Abietane Diterpenes from Medusantha martiusii and Their Anti-Neuroinflammatory Activity.

Seven new abietane diterpenoids, comprising medusanthol A-G (1-3, 5, 7-9) and two previously identified analogs (4 and 6), were isolated from the hexane extract of the aerial parts of Medusantha martiusii. The structures of the compounds were elucidated by HRESIMS, 1D/2D NMR spectroscopic data, IR spectroscopy, NMR calculations with DP4+ probability analysis, and ECD calculations. The anti-neuroinflammatory potential of compounds 1-7 was evaluated by determining their ability to inhibit the production of nitric oxide (NO) and the proinflammatory cytokine TNF-α in BV2 microglia stimulated with LPS and IFN-γ. Compounds 1-4 and 7 exhibited decreased NO levels at a concentration of 12.5 µM. Compound 1 demonstrated strong activity with an IC50 of 3.12 µM, and compound 2 had an IC50 of 15.53 µM; both compounds effectively reduced NO levels compared to the positive control quercetin (IC50 11.8 µM). Additionally, both compounds significantly decreased TNF-α levels, indicating their potential as promising anti-neuroinflammatory agents.

Highly Enantioselective Lewis Acid Catalyzed Conjugate Addition of Imidazo[1,2-a]pyridines to α,ß-Unsaturated 2-Acylimidazoles under Mild Conditions.

A highly enantioselective protocol for the conjugate addition of 2-arylimidazo[1,2-a]pyridines and other imidazo derivatives to α,ß-unsaturated 2-acylimidazoles is described. The method uses a previously reported chiral-at-metal rhodium catalyst and provides the corresponding adducts in yields of 25-98% with enantioselectivities up to er > 99:1. Additionally, the transformation proceeds under mild conditions using ethanol as the solvent at room temperature.

Book bans in political context: Evidence from US schools.

In the 2021-2022 school year, more books were banned in US school districts than in any previous year. Book banning and other forms of information censorship have serious implications for democratic processes, and censorship has become a central theme of partisan political rhetoric in the United States. However, there is little empirical work on the exact content, predictors of, and repercussions of this rise in book bans. Using a comprehensive dataset of 2,532 bans that occurred during the 2021-2022 school year from PEN America, combined with county-level administrative data, multiple book-level digital trace datasets, restricted-use book sales data, and a new crowd-sourced dataset of author demographic information, we find that (i) banned books are disproportionately written by people of color and feature characters of color, both fictional and historical, in children's books; (ii) right-leaning counties that have become less conservative over time are more likely to ban books than neighboring counties; and (iii) national and state levels of interest in books are largely unaffected after they are banned. Together, these results suggest that rather than serving primarily as a censorship tactic, book banning in this recent US context, targeted at low-interest children's books featuring diverse characters, is more similar to symbolic political action to galvanize shrinking voting blocs.

Characteristics associated with responsiveness to isometric handgrip training in medicated hypertensive patients: secondary data analysis.

OBJECTIVE: Isometric handgrip training (IHT) has been shown to reduce blood pressure (BP) in hypertensive patients. However, factors that predict responsiveness to IHT are largely unknown. The aim of this study was to investigate the patient characteristics associated with the antihypertensive response to IHT using a recommended statistical approach for evaluating interindividual responses. METHODS: Data from four randomized controlled trials were combined, totaling 81 patients undergoing IHT (48.8% women; 60 ±â€Š11 years) and 90 control patients (45.6% women; 62 ±â€Š12 years). IHT consisted of 4 × 2 min isometric contractions at 30% of maximal voluntary contraction, performed three times/week for 8-12 weeks. BP was measured at baseline and following IHT and control interventions. The interindividual variation was assessed by the standard deviation of the individual responses (SD ir ), and linear regression analyses were conducted to explore response predictors. RESULTS: IHT significantly decreased both SBP (-5.4; 95% confidence interval (CI) -9.5 to -1.3 mmHg) and DBP (-2.8; 95% CI -5.1 to -0.6 mmHg). The interindividual variation of BP change was moderate for systolic (SD ir  = 5.2 mmHg, 0.30 standardized units) and low for diastolic (SD ir  = 1.7 mmHg, 0.15 standardized units). Sex, age, and BMI were not associated with the antihypertensive effect of IHT. However, a higher baseline SBP ( b  = -0.467, P  < 0.001) and absence of dihydropyridine calcium channel blockers use ( b  = 0.340, P  = 0.001) were associated with greater BP reductions. CONCLUSION: IHT reduced BP in medicated hypertensive patients regardless of age, sex, and BMI. Patients with a higher baseline SBP and those not prescribed dihydropyridine calcium channel blockers were more responsive to IHT.

Warming and shifts in litter quality drive multiple responses in freshwater detritivore communities.

Aquatic detritivores are highly sensitive to changes in temperature and leaf litter quality caused by increases in atmospheric CO2. While impacts on detritivores are evident at the organismal and population level, the mechanisms shaping ecological communities remain unclear. Here, we conducted field and laboratory experiments to examine the interactive effects of changes in leaf litter quality, due to increasing atmospheric CO2, and warming, on detritivore survival (at both organismal and community levels) and detritus consumption rates. Detritivore community consisted of the collector-gathering Polypedilum (Chironomidae), the scraper and facultative filtering-collector Atalophlebiinae (Leptophlebiidae), and Calamoceratidae (Trichoptera), a typical shredder. Our findings reveal intricate responses across taxonomic levels. At the organismal level, poor-quality leaf litter decreased survivorship of Polypedilum and Atalophlebiinae. We observed taxon-specific responses to warming, with varying effects on growth and consumption rates. Notably, species interactions (competition, facilitation) might have mediated detritivore responses to climate stressors, influencing community dynamics. While poor-quality leaf litter and warming independently affected detritivore larvae abundance of Atalophebiinae and Calamoceratidae, their combined effects altered detritus consumption and emergence of adults of Atalophlebiinae. Furthermore, warming influenced species abundances differently, likely exacerbating intraspecific competition in some taxa while accelerating development in others. Our study underscores the importance of considering complex ecological interactions in predicting the impact of climate change on freshwater ecosystem functioning. Understanding these emergent properties contributes to a better understanding of how detritivore communities may respond to future environmental conditions, providing valuable insights for ecosystem management and conservation efforts.

Fermenting Acerola (Malpighia emarginata D.C.) and Guava (Psidium guayaba L.) Fruit Processing Co-Products with Probiotic Lactobacilli to Produce Novel Potentially Synbiotic Circular Ingredients.

This study evaluated the effects of acerola and guava fruit processing co-products fermented with probiotic Lactobacillus acidophilus LA-05 and Lacticaseibacillus paracasei L-10 on the abundance of different intestinal bacterial groups and microbial metabolic activity during 48 h of in vitro fecal fermentation. Digested fermented fruit co-products increased the relative abundance of beneficial bacterial groups while overall decreasing or maintaining the relative abundance of non-beneficial bacterial groups, suggesting selective stimulatory effects on beneficial bacterial intestinal populations. The fermented co-products stimulated microbial metabolic activity due to decreased pH, sugar consumption, short-chain fatty acid production, phenolic compound and metabolic profile alteration, and high antioxidant capacity during fecal fermentation. Acerola and guava co-products have high nutritional value and bioactive compounds whose fermentation with probiotics improves their potential functionalities. The results show that fermented fruit co-products could induce beneficial changes in the relative abundance of several bacterial groups as well as in the metabolic activity of the human intestinal microbiota. These results highlight their potential as novel and circular candidates for use as synbiotic ingredients.

Seroprevalence of Treponema pallidum infection in Brazilian indigenous people: a cross-sectional study.

Indigenous communities in Brazil have a complex epidemiological profile, which increases their chances of contracting sexually transmitted diseases. However, limited data is available on Treponema pallidum infections in this population. We investigated the seroprevalence and risk factors associated with T. pallidum infection in an indigenous population of Dourados, Mato Grosso do Sul. Blood samples were collected from September 2017 to March 2020, and the participants were interviewed to obtain comprehensive data on demography and sexual behavior. Serological tests were performed to detect T. pallidum infection. Besides conducting descriptive analysis, we performed Chi-squared tests and determined the bivariate odds ratio. The data were also analyzed using logistic regression. Among the 2190 invited individuals, 1927 (88%) were included in this study. The seroprevalence of T. pallidum infection was 2.91%. The results of a multivariate analysis showed that individuals who were 30-39 years old, with up to 4 years of school education, living in households without piped water, with a history of genital lesions, multiple sexual partners, and having a history of STIs had the highest seroprevalence of T. pallidum. This study showed that behavioral, social, and economic factors play an important role in the transmission of T. pallidum within the indigenous population. Thus, targeted intervention, including imparting education in the native language, mass testing initiatives, and implementing public policies to improve socioeconomic indicators, is needed to reduce the cases of syphilis in this community.

Teaching and learning in biophotonics: Crossing the bridge between educators and students.

As a rapidly growing field, biophotonics demonstrates an increasingly higher demand for interdisciplinary professionals and requires the implementation of a structured approach to educational and outreach activities focused on appropriate curriculum, and teaching and learning for audiences with diverse technical backgrounds and learning styles. Our study shows the main findings upon applying this approach to biophotonics workshops delivered 2 consecutive years while updating and improving learning outcomes, teaching strategies, workshop content based on student and teacher feedback. We provided resources for a variety of lecture-based, experimental, computer simulation activities. Quality of subject matter, teaching, and overall learning was rated as "Very good" or "Good" by 88%, 76%, and 82% of students in average, respectively. Application of our teaching strategies and materials during short- and long-term workshops/courses could potentially increase the interest in pursuing careers in the biophotonics field and related areas, leading to standardized approaches in designing education and outreach events across centers.

Frequency of MRI Low Signal Intensity in the Buccal Fat of Fetuses and Speculation as to What It May Reflect.

PURPOSE: We aimed to characterize the fetal buccal fat pad (BFP) on magnetic resonance imaging (MRI) to determine the frequency and types of sequences on which the BFP demonstrates low signal intensity and determine any possible correlation with timing of the MRI during fetal development. MATERIALS AND METHODS: A retrospective review of all fetal MR studies was performed, and a pediatric radiologist blinded to the referring and final fetal diagnosis as well as outcome evaluated the included cases. A positive buccal fat pad sign (BFS) was recorded as present if a round, symmetric, and bilateral area was seen in the submalar region of the face with the following signal characteristics: T1 hyperintensity, low signal on echo planar imaging (EPI), low signal on true fast imaging with steady-state free precession (TRUFI), and with restriction on diffusion-weighted imaging (DWI). RESULTS: A total of one hundred sixty-seven (167) fetal MRI studies: one hundred fourteen (114) body (68%) and fifty-three (53) neuro (32%) scans were reviewed during the study period. The BFS was most commonly seen on EPI (63%) and TRUFI (49%) sequences. Substantial agreement between TRUFI and EPI (κ = 0.68; p < 0.01); moderate agreement between TRUFI and T1 (κ = 0.53; p < 0.01) as well as T1 and EPI (κ = 0.53; p < 0.01), and fair agreement between EPI and Diffusion (κ = 0.28; p < 0.01) was observed. The median gestational age (GA) was 24 weeks (IQR 22-30 weeks). The fetuses with a positive BFS were significantly older (mean GA of 27 weeks or higher) than those without, for each sequence. CONCLUSIONS: The focal low signal in the fetal buccal fat pad, termed the fetal BFS, is a commonly encountered normal finding in the majority of fetal MRI scans on TRUFI and EPI sequences. This finding may be related to the presence and development of brown adipose tissue in the buccal fat pad resulting in T2* effects, but further studies are needed in order to confirm this. Further work can incorporate any of the sensitive sequences demonstrating low signal in brown adipose tissue to map its distribution and development in the fetus and beyond.

Pleonotoquinones, Cytotoxic Oxepinenaphthoquinones from Pleonotoma jasminifolia.

Two unusual naphthoquinones, named here as pleonotoquinones A (1) and B (2), were isolated along with two known anthraquinones (3 and 4) via chromatographic separations of an ethyl acetate extract of the roots of Pleonotoma jasminifolia. Compounds 1 and 2 are the first examples of quinones bearing a 2-methyloxepine moiety. The compounds were isolated with the aid of mass spectrometry and molecular networking, and their structures were resolved using 1D and 2D NMR and HRESIMS data. The isolated compounds were evaluated for their antiproliferative activity against human cancer cell lines, and compounds 1 and 2 displayed cytotoxicity against human colon cancer HCT116 cells (IC50 = 2.6 µM for compound 1 and IC50 = 4.3 µM for compound 2) and human liver cancer HepG2 cells (IC50 = 1.9 µM for compound 1 and IC50 = 6.4 µM for compound 2).

Thermally-treated asbestos-cement wastes as supplementary precursor for geopolymeric binders: CO2 emission and properties.

This article explores the impact of thermally treated asbestos-cement waste (ACWT) on metakaolin-based geopolymers, using liquid sodium silicate (LSS) and liquid potassium silicate (LKS) as alkali activators. Through statistical mixture design, various formulations were tested for rheological parameters, mineralogical composition, efflorescence mass, electrical conductivity, compressive strength, and CO2 emissions. Formulations with sodium silicate exhibited higher yield stress compared to those with potassium silicate, while flash setting occurred in LKS-activated mixtures with high ACWT content. Alkali activator content significantly affected mechanical strength and leachate electrical conductivity. CO2 emissions were higher for LKS-activated formulations but lower for those with more ACWT. Finally, by incorporating ACWT, it was possible to optimize the formulations, resulting in high compressive strength, reduced free ions, and reduced negative environmental impact.

Acute effects of ipsilateral semitendinosus and gracilis autograft anterior cruciate ligament reconstruction on lower limb muscle activation

There is little information regarding the acute repercussions of anterior cruciate ligament (ACL) reconstruction on muscle activation, especially on the proximal hip muscles. Thus, this study analyzed the acute effects of ACL reconstruction with doubled semitendinosus/gracilis (ST/G) autografts on lower limb muscle activation. Fourteen male recreational athletes that presented a primary unilateral ACL rupture and underwent the ACL reconstruction with an ST/G graft. Surface electromyographic (sEMG) signal were recorded from each participant during the maximal voluntary isometric contraction (MVIC) of the gluteus maximus and gluteus medius, vastus lateralis and vastus medialis, semitendinosus, biceps femoris, and medial gastrocnemius muscles and also during bipodal mini-squatting with open and closed eyes, before surgery and 15 days postoperatively. (sEMG) signal were normalized to isometric peak electromyography. The postoperative assessment showed reduced muscle activation in the gluteus maximus (p = 0.013, d:0.48) in non-operated limb and also in the muscle gluteus medius (p = 0.013, d:0.79), vastus medialis (p = 0.035, d:0.63) semitendinosus (p = 0.001, d:2.46), biceps femoris (p<0.001, d:1.5), and medial gastrocnemius (p = 0.001, d:1.45) during MVIC in the operated limb. The postoperative assessment also revealed alterations in the sEMG activity of the hip and local thigh muscles in the operated and non-operated limbs during mini-squatting with opened eyes and closed eyes (p<0.05). ACL reconstruction surgery with a doubled ST/G autograft may promote immediate changes in lower limb muscle activation of the operated and non-operated limb. (AU)

Paradoxical Activation of Oncogenic Signaling as a Cancer Treatment Strategy.

Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress response programs that counteract the inherent toxicity of such aberrant signaling. Although inhibition of oncogenic signaling pathways has been explored extensively, there is increasing evidence that overactivation of the same pathways can also disrupt cancer homeostasis and cause lethality. We show here that inhibition of protein phosphatase 2A (PP2A) hyperactivates multiple oncogenic pathways and engages stress responses in colon cancer cells. Genetic and compound screens identify combined inhibition of PP2A and WEE1 as synergistic in multiple cancer models by collapsing DNA replication and triggering premature mitosis followed by cell death. This combination also suppressed the growth of patient-derived tumors in vivo. Remarkably, acquired resistance to this drug combination suppressed the ability of colon cancer cells to form tumors in vivo. Our data suggest that paradoxical activation of oncogenic signaling can result in tumor-suppressive resistance. Significance: A therapy consisting of deliberate hyperactivation of oncogenic signaling combined with perturbation of the stress responses that result from this is very effective in animal models of colon cancer. Resistance to this therapy is associated with loss of oncogenic signaling and reduced oncogenic capacity, indicative of tumor-suppressive drug resistance.

Insular and prelimbic cortices control behavioral accuracy and precision in a temporal decision-making task in rats.

The anterior insular cortex (AIC) comprises a region of sensory integration. It appears to detect salient events in order to guide goal-directed behavior, code tracking errors, and estimate the passage of time. Temporal processing in the AIC may be instantiated by the integration of representations of interoception. Projections between the AIC and the medial prefrontal cortex (mPFC) - found both in rats and humans - also suggest a possible role for these structures in the integration of autonomic responses during ongoing behavior. Few studies, however, have investigated the role of AIC and mPFC in decision-making and time estimation tasks. Moreover, their findings are not consistent, so the relationship between temporal decision-making and those areas remains unclear. The present study employed bilateral inactivations to explore the role of AIC and prelimbic cortex (PL) in rats during a temporal decision-making task. In this task, two levers are available simultaneously (but only one is active), one predicting reinforcement after a short, and the other after a long-fixed interval. Optimal performance requires a switch from the short to the long lever after the short-fixed interval elapsed and no reinforcement was delivered. Switch behavior from the short to the long lever was dependent on AIC and PL. During AIC inactivation, switch latencies became more variable, while during PL inactivation switch latencies became both more variable and less accurate. These findings point to a dissociation between AIC and PL in temporal decision-making, suggesting that the AIC is important for temporal precision, and PL is important for both temporal accuracy and precision.

A Cytotoxicity Assay as an Alternative to the Murine Model for the Potency Testing of Bothrops jararaca Venom and Antivenom: An Intralaboratory Pre-validation Study.

Antivenom therapy is the only specific treatment for snakebite envenomation, and antivenom potency determination is key in the efficacy assurance quality control process. Nowadays, this process relies on the in vivo murine model - thus, the development of alternative in vitro methods is imperative. In the current study, the principle of the proposed method is the ability of Bothrops venom to induce cytotoxic effects in Vero cells, and the capacity to evaluate the inhibition of this cytotoxicity by the respective antivenom. After exposure to the venom/antivenom, the relative proportions of adherent (viable) cells were evaluated by direct staining with Coomassie Blue. The optical density (OD) of the lysed cell eluate was directly proportional to the number of adherent cells. This cytotoxicity-based alternative method could represent a potential candidate for validation as a replacement for the current in vivo test. The in vitro-determined cytotoxicity of the Brazilian Bothrops reference venom (expressed as the 50% effective concentration; EC50) was 3.61 µg/ml; the in vitro-determined 50% inhibitory concentration (IC50) of the Brazilian Bothrops reference antivenom was 0.133 µl/ml. From these two values, it was possible to calculate the potency of the reference antivenom. The results from the assays exhibited a good linear response, indicating that the method could be a potential candidate replacement method for use in antivenom quality control prior to lot release, subject to further validation.

Towards harmonized standards for freshwater biodiversity monitoring and biological assessment using benthic macroinvertebrates.

Monitoring programs at sub-national and national scales lack coordination, harmonization, and systematic review and analysis at continental and global scales, and thus fail to adequately assess and evaluate drivers of biodiversity and ecosystem degradation and loss at large spatial scales. Here we review the state of the art, gaps and challenges in the freshwater assessment programs for both the biological condition (bioassessment) and biodiversity monitoring of freshwater ecosystems using the benthic macroinvertebrate community. To assess the existence of nationally- and regionally- (sub-nationally-) accepted freshwater benthic macroinvertebrate protocols that are put in practice/used in each country, we conducted a survey from November 2022 to May 2023. Responses from 110 respondents based in 67 countries were received. Although the responses varied in their consistency, the responses clearly demonstrated a lack of biodiversity monitoring being done at both national and sub-national levels for lakes, rivers and artificial waterbodies. Programs for bioassessment were more widespread, and in some cases even harmonized among several countries. We identified 20 gaps and challenges, which we classed into five major categories, these being (a) field sampling, (b) sample processing and identification, (c) metrics and indices, (d) assessment, and (e) other gaps and challenges. Above all, we identify the lack of harmonization as one of the most important gaps, hindering efficient collaboration and communication. We identify the IUCN SSC Global Freshwater Macroinvertebrate Sampling Protocols Task Force (GLOSAM) as a means to address the lack of globally-harmonized biodiversity monitoring and biological assessment protocols.

Molecular Docking Analysis at the Human α7-nAChR and Proliferative and Evoked-Calcium Changes in SH-SY5Y Cells by Imidacloprid and Acetamiprid Insecticides.

Acetamiprid (ACE) and Imidacloprid (IMI) are widely-used neonicotinoid insecticides (NNIs) with functional activity at human acetylcholine nicotinic receptors and, therefore, with putative toxic effects. The objective of this study was the evaluation of the interactions between NNIs and α7-nAChR, as this receptor keeps intracellular Ca2+ ([Ca2+]i) to an optimum for an adequate neuronal functioning. Possible interactions between NNIs and the cryo-EM structure of the human α-7 nAChR were identified by molecular docking. Additionally, NNI effects were analyzed in neuroblastoma SH-SY5Y cells, as they naturally express α-7 nAChRs. Functional studies included proliferative/cytotoxic effects (MTT test) in undifferentiated SH-SY-5Y cells and indirect measurements of [Ca2+]i transients in retinoic acid-differentiated SH-SY-5Y cells loaded with Fluo-4 AM. Docking analysis showed that the binding of IMI and ACE occurred at the same aromatic cage that the specific α-7 nAChR agonist EVP-6124. IMI showed a better docking strength than ACE. According to the MTT assays, low doses (10-50 µM) of IMI better than ACE stimulated neuroblastoma cell proliferation. At higher doses (250-500 µM), IMI also prevailed over ACE and dose-dependently triggered more abrupt fluorescence changes due to [Ca2+]i mobilization in differentiated SH-SY5Y neurons. Indeed, only IMI blunted nicotine-evoked intracellular fluorescence stimulation (i.e., nicotine cross-desensitization). Summarizing, IMI demonstrated a superior docking strength and more robust cellular responses compared to ACE, which were likely associated with a stronger activity at α-7nAChRs. Through the interaction with α-7nAChRs, IMI would demonstrate its high neurotoxic potential for humans. More research is needed for investigating the proliferative effects of IMI in neuroblastoma cells.

KIO3-catalyzed selective oxidation of thiols to disulfides in water under ambient conditions.

Herein, we report a KIO3-catalyzed oxidative coupling of thiols to their corresponding disulfides in water, in a short time and at ambient temperature. The reaction has a broad scope and exhibits good functional group tolerance, resulting in the desired products in excellent yields. This approach allows the reuse of the reaction system in multiple cycles and scale-up. Furthermore, the current protocol demonstrates compatibility for in situ generation of disulfides and post application in C(sp2)-H bond sulfenylation.