The vibration response of soil is a key property in the field of agricultural soil tillage. Vibration components of tillage machinery are generally used to reduce tillage resistance and improve work efficiency, the pressure variation under low-frequency vibration will affect the fragmentation and dispersion of farmland soil. However, the gradient of pressure variation, frequency domain response, and effective transmission range are unclear. A new method based on DEM (Discrete Element Method) is presented to study the vibration response and pressure transmission under low-frequency vibration. Bench test results showed that peak pressure positively correlates with the vibration frequency and attenuates rapidly at the vibration distance of 100 to 250 mm. The results data were also selected to determine the simulation model parameters. Amplitude, vibration frequency, and soil depth were used as test factors in single-factor simulation tests, and their effects on the peak pressure, frequency domain response, and effective transmission distance were analyzed. The results showed a positive relationship between the peak pressure and the test factors. The peak pressure increases with a maximum gradient of 19.02 kPa/mm at a vibration distance of 50 mm. The amplitude, vibration frequency, and soil depth positively correlate with the dominant frequency amplitude. The main frequency is independent of amplitude and soil depth. At the vibration distance of 250 mm, the dominant frequency is approximately twice the vibration frequency at 7–11 Hz and approximately equal to the vibration frequency at 13–15 Hz. Multiple exponential functions were used to fit the peak pressure attenuation function, obtaining an effective transmission distance range of 347.15 to 550.37 mm for the 5kPa cut-off pressure. For a soil depth of 300 mm, the vertical shear wave diffusion angle is greater than the horizontal shear wave diffusion angle. The study clarifies the vibration response of soil under low-frequency vibration, which helps to design vibration type soil-engaging components of tillage machinery and match vibration parameters for energy saving and resistance reduction in soil tillage.

Background: Spinal pain is highly prevalent and in Spain it produces a very high economic cost and the scientific evidence supporting treatments shows low to moderate evidence for exercise. Therefore, the aim of this study was to assess the effectiveness of a therapeutic group exercise protocol in reducing pain intensity and disability in patients with spinal pain in primary health care setting. Methods: A total sample of 149 patients who suffered from chronic non-specific spinal pain. Patients received a therapeutic exercise protocol, including exercises of auto-mobilization of the neck and lumbar regions, as well as core stabilization exercises. Pain intensity and disability were evaluated before and after the therapeutic exercise protocol. Results: Statistically significant differences (P<0.05) were shown for pain intensity and disability of patients with neck and low back pain with an effect size from moderate to large. Conclusions: A therapeutic exercise protocol may provide beneficial effects on disability and pain intensity in patients with chronic non-specific spinal pain, including neck and low back pain conditions. Clinicians should consider the use of self-administered exercise protocols, demonstrate great effectiveness, and be less costly.

The increase and diversity of low-cost Air Quality (AQ) sensors, as well as their flexibility and low power consumption, offers us the opportunity to integrate them into a broad AQ wireless sensor networks with the aim of enabling real-time monitoring and higher spatial sampling density of pollution in all parts of the cities. Considering that the vast majority of the population lives in these cities and the increase in respiratory/allergic problems in a large part of the population, it is of great interest to offer services and applications to improve their quality of life. In the ECO4RUPA project we focus on this kind of service, proposing an inclusive and intelligent routing ecosystem carried out by using a network of low-cost AQ sensors with the support of 5G communications along with official AQ monitoring stations, assisted with artificial intelligence to improve the AQ monitoring data and by spatial interpolation techniques to enhance its spatial resolution. The goal of this service is to calculate healthy walking and/or cycling routes according to the particular citizen’s profile and needs. We provide and analyse the results of the proposed route planner under different scenarios (different time tables, congestion road traffic and routes) and different user’s profiles, with special interest on citizens with asthma and pregnant women, since both require special needs. In summary, our approach can lead to an approximately average reduction in pollution exposure of 17.82%, while experiencing an approximately average increase in distance travelled of 9.8 %.

Chondrosarcoma, represents approximately 0.1% of all neoplasms of the head and neck, being considered a rare disease, but with a relatively good prognosis. The 5-year overall survival (OS) rate is estimated at 70-80%, being considered a disease with a low growth rate. About 13% of all cases of chondrosarcoma, are located in the region of the head and neck. We present the case of a young patient treated multimodally, lost from the oncological records less than two years after the diagnosis, without evidence of disease progression. The early loss from the oncological follow-up programs of patients with a lower risk of early repalpse, without evidence of a recurrence or metastasis could be the consequence of a major complication among which we could assume an aspiration pneumonia secondary to a dysphagia, associated with an aggressive multidisciplinary treatment. Large tumor size and positive resection margins (R1 resection) are risk factors that support an intensive adjuvant approach in order to reduce the risk of recurrence, but the low grade of tumor, associating a lower risk of recurrence as well as the adverse events (AE) of adjuvant radiotherapy and chemotherapy justifies a more reserved therapeutic approach. Taking into account the longer life expectancy of these patients, it is recommended to use a more conformal irradiation technique in order to reduce doses to radiosensitive structures as well as to omit elective neck irradiation, taking into account the lower risk of lymph node involvement. The lack of guidelines that include very rare tumors including low grade chondrosarcoma of head and neck make a unified approach difficult, but the data presented even in case reports could contribute to choosing the regimen that offers the best therapeutic ratio.

With the rapid development of electronic and communication technology in military radar, the demand for microwave absorbing materials in low-frequency with thin layer is growing increasingly. In this study, flexible Co3O4/CC (carbon cloth) composites derives from Co-MOFs (metal-organic frameworks)/CC are prepared by hydrothermal and thermal treatment processes. The flexible precursors of Co-MOFs/CC are calcined with different calcination temperatures, which the material structure, dielectric properties and microwave absorption performance are changed. With the increase of calcination temperature, the minimum reflection loss of the corresponding Co3O4/CC composites gradually moves to the lower frequency with thinner thickness. In addition, the Co3O4/CC composites with 25 wt% filler loading ratio exhibit the minimum reflection loss (RL) of -46.59 dB at 6.24 GHz with 4.2 mm thickness. When the thickness is 3.70 mm, the effective absorption bandwidth is 3.04 GHz from 5.84 to 8.88 GHz. This study not only proves that the composite Co3O4/CC is a kind of outstanding microwave absorbing material with better flexibility, but also provides a useful inspiration for the low frequency and broadband microwave absorbing material.

Graphene quality for use in biosensors was assessed in fabricated chips by a set of methods that includes atomic force microscopy (AFM), Raman spectroscopy, and low-frequency noise. It is shown that local areas of residues on the graphene surface, which arisen due to the interaction of graphene with a photoresist at the initial stage of chips development, leads to a spread of chips resistance (R) within 1-10 kΩ and to an increase in the root mean square (RMS) roughness up to 10 times that can significantly impair reproducibility of graphene parameters in biosensors chips. It was observed that the control of the photoresist residues after photolithography (PLG) by AFM and subsequent additional cleaning allow reducing the spread of R values in chips to 1–1.6 kΩ and obtaining RMS roughness similar to the roughness in pristine graphene before PLG. Monitoring of the spectral density of low-frequency voltage fluctuation (SU), which provides integral information about the defect system and quality of the material, makes it possible to identify chips with low graphene quality and with inhomogeneously distributed compressive stresses areas by the type of frequency dependence SU (f).

Healthcare systems are mindful of the importance of proper diet and nutrition in reducing the risk of various chronic diseases resulting in hospitalizations. In this regard, they are focusing on promoting the intake of foods comprising various diets with health benefits, such as the ketogenic diet. In this meta-analysis, a total of 20 research studies on the effect of the ketogenic diet on the immune system were analyzed. The research studies were obtained from three databases: Google Scholar, PubMed, and Science Direct. From the meta-analysis, the odd ratio of a similar outcome of an improvement in the strength of immunity between the intervention and control group was 0.76. On the other hand, the p-value for the studies was 0.09, with 15 out of the 20 being considered statistically significant. The heterogeneity between the studies was I2 = 15%, signifying a low variability in the findings that is not by chance. The Ketogenic diet indeed has positive effects on immunity. Nonetheless, it can also result in negative effects that may harm human health.

The current revolution in communication and information technology is facilitating the Internet of Things (IoT) infrastructure. Wireless Sensor Networks (WSN) are a broad category of IoT applications. However, power management in WSN poses a significant challenge when the WSN is required to operate for a long duration without the presence of a consistent power source. In this paper, we develop a batteryless, ultra-low-power Wireless Sensor Transmission Unit (WSTx) depending on the solar-energy harvester and LoRa technology. We investigate the feasibility of harvesting ambient indoor light using polycrystalline photovoltaic (PV) cells with a maximum power of 1.4mW. The study provides comprehensive power management design details and a description of the anticipated challenges. The power consumption of the developed WSTx was 21.09µW during the sleep mode and 11.1mW during the operation mode. The harvesting system can harvest energy up to 1.2mW per second, where the harvested energy can power the WSTx for six hours with a maximum power efficiency of 85.714%.

The Brazilian livestock is predominantly extensive, with approximately 90% of the production being sustained on pasture, which occupies around 20% of the territory. In the current climate change scenario and where cropland is becoming a limited resource, there is a growing need for a more efficient land use and occupation. It is estimated that more than half of the Brazilian pastures have some level of degradation; however there is still no mapping of the quality of pastures on a national scale. In this study, we mapped and evaluated the spatio-temporal dynamics of pasture quality in Brazil, between 2010 and 2018, considering three classes of degradation: Absent (D0), Intermediate (D1), and Severe (D2). There was no variation in the total area occupied by pastures in the evaluated period, in spite of the accentuated spatial dynamics, with a retraction in the center-south and expansion to the north, over areas of ​​native vegetation. The percentage of non-degraded pastures increased ~12%, due to the recovery of degraded areas and the emergence of new pasture areas as a result of the prevailing spatial dynamics. However, about 44 Mha of the pasture area is currently severely degraded. The dynamics in pasture quality were not homogeneous in property size classes. We observed that in the approximately 2.68 million properties with livestock activity, the proportion with quality gains was twice as low in small properties compared to large ones, and the proportion with losses was three times greater, showing an increase in inequality between properties with more and less resources (large and small, respectively). The areas occupied by pastures in Brazil present an unique opportunity to increase livestock production and make available areas for agriculture, without the need for new deforestation in the coming decades.

Background: Simulation plays a crucial role in health studies, as it helps medical students apply their theoretical knowledge in real-life situations. Moulage is one of the techniques that helps in making simulation more realistic or high-fidelity. It uses special effects to emulate wounds for a better understanding of what the wound is like visually. Still, moulage is expensive, time-consuming, resource-intensive, and requires the training of staff, which is why we need to find low-cost substitutes for moulage materials. Method: When searching the database “PubMed” for the terms “Low-cost and Medical moulage”, we retrieved 222 studies, out of which when excluding results not related to low-cost, we obtained 62 studies, from which when removing studies that do not contain information regarding moulage, we found two papers, after referring to citations and cited articles of those papers, we ended up with six studies. Based on the selected articles and additional articles sourced from their reference list, a total of 11 studies were included in the review. Results: We understand that moulage is a technique that helps make simulations come alive, but the resources required to use it are at times, expensive, which is why we need to find methods to do low-cost moulage, and many studies address that it can be as simple as using homemade ingredients. Students from a previous study have talked about their opinions regarding the realistic component of moulage and whether if it is any different from other moulages. Most of the students agreed that the moulage ranked well in face and content validity. However, further innovations must be introduced in the field to be widely spread and lead to newer opportunities. Conclusion: Although the research done under moulage is limited, it is accepted that moulage is helpful for simulation-based studies and that low-cost moulage can help make medical studies a better experience for students studying it. Students have a favorable opinion on the realistic aspect of the low-cost moulage applied to them. Newer methods can be introduced to moulage, and it can be implemented in low-income countries.

Background: Simulations have historically aided training programs by providing a realistic and holistic replication of professional scenarios and procedures. Simulations have developed over the past 40 years to include varying fidelities and modalities of simulation. Learning in a simulation-centered environment has benefits, ranging from improved patient care to specific skills acquisition while catering to students’ numerous and varied learning approaches. Simulation is a multifaceted field that benefits all parties, the teachers, the learners, and the patients. The application of simulation to medical education and its amalgamation with other modes and substitutes allows for a more integrated learning and testing curriculum that advances the current trajectory of medical education. Such developments, however, are limited to resource rich areas, leaving behind low-middle income countries to use traditional, less evolved methodologies and practices. This review aimed to explore different aspects of simulation and focus specifically on low-cost task trainers and their accessibility. Method: The purpose of the study was to assess the accessibility of low-cost task trainers in terms of cost-effectiveness, distribution, validation, and frequency within specific specialties. To do so, 84 PubMed publications have been screened, and 39 filtered research studies have collected the necessary data. After analyzing the papers, we classified the following information – process, specialization, validation (y/n), costs, development location, and year of publication. Results: After carefully analyzing the accumulated data from the selected 39 publications, we found that most studies (i.e., 6 out of 39) were published in 2020. Emergency Medicine was the most common specialty for which low-cost trainers were developed (9 out of 39 procedural simulators); Otolaryngology followed this with 8 out of 39 trainers and general surgery with 7/39 of the task-trainers. The price ranges fluctuated and fell within the price bracket of USD 0 to USD 400 collectively. Our review also uncovered the concentration of development of such innovations solely in high income countries (HICs). Conclusion: Simulation is an invaluable tool applicable to a diverse range of phases of medical education. Future conjunction of simulation with low-cost substitutes along with increased encouragement and enthusiasm towards developing cost effective simulation-based learning environments (SBLEs) with the reserves and requirements of these areas in mind may prove to be a reliable option for low and middle resource settings

The term low-resourced has been tossed around in the field of natural language processing to a degree that almost any language that is not English can be called "low-resourced"; sometimes even just for the sake of making a mundane or mediocre paper appear more interesting and insightful. In a field where English is a synonym for language and low-resourced is a synonym for anything not English, calling endangered languages low-resourced is a bit of an overstatement. In this paper, I inspect the relation of the endangered with the low-resourced from my own experiences.

Abstract: Imaging devices of less than 300,000 pixels are mostly used for sewage conduit exploration due to the petty nature of the survey industry in Korea. P articular ly , devices of less than 100,000 pixels are still widely used, and the environment for image processing is very bitter . Since the sewage conduit image s covered in this study ha ve a very low resolution (240 × 320 = 76,800 pixels), it is very difficult to detect cracks. Because most of the resolution of the sewe r conduit images are very low in Korea, this problem of low resolution was selected as the subject of study. Cracks were detected through a total of six steps of improving the crack in Step 2, finding the optimal threshold value in Step 3, and applying an algorithm to detect cracks in Step 5. Cracks were effectively detected by the optimal parameters in Steps 2 and 3 and the user algorithm in Step 5. Desp ite the very low resolution, the cracked image s showed 96.4% accuracy of detection, and the non cracked image s showed 94.5% accuracy . Moreover, the analysis was excellent in quality , also . It is believed that the findings of this study can be effectively u sed for crack detection with low resolution images.

Biosensors are essential tools which have been traditionally used to monitor environmental pollution, detect the presence of toxic elements and biohazardous bacteria or virus in organic matter and biomolecules for clinical diagnostics. In the last couple of decades, the scientific community has witnessed their widespread application in the fields of military, health care, industrial process control, environmental monitoring, food-quality control, and microbiology. Biosensor technology has greatly evolved from the in vitro studies based on the biosensing ability of organic beings to the highly sophisticated world of nanofabrication enabled miniaturized biosensors. The incorporation of nanotechnology in the vast field of biosensing has led to the development of novel sensors and sensing mechanisms, as well as an increase in the sensitivity and performance of the existing biosensors. Additionally, the nanoscale dimension further assists the development of sensors for rapid and simple detection in vivo as well as the ability to probe single-biomolecules and obtain critical information for their detection and analysis. However, the major drawbacks of this include, but are not limited to potential toxicities associated with the unavoidable release of nanoparticles into the environment, miniaturization induced unreliability, lack of automation, and difficulty of integrating the nanostructured-based biosensors as well as unreliable transduction signals from these devices. Although the field of biosensors is vast, we intend to explore various nanotechnology enabled biosensors as part of this review article and provide a brief description of their fundamental working principles and potential applications.

Cuticular waxes are a mixture of hydrophobic very-long-chain fatty acids and their derivatives accumulated in the plant cuticle. Most studies define the role of cuticular wax largely based on reducing non-stomatal water loss. The present study investigated the role of cuticular wax in reducing both low-temperature and dehydration stress in plants using Arabidopsis thaliana mutants and transgenic genotypes altered in the formation of cuticular wax. cer3-6, a known Arabidopsis wax-deficient mutant (with distinct reduction in aldehydes, n-alkanes, secondary n-alcohols, and ketones compared to wild type (WT)), was most sensitive to water loss; while dewax, a known wax overproducer (greater alkanes and ketones compared to WT), was more resistant to dehydration compared to WT. Furthermore, cold-acclimated cer3-6 froze at warmer temperatures, while cold-acclimated dewax displayed freezing exotherms at colder temperatures compared to WT. GC-MS analysis identified a characteristic decrease in the accumulation of certain waxes (e.g. alkanes, alcohols) in Arabidopsis cuticles under cold acclimation, which was additionally reduced in cer3-6. Conversely, the dewax mutant showed a greater ability to accumulate waxes under cold acclimation. FTIR spectroscopy also supported observations in cuticular wax deposition under cold acclimation. Our data indicate cuticular alkane waxes along with alcohols and fatty acids can facilitate avoidance of both ice formation and leaf water loss under dehydration stress, and are promising genetic targets of interest.

Purpose: Novel coronavirus disease (COVID-19) is the current global concern. Radiotherapy (RT), commonly employed in cancer management, has been considered one of the potential treatments for COVID-19 pneumonia. Here, we present the final report of the pilot trial evaluating the efficacy and safety of low-dose whole-lung irradiation (LD-WLI) in patients with COVID-19 pneumonia. Methods and Materials: We enrolled patients with moderate COVID-19 pneumonia who were older than 60 years. Participants were treated with LD-WLI in a single fraction of 0.5 or 1.0Gy along with the national protocol of COVID-19. The primary endpoints were improvement of SpO₂, the number of hospital/ICU stay days, and the number of intubations after RT and the secondary endpoints were alterations of the c-reactive peptide, interleukin-6, ferritin, procalcitonin, and D-dimer. The response rate (RR) was defined as a rise in SpO₂ upon RT with rising or constant trend in the next two days, and clinical recovery (CR) included patients who were discharged from the hospital or acquired SpO₂ ≥93% on room air. Results: Between 21 May 2020 and 2 July 2020, ten patients were enrolled. The median age was 75 years, 80% were male, and 80% had comorbidities. The first five patients received a single 0.5Gy-WLI, and others received 1.0Gy. Patients were followed for 2-14 days (median 5.5 days). Following one day, nine patients experienced an improvement in SpO₂. Five patients were discharged (median 6^th day, range 2^nd-14^th day), and four patients died (median 7^th day, range 3^rd-10^th day). Overall, the RR and CR were 60.0% and 55.5%, respectively. The RR and CR rates of 0.5- and 1.0Gy group were 80% vs 40% and 75% vs 40%, respectively. No acute radiation-induced toxicity was recorded. Conclusions: LD-WLI with a single 0.5Gy fraction seems to be a more appropriate dose to warrant further evaluation in a large-scale, randomized trial.

We review a number of preconditioners for the advection-diffusion operator and for the Schur complement matrix which in turn constitute the building blocks for Constraint and Triangular Preconditioners to accelerate the iterative solution of the discretized and linearized Navier-Stokes equations. An intensive numerical testing is performed onto the driven cavity problem with low values of the viscosity coefficient. We devise an efficient multigrid preconditioner for the advection-diffusion matrix which, combined with the commuted BFBt Schur complement approximation, and inserted in a 2 x 2 block preconditioner, provides convergence of the GMRES method in a number of iteration independent of the meshsize for the lowest values of the viscosity parameter. The low-rank acceleration of such preconditioner is also investigated showing its great potential.

The concept of using special electrical circuit design realize a "cold resistors", that is, an active resistor circuitry with lowered effective noise temperature, was first introduced about 80 years ago. Later on, various kinds of artificial resistors were applied in different research areas, such as gravitational wave detection, photo-amplifiers and quartz oscillators. Their proofs of concepts were experimentally proved. Unfortunately, the complete theory was not found even though several attempts had been published, sometimes with errors. In this paper, we describe a correct and complete circuit theoretical model of a cold resistor system. The results are confirmed by computer simulations. A design tools for this circuit is also shown.

Number of confirmed cases of COVID-19 caused by SARS-CoV-2 exceeded 5 million as of May 21, 2020. Global average of the case fatality rate of COVID-19 is about 7% so far. There exist variations in case fatality rates among countries. Particularly, Singapore and Qatar have exceptionally low case fatality rates with 0.1% while France’s rate is almost 20%. Since no magic bullet treatment for COVID-19 exists, we investigated SARS-CoV-2 strains specific to Singapore in this study to identify a clade with low pathogenicity. Variant analysis revealed that a clade with variants ORF1ab L3606F, A4489V, S2015R, T2016K, and N P13L is common in Singapore. Based on our analysis of variants and historical case statistics, the clade is dominant in a recent surge. Therefore, we suggest that low case fatality rate of Singapore possibly is attributed to the clade. Although contribution of each variant to the low pathogenicity is not clear, L3606F alone does not accomplish such low pathogenicity from the comparison with case fatality data from Japan, where L3606F is dominant. Further investigation is necessary to conclude to validate this finding.

We report the negative effective mass metamaterials based on the electro-mechanical coupling exploiting plasma oscillations of a free electron gas. The negative mass appears as a result of vibration of a metallic particle with a frequency of ω which is close the frequency of the plasma oscillations of the electron gas m_2 relatively to the ionic lattice m_1. The plasma oscillations are represented with the elastic spring k_2=ω_p^2 m_2, where ω_p is the plasma frequency. Thus, the metallic particle vibrated with the external frequency ω is described by the effective mass m_eff=m_1+(m_2 ω_p^2)/(ω_p^2-ω^2 ) , which is negative when the frequency ω approaches ω_p from above. The idea is exemplified with two conducting metals, namely Au and Li.

In the last years, the development of low-cost GNSS sensors allowed monitoring in a continuous way movement related to natural processes like landslides with increasing accuracy and limited efforts. In this work, we present the first results of an experimental low-cost GNSS continuous monitoring applied to the unstable slope affecting the Madonna del Sasso Sanctuary (NW Italy). The courtyard of Sanctuary is built of two unstable blocks delimited by high cliff. Previous studies and non-continuous monitoring showed that blocks suffer a seasonal cycle of thermal expansion and long-term trend to downslope of few millimeters per year. The presence of continuous monitoring solution, could be an essential help to better understand the kinematics of unstable slope and to recognize the beginning of a possible paroxysm phase that could end with a failure of the unstable area. We tested the accuracy of the instruments and the first year of experimental measurements are presented. We also propose a methodological approach that considers the use of automatized procedures for the identification of anomalous trends and a risk communication strategy based on monitoring data.

A hydrothermal pretreatment of the microalga Nannochloropsis gaditana at mild temperatures has been studied in order to reduce N and O content in the biocrude obtained by hydrothermal liquefaction (HTL). The work is focused on the evaluation of temperature, reactor loading and time (factors) to maximize the yield of the pretreated biomass and the heteroatom contents transferred from the microalga biomass to the aqueous phase (responses). The study followed the factorial design and response surface methodology. An equation for every response has been obtained, which leads to the accurate calculation of the operating conditions required to obtain a given value of these responses. Temperature and time are critical factors with a negative effect on the pretreated biomass yield, but a positive one on the N and O recovery in the aqueous phase. The slurry concentration has to be low to increase heteroatom recovery and high to maximize the pretreated microalga yields

Over half of adult Americans now have diabetes or prediabetes and worse, this epidemic is now world-wide and shows no signs of slowing, with rates of both diabetes and diabetes-related health complications still rising. When advising patients with diabetes on food choices, many providers rely on nutrition guidelines provided by the American Diabetes Association (ADA), and these guidelines influence other recommendations across the globe. Given the alarming trends in diabetes, it is paramount to review the treatment guidelines to ensure they are based on rigorous and accepted scientific methods. Our review included the evidence cited by the ADA in support of its claims and recommendations for eating patterns to combat diabetes (see Description of Eating Patterns, Supplemental Appendix), as presented in the most current edition of the annual ADA’s Standards of Medical Care in Diabetes (2018 Standards). Our review also includes sources cited in the latest edition of the ADA’s Nutrition Therapy Recommendations for Adults with Diabetes (2014 Recommendations), which also informed the 2018 Standards. In October 2018 low carbohydrate was named as a recommended eating pattern by the ADA and European Association for the Study of Diabetes (EASD)⁵but only citations from the 2014 and early 2018 ADA documents were reviewed.

MEMThe PdNi film hydrogen sensors with Wheatstone bridge structure were designed and fabricated by the micro-electro-mechanical system (MEMS) technology. The integrated sensors consisted of four PdNi alloy film resistors. The interval two of them were shielded with silicon nitride film and used as reference resistance, while the others were used for hydrogen sensing. The PdNi alloy films and SiN films were deposited by magnetron sputtering. The morphology and microstructure of the PdNi films were characterized with X-ray diffraction (XRD). The output resistance signal was converted to millivolt output voltage signal for easy data acquisition. Hydrogen (H2) sensing properties of PdNi film hydrogen sensor with Wheatstone bridge structure was investigated under different temperatures (30℃, 50℃ and 70℃) and H2 concentrations (from 10 ppm to 0.4%). The hydrogen sensor demonstrated good response at different hydrogen concentrations and high repeatability in cycle testing under 0.4% H2 concentration. Under 10ppm hydrogen, the PdNi film hydrogen sensor had evident and collectable output voltage of 600 μV.

The beginning of industrialization human being has observed a variety of environmental troubles in the world. This industrialization has not only brought growth and affluence but ultimately troubled the ecosystem. One of the crashes is visible, in form of water contamination. Here the current study heavy metal contamination of water body has been discussed. Effluents from a great number of industries viz., tannery, textile, pigment & dyes, paint, wood processing, petroleum refining, electroplating, leather etc., have a major amount of heavy metals in their wastewater. The conventional technique of handling heavy metal pollution includes chemical oxidation, chemical precipitation, ion exchange, reverse osmosis, membrane separation, electrodialysis etc. These processes are expensive, energy intensive and frequently related with generation of poisonous by-product. Therefore, the adsorption has been examined as a cost-efficient technique of elimination of heavy metals from wastewater. In the current study different low-cost adsorbent has been a review as an abatement of heavy metal contamination from wastewater. These adsorbent comprise materials of natural origin like peat moss, zeolites, clay, and chitin are found to be an effective agent for removal of deadly heavy metals like Pb, Cd, Zn, Cu, Ni, Hg, Cr etc. Separately from these, a variety of agricultural wastes like rice husk, waste tea, neem bark, black gram; Turkish coffee, walnut shell etc. were also known as a powerful adsorbent for heavy metal removal. at the side of that low-cost industrial byproduct like fly ash, lignin, iron (III) hydroxide and red mud, coffee husks, Areca waste, tea factory waste, sugar beet pulp, battery industry waste, blast furnace sludge, waste slurry, sea nodule remains and grape stalk wastes have been discovered for their technical possibility to eliminate toxic heavy metals from impure water.

Computational Fluid Dynamics (CFD) is utilized to study entropy generation for the rarefied steady state laminar 2-D flow of air-Al2O3 nanofluid in square cavity equipped with two solid fins at the hot wall. Such flows are of great importance in industrial applications, such cooling of the electronic equipment’s and nuclear reactors. In the current study, effects of Knudsen number (Kn), Rayleigh number (Ra) and the nano solid particles volume fraction (ϕ) on the entropy generation are investigated. The values of parameters considered in this work are as follows: 0≤Kn≤0.1, 〖10〗^3≤Ra≤〖10〗^6,0≤ϕ≤0.2. Length of the fins (LF) is considered to be fixed and equals to 0.5 m, whereas the location of the fins with respect to the lower wall (HF) is set to 0.25 and 0.75 m. Simulations demonstrate that there is an inverse direct effect of Kn on the entropy generation. Moreover, it is found that when Ra is less than 104, the entropy generation, due to the flow, increases as ϕ increases. In addition, the entropy generation due to the flow will decrease at Ra greater than 104 as ϕ increases. Moreover, the entropy generation due to heat will increase as both the ϕ and Ra increase. In addition, a correlation model of the total entropy generation as a function of all of the investigated parameters in this study is proposed. Finally, an optimization technique is adapted to find out the conditions at which the total entropy generation is minimized

Recent advances in single-atom catalysis resulted in readily accessible materials whose application in most catalytic reactions mediated by conventional nanoparticle-based catalysts often results in higher activity and selectivity. Can we expect catalysis by atomically dispersed atoms to find practical applications? Which are the hurdles to be overcome prior to widespread uptake of atomically dispersed metals in industrial synthetic processes and in hydrogen fuel cells?

A The agri-food sector is in full renovation, continuously demanding new systems that allow farmers to facilitate their work. Efficient agricultural practices are essential for increasing farm profitability. Efficient agricultural practices can be increased by understanding and managing water neeeds. However, real-time monitoring of water needs is currently slow, and irrigation decisions are based on previous data or physical evidence. Furthermore, the prices of automatic systems for collecting data from several sources (soil and climate) are expensive and the autonomy is very low. Emerging Internet of Things (IoT) technologies such as wireless sensor networks can be used to collect vast amounts of data recorded via apps. By means of an LPWAN communication the farmer can know in real time the state of his crops thanks to a large number of sensors connected wirelessly and distributed across his farm. This paper presents a low consumption solution based on LoRaWAN technology. The wireless sensor node, called BoX, exhibits very low power since it has been optimized both in terms of hardware and software. The result is a higher degree of autonomy than commercial motes. That will allow the farmer to have all the information necessary to achieve an efficient management of his crops with full autonomy.

An ultra-low anti-reflection optical coating on both surfaces of a plastic cover slip was studied for use in confocal image measurement. The optical reflectance at a wavelength of 632.8 nm was less than 0.1% when the coated sample was placed in a liquid having a refractive index of 1.34 close to the aqueous solution of the biomaterial. The high- and low-index coating films, Substance-2 (PrTiO3) and silicon dioxide (SiO2), were measured by an ellipsometer to determine their optical refraction indices and extinction coefficients. Theoretically, when the two layer thicknesses are designed using the optical admittance diagram of the cover slip to approach the equivalent index of 1.34, a reflectance of 1.6×10-5% in the liquid could be obtained. Experimentally, the reflectance of the sample deposited on the two faces of the cover slip was 4.223±0.145% as measured in the air; and 0.050±0.002% as measured by a He-Ne laser in the liquid.

The atherosclerosis, a chronic and inflammatory disease that occurs when there are high levels of low-density lipoprotein (LDL) on plasma. This important risk factor for development of cardiovascular disease (CVD) is the main cause of death worldwide. MicroRNAs have recently emerged as potential biomarkers and therapeutic target for lipid metabolism disorders. In this review, we will provide profile of surrounding miRNAs that have demonstrated being regulators of PCSK9, LDLR and APOB100 genes. Recent work has identified the mir-148, mir-128, mir-27a/b, mir-185, mir-301, mir-130 as important regulators of this pathway because they decrease supply of LDL receptors through interaction with PCSK9. Inhibition of LDLR expression cause elevation of plasma LDL levels which induces atherosclerosis. While mir-30c, mir-122, mir-34 decrease MTTP, which promotes degradation of APOB100 preventing assembly and secretion of VLDL. We conclude that, when overexpressed, mir-148a, mir128 and mir-27a/b, mir-122 and mir-34 are related to decrease in LDLR, facilitating occurrence of atherosclerosis. While mir-30 has been linked to decreased atherosclerosis. Detection of miRNAs profile could be used in the future as a biomarker for disturbs linked to c-LDL uptake and in future anti-miRNAs therapies may be used in the treatment of atherosclerosis.

This paper seeks to model the crack propagation in of AAs (aluminum-alloys) 2524-T3 and 7050-T7452 subjected to fatigue loading at low temperature. Fatigue crack growth tests were performed on AAs 2524-T3 and 7050-T7452 subjected to constant-amplitude and actual random-spectra loading histories at room temperature of about 25 °C and at cryogenic temperature of -70 °C, respectively, to determine their crack growth properties and residual lives. The interaction mechanisms between cryogenic temperature and the fatigue load were deduced on the basis of the results of fractographic analysis. Temperature-dependent residual lives under actual random-spectrum load history were modeled based on a modified accumulation damage rule by accounting for the load interaction. Good correlation was achieved between the predictions and actual experiments, demonstrating the practical and effective use of the proposed method.

We report a preliminary exploration on the low-pressure Ar-O2 plasma generated by low-frequency alternating current (AC) power supply in the low-temperature Plasma Experimental Power Supply (CTP-2000S) for the first time. The electron density 〖(n〗_e), the electron temperature 〖(T〗_e) and the electron energy distribution function (EEDF) are measured by the single Langmuir probe in this experiment. Experimental results show that the ne increases with gas pressure rising, while the ne decreases with the oxygen concentrations rising. And, a plasma density peak is also observed with the AC power supply increase. A comparison between this work and the previous results by RF source suggests that the low-frequency AC power supply may be very fruitful exploration to generate the low-pressure plasma.

In order to enhance the efficiency of direct absorption solar collectors, this study carried out an experimental analysis about the optical and photothermal conversion performance of Fe3O4, ATO and Fe3O4/ATO nanofluids with total concentration of 0.1wt%. According to the results of experiments, Fe3O4 nanofluid outperform ATO nanofluid in terms of optical absorption; nevertheless, at wavelengths shorter than 600 nm, it also shows significant scattering reflection. The solar-weighted absorption coefficient of Fe3O4/ATO nanofluid rose from 0.863 (mFe3O4mTotal= 0.2) to 0.932 (mFe3O4mTotal= 0.8) when the optical path length increased from 0.01 m to 0.06 m. Additionally, the photothermal conversion efficiency of Fe3O4/ATO hybrid nanofluid was attained 0.932 at (mFe3O4mTotal= 0.2), above the 0.892 and 0.898 photothermal conversion efficiencies recorded for 0.1 wt% ATO and Fe3O4 nanofluids, respectively. When present together, the opposing optical characteristics of Fe3O4 and ATO boost photothermal conversion performance, which is anticipated to raise the efficiency of direct absorption solar collectors.

Stunting is a major public health issue in Aceh, Indonesia, requiring advanced analytical techniques for effective interventions. This study presents a novel hybrid machine learning framework designed to enhance the analysis of stunting through improved classification, predic-tive modeling, and clustering optimization. The framework utilizes Support Vector Machines (SVM) with Radial Basis Function (RBF) and Sigmoid kernels for classification. The RBF kernel achieved an accuracy of 91.3%, significantly outperforming the Sigmoid kernel's 85.6%. Linear Regression was employed for predictive modeling, yielding a Mean Squared Error (MSE) of 0.137, which indicates strong predictive accuracy. In clustering, the optimized K-Medoids method, in-corporating a weight product approach, demonstrated superior efficiency by requiring only 3 iterations for convergence, compared to 7 iterations for the conventional K-Medoids method. Additionally, it achieved a higher Calinski Harabasz Index of 93.7, compared to 85.2 for the conventional method. This comprehensive approach enhances accuracy and efficiency across classification, prediction, and clustering tasks, providing valuable insights for targeted interventions and policy development to address stunting in Aceh.

Artificial intelligence algorithms have gained widespread adoption in the field of air conditioning load prediction. However, their prediction accuracy is substantially influenced by the quality of training samples. Training samples that lack relevance to the predicted moments can introduce interference into the neural network's learning process, potentially leading to a state of local convergence during its iterative process. This, in turn, diminishes the robustness and generalization capabilities of the prediction model. To enhance the prediction accuracy of air conditioning load prediction models based on artificial intelligence algorithms, this study presents an artificial intelligence algorithm prediction model based on the method of sample similarity sample screening. Initially, the comprehensive similarity coefficient between samples is computed using the gray correlation analysis method, enriched with enhancements in information entropy. Subsequently, a subset of closely related samples is extracted from the original dataset and employed as the training dataset for the artificial intelligence prediction model. Finally, the trained artificial intelligence algorithm prediction model is deployed for air conditioning load prediction. The results illustrate that the method of screening training samples based on sample similarity effectively improves the prediction accuracy of BP neural network (BPNN) and extreme learning machine (ELM) prediction models. However, it is important to note that this approach may not be suitable for genetic algorithm BPNN (GABPNN) and support vector regression (SVR) models.

Transport infrastructure’s asphalt pavement deteriorates under the influence of destructive factors. Damages which have been occurred during its exploitation period are repaired, and when their further rehabilitation is economically and technically irrational, the asphalt pavement is recycled. The material from the asphalt pavement layer that has reached its limit state is milled out or broken and crushed and then is repeatedly used in the production of hot-mix asphalt (HMA) or warm-mix asphalt (WMA) mixtures. In this paper, the dynamics of the percentage recycling ratio (RR) of old asphalt pavement material was investigated. RR represents the quantity of reclaimed asphalt pavement (RAP) used in the production of HMA and WMA mixtures in Europe and the USA, divided by the total amount of RAP prepared in the country. Factors and goals affecting it are analyzed. An original system of 10 criteria that increase the RR country has been created. By applying different multiple criteria decision making (MCDM) methods and using the importance given to these criteria by 14 experts, the normalized subjective weights of the criteria were determined. Analytic Hierarchy Process (AHP), rank correlation, Average Rank Transformation into Weight - Linear (ARTIW-L) and Non-linear (ARTIW-N), Direct Percentage Weight (DPW) methods were used in the study. The results display that the RAP recycle rate is close to 100% in countries with a sustainable economic background. In the Baltic countries, it is mostly increased by the adequacy of regulatory documents, the strategy promoting asphalt recycling in the country, and the homogeneity and classifying of RAP. The number and capacity of RAP stocks, the number and productivity of asphalt milling equipment and the wear and tear of the asphalt pavement have the least influence on the increase of RR. The opinions of experts in assessing the significance of all criteria are consistent. The averages of the weights of criteria determined by four MCDM methods (AHP, ARTIW-L, ARTIW-N, DPW) made it possible to obtain more reliable results. These results can be used to make strategic decisions and to create a plan of practical actions to increase the RAP recycling rate in the developing countries.

Tourism is an important industry that promotes national economic and social progress. All-for-one tourism is a new concept of regionally coordinated development that uses the tourism industry as an engine to boost resource integration, industrial integration, and social sharing. Tourism service is the main embodiment of cultural ecosystem services for all-for-one tourism cities. Taking Liyang in China as an example, this paper used a combination of GIS spatial analysis and big data text mining to evaluate the tourism service from three aspects: the quality of tourism resources, the comprehensiveness of tourism service facilities, and the satisfaction of tourists. The results show that (1) the tourism service is better in the northwestern and eastern areas of the city, while it is lower in the northeastern and southwestern parts; (2) the hotspot areas should focus on improving the tour routes, the transport capacity, and excessive charges; the cold spot areas should work on ecological restoration and creating new tourism attractions by combining the local industries; (3) rural tourism integrating agriculture and visitation should be highlighted as a key growth point to improve the city’s tourism service function.

Farmers are continually looking for new reliable, objective and non-invasive methods for evaluation of ewe condition. Live weight (LW) and body condition score (BCS) are used by farmers as a basis to determine the condition of the animal. Body composition is an important aspect of monitoring animal condition. The body composition is the amount of fat, lean and bone; knowing the amount of each is important because the information can be used for better strategic management interventions. Experiments were conducted to establish the relationship between body composition and body parameters, at key life’s stages (weaning and pre-mating), using measurements automatically determined by an image processing ap-plication at Lincoln University sheep farm for 88 Coopworth ewes. Computerized Tomography technology was used to develop relationship with body parameters and a subset was used to validate the predicted model. Multivariate linear regression (MLR), artificial neural network (ANNs) and regression tree (RT) statistical analysis methods were evaluated to determine their efficacy to predict body fat, lean and bone. The results showed a correlation between fat, lean and bone determined by CT and the fat, lean, bone weight estimated by live weight and body parameters calculated using the image processing application with R2 values of 0.90 for fat, 0.72 for lean and 0.50 for bone using ANNs statistical model. From these results, farmers can utilize accurate measures of fat which will enhance nutritional and management practices.

Globally, increasing rates of obesity are one of the most important health issues. The association between breakfast skipping and body weight is contradictory between cross-sectional and interventional studies. The systematic review and meta-analyses aim to summarize this association based on observational longitudinal studies. We included prospective studies on breakfast skipping and overweight/obesity or weight change in adults. Literature was searched until September 2020 in PubMed and Web of Science. Summary RRs with a 95% CI were estimated in pairwise meta-analyses by applying a random-effects model. In total, 9 studies were included in the systematic review and 6 of them were included in the meta-analyses. The meta-analysis indicated an 13% increased RR for overweight/obesity when breakfast was skipped on ≥ 3 days per week compared to ≤ 2 days per week (95% CI: 1.06, 1.21, n=3 studies). The meta-analysis on weight change displays a 21% increased RR for weight gain for breakfast skippers compared to breakfast eaters (95% CI: 1.05, 1.40, n=2 studies). The meta-analysis on BMI change displayed no difference between breakfast skipping and eating (RR=1.02, 95% CI: 0.99, 1.05, n=2 studies). This study provides low meta-evidence for an increased risk for overweight/obesity and weight gain for breakfast skipping.

Exercise facilitates weight control, partly through effects on appetite regulation. Single bouts of exercise induce a short-term energy deficit without stimulating compensatory effects on appetite, whilst limited evidence suggests that exercise training may modify subjective and homeostatic mediators of appetite in directions associated with enhanced meal-induced satiety. However, large variability in responses exists between individuals. This article reviews the evidence relating to how adiposity, sex and habitual physical activity modulate exercise-induced appetite, energy intake and appetite-related hormone responses. The balance of evidence suggests that adiposity and sex do not modify appetite or energy intake responses to acute or chronic exercise interventions, but individuals with higher habitual physical activity levels may better adjust energy intake in response to energy balance perturbations. The effect of these individual characteristics and behaviours on appetite-related hormone responses to exercise remains equivocal. These findings support the continued promotion of exercise as a strategy for inducing short-term energy deficits irrespective of adiposity and sex, as well as the ability of exercise to positively influence energy balance over the longer term. Future well-controlled studies are required to further ascertain potential mediators of appetite responses to exercise.

Anthracnose stands as the primary obstacle to lupin cultivation, impeding development despite the considerable agronomic, ecological, and economic potential of such legume crops. This review explores recent efforts to unravel the complexities of anthracnose in domesticated lupins, focusing on both the plant perspective and the causative pathogenic agent, Colletotrichum lupini. Leveraging cutting-edge technologies has yielded crucial insights into various facets of this devastating disease, encompassing plant and pathogen biology, genetic and molecular regulations of the interaction, fungal diversity and population dynamics, and screening of plant genetic resources for anthracnose resistance. The lack of effective disease control measures, relying primarily on the use of disease-free seeds, highlights the need to develop anthracnose-resistant varieties. However, challenges arise from the intricacy of lupin's response to the disease, influenced by polygenic inheritance, in spite of loci with major effects, and environmental factors. The slow pace of genetic improvement underscores the need for more efficient breeding processes, including biotechnological approaches. This review offers a comprehensive overview of current progress and knowledge gaps, stressing the urgent need to further enhance understanding of C. lupini pathogenic mechanisms and lupin‘s resistance. Integrating advanced technologies and accelerated research efforts is paramount for achieving efficient disease management and sustainable lupin cultivation in the face of anthracnose challenges.

The construction of molecular robotic-like objects that imitate living things is an important challenge for current chemists. Such molecular devices are expected to perform their duties robustly to carry out mechanical motion, process information, and make independent decisions. Dissipative self-organization plays an essential role in meeting these purposes. To produce a micro-robot that can perform the above tasks autonomously as a single entity, a function generator is required. Although many elegant review articles featuring chemical devices that mimic biological mechanical functions have been published recently, the dissipative structure, which is the minimum requirement, has not been sufficiently discussed. This article aims to show clearly that dissipative self-organization is a phenomenon involving autonomy, robustness, mechanical functions, and energy transformation. Moreover, the author details the recent experimental results of an autonomous light-driven molecular device that achieves all of these features. In addition, a chemical model of cell-amplification is also discussed to focus on the generation of hierarchical movement by dissipative self-organization. By reviewing this research, it may be perceived that mainstream approaches to synthetic chemistry have not always been appropriate. In summary, the author proposes that the integration of catalytic functions is a key issue for the creation of autonomous microarchitecture.

The emergence of SARS/MERS drug resistant COVID-19 with high transmission and mortality has recently been declared a deadly pandemic causing economic chaos and significant health problems. Like all coronaviruses, SARS-CoV-2 is a large virus that has many druggable components within its proteome. In this study, we focused on repurposing approved and investigational drugs by identifying potential drugs that are predicted to effectively inhibit critical enzymes within SARS-CoV-2. We shortlisted seven target proteins with enzymatic activities known to be essential at different stages of the virus life cycle. For virtual screening, the energy minimization of a crystal structure or modeled protein was carried out using Protein Preparation Wizard (Schrödinger LLC, 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs (n=5903) that are already approved by worldwide regulatory bodies including the FDA, using the ZINC database. Screening was performed against viral targets using three sequential docking modes (i.e. HTVS, SP and XP). Our in-silico virtual screening identified ~290 potential drugs based on the criteria of energy, docking parameters, ligand and binding site strain and score. Drugs specific to each target protein were further analyzed for binding free energy perturbation by molecular mechanics (prime MM-GBSA) and pruning the hits to the top 32 candidates. A top lead from each target group was further subjected to molecular dynamics simulation (MDS) using the Desmond module to validate the efficacy of the screening pipeline. All of the simulated hit-target complexes were predicted to strongly interact and with highly stable binding. Thus, we have identified a number of approved and investigational drugs with high likelihood of inhibiting a variety of key SARS-CoV-2 proteins. Follow-up studies will continue to identify inhibitors suitable for combination therapy based on drug-drug synergy to thwart resistance. In addition, the screening hits that we have identified provide excellent probes for understanding the binding properties of the active sites of all seven targets, further enabling us to derive consensus molecules through computer-aided drug design (CADD). While infections are expanding at a rampant pace, it must be recognized that resistance will grow commensurately through either genetic shift and/or genetic drift to all small molecule drugs identified. Vaccines should provide a more permanent solution through prevention, but resistivity is still a possible scenario. Nevertheless, a persistent multi-target drug development program is essential to curb this ongoing pandemic and to keep reemergence in check.

Since the discovery of the human epidermal growth factor receptor 2 (HER2) as an oncogenic driver in a subset of breast cancers and the development of HER2 directed therapies, the prognosis of HER2 amplified breast cancers has increased meaningfully. Next to monoclonal anti-HER2 antibodies and tyrosine kinase inhibitors, the antibody-drug conjugate T-DM1 is a pillar of targeted treatment of advanced HER2-positive breast cancers. Currently, several HER2 directed antibody-drug conjugates are under clinical investigation for HER2 amplified but also HER2 expressing but not amplified breast tumors. In this article, we review the current preclinical and clinical evidence of the investigational drugs A166, ALT-P7, ARX788, DHES0815A, DS-8201a, RC48, SYD985, MEDI4276 and XMT-1522.

Anterior Cruciate Ligament (ACL) injuries rank among the most prevalent and severe types of injuries, significantly impacting both athletes and non-athletes alike. These injuries not only result in immediate physical impairment, such as intense pain, substantial swelling, and a marked loss of mobility, but also carry long-term health consequences that can alter a person's quality of life. Chronic pain, persistent instability, and an increased risk of developing osteoarthritis are among the lasting effects that can follow an ACL injury. An in-depth understanding of the biophysics behind ACL injuries is paramount for devising effective prevention and treatment protocols. Biophysics, which combines principles from physics with biological systems, provides crucial insights into the mechanical and structural integrity of the ACL and its susceptibility to injury under various conditions. This systematic review aims to collate and synthesize the current knowledge surrounding the biophysical mechanisms that underlie ACL injuries. The review encompasses a range of factors, including the biomechanical forces that place stress on the ligament, anatomical structures that may predispose individuals to injury, and physiological conditions that affect ligament health and resilience. Each of these factors plays a crucial role in the incidence and severity of ACL injuries. Biomechanical forces, for example, can involve sudden changes in direction or impact during physical activity, leading to excessive stress on the ACL. Anatomical factors might include variations in bone structure or ligament alignment that inherently increase the risk of injury. Additionally, physiological conditions such as muscle strength, flexibility, and overall ligament health can influence the likelihood and extent of an ACL injury. The findings of this review underscore the necessity of adopting integrated approaches in both injury prevention and rehabilitation. Such approaches must consider the multifaceted nature of ACL injuries, involving not only mechanical and anatomical aspects but also physiological and possibly even genetic factors. By emphasizing a multi-faceted understanding, interventions can be more effectively tailored to address the complex interplay of elements that contribute to ACL injuries. This holistic approach can lead to better outcomes for those at risk of or recovering from ACL injuries, enhancing the efficacy of prevention strategies and rehabilitation protocols.

Cervical cancer (CC) remains a significant global health challenge, characterized by its genetic heterogeneity and complex molecular landscape. The current study investigates the germline variants in proto-oncogenes and tumor suppressor genes among patients diagnosed with cervical cancer. Utilizing a custom NGS panel targeting 48 genes implicated in oncogenesis, we identified 148 nucleotide sequence alterations across the cohort. Of these, 35 variants (23.6%) were classified as benign, while 105 (70.9%) were categorized as variants of uncertain significance (VUS), whose clinical relevance remains to be elucidated. Moreover, we discovered seven pathogenic or likely pathogenic mutations, as well as a polymorphic variant rs1042522 in the TP53 gene, which has been previously associated with an increased risk of CC. Our findings contribute to the understanding of the molecular-genetic landscape of cervical cancer, highlighting the potential impact of rare germline mutations on the disease's pathogenesis and progression. This study underscores the importance of comprehensive genetic screening in improving the diagnostic and therapeutic strategies for cervical cancer patients.

Canine distemper virus (CDV) poses a substantial threat to diverse carnivores, leading to sys-temic and often fatal diseases. Accurate and prompt diagnosis is paramount for effective man-agement and curbing further transmission. This study evaluates the diagnostic efficacy of drop-let digital PCR (ddPCR) in comparison to conventional reverse transcription (RT-PCR) and quantitative reverse transcription real-time PCR (RT-qPCR). Seventy-six clinical samples were collected from dogs with CDV symptoms diagnosed by specialized veterinarians, and sixteen samples from asymptomatic individuals. Conventional PCR, quantitative real-time PCR, and ddPCR were deployed, and their diagnostic capabilities were meticulously assessed. DdPCR ex-hibited heightened analytical sensitivity, reaching a detection limit of 3 copies/μL, whereas RT-qPCR had a detection limit of 86 copies/μL. The comparative analysis between clinical diagnosis and molecular techniques, including RT-PCR and RT-qPCR, demonstrated low concordance, with Kappa coefficients of 0.268 and 0.324, respectively. In contrast, ddPCR, showed a moderate concordance, with a Kappa coefficient of 0.477. Sensitivity was 42.39% for RT-PCR, 57.89% for RT-qPCR and 72.37% for ddPCR, with 100% of specificity for all methods. This study under-scores ddPCR's superior sensitivity and concordance with clinical CDV diagnosis, even at low viral concentrations, suggesting it as a promising alternative for CDV diagnosis.

A synopsis of current knowledge of the diversity of the New Zealand landhopper fauna is provided. A combination of morphological and molecular analysis was employed on material from across New Zealand. Thirteen new endemic genera soon to be formally described have been discovered, including four belonging to the widespread families Talitridae and Arcitalitridae. These are families that had not been previously reported from New Zealand. We document the existence of at least 48 new provisional native species. This number far exceeds the 28 species currently described. Some described species are now shown to be species complexes and a few of these are very diverse with numerous cryptic species. Six changes to the existing taxonomy are proposed. Dallwitzia simularis (Hurley, 1957) is transferred from Makawidae Myers and Lowry, 2020 to Talitridae Rafinesque, 1815; Kellyduncania hauturu (Duncan, 1994) is reinstated as a member of Dana Lowry, 2011 and Kellyduncania (Lowry and Myers, 2019) is relegated to a synonym of Dana Lowry, 2011; Kanikania Duncan, 1994 is transferred from Makawidae Myers and Lowry, 2020 to Arcitalitridae Myers and Lowry, 2020; Parorchestia longicornis is transferred to Kanikania Duncan, 1994; Waematau kaitaia (Duncan, 1994) is transferred to Kohuroa Lowry, Myers and Nakano, 2019; and Waematau unuwhao (Duncan, 1994) is transferred to Omaiorchestia Lowry and Myers, 2019. This reduces the number of described genera from 17 to 16.

Accurate assessment of shale gas reserves hinges on a detailed characterization of gas and water distribution within shale reservoirs. Despite its importance, the nanoscale behavior of water and methane in deep shale formations, especially under elevated temperatures and pressures, remains poorly understood. This study proposes a novel molecular modeling approach to represent the complex nanocomposite porous media found in deep shale matrices. Leveraging quantitative data from experimental analyses of shale pore composition, we developed a molecular model that accurately reflects the intricate pore-slit structure within a composite of kerogen and illite, common constituents of shale. Employing a hybrid grand canonical Monte Carlo and molecular dynamics simulation technique, we investigated the micro-scale distribution and preferential adsorption sites of water and methane within the shale matrix. Our research further elucidates the impact of water on the pore structure of shale and delineates the co-occurrence patterns of water and methane. The simulations reveal that water and methane share similar adsorption preferences on kerogen surfaces, while methane does not exhibit specific adsorption preferences on water-bearing illite. We also find that the presence of water significantly alters the illite pore space, leading to a reduction in larger pore volumes and a concomitant increase in smaller pores. The decrease in methane content with increasing water content is more pronounced in the shrinkage cracks compared to the kerogen matrix pores and is particularly notable in the macropores of illite. The findings underscore the differential sensitivity of methane content to water levels across various shale pore types. These insights contribute to a deeper theoretical understanding of gas and water distribution mechanisms in deep shale reservoirs, offering valuable support for the evaluation of deep shale gas resource potential.

Atypical Polypoid Adenomyoma (APA) is a benign uterine lesion that occurs in women of reproductive age. The histological pattern is characterized by irregular epithelial proliferation and muscular stroma. Our work consists of a systematic review of the literature, including the description and analysis of a case study, and assesses the main immunohistochemical and molecular markers that contribute to making a differential diagnosis against endometrial adenocarcinoma. This allows offering patients conservative treatment compared to the radical management required for endometrial cancer, due to the significant physical and psychological consequences that one procedure or another can have on women's health. The goal of this research is to carry out an adequate diagnosis of APA by providing the necessary information to guide clinical management, establish patient prognosis, and minimize the emotional impact associated with the disease, all in combination with clinical and histopathological findings and complementary imaging tests. In conclusion, an appropriate immunohistochemical and molecular approach, along with the presumptive histological diagnosis, determine the correct classification of the lesion as APA and not as other malignant pathologies, which allows establishing a treatment protocol adjusted to the biological reality of this pathology.

Background and Objectives Neurofibromatosis 1 (NF1 MIM # 162200), also known as von Recklinghausen disease, is among the most common autosomal dominantly transmitted disorders characterized mainly by neurocutaneous manifestations such as café au lait spots, intertriginous freckling, various types of neurofibromas (cutaneous neurofibromas or plexiform tumors), neurological manifestations, and bone abnormalities. It occurs with an incidence of 1:3000–1:4000 cases. Cone-rod dystrophies belong to the large group of retinal dystrophies, a highly heterogeneous group of disorders clinically manifested mainly by damage to cone and rod cells and have a broad spectrum of clinical manifestations. Many genes are involved in their etiology, with more than 100 currently identified, including the CRX gene responsible for the autosomal dominant form of cone-rod dystrophy (ad CORD). Materials and Methods: The authors present an intriguing case of a patient diagnosed with Neurofibromatosis type 1 (NF1) as an infant and ocular involvement (myopia and astigmatism onset at age 15), which yielded a surprising molecular testing result. Results: Molecular DNA analysis identified a rare occurrence of two mutational variants, including a pathogenic variant in the NF1 gene, c.3871-2A, and a likely pathogenic variant in the CRX gene c.119G>A. Conclusions: The authors present this case to highlight the surprises offered by molecular testing in a condition where the diagnosis is usually based on clinical criteria, thus providing patients with competent genetic advice.

Powdery mildew is a severe disease causing substantial yield losses in wheat production worldwide. The Chinese wheat landrace Changanhongmai (CAHM) exhibits high resistance to the physiological race E09 of powdery mildew. This study aims to characterize the powdery mildew resistance gene in CAHM, and develop molecular markers for marker-assisted selection of wheat. To investigate the genetic characteristics of this resistant gene, we developed F1 plants, F2 generation population, and F2:3 families from a cross between CAHM and SY225. Genetic analysis demonstrated that all F1 plants were resistant to the disease, while the ratio of resistant to susceptible plants was 3: 1 in both the F2 population and F2:3 families, indicating that CAHM is inherited in a manner of single dominant powdery mildew resistance gene, which was tentatively designated as PmCAHM. By using bulk segregation analysis, we constructed a genetic map encompassing Xgwm273, Xwmc626, Xgwm11, Xgwm18, Xgdm28, Xgpw7812, Xgpw5195, Xwmc694 and PmCAHM. Among these markers, Xgpw7812 and Xgpw5195 were flanking markers tightly linked to PmCAHM at a genetic distance of 2.5 cM and 8.4 cM, respectively. Furthermore, nullisomic-tetrasomic analysis revealed that PmCAHM is located on chromosome 1B. These results indicate that PmCAHM differs from the internationally recognized powdery mildew resistance genes in both location and source. In addition, a new germplasm/line NW1748 with large seeds and powdery mildew resistance was developed from the cross and back cross populations of Fengyou 1718 (FY1718)/CAHM//FY 1718. Therefore, PmCAHM can serve as a novel powdery mildew resistance source for breeding of wheat by using NW1748 as the donor in the future.

This study comprehensively investigates Al2O3's mechanical properties, focusing on fracture toughness, surface energy, Young's modulus, and crack propagation. The density functional theory (DFT) is employed to model the vacancies in Al2O3, providing essential insights into this material’s structural stability and defect formation. The DFT simulations reveal a deep understanding of vacancy-related properties and their impact on mechanical behavior. In conjunction with molecular dynamics (MD) simulations, the fracture toughness and crack propagation in Al2O3 are explored, offering valuable information on material strength and durability. The surface energy of Al2O3 is also assessed using DFT, shedding light on its interactions with the surrounding environment. The combination of DFT and MD simulations provides a robust framework for a comprehensive understanding of Al2O3's mechanical properties, with implications for material science and engineering applications.

The major arboviruses belong mainly to the families Bunyaviridae, Togaviridae, and Flaviviridae amongst which chikungunya virus and dengue virus have emerged as a global public health problem. The main objective of the study was to develop a specific, sensitive, and cost-effective molecular multiplex RT-PCR and RT-qPCR assay for the rapid and simultaneous detection of CHIKV and the four serotypes of DENV for arbovirus surveillance. Specific primers of all virus were designed, one step multiplex RT-PCR (mRT-PCR) and RT-qPCR (mRT-qPCR) was developed using reference strains of CHIKV and DENV serotypes. The specificity of the test for all the viruses was confirmed by sequencing. The standard curves showed a high correlation coefficient, R2= 0.99, for DENV-2 and DENV-3; R2= 0.98, for DENV-4 and CHIKV; R2= 0.93, for DENV-1. The limits of detection were calculated to be 10-2 copies/µL for all viruses. The specificity and sensitivity of the newly developed mRT-PCR and mRT-qPCR were validated using positive serum samples collected in India and Burkina Faso. The sensitivity of mRT-PCR and mRT-qPCR are 91%, and 100% respectively. The specificity of both assays was 100% specific. mRT-PCR and mRT-qPCR assays are low cost and a combination of both will be a useful tool for arbovirus surveillance.

Chromoblastomycosis (CBM) and phaeohyphomycosis (FEO) are infections caused by melanized filamentous fungal agents, primarily found in tropical and subtropical regions. Both infections pose significant challenges for the correct identification of the causative agent due to their morphological similarity, making conventional methods of morphological analysis highly subjective. Therefore, molecular techniques are necessary for the precise determination of these species. In this regard, this study aimed to contribute to a new methodology based on PCR-RFLP for the identification of agents causing CBM and FEO. Sequences from the ITS region were used to identify potential restriction enzyme sites in silico, followed by in vitro validation using the selected restriction enzymes. The obtained results were compared with species identification through morphological analyses and sequencing. The results demonstrated that the PCR-RFLP applied in this study accurately identified two major agents of chromoblastomycosis, Fonsecaea pedrosoi and Fonsecaea monophora, as well as Cladophialophora bantiana and Exophiala dermatitidis, both causative agents of phaeohyphomycosis. In this context, the proposed assay can complement current methods for identifying these species, aiding in diagnosis, and contributing to the proper management of these infections.

Hepatocellular carcinoma (HCC) is characterized by uncontrolled cellular proliferation driven by aberrant signal transduction. Cells respond to potential carcinogenic signals by inducing cellular senescence (CS) as a defense mechanism. However, assessing CS levels in various tumors is challenging due to heterogeneity and the lack of universal CS markers. This study integrates single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data from HCC samples to analyze gene expression profiles. HCC-specific senescence-related pathways are identified, and genes from these pathways distinguish molecular subtypes associated with senescence in HCC. These subtypes exhibit significant variations in biological and clinical attributes. A specific CS risk model is developed, revealing associations between CS scores and prognosis, clinical staging, immune infiltration, immunotherapy response, and drug sensitivity. The key gene G6PD is identified as a potential senescence-related target in liver cancer. Molecular experiments confirm the effective suppression of HepG2 cell proliferation, invasion, and migration upon G6PD knockdown. In summary, this analysis enhances our understanding of HCC-specific senescence molecular features and introduces a novel senescence-related biomarker, offering promising implications for future research.

In recent years, the emergence of cancer drug resistance is one of the crucial tumor hallmarks which is supported by the level of genetic heterogeneity and complexities at cellular levels. Oxidative stress, immune evasion, metabolic reprogramming, overexpression of ABC transporters and stemness are among the several key contributing molecular and cellular response mechanisms. Topo-active drugs, e.g., doxorubicin and topotecan, are clinically active and are utilized extensively against a wide variety of human tumors and often results in the development of resistance and failure to therapy. Thus, there is an urgent need for an incremental and comprehensive understanding of mechanisms of cancer drug resistance specifically in the context of topo-active drugs. This review delves into the intricate mechanistic aspects of these intracellular and extracellular topo-active drug resistance mechanisms and explores use of potential combinatorial approaches by utilizing various topo-active drugs and inhibitors of pathways involved in drug resistance. We believe that this review will help guide basic scientists, pre-clinicians, clinicians, and policymakers toward holistic and interdisciplinary strategies that transcend resistance, renewing optimism in the ongoing battle against cancer.

In the last two decades, plant taxonomy has bloomed, following the development of a novel technique, namely DNA Barcoding. DNA barcodes are standardized sequences, ideally unique, coding or non-coding, either from the genome of the organism or from its organelles, that are used to identify/classify an organismal group; in short the method includes amplification of the DNA barcode, sequencing and comparison with a reference database containing the relevant sequences from different species. In plants, the use a universal DNA barcode, such as COI which is used in animals, has not been achieved so far. Several DNA barcodes from single loci as well as combinations of barcodes have been successfully used in various settings; additionally, as next generation sequencing becomes affordable, very long sequences- super barcodes, such as the chloroplast genome are being used successfully especially to distinguish between close species. In this review we summarize the work done on DNA barcoding in plants and discuss different approaches used so far.

Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinases that involve in regulation of cell proliferation, survival, and development. FGFR alterations including amplifications, fusions, rearrangements, and mutations can result downstream activation of tyrosine kinases leading to tumor development. Targeting those FGFR alterations has shown to be effective in cholangiocarcinoma, urothelial carcinoma, and myeloid/lymphoid neoplasms and there are currently four FGFR inhibitors approved by the Food and Drug Administration (FDA). There have been developments of multiple agents targeting FGFR pathway including selective FGFR inhibitors, ligand traps, monoclonal antibodies, and antibody drug conjugates. However, most of these agents have variable and low responses with some intolerable toxicities and acquired resistances. This review will summarize previous clinical experiences and current developments of agents targeting FGFR pathway and discuss future directions of FGFR targeting agents.

The SARS-CoV-2 have caused a devastating pandemic of all times in the recent human history. However, there is a serious paucity in high quality data on aggravating factors and mechanisms of co-infection. This study aimed to identify the trending patterns of bacterial co-infections and types and associated outcomes in three phases of the pandemic. Using quality hospital data, we have investigated the SARS-CoV-2 fatality rates, profiles, and types of bacterial co-infections before, during, and after COVID-19 vaccinations. Out of 389 isolates used in different aspects, 298 was examined before and during the pandemic (n=149 before, n=149 during), death rates were 32% during compared to only 7.4% before pandemic with significant association (P value = 0.000000075). Death rate was 34% in co-infected (n = 170) compared to non-co-infected patients (n = 128) indicating a highly significant value (P value = 0.00000000000088). However, analysis of patients without other respiratory problems (n=28) indicated that among the remaining 270 patients, death was 30% in co-infected patients (n=150) and only 0.8% in non-coinfected (n=120) with high significant P value= 0.00000000076. The trending patterns of co-infections before, during, and after vaccinations showed a significant decline in Staphylococcus aureus with concomitant peaks in Gram-negatives in totals of (n= 149 before/n= 149 during): Klebsiella pneumonia (n = 11/49 before/during; E. coli n=10/24, A. baumannii n=8/25, and Ps. Aeruginosa n= 5/16, and S. aureus 13/1. Nevertheless, in post vaccination phase, (n= 91) gender-specific co-infections were examined for potential differences in susceptibility. Methicillin resistant S. aureus (MRSA) dominated both genders followed by E. coli in males and females with the latter gender showing higher rates of isolations in both species. Klebsiella pneumoniae declined to third place mostly in male patients. The drastic decline in K. pneumoniae and Gram-negatives post-vaccination strongly imply a potential co-protection in vaccines. Future analysis would gain more insights into molecular mimicry.

The COVID-19 pandemic has had a substantial impact on global health, notably the virus's association with autoimmune illnesses. Autoimmune illnesses occur when the immune system of the body targets healthy cells, causing damage and inflammation. The potential impact of COVID-19 on autoimmune disorders, the hazards of COVID-19 vaccinations for persons with autoimmune diseases, and the potential risks of COVID-19 vaccines are all discussed in this essay. COVID-19 can cause autoimmune illnesses by causing inflammation, organ and tissue damage, and molecular mimicry, in which the immune system mistakenly assaults healthy cells for the virus. However, not everyone infected with COVID-19 develops autoimmune disorders. While some research has found a link between COVID-19 and autoimmune illnesses, this does not always suggest causation. Other factors, such as genetics and environment, may also play a role in the emergence of autoimmune illnesses. COVID-19 can aggravate existing autoimmune disorders by causing the immune system to attack healthy cells, making management more difficult and increasing the risk of consequences. People with autoimmune disorders, on the other hand, may not be at a higher risk of severe COVID-19 than the general population. Some research has found that persons with autoimmune disorders are more likely to have severe COVID-19, whereas others have found no difference. COVID-19 vaccinations may represent dangers to persons with autoimmune illnesses since they contain antigens that can activate the immune system. Furthermore, due to their already overactive immune systems, some vaccines may not perform as well for people with autoimmune disorders, and some people with autoimmune diseases may have severe reactions to immunizations, producing inflammation and other symptoms. COVID-19 may not be any more hazardous to those with autoimmune illnesses than it is to the general population. The connection between COVID-19 and autoimmune disorders is complicated and under investigation. While some research implies that people with autoimmune disorders have a higher risk of severe COVID-19, others demonstrate no difference in death rates between them and the general population. There are also counterarguments that COVID-19 can induce and exacerbate autoimmune disorders, as well as worries about COVID-19 vaccine hazards for people who have autoimmune diseases. More research is required to completely understand the influence of COVID-19 on autoimmune illnesses, as well as the dangers and benefits of vaccinations for these people.

Allergen immunotherapy (AIT) with aeroallergens is the only disease modifying treatment for patients with different allergic conditions. Despite the effectiveness of AIT has been evidenced in both randomized controlled trials and real word studies, it remains underused in less than 10% of subjects with allergic rhinitis (AR) and/or asthma (A). We aimed to determine the current eligibility for house dust mite (HDM) AIT by means of a Precision Allergy Molecular Diagnosis (PAMD@) model in a selected cohort of youngsters with different allergic phenotypes according to the available evidence. A complex response to both HDM and storage mite allergens was depicted regardless of the subjects´ basal atopic condition. No solely specific IgE binding responses to Der p 1, Der p 2 and/or Der p 23 were found in the studied cohort. Despite patients with A and atopic dermatitis showed significantly higher serum titers to 6 mite allergens than subjects with AR, no specific molecular profile could be regarded as disease specific. Given the increasing complexity of specific IgE responses to the local prevailing aeroallergens, the identification and presence of such molecules are needed in commercially available AIT in the era of precision medicine.

The exact, non perturbative, response theory developed within the field of nonequilibrium molecular dynamics, also known as TTCF (Transient Time Correlation Function) applies to quite general dynamical systems. Its key element is called dissipation function, because it represents the power dissipated by external fields acting on the particle system of interest, whose coupling with the environment is given by deterministic thermostats. This theory has been initially developed for time independent external perturbations, and then it has been extended to time dependent perturbations. It has also been applied to dynamical systems of different nature, and to oscillator models undergoing phase transitions, which cannot be treated withe.g. linear response theory. The present work includes time dependent stochastic perturbations, in the theory, using the Karhunen-Loeve theorem. This leads to three different investigations of a given process. One in which a single realization of the stochastic coefficients is fixed, and averages are taken only over the initial conditions, as in a deterministic process. In the second, the initial condition is fixed, and averages are taken with respect to the distribution of stochastic coefficients. In the last investigations, one averages over both initial conditions and stochastic coefficients. We conclude illustrating the applicability of the resulting exact response theory with simple examples.

Hyperlipidemia (HLP) is a metabolic disease caused by abnormal lipid metabolism. Recently, the prevalence of HLP caused by poor dietary habits in the population has been increasing yearly. In addition, the current clinical use of lipid-lowering drugs has significant ameliorating effects on lipid levels but these actions are accompanied by certain side effects. However, bioactive marine substances have been verified to have various physiological activities such as hypoglycemic, antioxidant, antithrombotic, and effects on blood pressure. Therefore, marine biological sources of hypolipidemic active substances have attracted much attention. Moreover, some of the identified active substances have been found to induce hypolipidemia by inhibiting cholesterol synthesis and absorption, or by improving the composition of intestinal microorganisms. This article introduces the sources and classification of marine-derived hypolipidemic active substances, and describes current progress in research on the main mechanism of the hypolipidemic activity of these substances.

We measured the anelastic, dielectric and structural properties of the metal-free molecular perovskite (ABX$_{3}$) (MDABCO)(NH$_{4}$)I$_{3}$, which has already been demonstrated to become ferroelectric below $T_{\text{C}}=$ 448~K. Both the dielectric permittivity measured in air on discs pressed from powder and the complex Young's modulus measured on resonating bars in vacuum show that the material starts deteriorating with loss of mass just above $T_{\text{C}}$, introducing defects and markedly lowering $T_{\text{C}}$. The elastic modulus softens of 50\% when heating through the initial $T_{\mathrm{C}}$, contrary to usual ferroelectrics, which are stiffer in the paraelectric phase. This suggests improper ferroelectricity, where the primary order parameter of the transition is not the electric polarization, but the orientational order of the MDABCO molecules. The degraded material presents thermally activated relaxation peaks in the elastic energy loss, whose intensities increase together with the decrease of ~$T_{\mathrm{C}}$. The peaks are much broader than pure Debye, due to the general loss of crystallinity, also apparent from X-ray diffraction, but their relaxation times have parameters typical of point defects. It is argued that the major defects should be of the Schottky type, mainly due to the loss of (MDABCO)$^{2+} $ and I$^{-}$, leaving charge neutrality, and possibly also (NH$_{4}$)$^{+}$ vacancies. The focus is on an anelastic relaxation process peaked around 200~K at $\sim 1$~kHz, whose relaxation time follows the Arrhenius law with $\tau $$_{0}$~$\sim $\ $10^{-13}$\ s and $E\simeq 0.4$~eV. This peak is attributed to I vacancies (V$_{\text{X}}$) hopping around MDABCO vacancies (V$_{\text{A}}$) and its intensity presents a peculiar dependence on temperature and content of defects. The phenomenology is thoroughly discussed in terms of lattice disorder introduced by defects and of partition of V$_{\text{X}}$ among sites that are far from and close to the cation vacancies. A method is proposed for calculating the relative concentrations of V$_{\text{X}}$, that are untrapped, paired with V$_{\text{A}}$ or forming V$_{\text{X}}$--V$_{\text{A}}$--V$_{\text{X}}$ complexes.

Avipoxvirus (APV), a linear dsDNA virus belonging to the subfamily Chordopoxvirinae of the family Poxviridae, infects more than 278 species of domestic and wild birds. It is responsible for causing the avian pox disease, which is characterized by its cutaneous and diphtheric forms. With a high transmission capacity, it can cause high economic losses and damage to the ecosys-tem. Several diagnostic methods are available and vaccination of birds can be an effective pre-ventive measure. To update the molecular characterization and phylogenetic analysis of viruses isolated in Portugal between 2017 and 2023, ten APV-positive samples were analyzed. A P4b gene fragment was amplified by PCR and the nucleotide sequence of the amplicons was deter-mined by Sanger sequencing. The sequences obtained were aligned using ClustalW, and a max-imum likelihood phylogenetic tree was constructed. With this study, it was possible to verify that the analyzed sequences are distributed in subclades A1, A2, B1, and B3. Since some of them are quite similar to others from different countries and obtained in different years, it is possible to conclude that there have been several viral introductions in Portugal. Finally, it was possible to successfully update the data on avipoxviruses in Portugal.

The dengue virus (DENV) is an arbovirus belonging to the Flaviviridae family; the species comprises four antigenically distinct serotypes (DENV–1, DENV–2, DENV–3, and DENV–4), which are further subdivided into genotypes. The virus is transmitted to humans through mosquito bites, primarily from the Aedes spp. genus. Dengue is endemic in various parts of the world, including tropical and subtropical regions of Asia, Latin America, Africa, and Oceania. In Brazil, the state of Tocantins, located in north-central Brazil, has experienced a significant number of arboviral disease cases, particularly dengue. This study aimed to monitor DENV circulation within the state by conducting full genome sequencing of viral genomes recovered from 61 patients between June 2021 and July 2022. During this period, both DENV-1 and DENV-2 serotypes were identified. Our findings confirm the circulation of DENV serotypes 1 and 2 in Tocantins, affecting males and females equally, with younger age groups (4 to 43 years old) being the most susceptible. Phylogenetic analysis revealed that the circulating viruses belong to DENV–1 genotype V American and DENV–2 genotype III Southeast Asian/American. The Bayesian analysis of DENV-1 Genotype V sequenced here is closely related to genomes previously sequenced in the state of São Paulo. Regarding DENV-2 genotype III genomes, these are clustered in a distinct, well-supported subclade, along with previously reported isolates from the states of Goiás and São Paulo. In both cases, our results suggest that multiple introductions of these genotypes occurred in the Tocantins state. This observation highlights the significant impact of major population centers in Brazil on virus dispersion, including other Latin-American countries and the USA. In the SNP analysis, DENV-1 displayed 122 distinct missense mutations, while DENV-2 had 44, with significant mutations predominantly occurring in the envelope and NS5 proteins. The analyses performed here reveal the concomitant circulation of distinct DENV-1 and -2 genotypes in some Brazilian states, underscoring the dynamic evolution of the DENV and the ongoing significance of surveillance efforts in supporting public health policies.

In this paper we present methodology for precise calibration of Molecular Beam Epitaxy (MBE) growth process and achieving run to run stability of growth parameters. We present the analysis of the influence of fluxes stability during the growth of long wavelength quantum cascade laser structures designed for the range λ ~ 12–16 µm on wavelength accuracy with respect to desired emission wavelength. The active region of the lasers has a complex structure of nanometer thickness InxGa1-xAs/InyAl1-yAs superlattice. As a consequence, the compositional and thickness control of the structure via bulk growth parameters is rather difficult. To deal with this problem we employ methodology based on double-superlattice test structures, that precede the growth of the actual structures. The test structures are analyzed by high-resolution X-ray diffraction which allows to calibrate the growth of the complex active region of quantum cascade laser structures. We also study theoretically the effect of individual flux changes on emission wavelength and gain parameters of the laser. The results of simulations allow for determination of flux stability tolerance, preserving acceptable parameters of the laser and provide means of emission wavelength control. The proposed methodology was verified by the growth of laser structures for emission at around 13.5 μm.

Background: Diabetic patients are more likely to experience morbidity and mortality as a result of microvascular complications such as retinopathy, neuropathy, nephropathy, and stroke. There are many synthetic anti-diabetic agents available which are expensive and have undesirable pathological effects. Thus, it is essential to look for cost-effective, natural, and safe antidiabetic agents. The aim of this study was to screen phytoconstituent and evaluate the in-vitro and in-silico α-amylase inhibitory activity of ethanolic extract of Adhatoda vasica leaves. Method: The extraction of Adhatoda vasica leaves was performed with ethanol through Soxhlet extraction process. Different concentrations (0.1 mg/ml to 1 mg/ml) of ethanolic extract, Acarbose, and Sitagliptin, were prepared and all concentrations were evaluated for α-amylase inhibitory activity through the spectrophotometric method. Molecular docking (AutodockVina 1.2.0) and toxicity profiling (SToPToX web server) studies were performed. Results: The plant extract showed highest inhibition of α-amylase (56.763±0.0035) at a concentration of 1 mg/ml. This inhibitory activity was supported by the in-silico study. Vasicoline (C5) and quercetin (C9), active constitute of plant Adhatoda vasica, showed the best binding energy of 8.3 and 8.0 Kcal/mol respectively with α-amylase enzyme (PDBID: 4W93). Toxicity study revealed the safety profile of plant extract. Conclusion: It was concluded that Adhatoda vasica leaves possess some bioactive compounds which are responsible for controlling blood glucose levels and its identification, purification, and isolation may lead to the development of newer therapeutic agent with lesser side effects.

Norepinephrine (NE) uptake through the NE transporter (NET) is the primary mechanism to ter-minate the action of this neurotransmitter. Dysregulation of brain NE levels is associated with various conditions, including attention deficits, depression, and Alzheimer's disease. Recently, we identified an interaction between the related dopamine (DA) transporter (DAT) and G protein βγ subunits. Activation of Gβγ in cells and brain slices leads to DA efflux through DAT. However, the potential interaction between Gβγ and NET has not been reported. Here, we used a combina-tion of molecular modeling approaches to elucidate the structural details of the NET/Gβγ inter-action, supported by experimental evidence. Through 1.5µs of molecular dynamic simulation, we observed a favorable NET/Gβγ interaction mediated by the intracellular carboxy terminus of NET. As a consequence, the binding energy of NE for NET also changes resulting in alterations of the electrostatic profile of NET. We propose that these changes mediate the NE efflux effect. Fi-nally, we provide experimental evidence demonstrating that Gβγ physically interacts with NET and that the Gβγ activator mSIRK induces NE efflux through the transporter. These findings identified a novel interaction between Gβγ and NET and highlighted its potential implications in the regulation of NE neurotransmission and associated disorders.

The chemical feedback between building blocks in templated polymerization of diblock copolymers and their consecutive micellization was studied for the first time by means of coarse-grained molecular dynamics simulations. Using a stochastic polymerization model, we were able to reproduce the experimental findings on the effect of chemical feedback on the polymerization rates at low and high solution concentrations. The size and shape of micelles were computed using a newly development software in python conjugated with graph theory. In full agreement with the experiments, our simulations revealed that micelles formed by the templated micellization are more spherical and have lower radius of gyration than those formed by the traditional two-step micellization method. Understanding the underlying mechanisms in templated reaction/assembly of polymers will help for rational design of new synthetic supramolecular materials.

A large amount of steel slag (SS) and CO2 are generated in the steelmaking process. The indirect CO2 capture using SS is a promising way for co-treatment of the wastes. Ammonium salt solution is widely used to extract Ca2+ from the SS since it is recyclable. Several works have focus on improving the carbonation rate by adjusting various parameters (e.g., temperature and pH). However, there is little detail information about the associating behaviors and interaction strength between the various ions in the ammonia solution during the carbonation process. In this work, the Ca2+–CO32-–NH4+–Cl-–H2O system was established by using Material studio software. The effects of temperature and concentration of CO32- on CaCO3 growth were explored at the atomic scale by calculating the binding energy, mean square displacement, and diffusion coefficient between particles. Furthermore, the microstructure, bonding characteristics, and occurrence behavior of each particle were studied though molecular dynamics simulation methods. The results showed that with the increase of temperature (20–80 ℃), the binding ability and diffusion coefficients of Ca2+ and CO32- increase in the system, which is beneficial to the formation of CaCO3 clusters. With the increase of the concentration of CO32- (15–25 vol.%), the binding ability and diffusion coefficient of Ca2+ and CO32- in the system are enhanced, which is beneficial to the formation of CaCO3 clusters.

The amino acid composition of the active site in an enzyme is influential on its substrate selectivity. For CYP2E1, the role of PHE residues in the formation of effective orientations for its activity toward aromatic substrates remains unclear. In this study, molecular docking and molecular dynamics analysis were performed toward the interactions between PHEs in the active site of human CYP2E1 and various aromatic compounds as confirmed CYP2E1 substrates. The results indicated that the orientation of 1-methylpyrene (1-MP) in the active site was highly modulated by the PHEs, PHE478 contributing to the binding free energy most significantly. Furthermore, by building a random forest model the relationship between each of 19 molecular descriptors of PCB congeners (from molecular docking, quantum mechanics, and physicochemical properties) and established human CYP2E1-dependent mutagenicity of a series of polychlorinated biphenyls (PCBs), which have been proven to be human carcinogens and endocrinal disrupters, was investigated. The presence of PHEs did not appear to significantly modify the electronic or structural feature of each bound ligand (PCB), instead, the flexibility of the molecular conformation of PHEs contributed substantially to the effective binding energy and orientation. It is supposed that PHE residues adjust their own conformation to permit a suitable space for the ligand binding and form an orientation favorable for a biochemical reaction. This study has provided some insights into the role of PHEs in guiding the interactive adaptation of the active site of human CYP2E1 for the binding and metabolism of aromatic substrates.

Antibiotic resistance among bacterial pathogens is recognized as a major threat to human health worldwide. The emergence of multidrug-resistant bacteria can also be found in the community settings, apart from hospital environment, which indicates that reservoirs of antibiotic resistance genes do exist outside the hospital. The growth of antibiotic resistance is a consequence of bacterial adaptations in response to selective pressures. To survive in this hostile environment, bacteria develop defence mechanisms such as chemical modification of antibiotics, enzyme-catalysed antibiotic degradation, altered permeability, antibiotic efflux, mutation of target sites and biofilm formation, resulting in resistance to nearly all currently available antibiotics used in the clinical practice. The present review summarizes insights into the molecular mechanisms underlying the antibiotic resistance which is useful for planning strategies to combat antibiotic resistance and devise innovative therapeutic tools to fight against multidrug-resistant bacterial species.

;Yams are economic and medicinal crops with a long growth cycle, spanning between 9-11 months due to the prolonged tuber dormancy. Tuber dormancy has constituted a major constraint in yam production and genetic improvement. In this study, we performed non-targeted comparative metabolomic profiling of tubers of two white yam genotypes, (Obiaoturugo and TDr1100873), to identify metabolites and associated pathways that regulate yam tuber dormancy using gas chromatography-mass spectrometry (GC-MS). Yam tubers were sampled between 42 days after physiological maturity (DAPM) till tuber sprouting. The sampling points include 42-DAPM, 56-DAPM, 87DAPM, 101-DAPM, 115-DAPM, and 143-DAPM. A total of 949 metabolites were annotated, 559 in TDr1100873 and 390 in Obiaoturugo. 39 differentially accumulated metabolites (DAMs) were identified across the studied tuber dormancy stages in the two genotypes. 27 DAMs were conserved between the two genotypes, whereas, 5 DAMs were unique in the tubers of TDr1100873 and 7 DAMs were in the tubers of Obiaoturugo. The differentially accumulated metabolites (DAMs) spread across 14 major functional chemical groups. Amines and biogenic polyamines, amino acids and derivatives, Alcohols, flavonoids, alkaloids, phenols, esters, coumarins and phytohormone positively regulated yam tuber dormancy induction and maintenance, whereas, fatty acids, lipids, nucleotides, carboxylic acids, sugars, terpenoids, benzoquinones, and benzene derivatives positively regulated dormancy breaking and sprouting in tubers of both yam genotypes. Metabolite set enrichment analysis (MSEA) revealed that 12 metabolisms were significantly enriched during yam tuber dormancy stages. Metabolic pathway topology analysis further revealed that six metabolic pathways (linoleic acid metabolic pathway, phenylalanine metabolic pathway, galactose metabolic pathway, starch and sucrose metabolic pathway, alanine-aspartate-glutamine metabolic pathways and purine metabolic pathway) exerted significant impact on yam tuber dormancy regulation. This result provides vital insights into molecular mechanisms regulating yam tuber dormancy.

The outbreak of Coronavirus, as well as its emerging potential consequences, has become a global challenge worldwide, demanding effective and controlled therapeutic strategies. Potential drug candidates could achieve that with minimal toxicity. The current investigation selected 2-Deoxy-D-glucose prescribed by Defense Research and Development Organization (DRDO), India. The derivative and modified form was tested through in silico analysis against COVID-19 main protease complex with N3 inhibitor. The derived form of 2-Deoxy-D-glucose was generated by replacing the hydroxy group with a hydrogen atom, and Cypate 2-Deoxy-D-glucose was chosen as a derivative against the COVID-19 main protease complex. A molecular docking approach was adopted to identify the stable and competent form among the modified and derivative forms of 2-Deoxy-D-glucose based on binding energy. By further promoting the stabilized complex, these compounds' toxicity was also scrutinized through ADMET analysis to predict the potential candidate. The current investigation suggested that the modified version of 2-Deoxy-D-glucose was more stable with minimal toxicity against COVID-19 main protease.

The permeation of dioxin-like pollutants, namely, chlorinated dibenzodioxins and dibenzofurans, through lipid membranes has been simulated using classic molecular dynamics (CMD) combined with the umbrella sampling approach. The most toxic forms of chlorinated dibenzodioxin and dibenzofuran, 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD) and 2,3,7,8-tetrachlorodibenzofuran (TCDF), and a dioleyl-phosphatidylcholine (DOPC) lipid membrane of 50 Å wide have been chosen for our study. The free energy profile shows the penetration process is largely favoured thermodynamically (DG≈-12 kcal/mol), with a progressively decrease of the free energy until reaching the energy minima at distances of 8Å and 9.5Å from the centre of the membrane for, respectively, TCDD and TCDF. At the centre of the membrane, both molecules display subtle local maxima with free energy differences of 0.5 and 1 kcal/mol with respect to the energy minima for TCDD and TCDF, respectively. Furthermore, the intermolecular interactions between the molecules and the lipid membrane have been characterized at the minima and the local maxima using hybrid quantum mechanics/molecular mechanics energy decomposition analysis (QM/MM-EDA). Total interaction energies of -17.5 and -16.5 kcal/mol have been found at the energy minima for TCDD and TCDF, respectively. In both cases, the dispersion forces govern the molecule-membrane interactions, no significant changes have been found at the local maxima, in agreement with the classical free energy profile. The small differences found in the results obtained for TCDD and TCDF point out the adsorption and diffusion processes through the cell membrane are not related to the different toxicity shown by these pollutants.

2-Methylquinazolin-4(3H)-one was prepared by reaction of anthranilic acid, acetic anhydride and ammonium acetate. The reaction of 2-methylquinazolin-4(3H)-one with N-aryl-2-chloroacetamides in acetone in the presence of potassium carbonate gave nine N-aryl-2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetamide compounds. The structures of these compounds were elucidated on the basis of their IR, 1H-NMR, 13C-NMR and HR-MS spectral data. These synthesized compounds containing the 2-methyl-3,4-dihydroquinazolin-4-one moiety exhibited excellent activity against Aedes aegypti mosquito larvae with LC50 values in the range of 2.085-4.201 μg/mL after 72 h exposure. Interestingly, these compounds did not exhibit toxicity to the non-target organism Diplonychus rusticus. In silico molecular docking revealed acetylcholine binding protein (AChBP) and acetylcholinesterase (AChE) to be potential molecular targets. These data indicated the larvicidal potential and environmental friendliness of these N-aryl-2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetamide derivatives.

Antarctica is one of the most inhospitable continents on the planet, with lichens and mosses being the most common terrestrial organisms in ice-free areas. Antarctica is represented by only two species of Angiosperms, Deschampsia antarctica Desv. (Poaceae) and Colobanthus quitensis (Kunth) Bartl. (Caryophyllaceae). In this study, we characterized fungi isolated from the leaves of this grass species. The fungi were isolated from 4 individual plants from Half Moon Island (246 leave fragments investigated), and 7 from King George Island - Keller Peninsula (with 111 leave fragments investigated) Antarctica. Neoascochyta paspali, Phaeosphaeria elongata, Pyrenophora cf. chaetomioides and Alternaria sp. were associated with the plant and identified through analysis of the sequences of the internal transcribed spacer region (ITS) of the rDNA and nuclear ribosomal large subunit rRNA gene (LSU) as well as macro and micro-morphological characteristics. The isolates showed a better growth rate ranging from 10–20°C. An interesting result was that the fungi are already recognize as both plant pathogens and endophytic fungi. The results demonstrate that D. antarctica is an interesting fungal source. Those species might provide important information about the relationship on the endemic Antarctic biota.

Whole-genome sequencing has advanced our understanding of the population structure of the pathogenic species complex Cryptococcus gattii, which has allowed for the phylogenomic specification of previously described major molecular type groupings and novel lineages. Recently, isolates collected in Mexico in the 1960s were determined to be genetically distant from other known molecular types and were classified as VGVI. We sequenced four clinical isolates and one veterinary isolate collected in the southwestern U.S. and Argentina during 2012-2021. Phylogenomic analysis groups these genomes with those of the Mexican VGVI isolates, expanding VGVI into a clade and establishing this molecular type as a clinically important population. These findings also potentially expand the known Cryptococcus ecological range with a previously unrecognized endemic area.

Eukaryotic cells contain membranes with various curvatures, from the near-plane plasma membrane to the highly curved membranes of organelles, vesicles, and membrane protrusions. These curvatures are generated and sustained by curvature-inducing proteins, peptides, and lipids, and describing these mechanisms is an important scientific challenge. In addition to that, some molecules can sense membrane curvature and a thereby be trafficked to specific locations. The description of curvature-sensing is another fundamental challenge. Curved lipid membranes and their interplay with membrane-associated proteins can be investigated with molecular dynamics (MD) simulations, given the right tools. Various methods for simulating curved membranes with MD are discussed here, including tools for setting up simulation of vesicles, and methods for sustaining membrane curvature. The latter are divided into methods that exploit scaffolding virtual beads, methods that use curvature-inducing molecules, and methods applying virtual forces. The variety of simulation tools allow the researcher to closely match the conditions of experimental studies of membrane curvatures.

Molecular communication (MC) is a promising bio-inspired paradigm for exchanging molecule information among nanomachines. This paper proposes a synchronisation-assist photolysis MC system that aims to transmit the bio-sensing signal of the tumour microenvironment, facilitated by mitigating redundant molecules for improved bit error rate (BER) performance. Benefits from bio-compatible MC, biosensors could transmit bio-sensing signals of the tumour in $vivo$ instead of converting them to electrical signals. Due to diffusion motion's slow and stochastic nature, inter-symbol interference (ISI), resulting from previous symbols' residual information molecules, inevitably occurs in diffusion-based MC. ISI is one of the challenges in diffusion-based MC, which significantly impacts signal detection. Inspired by on-off keying (OOK) modulation, the proposed modulation implements a switch of molecules and light alternatively. The light emitted is triggered by a synchronisation signal, and the photolysis reactions could reduce the redundant molecules. An expression for the relevant channel impulse response (CIR) is derived from a hybrid channel model of diffusion and photolysis-reaction. This paper implements the maximum posterior estimation scheme to find the optimal decision threshold and analysis the BER performance in terms of different time intervals of the system. Numerical simulations demonstrate that the proposed method can improve the channel capacity and BER performance. We believe that our work may pave the way for MC application in bio-sensing.

Systematics plays the most crucial role in biodiversity conservation which is at stake due to anthropogenic activities and environmental degradations. The ever-increasing decline of classical taxonomic expertise drives the need to develop molecular marker-based tools for quick, efficient, and reliable detection of organisms, to assess their ecological impacts for deepening our understanding of systematic and evolutionary relationships between organisms which is central to biology. The pace of alpha taxonomy has quickened by its integration with an increasingly fashionable and novel concept called DNA barcoding which utilizes a short genetic marker or barcode to categorize species for enhanced biodiversity assessment. As a supplementary but not complete alternative of systematics research, DNA barcoding, however, not error-free, brings precision in identification by solving existing problems of classical taxonomy and phylogenetics, irrespective of the growth stage of organisms, particularly for known taxa rather than unknown ones. Mitochondrial gene Cytochrome C Oxidase 1 (COI) serves as a universal animal barcode but there is no such universal barcode for plants and developing a suitable one is more challenging. With the recent advancement of Next Generation Sequencing (NGS), DNA metabarcoding technology is advancing rapidly. Still, ambiguity and error prevail with the correct identification of species due to some problems. After extensive analysis of the existing DNA barcoding papers, this review discusses commonly used DNA barcodes in plants and animals, their roles, advantages, limitations to solve existing problems of conservation biology and add the author’s views and recommendations.

Metamorphosis is a critical process for most anurans to transition from water to land. The appearance of air-breathing lungs occurs during the change in oxygen medium from water to air. Revealing the structural construction and molecular switches of lung organogenesis is essential to understand the realization of air-breathing function. In this study, histology and transcriptomics were combinedly conducted to explore these issues in Microhyla fissipes lungs during metamorphosis. During the pro-metamorphic phase, histological structure improving of the alveolar wall was accompanied by robust substrate metabolism and protein turnover. The lungs, at the metamorphic climax phase, are characterized by an increased number of cilia in the alveolar epithelial cells and collagenous fibers in the connective tissues, corresponding to the transcriptional upregulation of cilia and extracellular matrix-related genes. The post-metamorphic lungs strengthen the contracting function, as suggested by the thickened muscle layer and the upregulated expression of genes involved in muscle contraction. The blood–gas barrier is fully developed in adult lungs whose transcriptional features are tissue growth and differentiation regulation and immunity. Importantly, significant transcriptional switches of pulmonary surfactant protein and hemoglobin facilitate air-breathing. Our results illuminated four key steps of lung development for amphibians to transition from water to land.

ATP Synthase is an essential molecule in cell and molecular biology. It is responsible for the production of ATP during cellular respiration, a molecule that provides the energy required to drive a number of cellular processes. In this paper, I explore the rotational physics of ATP Synthase’s rotor, a part of the protein that spins during the production of ATP. Firstly, I discuss some elementary rotational kinematics of the rotor. I then derive two alternate formulations for the total linear acceleration of the rotor. Finally, I derive formulas for the moment of inertia, angular momentum, net torque, and kinetic energy of the rotor. Through this, I hope to provide a theoretical and mathematical insight into the mechanics of ATP Synthase during the production of ATP.

The exploration of alternative antimalarial therapeutics is a requisite for the emergence of resistance against Artemisinin. Considering the required cost and time length of classical small molecule drug discovery process, phytochemical screening of traditionally used medicinal plant which are repertoire of active compounds with antimalarial activity has become popular. To investigate the antimalarial property of traditionally used medicinal plants, a number of Erythrina spp have been reviewed systematically where less studied E. fusca has been selected for further analysis. Phytochemical investigation yielded five compounds namely; Phaseolin, Phytol, β-amyrin, Lupeol, and Stigmasterol. In-vitro antimalarial drug sensitivity HRP-II ELISA was carried out against chloroquine (CQ) sensitive 3D7 and CQ-resistant Dd2 strains. Extracts showed significant antimalarial activity against 3D7 and Dd2 strains (IC₅₀ 4.94 – 22 µg/mL) and these compounds have been reported here for the first time. Molecular docking analysis showed high binding energy (−9.0 ± 0.32 kcal/mole) indicating high degree of interaction between Phaseolin and 14 clinically important Plasmodium falciparum proteins at the active site. Stable interaction was also observed between ligand and protein from molecular dynamics simulation analysis with high free energy (−75.156 ± 11.459) that substantiates the potential of Phaseolin as an antimalarial drug candidate.

A cryptic invader of the genus Persicaria is recently increasing in the damper, northern parts of La Palma and Gran Canaria in the Canary Islands (Spain) and locally behaves as an invasive species. Examination of historical herbarium specimens showed this species to be present in Gran Canaria since the 1960’s and the same probably applies to La Palma. Up to now, this species had been assigned to the Old World weed P. maculosa. However, morphologically these plants clearly correspond with P. hydropiperoides, a common and widespread weed native to the New World, and morphologically similar indeed to P. maculosa. Diagnostic features for these two species, as well as for another similar species (P. decipiens, originally described from the Canary Islands), are compared, thoroughly discussed and copiously illustrated. The current distribution, ecology and naturalization status of P. hydropiperoides in the Canary Islands are also assessed. The variability of P. hydropiperoides is discussed, more precisely the taxonomic position of a southern ‘race’ of it that is sometimes referred to as a distinct species, P. persicarioides. In addition to our morphology-based study, a molecular phylogenetic analysis has been conducted on the nuclear ITS region and the plastid DNA region trnL-F.

Molecular Dynamics (MD) simulations model motion of molecules in atomistic detail and aid in drug design. While simulations on large systems may require several days to complete, analysis of terabytes of data generated in the process could also be time consuming. Recent studies captured exciting and dramatic drug-receptor interactions under cell-like complex conditions. Such advances make simulations of biomolecular interactions more realistic, insightful, and informative and have potential to make drug design more realistic. However, currently available resources and techniques do not provide, in reasonable time, a comprehensive understanding of events seen in simulations. We demonstrate that big data approach results in significant speedups, and provides rapid insights into simulations performed. Advancing this improvement, we propose a scalable, self-tuning, and responsive framework based on Cloud-infrastructure to accomplish the best possible MD studies with given priorities and within available resources.

Oncogenic protein E6 from Human Papilloma Virus 16 (HPV-16) mediates the degradation of Membrane-associated guanylate kinase with inverted domain structure-1 (MAGI-1), throughout the interaction of its protein binding motif (PBM) with the Discs-large homologous regions 1 (PDZ1) domain of MAG1-1. Generic variation in the E6 gene that translates to changes in the protein’s amino acidic sequence modifies the interaction of E6 with the cellular protein MAGI-1. MAGI-1 is a scaffolding protein found at tight junctions of epithelial cells, where it interacts with a variety of proteins regulating signaling pathways. MAGI-1 is a multidomain protein containing two WW (rsp-domain-9), one guanylate kinase-like, and six PDZ domains. PDZ domains played an important role in the function of MAGI-1 and served as targets for several viral proteins including the HPV-16 E6. The aim of this work was to evaluate, with an in silico approach, employing molecular dynamics simulation and protein-protein docking, the interaction of the intragenic variants E-G350 (L83V), E-C188/G350 (E29Q/L83V), E-A176/G350 (D25N/L83V), E6-AAa (Q14H/H78Y/83V) y E6-AAc (Q14H/I27RH78Y/L83V) and E6-reference of HPV-16 with MAGI-1. We found that variants E-G350, E-C188/G350, E-A176/G350, AAa and AAc increase their affinity to our two models of MAGI-1 compared to E6-reference.

Silybum Marianum, is a plant belonging to the family Asteraceae. For many centuries it has been used a natural remedy for many diseases like Liver and Biliary tract diseases. It is effective as an anti-oxidant and is used in a variety of diseases. This study was conducted to check the effects of Silybum Marianum on PARP protein (4UND protein).The Molecular Docking techniques was chosen to check the effects of different chemical constituents of Silybum marianum on DNA damaging protein. For this purpose, different PARP inhibitor drugs were taken as standard. The Molecular Docking of the chemical constituents of Silybum marianum was performed using 4UND protein with the help of PyRx software along with BIOVIA Drug Discovery studio software. The result of molecular docking showed that some of the chemical constituent have higher binding affinity than standard PARP inhibitor drugs.

Muscle is one of the most critical organs for mammals, which governs multiple movement and physiological functions. Circular RNA (circRNA) is a kind of novel endogenous RNA without 5'-Caps and 3'-poly(A) structures formed by pre-mRNA's back-splicing. RNA binding proteins (RBPs) control the production and degradation of circRNA, help nucleus-cytoplasm transport and locate circRNA, and regulate circRNA translation. Therefore, circRNAs and the chaperoned RBPs play critical roles in muscle growth, development, and disease progression. In this review, we systematically characterize the possible molecular mechanism of circRNA-protein interactions. Also, we summarize the latest researches on circRNA-protein interactions in muscle development and diseases. Besides, we provide several valid prediction methods and experimental verification approaches. Our review reveals the importance of circRNAs and their protein chaperones and provides a reference for further study in this field.

In this work, a tool for estimating the contact angle from the molecular dynamics simulations is developed and presented. The tool (Achilles) can detect water droplet on hydrophobic and hydrophilic surfaces. The tool can reconstruct the droplets broken across the periodic boundaries. Further a neighbor density based accurate filter is used to find the droplet liquid vapor interface and a circle is fitted using it after removing the dense layers of water next to solid surface. This fitted circle is solved for contact angle and results are outputted in the form of graphical images and text. The entire content of the internal computations of the tool is broken down into 4 phases and users can monitor the outcomes at every phase through output images. The tool is tested using sample molecular dynamics results of water droplet on hydrophobic and hydrophilic surfaces. We believe this tool can be a good addition to the molecular dynamics simulation community who work on the interfacial physics, droplet evaporation, super hydrophobic surfaces, and wettability etc.

In this paper, we introduce a simple yet powerful and working version of the molecular dynamics code using the Python 3.9 language. The code contents are published in the link given in the appendix 1. The structure and components of the program is given in detail using flowcharts and code snippets. The program consists of major features like velocity verlet integrator, thermostats, COM removal, input and output modules, virial, pressure, and other thermodynamic quantities estimation etc. The author believes that this program will be helpful to graduate students who perform research in molecular dynamics simulations who intend to write their own code instead of the sophisticated open source packages.

Epithelial-mesenchymal transition (EMT) plays an important role in the acquisition of cancer stem cell (CSC) feature and drug resistance, which are the main hallmarks of cancer malignancy. Although previous findings have shown that several signaling pathways are activated in cancer progression, the precise mechanism of signaling pathways in EMT and CSCs are not fully understood. In this study, we focused on the intestinal and diffuse-type gastric cancer (GC), and analyzed the gene expression of public RNAseq data to understand the molecular pathway regulation in different subtypes of gastric cancer. Network pathway analysis was performed by Ingenuity Pathway Analysis (IPA). Total 2815 probe set IDs were significantly different between intestinal- and diffuse-type GC data in cBioPortal Cancer Genomics. The 10 genes including male-specific lethal 3 homolog (Drosophila) pseudogene 1 (MSL3P1), CDC28 protein kinase regulatory subunit 1B (CKS1B), DEAD-box helicase 27 (DDX27), golgi to ER traffic protein 4 (GET4), chromosome segregation 1 like (CSE1L), translocase of outer mitochondrial membrane 34 (TOMM34), YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), ribonucleic acid export 1 (RAE1), par-6 family cell polarity regulator beta (PARD6B), and MRG domain binding protein (MRGBP) were found to have difference in gene expression in intestinal- and diffuse-type GC. Total 463 direct relationships with 3 molecules (MYC, NTRK1, UBE2M) were found in the biomarker-filtered network generated by network pathway analysis. The networks and features in intestinal- and diffuse-type GC have been investigated and profiled in bioinformatics. Our results revealed the signaling pathways networks in intestinal- and diffuse-type GC, bringing new light for the elucidation of drug resistance mechanisms in CSCs.

Brucella abortus is a facultative intracellular Gram-negative bacterium that causes chronic persistent infections in humans and livestock. In this study, conventional bio-typing, multiple-locus variable-number tandem repeat analysis (MLVA), and whole-genome sequencing-single-nucleotide polymorphism (WGS-SNP) were used to investigate the molecular epidemiology characteristics of Brucella abortus strains in China and their relationships to world lineages. A total of 100 strains were collected from 1953 to 2013, suggesting that B. abortus circulated in China in the past five decades. Moreover, most strains were mainly distributed in the northwest area. During this period, seven biovars were found, indicating that B. abortus displayed a high diversity of biovars and that the main epidemic areas are in the northern provinces. Strains have high genetic diversity, and bruce07 is the most helpful locus for genotyping of this population. Moreover, 17 MLVA-11 genotypes were found; 13 of them are of known genotypes and four are unassigned genotypes, indicating that B. abortus in this study had several geographic origins. Still, strains from unassigned genotypes may originate from China. Many shared MLVA-16 genotypes were observed in strains from the same provinces in Northern China, which confirmed a brucellosis outbreak within northern regions. WGS-SNP analysis showed that eight Chinese strains formed a ladder-like phylogram (C. Ⅶ) with strains from nine countries, including Uganda, Iraq, Russia, Georgia, Spain, Italy, Egypt, Mongolia, and China; strains were introduced to these countries from a single source. Notably, Chinese strains were closely related to strains from Russia and Mongolia; frequent animal (cattle) trade and exchanges may promote this process. We will provide new and insightful information for strength surveillance and control of B. abortus brucellosis in China.

The natural products and conventional chemotherapeutic drugs are believed to increase the cure rates of anti-cancer treatment while reducing their toxicity. The current study investigates the cytotoxic and apoptogenic effects of bioactive compounds from Monotheca buxifolia on Hep G2 cell lines. The effect on the viability of Hep G2 cells was evaluated by MTT assay; Morphological changes were studied, the apoptotic activity was demonstrated through Annexin-V-FITC/ PI, a molecular dynamics simulation study was conducted to explore the binding pattern of the compounds in the active site of the PPRAδ protein. The isolated compounds lauric acid, oleanolic acid, and bis(2-ethylhexyl) phthalate inhibited the growth of hepatocellular cancer cells, as determined by MTT assay and annexin V-FITC/PI. The IC50 value for lauric acid was 56.4584 ± 1.20 µg/ml, that for oleanolic acid was 31.9421 ± 1.03 µg/ml, and that for bis(2-ethylhexyl) phthalate was 83.8019 ± 2.18 µg/ml. After 24 h of treatment, 29.5% of Hep G2 cells treated with lauric acid, 52.1% of those treated with oleanolic acid, and 22.4% of those treated with bis(2-ethylhexyl) phthalate were apoptotic. Morphological assay and Hoechst staining microscopy revealed the morphological alterations of cell membrane accompanied by nuclear condensation after treatment. The high fluctuation indicates the high potency and adopting various interactions, and vice versa, the oleanolic acid showed highly residues fluctuation, which remains stable in the active site of PPARδ protein and involved in various interactions while remaining locally fluctuated in the binding site the other two compounds. In conclusion, a significant apoptogenic effect was exhibited by lauric acid, oleanolic acid, and bis(2-ethylhexyl) phthalate against HepG2 cells in inducing apoptosis. Our findings indicate that these bioactive compounds hold promise as potential therapeutic for hepatocellular carcinoma.

Mutation in the ethionamide (ETH) activating enzyme, EthA, is the main factor determining resistance to this drug, used to treat TB patients infected with MDR and XDR Mycobacterium tuberculosis isolates. Many mutations in EthA of ETH resistant (ETH-R) isolates have been described but their roles in resistance remain uncharacterized, partly because structural studies on the enzyme are lacking. Thus, we took a two-tier approach to evaluate two mutations (Y50C and T453I) found in ETH-R clinical isolates. First, we used a combination of comparative modeling, molecular docking, and molecular dynamics to build an EthA model in complex with ETH that has hallmark features of structurally characterized homologs. Second, we used free energy computational calculations for the reliable prediction of relative free energies between the wild type and mutant enzymes. The ΔΔG values for Y50C and T453I mutant enzymes in complex with FADH₂-NADP-ETH were 3.34 (+/−0.55) and 8.11 (+/−0.51) kcal/mol, respectively, compared to the wild type complex. The positive ΔΔG values indicate that the wild type complex is more stable than the mutants, with the T453I complex being the least stable. These are the first results shedding light on the molecular basis of ETH resistance, namely reduced complex stability of mutant EthA.

COVID-19, a rapidly spreading new strain of coronavirus, has affected more than 150 countries and received worldwide attention. The lack of efficacious drugs or vaccines against SARS-CoV-2 has further worsened the situation. Thus, there is an urgent need to boost up research for the development of effective therapeutics and affordable diagnostic against COVID-19. The crystallized form of SARS-CoV-2 main protease (Mpro) was demonstrated by a Chinese researcher Liu et al. (2020) which is a novel therapeutic drug target. This study was conducted to evaluate the efficacy of medicinal plant-based bioactive compounds against COVID-19 Mpro by molecular docking study. Molecular docking investigations were performed by using Molegro Virtual Docker 7 to analyze the inhibition probability of these compounds against COVID-19. COVID-19 Mpro was docked with 80 flavonoid compounds and the binding energies were obtained from the docking of (PDB ID: 6LU7: Resolution 2.16 Å) with the native ligand. According to obtained results, hesperidin, rutin, diosmin, apiin, diacetylcurcumin, (E)-1-(2-Hydroxy-4-methoxyphenyl)-3-[3-[(E)-3-(2-hydroxy-4- methoxyphenyl)-3-oxoprop-1-enyl]phenyl]prop-2-en-1-one, and beta,beta'-(4-Methoxy-1,3- phenylene)bis(2'-hydroxy-4',6'-dimethoxyacrylophenone have been found as more effective on COVID-19 than nelfinavir. So, this study will pave a way for doing advanced experimental research to evaluate the real medicinal potential of these compounds to cure COVID-19.

On the primitive Earth, both L- and D-amino acids would have been present. However, only L-amino acids are essential blocks to construct proteins in modern life. To study the relative stability of D-amino acid substituted peptides, a variety of computational methods were applied. Ten prebiotic amino acids (Gly, Ala, Asp, Glu, Ile, Leu, Pro, Ser, Thr, and Val) were previously determined by multiple meteorite, spark discharge, and hydrothermal vent studies. Some previously reported early Earth polypeptide analogs were focused on in this study. Tripeptides composed of only Asp, Ser, and Val exemplified that different positions (i.e., N-terminus, C-terminus, and middle) made a difference in the minimal folding energy of peptides, while the chemical classification of amino acid (hydrophobic, acidic, or hydroxylic) did not show a significant difference. Hierarchical cluster analysis for dipeptides with all possible combinations of the proposed ten prebiotic amino acids and their D-amino acid substituted derivatives generated five clusters. Primordial simple polypeptides were modeled to test the significance of molecular fluctuations, secondary structure occupancies, and folding energy differences based on these clusters. We found peptides with α-helices, long β-sheets, and long loops are usually less sensitive to D-amino acid replacements in comparison to short β-sheets. Intriguingly, amongst 129 D-amino acid residues, mutation sensitivity profiles presented that the ratio of more to less stable residues was about 1. In conclusion, some combinations of a mixture of L- and D-amino acids can potentially act as essential building blocks of life.

Molecular visualisation is fundamental in the current scientific literature, textbooks and dissemination materials, forming an essential support for presenting results, reasoning on and formulating hypotheses related to molecular structure. Visual exploration has become easily accessible on a broad variety of platforms thanks to advanced software tools that render a great service to the scientific community. These tools are often developed across disciplines bridging computer science, biology and chemistry. Here we first describe a few Swiss Army knives geared towards protein visualisation for everyday use with an existing large user base, then focus on more specialised tools for peculiar needs that are not yet as broadly known. Our selection is by no means exhaustive, but reflects a diverse snapshot of scenarios that we consider informative for the reader. We end with an account of future trends and perspectives.