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Artificial intelligence (AI) carries the potential for unprecedented disruption in radiology, with possible positive and negative consequences. The integration of AI in radiology holds the potential to revolutionize healthcare practices by advancing diagnosis, quantification, and management of multiple medical conditions. Nevertheless, the ever-growing availability of AI tools in radiology highlights an increasing need to critically evaluate claims for its utility and to differentiate safe product offerings from potentially harmful, or fundamentally unhelpful ones. This multi-society paper, presenting the views of Radiology Societies in the USA, Canada, Europe, Australia, and New Zealand, defines the potential practical problems and ethical issues surrounding the incorporation of AI into radiological practice. In addition to delineating the main points of concern that developers, regulators, and purchasers of AI tools should consider prior to their introduction into clinical practice, this statement also suggests methods to monitor their stability and safety in clinical use, and their suitability for possible autonomous function. This statement is intended to serve as a useful summary of the practical issues which should be considered by all parties involved in the development of radiology AI resources, and their implementation as clinical tools. • The incorporation of artificial intelligence (AI) in radiological practice demands increased monitoring of its utility and safety. • Cooperation between developers, clinicians, and regulators will allow all involved to address ethical issues and monitor AI performance. • AI can fulfil its promise to advance patient well-being if all steps from development to integration in healthcare are rigorously evaluated. [ABSTRACT FROM AUTHOR]

Background: Gastroparesis (GP) occurs in patients after upper gastrointestinal surgery, in patients with diabetes or systemic sclerosis and in idiopathic GP patients. As pyloric dysfunction is considered one of the underlying mechanisms, measuring this mechanism with EndoFLIP™ can lead to a better understanding of the disease. Methods: Between November 2021 and March 2022, we performed a retrospective single-centre study of all patients who had non-surgical GP, post-surgical GP and no sign of GP after esophagectomy and who underwent our post-surgery follow-up program with surveillance endoscopies and further exams. EndoFLIP™ was used to perform measurements of the pylorus, and distensibility was measured at 40 ml, 45 ml and 50 ml balloon filling. Results: We included 66 patients, and successful application of the EndoFLIP™ was achieved in all interventions (n = 66, 100%). We identified 18 patients suffering from non-surgical GP, 23 patients suffering from GP after surgery and 25 patients without GP after esophagectomy. At 40, 45 and 50 ml balloon filling, the mean distensibility in gastroparetic patients was 8.2, 6.2 and 4.5 mm2/mmHg; 5.4, 5.1 and 4.7 mm2/mmHg in post-surgical patients suffering of GP; and 8.5, 7.6 and 6.3 mm2/mmHg in asymptomatic post-surgical patients. Differences between symptomatic and asymptomatic patients were significant. Conclusion: Measurement with EndoFLIP™ showed that asymptomatic post-surgery patients seem to have a higher pyloric distensibility. Pyloric distensibility and symptoms of GP seem to correspond. [ABSTRACT FROM AUTHOR]

• Implementing BGI measures alone does not guarantee a more sustainable environment. • The UWU model simulated the effectiveness index by involving stakeholders. • Simulation results show higher effectiveness of BGI measures combined with IUWM. • The community participated in the application of the UWU model for the first time. Addressing urban water management challenges requires a holistic view. Sustainable approaches such as blue-green infrastructure (BGI) provide several benefits, but assessing their effectiveness demands a systemic approach. Challenges are magnified in informal areas, leading to the combination of integrated urban water management (IUWM) with BGI as a proposed solution by this research. We employed the Urban Water Use (UWU) model to assess the effectiveness index (EI) of BGI measures in view of IUWM after stakeholder consultation. The procedure in this novel assessment includes expert meetings for scenario building and resident interviews to capture the community's vision. To assess the impact of IUWM on the effectiveness of BGI measures, we proposed a simulation with BGI only and then three simulations with improvements to the water and sewage systems. The results of the EI analysis reveal a substantial improvement in the effectiveness of BGI measures through IUWM combination. Moreover, we offer insights into developing strategies for UWU model application in informal settlements, transferrable to diverse urban areas. The findings hold relevance for policymakers and urban planners, aiding informed decisions in urban water management. [Display omitted] [ABSTRACT FROM AUTHOR]

Accurate information on tree species distribution in urban areas can offer insights into how street trees provide ecosystem services, such as air pollution mitigation and surface cooling. This article presents a method to improve tree species classification in a tropical urban area using LiDAR-derived structural properties of individual tree crowns (ITCs) and digital aerial images. We extracted four LiDAR features, including surface normals of tree leaves, intensity, tree height, and leaf area index (LAI). We conducted two experiments: In the first, we trained encoder-decoder convolutional neural networks using a stack of optical bands and one LiDAR feature at a time. In the second, we developed an optical-LiDAR fusion strategy that combined feature maps from two encoder-decoder networks. One network was trained with optical bands only, while the other was trained with the LiDAR features that improved classification accuracy in the first experiment. Our experiment results demonstrated the usefulness of surface normals and intensity in discriminating among tree species. We found that the optical-LiDAR fusion strategy increased the average F1-score by 12.6 percentage points compared to only optical bands. We also employed the new segment anything (SAM) model to automatically delineate ITCs. SAM outlined ITCs with a boundary F1-score of 98%. The SAM-delineated ITCs were used to improve raw model predictions and produce reliable species maps. This study contributes to mapping and monitoring urban tree species in tropical areas. • We show an approach to improve urban tree species classification. • Our approach is based on fusing aerial images and LiDAR with deep-learning. • Our fusion strategy improved the average F1-score by 12.6% points. • Surface normals from 3D LiDAR point clouds are useful to discriminate species. • Our study contributes to mapping and monitoring urban tree species in tropical areas. [ABSTRACT FROM AUTHOR]

We report the clinicopathological manifestations of canine adenovirus type 1 (CAV 1) infection in captive-born naturally infected maned wolves (Chrysocyon brachyurus). Two 3-month-old maned wolves presented with lethargy, emesis, dehydration, pallor, hypothermia, leucocytosis, neutrophilia, lymphopaenia and thrombocytopaenia. One of the puppies died shortly after admission, with gross changes that included marked gastrointestinal petechiae, splenomegaly, hepatomegaly and pulmonary haemorrhage. Histologically, large eosinophilic intranuclear body inclusions were found in the liver and kidneys. The other wolf had elevated alkaline phosphatase, alanine aminotransferase and creatine kinase activities, and later developed anaemia, hypoalbuminaemia, bilirubinaemia, bilirubinuria, haematuria and proteinuria. Ultrasound demonstrated hepatomegaly, splenomegaly, inguinal lymphadenomegaly and lesions suggestive of gastritis and enteritis. Despite supportive treatment, the animal died. At necropsy, there was icterus, subcutaneous oedema in the inguinal region and hindlimbs, subchondral haemorrhage of articular cartilage of the femoral-tibial-patellar and tarsal joints of both hindlimbs, lymphadenomegaly, bronchopneumonia, hepatomegaly and petechiae in the gastrointestinal mucosa. Microscopically, there was a severe necrotizing hepatitis with intranuclear viral inclusions, fibrinous-necrotizing splenitis, non-suppurative meningoencephalitis and interstitial nephritis. A quantitative PCR test for CAV 1 using DNA extracted from peripheral blood was positive. The clinicopathological findings are similar to those of CAV 1 infection in dogs and other canids. [Display omitted] [ABSTRACT FROM AUTHOR]

Objectives: We investigated the attitudes of radiologists, information technology (IT) specialists, and industry representatives on artificial intelligence (AI) and its future impact on radiological work.Materials and Methods: During a national meeting for AI, eHealth, and IT infrastructure in 2019, we conducted a survey to obtain participants' attitudes. A total of 123 participants completed 28 items exploring AI usage in medicine. The Kruskal-Wallis test was used to identify differences between radiologists, IT specialists, and industry representatives.Results: The strongest agreement between all respondents occurred with the following: plausibility checks are important to understand the decisions of the AI (93% agreement), validation of AI algorithms is mandatory (91%), and medicine becomes more efficient in the age of AI (86%). In contrast, only 25% of the respondents had confidence in the AI results, and only 17% believed that medicine will become more human through the use of AI. The answers were significantly different between the three professions for four items: relevance for protocol selection in cross-sectional imaging (p = 0.034), medical societies should be involved in validation (p = 0.028), patients should be informed about the use of AI (p = 0.047), and AI should be part of medical education (p = 0.026).Conclusion: Currently, a discrepancy exists between high expectations for the future role of AI and low confidence in the results. This attitude was similar across all three groups. The demand for plausibility checks and the need to prove the usefulness in randomized controlled studies indicate what is needed in future research. [ABSTRACT FROM AUTHOR]

• Light touch effects on postural sway with additional cognitive task were assessed. • The performance of suprapostural tasks remained similar while postural sway reduced. • Light touch affected supraspinal (Rambling) and peripheral (Trembling) mechanisms. • The cognitive task affected mostly the supraspinal mechanism of postural control. • Light touch with cognitive task reduced both components of postural sway. The light touch (LT) of the fingertip on a rigid surface and the performance of a cognitive task (CT) affect the postural control. The current study examined the mechanisms involved in the control of postural sway (i.e., Rambling and Trembling components of the center of pressure) with the LT and CT performed individually or simultaneously. Thirteen adults stood on a force plate for 70 s while performed the LT, CT (visual searching of specific letters) or both tasks simultaneously. COP, Rambling , and Trembling mean amplitude and speed were computed. COP and Rambling trajectories were highly and Trembling moderately reduced with LT. The CT affected mainly the Rambling component, supporting the role of supraspinal control of postural sway. These findings suggested that while LT influences both supraspinal and peripheral control mechanisms, CT influences mostly the supraspinal mechanisms involved in postural sway. The combined effects of LT and CT improve the postural control with no negative consequences on CT performance. [ABSTRACT FROM AUTHOR]

The peptides ocellatin-LB1, −LB2 and −F1 have previously been isolated from anurans of the Leptodactylus genus and the sequences are identical from residue 1–22, which correspond to ocellatin-LB1 sequence (GVVDILKGAAKDIAGHLASKVM-NH 2 ), whereas ocellatin-LB2 carries an extra N and ocellatin-F1 extra NKL residues at their C-termini. These peptides showed different spectra of activities and biophysical investigations indicated a direct correlation between membrane-disruptive properties and antimicrobial activities, i.e. ocellatin-F1 > ocellatin-LB1 > ocellatin-LB2. To better characterize their membrane interactions, we report here the detailed three-dimensional NMR structures of these peptides in TFE- d 2 :H 2 O (60:40) and in the presence of zwitterionic DPC- d 38 and anionic SDS- d 25 micellar solutions. Although the three peptides showed significant helical contents in the three mimetic environments, structural differences were noticed. When the structures of the three peptides in the presence of DPC- d 38 micelles are compared to each other, a more pronounced curvature is observed for ocellatin-F1 and the bent helix, with the concave face composed mostly of hydrophobic residues, is consistent with the micellar curvature and the amphipathic nature of the molecule. Interestingly, an almost linear helical segment was observed for ocellatin-F1 in the presence of SDS- d 25 micelles and the conformational differences in the two micellar environments are possibly related to the presence of the extra Lys residue near the peptide C-terminus, which increases the affinity of ocellatin-F1 to anionic membranes in comparison with ocellatin-LB1 and -LB2, as proved by isothermal titration calorimetry. To our knowledge, this work reports for the first time the three-dimensional structures of ocellatin peptides. [ABSTRACT FROM AUTHOR]

Climate crisis requires intergenerational groups' participation to reduce their vulnerability and to promote disaster risk mitigation public policies. This paper analyzes what and how social innovations can nurture risk mitigation public policies to enhance flood resilience in small cities. A mixed-methods approach, which considered a survey with 231 participants (54% women, 45% men, and 1% non-identified) and the facilitation of a seminar with participatory methodologies, was implemented between August and October 2021, engaging municipal secretariats, civil defense, an NGO, schools, and residents of São Luiz do Paraitinga, Brazil. Most participants (205 out of 231 surveyed respondents) indicated that floods are the main hazards, and 90% stated that municipal authorities should lead prevention measures prioritizing ten social innovation actions to avoid and reduce the disaster risks. The survey's results were shared during a seminar that included serious gaming activities to identify, discuss and formulate implementation pathways (how, when, with whom, with what resources) for the prioritized social innovation actions. Among the measures are prevention and evacuation plans, which were significantly correlated (0.749), as well as natural areas restoration and conservation plans, risk areas tours, and children and youth engagement in disaster risk reduction. [ABSTRACT FROM AUTHOR]

Highlights • Active tDCS of the unaffected M1 (M1 UH) was safe within six weeks after stroke. • One subject reported paresthesias in the paretic arm during active tDCS of M1 UH. • Sleepiness was more frequent after active tDCS of M1 UH than sham. [ABSTRACT FROM AUTHOR]

This work describes the numerical simulation of natural convection heat transfer of Cu–water nanofluids in a square enclosure for Rayleigh numbers varying from 10 3 up to 10 5 . Two different numerical approaches were used: the finite volume method and the finite element method. The nanofluids were assumed to be single-phase fluids with modified thermal properties obtained from experimental results and theoretical models. The results showed that the Nusselt number for nanofluids was basically the same as that obtained for the base fluid. Therefore, the enhancement observed in the heat transfer coefficient was significant due to the augmentation in the thermal conductivity. [ABSTRACT FROM AUTHOR]

The last decades are witnessing a growing concern about environmental impacts due to human activities. Within this context, studies are being developed to understand the impacts on the diversity of natural elements. This article presents a method to identify geomorphological diversity hotspots at a detailed scale through a quantitative approach, which was applied to a protected coastal area in Rio de Janeiro State, SE Brazil. These hotspots are understood as areas that present significant diversity of landforms and, at the same time, risks of degradation, which justifies the definition of priorities for the territorial management aiming at nature conservation purposes. The results allowed the identification of five hotspots, showing that, even though the area is legally protected, it still faces problems related to threats caused by human activities. Therefore, specific problems of territorial management in a protected area were identified through the creation of a product that indicates the priority areas for conservation in a different way and can be easily applied as a tool to support managers. Furthermore, several subproducts were created in the process, which also can be used for other purposes. • The hotspot map is a tool for the definition of priority areas for conservation. • Threat fronts and threatened landforms can be identified by the threat index map. • All the index and subindex maps present relevant management information. [ABSTRACT FROM AUTHOR]

Studies have evaluated how the urban expansion process impacts ecosystem services and human well-being in coastal areas. Conceptual models have been proposed to analyze this cause-effect relationship, such as DPSWIR (Driving Force-Pressure-State-Impact-Well-being-Response). However, analysis of the effects on human well-being, including health, is explored to a limited extent in the model. This study proposes to adapt the DPSIWR model to better integrate the potential effects on human health and well-being in the analysis due to the loss of coastal ecosystem services caused by the urban expansion process. As a case study, the model is applied to the municipality of Armação dos Búzios, in the southeast of Brazil. From a temporal analysis in which urban expansion was measured in the period between 1976 and 2019, it was registered that the urban area in the municipality went from 1.9% of the territory in 1976 to 20.5% in 2019. Consequently, the ecosystems and their services have been severely affected, which can harm subsistence, security, social relations, and the health of the population. The main group of services impacted by urban expansion was the regulation and maintenance, especially the ones related to the regulation of water flow. These findings indicate an alert for decision makers, mainly regarding the risk of flood events and the emergence of parasitic infectious diseases. As a management response, it is important to consider the integration of environmental and health policies in coastal urban planning plans and strategies. For this, there is a need for better coordination between the public health, urban planning and environment sectors in the municipality. This study proposes a management tool that contributes to an integrated assessment between the aspects of planning, environmental conservation and effects on public health and social well-being, allowing a broader and holistic view of the reality of the territory, thus contributing to the establishment good governance practices. [Display omitted] • We proposed to adapt the DPSIWR framework to improve coastal urban planning. • We analyzed the impacts of urban expansion on ecosystem services and human well-being. • Urban expansion impacts mainly regulation and maintenance services in the study area. • Loss of coastal ecosystem servises can increase the emergence of cases of diseases. [ABSTRACT FROM AUTHOR]

Non-Newtonian fluids are a constant presence in several industrial applications so it becomes interesting to understand their behavior and to optimize their use. One behavior of commercial interest is the viscoplastic behavior characterized by an abrupt change of the apparent viscosity when a certain amount of stress is achieved. The present work performs a study of the effect of Reynolds number, the plastic number, and the flow intensity over flow parameters of industrial interest, namely, mean Nusselt number, displacement efficiency, and head loss. The mechanical model is approximated by a finite volume method implemented by an OpenFOAM® routine developed by the authors. The SMD model was chosen to model the viscoplastic behavior. The adopted geometry is of a planar channel with an abrupt expansion followed by an abrupt contraction. The channel walls are kept insulated and heat transfer occurs only at the cavity formed between the expansion and contraction planes. For the studied range of parameters, mean Nusselt number has a positive dependence on Reynolds number and flow intensity but a negative dependence on plastic number; displacement efficiency has a positive dependence on Reynolds number and flow intensity but a negative dependence on plastic number. The head loss has a negative dependence on Reynolds number and plastic number and an overall positive dependence on flow intensity. [ABSTRACT FROM AUTHOR]

Cururu toad (Rhinella marina group) is widely distributed in Brazil. Lesser grison (Galitic cuja) is a South American mustelid. This is the first report of natural poisoning in a free-ranging lesser grison by Rhinella toad parotoid gland secretion (PGS). Five minutes after biting a toad, the lesser grison developed convulsion, dying within 1.5 h. Mass spectrometry analysis of a milky-whitish secretion found in the lesser grison oral cavity allowed identification of a bufotoxin and a new bufonid peptide. • A free-ranging lesser grison had a lethal poisoning after an attempted predation on Rhinella sp. • The lesser grison (Galitic cuja) exposed to the cururu toad poison developed lethal neurologic signs. • A bufotoxin was detected in the toad secretion collected from the oral cavity of the affected lesser grison. • A novel bufonid peptide was discovered in the toad secretion collected from the oral cavity of the affected lesser grison. [ABSTRACT FROM AUTHOR]

Objectives: To compare objective and subjective image quality between low keV virtual monoenergetic images (VMI) of the excretory phase and conventional venous phase images derived from spectral dual-energy CT (DECT) in the assessment of urothelial carcinoma.Methods: 26 consecutive patients with histologically confirmed urothelial carcinoma who received clinically indicated venous- and excretory phase abdominal CT scans were included retrospectively. Attenuation, image noise as well as signal- and contrast-to-noise-ratio (SNR, CNR) in venous and excretory phase CT and excretory phase VMI from 40 to 70 keV were obtained from ROI-based measurements in the following regions: urothelial carcinoma, liver, pancreas, renal cortex, subcutaneous fat, renal vein/artery, portal vein, urinary bladder wall, lymph nodes, prostate/uterus. Subjective vessel contrast and delineation of primary tumor manifestations and distant metastases were rated on 5-point Likert scales.Results: In comparison to venous phase CT, attenuation and SNR in excretory phase VMI40keV were higher (p < 0.001), except for liver parenchyma, where they were comparable (p = 0.07 and p = 0.17, respectively). Regarding image noise, no significant difference was found between venous phase CT and excretory phase VMI40keV (p-range: 0.08-1.00), except for liver, portal vein and renal artery, where it was lower in VMI40keV (p < 0.05). CNR of urothelial carcinoma to circumjacent bladder wall was significantly higher in excretory phase VMI40keV compared to venous phase CT. Subjective vessel contrast and delineation of primary tumor and distant metastases received equivalent or higher Likert scores in excretory phase VMI40keV than in venous phase CT.Conclusion: This feasibility study indicates that in the assessment of urothelial carcinoma, virtual monoenergetic excretory phase images at 40 keV acquired with spectral DECT could be feasible to maintain subjective and objective image quality as provided by conventional venous phase images. Still, equivalence with regards to metastatic lesion detection requires further investigation before employing this technique in a potential signal-scan, single-bolus approach. [ABSTRACT FROM AUTHOR]

This paper deals with the numerical simulation of natural convection inside a closed cavity of multi-walled carbon nanotubes and diamond nanoparticles dispersed in pure mineral oil. The data of the thermal conductivity and viscosity of the nanofluids were obtained experimentally, while specific heat and density were evaluated by the first law of thermodynamic and mass conservation principle, respectively. The physical model considered is a 2D cavity with adiabatic horizontal walls, where the left vertical wall with high temperature and the right vertical wall with low temperature and all walls with no-slip boundary conditions. The simulations were performed in a numerical code based on the Finite Volume Method-FVM, where second order temporal and spatial schemes were used. The results showed that only the Nusselt number for MWCNT based nanofluids increased in comparison to the mineral oil for the same Grashof number. However, the comparison between the convective coefficient for nanofluids and mineral oil showed that nanofluids presented better convection characteristics, for the same Grashof number. Furthermore, the diamond nanofluid with higher volumetric concentration presented the maximum increase of the convection coefficient, about 23%, though this nanofluid did not presentthe higher Nusselt number in comparison to the other nanofluids analyzed. [ABSTRACT FROM AUTHOR]

An extraction procedure using Tris-HCl buffer solution was employed in order to extract water-soluble proteins from seed samples of oat, wheat and soybean. Initially, the total protein concentration was determined by the Bradford method in each solution, after the extraction procedure. The soybean sample showed a higher concentration of total protein compared to the others. The protein extracts obtained were separated by reverse-phase chromatography (RP-HPLC-UV). The protein fractions were collected and analyzed by graphite furnace atomic absorption spectrometry (GFAAS) and matrix-assisted laser desorption/ionization (MALDI-TOF-MS) for determination of Cu, Fe, Mn and Zn and identification of proteins, respectively. The combination of techniques such as RP-HPLC-UV, GFAAS and MALDI-TOF-MS allowed the identification of several proteins bound to metals present in the seed samples. [ABSTRACT FROM AUTHOR]

Highlights: [•] Elastic effects on complex flows of viscoplastic fluids. [•] Numerical simulation of viscoplastic fluids with elasticity, using finite element technique. [•] Flow of elasto-viscoplastic fluid inside a cavity. [ABSTRACT FROM AUTHOR]

Abstract: (1H-Pyridin-4-ylidene)amines containing lipophilic side chains at the imine nitrogen atom were prepared as potential clopidol isosteres in the development of antimalarials. Their antiplasmodial activity was evaluated in vitro against the Plasmodium falciparum W2 (chloroquine-resistant) and FCR3 (atovaquone-resistant) strains. The most active of these derivatives, 4m, had an IC50 of 1μM against W2 and 3μM against FCR3. Molecular modeling studies suggest that (1H-pyridin-4-ylidene)amines may bind to the ubiquinol oxidation Qo site of cytochrome bc 1. [Copyright &y& Elsevier]

Abstract: Molecular docking studies of two duplex DNA sequences as target fragments and allopsoralen as ligand were performed. The calculated interaction energies showed that the ligand can be docked into the minor groove as well as become intercalated. However, unlike psoralen, allopsoralen preferred binding mode for non-poly-TA sequences is minor groove binding. Calculated energies for intercalation between different base pairs suggest that the predicted sequence selectivity for allopsoralen is analogous to that observed for psoralen. Intercalation is favored in 5′-TpA sites in poly-TA sequences. [Copyright &y& Elsevier]

• SILAC proteomics approach yielded important cisplatin resistance biomarkers in NSCLC. • Cisplatin resistance upregulated NER-based repair and downregulated mRNA splicing-related pathways. • STAT3 KO conferred epithelial morphology and sensitized to mTOR inhibition. • Cisplatin responsiveness is dependent on STAT3 and mTOR crosstalk in NSCLC cells. • Synergistically inhibition of STAT3 and mTOR is possibly a potential approach against NSCLC. Lung cancer is the second leading cause of cancer death worldwide and is strongly associated with cisplatin resistance. The transcription factor signal transducer and activator of transcription 3 (STAT3) is constitutively activated in cancer cells and coordinates critical cellular processes as survival, self-renewal, and inflammation. In several types of cancer, STAT3 controls the development, immunogenicity, and malignant behavior of tumor cells while it dictates the responsiveness to radio- and chemotherapy. It is known that STAT3 phosphorylation at Ser727 by mechanistic target of rapamycin (mTOR) is necessary for its maximal activation, but the crosstalk between STAT3 and mTOR signaling in cisplatin resistance remains elusive. In this study, using a proteomic approach, we revealed important targets and signaling pathways altered in cisplatin-resistant A549 lung adenocarcinoma cells. STAT3 had increased expression in a resistance context, which can be associated with a poor prognosis. STAT3 knockout (SKO) resulted in a decreased mesenchymal phenotype in A549 cells, observed by clonogenic potential and by the expression of epithelial-mesenchymal transition markers. Importantly, SKO cells did not acquire the mTOR pathway overactivation induced by cisplatin resistance. Consistently, SKO cells were more responsive to mTOR inhibition by rapamycin and presented impairment of the feedback activation loop in Akt. Therefore, rapamycin was even more potent in inhibiting the clonogenic potential in SKO cells and sensitized to cisplatin treatment. Mechanistically, STAT3 partially coordinated the cisplatin resistance phenotype via the mTOR pathway in non-small cell lung cancer. Thus, our findings reveal important targets and highlight the significance of the crosstalk between STAT3 and mTOR signaling in cisplatin resistance. The synergic inhibition of STAT3 and mTOR potentially unveil a potential mechanism of synthetic lethality to be explored for human lung cancer treatment. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) and arterial hypertension are considered serious public health problems. Several studies have shown that oxidative stress is usually related to the onset of DM and hypertension, as well their associated complications. Moreover, the levels of some minerals are closely related to the pathophysiology of these diseases. Thus, in this study we aimed to evaluate the effect of metformin on the redox profile and mineral levels in the serum of patients with DM type 2 and hypertension. We also tested the effect of metformin on the viability and redox profile of peripheral blood mononuclear cells (PBMCs) for 24 h. As expected, we found that patients with type 2 DM and hypertension + type 2 DM had higher fasting glucose and triglyceride levels. As groundbreaking research, we found that both patients DM type 2 and Hypertension + DM type 2 had reduced myeloperoxidase (MPO) activity. On the other hand, the levels of total thiols (PSH) and vitamin C were increased. There was no statistical significance for the alterations in mineral levels. In addition, metformin treatment had no cytotoxic effect on PBMCs. Similarly, in patients of both groups, MPO activity was reduced and PSH levels were increased in PBMCs. We have shown that metformin is a drug with a protective effect in patients with DM type 2 against oxidative stress by reducing MPO activity and improving the levels of PSH and antioxidant defenders such as vitamin C. The results of in vitro assays support the antioxidant effect of metformin. Furthermore, we suggest studies to assess the biochemical mechanisms of metformin and how it can be used in a pharmacological therapeutic perspective against oxidative damage. [Display omitted] • Several studies suggest that metformin has an antioxidant effect. • We showed in vivo and in vitro that metformin has an antioxidant effect. • Patients with type 2 DM and under drug therapy with metformin have levels of PSH and vitamin C improved. • We suggest that future clinical trial research be carried out to fully understand the mechanisms involved. [ABSTRACT FROM AUTHOR]

• We developed a novel portable and label-free PEC genosensor for SARS-CoV-2. • GSH-AuNPs and c-g-C 3 N 4 were synthesized for genosensor development. • Photocurrent decreases as ssDNA target concentration increases. • Genosensor detected SARS-CoV-2 in human saliva samples. • Saliva samples results were compared using RT-PCR. Fast, sensitive, simple, and cheap sensors are highly desirable to be applied in the health system because they improve point-of-care diagnostics, which can reduce the number of cases of infection or even deaths. In this context, here we report the development of a label-free genosensor using a screen-printed electrode modified with 2D-carbonylated graphitic carbon nitride (c-g- C 3 N 4), poly(diallyldimethylammonium) chloride (PDDA), and glutathione-protected gold nanoparticles (GSH-AuNPs) for photoelectrochemical (PEC) detection of SARS-CoV-2. We also made use of Arduino and 3D printing to miniaturize the sensor device. The electrode surface was characterized by AFM and SEM techniques, and the gold nanoparticles by UV–Vis spectrophotometry. For SARS-CoV-2 detection, capture probe DNA was immobilized on the electrode surface. The hybridization of the final genosensor was tested with a synthetic single-strand DNA target and with natural saliva samples using the photoelectrochemistry method. The device presented a linear range from 1 to 10,000 fmol L−1 and a limit of detection of 2.2 and 3.4 fmol L−1 using cpDNA 1A and 3A respectively. The sensibility and accuracy found for the genosensor using cpDNA 1A using biological samples were 93.3 and 80% respectively, indicating the potential of the label-free and portable genosensor to detect SARS-CoV-2 RNA in saliva samples. [ABSTRACT FROM AUTHOR]

This study aimed to identify the least aggressive and highest yield extraction method to obtain bioactive compounds from Inga marginata Willd fruits, determine the chemical components, and evaluate the extracts'' antimicrobial and cytotoxic activity. The extraction efficiency was expressed by the total phenolic and total flavonoid content and antioxidant activity (DPPH, IC 50 , and ORAC) using conventional, ultrasound, and microwave-assisted extraction. The highest bioactive compound content was achieved using 5 min at 60 °C for total phenolic content (214.98 mg GAE g−1), total flavonoid content (22.90 mg EQ g−1), DPPH (45.98 μmol TEAC g−1), inhibitory capacity (0.80 mg mL−1), and ORAC (167.25 μmol Trolox g−1) using ultrasonic extraction, and the extract inhibited the growth of all microorganisms tested. Thirteen chemical compounds were determined by ESI-ToF-MS, confirming the high phytochemical capacity of the extract. Lastly, the Inga extract showed no cytotoxicity at the concentrations used. [Display omitted] • Ultrasound-assisted extraction had greater efficiency in bioactive compound yield. • The natural Inga extract had high antioxidant and antimicrobial capacity. • The temperature significantly affected all determinations and extraction methods. • Twelve phytochemicals and one sugar were identified. • The Inga peel and pulp extract did not show toxicity at the cellular level. [ABSTRACT FROM AUTHOR]

Animal venoms are complex mixtures, including peptides, proteins (i.e., enzymes), and other compounds produced by animals in predation, digestion, and defense. These molecules have been investigated regarding their molecular mechanisms associated with physiological action and possible pharmacological applications. Recently, we have described the presence of a type of angiotensin converting enzyme (ACE) activity in the venom of Thalassophryne nattereri . It is a zinc-dependent peptidase with a wide range of effects. By removing dipeptide His-Leu from terminal C, the ACE converts angiotensinI (AngI) into angiotensin II (AngII) and inactivates bradykinin, there by regulating blood pressure and electrolyte homeostasis. The fractionation of T. nattereri venom in CM-Sepharose indicated a peak (CM2) with angiotensin-converting activity, converting AngI into Ang II. Electrophoresis on polyacrylamide gel (12%) revealed one band with 30 kDa for CM2 similar in size to natterins, which are toxins with proteolytic activity found in T. nattereri venom. Mass spectrometry indicated that the protein sequence of the ACE purified from T. nattereri venom corresponds to natterin 1. The isolated protein has also demonstrated inhibition through captopril and EDTA and is characterized as a classic ACE. Thus, the isolated enzyme purified from T. nattereri venom is the first ACE isolated from fish venom. [ABSTRACT FROM AUTHOR]