Aging-related biomarkers in testicular cancer survivors after different oncologic treatments.

PURPOSE: Testicular cancer survivors (TCS) exposed to chemotherapy have an increased expression of CDKN2A/p16INK4a and a lymphocyte phenotype associated with immunosenescence. We seek to define whether the immunosenescent phenotype is associated with chemotherapy. METHODS: Case-control study of TCS, disease-free ≥3 months and stratified by primary treatment modality into orchiectomy only, chemotherapy, or bone marrow transplant (BMT). Each group was compared with age-matched healthy controls (HC). We measured the relative proportions of lymphocyte subpopulations using flow cytometry, levels of C-reactive protein, and relative expression of CDKN2A/p16INK4a quantified by qPCR. RESULTS: We included 65 patients; 19 were treated with orchiectomy only, 35 received different doses of chemotherapy, and 11 underwent BMT. The chemotherapy and BMT groups had decreased naïve CD4 cells compared to HC. The chemotherapy group showed increased central and effector memory CD4 cells, as well as effector and terminally differentiated CD8 cells, compared to HC. Chemotherapy (chemotherapy 1.84 vs. HC 0.92; p < 0.01) and BMT (BMT 6.96 vs. HC 1.25; p < 0.005) groups had higher expression of CDKN2A/p16INK4a compared to HC. The orchiectomy group showed no significant difference with HC (orchiectomy 1.73 vs. HC 1.01; p = 0.17). CRP levels were higher in all groups when compared with HC; in the orchiectomy group, they were only marginally increased (chemotherapy 0.22 vs. HC 0.06; p < 0.01; BMT 0.26 vs. HC 0.06; p < 0.01; orchiectomy 0.09 vs. HC 0.07; p < 0.01). CONCLUSIONS: Among TCS, only patients exposed to cytotoxic agents developed an immunosenescent phenotype. This finding supports the attribution of this alteration to the cytotoxic treatment.

In silico analysis of non-structural protein 12 sequences from SARS-COV-2 found in Manaus, Amazonas, Brazil, reveals mutations linked to higher transmissibility.

The disease coronavirus COVID-19 has been the cause of millions of deaths worldwide. Among the proteins of SARS-CoV-2, non-structural protein 12 (NSP12) plays a key role during COVID infection and is part of the RNA-dependent RNA polymerase complex. The monitoring of NSP12 polymorphisms is extremely important for the design of new antiviral drugs and monitoring of viral evolution. This study analyzed the NSP12 mutations detected in circulating SARS-CoV-2 during the years 2020 to 2022 in the population of the city of Manaus, Amazonas, Brazil. The most frequent mutations found were P323L and G671S. Reports in the literature indicate that these mutations are related to transmissibility efficiency, which may have contributed to the extremely high numbers of cases in this location. In addition, two mutations described here (E796D and R914K) are close and have RMSD that is similar to the mutations M794V and N911K, which have been described in the literature as influential on the performance of the NSP12 enzyme. These data demonstrate the need to monitor the emergence of new mutations in NSP12 in order to better understand their consequences for the treatments currently used and in the design of new drugs.

Irrigation with saline water in the cultivation of mini watermelon under phosphate fertilization.

The objective of this study was to evaluate the water status, photosynthetic pigments, and photochemical efficiency of mini watermelon plants under salt stress and phosphate fertilization. The experiment was conducted in pots under greenhouse conditions in Pombal, PB, Brazil. The experimental design used was randomized blocks in a 5 × 4 factorial scheme, with five levels of electrical conductivity of irrigation water - ECw (0.3, 1.3, 2.3, 3.3, and 4.3 dS m-1) and four doses of phosphorus (60, 80, 100, and 120% of the recommendation), with three replicates. The relative water content in the tissues decreased with the increase in ECw levels in all phosphorus doses, with decreases of 7.05, 7.81 and 8.83% per unit increase in ECw, in plants fertilized with 80, 100 and 120% P2O5. On the other hand, ECw levels increased electrolyte leakage, regardless of phosphorus doses of the recommendation. The synthesis of photosynthetic pigments and the quantum efficiency of photosystem II were inhibited by increasing water salinity from 0.3 dS m-1 in plants grown under phosphorus doses above 60% of the recommendation. Water salinity from 0.3 dS m-1 reduced chlorophyll b contents, initial, maximum, and variable fluorescence of mini watermelon plants, with a decrease of 11.86, 4.51, 4.53, and 4.54% per unit increment of ECw, respectively.

Salicylic acid does not relieve salt stress on gas exchange, chlorophyll fluorescence, and hydroponic melon growth.

The objective of this study was to evaluate the salicylic acid applications in attenuating the harmful effects of saline nutrient solution on the physiology and growth of 'Gaúcho' melon cultivated in the NFT hydroponic system. The experiment was conducted in a greenhouse, in Pombal-PB, Brazil. The cultivation system used was the Nutrient Film Technique - NFT hydroponics. A completely randomized split-plot design was used, with the plot referring to four levels of salinity in the nutrient solution - ECns (2.1 control, 3.2, 4.3, and 5.4 dS m-1) and the sub-plot four concentrations of salicylic acid (SA) (0, 1.5, 3.0, and 4.5 mM), applied via foliar spray, with six replications. Nutrient solution of 4.3 and 5.4 dS m-1 electrical conductivity promotes higher maximum and variable fluorescence, respectively. The stomatal conductance, transpiration, stem diameter, main branch length, leaf dry mass, and stem dry mass of 'Gaúcho' melon plants decrease with the increase in salinity of the nutrient solution. Salicylic acid increases the initial fluorescence and the main branch length of 'Gaúcho' melon plants in hydroponic cultivation. Salicylic acid at a concentration of 1.5 to 4.5 mM did not attenuate the effects of salt stress on the internal CO2 concentration, CO2 assimilation rate, and root dry mass of 'Gaúcho' melon plants.

Morphology of 'Crioula' guava seedlings under irrigation with increasing salinity water and nitrogen/potassium fertilization.

Several studies have been conducted evaluating the management of fertilizers as strategies to mitigate the deleterious effects of salt stress, so the objective of this work was to evaluate the quality of 'Crioula' guava seedlings under irrigation with water of different salinity levels and fertilized with combinations of nitrogen and potassium. The experiment was performed in a protected (screened) environment using a randomized block design and analyzed in a 5 × 4 factorial scheme, with four replicates, with the plot formed by two plants. The treatments were formed from the combination of the factor electrical conductivity of irrigation water (ECw 0.3, 1.1, 1.9, 2.7 and 3.5 dS m-1), with the factor combinations (C) of nitrogen (N) and potassium (K2O) doses, being C1 = 70% N + 50% K2O, C2 = 100% N + 75% K2O, C3= 130% N + 100% K2O and C4= 160% N + 125% K2O. The recommended dose of 100% N and K, respectively, was 541.1 mg N dm-3 soil and 798.6 mg K dm-3 soil. The combinations of N and K fertilization corresponding to 70% N + 50% K2O and 100% N + 75% K2O of the recommended doses promoted greater growth of 'Crioula' guava seedlings. Water with ECw of 2.1 dS m-1 promotes the formation of quality 'Crioula' guava seedlings.

Recombinant human TIM-3 ectodomain expressed in bacteria and recovered from inclusion bodies as a stable and active molecule.

Introduction: Microbial systems, such as Escherichia coli, as host recombinant expression is the most versatile and the cheapest system for protein production, however, several obstacles still remain, such as recovery of soluble and functional proteins from inclusion bodies, elimination of lipopolysaccharides (LPS) contamination, incomplete synthesis, degradation by proteases, and the lack of post-translational modifications, which becomes even more complex when comes to membrane proteins, because they are difficult not only to produce but also to keep in solution in its active state. T-cell Immunoglobulin and Mucin domain 3 (TIM-3) is a type I transmembrane protein that is predominantly expressed on the surface of T lymphocytes, natural killer (NK) cells, dendritic cells, and macrophages, playing a role as a negative immune checkpoint receptor. TIM-3 comprises a single ectodomain for interaction with immune system soluble and cellular components, a transmembrane domain, and a cytoplasmic tail, responsible for the binding of signaling and scaffolding molecules. TIM-3 pathway holds potential as a therapeutic target for immunotherapy against tumors, autoimmunity, chronic virus infections, and various malignancies, however, many aspects of the biology of this receptor are still incompletely understood, especially regarding its ligands. Methods: Here we overcome, for the first time, the challenge of the production of active immune checkpoint protein recovered from bacterial cytoplasmic inclusion bodies, being able to obtain an active, and non-glycosylated TIM-3 ectodomain (TIM-3-ECD), which can be used as a tool to better understand the interactions and roles of this immune checkpoint. The TIM-3 refolding was obtained by the association of high pressure and alkaline pH. Results: The purified TIM-3-ECD showed the correct secondary structure and was recognized from anti-TIM-3 structural-dependent antibodies likewise commercial TIM-3-ECD was produced by a mammal cells system. Furthermore, immunofluorescence showed the ability of TIM-3-ECD to bind to the surface of lung cancer A549 cells and to provide an additional boost for the expression of the lymphocyte activation marker CD69 in anti-CD3/CD28 activated human PBMC. Discussion: Taken together these results validated a methodology able to obtain active checkpoint proteins from bacterial inclusion bodies, which will be helpful to further investigate the interactions of this and others not yet explored immune checkpoints.

Salicylic acid concentrations and forms of application mitigate water stress in sour passion fruit seedlings.

The present study aimed to evaluate concentrations and forms of application of salicylic acid used for water stress mitigation on the gas exchange and growth of yellow passion fruit. The experimental design was arranged in randomized blocks in a 4 × 4 × 2 factorial scheme, with four concentrations of salicylic acid (SA) via foliar application (0.0, 0.7, 1.4, and 2.1 mM), four SA concentrations via fertigation (0.0, 0.7, 1.4, and 2.1 mM), and two irrigation depths estimated based on the actual evapotranspiration - ETr (50 and 100% of ETr), with three replications. Water stress negatively affected the physiology and growth of yellow passion fruit seedlings at 75 days after sowing (DAS). The application of salicylic acid, regardless of the form of application, attenuates the effects of water stress on gas exchange and growth of yellow passion fruit, with the best results obtained when applying a concentration of 1.30 mM via leaf or 0.90 mM via fertirrigation. The combination of foliar application of AS and fertigation contributed to improve photosynthetic and growth parameters under water conditions of 50 and 100% of ETr. The foliar application of AS presents superior responses to the application via fertigation. These results reinforce the hypothesis that the attenuation of water stress by salicylic acid is related to the maintenance of gas exchange, which depends on the concentration and form of application, and studies testing combinations throughout the crop cycle become promising for advances in knowledge from the action of this phytohormone on abiotic stress.

Mineral composition and production of guava under salt stress and salicylic acid.

The limitation in the quality of water sources for irrigation in the semi-arid region of northeastern Brazil is increasingly present, so it is necessary to use water with high concentrations of salts for agricultural production, which makes the use of elicitors essential to mitigate the harmful effects of salinity on plants. Given the above, the objective of this study was to evaluate the effects of foliar application of salicylic acid on the mineral composition and production of guava plants under salt stress conditions in the post-grafting phase. The experiment was carried out under greenhouse conditions, in a randomized block design, in a 2 × 4 factorial scheme, with two levels of electrical conductivity of irrigation water (0.6 and 3.2 dS m-1) and four concentrations of salicylic acid (0, 1.2, 2.4, and 3.6 mM), with three replicates. During the flowering stage of guava, N, P, and K contents accumulated in the leaves according to the following order of concentration: N > K > P. Foliar application of 1.2 mM of salicylic acid increases the leaf contents of N, P, and K in guava plants grown under irrigation with water of 0.6 dS m-1. Water salinity of 3.2 dS m-1 reduces the growth and production components of guava plants.

Risk assessment of ionizing radiation and radiological thresholds to compound an environmental baseline for the unconventional gas industry.

The exploration of unconventional hydrocarbons may be very effective in promoting economic development and confronting energy crisis around the world. However, the environmental risks associated with this practice might be an impediment if not adequately dimensioned. In this context, naturally occurring radioactive materials and ionizing radiation are sensitive aspects in the unconventional gas industry that may compromise the environmental sustainability of gas production and they should be properly monitored. This paper provides a radioecological assessment of the São Francisco Basin (Brazil) as part of an environmental baseline evaluation regarding the Brazilian potential for exploring its unconventional gas reserves. Eleven and thirteen samples of surface waters and groundwater were analyzed for gross alpha and beta using a gas flow proportional counter. A radiological background range was proposed using the ± 2 Median Absolute Deviation method. Using geoprocessing tools, the annual equivalent doses and lifetime cancer risk indexes were spatialized. Gross alpha and beta background thresholds in surface water ranged from 0.04-0.40 Bq L-1 to 0.17-0.46 Bq L-, respectively. Groundwater radiological background varies from 0.006-0.81 Bq L-1 to 0.06-0.72 Bq L-1 for gross alpha and beta, respectively. All environmental indexes are relatively higher in the south of the basin, probably a direct response to the local volcanic formations. Traçadal fault and local gas seepages might also influence the gross alpha and beta distribution. All samples have radiological indexes below the environmental thresholds, and should remain at acceptable levels with the development of the unconventional gas industry in Brazil.

Morphophysiology and production of bell pepper grown under salt stress and salicylic acid foliar application.

Considering the relevance of bell pepper and the limitations imposed by the deleterious effects of salt stress, especially in semi-arid regions, it is extremely important to establish strategies that can facilitate the use of saline water in vegetable production. In this scenario, this study aimed to evaluate the effect of the frequency of foliar application of salicylic acid on the morphophysiology and production of the bell pepper cv. "All Big" irrigated with saline water. The study was conducted at a greenhouse in Campina Grande - PB. The treatments were distributed in a completely randomized design and set up in a 4 × 4 factorial arrangement with three replications, corresponding to four application frequencies of salicylic acid (F1- No application of salicylic acid, F2 - Weekly application, F3- fortnightly application, and F4- monthly application) and four levels of electrical conductivity of irrigation water - ECw (0.8, 1.6, 2.4 and 3.2 dS m-1). The fortnightly application of salicylic acid at a concentration of 1.0 mM mitigated the effects of salt stress on the morphophysiology and production components of bell pepper cv. All Big cultivated with ECw of up to 2.4 dS m-1, which reinforces the hypothesis that salicylic acid can act as a signaling molecule and reduce the effects of saline stress in bell pepper, enabling the use of brackish water in agricultural activity, mainly in semi-arid regions of northeastern Brazil, which have a shortage of fresh water.