Pyriproxyfen is an insecticide used worldwide that acts as a biomimetic of juvenile hormone. This study investigated metabolic and synaptic impairments triggered by pyriproxyfen using zebrafish ...acetylcholinesterase (zbAChE) and mitochondria as markers. A brain zbAChE assay was performed in vitro and in vivo covering a range of pyriproxyfen concentrations (0.001–10 μmol/L) to assess inhibition kinetics. Docking simulations were performed to characterize inhibitory interactions. Zebrafish male adults were acutely exposed to 0.001, 0.01 and 0.1 μg/mL pyriproxyfen for 16 h. Mitochondrial respiration of brain tissues was assessed. ROS generation was estimated using H2DCF-DA and MitoSOX. Calcium transport was monitored by Calcium Green™ 5 N. NO synthesis activity was estimated using DAF-FM-DA. Brain acetylcholinesterase showed an in vivo IC20 of 0.30 μmol/L pyriproxyfen, and an IC50 of 92.5 μmol/L. The inhibitory effect on zbAChE activity was competitive-like. Respiratory control of Complex I/II decreased significantly after insecticide exposure. The MitoSOX test showed that O2− generation had a pyriproxyfen dose-dependent effect. Brain tissue lost 50% of Ca2+ uptake capacity at 0.1 μg/mL pyriproxyfen. Ca2+ release showed a clear mitochondrial impairment at lower pyriproxyfen exposures. Thus, Ca2+ transport imbalance caused by pyriproxyfen may be a novel deleterious mechanism of action. Overall, the results showed that pyriproxyfen can compromise multiple and interconnected pathways: (1) zbAChE impairment and (2) the functioning of the electron transport chain, ROS generation and calcium homeostasis in zebrafish brain mitochondria. Considering the many similarities between zebrafish and human, more caution is needed when pyriproxyfen is used in both urban and agricultural pest control.
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•A multilevel approach to pyriproxyfen neurotoxicity was performed.•In vitro exposure of zbAChE to pyriproxyfen showed competitive-like inhibition.•Brain O2$− production was dependent on the dose of pyriproxyfen;•Calcium transport was changed after pyriproxyfen exposure.•Pyriproxyfen showed that NOS activity is not a major route to cellular impairment.
Growing evidences have associated Zika virus (ZIKV) infection with congenital malformations, including microcephaly. Nonetheless, signaling mechanisms that promote the disease outcome are far from ...being understood, affecting the development of suitable therapeutics. In this study, we applied shotgun mass spectrometry (MS)-based proteomics combined with cell biology approaches to characterize altered molecular pathways on human neuroprogenitor cells (NPC) and neurons derived from induced pluripotent stem cells infected by ZIKV-BR strain, obtained from the 2015 Brazilian outbreak. Furthermore, ZIKV-BR infected NPCs showed unique alteration of pathways involved in neurological diseases, cell death, survival and embryonic development compared to ZIKV-AF, showing a human adaptation of the Brazilian viral strain. Besides, infected neurons differentiated from NPC presented an impairment of neurogenesis and synaptogenesis processes. Taken together, these data explain that CNS developmental arrest observed in Congenital Zika Syndrome is beyond neuronal cell death.
Colorectal cancer is the leading cause of cancer death worldwide. The first and second lines of treatment for metastatic colorectal cancer (mCRC) include chemotherapy based on 5-fluorouracil. ...However, treatment following progression on the first and second line is still unclear. We searched PubMed, Scopus, Cochrane, and Web of Science databases for studies investigating the use of trifluridine-tipiracil with bevacizumab versus trifluridine-tipiracil alone for mCRC. We used RStudio version 4.2.3; and we considered p < 0.05 significant. Seven studies and 1,182 patients were included - 602 (51%) received trifluridine-tipiracil plus bevacizumab. Compared with control, the progression-free survival (PFS) (HR 0.52; 95% CI 0.42-0.63; p < 0.001) and overall survival (OS) (HR 0.61; 95% CI 0.52-0.70; p < 0.001) were significantly higher with bevacizumab. The objective response rate (ORR) (RR 3.14; 95% CI 1.51-6.51; p = 0.002) and disease control rate (DCR) (RR 1.66; 95% CI 1.28-2.16; p = 0.0001) favored the intervention. Regarding adverse events, the intervention had a higher rate of neutropenia (RR 1.38; 95% CI 1.19-1.59; p = 0.00001), whereas the monotherapy group had a higher risk of anemia (RR 0.60; 95% CI 0.44-0.82; p = 0.001). Our results support that the addition of bevacizumab is associated with a significant benefit in PFS, OS, ORR and DCR.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We consider planar massless scalar waves impinging upon a Kerr black hole, for general angles of incidence. We compute the absorption cross section via the partial wave approach, and present a ...gallery of results. In the low-frequency regime, we show that the cross section approaches the horizon area; in the high-frequency regime, we show that the cross section approaches the geodesic capture cross section. In the aligned case, we extend the complex angular momentum method to obtain a "sinc" approximation, which relates the regular high-frequency oscillations in the cross section to the properties of the polar null orbit. In the nonaligned case, we show, via a semianalytic approximation, that the reduction in symmetry generates a richer, less regular absorption cross section. We separate the absorption cross section into corotating and counterrotating contributions, showing that the absorption is larger for counterrotating waves, as expected.
A simple approach to exfoliate and functionalize MoS2 in a single‐step is described, which combines the dispersion of MoS2 in polybutadiene solution and ultrasonication processes. The great advantage ...of this process is that a colloidal stability of MoS2 in nonpolar solvent is achieved by chemically bonding polybutadiene on the perimeter edge sites of MoS2 sheets. In addition, elastomeric nanocomposite has been prepared with singular mechanical properties using functionalized MoS2 as nanofiller in a polybutadiene matrix with a subsequent vulcanization reaction.
2D MoS2 with few layers was achieved by a top‐down approach. In this exfoliation process, the MoS2 nanosheets were functionalized with polybutadiene chains (see figure) attached selectively onto the perimeter edge of the MoS2 through an organosulfur reaction. The process leads to 2D‐MoS2 with 4–6 layers of thickness with a colloidal stability in toluene that opens new possibilities for application of 2D‐MoS2 as a nanofiller.
Hydrogen-fueled internal combustion engines (H2ICEs) represent a promising technology for decarbonizing the transport sector. In pursuit of this goal, research is needed on lean hydrogen–air ...combustion under engine conditions aiming to mitigate NOx emissions. However, there is a limited amount of experimental data focusing on flame development at high pressure and temperature, especially in ultra-lean mixtures, which are recently considered to play an important role for future H2ICEs. This study investigates the behavior of very-lean to ultra-lean hydrogen–air flames (0.20 <ϕ< 0.55) in an optical spark-ignition engine, focusing on the early flame development phase. Fuel–air equivalence ratio and engine speed (900 <N< 1500 rpm) effects on hydrogen combustion are addressed with pressure-based heat release analysis and chemiluminescence flame imaging techniques. The findings revealed an intrinsic association between these two approaches. Hydrogen flames development measured before 2% of Mass Fraction Burned (MFB) strongly correlates with pressure-based quantities up to 50% MFB, underscoring the critical role of understanding the early flame phase for predicting total combustion duration and in-cylinder pressure traces. A model for hydrogen turbulent flames in the initial combustion stages is formulated based on the Zimont equation and the experimental data. An equation for 0D/1D combustion duration prediction up to 10% MFB is proposed, demonstrating its validity from the wrinkled flame to the well-stirred reactor premixed combustion regimes. Additionally, flame chemiluminescence images for each zone within the Peters–Borghi diagram are presented, offering valuable insights into the diverse characteristics of these flames.
The use of new psychoactive substances (NPS) has become a problem that affects many countries. Because new chemical structures appear frequently and reliable reference data do not always exist, ...identifying these compounds is an operational problem. Theoretical chemistry associated with statistical methods has scarcely been used to tackle such problems and can provide an unvaluable aid. In this study, we have employed quantum chemistry tools to simulate NMR spectra and to evaluate, as a paradigm, the main differences between amphetamines and cathinones. We have generated and examined the 1H and 13C chemical shifts of 21 homologous amphetamine and cathinone structures. In our computational approach, we used a test set and a proof set to generate the shifted factors on the basis of experimental observations. We employed three different DFTs (B3LYP, M062X, and PBE0) with a TZVP basis set and different solvents (water, ethanol, chloroform, and gas-phase). To evaluate the data, we applied statistical approaches, which allowed us to assess the methods and to distinguish between the studied NPS. This study provided reliable information that helps to explain how NMR evaluation differs in assessing these molecules and promoting their discrimination in forensic analysis.
•We study 42 amphetamine-type stimulants by theoretical simulation nuclear magnetic resonance spectra.•We use three DFT methods and different continuum models for solvents to calculate the influence of the medium.•We apply chemometric methods to predict the differences in NMR chemical shifts between amphetamines and cathinones.•The results provide information to understand how NMR allows chemical differentiation between amphetamines and cathinones.
Objective
To investigate the perception of hunger and satiety and its association with nutrient intake in women who regain weight in the postoperative period after bariatric surgery.
Methods
...Cross-sectional study of adult women divided into three groups: weight regain (
n
= 20), stable weight (
n
= 20) (both at least 24 months after Roux-en-Y gastric bypass surgery), and non-operated obesity (
n
= 20). A visual analogue scale measured hunger/satiety perception while fasting, immediately after finishing a test meal, and 180 min after finishing the test meal. The incremental area above or under the curve was calculated. Food intake was analyzed by 3 days of food recall and adjusted for intraindividual variation. To make between-group comparisons, Mann-Whitney, ANOVA, Kruskal-Wallis, and independent-samples
T
tests and Pearson’s correlation were used.
Results
There were no between-group differences in incremental areas of hunger/satiety, but protein intake was significantly lower among patients who regained weight compared with those who had stable body weight (0.99 ± 0.23 g/kg body weight vs. 1.17 ± 0.21 g/kg body weight,
p
= 0.047). In the group that regained weight, satiety was correlated positively with usual dietary protein density (
r
= 0.541;
p
= 0.017) and negatively with usual carbohydrate intake (
r
= − 0.663;
p
= 0.002).
Conclusion
Women who regained weight presented similar perceptions of hunger/satiety to those of patients without weight regain and with non-operated obesity. In patients who regained weight postoperatively, satiety perception was correlated positively with usual dietary protein density and inversely with usual carbohydrate intake.
The brown alga Sargassum furcatum and three families of amphipods (Ampithoidae, Caprellidae and Hyalidae) associated to that algae were evaluated as bioindicators of petroleum hydrocarbons input into ...the marine environment of São Sebastião Channel, in southeastern region of Brazil. The n-alkanes pattern were mainly associated with the natural composition of the macroalgae and amphipods, although some indicatives of petroleum hydrocarbons such as unresolved complex mixture and the no predominance of odd over even n-alkanes have been observed in some samples. Total PAHs ranged from 33.4 to 2010 ng g−1 dry weight with the predominance of low molecular weight PAHs, mostly of naphthalene and alkyl-naphthalenes, which also suggested petroleum input. Even in low concentration, Sargassum furcatum and amphipods species studied seems to be good indicators of the introduction of petroleum hydrocarbons.
•Sargassum and amphipods seem to be good indicators of hydrocarbons contamination•The PAHs composition found in both organisms were indicative of petroleum inputs•Different families of amphipods bioaccumulate distinct amounts of hydrocarbons
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