Deciphering Stereoselectivity in Hurd-Claisen Rearrangements: A Comprehensive Study of Electrostatic Interactions from Shubin's Energy Decomposition Analysis.

In this study, we explore the stereoselectivity of Hurd-Claisen Rearrangements, focusing on the influence of two electron-withdrawing groups and eight diverse substituents. Utilizing the Curtin-Hammett principle, we performed energy calculations for reactions, products, and transition states using the M062X/def2TZVPP compound model. Our analysis reveals that kinetic factors predominantly dictate the reaction equilibrium. A key aspect of our research is the application of Shubin's energy decomposition analysis to optimized transition states, highlighting the significant role of electrostatic interactions in determining stereoselectivity. We further dissected each transition state into four fragments: the electron-withdrawing groups ( C O 2 E t ${CO_2 Et}$ , C N ${CN}$ ), the Hurd group ( H ${H}$ ), various substituents ( C H 3 ${CH_3 }$ , E t ${Et}$ , S P r o p ${SProp}$ , T B u t ${TBut}$ , I s o B u t ${IsoBut}$ , N H 2 P h ${NH_2 Ph}$ , N O 2 P h ${NO_2 Ph}$ , P h ${Ph}$ ), and the central fragment. This fragmentation approach enabled an in-depth analysis of group dipole moments, providing insights into the electrostatic forces at play. Our findings shed light on the intricate mechanisms driving stereoselectivity in Hurd-Claisen Rearrangements and enhance the understanding of molecular interactions, offering valuable implications for organic synthesis.

Revisiting Biginelli-like reactions: solvent effects, mechanisms, biological applications and correction of several literature reports.

This study critically reevaluates reported Biginelli-like reactions using a Kamlet-Abboud-Taft-based solvent effect model. Surprisingly, structural misassignments were discovered in certain multicomponent reactions, leading to the identification of pseudo three-component derivatives instead of the expected MCR adducts. Attempts to replicate literature conditions failed, prompting reconsideration of the described MCRs and proposed mechanisms. Electrospray ionization (tandem) mass spectrometry, NMR, melting points, elemental analyses and single-crystal X-ray analysis exposed inaccuracies in reported MCRs and allowed for the proposition of a complete catalytic cycle. Biological investigations using both pure and "contaminated" derivatives revealed distinctive features in assessed bioassays. A new cellular action mechanism was unveiled for a one obtained pseudo three-component adduct, suggesting similarity with the known dihydropyrimidinone Monastrol as Eg5 inhibitors, disrupting mitosis by forming monoastral mitotic spindles. Docking studies and RMSD analyses supported this hypothesis. The findings described herein underscore the necessity for a critical reexamination and potential corrections of structural assignments in several reports. This work emphasizes the significance of rigorous characterization and critical evaluation in synthetic chemistry, urging a careful reassessment of reported synthesis and biological activities associated with these compounds.

Cannabidiol induces systemic analgesia through activation of the PI3Kγ/nNOS/NO/KATP signaling pathway in neuropathic mice. A KATP channel S-nitrosylation-dependent mechanism.

BACKGROUND: Cannabidiol (CBD) is the second most abundant pharmacologically active component present in Cannabis sp. Unlike Δ-9-tetrahydrocannabinol (THC), it has no psychotomimetic effects and has recently received significant interest from the scientific community due to its potential to treat anxiety and epilepsy. CBD has excellent anti-inflammatory potential and can be used to treat some types of inflammatory and neuropathic pain. In this context, the present study aimed to evaluate the analgesic mechanism of cannabidiol administered systemically for the treatment of neuropathic pain and determine the endogenous mechanisms involved with this analgesia. METHODS: Neuropathic pain was induced by sciatic nerve constriction surgery, and the nociceptive threshold was measured using the paw compression test in mice. RESULTS: CBD produced dose-dependent antinociception after intraperitoneal injection. Selective inhibition of PI3Kγ dose-dependently reversed CBD-induced antinociception. Selective inhibition of nNOS enzymes reversed the antinociception induced by CBD, while selective inhibition of iNOS and eNOS did not alter this antinociception. However, the inhibition of cGMP production by guanylyl cyclase did not alter CBD-mediated antinociception, but selective blockade of ATP-sensitive K+ channels dose-dependently reversed CBD-induced antinociception. Inhibition of S-nitrosylation dose-dependently and completely reversed CBD-mediated antinociception. CONCLUSION: Cannabidiol has an antinociceptive effect when administered systemically and this effect is mediated by the activation of PI3Kγ as well as by nitric oxide and subsequent direct S-nitrosylation of KATP channels on peripheral nociceptors.

Single-Nucleotide Polymorphisms Associated with Mercury Levels and Neurological Symptoms: An Overview.

Mercury (Hg) pollution is a global public health concern because of its adverse effects on the environment and health. Single-nucleotide polymorphisms (SNPs) have been associated with Hg levels and outcomes. The aim of this review was to describe the research and discuss the evidence on the genetic susceptibility of Hg-exposed individuals to the development of neurocognitive disorders. A systematic review was performed to identify the genes/SNPs associated with Hg toxicokinetics and that, therefore, affect neurological function in exposed populations. Observational and experimental studies were identified by screening three databases. Thirteen articles were included (quality score 82-100%) and 8124 individuals were evaluated. Hg exposure was mainly fish consumption (77%) and, in 31% of the studies, the Hg levels exceeded the reference limits. Genetic susceptibility to higher Hg levels and neurotoxicity risk in Hg poisoning were associated with eight (ALAD rs1800435, CYP3A4 rs2740574, CYP3A5 rs776746, CYP3A7 rs2257401, GSTP1 rs1695, MT1A rs8052394, MT1M rs2270836, and MT4 rs11643815) and three (MT1A rs8052394, MT1M rs2270837, and MT2A rs10636) SNPs, respectively, and rs8052394 was associated with both outcomes. The MT1A rs8052394 SNP may be used as a susceptibility biomarker to identify individuals at greater risk for higher Hg levels and the development of neurocognitive disorders in metal-exposed populations.

Micellar solution of [223Ra]RaCl2: Reaching renal excretion, potent efficacy in osteoblastic osteosarcoma in PDX model, biochemistry alterations and pharmacokinetics.

Despite the successful use of the radiopharmaceutical radium-223 dichloride ([223Ra]RaCl2) for targeted alpha therapy of castration-resistant prostate cancer patients with bone metastases, some short-term side effects, such as diarrhea and vomiting, have been documented, causing patient discomfort. Hence, we prepared a nanosized micellar solution of [223Ra]RaCl2 and evaluated its biodistribution, pharmacokinetics, and induced biochemical changes in healthy mice up to 96 h after intraperitoneal administration as an alternative to overcome the previous limitations. In addition, we evaluated the bone specificity of micellar [223Ra]RaCl2 in patient-derived xenografts in the osteosarcoma model. The biodistribution studies revealed the high bone-targeting properties of the micellar [223Ra]RaCl2. Interestingly, the liver uptake remained significantly low (%ID/g = 0.1-0.02) from 24 to 96 h after administration. In addition, the micellar [223Ra]RaCl2 exhibited a significantly higher uptake in left (%ID/g = 0.85-0.23) and right (%ID/g = 0.76-0.24) kidneys than in small (%ID/g = 0.43-0.06) and large intestines (%ID/g = 0.24-0.09) over time, suggesting its excretion pathway is primarily through the kidneys into the urine, in contrast to the non-micellar [223Ra]RaCl2. The micellar [223Ra]RaCl2 also had low distribution volume (0.055 ± 0.003 L) and longer elimination half-life (28 ± 12 days). This nanosystem was unable to change the enzymatic activities of alanine aminotransferase, aspartate aminotransferase, gamma GT, glucose, and liquiform lipase in the treated mice. Finally, microscopic examination of the animals' osteosarcoma tumors treated with micellar [223Ra]RaCl2 indicated regression of the tumor, with large areas of necrosis. In contrast, in the control group, we observed tumor cellularity and cell anaplasia, mitotic figures and formation of neoplastic extracellular bone matrix, which are typical features of osteosarcoma. Therefore, our findings demonstrated the efficiency and safety of nanosized micellar formulations to minimize the gastrointestinal excretion pathway of the clinical radiopharmaceutical [223Ra]RaCl2, in addition to promoting regression of the osteosarcoma. Further studies must be performed to assess dose-response outcomes and organ/tissue dosimetry for clinical translation.

Nitric oxide and potassium channels but not opioid and cannabinoid receptors mediate tramadol-induced peripheral antinociception in rat model of paw pressure withdrawal.

Tramadol, an analgesic classified as an "atypical opioid", exhibits both opioid and non-opioid mechanisms of action. This study aimed to explore these mechanisms, specifically the opioid-, cannabinoid-, nitric oxide-, and potassium channel-based mechanisms, which contribute to the peripheral antinociception effect of tramadol, in an experimental rat model. The nociceptive threshold was determined using paw pressure withdrawal. To examine the mechanisms of action, several substances were administered intraplantarly: naloxone, a non-selective opioid antagonist (50 µg/paw); AM251 (80 µg/paw) and AM630 (100 µg/paw) as the selective antagonists for types 1 and 2 cannabinoid receptors, respectively; nitric oxide synthase inhibitors L-NOArg, L-NIO, L-NPA, and L-NIL (24 µg/paw); and the enzyme inhibitors of guanylatocyclase and phosphodiesterase of cGMP, ODQ, and zaprinast. Additionally, potassium channel blockers glibenclamide, tetraethylammonium, dequalinium, and paxillin were used. The results showed that opioid and cannabinoid receptor antagonists did not reverse tramadol's effects. L-NOarg, L-NIO, and L-NPA partially reversed antinociception, while ODQ completely reversed, and zaprinast enhanced tramadol's antinociception effect. Notably, glibenclamide blocked tramadol's antinociception in a dose-dependent manner. These findings suggest that tramadol's peripheral antinociception effect is likely mediated by the nitrergic pathway and sensitive ATP potassium channels, rather than the opioid and cannabinoid pathways.

Percepção de gestantes quanto à atuação do enfermeiro no pré-natal / Perception of pregnant women regarding the performance of nurses in prenatal care / Percepción de las gestantes sobre la actuación del enfermero en el prenatal

Objetivo: identificar a percepção de gestantes quanto à atuação do enfermeiro no pré-natal. Método: pesquisa fenomenológica que entrevistou 10 gestantes de um município de Minas Gerais, Brasil. Os depoimentos foram organizados em categorias e analisados segundo a fenomenologia social de Alfred Schütz e literatura temática. Resultados: emergiram as categorias "Assistência centrada em ações técnicas", "Fragilidade na comunicação entre enfermeiro e gestante" e a expectativa de "orientações qualificadas desenvolvidas mediante atividades coletivas". Considerações finais: os resultados suscitam a necessidade de valorizar os aspectos subjetivos e comunicacionais no pré-natal, para além das ações técnicas, com vistas a efetivação do vínculo entre os atores, ampliação da adesão e da qualidade do pré-natal. Para tal, recomenda-se atividades de educação permanente

Objective: to identify the perception of pregnant women regarding the role of nurses in prenatal care. Method: phenomenological research that interviewed 10 pregnant women in a city in Minas Gerais, Brazil. The statements were organized into categories and analyzed according to Alfred Schütz's social phenomenology and thematic literature. Results: the categories "Care centered on technical actions", "Fragility in communication between nurse and pregnant woman" and the expectation of "qualified guidelines developed through collective activities" emerged. Final considerations: the results raise the need to value subjective and communicational aspects in prenatal care, in addition to technical actions, with a view to establishing the bond between actors, expanding adherence and quality of prenatal care. To this end, continuing education activities are recommended

Objetivos: identificar la percepción de las gestantes sobre el papel del enfermero en el prenatal. Método: investigación fenomenológica que entrevistó a 10 mujeres embarazadas en una ciudad de Minas Gerais, Brasil. Los enunciados fueron organizados en categorías y analizados según la fenomenología social y la literatura temática de Alfred Schütz. Resultados: surgieron las categorías "Cuidado centrado en acciones técnicas", "Fragilidad en la comunicación entre enfermero y gestante" y la expectativa de "orientaciones calificadas desarrolladas a través de actividades colectivas". Consideraciones finales: los resultados plantean la necesidad de valorar los aspectos subjetivos y comunicacionales en el prenatal, además de las acciones técnicas, con miras a establecer el vínculo entre los actores, ampliando la adherencia y la calidad del prenatal. Para ello, se recomiendan actividades de educación continua

Systematization of perioperative nursing care in robotic surgery: instrument validation.

OBJECTIVE: To develop and validate an instrument to assist in the systematization of perioperative nursing care in robotic surgery. METHODS: Methodological study developed in four phases: content survey; textual elaboration; content validation by the group of expert judges and target audience; and elaboration of the electronic instrument layout. RESULTS: Eleven expert judges and seven evaluators of the target audience participated. For validation, the Content Validity Index (CVI) was used with a 0.78 cutoff point. The instrument total CVI after evaluation was 0.90 by the expert judges and 0.88 by the target audience. CONCLUSION: The tool built was proved satisfactory for the systematization of perioperative nursing care. The instrument construction was based on the updated scientific literature and validated by the expert judges and target audience.

Kisspeptin (Kp-10) inhibits in vitro osteogenic differentiation of multipotent mesenchymal stromal cells extracted from the bone marrow of adult rats.

Kisspeptin (Kp-10) is a neuropeptide that binds to GPR54 receptors, exerting several functions mainly in the nervous and reproductive systems of the body. However, its effects and mechanisms of action on the skeletal system remain poorly understood. This study evaluated the effects of different concentrations of Kp-10 on in vitro osteogenic differentiation of multipotent mesenchymal stromal cells (MSCs) extracted from the bone marrow (BM) of adult Wistar rats. Two-month-old female rats were euthanized to extract BM from long bones to obtain MSCs. Four experimental groups were established in vitro: a control and Kp-10 at concentrations of 0.01, 0.05 and, 0.1 µg/mL. After induction of osteogenic differentiation, cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl tetrazolium bromide (MTT) assay, alkaline phosphatase activity, collagen synthesis, percentage of area covered by MSCs/field and mineralized nodules/field, and immunocytochemistry of the GPR54 receptor tests. Furthermore, evaluation of gene transcripts for type I collagen, Runx-2, Bmp-2, bone sialoprotein, osteocalcin and osteopontin was performed using real-time RT-qPCR. It was observed that MSCs expressed GPR54 receptor to which Kp-10 binds during osteogenic differentiation, promoting a negative effect on osteogenic differentiation. This effect was observed at all the Kp-10 concentrations in a concentration-dependent manner, characterized by a decrease in the activity of alkaline phosphatase, collagen synthesis, mineralized nodules, and decreased expression of gene transcripts for type I collagen, osteocalcin, osteopontin, and Runx-2. Thus, Kp-10 inhibits in vitro osteogenic differentiation of MSCs extracted from the BM of adult Wistar rats.

Euterpe oleracea extract (açaí) exhibits cardioprotective effects after chemotherapy treatment in a breast cancer model.

BACKGROUND: Açaí, a Brazilian native fruit, has already been demonstrated to play a role in the progress of breast cancer and cardiotoxicity promoted by chemotherapy agents. Thus, the present study aimed to evaluate the combined use of açaí and the FAC-D chemotherapy protocol in a breast cancer model in vivo. METHODS: Mammary carcinogenesis was induced in thirty female Wistar rats by subcutaneous injection of 25 mg/kg 7,12-dimethylbenzanthracene (DMBA) in the mammary gland. After sixty days, the rats were randomized into two groups: treated with 200 mg/kg of either açaí extract or vehicle, via gastric tube for 45 consecutive days. The FAC-D protocol was initiated after 90 days of induction by intraperitoneal injection for 3 cycles with a 7-day break each. After treatment, blood was collected for haematological and biochemical analyses, and tumours were collected for macroscopic and histological analyses. In the same way, heart, liver, and kidney samples were also collected for macroscopic and histological analyses. RESULTS: Breast cancer was found as a cystic mass with a fibrotic pattern in the mammary gland. The histological analysis showed an invasive carcinoma area in both groups; however, in the saline group, there was a higher presence of inflammatory clusters. No difference was observed regarding body weight, glycaemia, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and urea in either group. However, açaí treatment decreased creatine kinase (CK), creatine kinase MB (CKMB), troponin I and C-reactive protein levels and increased the number of neutrophils and monocytes. Heart histopathology showed normal myocardium in the açaí treatment, while the saline group presented higher toxicity effects with loss of architecture of cardiac tissue. Furthermore, the açaí treatment presented greater collagen distribution, increased hydroxyproline concentration and lower H2AX immunostaining in the heart samples. CONCLUSION: Açaí decreased the number of inflammatory cells in the tumor environment and exhibited protection against chemotherapy drug cardiotoxicity with an increased immune response in animals. Thus, açaí can be considered a promising low-cost therapeutic treatment that can be used in association with chemotherapy agents to avoid heart damage.

Influence of interleukin-8 polymorphism on endometriosis-related pelvic pain.

Endometriosis presents a pro-inflammatory microenvironment influenced by cytokines, such as interleukin (IL)-8, which expression may be influenced by genetic polymorphisms. Therefore, we aimed to investigate the role of interleukin (IL)-8 rs4073 polymorphism in endometriosis' development and its related symptoms. A case-control study was conducted with 207 women with endometriosis and 193 healthy controls. Polymorphism was genotyped using a TaqMan validated assay. Associations were evaluated by binary logistic regression, using odds ratios (OR) and 95 % confidence intervals (CI), and P ≤ 0.05 was considered significant. Cases were younger (36 ± 6.8 versus 39 ± 8.4) and had lower body mass index (26.5 ± 5.3 versus 35.7 ± 6.3 Kg/m2) than controls (P < 0.001). Higher prevalence of symptoms and infertility was observed in cases, compared to controls (P < 0.001). Minor allele frequencies of IL-8 rs4073 (T) were 42.3 % and 39.9 % for cases and controls, respectively, and no associations were found between IL and 8 rs4073 polymorphism and endometriosis' prevalence or staging. However, the polymorphism was associated with chronic pelvic pain among cases (OR = 0.54; 95 %CI = 0.29-0.98). The IL-8 rs4073A > T polymorphism may contribute to lower IL-8 expression and, consequently, decrease endometriosis-related pelvic pain. These findings can support the early diagnosis of endometriosis' painful symptoms, preventing its complications, and allowing an individualized treatment.

(Ro)vibrational Spectroscopic Constants, Lifetime and QTAIM Evaluation of Fullerene Dimers Stability.

The iconic caged shape of fullerenes gives rise to a series of unique chemical and physical properties; hence a deeper understanding of the attractive and repulsive forces between two buckyballs can bring detrimental information about the structural stability of such complexes, providing significant data applicable for several studies. The potential energy curves for the interaction of multiple van der Waals buckyball complexes with increasing mass were theoretically obtained within the DFT framework at ωB97xD/6-31G(d) compound model. These potential energy curves were employed to estimate the spectroscopic constants and the lifetime of the fullerene complexes with the Discrete Variable Representation and with the Dunham approaches. It was revealed that both methods are compatible in determining the rovibrational structure of the dimers and that they are genuinely stable, i.e., long-lived complexes. To further inquire into the nature of such interaction, Bader's QTAIM approach was applied. QTAIM descriptors indicate that the interactions of these closed-shell systems are dominated by weak van der Waals forces. This non-covalent interaction character was confirmed by the RDG analysis scheme. Indirectly, QTAIM also allowed us to confirm the stability of the non-covalent bonded fullerene dimers. Our lifetime calculations have shown that the studied dimers are stable for more than 1 ps, which increases accordingly with the number of carbon atoms.

Intensity-Dependent Influence of Interoceptive Accuracy on Psychophysiological Responses During Aerobic Exercise in Physically Inactive Men.

We aimed to investigate the influence of interoceptive accuracy on affective valence, arousal, and ratings of perceived exertion (RPE) during 20 minutes of aerobic exercise at both moderate and heavy intensity among physically inactive men. We divided our participant sample into men with poor heartbeat perception (PHP, n = 13) and good heartbeat perception (GHP, n = 15), based on their cardioceptive accuracy. We measured their heart rate reserve (%HRreserve), perceived affective valence (Feeling Scale; +5/-5), perceived arousal (Felt Arousal Scale, 0-6), and ratings of perceived effort (RPE; Borg scale 6-20) every five minutes during an exercise session on a bicycle ergometer. During moderate-intensity aerobic exercise, the GHP group presented a greater decline in affective valence (p = 0.010; d = 1.06) and a greater increase in RPE (p = 0.004; d = 1.20) compared to the PHP group, with no group differences in %HRreserve (p = 0.590) and arousal (p = 0.629). Psychophysiological and physiological responses to the heavy-intensity aerobic exercise were not different between groups. We concluded that the influence of interoceptive accuracy on psychophysiological responses during submaximal fixed-intensity aerobic exercise was intensity-dependent in these physically inactive men.

Anos de vida perdidos ajustados pela incapacidade decorrentes de distúrbios musculoesqueléticos em profissionais de enfermagem oncológica / Disability adjusted life years due to musculoskeletal disorders in oncology nursing professionals / Años de vida perdidos ajustados por discapacidad por trastornos musculoesqueléticos en profesionales de enfermería oncologica

Objetivos: Estimar Anos de Vida Perdidos Ajustados pela Incapacidade - DALY decorrentes de distúrbios musculoesqueléticos em profissionais de enfermagem nas unidades hospitalares de uma instituição oncológica. Métodos: Estudo ecológico, utilizando banco de dados institucionais. Valores absolutos de DALY foram transformados em taxas por 100 mil habitantes, e calculadas por categoria profissional, sexo e faixa etária. Resultados: Estimou-se 3,78 DALY (2.136/100 mil) entre todos os profissionais de enfermagem; entre Técnicos de enfermagem 2,62 DALY (2186//100 mil); e entre Enfermeiros 1,15 DALY (2024/100mil). Maior DALY ocorreu entre técnicos de enfermagem, sexo feminino, faixa etária de 50 a 59 anos, cujo valor é 0,98 (3.161/100mil). As Dorsopatias geraram mais DALY (1,97 DALY), destacando-se as lombalgias e cervicalgias. Dos diagnósticos encontrados, 54% referiam-se a Doenças Osteomusculares Relacionadas ao Trabalho, e apresentaram 2,62 DALY (69% do total de DALY). Conclusão: Houve uma grande quantidade de DALY decorrente de doenças musculoesqueléticas entre os profissionais de enfermagem da instituição.

Objectives: To estimate Disability-Adjusted Life Years Lost - DALY due to musculoskeletal disorders in nursing professionals in the hospital units of an oncology institution. Methods: Ecological study, using institutional database. Absolute DALY values were transformed into rates per 100,000 inhabitants and calculated by professional category, sex and age group. Results: It was estimated 3.78 DALY (2,136/100 thousand) among all nursing professionals, among Nursing Technicians 2.62 DALY (2186//100 thousand) and among Nurses 1.15 DALY (2024/100 thousand). Higher DALYs occurred among female nursing technicians, aged 50 to 59 years with 0.98 DALY (3,161/100,000). Dorsopathies generated more DALY (1.97 DALY), especially low back pain and neck pain. Of the diagnoses found, 54% referred to Work-Related Musculoskeletal Diseases, and presented 2.62 DALYs (69% of the total DALY). Conclusion: There was a large amount of DALY due tomusculoskeletal disorders among nursing professionals at the institution.

Objetivos: Estimar los Años de Vida Ajustados en función de la Discapacidad (AVAD) derivada de los trastornos musculoesqueléticos entre los profesionales de enfermería en centros de una institución de oncología. Métodos: Estudio ecológico, basado en datos institucionales.Los valores absolutos de AVAD encontrados se transformaron en tasas por 100.000 habitantes, y se calcularon según categoría profesional, sexo y grupo de edad. Resultados:Se estimaron 3,78 AVAD (2.136/100.000) entre los profesionales de enfermería; 2,62 AVAD (2186/100.000) entre los técnicos de enfermería; y 1,15 AVAD (2.024/100.000) entre los enfermeros. El mayor AVAD ocurrió entre los técnicos de enfermería, del sexo femenino, de entre 50 y 59 años de edad, con el valor de 0,98 (3.161/100.000). Las dorsopatías generaron más AVAD (1,97 AVAD), especialmente lumbalgia y cervicalgia. El 54% de losdiagnósticos se refieren a Enfermedades Musculoesqueléticas Relacionadas con el Trabajo, con 2,62 AVAD (69% del total de AVAD). Conclusión: Existe una alta carga de enfermedad musculoesquelética entre los profesionales de enfermería de la institución en estudio.

Lessons from the invasion front: Integration of research and management of the lionfish invasion in Brazil.

After successful invasions in the Caribbean and Mediterranean, lionfish (Pterois spp.) have recently invaded another important biogeographical region -the Brazilian Province. In this article, we discuss this new invasion, focusing on a roadmap for urgent mitigation of the problem, as well as focused research and management strategies. The invasion in Brazil is already in the consolidation stage, with 352 individuals recorded so far (2020-2023) along 2766 km of coastline. This includes both juveniles and adults, including egg-bearing females, ranging in length from 9.1 to 38.5 cm. Until now, most of the records in the Brazilian coast occurred in the equatorial southwestern Atlantic (99%), mainly on the Amazon mesophotic reefs (15% of the records), northeastern coast of Brazil (45%), and the Fernando de Noronha Archipelago (41%; an UNESCO World Heritage Site with high endemism rate). These records cover a broad depth range (1-110 m depth), twelve protected areas, eight Brazilian states (Amapá, Pará, Maranhão, Piauí, Ceará, Rio Grande do Norte, Paraíba, and Pernambuco) and multiple habitats (i.e., mangrove estuaries, shallow-water and mesophotic reefs, seagrass beds, artificial reefs, and sandbanks), indicating a rapid and successful invasion process in Brazilian waters. In addition, the lack of local knowledge of rare and/or cryptic native species that are potentially vulnerable to lionfish predation raises concerns regarding the potential overlooked ecological impacts. Thus, we call for an urgent integrated approach with multiple stakeholders and solution-based ecological research, real-time inventories, update of environmental and fishery legislation, participatory monitoring supported by citizen science, and a national and unified plan aimed at decreasing the impact of lionfish invasion. The experience acquired by understanding the invasion process in the Caribbean and Mediterranean will help to establish and prioritize goals for Brazil.

Sensitive hydrazine detection and quantification with a fluorescent benzothiadiazole sensor: selective lipid droplets and in vivo imaging.

In this work, we describe the design, synthesis, characterization, photophysical evaluation, DFT calculations, and application of two novel fluorescent benzothiadiazole (BTD) sensors for hydrazine detection and quantification at the cellular and multicellular (in vivo) levels. The two probes were fully characterized, and their photophysical properties were evaluated. We tested the designed fluorogenic dye (named BTD-CHO) as a selective sensor for the rapid, sensitive, and selective detection of hydrazine. When treated with N2H4, the probe affords a new derivative named BTD-HZN, releasing water as the only byproduct. BTD-CHO exhibited a preference for lipid droplets (LDs) and accumulated inside these organelles. Hydrazine detection in LDs could be carried out by the in situ formation of BTD-HZN inside live cells. We efficiently visualized the lipids of a challenging cellular model, microalgae (Chlorella sorokiniana), using these sensors. In vivo experiments indicated rapid and efficient detection of the analyte using C. elegans and zebrafish (Danio rerio) as the multicellular models.

Clotrimazole is effective, safe and tolerable for the treatment of endometriosis and functions by downregulating inducible nitric oxide synthase and modulating oxidative stress biomarkers.

This study investigated the mechanism of action of clotrimazole (CTZ) and its adverse effects in a model of endometriosis. After autologous endometrial implantation, 18 rats were randomized into two treatment groups: 200 mg/kg CTZ or vehicle for 15 consecutive days. The lesion growth, implant size, glandular atrophy, nitric oxide (NO) serum levels, number of macrophage cells and inducible nitric oxide synthase (iNOS) immunoreactivity were significantly reduced in the CTZ group compared with the control. CTZ (p < 0.05) reduced the lipid peroxidation and protein carbonylation levels in the liver but did not alter the superoxide dismutase (SOD), glutathione (GSH) or glutathione S-transferase (GST) levels in the brain; however, the drug significantly reduced SOD activity and enhanced GST activity in the liver. These results suggest that CTZ interferes with reactive nitrogen species production by downregulating iNOS expression and thus enhances the antioxidant system to promote atrophy and regression of endometriotic lesions, without adverse effects on the brain and/or liver.

Chronic Mercury Exposure and GSTP1 Polymorphism in Munduruku Indigenous from Brazilian Amazon.

Genetic polymorphisms may be involved with mercury levels and signs and symptoms of intoxication from this exposure. Therefore, the aims were to describe the frequency of the GSTP1 polymorphism and to evaluate its effects on mercury levels and neurological signs in three Munduruku indigenous villages in the Brazilian Amazon. One-hundred-and-seven indigenous (over 12 years old) were included and genotyped (rs1695) using a TaqMan validated assay. Then, associations were evaluated by binary logistic regression, using odds ratios (OR) and 95% confidence intervals (CI). Mean age was 27.4 ± 13.9 years old, 52.3% were male, mean hair mercury concentration was 8.5 ± 4.3, exceeding the reference limit (≥6.0 µg/g), and were different among the three villages: 13.5 ± 4.6 µg/g in Sawré Aboy, 7.4 ± 2.3 µg/g in Poxo Muybu and 6.9 ± 3.5 µg/g in Sawré Muybu. The minor allele frequency of GSTP1 G was significantly different among the villages: 57% Sawré Muybu, 21% Poxo Muybu and 15% Sawré Aboy. Finally, after adjustment, GSTP1 GG and GA genotypes were associated with lower levels of Hg (OR = 0.13; CI95% = 0.03-0.49) and abnormal somatosensory signs (OR = 3.7; 95%IC = 1.5-9.3), respectively. In conclusion, monitoring this population is imperative to identify individuals at higher risk of developing signs of chronic mercury exposure based on the genetic profile.