Intratumor Regulatory Noncytotoxic NK Cells in Patients with Hepatocellular Carcinoma

Previous studies support the role of natural killer (NK) cells in controlling hepatocellular carcinoma (HCC) progression. However, ambiguity remains about the multiplicity and the role of different NK cell subsets, as a pro-oncogenic function has been suggested. We performed phenotypic and functional characterization of NK cells infiltrating HCC, with the corresponding nontumorous tissue and liver from patients undergoing liver resection for colorectal liver metastasis used as controls. We identified a reduced number of NK cells in tumors with higher frequency of CD56(BRIGHT)CD16(-) NK cells associated with higher expression of NKG2A, NKp44, and NKp30 and downregulation of NKG2D. Liver-resident (CXCR6(+)) NK cells were reduced in the tumors where T-bet(hi)Eomes(lo) expression was predominant. HCCs showed higher expression of CD49a with particular enrichment in CD49a(+)Eomes(+) NK cells, a subset typically represented in the decidua and playing a proangiogenic function. Functional analysis showed reduced TNF-alpha production along with impaired cytotoxic capacity that was inversely related to CXCR6(-), T-bet(hi)Eomes(lo), and CD49a(+)Eomes(+) NK cells. In conclusion, we identified a subset of NK cells infiltrating HCC, including non-liver-resident cells that coexpressed CD49a and Eomes and showed reduced cytotoxic potential. This NK cell subset likely plays a regulatory role in proangiogenic function

Phenotypic characterization of the rudá x and 277 common bean ril population.

The main objective of this work was to quantify the phenotypic diversity of the RIL population derived from crosses between Rudá and AND 277, a potential new core mapping population for common bean

Pemetrexed enhances membrane PD-L1 expression and potentiates T cell-mediated cytotoxicity by anti-PD-L1 antibody therapy in non-small-cell lung cancer

Immunotherapy has significantly changed the treatment landscape for advanced non-small-cell lung cancer (NSCLC) with the introduction of drugs targeting programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1). In particular, the addition of the anti-PD-1 antibody pembrolizumab to platinum-pemetrexed chemotherapy resulted in a significantly improved overall survival in patients with non-squamous NSCLC, regardless of PD-L1 expression. In this preclinical study, we investigated whether chemotherapy can modulate PD-L1 expression in non-squamous NSCLC cell lines, thus potentially affecting immunotherapy efficacy. Among different chemotherapeutic agents tested, only pemetrexed increased PD-L1 levels by activating both mTOR/P70S6K and STAT3 pathways. Moreover, it also induced the secretion of cytokines, such as IFN-γ and IL-2, by activated peripheral blood mononuclear cells PBMCs that further stimulated the expression of PD-L1 on tumor cells, as demonstrated in a co-culture system. The anti-PD-1/PD-L1 therapy enhanced T cell-mediated cytotoxicity of NSCLC cells treated with pemetrexed and expressing high levels of PD-L1 in comparison with untreated cells. These data may explain the positive results obtained with pemetrexed-based chemotherapy combined with pembrolizumab in PD-L1-negative NSCLC and can support pemetrexed as one of the preferable chemotherapy partners for immunochemotherapy combination regimens

Targeting p53 and histone methyltransferases restores exhausted CD8+ T cells in HCV infection

Hepatitis C virus infection (HCV) represents a unique model to characterize, from early to late stages of infection, the T cell differentiation process leading to exhaustion of human CD8+ T cells. Here we show that in early HCV infection, exhaustion-committed virus-specific CD8+ T cells display a marked upregulation of transcription associated with impaired glycolytic and mitochondrial functions, that are linked to enhanced ataxia-telangiectasia mutated (ATM) and p53 signaling. After evolution to chronic infection, exhaustion of HCV-specific T cell responses is instead characterized by a broad gene downregulation associated with a wide metabolic and anti-viral function impairment, which can be rescued by histone methyltransferase inhibitors. These results have implications not only for treatment of HCV-positive patients not responding to last-generation antivirals, but also for other chronic pathologies associated with T cell dysfunction, including cancer

Classificação multivariada de curvas de progresso da requeima do tomateiro entre acessos do banco de germaplasma de hortaliças da UFV

O objetivo deste trabalho foi apresentar uma metodologia de análise de experimentos em fitopatologia que considera a comparação de curvas de progressos de doenças na presença de um grande número de tratamentos por meio da análise de cluster. Foram cultivados 42 acessos do Banco de Germoplasma de Hortaliças (BGH) da Universidade Federal de Viçosa (UFV). Ajustou-se o modelo exponencial aos dados de percentagem de severidade de requeima, e as estimativas obtidas quanto à incidência inicial da doença (yo) e taxa de progresso da doença (r) foram submetidas à análise de variância multivariada (Manova), seguindo o delineamento de blocos casualizados. As médias ajustadas foram submetidas à análise de agrupamento hierárquico, o método centroide. Observou-se um número ótimo de seis grupos distintos.The objective of this paper was to present a methodology for the analysis of experiments in plant pathology that considers the comparison of disease progress curves in the presence of a large number of treatments by cluster analysis. Forty-two accessions were grown from the Germoplasma Vegetable Bank (BGH), of Universidade Federal de Viçosa (UFV). The exponential model was fitted to the data of late blight severity percentage, and the obtained parameter estimates obtained on the initial incidence of the disease (yo) and rate of disease progression (r) - were submitted to the multivariate analysis of variance (MANOVA). The adjusted means were submitted to the cluster analysis. An optimal number of six distinct groups was observed

The future of Cybersecurity in Italy: Strategic focus area

This volume has been created as a continuation of the previous one, with the aim of outlining a set of focus areas and actions that the Italian Nation research community considers essential. The book touches many aspects of cyber security, ranging from the definition of the infrastructure and controls needed to organize cyberdefence to the actions and technologies to be developed to be better protected, from the identification of the main technologies to be defended to the proposal of a set of horizontal actions for training, awareness raising, and risk management

Survival and Recurrence of Endocarditis following Mechanical vs. Biological Aortic Valve Replacement for Endocarditis in Patients Aged 40 to 65 Years: Data from the INFECT-Registry

Background: Infective endocarditis (IE) is a serious disease, and in many cases, surgery is necessary. Whether the type of prosthesis implanted for aortic valve replacement (AVR) for IE impacts patient survival is a matter of debate. The aim of the present study is to quantify differences in long-term survival and recurrence of endocarditis AVR for IE according to prosthesis type among patients aged 40 to 65 years. Methods: This was an analysis of the INFECT-REGISTRY. Trends in proportion to the use of mechanical prostheses versus biological ones over time were tested by applying the sieve bootstrapped t-test. Confounders were adjusted using the optimal full-matching propensity score. The difference in overall survival was compared using the Cox model, whereas the differences in recurrence of endocarditis were evaluated using the Gray test. Results: Overall, 4365 patients were diagnosed and operated on for IE from 2000 to 2021. Of these, 549, aged between 40 and 65 years, underwent AVR. A total of 268 (48.8%) received mechanical prostheses, and 281 (51.2%) received biological ones. A significant trend in the reduction of implantation of mechanical vs. biological prostheses was observed during the study period (p < 0.0001). Long-term survival was significantly higher among patients receiving a mechanical prosthesis than those receiving a biological prosthesis (hazard ratio [HR] 0.546, 95% CI: 0.322–0.926, p = 0.025). Mechanical prostheses were associated with significantly less recurrent endocarditis after AVR than biological prostheses (HR 0.268, 95%CI: 0.077–0.933, p = 0.039). Conclusions: The present analysis of the INFECT-REGISTRY shows increased survival and reduced recurrence of endocarditis after a mechanical aortic valve prosthesis implant for IE in middle-aged patients

Effect of age, sex and gender on pain sensitivity: A narrative review

© 2017 Eltumi And Tashani. Introduction: An increasing body of literature on sex and gender differences in pain sensitivity has been accumulated in recent years. There is also evidence from epidemiological research that painful conditions are more prevalent in older people. The aim of this narrative review is to critically appraise the relevant literature investigating the presence of age and sex differences in clinical and experimental pain conditions. Methods: A scoping search of the literature identifying relevant peer reviewed articles was conducted on May 2016. Information and evidence from the key articles were narratively described and data was quantitatively synthesised to identify gaps of knowledge in the research literature concerning age and sex differences in pain responses. Results: This critical appraisal of the literature suggests that the results of the experimental and clinical studies regarding age and sex differences in pain contain some contradictions as far as age differences in pain are concerned. While data from the clinical studies are more consistent and seem to point towards the fact that chronic pain prevalence increases in the elderly findings from the experimental studies on the other hand were inconsistent, with pain threshold increasing with age in some studies and decreasing with age in others. Conclusion: There is a need for further research using the latest advanced quantitative sensory testing protocols to measure the function of small nerve fibres that are involved in nociception and pain sensitivity across the human life span. Implications: Findings from these studies should feed into and inform evidence emerging from other types of studies (e.g. brain imaging technique and psychometrics) suggesting that pain in the older humans may have unique characteristics that affect how old patients respond to intervention

Fungal Planet description sheets: 868-950

Novel species of fungi described in this study include those from various countries as follows: Australia, Chaetomella pseudocircinoseta and Coniella pseudodiospyri on Eucalyptus microcorys leaves, Cladophialophora eucalypti, Teratosphaeria dunnii and Vermiculariopsiella dunnii on Eucalyptus dunnii leaves, Cylindrium grande and Hypsotheca eucalyptorum on Eucalyptus grandis leaves, Elsinoe salignae on Eucalyptus saligna leaves, Marasmius lebeliae on litter of regenerating subtropical rainforest, Phialoseptomonium eucalypti (incl. Phialoseptomonium gen. nov.) on Eucalyptus grandis × camaldulensis leaves, Phlogicylindrium pawpawense on Eucalyptus tereticornis leaves, Phyllosticta longicauda as an endophyte from healthy Eustrephus latifolius leaves, Pseudosydowia eucalyptorum on Eucalyptus sp. leaves, Saitozyma wallum on Banksia aemula leaves, Teratosphaeria henryi on Corymbia henryi leaves. Brazil, Aspergillus bezerrae, Backusella azygospora, Mariannaea terricola and Talaromyces pernambucoensis from soil, Calonectria matogrossensis on Eucalyptus urophylla leaves, Calvatia brasiliensis on soil, Carcinomyces nordestinensis on Bromelia antiacantha leaves, Dendryphiella stromaticola on small branches of an unidentified plant, Nigrospora brasiliensis on Nopalea cochenillifera leaves, Penicillium alagoense as a leaf endophyte on a Miconia sp., Podosordaria nigrobrunnea on dung, Spegazzinia bromeliacearum as a leaf endophyte on Tilandsia catimbauensis, Xylobolus brasiliensis on decaying wood. Bulgaria, Kazachstania molopis from the gut of the beetle Molops piceus. Croatia, Mollisia endocrystallina from a fallen decorticated Picea abies tree trunk. Ecuador, Hygrocybe rodomaculata on soil. Hungary, Alfoldia vorosii (incl.Alfoldia gen. nov.) from Juniperus communis roots, Kiskunsagia ubrizsyi (incl. Kiskunsagia gen. nov.) from Fumana procumbens roots. India, Aureobasidium tremulum as laboratory contaminant, Leucosporidium himalayensis and Naganishia indica from windblown dust on glaciers. Italy, Neodevriesia cycadicola on Cycas sp. leaves, Pseudocercospora pseudomyrticola on Myrtus communis leaves, Ramularia pistaciae on Pistacia lentiscus leaves, Neognomoniopsis quercina (incl. Neognomoniopsis gen. nov.) on Quercus ilex leaves. Japan, Diaporthe fructicola on Passiflora edulis × P. edulis f. flavicarpa fruit, Entoloma nipponicum on leaf litter in a mixed Cryptomeria japonica and Acer spp. forest. Macedonia, Astraeus macedonicus on soil. Malaysia, Fusicladium eucalyptigenum on Eucalyptus sp. twigs, Neoacrodontiella eucalypti (incl. Neoacrodontiella gen. nov.) on Eucalyptus urophylla leaves. Mozambique, Meliola gorongosensis on dead Philenoptera violacea leaflets. Nepal, Coniochaeta dendrobiicola from Dendriobium lognicornu roots. New Zealand, Neodevriesia sexualis and Thozetella neonivea on Archontophoenix cunninghamiana leaves. Norway, Calophoma sandfjordenica from a piece of board on a rocky shoreline, Clavaria parvispora on soil, Didymella finnmarkica from a piece of Pinus sylvestris driftwood. Poland, Sugiyamaella trypani from soil. Portugal, Colletotrichum feijoicola from Acca sellowiana. Russia, Crepidotus tobolensis on Populus tremula debris, Entoloma ekaterinae, Entoloma erhardii and Suillus gastroflavus on soil, Nakazawaea ambrosiae from the galleries of Ips typographus under the bark of Picea abies. Slovenia, Pluteus ludwigii on twigs of broadleaved trees. South Africa, Anungitiomyces stellenboschiensis (incl. Anungitiomyces gen. nov.) and Niesslia stellenboschiana on Eucalyptus sp. leaves, Beltraniella pseudoportoricensis on Podocarpus falcatus leaf litter, Corynespora encephalarti on Encephalartos sp. leaves, Cytospora pavettae on Pavetta revoluta leaves, Helminthosporium erythrinicola on Erythrina humeana leaves, Helminthosporium syzygii on a Syzygium sp. barkcanker, Libertasomyces aloeticus on Aloe sp. leaves, Penicillium lunae from Musa sp. fruit, Phyllosticta lauridiae on Lauridia tetragona leaves, Pseudotruncatella bolusanthi (incl. Pseudotruncatellaceae fam. nov.) and Dactylella bolusanthi on Bolusanthus speciosus leaves. Spain, Apenidiella foetida on submerged plant debris, Inocybe grammatoides on Quercus ilex subsp. ilex forest humus, Ossicaulis salomii on soil, Phialemonium guarroi from soil. Thailand, Pantospora chromolaenae on Chromolaena odorata leaves. Ukraine, Cadophora helianthi from Helianthus annuus stems. USA, Boletus pseudopinophilus on soil under slash pine, Botryotrichum foricae, Penicillium americanum and Penicillium minnesotense from air. Vietnam, Lycoperdon vietnamense on soil. Morphological and culture characteristics are supported by DNA barcodes