Search Results (57)

A one-pot synthetic methodology that combines an Ugi-Zhu three-component reaction (UZ-3CR) with a cascade sequence (intermolecular aza Diels–Alder cycloaddition/intramolecular N-acylation/decarboxylation/dehydration) using microwave-heating conditions, ytterbium (III) triflate (Yb(OTf)₃) as the catalyst, and chlorobenzene (for the first time in a multi-component reaction (MCR)) as the solvent, was developed to synthesize twelve new fluorinated-pyrrolo[3,4-b]pyridin-5-ones containing a 4-amino-7-chloroquinoline moiety, yielding 50–77% in 95 min per product, with associated atom economies around 88%, also per product. Additionally, by in vitro tests, compounds 19d and 19i were found to effectively stop early SARS-CoV-2 replication, IC₅₀ = 6.74 µM and 5.29 µM, at 0 h and 1 h respectively, while cell viability remained above 90% relative to the control vehicle at 10 µM. Additional computer-based studies revealed that the most active compounds formed strong favorable interactions with important viral proteins (M_pro, NTDα and NTDo) of coronavirus, supporting a two-pronged approach that affects both how the virus infects the cells and how it replicates its genetic material. Finally, quantum chemistry analyses of non-covalent interactions were performed from Density-Functional Theory (DFT) to better understand how the active compounds hit the virus. Full article

Chagas disease (ChD) caused by Trypanosoma cruzi remains a major public health concern, affecting approximately 8 million people worldwide. However, the number of undiagnosed cases is likely much higher. Existing treatments rely on benznidazole and nifurtimox which, despite their efficacy during the acute phase of infection, are often associated with severe side effects that can be life-threatening. As a promising alternative, actinomycetes—which are renowned for producing pharmacologically and industrially relevant metabolites—have demonstrated potent antimicrobial properties; however, their antiparasitic potential remains largely unexplored. This study evaluated the anti-trypanocidal activities of extracellular metabolites produced by Streptomyces thermocarboxydus strain Chi-43 (ST-C43) and Streptomyces sp. strain Chi-104 (S-C104) against epimastigote, trypomastigote, and amastigote forms of T. cruzi. The strains were cultured in ISP2 broth, and their extracellular metabolites were assessed via antiparasitic diffusion assays in microplates. The 50% lethal concentration (LC₅₀) values ranged from 102 to 116 μg/mL against epimastigotes and trypomastigotes. The antiparasitic activity was confirmed through 3-(4,5-dimetiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-based spectrophotometric assays and optical microscopy. Toxicity assays revealed that the extracellular metabolites were non-toxic to Artemia salina, non-cytotoxic to Huvecs, and non-hemolytic to human erythrocytes. Dose–response regression analysis showed statistically significant differences (p ≤ 0.05). LC-MS/MS analysis identified amphomycin and K-252c aglycone staurosporine as the active antiparasitic compounds. These findings highlight the potential of Streptomyces-derived extracellular metabolites as novel, selective, and safe anti-T. cruzi agents. Nevertheless, further studies in murine or preclinical models are needed to validate their efficacy and support future clinical applications for the treatment of ChD. Full article

In this work, the position control of a cable-driven soft robot is proposed through the approximation of its kinematic model. This approximation is derived from artificial learning rules via neural networks and experimentally observed data. To improve the learning process, a combination of active sampling and Model Agnostic Meta Learning is carried out to improve the data based model to be used in the control stage through the inverse velocity kinematics derived from the data based modeling along with a self differentiation procedure to come up with the pseudo inverse of the robot Jacobian. The proposal is verified in a designed and constructed cable-driven soft robot with three actuators and position measurement through a vision system with three-dimensional motion. Some preliminary assessments (tension and repeatability) were performed to validate the robot movement generation, and, finally, a 3D reference trajectory was tracked using the proposed approach, achieving competitive tracking errors. Full article

Moringa oleifera (MO) leaf infusion has gained attention for its potential therapeutic effects, particularly in metabolic health, due to its rich content of bioactive compounds, including polyphenols. The study evaluates the antioxidant properties and metabolic effects of the prophylactic administration of MO infusion in a high-fat diet (HFD)-induced murine model. First, polyphenol content (0.45 mg/g) and antioxidant activity (45.39%) were determined using Folin-Ciocalteu, DPPH, phosphomolybdenum, ferrocyanide, and anti-browning assays. In the in vivo phase, BALB/c mice were divided into three groups: a balanced diet group, a negative control group, and an HFD group supplemented with MO infusion. Over eight months, biochemical analyses, psychomotor tests, glucose tolerance assessments, and liver histopathology were conducted. MO infusion significantly reduced food intake, weight gain, lipid profiles, and liver inflammation compared to the negative control group, while promoting a metabolic profile similar to that of the balanced diet group. Additionally, it positively influenced psychomotor performance, reinforcing its neuroactive potential. These findings suggest that MO leaf infusion may serve as a functional beverage with protective effects against metabolic disorders, offering a promising natural strategy for managing obesity-related health issues. Full article

The transition of agriculture towards sustainability faces significant obstacles, such as increased demand for food, food insecurity, climate variability, biodiversity loss, and food waste, among others. Moreover, agricultural activities must address ethical practices within sustainable development. The literature frequently mentions two approaches to meet these challenges: agroecology and sustainable agriculture. This study aims to delineate the conceptual boundaries of agroecology and sustainable agriculture while elucidating their interconnection. It seeks to clarify the scope and limitations inherent in these agricultural practices, which is critical given the centrality of sustainable agriculture in agrarian studies. By establishing these boundaries, the research outlines the methodologies to identify the relevant variables and indicators required for effective stakeholder engagement within agricultural systems. A systematic literature review was conducted using the PRISMA method. The databases searched were Science Direct, Scopus, Nature, and Google Scholar. The inclusion criteria were (i) written in English or Spanish, (ii) published in a peer-reviewed academic journal, and (iii) related to the conceptualization of agroecology and sustainable agriculture. Publications were selected following the method’s identification, screening, eligibility, and inclusion guidelines. The main distinctions between the concepts are the scale and the scope. Agroecology reveals limitations to achieving impacts on food security and agriculture’s challenges in a large-scale system better suited for rural communities and small farms seeking locally adapted solutions. On the other hand, the literature reveals that it is crucial to adopt a multi-scale systems approach to meet the growing food demands of the global population, for which sustainable agriculture may be more effective. Full article

In amnestic mild cognitive impairment (aMCI), neuroinflammation evolves during disease progression, affecting microglial function and potentially accelerating the pathological process. Currently, no effective treatment exists, leading to explorations of various symptomatic approaches, though few target the underlying physiological mechanisms. Modulating inflammatory processes may be critical in slowing disease progression. Cognitive stimulation (CS) and transcranial direct current stimulation (tDCS) applied to the left dorsolateral prefrontal cortex (l-DLPFC) show promise, but the results are heterogeneous. Thus, a randomized, double-blind, placebo-controlled clinical trial is currently underway. The first-stage results were examined after three weeks of intervention in two groups: active tDCS combined with CS and sham tDCS combined with CS. Twenty-two participants underwent two assessments: T0 (baseline) and T1 (after 15 sessions of tDCS, active or sham, and 9 sessions of CS). The results demonstrated that CS improved cognition, increased brain-derived neurotrophic factor (BDNF) levels, and reduced peripheral proinflammatory cytokine levels (interleukin IL-6 and chemokine CX3CL1) in serum. This decrease in IL-6 may promote microglial proliferation and survival as a modulatory effect response, while the increase in BDNF might suggest a regulatory mechanism in microglia–neuron interaction responses. However, tDCS did not enhance the cognitive or modulatory effects of CS, suggesting that longer interventions might be required to achieve substantial benefits. Full article

Background/Objectives: Patients with diabetes have been reported to experience a higher prevalence of shoulder disorders compared to those without diabetes or with other medical conditions. However, the specific types of shoulder injuries and the extent of functional impairment associated with diabetes mellitus remain unclear. This study aimed to assess the association between diabetes and specific shoulder injuries, as well as the degree of functional impairment in affected patients. Methods: A case–control study was conducted involving 136 patients with shoulder functional impairment (UCLA Shoulder Scale ≤ 27). The study included 38 patients with diabetes and 98 non-diabetic controls. Shoulder injuries were diagnosed using ultrasonography, focusing on the supraspinatus tendon, long head of the biceps tendon, subscapularis tendon, and the presence of adhesive capsulitis or rotator cuff tears. Results: Diabetic patients had significantly higher rates of poor shoulder function compared to non-diabetic controls (89.47% vs. 63.26%, adjusted OR [adOR] 5.22, 95% CI 1.57–17.32, p = 0.007). While both groups had high rates of supraspinatus and long head of the biceps tendon injuries (~80%), no significant differences were found between them (p > 0.300). However, diabetic patients were more than three times as likely to have subscapularis tendon injuries (adOR 3.15, 95% CI 1.26–7.90, p = 0.014) and massive rotator cuff tears (adOR 3.76, 95% CI 1.16–12.15, p = 0.027). Additionally, diabetes was associated with a fourfold increased risk of adhesive capsulitis (adOR 4.16, 95% CI 1.20–14.47, p = 0.025). Conclusions: Diabetes mellitus is linked to greater functional and structural deterioration of the shoulder, highlighting the importance of considering diabetes as a risk factor for specific shoulder injuries. Early diagnosis and treatment may improve outcomes for diabetic patients with shoulder disorders. Full article

Liver cancer is the fourth leading cause of cancer-related death worldwide. In Mexico, there is a high burden of liver cancer mortality in rural states, affecting both women and men equally. Thus, we aimed to describe the demographic and clinical characteristics of hepatocellular cancer (HCC) by sex in Mexico. Demographic and clinical information was extracted retrospectively from the medical records of patients with HCC initially treated (2015–2022) at institutions participating in a national survey across the country. The male-to-female ratio was calculated at the national and regional levels, and the results were stratified by sex. Among 697 HCC patients, the age at diagnosis was 65.4 ± 11.9 years and 20% were diagnosed at ≥75 years. The male-to-female ratio was 1.4:1, ranging from 1:1 in the northwestern and southwestern regions, to 2.1:1 in the western region. The proportion of cirrhosis was similar between the sexes; however, the etiology of cirrhosis differed: cryptogenic cirrhosis was higher in women and alcohol consumption was higher in men. Men had a higher proportion of advanced HCC, poor/undifferentiated tumors, and ≥4 nodules than women. HCC in the Mexican population affects both men and women at a 1.4:1 male-to-female ratio. This unique proportion by sex could be explained by the differences in the prevalence of risk factors across our heterogeneous country. Full article

Articular cartilage lesions are challenging to regenerate, prompting the investigation of novel biomaterial-based therapeutic approaches. Extracellular matrix (ECM)-derived biomaterials are a promising option for this purpose; however, to date, the combination of amniotic membrane (AMM) and articular cartilage (ACM) has not been tested. This study evaluated different concentrations of soluble extracts from the decellularized ECM of amniotic membrane (dAMM) and articular cartilage (dACM), both individually and in combination, to determine their ability to maintain the chondrogenic phenotype in human chondrocytes. After the decellularization process 90–99% of the cellular components were removed, it retains nearly 100% of type 2 collagen and 70% of aggrecan (ACAN) for dACM, and approximately 90% of type IV collagen and 75% of ACAN for dAMM. The biological activity of soluble extracts from dACM and dAMM were evaluated on human chondrocytes. After 72 h, 1.5 mg/mL of dACM and 6 mg/mL of dAMM significantly increased (p < 0.05) the proliferation and expression of SOX9 and ACAN. Also, the combination of both (1.5 mg/mL dACM and 6 mg/mL dAMM) showed synergistic effects, enhancing chondrocyte proliferation, maintaining chondrogenic lineage, and increasing the production of cartilage ECM components, such as COLII (1.5-fold), SOX9 (2-fold), and ACAN (2-fold). These results suggest that the combined use of dACM and dAMM has potential for cartilage regeneration. Full article

Vitamin D3 or calcitriol (VitD3) has been shown to have anticancer and anti-inflammatory activity in in vitro models and clinical studies. However, its effect on HPV-16-related cancer has been sparsely explored. In this study, we aimed to determine whether monotherapy or combination therapy with cisplatin (CP) reduces tumor growth and affects survival and systemic inflammation. Treatments were administered to C57BL/6 mice with HPV-16-related tumors (TC-1 cells) as follows: (1) placebo (100 µL vehicle, olive oil, orally administered daily); (2) VitD3 (3.75 µg/kg calcitriol orally administered daily); (3) CP (5 mg/kg intraperitoneally, every 7 days); and (4) VitD3+CP. Tumor growth was monitored for 25 days, survival for 60 days, and the neutrophil-to-lymphocyte ratio (NLR) was evaluated on days 1 (baseline), 7, and 14. VitD3+CP showed greater success in reducing tumor volume compared to CP monotherapy (p = 0.041), while no differences were observed between CP and VitD3 monotherapy (p = 0.671). Furthermore, VitD3+CP prolonged survival compared to CP (p = 0.036) and VitD3 (p = 0.007). Additionally, at day 14 the VitD3 and VitD3+CP groups showed significantly lower NLR values than the CP group (p < 0.05, for both comparisons). Vitamin D3 could be a promising adjuvant in the treatment of cervical cancer or solid tumors and deserves further investigation. Full article

Wearable Biosensor Technology (WBT) has emerged as a transformative tool in the educational system over the past decade. This systematic review encompasses a comprehensive analysis of WBT utilization in educational settings over a 10-year span (2012–2022), highlighting the evolution of this field to address challenges in education by integrating technology to solve specific educational challenges, such as enhancing student engagement, monitoring stress and cognitive load, improving learning experiences, and providing real-time feedback for both students and educators. By exploring these aspects, this review sheds light on the potential implications of WBT on the future of learning. A rigorous and systematic search of major academic databases, including Google Scholar and Scopus, was conducted in accordance with the PRISMA guidelines. Relevant studies were selected based on predefined inclusion and exclusion criteria. The articles selected were assessed for methodological quality and bias using established tools. The process of data extraction and synthesis followed a structured framework. Key findings include the shift from theoretical exploration to practical implementation, with EEG being the predominant measurement, aiming to explore mental states, physiological constructs, and teaching effectiveness. Wearable biosensors are significantly impacting the educational field, serving as an important resource for educators and a tool for students. Their application has the potential to transform and optimize academic practices through sensors that capture biometric data, enabling the implementation of metrics and models to understand the development and performance of students and professors in an academic environment, as well as to gain insights into the learning process. Full article

This dataset was acquired during collaboration and competition tasks performed by sixteen subject pairs (N = 32) of one female and one male under different (face-to-face and online) modalities. The collaborative task corresponds to cooperating to put together a 100-piece puzzle, while the competition task refers to playing against each other in a one-on-one classic 28-piece dominoes game. In the face-to-face modality, all interactions between the pair occurred in person. On the other hand, in the online modality, participants were physically separated, and interaction was only allowed through Zoom software with an active microphone and camera. Electroencephalography data of the two subjects were acquired simultaneously while performing the tasks. This article describes the experimental setup, the process of the data streams acquired during the tasks, and the assessment of data quality. Full article

Natural 4-1BBL (CD137L) is a cell membrane-bound protein critical to the expansion, effector function, and survival of CD8⁺ T cells. We reported the generation of an active soluble oligomeric construct, SA-4-1BBL, with demonstrated immunoprevention and immunotherapeutic efficacy in various mouse tumor models. Herein, we developed an oncolytic adenovirus (OAd) for the delivery and expression of SA-4-1BBL (OAdSA-4-1BBL) into solid tumors for immunotherapy. SA-4-1BBL protein expressed by this construct produced T-cell proliferation in vitro. OAdSA-4-1BBL decreased cell viability in two mouse lung cancer cell lines, TC-1 and CMT64, but not in the non-cancerous lung MM14.Lu cell line. OAdSA-4-1BBL induced programmed cell death types I and II (apoptosis and autophagy, respectively), and autophagy-mediated adenosine triphosphate (ATP) release was also detected. Intratumoral injection of OAdSA-4-1BBL efficiently expressed the SA-4-1BBL protein in the tumors, resulting in significant tumor suppression in a syngeneic subcutaneous TC-1 mouse lung cancer model. Tumor suppression was associated with a higher frequency of dendritic cells and an increased infiltration of cytotoxic CD8⁺ T and NK cells into the tumors. Our data suggest that OAdSA-4-1BBL may present an efficacious alternative therapeutic strategy against lung cancer as a standalone construct or in combination with other immunotherapeutic modalities, such as immune checkpoint inhibitors. Full article

Within STEM (Science, Technology, Engineering, and Mathematics) education, integrating real-world problem scenarios is paramount. Within interdisciplinary education, modeling is an approach to fostering student learning and skill development in a student-centered learning environment. This study focuses on an integrated physics and mathematics course in STEM education based on modeling for first-year engineering students. The main objectives of this study are to analyze students’ models, assess the effectiveness of the pedagogical approach, and evaluate the benefits of integrative education. This study uses a Model-Application Activity as a closure for the quadratic model and extends the models built to a two-dimensional motion situation. The core activity involves a real-world experiment where students attempt to roll a ball down a ramp into a cup. While most groups successfully constructed theoretical models, only a few hit the target, highlighting the complexities of applying theoretical knowledge to real-world scenarios. The study also emphasizes the seamless integration of physics and mathematics, enriching the learning experience and making the models more robust and versatile. Despite the promising results, the study identifies a gap between theoretical understanding and practical application, suggesting the need for more hands-on activities in the curriculum. In conclusion, this study underlines the value of integrating physics and mathematics through modeling and a student-centered approach, setting the stage for future research to enhance the effectiveness of STEM education. Full article