Bioguided Fractionation of Phyllanthus spp.: Unveiling Anticancer Potential through Metabolomic Correlation and ADMETox Insights.

Cancer remains a significant global health concern, with mortality rates steadily rising and prompting an urgent search for effective treatments. This study focuses on the medicinal properties of plants from the Phyllanthus genus, specifically Phyllanthus amarus and Phyllanthus niruri, which have shown promise in traditional medicine. Through bioguided fractionation using preparative high-performance liquid chromatography (HPLC), bioactive compounds were isolated and identified using ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-QTOF-MSE) and nuclear magnetic resonance (NMR) spectroscopy. Chemometric analyses such as principal component analysis (PCA) aided in understanding metabolite distribution. Biological assays demonstrated cytotoxic activities of specific fractions against cancer cell lines, notably the PhyN 4n fraction from P. niruri, which induced S-phase cell cycle arrest and apoptosis in HL60 cells. These findings underscore the anticancer potential of Phyllanthus species and lay the groundwork for future drug development efforts. The study's integration of advanced analytical techniques, chemometrics, and biological assays provides valuable insights for harnessing natural products in the fight against cancer.

Multi-scale modeling of 2D GaSe FETs with strained channels.

Electronic devices based on bidimensional materials (2DMs) are the subject of an intense experimental research, that demands a tantamount theoretical activity. The latter must be hold up by a varied set of tools able to rationalize, explain and predict the operation principles of the devices. However, in the broad context of multi-scale computational nanoelectronics, there is currently a lack of simulation tools connecting atomistic descriptions with semi-classical mesoscopic device-level simulations and able to properly explain the performance of many state-of-the-art devices. To contribute to filling this gap we present a multi-scale approach that combines fine-level material calculations with a semi-classical drift-diffusion transport model. Its use is exemplified by assessing 2DM field effect transistors with strained channels, showing excellent capabilities to capture the changes in the crystal structure and their impact into the device performance. Interestingly, we verify the capacity of strain in monolayer GaSe to enhance the conduction of one type of carrier, enabling the possibility to mimic the effect of chemical doping on 2D materials. These results illustrate the great potential of the proposed approach to bridge levels of abstraction rarely connected before and thus contribute to the theoretical modeling of state-of-the-art 2DM-based devices.

Effects of aerobic exercise training on metabolism of nitric oxide and endothelin-1 in lung parenchyma of rats with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and proliferative obstruction of pulmonary vessels, which promotes a progressive increase in pulmonary vascular resistance (PVR). The effect of exercise training on oxidative stress, metabolism, and markers of nitric oxide (NO) and endothelin-1 (ET-1) was analyzed in the lung tissue of rats with PAH induced by monocrotaline (MCT).Twenty-four Wistar rats were divided into four groups (5-7 animals): sedentary control (SC), sedentary MCT (SM), trained control (TC), and trained MCT (TM). The TC and TM groups participated in a treadmill training protocol (60% VO2 max) for 5 weeks, 3 weeks of which were performed after the injection of MCT (60 mg/kg i.p.) or saline. MCT administration promoted an increase in PVR and right ventricle hypertrophy, and reduction of right ventricle systolic function assessed by echocardiography. These changes were not improved by exercise training. The activity of NO synthase was reduced in the animals of the TC, TM, and SM groups. No significant differences were found in total nitrite concentration and expression of endothelial NO synthase. Moreover, the TM group showed strong staining for iNOS and nitrotyrosine, suggesting an increase in oxidative stress in these animals. In parallel, reduced expression of type B ET-1 receptors was noticed in the SM and TM groups in comparison to controls. In conclusion, the aerobic training protocol was unable to mitigate changes in the metabolism of NO and ET-1, probably because of the disease severity in these animals, especially in the TM group.

A straight choice: avoiding septal re-deviation using titanium plates. A 16 year retrospective patient follow-up evaluation.

BACKGROUND: To propose a new surgical technique for fixing the nasal septum to the midline, for long term prevention of nasal obstruction, in secondary and select cases of primary septoplasty. METHODOLOGY: Retrospective study, within hospital medical center. PATIENTS: Two hundred and twenty two patients who underwent septoplasty. Data collection occurred consecutively between March 1st of 2000 and May 1st 2016. Twenty six percent females and seventy four percent males. MAIN OUTCOME MEASURES: Patterns of septal deformity, materials used for titanium plates, surgical results, symptom improvement, and surgical complications were investigated. RESULTS: A total of 222 patients were included in this study. 163 patients (73%) had no previous nasal surgery. Fifty nine patients (27%) presented with a previous nasal surgery. Sixteen year follow up included more than 90% of patients and resulted in an overall 2.7% revision rate. CONCLUSIONS: The use of titanium plate for septoplasty has shown to be simple, safe, and easy to learn technique in both secondary and select cases of primary septoplasty. Most importantly the results indicate a long term prevention of the.

Effect of exercise while utilizing a device with an arm compression sleeve to reduce lymphedema.

BACKGROUND: Lymphedema is one complication of breast cancer treatment and there is no consensus that identified one single therapy in the treatment of lymphedema; therfore an association of methods is recommended and one of these is exercising. The aim of this study was to evaluate the utilization of exercising with a facilitating device along with an arm compression sleeve to reduce the size of lymphedematous arms. MATERIALS AND METHODS: Thirty women from a rehabilitation group with arm lymphedema resulting from the surgical, chemotherapeutic, and radiotherapeutic treatment of breast cancer were enrolled sequentially on arriving in the clinic. While sitting in an upright position and wearing an arm compression sleeve, patients were submitted to a one-hour session of active exercising consisting of four 12-minute stints with three-minute intervals to rest. The change in lymphedema was evaluated by water volumetry before and immediately after the session. The active exercising device is similar to the pedaling system of a bicycle. The paired t-test was employed for statistical analysis. An alpha error of 5% (p-value < 0.05) was considered acceptable. RESULTS: A statistically significant reduction (p-value < 0.004) was noted in the size of the arm. CONCLUSION: Active exercising using a facilitating device and under supervision may reduce the size of lymphedematous arms.

Reconfigurable frequency multipliers based on graphene field-effect transistors.

Run-time device-level reconfigurability has the potential to boost the performance and functionality of numerous circuits beyond the limits imposed by the integration density. The key ingredient for the implementation of reconfigurable electronics lies in ambipolarity, which is easily accessible in a substantial number of two-dimensional materials, either by contact engineering or architecture device-level design. In this work, we showcase graphene as an optimal solution to implement high-frequency reconfigurable electronics. We propose and analyze a split-gate graphene field-effect transistor, demonstrating its capability to perform as a dynamically tunable frequency multiplier. The study is based on a physically based numerical simulator validated and tested against experiments. The proposed architecture is evaluated in terms of its performance as a tunable frequency multiplier, able to switch between doubler, tripler or quadrupler operation modes. Different material and device parameters are analyzed, and their impact is assessed in terms of the reconfigurable graphene frequency multiplier performance.

CYP2D6 in the brain: genotype effects on resting brain perfusion.

The cytochrome P450 2D6 (CYP2D6) is a genetically polymorphic enzyme involved in the metabolism of several psychoactive drugs. Beside its expression in the liver, CYP2D6 is highly expressed in several regions of the brain, such as the hippocampus, thalamus, hypothalamus and the cortex, but its function in the brain is not well understood. The CYP2D6 enzyme may also have a physiological role due to its involvement in neurotransmitter biotransformation. In this study, CYP2D6 genotyping was performed in N=188 healthy individuals and compared with brain perfusion levels at rest, which may reflect an ongoing biological process regulating the reactivity of the individual to emotional stimuli and the detection of signals evoking fear. Relative to N=42 matched extensive metabolizers, N=14 poor metabolizers were associated with 15% higher perfusion levels in the thalamus (P=0.03 and 0.003). Effects were also present in the whole (N=188) sample divided into metabolizer groups, or finely graded into seven CYP2D6 activity levels. A weaker effect was observed in the right hippocampus (P=0.05). An exploratory analysis, extended to the whole brain, suggested the involvement of CYP2D6 in regions associated with alertness or serotonergic function. These findings support the hypothesis of a functional role of CYP2D6 in the brain.

Graphene BioFET sensors for SARS-CoV-2 detection: a multiscale simulation approach.

Biological Field-Effect Transistors (BioFETs) have already demonstrated enormous potential for detecting minute amounts of ions and molecules. The use of two-dimensional (2D) materials has been shown to boost their performance and to enable the design of new applications. This combination deserves special interest in the current pandemic caused by the SARS-CoV-2 virus which demands fast, reliable and cheap detection methods. However, in spite of the experimental advances, there is a lack of a comprehensive and in-depth computational approach to capture the mechanisms underlying the sensor behaviour. Here, we present a multiscale platform that combines detailed atomic models of the molecules with mesoscopic device-level simulations. The fine-level description exploited in this approach accounts for the charge distribution of the receptor, its reconfiguration when the target binds to it, and the consequences in terms of sensitivity on the transduction mechanism. The results encourage the further exploration of improved sensor designs and 2D materials combined with diverse receptors selected to achieve the desired specificity.

A DNA Extraction Method for Insects From Sticky Traps: Targeting a Low Abundance Pest, Phthorimaea absoluta (Lepidoptera: Gelechiidae), in Mixed Species Communities.

Invasive insects can cause catastrophic damage to ecosystems and cost billions of dollars each year due to management expenses and lost revenue. Rapid detection is an important step to prevent invasive insects from spreading, but improvements in detection capabilities are needed for bulk collections like those from sticky traps. Here we present a bulk DNA extraction method designed for the detection of Phthorimaea absoluta Meyrick (Lepidoptera: Gelechiidae), an invasive moth that can decimate tomato crops. We test the extraction method for insect specimens on sticky traps, subjected to different temperature and humidity conditions, and among mock insect communities left in the field for up to 21 d. We find that the extraction method yielded high success (>92%) in recovering target DNA across field and lab trials, without a decline in recovery after three weeks, across all treatments. These results may have a large impact on tomato growing regions where P. absoluta is in the early stages of invasion or not yet present. The extraction method can also be used to improve detection capabilities for other bulk insect collections, especially those using sticky traps, to the benefit of pest surveys and biodiversity studies.

Effect of medium/ω-6 long chain triglyceride-based emulsion on leucocyte death and inflammatory gene expression.

Lipid emulsion (LE) containing medium/ω-6 long chain triglyceride-based emulsion (MCT/ω-6 LCT LE) has been recommended in the place of ω-6 LCT-based emulsion to prevent impairment of immune function. The impact of MCT/ω-6 LCT LE on lymphocyte and neutrophil death and expression of genes related to inflammation was investigated. Seven volunteers were recruited and infusion of MCT/ω-6 LCT LE was performed for 6 h. Four volunteers received saline and no change was found. Blood samples were collected before, immediately afterwards and 18 h after LE infusion. Lymphocytes and neutrophils were studied immediately after isolation and after 24 and 48 h in culture. The following determinations were carried out: plasma-free fatty acids, triacylglycerol and cholesterol concentrations, plasma fatty acid composition, neutral lipid accumulation in lymphocytes and neutrophils, signs of lymphocyte and neutrophil death and lymphocyte expression of genes related to inflammation. MCT/ω-6 LCT LE induced lymphocyte and neutrophil death. The mechanism for MCT/ω-6 LCT LE-dependent induction of leucocyte death may involve changes in neutral lipid content and modulation of expression of genes related to cell death, proteolysis, cell signalling, inflammatory response, oxidative stress and transcription.

Multi-scale analysis of radio-frequency performance of 2D-material based field-effect transistors.

Two-dimensional materials (2DMs) are a promising alternative to complement and upgrade high-frequency electronics. However, in order to boost their adoption, the availability of numerical tools and physically-based models able to support the experimental activities and to provide them with useful guidelines becomes essential. In this context, we propose a theoretical approach that combines numerical simulations and small-signal modeling to analyze 2DM-based FETs for radio-frequency applications. This multi-scale scheme takes into account non-idealities, such as interface traps, carrier velocity saturation, or short channel effects, by means of self-consistent physics-based numerical calculations that later feed the circuit level via a small-signal model based on the dynamic intrinsic capacitances of the device. At the circuit stage, the possibilities range from the evaluation of the performance of a single device to the design of complex circuits combining multiple transistors. In this work, we validate our scheme against experimental results and exemplify its use and capability assessing the impact of the channel scaling on the performance of MoS2-based FETs targeting RF applications.

A Crystallographic Snapshot of SARS-CoV-2 Main Protease Maturation Process.

SARS-CoV-2 is the causative agent of COVID-19. The dimeric form of the viral Mpro is responsible for the cleavage of the viral polyprotein in 11 sites, including its own N and C-terminus. The lack of structural information for intermediary forms of Mpro is a setback for the understanding its self-maturation process. Herein, we used X-ray crystallography combined with biochemical data to characterize multiple forms of SARS-CoV-2 Mpro. For the immature form, we show that extra N-terminal residues caused conformational changes in the positioning of domain-three over the active site, hampering the dimerization and diminishing its activity. We propose that this form preludes the cis and trans-cleavage of N-terminal residues. Using fragment screening, we probe new cavities in this form which can be used to guide therapeutic development. Furthermore, we characterized a serine site-directed mutant of the Mpro bound to its endogenous N and C-terminal residues during dimeric association stage of the maturation process. We suggest this form is a transitional state during the C-terminal trans-cleavage. This data sheds light in the structural modifications of the SARS-CoV-2 main protease during its self-maturation process.

Assessing Soybean Genotypes for Resistance to Helicoverpa armigera (Lepidoptera: Noctuidae).

Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) is an important pest capable of colonizing several species of cultivated plants, including soybean [Glycine max (L.) Merrill]. The primary management strategy for this insect is chemical control and adoption of Bt plants. However, alternative environmentally friendly strategies should be investigated and adopted as available for sustainable management of this insect pest. One potential underutilized method for insect control is plant resistance. The objective of this study was to categorize resistance (antixenosis and antibiosis) of 22 soybean genotypes on H. armigera in a laboratory setting. A preliminary experiment was conducted using soybean leaves and pods to determine the most promising genotypes for resistance. For each selected genotype, we collected biological parameters, leaf intake, and performed confinement tests. The genotypes PI 227687, PI 274453, PI 274454, PI 229358, PI 171451, 'IAC 17', and 'IAC 19' expressed resistance against H. armigera. Each genotype lowered larval survivorship. The genotypes PI 229358, PI 227687, PI 274453, and PI 274454 expressed resistance by prolonging larval development and reducing fifth-instar larvae weight. 'IAC 19' reduced leaf consumption and lowered the weight of fifth-instar larvae. Antixenosis was found in genotypes PI 227687, PI 274454, and 'IAC 19'. These genotypes might be used in breeding programs focusing on soybean resistance to lepidopterans.

Subjective response to antipsychotics in bipolar disorders: A review of a neglected area.

BACKGROUND: The term "subjective response to antipsychotic" (SRA) refers to changes in the subjective state experienced due to antipsychotic (AP) exposition that is independent of the therapeutic or physical side effects of these drugs. This dimension of analysis has been extensively explored in schizophrenic disorders, finding that negative SRA is an early and independent predictor of compliance as well as a successful pathway to construct current theoretical frameworks of these disorders. There is an increasing use of AP in bipolar disorders' treatment (BD) but no reviews on the topic have been published to date in this population. The aim of this work is to review published data of SRA in BD patients and to discuss their clinical and theoretical implications. METHODS: An extensive search in online databases was performed. Reports were reviewed and included if they described SRA in BD or included instruments aimed to assess it. Reports of cognitive, sexual, motor autonomic side effects were excluded. Findings were summarized in a narrative fashion. RESULTS: Nine reports fulfilled the inclusion criteria and were included in the revision, reporting data from 1282 BD patients. Among these, three were prospective studies and three explored relations between SRA and treatment compliance. CONCLUSIONS: There is an asymmetry between the increase in the use of antipsychotics in BD and the lack of data regarding the SRA. Phenomenologically, SRA in BD is similar to that found in schizophrenic subjects. Some of these symptoms may be misdiagnosed as depressive symptoms. The existing data show that SRA has a strong correlation with treatment compliance as well as a promising way to develop theoretical paradigms for these disorders.

Resistive Switching and Charge Transport in Laser-Fabricated Graphene Oxide Memristors: A Time Series and Quantum Point Contact Modeling Approach.

This work investigates the sources of resistive switching (RS) in recently reported laser-fabricated graphene oxide memristors by means of two numerical analysis tools linked to the Time Series Statistical Analysis and the use of the Quantum Point Contact Conduction model. The application of both numerical procedures points to the existence of a filament connecting the electrodes that may be interrupted at a precise point within the conductive path, resulting in resistive switching phenomena. These results support the existing model attributing the memristance of laser-fabricated graphene oxide memristors to the modification of a conductive path stoichiometry inside the graphene oxide.

Assessment of three electrolyte-molecule electrostatic interaction models for 2D material based BioFETs.

BioFETs based on two-dimensional materials (2DMs) offer a unique opportunity to enhance, at a low cost, the sensitivity of current biosensors enabling the design of compact devices compatible with standard CMOS technology. The unique combination of large exposed surface areas and minimal thicknesses of 2DMs is an outstanding feature for these devices, and the assessment of their behaviour requires combined experimental and theoretical efforts. In this work we present a 2D-material based BioFET simulator including complex electrolyte reactions and analysing different models for the electrolyte-molecule interaction. These models describe how the molecular charge is screened by the electrolyte ions when their distributions are modified. The electrolyte simulation is validated against experimental results as well as against the analytical predictions of the Debye-Hückel approximation. The role of the electrolyte charge screening as well as the impact of the interaction model on the device responsivity are analysed in detail. The results are discussed in order to conclude about the consequences of employing different interaction approximations for the simulation of BioFETs and more generally on the correct modelling of biomolecule-device interaction in BioFETs.

Physiological action of oestradiol on the acrosome reaction in human spermatozoa.

The acrosome is a secretory vesicle located in the sperm head. The acrosome reaction consists in the fusion of the sperm plasma membrane with the external acrosomal membrane. It has been observed that this reaction does not take place in spermatozoa incubated in cervical mucus, hydrogel that contains high concentrations of oestradiol in the peri-ovulatory period. The objective of the present study was to analyse the influence of oestradiol on the acrosome reaction in human spermatozoa to evaluate the possible inhibitory effect of this hormone. Spermatozoa were incubated in progesterone (10.1 nmol l(-1)); oestradiol plus progesterone (oestradiol at 840 pmol l(-1) and progesterone at 10.1 nmol l(-1)), oestradiol (840 pmol l(-1)) and control (without steroidal hormones) for 30 min, 60 min, 240 min and 24 h. The acrosome reaction was evaluated by stain with Hoechst 33258 and fluorescein isothiocyanate-conjugated Pisum sativum agglutinin lectin. Progesterone-incubated spermatozoa showed the highest percentage of acrosome reaction (P < 0.05). Spermatozoa incubated with oestradiol and oestradiol plus progesterone showed the lowest percentage of acrosome reaction. The present study demonstrates the inhibitory role of oestradiol on the acrosome reaction, stimulated by progesterone in human spermatozoa under physiological conditions.

Perfil de consulta ambulatoria otorrinolaringológica en pandemia por COVID-19 / Profile of patients in otorhinolaryngological consultation in a COVID-19 pandemic

Introducción: La patología otorrinolaringológica (ORL) presenta alta incidencia en atención primaria, alcanzando hasta 49% de las consultas, sin embargo, la pandemia por SARS-CoV-2 repercutió de manera transversal en los servicios sanitarios, pudiendo haber influido en el perfil de consulta, por lo que se requiere un análisis para la elaboración de estrategias que permitan asegurar la atención sanitaria ante eventos de esta magnitud. Objetivo: Analizar el perfil de consulta libre por patología ORL ambulatoria en un centro médico privado en La Serena durante los años 2019 y 2020. Material y Método: Estudio analítico de corte transversal sobre consultas ambulatorias durante los años 2019 y 2020 realizadas en un centro privado de atención abierta en La Serena. Se estimaron frecuencias en números absolutos y proporciones, estimación de promedios y medianas. Resultados: Durante 2019 hubo un total de 11.932 consultas y en 2020 hubo 9.576. Se observó un predominio de sexo femenino en las consultas de 51% en ambos años. La mediana en 2019 fue de 35 años y en 2020 de 39 años. En 2020 las patologías con mayor consulta fueron nariz (44%), oído (37%) y faringolaringe (14%). Existió un aumento significativo en la consulta por patología cocleovestibular durante 2020. Conclusión: En 2020 hubo una disminución del 19,7% de las consultas dado, probablemente, a las restricciones de movilidad y aforos. Existió un aumento significativo en la proporción de consultas por patologías cocleovestibulares, como vértigo periférico, hipoacusia súbita y tinnitus, atribuido probablemente al estrés emocional generado por la pandemia.

Introduction: Otolaryngological (ENT) pathology presents high incidence in primary care reaching up to 49% of morbidity consultations, however, the pandemic by SARS-CoV-2 had a transversal impact on health services, and may have influenced the consultation profile, so an analysis is required for the development of strategies to ensure health care in the face of events of this magnitude. Aim: To analyze the profile of spontaneous consultation for outpatient ENT pathology in a medical center in La Serena city during 2019 and 2020. Material and Methods: Cross-sectional analytical study of outpatient consultations during the years 2019 and 2020 performed in a private open care center in the commune of La Serena. Frequencies were estimated in absolute numbers and proportions; averages and medians were estimated. Results: During 2019 there were a total of 11,932 consultations and in 2020 there were 9,576. There was a predominance of female sex in the consultations of 51%. The median in 2019 was 35 years and in 2020 it was 39 years. In 2020, the pathologies with the highest number of consultations were nose (44%), ear (37%) and laryngopharynx (14%). There was an increase in consultation for cochleovestibular pathology during 2020. Conclusion: In 2020 there was a 19.7% of consultation decrease probably due to mobility and capacity restrictions. There was a significant increase in the proportion of consultations for cochleovestibular pathologies such as peripheral vertigo, hearing loss and tinnitus, probably attributed to the emotional stress generated by the pandemic.