to the plastic; 2) the clonogenic potential by Colony Forming Unit (CFU) assay; 3) their ability to differentiate in 3 mesodermal lineages (adipocytes, osteocytes and chondrocytes). AD-MSCs are able to differentiate in adipocytes, osteocytes and chondrocytes as confirmed by Oil Red’O staining, von Kossa staining and histological analysis respectively. This first characterization is essential for the second part of our study in which we are planning to use AD-MSCs in vivo to restore renal function after an induced ischemic damage in experimental animals.
Status of Institutional Review Board Meetings Conducted Through Web Conference Systems in Japanese National University Hospitals During the COVID-19 Pandemic: Questionnaire Study

Background With the global proliferation of the novel COVID-19 disease, conventionally conducting institutional review board (IRB) meetings has become a difficult task. Amid concerns about the suspension of drug development due to delays within IRBs, it has been suggested that IRB meetings should be temporarily conducted via the internet. Objective This study aimed to elucidate the current status of IRB meetings conducted through web conference systems. Methods A survey on conducting IRB meetings through web conference systems was administered to Japanese national university hospitals. Respondents were in charge of operating IRB offices at different universities. This study was not a randomized controlled trial. Results The survey was performed at 42 facilities between the end of May and early June, 2020, immediately after the state of emergency was lifted in Japan. The survey yielded a response rate of 74% (31/42). Additionally, while 68% (21/31) of facilities introduced web conference systems for IRB meetings, 13% (4/31) of the surveyed facilities postponed IRB meetings. Therefore, we conducted a further survey of 21 facilities that implemented web conference systems for IRB meetings. According to 71% (15/21) of the respondents, there was no financial burden for implementing these systems, as they were free of charge. In 90% (19/21) of the facilities, IRB meetings through web conference systems were already being conducted with personal electronic devices. Furthermore, in 48% (10/21) of facilities, a web conference system was used in conjunction with face-to-face meetings. Conclusions Due to the COVID-19 pandemic, the number of reviews in clinical trial core hospitals has decreased. This suggests that the development of pharmaceuticals has stagnated because of COVID-19. According to 71% (15/21) of the respondents who conducted IRB meetings through web conference systems, the cost of introducing such meetings was US $0, showing a negligible financial burden. Moreover, it was shown that online deliberations could be carried out in the same manner as face-to-face meetings, as 86% (18/21) of facilities stated that the number of comments made by board members did not change. To improve the quality of IRB meetings conducted through web conference systems, it is necessary to further examine camera use and the content displayed on members’ screens during meetings. Further examination of all members who use web conference systems is required. Our measures for addressing the requests and problems identified in our study could potentially be considered protocols for future IRB meetings, when the COVID-19 pandemic has passed and face-to-face meetings are possible again. This study also highlights the importance of developing web conference systems for IRB meetings to respond to future unforeseen pandemics.
Studies on storage loss of Oyster mushroom during summer season

Oyster mushroom can be well stored for three days in Zero energy cool chamber (ZECC), due to differences in temperature and humidity inside the ZECC as compare to normal room condition. Experimental results revealed that oyster mushroom stored in that in ZECC has minimum physiological weight loss and spoilage loss (13 and 18.4 percent respectively) as compare to farmers practice, where it is totally spoiled in three days when stored in polythene bag and dried (29.5% weight loss).
Synergizing sunitinib and radiofrequency ablation to treat hepatocellular cancer by triggering the antitumor immune response

Background Minimally invasive radiofrequency ablation (RFA) is used as a first-line treatment option for hepatocellular cancer (HCC) with the weaknesses of incomplete ablation, tumor recurrence, and inferior outcomes. To overcome this limitation, we proposed to develop sunitinib-RFA integrated therapy with a potential of activating anti-HCC immune response. Methods Using our unique murine model, we developed a novel RFA platform with a modified human cardiac RF generator. Therapeutic efficacy of sunitinib–RFA combined treatment in HCC was tested in this platform. Tumor progression was monitored by MRI; tumor necrosis and apoptosis were detected by H&E and terminal deoxynucleotidyl transferase dUTP nick end labeling; immune reaction was defined by flow cytometry; and signaling molecules were examined with real-time PCR (qPCR), western blot, and immunohistochemical staining. Results A significantly reduced tumor growth and extended lift span were observed in the mice receiving combined treatment with RFA and sunitinib. This combined treatment significantly increased the frequency of CD8+ T cell, memory CD8+ T cell, and dendritic cells (DCs); decreased the frequency of regulatory T cells; and activated tumor-specific antigen (TSA) immune response in tumor microenvironment. We found that RFA caused PD-1 upregulation in tumor-infiltrated T cells by boosting hepatocyte growth factor (HGF) expression, which was suppressed by sunitinib treatment. We have also demonstrated that sunitinib suppressed VEGF’s effect in enhancing PD-L1 expression in DCs and attenuated heat-sink effect. The results indicate that RFA induced tumor destruction and release of in situ TSAs which can activate a tumoricidal immune response in sunitinib-treated mice, significantly improving anti-HCC therapeutic efficacy. Conclusions Sunitinib enables RFA-released in situ TSA to ignite an effective anti-tumor immune response by suppressing HGF and VEGF signaling pathways. Sunitinib–RFA as a synergistic therapeutic approach significantly suppresses HCC growth.
Structure and assembly of a Clostridioides difficile spore polar appendage

Clostridioides difficile, a strict anaerobic spore-former, is the main cause of nosocomial disease associated to antibiotic therapy in adults and a growing concern in the community. Spores are the main infectious, persistence and transmission vehicle. Spore germination occurs in the intestine and the resulting vegetative cells will produce the toxins responsible for the disease symptoms, and spores. During sporulation, a wild type population bifurcates into two main spore morphotypes, with or without a thick exosporium. We show that this bifurcation extends to the formation of spores with a robust polar appendage or spores with a short appendage or that lack this structure. The cysteine-rich CdeM protein localizes to the appendage and around the entire surface of the spore, and is a major structural component of the exosporium, which we show is continuous with the appendage. In a CdeM mutant, when present, the polar appendage is short and disorganized. We show that wild type and cdeM spores with a short or no appendage germinate poorly in response to taurocholate, compared to those with an appendage. cdeM spores of the two types, however, germinate faster than their wild type counterparts. Thus, while the absence of CdeM may increase the permeability of spores to taurocholate, proper assembly of the appendage is also important for germination. Consistent with an overall enhancement of germination, a cdeM mutant shows increased virulence in a hamster model of disease. For a wild type population, spores with a short or no appendage germinate slower than the appendage-bearing spores. Differences in transmission, persistence and disease severity may result, in part, from their proportion in a spore population.
Danos do percevejo Dichelops melacanthus (Dallas, 1851) (Heteroptera: Pentatomidae) na cultura do milho

Apesar do percevejo Dichelops melacanthus nao ser considerado uma praga chave na cultura do milho, ultimamente este inseto e encontrado com mais frequencia nesta cultura. O objetivo deste trabalho foi verificar o efeito de diferentes niveis populacionais do percevejo D. melacanthus , sobre plantas de milho. Para tanto, experimentos em casa de vegetacao e a campo foram conduzidos testando-se 4 diferentes populacoes do inseto: 0 (testemunha), 1, 2 e 4 percevejos infestados no estadio V2, durante 15 dias, em 10 plantas vaso -1 (casa de vegetacao) ou em 10 plantas m -2 (campo). Avaliou-se parâmetros morfologicos, producao de massa seca de planta, nivel de dano, produtividade final de graos e nivel de dano economico. Os experimentos contaram com quatro repeticoes distribuidos no delineamento experimental inteiramente casualizado (casa de vegetacao) ou em blocos ao acaso (campo). Os dados foram submetidos a analise de variância, teste de Tukey ou analise de regressao a 5% de probabilidade. Os resultados obtidos tanto no experimento a campo quanto em casa de vegetacao demonstraram claramente a interferencia do percevejo sobre parâmetros morfologicos, como diâmetro de colmo e area foliar, e producao de massa seca das plantas de milho na sua fase inicial. A produtividade final de graos pode ser reduzida em ate 11% a cada percevejo m -2 .
Mechanochemical Synthesis and Potentiation of the Antimicrobial Activity of 4-[3-(4-methoxyphenyl)-allylideneamino]-1,5-dimethyl-2-phenylpyrazol-3-one by Metal Chelation

A Schiff base ligand, 4-[3-(4-methoxyphenyl)-allylideneamino]-1,5-dimethyl-2-phenylpyrazol-3-one has been synthesized by the condensation of Methoxycinnamaldehyde and 4-aminoantipyrine. Its divalent metal complexes of Co, Ni, and Cu were also synthesized using the mechanochemical solvent-free method. The ligand and the complexes were characterized by FTIR, UV/visible, 1H NMR, 13C NMR, and GC-MS. The ligand behaved as a bidentate donor by using its carbonyl and azomethine N as binding sites for the metals. The ligand showed low activity against some microbes but the complexes were remarkably active against the fungi species.
Tissue-expression profiles unveils the gene interaction of hepatopancreas, eyestalk, and ovary in precocious female Chinese mitten crab, Eriocheir sinensis

Sexual precocity is a serious and common biological phenomenon in animal species. Large amount of precocity individuals was identified in Chinese mitten crab, Eriocheir sinensis, which caused huge economical loss every year. However, the underlying genetic basis of precocity in E. sinensis is still lack. In this study, histology observation, comparative transcriptome was conducted among different stages of precocious one-year old and normal two-year old E. sinensis, tissue-expression profiles of ovary, hepatopancreas, and eyestalk tissues were presented and compared. Genes associated with lipid metabolic process, lipid transport, vitelline membrane formation, vitelline synthesis and neuropeptide hormone related genes were upregulated in the ovary, hepatopancreas and eyestalk of precocious E. sinensis. Our results indicated eyestalk involved in neuroendocrine system providing neuropeptide hormone that may induce vitellogenesis in hepatopancreas and further stimulate ovary development. Hepatopancreas is a site for energy storage, vitellogenin synthesis and may assist to induce oogenesis through lipid transport in precocious E. sinensis. The genetic basis of precocity in E. sinensis is an integrated gene regulatory network of eyestalk, hepatopancreas, and ovary tissues. Our study provides effective convenient phenotype measurement method for identification of potential precocious E. sinensis detection, and valuable genetic resources and novel insights into the research of molecular mechanism of precocity in E. sinensis.
Concordance of HPV, conventional smear, colposcopy, and conization results in cervical dysplasia

Cervical cancer screening algorithms are increasingly focused on Human Papillomavirus (HPV)‐based screening while the accuracy of using abnormal cytological findings to detect dysplastic lesions still remains important. This retrospective study correlated the results of conventional cervical cytology, colposcopy guided biopsy, and cold knife conization (CKC) procedures performed in a tertiary center.
Computational mechanisms of curiosity and goal-directed exploration

Successful behaviour depends on the right balance between maximising reward and soliciting information about the world. Here, we show how different types of information-gain emerge when casting behaviour as surprise minimisation. We present two distinct mechanisms for goal-directed exploration that express separable profiles of active sampling to reduce uncertainty. ‘Hidden state’ exploration motivates agents to sample unambiguous observations to accurately infer the (hidden) state of the world. Conversely, ‘model parameter’ exploration, compels agents to sample outcomes associated with high uncertainty, if they are informative for their representation of the task structure. We illustrate the emergence of these types of information-gain, termed active inference and active learning, and show how these forms of exploration induce distinct patterns of ‘Bayes-optimal’ behaviour. Our findings provide a computational framework to understand how distinct levels of uncertainty induce different modes of information-gain in decision-making.
Floristic Diversity and Important Value Indices of Tree Species in Lower Kanchenjunga Singhalila Ridge Eastern Nepal

The present paper is based on the finding of floristic diversity inventory research work conducted in Lower Kanchenjungha Singhalila Ridge, in Nepal side of Eastern Himalaya. Knowledge on floristic diversity of an area can reflect the total resources, their use patterns and conservation status which have a key role for making conservation strategies and policies. Analysis of vegetation helps to develop detailed picture of plant communities of that region. A total of 299 plant species belonging to 184 genera and 86 families were found in the Lower Kanchenjungha Singhalila Ridge. Dicotyledonous flora includes 69 families, 150 genera and 229 species whereas Monocotyledonous flora includes 15 families, 32 genera and 39 species. On the basis of floristic analysis Rosaceae was found to be the largest family with 23 species followed by Ericaceae 17, and Lauraceae 9 species. Current study furnishes three new addition to the flora of Nepal viz. Begonia flaviflora H. Hara (Begoniaceae), Carex cruciate Wahlenberg var. argocarpa C. B. Clarke (Cyperaceae), and Strobilanthes helicta Anderson (Acanthaceae). Of this total, 30 woody tree species with 551 individuals and 23 genera were recorded from the altitudinal range of 2100 - 3000 m of study area. The highest relative frequency was recorded by Lithocarpus pachyphylla (18.48%), Symplocos ramosissima (16.30%), Rhododendron falconeri (13.95%), Symplocos dryophylla (10.20%). Eurya acuminate and Symplocos species were found to be dominant in lower elevation whereas Lithocarpus pachyphylla and Rhododendron species were found to be dominant in upper elevation.
Recombination suppression and evolutionary strata around mating‐type loci in fungi: documenting patterns and understanding evolutionary and mechanistic causes

Summary Genomic regions determining sexual compatibility often display recombination suppression, as occurs in sex chromosomes, plant self‐incompatibility loci and fungal mating‐type loci. Regions lacking recombination can extend beyond the genes determining sexes or mating types, by several successive steps of recombination suppression. Here we review the evidence for recombination suppression around mating‐type loci in fungi, sometimes encompassing vast regions of the mating‐type chromosomes. The suppression of recombination at mating‐type loci in fungi has long been recognized and maintains the multiallelic combinations required for correct compatibility determination. We review more recent evidence for expansions of recombination suppression beyond mating‐type genes in fungi (‘evolutionary strata’), which have been little studied and may be more pervasive than commonly thought. We discuss testable hypotheses for the ultimate (evolutionary) and proximate (mechanistic) causes for such expansions of recombination suppression, including (1) antagonistic selection, (2) association of additional functions to mating‐type, such as uniparental mitochondria inheritance, (3) accumulation in the margin of nonrecombining regions of various factors, including deleterious mutations or transposable elements resulting from relaxed selection, or neutral rearrangements resulting from genetic drift. The study of recombination suppression in fungi could thus contribute to our understanding of recombination suppression expansion across a broader range of organisms.
Variation in pancreatic amylase gene copy number among Eurasian badgers (Carnivora, Mustelidae,
 Meles
 ) and its relationship to diet

Occurrence of copy number variation (CNV) of gene loci is important in the adaptation of species and populations to their environments. High copy numbers of mammalian genes encoding the digestive enzyme amylase, which plays a role in starch digestion, have been associated with adaptation to high-starch foods. Here, we investigated CNV in the pancreatic amylase gene (AMY2) in Eurasian badgers (Meles species) and related taxa using real-time quantitative PCR. We found that Meles anakuma and M. meles, as well as the other mustelids Mustela sibirica, Martes melampus and Martes zibellina, had only one copy of the AMY2 locus, whereas in Meles leucurus the copy number varied between one and four. The AMY2 copy number also varied significantly among M. leucurus populations. This suggests that M. leucurus is better adapted to a diet rich in starch and/or glycogen than its congeners. As Meles spp. are basically omnivorous but favor a carnivoran diet, for example, earthworms and amphibians, we speculate that the CNV is related to the dearth of animal food in the range of M. leucurus, which enforces a more vegetal diet. This in turn would favor more efficient digestion of dietary starch, which could be achieved by increasing the copy number of AMY2 .