Autonomous University of Chile

Carbonic anhydrase isoforms I and II (hCA-I and hCA-II) are metalloenzymes involved in essential physiological processes and represent relevant therapeutic targets for disorders such as glaucoma and osteoporosis. Chalcones have emerged as promising scaffolds for carbonic anhydrase inhibition; however, their structure-activity relationships, particularly for non-sulfonamide derivatives, remain insufficiently explored from a computational point of view. In this study, a dataset of 118 chalcone derivatives has been analyzed by using a three-dimensional quantitative structure-activity relationship (3D-QSAR) modeling, which comprises Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Index Analysis (CoMSIA). The developed models exhibited strong internal consistency and predictive capability for both isoforms. For hCA-I, steric, electrostatic, hydrophobic, and hydrogen bond acceptor fields has been identified as key contributors to inhibitory activity, whereas for hCA-II, hydrogen bond donor features played a more prominent role. Molecular docking and molecular dynamics simulations have been employed as complementary approaches to analyze ligand-protein interactions and binding stability. In addition, quantum chemical descriptors, derived from density functional theory, that have been integrated with the 3D-QSAR analysis, reveal a consistent correspondence between contour map features and the distribution of frontier molecular orbitals and molecular electrostatic potential. Furthermore, ADME-based pharmacokinetic properties of the proposed compounds have been evaluated to assess their potential drug-likeness. Based on the integrated computational analysis, six new chalcone derivatives, with predicted inhibitory activity in the nanomolar range, are proposed. Overall, this study provides a consistent physicochemical framework for understanding the inhibitory activity of chalcone derivatives and highlights key molecular features that may guide the modulation of activity across hCA-I and hCA-II isoforms.

Artificial intelligence (AI) has the potential to contribute to environmental protection, as some initiatives have shown; yet, there are some questions about its effectiveness in dealing with environmental challenges and the advancement of sustainable development, as noted by international AI standard-setting instruments. This is because the environment is a complex system, where interactions between natural elements and (mostly local) human dynamics, often driven by inconsistent reasons, can result in unexpected outcomes. Thus, to effectively address environmental issues, it is necessary to consider natural cause–effect relationships as well as human motivations and socio-cultural factors like local practices. The problem is that environmental sustainability efforts based on digital technologies, including AI, are dominated by Eurocentric and technology-based perspectives and conventional sciences, overlooking local knowledge, an approach which may not provide all the answers. To overcome this, it is necessary to rely on other sources of information, in particular Indigenous peoples’ traditional knowledge, which tends to reflect a worldview that favors conservation of natural resources; however, this reliance is not reflected in international law. This paper argues that, by implementing two well-recognized international law principles, public participation and precaution, the consideration of traditional knowledge in the development and building AIs for environmental protection becomes a requirement, as a vital factor in avoiding the materialization of potential harm. This in turn entails the implementation of effective participatory mechanisms for Indigenous peoples and following guidelines that prioritize Indigenous ownership and control over this data, challenging existing colonial approaches embedded in the development of AI technologies.

Evaluate the perispinal neurovascular response (NVR) in a pilot case-control study of 3 incomplete spinal cord transection patients, using non-invasive functional near-infrared spectroscopy (fNIRS). The NVR was evaluated in 3 patients with SCI (one AIS-C and two AIS-B) using fNIRS and compared with a healthy group of 42 subjects. NVR was triggered by painless electrical stimulation of the median nerve. HbO2 changes were measured with an 8-channel fNIRS at cervical and lumbar levels. Patient 1 (T12 injury, 8-month rehabilitation) shows near-normal NVR in the lower thoracic channels, consistent with AIS-C recovery. Patient 2 (T11 injury, 10-month rehabilitation, severe neuropathic pain) with AIS-B status, and Patient 3 (T7 injury, 36-month rehabilitation) exhibited attenuated upper-thoracic NVR responses, correlating with AIS-B status. Median nerve conduction velocities were normal across patients. fNIRS detected distinct NVR patterns correlated with injury level and rehabilitation progress, suggesting its utility for tracking functional recovery. This first-in-human application highlights fNIRS as a promising tool for assessing spinal cord injury.

The routine prophylactic use of antibiotics in sperm preservation for reproductive biotechnologies poses increasing concerns due to its potential role in promoting antimicrobial resistance. Therefore, developing storage systems that maintain sperm quality without antibiotics is essential. In dogs, chilled sperm is vital in assisted reproduction for genetic improvement and breed conservation. Typically, a 20% Tris-egg yolk extender with broad-spectrum antibiotics supports semen preservation for up to 3 days. This study evaluated a Tris-egg yolk medium without antibiotics, stored at 5 °C, as an alternative for short-term preservation of canine sperm. Eight ejaculates from dogs of different breeds were divided into two aliquots: a control group diluted in Tris-egg yolk with ampicillin, and a treatment group without antibiotics. Samples were stored at 5 °C and analyzed at 0, 24, and 48 h to assess motility, plasma membrane and acrosome integrity, intracellular oxidative stress, and mitochondrial membrane potential. No significant differences were found between treatments in most quality parameters during storage. However, storage time negatively affected membrane and acrosome integrity, as well as mitochondrial function, while slightly increasing oxidative stress. These results indicate that, under controlled short-term refrigeration conditions, canine sperm diluted in a Tris-egg yolk extender without antibiotics maintains functional parameters comparable to antibiotic-supplemented media for up to 48 h, despite time-dependent sub lethal cellular alterations.

Understanding trends in height and BMI, along with trajectories of weight status, is crucial to identifying the optimal timing for intervention. The objective of this study was to describe trends in height and BMI among children and adolescents and identify the trajectory of weight status over time. This was a longitudinal study with data collected annually (2013-2020). A total of 41 325 students aged 5-18 years from forty-seven schools participated in the study, and a subsample of 11 535 participants with at least five BMI measurements was used for the analyses. Mixed-effects analysis showed significant increases in height over the years for boys (0·19 cm, standard error 0·01, P < 0·001) and girls (0·15 cm, standard error 0·01, P < 0·001). Regarding BMI, an increasing trend over the years was also found in boys (0·04 kg/m2, se 0·01, P < 0·001) and girls (0·04 kg/m², se 0·01, P < 0·001). Analysing weight status trajectories, three groups were identified: consistently normal weight (males 63·7 %, females 64·5 %), increasingly overweight (males 21·8 %, females 20·7 %) and increasingly obese (males 14·5 %, females 14·8 %). We conclude that in adolescence, height was below expected, indicating that children are not reaching their maximum growth potential. Furthermore, the identification of increasing trajectories of overweight and obesity, starting in childhood, emphasises the progressive nature of excessive weight gain before adulthood. These findings highlight the early onset of nutritional deviations in this population, suggesting the need for interventions to promote healthy weight as children transition into adolescence to mitigate future health risks.