IL-27-engineered CAR.19-NK-92 cells exhibit enhanced therapeutic efficacy.

Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells has shown promising results in early-phase clinical studies. However, advancing CAR-NK cell therapeutic efficacy is imperative. In this study, we investigated the impact of a fourth-generation CD19-targeted CAR (CAR.19) coexpressing IL-27 on NK-92 cells. We observed a significant improvement in NK-92 cell proliferation and cytotoxicity activity against B-cell cancer cell lines, both in vitro and in a xenograft mouse B-cell lymphoma model. Our systematic transcriptome analysis of the activated NK-92 CAR variants further supports the potential of IL-27 in fourth-generation CARs to overcome limitations of NK cell-based targeted tumor therapies by providing essential growth and activation signals. Integrating IL-27 into CAR-NK cells emerges as a promising strategy to enhance their therapeutic potential and elicit robust responses against cancer cells. These findings contribute substantially to the mounting evidence supporting the potential of fourth-generation CAR engineering in advancing NK cell-based immunotherapies.

Towards a species-level phylogeny for Neotropical Myrtaceae: Notes on topology and resources for future studies.

PREMISE: Increasingly complete phylogenies underpin studies in systematics, ecology, and evolution. Myrteae (Myrtaceae), with ~2700 species, is a key component of the exceptionally diverse Neotropical flora, but given its complicated taxonomy, automated assembling of molecular supermatrices from public databases often lead to unreliable topologies due to poor species identification. METHODS: Here, we build a taxonomically verified molecular supermatrix of Neotropical Myrteae by assembling 3909 published and 1004 unpublished sequences from two nuclear and seven plastid molecular markers. We infer a time-calibrated phylogenetic tree that covers 712 species of Myrteae (~28% of the total diversity in the clade) and evaluate geographic and taxonomic gaps in sampling. RESULTS: The tree inferred from the fully concatenated matrix mostly reflects the topology of the plastid data set and there is a moderate to strong incongruence between trees inferred from nuclear and plastid partitions. Large, species-rich genera are still the poorest sampled within the group. Eastern South America is the best-represented area in proportion to its species diversity, while Western Amazon, Mesoamerica, and the Caribbean are the least represented. CONCLUSIONS: We provide a time-calibrated tree that can be more reliably used to address finer-scale eco-evolutionary questions that involve this group in the Neotropics. Gaps to be filled by future studies include improving representation of taxa and areas that remain poorly sampled, investigating causes of conflict between nuclear and plastid partitions, and the role of hybridization and incomplete lineage sorting in relationships that are poorly supported.

The evolution of ecological specialization underlies plant endemism in the Atlantic Forest.

BACKGROUND AND AIMS: The evolution of ecological specialization is favoured under divergent selection imposed by increased environmental heterogeneity, although specialization can limit the geographical range of organisms, thus promoting endemism. The Atlantic Forest (AF) is an ancient montane domain with high plant endemism, containing different environments for plant specialization. Miconia is the most diverse genus of woody flowering plant within the AF domain, including AF-endemic and non-endemic lineages. We hypothesized that Miconia species have faced increased environmental heterogeneity and consequently have been selected towards increased specialization in the AF domain, and this increased specialization has greatly reduced species geographical ranges, ultimately promoting endemism. Hence, we made the following predictions: (1) AF-endemic species should face greater environmental heterogeneity than non-endemic species; (2) AF-endemic species should be more specialized than non-endemic species; (3) specialization should lead to smaller geographical ranges; (4) specialization and small geographical ranges among AF-endemic species should conform to a selection-driven evolutionary scenario rather than to a neutral evolutionary scenario; and (5) small geographical ranges among AF-endemic species should date back to the occupation of the AF domain rather than to more recent time periods. METHODS: We used geographical, environmental and phylogenetic data on a major Miconia clade including AF-endemic and non-endemic species. We calculated Rao's Q to estimate the environmental heterogeneity faced by species. We used georeferenced occurrences to estimate the geographical ranges of species. We applied environmental niche modelling to infer species niche breadth. We inferred the most likely evolutionary scenario for species geographical range and niche breadth via a model-fitting approach. We used ancestral reconstructions to evaluate species geographical range throughout time. KEY RESULTS: Atlantic Forest-endemic species faced 33-60 % more environmental heterogeneity, with the increase being associated with montane landscapes in the AF. The AF-endemic species were 60 % more specialized overall, specifically over highly variable environmental gradients in AF montane landscapes. Specialization strongly predicted small geographical ranges among AF-endemic species and was a major range-limiting factor among endemic lineages. The AF-endemic species have evolved towards specialization and small geographical ranges under a selection-driven regime, probably imposed by the great environmental heterogeneity in AF montane landscapes. The AF-endemic species underwent a major reduction of geographical range immediately after their evolution, indicating a long-standing effect of selective pressures in the AF domain. CONCLUSION: Environmental heterogeneity imposes selective pressures favouring ecological specialization and small geographical ranges among plant lineages in the AF domain. This selection-driven process has probably promoted plant endemism in the AF domain throughout its history.

Final size and partial distance estimate for a two-group SEIRD model.

In this paper we consider a SEIRD epidemic model for a population composed by two groups of individuals with asymmetric interaction. Given an approximate solution for the two-group model, we estimate the error of this approximation to the unknown solution to the second group based on the known error that the approximation has with respect to the solution to the first group. We also study the final size of the epidemic for each group. We illustrate our results with the spread of the coronavirus disease 2019 (COVID-19) pandemic in the New York County (USA) for the initial stage of the contamination, and in the cities of Petrolina and Juazeiro (Brazil).

Anti-Leishmania spp. antibody detection in domestic cats from a visceral leishmaniasis transmission area.

Feline leishmanial infection is reported worldwide, but the epidemiological role of domestic cats in the leishmaniasis cycle remains unclear, and cats might act as cryptic reservoir hosts in endemic areas with no feline leishmaniosis cases. Considering that, a serological screening for anti-Leishmania spp. antibodies was performed by indirect immunofluorescence antibody test (IFAT) in 389 necropsied cats' serum samples from a new visceral leishmaniasis transmission area with no feline leishmanial infection reported to unveil if the cats are being exposed to the parasite. The overall seroprevalence for Leishmania spp. was 11.05% (43/389). No association was found between sex, neutering status, age group, breed, coat length, feline immunodeficiency virus (FIV) infection, and Leishmania spp. antibody detection. A positive association was found with coat color (cats within the orange spectrum with white [particolor]) (OR = 2.47, CI 95% 1 - 6.13, P = 0.044) and a negative association (OR = 0.38, CI 95% 0.18 - 0.79, P = 0.01) between feline leukemia virus (FeLV) infection and IFAT positivity for Leishmania spp. Therefore, it is concluded that the seroprevalence found was greater than 10%, indicating contact of the protozoan with cats in the region served.

All-triploid offspring in the yellowtail tetra Astyanax altiparanae Garutti & Britski 2000 (Teleostei, Characidae) derived from female tetraploid × male diploid crosses.

This study aimed to evaluate the ploidy and survival of larvae resulting from crosses between tetraploid females and diploid males of yellowtail tetra Astyanax altiparanae, both females (three diploids and three tetraploids) and males (n = 3 diploids). Breeders were subjected to hormonal induction with pituitary gland extract from common carp fish (Cyprinus carpio). Females received two doses at concentrations of 0.3 and 3.0 mg/kg -1 body weight and at intervals of 6 h. Males were induced with a single dose of 3.0 mg/kg -1 applied simultaneously with the second dose in females. Oocytes from each diploid and tetraploid female were fertilized with semen from the same male, resulting in two crosses: cross 1 (diploid male and diploid female) and cross 2 (diploid male and tetraploid female). The procedures were performed with separate females (diploid and tetraploid) and diploid males for each repetition (n = 3). For ploidy determination, 60 larvae from each treatment were analyzed using flow cytometry and cytogenetic analyses. As expected, flow cytometry analysis showed that progenies from crosses 1 and 2 presented diploid and triploid individuals, respectively, with a 100% success rate. The same results were confirmed in the cytogenetic analysis, in which the larvae resulting from cross 1 had 50 metaphase chromosomes and those from cross 2 had 75 chromosomes. The oocytes have a slightly ovoid shape at the time of extrusion. Diploid oocytes had a size of 559 ± 20.62 µm and tetraploid of 1025.33 ± 30.91 µm. Statistical differences were observed between eggs from crosses 1 and 2 (P = 0.0130). No significant differences between treatments were observed for survival at the 2-cell stage (P = 0.6174), blastula (P = 0.9717), gastrula (P = 0.5301), somite (P = 0.3811), and hatching (P = 0.0984) stages. In conclusion, our results showed that tetraploid females of the yellowtail tetra A. altiparanae are fertile, present viable gametes after stripping and fertilization using the 'dry method', and may be used for mass production of triploids. This is the first report of these procedures within neotropical characins, and which can be applied in other related species of economic importance.

Schinus terebinthifolius Raddi (Brazilian pepper) leaves extract: in vitro and in vivo evidence of anti-inflammatory and antioxidant properties.

The aim of this work was to evaluate the anti-inflammatory and antioxidant effects of ethyl acetate extract obtained from the leaves of Brazilian peppertree Schinus terebinthifolius Raddi (EAELSt). Total phenols and flavonoids, chemical constituents, in vitro antioxidant activity (DPPH and lipoperoxidation assays), and cytotoxicity in L929 fibroblasts were determined. In vivo anti-inflammatory and antioxidant properties were evaluated using TPA-induced ear inflammation model in mice. Phenol and flavonoid contents were 19.2 ± 0.4 and 93.8 ± 5.2 of gallic acid or quercetin equivalents/g, respectively. LC-MS analysis identified 43 compounds, of which myricetin-O-pentoside and quercetin-O-rhamnoside were major peaks of chromatogram. Incubation with EAELSt decreased the amount of DPPH radical (EC50 of 54.5 ± 2.4 µg/mL) and lipoperoxidation at 200-500 µg/mL. The incubation with EAELSt did not change fibroblast viability up to 100 µg/mL. Topical treatment with EAELSt significantly reduced edema and myeloperoxidase activity at 0.3, 1, and 3 mg/ear when compared to the vehicle-treated group. In addition, EAELSt decreased IL-6 and TNF-α levels and increased IL-10 levels. Besides, it modulated markers of oxidative stress (reduced total hydroperoxides and increased sulfhydryl contents and ferrium reduction potential) and increased the activity of catalase and superoxide dismutase, without altering GPx activity.

Molecular targets for the development of new acaricides against Rhipicephalus microplus: a review.

The cattle tick Rhipicephalus microplus is an ectoparasite with high economic importance to bovine culture, mainly in tropical and subtropical regions. The resistance of the tick from the commercial acaricides has hindered its control, thus motivating the search for new strategies. The purpose of this study was to perform a critical review about the main molecular targets of R. microplus that are useful for the discovery of new acaricides. Bibliographic search was conducted in the databases PubMed, ScienceDirect and CAB Direct, using the following descriptors: 'Rhipicephalus microplus', 'Boophilus microplus', 'molecular targets' and 'action', published between 2010 and 2021. Out of the 212 publications identified, 17 articles were selected for study inclusion. This review described 14 molecular targets and among these 4 are targets from commercial acaricides. Most of them are enzymes to catalyse important reactions to tick survival, related to energetic metabolism, mechanisms of biotransformation and neurotransmission. The data will be helpful in the development of new more effective and selective acaricides.

Pendimethalin biodegradation by soil strains of Burkholderia sp. and Methylobacterium radiotolerans.

Pendimethalin herbicide is widely used and persists in the environment as a contaminant causing negative impacts, including for human health. Microorganisms have the capacity to remove many contaminants from the environment. Thus, the aim of this work was to evaluate the efficiency of soil bacterial species prospected by molecular modelling of cytochrome P450 in to degrade pendimethalin. Strains of Burkholderia sp. and Methylobacterium radiotolerans were cultivated in a mineral saline medium enriched with 281 mg/L pendimethalin (MSPEN) and another containing glucose 1.0 g/L as extra carbon source (MSPENGLI). Both strains were able to degrade pendimethalin under the two conditions experienced. Burkholderia sp. F7G4PR33-4 was more efficient in degrading 65% of the herbicide in MSPEN medium, with 49.3% in MSPENGLI; while Methylobacterium radiotolerans A6A1PR46-4 degraded 55.4% in MSPEN and 29.8% in MSPENGLI mediums. These findings contribute to the expansion of knowledge on the competence of isolates of these two bacterial genera in degrading herbicidal xenobiotics and biotechnological potential for pendimethalin degradation and bioremediation.

Artefacts at different distances from titanium and zirconia implants in cone-beam computed tomography: effect of tube current and metal artefact reduction.

OBJECTIVES: To evaluate the effect of cone-beam computed tomography (CBCT) tube current (mA) on the magnitude of artefacts at different distances from titanium or zirconia implants, with and without activation of a proprietary metal artefact reduction (MAR). MATERIAL AND METHODS: Human mandibles were scanned on an OP300 Maxio CBCT unit (Instrumentarium, Tuusula, Finland) before and after the installation of dental implants, with four different tube currents (4 mA, 6.3 mA, 8 mA and 10 mA), with and without activation of proprietary MAR. The effect of mA on the standard deviation (SD) of gray values and contrast to noise ratio (CNR) were assessed in regions of interest located 1.5 cm, 2.5 cm, and 3.5 cm from implants. RESULTS: In the presence of titanium implants, a significant decrease in SD was found by increasing tube current from 4 mA to 6.3 mA or 8 mA. For zirconia implants, 8 mA yielded better results for all distances. MAR improved CNR in the presence of zirconia implants at all distances, whereas no differences were observed with the use of MAR for titanium implants. CONCLUSION: Increased tube current can improve overall image quality in the presence of implants, at all the distances tested. When a zirconia implant is present, such increase in mA should be higher in comparison to that for examinations with titanium implants. Activation of OP300 Maxio proprietary MAR improved image quality only among examinations with zirconia implants. CLINICAL RELEVANCE: Artefact-generating implants are common in the field of view of CBCT examinations. Optimal exposure parameters, such as tube current, ensure high image quality with lowest possible radiation exposure.

The role of postnatal estrogen deficiency on cranium dimensions.

OBJECTIVES: The aim of this study was investigate the cranium dimensions of adult female rats, who suffered estrogen deficiency during the prepubertal stage, to assess the impact of estrogen deficiency on craniofacial morphology. MATERIAL AND METHODS: Twenty-two female Wistar rats were divided into ovariectomy (OVX) (n = 11) and sham-operated control (n = 11) groups. Bilateral ovariectomy were performed in both groups at 21 days old (prepubertal stage), and rats were euthanized at an age of 63 days (post-pubertal stage). Micro-CT scans were performed with rat skulls, and the cranium morphometric landmark measurements were taken in the dorsal, lateral, and ventral view positions. Differences in measurements between the OVX and sham control groups were assessed using t test with an established alpha error of 5%. RESULTS: The measures of the rats' skull showed that the inter-zygomatic arch width and anterior cranial base length were significantly larger in OVX group (p = 0.020 and p = 0.050, respectively), whereas the length of parietal bone was significantly higher in the sham group (p = 0.026). For the remaining measurements no significant differences between groups were detected (p > 0.05). CONCLUSION: This study provides evidence that ovariectomized rats had alterations in cranial bone dimensions, demonstrating that estrogens during puberty are important for skull morphology. CLINICAL RELEVANCE: To understand the role of estrogen on the postnatal cranium development will impact the clinical diagnose and therapy during childhood and adolescence.

Methylglyoxal disturbs DNA repair and glyoxalase I system in Saccharomyces cerevisiae.

Methylglyoxal (MG) is a highly reactive aldehyde able to form covalent adducts with proteins and nucleic acids, disrupting cellular functions. In this study, we performed a screening of Saccharomyces cerevisiae (S. cerevisiae) strains to find out which genes of cells are responsive to MG, emphasizing genes against oxidative stress and DNA repair. Yeast strains were grown in the YPD-Galactose medium containing MG (0.5 to 12 mM). The tolerance to MG was evaluated by determining cellular growth and cell viability. The toxicity of MG was more pronounced in the strains with deletion in genes engaged with DNA repair checkpoint proteins, namely Rad23 and Rad50. MG also impaired the growth and viability of S. cerevisiae mutant strains Glo1 and Gsh1, both components of the glyoxalase I system. Differently, the strains with deletion in genes encoding for antioxidant enzymes were apparently resistant to MG. In summary, our data indicate that DNA repair and MG detoxification pathways are keys in the control of MG toxicity in S. cerevisiae.

Free-floating thrombus in lower limb deep veins and May-Thurner syndrome: case report.

Free-floating thrombus in the deep venous system has a high potential to cause pulmonary embolization. It can also be found in patients with superficial venous thrombosis (SVT) that extends to a deep vein. There are still no defined criteria for treatments described in the literature, which range from anticoagulation and fibrinolytic treatments with vena cava filter implants, through open or endovascular thrombectomies, to more invasive procedures such as surgical interruption with ligation of the venous system. We present the case of a patient with extensive deep venous thrombosis affecting the iliofemoral-popliteal territory with a floating thrombus extending from the left common iliac vein to the inferior vena cava. Treatment was performed with fibrinolytic therapy delivered with a multiperforated catheter, supplemented with anticoagulation with heparin and daily control angiography. At the end of the treatment, a significant stenosis was identified in the left common iliac vein, and angioplasty was performed with stenting.

3D-Printed Low-Cost Spectroelectrochemical Cell for In Situ Raman Measurements.

Raman spectroelectrochemistry is a powerful technique for characterizing structural changes of materials during electrochemical reactions and investigating the mechanism of film deposition and adsorption processes on the surfaces of electrodes. Moreover, in situ measurements enable identification of catalytic sites and reaction intermediates, which facilitates the comprehension of reaction mechanisms. The limitations of this technique include the high-cost and the complexity of the experimental arrangement required by commercial spectroelectrochemical cells (SEC). Thus, 3D-printing technology emerges as an excellent alternative for the production of SEC, with desirable shape, low-cost, and robustness in a short period of time. In this work, an SEC and a 3D-printed working electrode were fabricated from acrylonitrile-butadiene-styrene (ABS) and conductive graphene polylactic acid (PLA) filaments, respectively. The proposed SEC and the 3D-printed electrode were printed within 3.5 h with an estimated cost of materials of less than US $2. Then, the 3D-printed SEC and the electrode were used in a study of structural changes of Prussian blue according to different voltage bias.

A short peptide with selective anti-biofilm activity against Pseudomonas aeruginosa and Klebsiella pneumoniae carbapenemase-producing bacteria.

Biofilm-related infections represent an enormous clinical challenge nowadays. In this context, diverse studies are underway to develop effective antimicrobial agents targeting bacterial biofilms. Here, we describe the antibacterial and anti-biofilm activities of a short, cationic peptide named R5F5, obtained from sliding-window analysis based on a peptide (PcDBS1R5) derived from Plasmodium chabaudi. Ten fragments were generated (R5F1 to F10) and submitted to initial antibacterial assays against Pseudomonas aeruginosa. As a result, R5F5 showed the highest antimicrobial activity. We therefore carried out further antibacterial and anti-biofilm assays against P. aeruginosa and Klebsiella pneumoniae carbapenemase-producing bacterial strains. R5F5 revealed selective anti-biofilm activity, as the peptide inhibited >60% biofilm formation in all cases from 8 to 64 µg·mL-1. Moreover, R5F5 was not hemolytic against mice erythrocytes at 640 µg mL-1. Cytotoxic effects on human lung fibroblast cells were not detected at 160 µg·mL-1. Structural studies revealed that R5F5 presents random coil conformations in water and 50% 2,2,2-trifluoroethanol (TFE)/water (v/v), whereas amphipathic, extended conformations were observed in contact with sodium dodecyl sulfate (SDS) micelles. Thus, here we report a novel peptide with selective anti-biofilm activity against susceptible and resistant bacterial strains, with no toxicity toward mammalian cells and that adopts a stable structure in anionic environment.

The impact of attention deficit hyperactivity disorder in obsessive-compulsive disorder subjects.

BACKGROUND: Recent findings suggest an association between attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). Thus, we evaluated the clinical associated features of ADHD in a large sample of adult OCD patients. METHODS: A cross-sectional study including 955 adult patients with OCD from the Brazilian Research Consortium of Obsessive-Compulsive Spectrum Disorders (C-TOC). Clinical characteristics in adult OCD patients with and without comorbid ADHD were compared using Fisher's exact test, t-tests or Mann-Whitney tests. Bivariate analyses were followed by logistic regression analysis to identify clinical characteristics independently associated with ADHD comorbidity. RESULTS: The lifetime prevalence of ADHD in adult OCD patients was 13.7%. The current results indicate that OCD + ADHD patients were more severe, had an earlier onset of the obsessive-compulsive symptoms, a higher history of rheumatic fever, with higher frequencies of sensory phenomena and comorbidity with Tourette syndrome. They also had an increased risk for academic impairment and suicide attempts. CONCLUSION: Adult OCD patients with ADHD present some specific clinical features and may represent a special subgroup of adult OCD. Future studies should focus on the development of interventions more tailored to the phenotype of this subgroup of patients.

Elevated levels of inflammatory markers in women with rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune and progressive disease. Evidence indicates that inflammatory mediators may contribute to the genesis and/or evolution of this clinical condition. Thus, the objective was to evaluate and compare the plasma levels of Interleukin-17 (IL-17), Tumor Necrosis Factor-Alpha (TNF-α) and Complement 3 (C3) in women with RA and healthy controls (HC), as well as to evaluate the association them with the disease activity. 25 women with RA and 15 HC were recruited. Plasma levels of biomarkers were measured by ELISA. All statistical analyzes were performed with a significance level set at α = 0.05. In the women with RA, the median age was 55 and, in the HC, was 50 years. The median value of DAS-28 was 3.79. The plasma levels of IL-17 (p = .03), TNF-α (p ≤ 0.01) and C3 (p ≤ 0.01) were higher in women with RA. The ROC curve showed that TNF- α has a higher discriminating ability than IL-17 and C3. DAS-28 score correlated significantly with C3 levels in women with RA (r = 0.91; p < .01). These findings reaffirm the participation of the immune system in pathophysiology of RA, suggest that TNF-α levels may be a good biomarker and that elevated C3 levels contribute to the worsening of the disease.

Venous revascularization to treat posterior nutcracker syndrome by transposition of the left gonadal vein: case report.

The Nutcracker Syndrome is manifest in the presence of a symptomatic entrapment of the left renal vein between the abdominal aorta and the superior mesenteric artery. In a more ephemeral variation of this disorder, called the Posterior Nutcracker Syndrome, the renal vein is not compressed anterior to the aorta, but posteriorly, between the artery and the spine. Although there are multiple treatment options, current techniques aim to relieve the symptoms and reduce venous pressure on the left renal vein. This report describes a case of Posterior Nutcracker Syndrome in which the management approach chosen was open surgery, transposing the gonadal vein distally, to the inferior cava vein.

Treatment of type 1A endoleak using coil embolization: a case report.

In a type 1A endoleak, the endograft is unable to fully seal the proximal aneurysm neck and blood flow leaks between the wall of the aortic neck and the graft material. This article reports a case in which coil embolization was used and presents a literature review (PubMed, LILACS, and SciELO). Searches were run for articles published in the past 5 years using the descriptors "endoleak 1A", "coil embolization," and "treatment". Type 1A endoleak occurs in 1.1% of patients within 30 days of graft placement. Treatment of an endoleak is obligatory and usually consists of sealing the proximal graft neck using stents and balloons to expand the landing zone or to increase the radial force of the graft. Some studies have suggested using embolization techniques with cyanoacrylate, fibrin glue, and Onyx, demonstrating success rates that exceed 97%. However, correction of type 1A endoleak using coil embolization has seldom been described.