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Abstract Scientists and researchers have been searching for drugs targeting the main protease (Mpro) of SARS-CoV-2, which is crucial for virus replication. This study employed a virtual screening based on molecular docking to identify benzoylguanidines from an in-house chemical library that can inhibit Mpro on the active site and three allosteric sites. Molecular docking was performed on the LaSMMed Chemical Library using 88 benzoylguanidine compounds. Based on their RMSD values and conserved pose, three potential inhibitors (BZG1, BZG2, and BZG3) were selected. These results indicate that BZG1 and BZG3 may bind to the active site, while BZG2 may bind to allosteric sites. Molecular dynamics data suggest that BZG2 selectively targets allosteric site 3. In vitro tests were performed to measure the proteolytic activity of rMpro. The tests showed that BZG2 has uncompetitive inhibitory activity, with an IC50 value of 77 µM. These findings suggest that benzoylguanidines possess potential as Mpro inhibitors and pave the way towards combating SARS-Cov-2 effectively.

Abstract Background Lung cancer is the leading cause of cancer-related death in the world. In contrast to many other cancers, a direct connection to modifiable lifestyle risk in the form of tobacco smoke has long been established. More than 50% of all smoking-related lung cancers occur in former smokers, 40% of which occur more than 15 years after smoking cessation. Despite extensive research, the molecular processes for persistent lung cancer risk remain unclear. We thus set out to examine whether risk stratification in the clinic and in the general population can be improved upon by the addition of genetic data and to explore the mechanisms of the persisting risk in former smokers. Methods We analysed transcriptomic data from accessible airway tissues of 487 subjects, including healthy volunteers and clinic patients of different smoking statuses. We developed a computational model to assess smoking-associated gene expression changes and their reversibility after smoking is stopped, comparing healthy subjects to clinic patients with and without lung cancer. Results We find persistent smoking-associated immune alterations to be a hallmark of the clinic patients. Integrating previous GWAS data using a transcriptional network approach, we demonstrate that the same immune- and interferon-related pathways are strongly enriched for genes linked to known genetic risk factors, demonstrating a causal relationship between immune alteration and lung cancer risk. Finally, we used accessible airway transcriptomic data to derive a non-invasive lung cancer risk classifier. Conclusions Our results provide initial evidence for germline-mediated personalized smoke injury response and risk in the general population, with potential implications for managing long-term lung cancer incidence and mortality.

Abstract Structures in nature are often multi‐material, and their structures have a fine balance between segregation and aggregation (mixed, but not scrambled) that provides functionality. Chaotic fabrication, a technology that exploits the ability of chaotic advection to create predictable and reproducible multilayered structures, excels at producing materials where this balance can be achieved and finely tuned. This method is based on the use of chaotic mixing systems, which can produce constructs with highly organized internal micro‐architecture in a simple and cost‐effective way. This manuscript provides a perspective on how chaotic printing can be a great enabler in the manufacture of advanced materials, including living tissues. Chaotic printing may overcome many of the critical hurdles that are currently faced in manufacturing and biofabrication (e.g., creating a wide array of interfaces, reaching high resolutions rapidly and at low cost, and producing densely vascularized tissues). The manuscript introduces the technology, explains how the idea originated, presents a timeline that provides a recapitulation of the milestones achieved so far, describes the main characteristics, advantages, limitations, and challenges of the technology, and concludes with future perspectives on the evolution and use of this versatile method.

Background: Pre-Hispanic agroecosystems in Mexico City have changed the kind of crops, management practices, tools, and inputs, seriously impacting their biocultural value and sustainability. Previous studies have demonstrated these changes' economic, cultural, and political consequences. However, their effects on biodiversity have not been considered. The present study characterized the management carried out in three agroecosystems in the southeastern area of Mexico City and its possible relationship with agrobiodiversity. Objective: To evaluate the contribution of diversity, abundance, and composition of weeds as components of the sustainability of agroecosystems in Milpa Alta, Tláhuac, and Xochimilco municipalities. Methodology: 179 interviews were conducted with campesinos. Weeds sampling in 30 plots, recording the abundance and frequency of each species. These data were used to estimate different ecological parameters. Information on management practices was transformed to develop an “agroecosystem sustainability index.” A multivariate analysis was applied to compare weed attributes between agroecosystems and spaces and to detect possible relationships between the index and ecological parameters. Results: 156 species were recorded. The slope had the highest diversity, and ciénega had the lowest. More than half of the weeds were native, and the slope exhibited the highest number. The Importance Value indicated no dominant species on the slope, opposite to chinampa and ciénega. Species composition also differed between the three agroecosystems. Chinampa was impacted the most, whereas the slope was least affected. Implications: The displacement of traditional crops and agricultural practices and the incorporation of technological practices have modified the ecological attributes of weeds, like their abundance and composition. Conclusion: Starting from the argument that ecological attributes of weeds can be used as an indicator of sustainability, the slope resulted in the agroecosystem being most sustainable and should be used as a model to recover the agrobiodiversity of ciénegas and chinampas.

Este estudio examina la motivación de los 197 tiroteos masivos habidos en el periodo de 1966 a 2023 a partir del análisis de cuatro variables extraídas de The Violence Project: psicosis, problemas laborales, misoginia y búsqueda de fama. Los resultados mostraron que un 48,2 % de los casos se encuentran motivados por una o más de las variables seleccionadas. La psicosis fue la motivación más prevalente, aunque está presente en menos de un tercio de los casos. El segundo motivo más frecuente fueron los problemas laborales. La búsqueda de fama fue el tercer factor motivacional en cuanto a prevalencia y el único que ha experimentado un aumento significativo en la última década analizada. Ello podría estar asociado a la mayor visibilidad de estos sucesos luctuosos, debido al auge de Internet. La misoginia está presente en un 4,1 % de los casos. Por lo general se encuentran evidencias del predominio de un único motivo en los tiroteos masivos incluidos en el estudio. Sin embargo, el análisis de factores personales y ambientales, tanto del presente como de la historia de los perpetradores, sugiere la conveniencia de profundizar en estos hechos y alejarse de análisis simplistas a la hora de indagar sobre las razones que llevan a estos asesinos a cometer estas masacres.

This study aimed to investigate the relationship between measures of body condition score (BCS) during the transition period and milk yield, reproductive performance, and occurrence of metritis and ketosis in cows. A total of 5026 lactations of 2424 Holstein cows from a single dairy farm were assessed for BCS (5-point scale; 0.25-point increments) 15 days precalving, at calving, and first service. ΔBCS were classed as 0.75 from 15 days precalving to parturition and from calving to first artificial insemination. BCS classes at parturition were 3.75. 305-d milk yield was the highest in cows with BCS change (ΔBCS) 0.75. The overall pregnancy rate was least [281/836 (33.6%); p0.75 units of BCS, and greatest for cows that lost 0.75 BCS between calving and the first artificial insemination (AI) [175/836 (20.9 %); p

El presente artículo analiza el ejercicio del fotoperiodismo en España y, en concreto, se centra en el estudio del archivo gráfico de la Agencia efe (1939-) y su producción propia, desarrollada dentro y fuera de sus fronteras. Se ha tenido en consideración, como parte de este proceso, la adquisición de fondos y, del mismo modo, también se ha tenido presente la creación, en el año 2000, del archivo gráfico digital: La Fototeca, herencia de la clasificación temática del analógico y del nomenclátor y, en este proceso, se ha aportado como resultado de las conclusiones –a través de fuentes primarias y la observación directa- el sistema de documentación empleado, poniendo énfasis en la clasificación temática utilizada.

Although sandy islands in arid environments are vital protection sites for endemic species, they face constant natural and anthropogenic hazards, such as storm surge impacts and the occasional presence of off-road vehicles. Monitoring the sedimentary dune-beach displacement and balance is essential because sediment transportation usually does not depend on external sources, such as rivers. The latest generation of geomatic applications may be relevant to understanding coastal vulnerability due to their ability to acquire and process spatial data at unprecedented scales. The objective of this study was to analyze the sedimentary dynamics of a distinctive dune corridor on Altamura Island in the Gulf of California, Mexico. We compared three ultra-high spatial resolution digital surface models (DSMs) with geomorphic change detection (DoD), covering the 1150 m coastal stretch. We used light detection and ranging (LiDAR) data and analyzed changes in the coastline with the semi-automatic CoastSat tool. Although the orthomosaics and the DSM collected in April, June, and October 2021 show different conditions in sediment distribution along the beach-dune interface, depending on the direction and intensity of the wind, the two DoDs showed a constant sediment distribution balance of ~13 M m3 between April and June and June and October. LiDAR data along the 40-km length of the sandy island indicate that the entire island could present a similar sedimentation pattern between the dune and beach interface. The CoastSat data indicate a constant accretion of 125 m in the beach-ocean interface between 2015 and 2022. This study demonstrates that the sediment balance between the dune and the beach on arid sandy islands is vital for conserving their shoreline and all associated coastal ecosystems.

Aim: The present study aims to analyze the impact on cognitive recovery of an interdisciplinary treatment for acute and severe psychiatric patients. Methods: The present research is a naturalistic observational study of 130 adults (mean age of 47.68 years, 68% women). Clinical severity was assessed using Brief Psychiatry Rating Scale (BPRS), Montgomery-Asberg Depression Rating Scale (MADRS), and Hamilton Anxiety Rating Scale (HARS). Functional performance was evaluated using the Functioning Assessment Short Test (FAST), and cognitive impairment by applying the Montreal Cognitive Assessment (MoCA). Patients were clustered into four diagnostic groups (non-affective psychosis, bipolar, depressive, and personality disorders) and had individualized psychopharmacological treatment. They receive a transdiagnostic group program including several interventions that have shown evidence of beneficial effects over the different cognitive domains impaired in mental illness (attention, speed of processing, memory, working memory, reasoning, and problem-solving), as well as social cognition domains (emotion processing and social skills), in combination with psychoeducation and some strategies oriented to achieve healthy lifestyle routines (balanced diet, physical exercise, sleep hygiene, and smoking and alcohol cessation). Results: All clinical scales scores were improved after the end of treatment compared with those achieved at admission (BPRS, MADRS, and HARS scores below the cut-off point for establishing a case diagnosis). MoCA scores improved after the end of treatment concerning admission, both in the total score and in the differentiated cognitive domains, excluding orientation, which remained unchanged in the whole of the sample studied. No statistical significance was found in any comparisons between different diagnostic groups. No correlation between MoCA scores and BPRS, MADRS, or HARS scores at admission or discharge was found. Conclusions: These results show that the interdisciplinary therapeutic intervention can be effective for recovering cognitive impairment associated with mental disorders, irrespective of the diagnosis.

Considering a circular economy perspective, this study evaluates the possible effect of targeted short-term supplementation with Withania somnifera L. (WS; Ashwagandha) on ram’s seminal quality, socio-sexual behaviors, and blood constituents. Black Belly rams (n = 20) received a basal diet comprising feed-leftovers from dairy cows in the north-arid Mexico (i.e., Comarca Lagunera CL). The experimental units, with proven libido and fertility, were homogeneous in terms of age (3.41 ± 0.21 yr.), live weight (LW; 53.8 ± 3.3 kg), body condition (BC; 2.96 ± 0.01 units), initial sperm concentration (2387 ± 804 × 106), and viability (23.9 ± 15.6%). Rams were randomly assigned during the transition reproductive period (i.e., May to Jun; 25° NL) to three treatment groups: non-supplemented control group (CONT; n = 6), low WS-supplemented (LWS; i.e., 100 mg kg LW−1 d−1 × 40 d; n = 7), and high-WS-supplemented (HWS; i.e., 200 mg kg LW−1 d−1 × 40 d; n = 7). The basal leftover diet was offered twice daily (0700 and 1600 h); the experimental period (EP) lasted 47 d. No differences (p > 0.05) among treatments occurred regarding LW and BCS at the onset of the EP. Whereas the greater scrotal circumference (SCRC, cm) arose in the LWS and CONT rams, an increased ejaculated volume (VOLEJA, mL) occurred in the WS-rams. A total of 5/9 (i.e., 55%) appetitive and 3/3 (i.e., 100%) consummatory sexual behaviors favored (p < 0.05) the WS-rams, particularly the HWS rams, towards the final EP. The same was true (p < 0.05) regarding the hemogram variables white blood cell count (×109 cells L−1), hemoglobin concentration (g dL−1), and medium corpuscular volume (fL). This study, based on a rethink–reuse–reduce enquiry approach, enabled connectedness between two noteworthy animal systems in the CL: dairy cows and meat sheep schemes. Certainly, the use of dairy cow feed-leftovers aligned with the short-term supplementation with WS promoted enhanced testicular function, augmented seminal volume, and an increased sexual behavior in Black Belly rams in northern Mexico. Finally, while our research outcomes should enhance not only the resilience and sustainability of sheep production and the well-being of sheep-producers and their families, it may also embrace clinical translational applications.

Background: A circadian rhythm of myocardial infarction has been described but there is little data on its relation with seasons and months. Methods: From June 2013 to June 2018, we analyzed the alerts for acute ST-segment elevation myocardial infarction (STEMI) in a Spanish region with 6.64 million inhabitants, universal health coverage, and an organized STEMI reperfusion network. We selected those patients which an identifiable culprit plaque. Results: We recruited 6765 cases of STEMI due to type I acute myocardial infarction (type-I AMI), with mean age of 63.2 years (range 17–101, standard deviation [SD] 13.7), 5238 were males (77.4%) and 2801 (41.9%) were 65 years or older. The hourly distribution followed a fixed pattern in all months, with most of the events occurring between 6:00 AM and 4:00 PM, a peak at approximately 01:00 PM and a valley between 10:00 PM and 06:00 AM. No significant difference was found when comparing the mean time to first medical contact between July (the month with more daylight hours) and December (the month with shortest days). No significant differences were found between male and female patients, or between patients aged 65 years or older and younger patients. There was a close correlation between the number of events per month and the number of events occurring during the day (6 AM to 6 PM, r = 0.988, p = 0.001) and during the night (6 PM to 6 AM, r = 0.944, p < 0.001), with different slopes of the regression lines (t-test, p < 0.001), so that the difference between day-night occurrences increased with the total incidence. Conclusions: There is a circadian pattern in the presentation of STEMI that is not influenced by sex and age. The different incidence of STEMI at different times of the year does not affect the circadian pattern in terms of the shape of the curve or the mean time of presentation, although diurnal events increase more than nocturnal events, suggesting that triggers are most likely to act during vulnerable periods as determined by a circadian-based rhythm.

The Sn-doping effects on the electrical conduction and optical properties of GaAs(631)A epilayers grown by molecular beam epitaxy were investigated. We found that the conduction type conversion, frequently observed in the doping of layers grown on high-index substrates, is avoided when tin-doping is implemented. The maximum free-carrier concentration (n) obtained in GaAs(631):Sn was 2 × 1019 cm−3, an order of magnitude higher than previously reported for GaAs(631):Si, and within the same order of magnitude for the growth of GaAs(100):Si. The electron mobility was suitable for many optoelectronic applications. Raman spectroscopy showed low lattice disorder in (631) oriented samples, compared with singular (100) samples. The photoluminescence characterization of the samples revealed the blueshift of the optical transitions close to E0 associated with the Moss–Burstein effect for Sn doping. Photoreflectance spectroscopy was used to study the doping properties at the critical points E1 and E1 + Δ1, where the major affectation with n was perceived in the broadening parameter Γ. [ABSTRACT FROM AUTHOR]