Allelic variability in the Rpp1 locus conferring resistance to Asian soybean rust revealed by genome-wide association.

Soybean is a crucial crop for the Brazilian economy, but it faces challenges from the biotrophic fungus Phakopsora pachyrhizi, which causes Asian Soybean Rust (ASR). In this study, we aimed to identify SNPs associated with resistance within the Rpp1 locus, which is effective against Brazilian ASR populations. We employed GWAS and re-sequencing analyzes to pinpoint SNP markers capable of differentiating between soybean accessions harboring the Rpp1, Rpp1-b and other alternative alleles in the Rpp1 locus and from susceptible soybean cultivars. Seven SNP markers were found to be associated with ASR resistance through GWAS, with three of them defining haplotypes that efficiently distinguished the accessions based on their ASR resistance and source of the Rpp gene. These haplotypes were subsequently validated using a bi-parental population and a diverse set of Rpp sources, demonstrating that the GWAS markers co-segregate with ASR resistance. We then examined the presence of these haplotypes in a diverse set of soybean genomes worldwide, finding a few new potential sources of Rpp1/Rpp1-b. Further genomic sequence analysis revealed nucleotide differences within the genes present in the Rpp1 locus, including the ULP1-NBS-LRR genes, which are potential R gene candidates. These results provide valuable insights into ASR resistance in soybean, thus helping the development of resistant soybean varieties through genetic breeding programs.

Nitric oxide-releasing photocrosslinked chitosan cryogels.

The highly porous morphology of chitosan cryogels, with submicrometric-sized pore cell walls, provides a large surface area which leads to fast water absorption and elevated swelling degrees. These characteristics are crucial for the applications of nitric oxide (NO) releasing biomaterials, in which the release of NO is triggered by the hydration of the material. In the present study, we report the development of chitosan cryogels (CS) with a porous structure of interconnected cells, with wall thicknesses in the range of 340-881 nm, capable of releasing NO triggered by the rapid hydration process. This property was obtained using an innovative strategy based on the functionalization of CS with two previously synthesized S-nitrosothiols: S-nitrosothioglycolic acid (TGA(SNO)) and S-nitrosomercaptosuccinic acid (MSA(SNO)). For this purpose, CS was previously methacrylated with glycidyl methacrylate and subsequently submitted to photocrosslinking and freeze-drying processes. The photocrosslinked hydrogels thus obtained were then functionalized with TGA(SNO) and MSA(SNO) in reactions mediated by carbodiimide. After functionalization, the hydrogels were frozen and freeze-dried to obtain porous S-nitrosated chitosan cryogels with high swelling capacities. Through chemiluminescence measurements, we demonstrated that CS-TGA(SNO) and CS-MSA(SNO) cryogels spontaneously release NO upon water absorption at rates of 3.34 × 10-2 nmol mg-1 min-1 and 1.27 × 10-1 nmol mg-1 min-1, respectively, opening new perspectives for the use of CS as a platform for localized NO delivery in biomedical applications.

Role of Vaccination Strategies to Host-Pathogen Dynamics in Social Interactions.

This study presents extended Immunity Agent-Based Model (IABM) simulations to evaluate vaccination strategies in controlling the spread of infectious diseases. The application of IABM in the analysis of vaccination configurations is innovative, as a vaccinated individual can be infected depending on how their immune system acts against the invading pathogen, without a pre-established infection rate. Analysis at the microscopic level demonstrates the impact of vaccination on individual immune responses and infection outcomes, providing a more realistic representation of how the humoral response caused by vaccination affects the individual's immune defense. At the macroscopic level, the effects of different population-wide vaccination strategies are explored, including random vaccination, targeted vaccination of specific demographic groups, and spatially focused vaccination. The results indicate that increased vaccination rates are correlated with decreased infection and mortality rates, highlighting the importance of achieving herd immunity. Furthermore, strategies focused on vulnerable populations or densely populated regions prove to be more effective in reducing disease transmission compared to randomly distributed vaccination. The results presented in this work show that vaccination strategies focused on highly crowded regions are more efficient in controlling epidemics and outbreaks. Results suggest that applying vaccination only in the densest region resulted in the suppression of infection in that region, with less intense viral spread in areas with lower population densities. Strategies focused on specific regions, in addition to being more efficient in reducing the number of infected and dead people, reduce costs related to transportation, storage, and distribution of doses compared to the random vaccination strategy. Considering that, despite scientific efforts to consolidate the use of mass vaccination, the accessibility, affordability, and acceptability of vaccines are problems that persist, investing in the study of strategies that mitigate such issues is crucial in the development and application of government policies that make immunization systems more efficient and robust.

Evaluation of total, soluble and ionic fluoride concentration in whitening and desensitizing toothpastes.

PURPOSES: Due to the popularity and increasing launch of toothpastes with whitening and sensitivity properties on the market, this study aimed to evaluate the fluoride concentrations in these products, since the concentrations of fluoride directly interfere with the anti-caries potential. METHODS: This is an experimental, in vitro study, where 37 samples from different batches (n = 3) purchased in different countries, were analysed in duplicate, via the ion-selective electrode technique to verify the concentration (µg/g or ppm F-) of total fluoride (TF), total soluble fluoride (TSF) and ionic fluoride (IF). For a comparative data analysis, ANOVA was applied followed by a Tukey's test for multiple comparisons. The level of confidence adopted was 95%. RESULTS: In the 37 assessed toothpastes, 45.9% contained NaF and 54.1% sodium monofluorophosphate (MFP). The TF found in the formulations ranged from 902.8 to 1539.4 ppm of F (mean: 1165.2 ± 179.3); fluoride concentration in the TSF fraction ranged from 708.8 to 1306.7 ppm of F (mean: 959.5 ± 162.4); IF results ranged from 101.9 to 1162.3 ppm of F (642.2 ± 294.1). Significant differences (p < 0.05) were found in the concentrations of the 59.5% assessed toothpastes in comparisons between declared and measured total fluoride (TF) concentrations, as well as in 62.2% when total fluoride (TF) and total soluble fluoride (TSF) were compared. CONCLUSIONS: In this study, most of the samples evaluated showed discrepancies when compared to the information declared by the manufacturers. In addition, the soluble concentrations found in half of the samples were lower than total concentrations and this may affect anti-caries effectiveness.

A comprehensive benchmark investigation of quantum chemical methods for carbocations.

The application of various density functional approximations (DFAs) and an emphasis on popular methods without any consensus have prevailed in computational studies dedicated to carbocations. More importantly, an extensive and rigorous benchmark investigation on density functionals for the class is still lacking. To close this gap, we present a comprehensive benchmark study of quantum chemical methods on a series of classical and nonclassical carbocations, the CARBO33 dataset. We evaluate a total of 107 DFT methods from all rungs giving particular attention to double hybrid density functionals as the potential of the class has been largely undermined in the context of carbocations. To support our findings, DLPNO-CCSD(T) at the complete basis set (CBS) limit and W1-F12 are used as reference methods. Our results indicate that the composite CBS-QB3 method performs poorly and should not be adopted for target energies. Oftentimes, the tested DFAs of a lower rung perform better than several DFAs in a higher rung of Perdew's "Jacob's ladder". Nonetheless, double hybrids DSD-PBEP86-NL and ωB97X-2-D3(BJ) stand out by showing the overall best performance. Among the hybrids evaluated, about half of them show mean absolute deviation (MAD) below 1.1 kcal mol-1, including the popular hybrids M06-2X and mPW1PW91. In this family, MN15-D3(BJ) performs particularly well (MAD = 0.77 kcal mol-1) displaying reliable results across various tests. Highly popular B3LYP exhibited one of the worst performances (MAD = 4.74 kcal mol-1), and we do not recommend its application to carbocations. We also assess the 24 general-purpose basis sets of single- up to quadruple-ζ quality. The best compromise between accuracy and computational cost is achieved with cc-pVTZ followed by def2-TZVP. Computations on larger structures of general interest, including terpene carbocations, are also presented for selected DFT methods confirming general trends in the results.

Nitric Oxide-Releasing Supramolecular Cellulose Nanocrystal/Silsesquioxane Foams.

Cellulose nanocrystals (CNC)-based foams are promising tissue engineering materials that may facilitate implant-tissue integration and allow localized and controlled drug delivery. Herein, hybrid CNC-based foams, which are ultralightweight (30-100 mg cm-3 ), highly porous (>95%), ominiphilic and superabsorbent (1500-3000 wt% of water and/or toluene uptake) are obtained by the in situ condensation of poly(ethylene glycol) ditriethoxysilyl (TES-PEG-TES) into a 3D network, where silsesquioxane nanoparticles (SS-NP) are the crosslinking nodes, and CNC are entrapped forming ionic interactions, in a supramolecular structure. In a new approach, using 3-mercaptopropyltrimethoxysilane, sulfhydryl groups are inserted on the SS-NP periphery and S-nitrosated to enable the functionalization of SS-NP with S-nitrosothiol groups, which can nitric oxide (NO), in a process triggered by the hydration of the foams and modulated by their supramolecular structure. CNC-SS-PEG foams exhibit elevated thermal and structural stability, compressive strength compatible with various soft human tissues, and NO release rates (1-18 pmol mg-1 min-1 ) within the range of the beneficial NO actions. Thus, the CNC-SS-PEG foams herein described represent a new platform of supramolecular hybrid materials for localized delivery of NO, with potential uses in tissue engineering and other biomedical applications.

Impact on quality of life in obstructive sialadenitis predicting outcomes after sialendoscopy.

PURPOSE: Sialendoscopy is a minimally invasive procedure considered a paradigm shift in the treatment of obstructive sialadenitis. However, it shows an average need for revision procedure in up to 24% of operated cases. This study analyzed whether patient-related variables could predict the need for a revision during postoperative follow-up. METHODS: From 2012 to 2020, this prospective comparative study analyzed demographic data as well as preoperative responses to the "Manukau Salivary Symptoms Score" (MSSS) questionnaire as predictors of the need for a revision procedure due to symptoms recurrence. RESULTS: 188 sialendoscopies (39.4% for stones/60.6% for stenoses) in 112 parotid (59.6%) and 76 submandibular glands (40.4%) were included in this study. Forty patients (21.3%) required a revision procedure. The variable "Impact on quality of life" in the preoperative period of patients with sialoliths showed that the likelihood of a revision procedure increases by 33.6% with each increase in the 10-point Likert scale presented in the MSSS (p = 0.010, OR = 1336, CI = 1.071 to 1.667). This finding was not influenced by the location of the sialolith in the duct (p = 0.415), size (p = 0.058) or number of stones (P = 0.476). Other demographic variables related to the patient showed no association with the need of a revision procedure. CONCLUSION: Further studies should be performed to exclude the influence of other variables on the results; however, special attention should be given to patients who report a greater pre-operative impact on quality of life due to sialolithiasis. LEVEL OF EVIDENCE: II.

Frequency and characterization of potential drug interactions in dentistry-a cross-sectional study.

AIM: This study aimed to identify medications taken by patients before dental appointments and to simulate and characterize their interactions with medications often prescribed by dental surgeons. MATERIALS AND METHODS: A retrospective cross-sectional study evaluated 320 medical records, 118 from the Emergency Service (ES) archives, and 202 from elective appointments at the Dental Clinic (DC) of a university in southern Brazil. Drug interactions were identified and classified according to severity using the Medscape® application into four grades: (1) Minor, (2) Monitor closely, (3) Serious, or (4) Contraindicated. Descriptive and inferential statistical analyses were carried out (α = 5%). RESULTS: Preexisting systemic conditions were noted in 55.9% of the medical records from the ES and 64.35% from the DC. In the ES records, 47.45% contained information on continuous use medication for treatment of systemic conditions and 59.40% of DC records contained such information. A total of 359 potential interactions were found. Drug interactions with analgesics were most frequent, accounting for 50.41% of the sample. CONCLUSIONS: The most prevalent drug interaction severity was grade 2: monitor or use with caution. Many patients take medications to treat systemic conditions and seek dental care, generating a significant possible source of drug interactions. CLINICAL RELEVANCE: Prescribers must carefully analyze the patients' medical histories and obtain accurate data regarding their use of medications to be able to assess the risk-benefit relationships of possible combinations.

Role of miRNAs in Human T Cell Leukemia Virus Type 1 Induced T Cell Leukemia: A Literature Review and Bioinformatics Approach.

Human T cell leukemia virus type 1 (HTLV-1) was identified as the first pathogenic human retrovirus and is estimated to infect 5 to 10 million individuals worldwide. Unlike other retroviruses, there is no effective therapy to prevent the onset of the most alarming diseases caused by HTLV-1, and the more severe cases manifest as the malignant phenotype of adult T cell leukemia (ATL). MicroRNA (miRNA) dysfunction is a common feature of leukemogenesis, and it is no different in ATL cases. Therefore, we sought to analyze studies that reported deregulated miRNA expression in HTLV-1 infected cells and patients' samples to understand how this deregulation could induce malignancy. Through in silico analysis, we identified 12 miRNAs that stood out in the prediction of targets, and we performed functional annotation of the genes linked to these 12 miRNAs that appeared to have a major biological interaction. A total of 90 genes were enriched in 14 KEGG pathways with significant values, including TP53, WNT, MAPK, TGF-ß, and Ras signaling pathways. These miRNAs and gene interactions are discussed in further detail for elucidation of how they may act as probable drivers for ATL onset, and while our data provide solid starting points for comprehension of miRNAs' roles in HTLV-1 infection, continuous effort in oncologic research is still needed to improve our understanding of HTLV-1 induced leukemia.

3D printed nitric oxide-releasing poly(acrylic acid)/F127/cellulose nanocrystal hydrogels.

Hydrogels have been used as matrices for the topical delivery of nitric oxide (NO) for achieving vasodilation, wound healing and analgesic actions. More recently, supramolecular hydrogels comprised of poly(acrylic acid) (PAA) and micellar Pluronic F127 (F127), prepared by thermal reaction, emerged as a suitable matrix for the incorporation of hydrophilic NO donors, such as S-nitrosoglutathione (GSNO). Herein, we describe an innovative method for the three-dimensional (3D) printing of cellulose nanocrystal (CNC)-containing and semi-interpenetrating PAA/F127 hydrogels by PAA photopolymerization via digital light processing (DLP), in the absence of organic solvents. Scanning electron microscopy showed that, differently from typical porous PAA-based hydrogels, the 3D printed PAA/F127/CNC hydrogels have dense morphology. By using transmission electron microscopy we confirmed for the first time the presence of F127 micelles in the printable resin, and their preservation after the photopolymerization process. The F127 micelles conferred compressive recoverability to the 3D printed PAA/F127/CNC hydrogels, widening their potential applications as soft biomaterials. PAA/F127/CNC hydrogels charged with GSNO are shown to release NO spontaneously upon hydration at initial rates that depend on the GSNO charge and are higher in the presence of CNC. As local NO release may exert cell proliferation action, 3D printed PAA/F127/CNC/GSNO hydrogels may serve as a versatile soft biomaterial for local NO delivery in regenerative medicine and other biomedical applications.

The Effects of Perinodular Features on Solid Lung Nodule Classification.

Lung cancer is the most lethal malignant neoplasm worldwide, with an annual estimated rate of 1.8 million deaths. Computed tomography has been widely used to diagnose and detect lung cancer, but its diagnosis remains an intricate and challenging work, even for experienced radiologists. Computer-aided diagnosis tools and radiomics tools have provided support to the radiologist's decision, acting as a second opinion. The main focus of these tools has been to analyze the intranodular zone; nevertheless, recent works indicate that the interaction between the nodule and its surroundings (perinodular zone) could be relevant to the diagnosis process. However, only a few works have investigated the importance of specific attributes of the perinodular zone and have shown how important they are in the classification of lung nodules. In this context, the purpose of this work is to evaluate the impact of using the perinodular zone on the characterization of lung lesions. Motivated by reproducible research, we used a large public dataset of solid lung nodule images and extracted fine-tuned radiomic attributes from the perinodular and intranodular zones. Our best-evaluated model obtained an average AUC of 0.916, an accuracy of 84.26%, a sensitivity of 84.45%, and specificity of 83.84%. The combination of attributes from the perinodular and intranodular zones in the image characterization resulted in an improvement in all the metrics analyzed when compared to intranodular-only characterization. Therefore, our results highlighted the importance of using the perinodular zone in the solid pulmonary nodules classification process.

S-nitrosothiol-terminated poly(vinyl alcohol): Nitric oxide release and skin blood flow response.

Polymeric biomaterials capable of delivering nitric oxide (NO) topically can be used to enhance skin blood flow (SkBF) and accelerate wound healing. Herein, we used reversible addition-fragmentation chain transfer radical (RAFT) polymerization to synthesize the first poly(vinyl alcohol) (PVA) functionalized with terminal NO-releasing S-nitrosothiol (RSNO) groups for topical NO delivery. This strategy was based on the synthesis of a precursor amino-terminated PVA (PVA-NH2), which was next functionalized with iminothiolane yielding 4-imino-4-amino-PVA-butane-1-thiol (PVA-SH), and finally S-nitrosated yielding S-nitroso 4-imino-4-amino-PVA-butane-1-thiol (PVA-SNO). Real-time chemiluminescence NO detection showed that blended films of pure PVA with PVA-SNO with mass ratios 30:70, 50:50 and 70:30 release NO with initial rates ranging from 1 to 12 nmol g-1 min-1, and lead to a 2 to 10-fold dose-response increase in the SkBF, after topical application on the ventral forearm of volunteers. These results show that PVA-SNO is a potential platform for topical NO delivery in biomedical applications.

Development and validation a task-specific checklist for a microsurgical varicocelectomy simulation model.

PURPOSE: To develop and validate a new test of specific technical skills required for microsurgical varicocelectomy. MATERIALS AND METHODS: An electronic questionnaire was sent to 558 members of the Brazilian Society of Urology for the validation of the task-specific checklist (TSC) for assessment of microsurgical varicocelectomy. Participants who had experience in this procedure were selected as judges. For construct validation, 12 participants including attending urologists and urological residents in training were recruited for voluntary participation. We formed a group of three experts and a group of nine novices, who had to perform the steps of microsurgical varicocelectomy on a simulation model using human placenta. Each participant was filmed and two blinded raters would then evaluate their performance using the TSC of microsurgical varicocelectomy. RESULTS: 14 judges were recruited. The assessment tool was reformulated, according to the judges suggestions and had the content validity achieved. The final version of the TSC was comprised of the task-specific score, a series of 4 items scored in a binary fashion designed for microscopic sub-inguinal varicocelectomy. The differences between the performance of participants with different levels of experience reflected the construct validity. The reliability between the raters was high. The mean time required to complete the training of microsurgical varicocelectomy in simulation model was significantly shorter for experts compared to novices (201 vs. 496 seconds, p=0.01). CONCLUSIONS: This preliminary study suggests that the task-specific checklist of microsurgical varicocelectomy is reliable and valid in assessing microsurgical skills.

COVID 19: sexual vulnerabilities and gender perspectives in Latin America.

Epidemics have gender aspects that are usually rarely addressed in mitigation efforts. Particularly unequal societies, such as those in Latin America, have tended to experience a more drastic impact during the coronavirus disease 2019 (COVID-19) pandemic, thus deepening the inequalities.

Long-term decomposition of aqueous S-nitrosoglutathione and S-nitroso-N-acetylcysteine: Influence of concentration, temperature, pH and light.

Primary S-nitrosothiols (RSNOs) have received significant attention for their ability to modulate NO signaling in many physiological and pathophysiological processes. Such actions and their potential pharmaceutical uses demand a better knowledge of their stability in aqueous solutions. Herein, we investigated the effects of concentration, temperature, pH, room light and metal ions on the long-term kinetic behavior of two representative primary RSNOs, S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylcysteine (SNAC). The thermal decomposition of GSNO and SNAC were shown to be affected by the auto-catalytic action of the thiyl radicals. At 25 °C in the dark and protected from the catalytic action of metal ions, GSNO and SNAC solutions 1 mM showed half-lives of 49 and 76 days, and apparent activation energies of 84 ±â€¯14 and 90 ±â€¯6 kJ mol-1, respectively. Both GSNO and SNAC exhibited increased stability in the pH range 5-7. At high pH the decomposition pathway of GSNO involves the formation of an intermediate (GS-NO22-), which decomposes generating GSH and nitrite. GSNO solutions displayed lower sensitivity to the catalytic action of metal ions than SNAC and the exposure to room light led to a 5-fold increase in the initial rates of decomposition of both RSNOs. In all comparisons, SNAC solutions showed higher stability than GSNO solutions. These findings provide strategic information about the stability of GSNO and SNAC and may open new perspectives for their use as experimental or therapeutic NO donors.

Microbial characterization of Arachis pintoi and its silages at different fermentation periods.

The microbial community present in forage peanut, a tropical legume, and its silages are unknown. For this reason, we used the Ion Torrent platform to study the bacterial community present in this legume during silage fermentation. Forage peanut was harvested at the start of flowering with a backpack mower and was chopped with a stationary ensilage cutter and then ensiled in bags measuring 25.40 cm × 35.56 cm, in triplicate. The bags were opened after 1, 3, 7, 14, 28 and 56 days of fermentation. Primers targeting the 16S rDNA gene were used, and the PCR products were used in library preparation and sequencing using the Ion Torrent platform. In total, 721,837 sequences were obtained and processed using the program MOTHUR v.23.0. The sequencing result revealed that the genus Weissella was present at the different periods of fermentation of peanut silage in greater amounts than the other genera (Bacillus, Rummeliibacillus, Enterococcus, Lactobacillus, Pediococcus). The six libraries constructed reached high coverage value (0.999). Comparison of the number of operational taxonomic units (OTUs) between the forage crop and the silages with 14 and 56 days of fermentation revealed that some sequences were exclusive to the plant and others to fermentation periods. The silage with 28 days of fermentation remained distant from the other fermentation periods in regard to microbial diversity. Knowledge of the diversity of different bacterial genera through sequence analysis can guide bioprospecting studies.

Acute effects of photobiomodulation therapy (PBMT) combining laser diodes, light-emitting diodes, and magnetic field in exercise capacity assessed by 6MST in patients with COPD: a crossover, randomized, and triple-blinded clinical trial.

Chronic obstructive pulmonary disease (COPD) is characterized by dyspnea, as well as musculoskeletal and systemic manifestations. Photobiomodulation therapy (PBMT) with use of low-level laser therapy (LLLT) and/or light-emitting diode therapy (LEDT) is an electrophysical intervention that has been found to minimize or delay muscle fatigue. The aim of this study was to evaluate the acute effect of PBMT with combined use of lasers diodes, light-emitting diodes (LEDs), magnetic field on muscle performance, exercise tolerance, and metabolic variables during the 6-minute stepper test (6MST) in patients with COPD. Twenty-one patients with COPD (FEV1 46.3% predicted) completed the 6MST protocol over 2 weeks, with one session per week. PBMT/magnetic field or placebo (PL) was performed before each 6MST (17 sites on each lower limb, with a dose of 30 J per site, using a cluster of 12 diodes 4 × 905 nm super-pulsed laser diodes, 4 × 875 nm infrared LEDs, and 4 × 640 nm red LEDs; Multi Radiance Medical™, Solon, OH, USA). Patients were randomized into two groups before the test according to the treatment they would receive. Assessments were performed before the start of each protocol. The primary outcomes were oxygen uptake and number of steps, and the secondary outcome was perceived exertion (dyspnea and fatigue in the lower limbs). PBMT/magnetic field applied before 6MST significantly increased the number of steps during the cardiopulmonary exercise test when compared to the results with placebo (129.8 ± 10.6 vs 116.1 ± 11.5, p = 0.000). PBMT/magnetic field treatment also led to a lower score for the perception of breathlessness (3.0 [1.0-7.0] vs 4.0 [2.0-8.0], p = 0.000) and lower limb fatigue (2.0 [0.0-5.0] vs 4.0 [0.0-7.0], p = 0.001) compared to that with placebo treatment. This study showed that the combined application of PBMT and magnetic field increased the number of steps during the 6MST and decreased the sensation of dyspnea and lower limb fatigue in patients with COPD.

Effects and parameters of the photobiomodulation in experimental models of third-degree burn: systematic review.

This systematic review was performed to identify the role of photobiomodulation therapy in experimental models of third-degree burns used to induce oxidative stress. EMBASE, PubMed, and CINAHL databases were searched for studies published between January 2003 and January 2018 on the topics of photobiomodulation therapy and third-degree burns. Any study that assessed the effects of photobiomodulation therapy in animal models of third-degree burns was included in the analysis. A total of 17 studies were selected from 1182 original articles targeted on photobiomodulation therapy and third-degree burns. Two independent raters with a structured tool for rating the research quality critically assessed the articles. Although the small number of studies limits the conclusions, the current literature research indicates that photobiomodulation therapy can be an effective short-term approach to accelerate the healing process of third-degree burns, to increase and modulate the inflammatory process, to accelerate the proliferation of fibroblasts, and to enhance the quality of the collagen network. However, differences still exist in the terminology used to describe the parameters and the dose of photobiomodulation therapy.

Piper Essential Oils Inhibit Rhizopus oryzae Growth, Biofilm Formation, and Rhizopuspepsin Activity.

Piper is the largest genus of the Piperaceae family. The species of this genus have diverse biological activities and are used in pharmacopeia throughout the world. They are also used in folk medicine for treatment of many diseases in several countries including Brazil, China, India, Jamaica, and Mexico. In Brazil, Piper species are distributed throughout the national territory, making this genus a good candidate for biological activity screening. During our studies with Piper essential oils, we evaluated its activity against Rhizopus oryzae, the main agent of mucormycosis. The main compounds of seven Piper essential oils analyzed were Piper callosum-safrole (53.8%), P. aduncum-dillapiole (76.0%), P. hispidinervum-safrole (91.4%), P. marginatum-propiopiperone (13.2%), P. hispidum-γ-terpinene (30.9%), P. tuberculatum-(E)-caryophyllene (30.1%), and Piper sp.-linalool (14.6%). The minimum inhibitory concentration of Piper essential oils against R. oryzae ranged from 78.12 to >1250 µg/mL. The best result of total inhibition of biofilm formation was obtained with Piper sp. starting from 4.88 µg/mL. Considering the bioactive potential of EOs against planktonic cells and biofilm formation of R. oryzae could be of great interest for development of antimicrobials for therapeutic use in treatment of fungal infection.

Development of a pharmacophore for cruzain using oxadiazoles as virtual molecular probes: quantitative structure-activity relationship studies.

Chagas's is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. According to the World Health Organization, 7 million people are infected worldwide leading to 7000 deaths per year. Drugs available, nifurtimox and benzimidazole, are limited due to low efficacy and high toxicity. As a validated target, cruzain represents a major front in drug discovery attempts for Chagas disease. Herein, we describe the development of 2D QSAR ([Formula: see text] = 0.81) and a 3D-QSAR-based pharmacophore ([Formula: see text] = 0.82) from a series of non-covalent cruzain inhibitors represented mostly by oxadiazoles (lead compound, IC50 = 200 nM). Both models allowed us to map key intermolecular interactions in S1', S2 and S3 cruzain sub-sites (including halogen bond and C‒H/π). To probe the predictive capacity of obtained models, inhibitors available in the literature from different classes displaying a range of scaffolds were evaluate achieving mean absolute deviation of 0.33 and 0.51 for 2D and 3D models, respectively. CoMFA revealed an unexplored region where addition of bulky substituents to produce new compounds in the series could be beneficial to improve biological activity.