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Variously substituted methylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one) derivatives were synthesized in 83–96% yield by the reaction of substituted benzaldehyde with 5, 5-dimethyl-1, 3-cyclohexanedione in the presence of CuO nanoparticles (NPs). Tandem grinding involves Knoevenagel condensation followed by the Michael addition in sequence for the formation of 2, 2’-arylmethylenebis (3-hydroxy-5, 5-dimethyl-2-cyclohexene-1-one) derivatives. Copper oxide NPs were synthesized by sol-gel method. The characterization of CuO NPs was done on the basis of PXRD, FTIR, SEM and TEM techniques. The synthesized derivatives were characterized on the basis of spectral analyses and corresponding melting points reported in the literature.

The quadricuspid aortic valve is a rare congenital anomaly, usually associated with aortic regurgitation requiring surgical intervention. It may be associated with other congenital anomalies such as coronary anomalies, patent ductus arteriosus, ventricular septal defect, pulmonary stenosis, and subaortic stenosis. The diagnosis is generally established by either transthoracic or transesophageal echocardiography. Herein, we report a case of a 52-year-old woman who was diagnosed to have quadricuspid aortic valve by intraoperative transesophageal echocardiography.

Gram-negative bacteria show more drug-resistant than Gram-positive bacteria due to unique structural attribute and cause significant morbidity and mortality across the globe. Such characteristic structure is an organelle lipopolysaccharide (LPS) on the outer membrane (OM) of cell wall essential for growth and survival of bacteria. LPS is a major cell wall component formed by dedicated transenvelope multiprotein complexes that shield the underlying peptidoglycan layer and play a key role in host–pathogen interactions with the innate immune system. Moreover, which constitutes the surface-exposed molecules with lipid portion in the outer leaflet of the OM that able to show antibiotic resistance and also responsible for the variety of biological effects associated with bacterial sepsis. LPS synthesis and structure are a conserved subject in infections during bacterial adaptive changes. Such changes ensue immune evasion, prolonged inflammation and augmented antibiotic resistance by working as molecular decoys which titrate the antimicrobials away from its intracellular antibiotic target. Herein, this review summarises the key features of LPS structure, function and biosynthesis. Moreover, it highlights the broad-spectrum conserved targets in the Raetz pathway without an alternative way for LPS biosynthesis vital for the development of novel therapeutic interventions against Gram-negative pathogens.

α-Synuclein (aSyn) aggregation is an attractive target for therapeutic development for a range of neurodegenerative conditions, collectively termed synucleinopathies. Here, we probe the mechanism of action of a peptide 4554W, (KDGIVNGVKA), previously identified through intracellular library screening, to prevent aSyn aggregation and associated toxicity. We utilize NMR to probe association and identify that 4554W associates with a “partially aggregated” form of aSyn, with enhanced association occurring over time. We also report the ability of 4554W to undergo modification through deamidation of the central asparagine residue, occurring on the same timescale as aSyn aggregation in vitro, with peptide modification enhancing its association with aSyn. Additionally, we report that 4554W can act to reduce fibril formation of five Parkinson’s disease associated aSyn mutants. Inhibitory peptide binding to partially aggregated forms of aSyn, as identified here, is particularly attractive from a therapeutic perspective, as it would eliminate the need to administer the therapy at pre-aggregation stages, which are difficult to diagnose. Taken together the data suggest that 4554W could be a suitable candidate for future therapeutic development against wild-type, and most mutant aSyn aggregation.

Matrix metalloproteinases (MMPs) are secretary or membrane type proteolytic enzymes that act on extracellular matrix protein components such as collagens, gelatins, elastins, laminins, fibronectins, and integrins. MMPs are synthesized as zymogens and are activated to functional forms on autoproteolysis or by other proteases. Naturally, the activity of MMPs was regulated by specific tissue inhibitors of metalloproteinases and transcriptionally regulated by miRNAs. MMPs have an important role in tissue remodeling by regulating cell death, morphogenesis, and wound healing activity. Overexpression of MMPs leads to various pathologies predominantly cancer, cardiovascular, and neurological diseases. Impact of MMPs on breast cancer progressions such as proliferation, angiogenesis, invasion, and metastasis are focused in this review.

The overuse of pesticides in agriculture has led to widespread pollution of soils and water resources, becoming a problem of great concern. Nowadays, special attention is given to neonicotinoids, particularly acetamiprid, the only neonicotinoid insecticide allowed for outdoor use in the European Union. Once acetamiprid reaches the soil, adsorption/desorption is the main process determining its bioavailability and environmental fate. Therefore, in this work, the adsorption/desorption behaviour of acetamiprid in 60 agricultural soils was studied. The results indicate that acetamiprid has a low affinity for soil constituents, with values ranging from 0.2 to 4.28 L kg -1 for K d(ads). At the same time, acetamiprid shows high desorption levels (up to 96.3%), indicating that it is poorly retained in soils, thus presenting high bioavailability and a potential risk for transport to other environmental compartments. Regarding the influence of soil properties on the adsorption/desorption process, soils with a high content of organic matter, clay, and exchangeable basic cations showed higher retention of acetamiprid, with greater adsorption and lower desorption. Finally, robust and universal models were successfully developed to predict the adsorption and desorption behaviour of acetamiprid in soil., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

The human antibiotics cefuroxime (CXM) and azithromycin (AZI) are among the most commonly prescribed. A significant portion of both are excreted and has been detected in sewage treatment plant effluents. The increasing use of such effluents in crops for irrigation and as fertilisers poses a threat to soil microbiota because of the presence of antibiotics. The lack of studies on CXM and AZI in soils hinders our understanding of their potential toxic effects on soil bacterial communities and ecosystem services. This study significantly contributes to the literature by quantifying the toxicity of CXM and AZI at varying concentrations in 12 different crop soils and tracking their evolution over time. The study also examined whether antibiotic pressure led to the development of more tolerant bacterial communities. The results of this study are the values of the logarithm of the antibiotic concentration at which 50 % of bacterial growth is inhibited (Log IC 50 ) and indicate that both antibiotics are toxic to soil bacteria. The direct toxicity of CXM (1 day after contamination) was higher (Log IC 50 : 0.9 = 7.9 mg kg -1 ) than that of AZI (Log IC 50 : 3.4 = 2362 mg kg -1 ). However, bacterial growth was less affected by CXM over time, whereas AZI remained toxic in some soils until day 42 (Log IC 50 : 3.2 = 1533 mg kg -1 and 3.4 = 2291 mg kg -1 , respectively). The overall results indicate that selective pressure exerted by antibiotics generates antibiotic tolerance in soils, even at the lowest antibiotic concentration studied (7.8 mg kg -1 ). The general trend was to increase tolerance to higher antibiotic concentrations up to the highest concentration studied (2000 mg kg -1 ). However, the degree of tolerance developed was highly dependent on soil type. More studies should be conducted to quantitatively assess the toxic and tolerance-developing effects of antibiotics in soils. Such information will be valuable for identifying which antibiotics pose a threat to the soil microbiota and consequently to human health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Fire regimes in mountain landscapes of southern Europe have been shifting from their baselines due to rural abandonment and fire exclusion policies. Understanding the effects of fire on biodiversity is paramount to implement adequate management. Herein, we evaluated the relative role of burn severity and heterogeneity on bird abundance in an abandoned mountain range located in the biogeographic transition between the Eurosiberian and Mediterranean region (the Natural Park 'Baixa Limia-Serra do Xurés'). We surveyed the bird community in 206 census plots distributed across the Natural Park, both inside and outside areas affected by wildfires over the last 11 years (from 2010 to 2020). We used satellite images of Sentinel 2 and Landsat missions to quantify the burn severity and heterogeneity of each fire within each surveyed plot. We also accounted for the past land use (forestry or agropastoral use) by using a land cover information for year 2010 derived from satellite image classification. We recorded 1735 contacts from 28 bird species. Our models, fitted by using GLMs with Poisson error distribution (pseudo-R 2 -average of 0.22 ± 0.13), showed that up to 71% of the modeled species were linearly correlated with at least one attribute of the fire regime. The spatiotemporal variation in burnt area and severity were relevant factors for explaining the local abundance of our target species (39% of the species; Akaike weights >0.75). We also found a quadratic effect of at least one fire regime attribute on bird abundance for 60% of the modeled species. The past land use, and its legacy after 10 years, was critical to understand the role of fire (Akaike weights >0.75). Our findings confirm the importance of incorporating remotely sensed indicators of burn severity into the toolkit of decision makers to accurately anticipate the response of birds to fire management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Reducing the toxicity caused by antibiotics on bacterial communities in the soil is one of the great challenges of this century. For this, the effectiveness of amending the soil with different bioadsorbents such as crushed mussel shell (CMS), pine bark (PB) and biomass ash (BA), as well as combinations of them (CMS + PB and PB + BA) was studied at different doses (0 g kg -1 to 48 g kg -1 ). Soil samples were spiked, separately, with increasing doses (0-2000 mg kg -1 ) of cefuroxime (CMX), amoxicillin (AMX), clarithromycin (CLA), azithromycin (AZI), ciprofloxacin (CIP) and trimethoprim (TMP). Their toxicity on bacterial growth was estimated using the tritium-labeled leucine ( 3 H) incorporation method. Toxicity was observed to behave differently depending on the antibiotic family and bioadsorbent, although in different magnitude and at different doses. The toxicity of β-lactams (AMX and CXM) was reduced by up to 54% when the highest doses of bio-adsorbents were added due to the increase in pH (CMS and BA) and carbon (PB) contribution. Macrolides (CLA and AZI) showed slight toxicity in un-amended soil samples, which increased by up to 65% with the addition of the bio-adsorbents. The toxicity of CIP (a fluoroquinolone) increased with the dose of the bio-adsorbents, reaching up to 20% compared with the control. Finally, the toxicity of TMP (a diaminopyrimidine) slightly increased with the dose of bio-adsorbents. The by-products that increase soil pH are those that showed the highest increases of CLA, AZI, CIP and TMP toxicities. These results could help to prevent/reduce environmental pollution caused by different kinds of antibiotics, selecting the most appropriated bio-adsorbents and doses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The presence of emerging pollutants, and specifically antibiotics, in agricultural soils has increased notably in recent decades, causing growing concern as regards potential environmental and health issues. With this in mind, the current study focuses on evaluating the toxicity exerted by three antibiotics (amoxicillin, trimethoprim, and ciprofloxacin) on the growth of soil bacterial communities, when these pollutants are present at different doses, and considered in the short, medium, and long terms (1, 8 and 42 days of incubation). Specifically, the research was carried out in 12 agricultural soils having different physicochemical characteristics and was performed by means of the leucine ( 3 H) incorporation method. In addition, changes in the structure of soil microbial communities at 8 and 42 days were studied in four of these soils, using the phospholipids of fatty acids method for this. The main results indicate that the most toxic antibiotic was amoxicillin, followed by trimethoprim and ciprofloxacin. The results also show that the toxicity of amoxicillin decreases with time, with values of Log IC 50 ranging from 0.07 ± 0.05 to 3.43 ± 0.08 for day 1, from 0.95 ± 0.07 to 3.97 ± 0.15 for day 8, and from 2.05 ± 0.03 to 3.18 ± 0.04 for day 42, during the incubation period. Regarding trimethoprim, 3 different behaviors were observed: for some soils the growth of soil bacterial communities was not affected, for a second group of soils trimethoprim toxicity showed dose-response effects that remained persistent over time, and, finally, for a third group of soils the toxicity of trimethoprim increased over time, being greater for longer incubation times (42 days). As regards ciprofloxacin, this antibiotic did not show a toxicity effect on the growth of soil bacterial communities for any of the soils or incubation times studied. Furthermore, the principal component analysis performed with the phospholipids of fatty acids results demonstrated that the microbial community structure of these agricultural soils, which persisted after 42 days of incubation, depended mainly on soil characteristics and, to a lesser extent, on the dose and type of antibiotic (amoxicillin, trimethoprim or ciprofloxacin). In addition, it was found that, in this research, the application of the three antibiotics to soils usually favored the presence of fungi and Gram-positive bacteria., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The presence of antibiotics in soils may increase the selection pressure on soil bacterial communities and cause tolerance to these pollutants. The temporal evolution of bacterial community tolerance to different concentrations of tetracycline (TC), oxytetracycline (OTC) and chlortetracycline (CTC) was evaluated in two soils. The results showed an increase of soil bacterial community tolerance to TC, CTC and OTC only in samples polluted with the highest antibiotic concentrations tested (2000 mg kg -1 ). The magnitude of those increases was higher in the soil with the lower organic carbon content (1.6%) than in the soil with an organic carbon content reaching 3.4%. In the soil with low organic carbon content, the time-course evolution showed a maximum increase in the tolerance of bacterial communities to tetracycline antibiotics between 45 and 100 incubation days, while for longer incubation times (360 days) the tolerance decreased. In the soil with high organic carbon content, a similar behavior was found for OTC. However, for CTC and TC, slightly increases and decreases (respectively) were found in the bacterial community tolerance at intermediate incubation times, followed by values close to zero for TC after 360 days of incubation, while for CTC they remained higher than in the control. In conclusion, soil pollution due to tetracyclines may cause bacterial community tolerance to these antibiotics when present at high concentrations. In addition, the risk is higher in soils with low organic matter content, and it decreases with time., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The effect of fire severity and recurrence on the recovery of enzymatic activities (β-glucosidase, urease, acid phosphatase) and bacterial activity was monitored. Unburned and burned soil samples from soil affected by a high severity wildfire and by a low severity experimental fire were subjected in laboratory to a temperature gradient to simulate different fire severities. These samples were subjected to a second laboratory heat treatment to simulate the effect of recurrence. Soil temperature was measured and used to calculate the degree-hours reached by the soil. The results showed: a) a strong effect of repeated soil heating at different temperatures on soil microbial activity; b) a different sensitivity of enzymatic activities and bacterial activity to fire, c) the magnitude of changes in these biochemical properties was related to the extent of heat supplied to samples and the previous fire/heat history, and d) degree-hours are adequate to quantify the severity of heat treatments and to examine their effects on soil microbial activity. The relationships between degree-hours and the different biochemical properties analyzed clearly demonstrate that the usefulness of these biochemical properties to detect the soil microbial community response to the heat stress followed the order: urease activity > acid phosphatase activity > β-glucosidase activity ≫ bacterial activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

The increase of concentrations of tetracycline antibiotics in agricultural soils worldwide is of special concern, due to its potential toxic effects on soil bacterial communities. In the present work, the reuse of two waste/by-product materials as soil amendments was tested as a preventive practice for reducing tetracycline antibiotics toxicity in soils. Pine bark (PB), with high percentage of organic carbon, and crushed mussel shell (CMS), a frequent natural liming material, were added to 4 soils in doses 0, 6, 12 and 48 g of by-product per kg -1 of soil (dry weight) of each one (separately). The soils and soil-waste mixtures were then spiked with tetracycline (TC), oxytetracycline (OTC) and chlortetracycline (CTC). After one day of incubation, the bacterial growth was estimated in soils and soil-mixtures using the leucine incorporation technique. The addition of PB to the soils showed two different behaviors, depending on the antibiotics. The toxicity of TC and OTC decreased with the addition of PB (toxicities going from 6 to 25% and from 5 to 36%, respectively). However, CTC toxicity did not change, or even increased in response to the PB amendment. Regarding soil amendment with CMS, it was not effective to prevent the toxicity of any of the three antibiotics studied., (Copyright © 2020. Published by Elsevier Inc.)

The toxicity exerted by the antibiotic sulfadiazine on the growth of soil bacterial communities was studied in two agricultural soils for a period of 100 days. In the short-term (2 days of incubation), the effect of sulfadiazine on bacterial growth was low (no inhibition or inhibition <32% for a dose of 2000 mg·kg -1 ). However, sulfadiazine toxicity increased with time, achieving values of 40% inhibition, affecting bacterial growth in both soils after 100 days of incubation. These results, which were here observed for the first time for any antibiotic in soil samples, suggest that long-term experiments would be required for performing an adequate antibiotics risk assessment, as short-term experiments may underestimate toxicity effects.

Inflammation is involved in the pathogenesis of several age-related ocular diseases, such as macular degeneration (AMD), diabetic retinopathy, and glaucoma. The delivery of anti-inflammatory siRNA to the retinal pigment epithelium (RPE) may become a promising therapeutic option for the treatment of inflammation, if the efficient delivery of siRNA to target cells is accomplished. Unfortunately, so far, the siRNA delivery system selection performed in dividing RPE cells in vitro has been a poor predictor of the in vivo efficacy. Our study evaluates the silencing efficiency of polyplexes, lipoplexes, and lipidoid-siRNA complexes in dividing RPE cells as well as in physiologically relevant RPE cell models. We find that RPE cell differentiation alters their endocytic activity and causes a decrease in the uptake of siRNA complexes. In addition, we determine that melanosomal sequestration is another significant and previously unexplored barrier to gene silencing in pigmented cells. In summary, this study highlights the importance of choosing a physiologically relevant RPE cell model for the selection of siRNA delivery systems. Such cell models are expected to enable the identification of carriers with a high probability of success in vivo, and thus propel the development of siRNA therapeutics for ocular disease.

Preclinical in vivo tests of retinal drug responses are carried out in mice and rats, often after intravitreal injections. However, quantitative pharmacokinetics in the mouse eye is poorly understood. Ocular pharmacokinetics studies are usually done in rabbits. We investigated elimination of three compounds ([ 99m Tc]Tc-pentetate, [ 111 In]In-pentetreotide, [ 99m Tc]Tc-human serum albumin with molecular weights of 510.2 Da, 1506.4 Da, and 66.5 kDa, respectively) from mouse vitreous using imaging with single photon emission computed tomography/computed tomography (SPECT/CT). Increasing molecular weight decreased elimination of the compounds from the mouse eyes. Half-lives of [ 99m Tc]Tc-pentetate, [ 111 In]In-pentetreotide, and [ 99m Tc]Tc-human serum albumin in the mouse eyes were 1.8 ± 0.5 h, 4.3 ± 1.7 h, and 30.0 ± 9.0 h, respectively. These values are 3-12-fold shorter than half-lives of similar compounds in the rabbit vitreous. Dose scaling factors were calculated for mouse-to-rabbit and mouse-to-man translation. They were 27-90 and 38-126, respectively, for intravitreal injections in rabbit and man. We show ocular pharmacokinetic parameters for mice and interspecies scaling factors that may augment ocular drug discovery and development.

The effects of adding two winery wastes, perlite waste (PW) and bentonite waste (BW), to an acid vineyard soil were assessed using some chemical and biological soil properties in a field study that lasted 18 months. The addition of PW (up to 81 Mg ha -1 ) had neither significant nor permanent effects on soil characteristics such as the pH, organic matter content or nutrient concentrations, the amounts of copper or zinc, or the electrical conductivity. Moreover, no persistent negative effects were found on the enzymatic activities after PW application. In contrast, soil that was amended with up to 71 Mg BW ha -1 showed increases in its soil pH values, exchangeable potassium and water soluble potassium and phosphorus contents. In addition, it caused significant increases in the electrical conductivity and water-soluble Cu. In addition, the phosphomonoesterase enzymatic activity decreased significantly (up to 28%) in response to the amendment with 71 Mg BW ha -1 . These results showed that adding BW and PW to the soil may be a good agronomic practice for recycling these types of wastes. However, in the case of PW, its use as a soil amendment must be performed with caution to control its possible harmful effects., (Copyright © 2017 Elsevier Ltd. All rights reserved.)