Insulated Gate Bipolar Transistor (IGBT) may convey high current and sustain high breakdown voltages; it may provide high power control. In a sense, how IGBT demonstrates the capability of power control was not specifically described, and the equivalent bipolar junction transistors (BJT) activated by an applied bias to the insulated gate is intriguing. As seen in Figure 1, IGBT shows an equivalent circuit structure containing two types of BJT, (NPN-type Bipolar transistor and PNP-type Bipolar transistor), which can be modeled as diode-associated transistor. Apparently, as a bias applies to the controlling gate, the channel beneath the gate oxide gets strongly inversed and turns out to be conductive just like what happens on metal-oxide-silicon field effect transistor (MOSFET), which provides necessary igniting currents to both BJTs and thus causes high current gain flowing through them-selves from the bottom. A proposed and renewed formula provides addressing the above scenario and successfully fitting the measured data that forms the characteristic curves. Some parameters in the proposed formula, which includes size and mobility associated constant, threshold voltage, and Early-Voltage-related lambda for MOSFET, explain and explore the underlying physics. IGBT thus enjoy high input impedance and high current gain due to MOSFET (Insulated Gate) and BJT, respectively. This formula combines both merits of MOSFET and BJT in order to fit the measured data. Indeed, the formula intimately fits IGBT electrical characteristic curves, and thus may be qualified and served as a model. The new model is then advisable for designing power integrated circuit to exactly achieve power saving, power control, and power efficiency.

This review article focuses on the role of Artificial Intelligence (AI) in transforming healthcare in Africa, specifically in combatting infectious diseases, neglected tropical diseases (NTDs), and antimicrobial resistance. We provide a comprehensive overview of the significance of AI in the healthcare industry, highlighting its urgency and importance in addressing these specific health challenges in Africa. We begin by discussing the role of AI in infectious disease surveillance and outbreak detection. We explore how AI technology can be employed for real-time tracking and prediction of outbreaks, providing examples of successful AI applications in infectious disease surveillance within the African context.Next, we examine the potential of AI-enabled diagnosis and treatment for faster and more accurate diagnoses of infectious diseases and NTDs. We highlight specific examples of AI applications in diagnosing and treating these diseases in Africa, showcasing the potential of AI to improve clinical outcomes and save lives.Furthermore, we focus on how AI-driven drug discovery and development can expedite the search for new treatments for infectious diseases and combat antimicrobial resistance. We present examples of AI applications in drug discovery within the African context, illustrating the potential for AI to revolutionize the development of effective therapeutics.In addition, we delve into how AI-powered public health interventions can enhance the design and implementation of targeted interventions. We explore how AI can optimize resource allocation and facilitate data-driven decision-making processes, providing examples of AI applications in public health in Africa.Finally, we address the challenges and limitations of implementing AI in combatting infectious diseases, NTDs, and antimicrobial resistance in Africa. We discuss potential barriers and ethical concerns surrounding AI applications in healthcare, aiming to encourage informed and responsible utilization of AI technologies.Overall, this review emphasizes the importance and potential of AI in combatting infectious diseases, NTDs, and antimicrobial resistance in Africa. It positions AI as a catalyst for revolutionizing healthcare in the region, leading to more effective disease surveillance, diagnosis, treatment, drug discovery, and public health interventions.

Wavelength selective switches (WSSs) are essential elements for wavelength division multiplexing (WDM) optical networks, as they offer cost-effective, high port-count and flexible spectral channel switching. This work proposes a new hybrid WSS architecture that leverages the beam shaping and steering features of uniform silicon nitride (SiN) based end-fire optical phased arrays (OPAs). By introducing beamforming to a WSS system, the spectral channels on the liquid crystal on silicon (LCoS) panel can be tailored and arranged properly, depending on the optical configuration, using the beam control capabilities of OPAs. Combining 3D-FDTD and ray tracing simulations, the study shows that by reducing the input beam dimensions with proper sizing of the OPAs, the WSS design with the null-steering OPAs layout and 4×No switch size features increased spectral resolution. This extensive beamforming study on the steering-enabled layout reveals the acquirement of an even higher input channel number, achieving up to the 8×No WSS scheme with flexible channel routing on the LCoS panel. Such implementation of beamsteerers can unlock an extra degree of freedom for the switching capabilities of hybrid WSS devices. The results show great promise for the introduction of OPAs in WSS systems and provide valuable insight for the design of future wireless communication links and WDM systems.

Improper disposal of waste plastic has caused serious ecological and environmental pollution problems. Transforming plastics into high value-added chemicals can not only achieve efficient recycling of waste plastics, but also an effective way to control white pollution. The catalyst selectively breaks the C-C bond of polyolefin plastic under heat treatment and converts it into liquid fuel, thus realizing sustainable recycling of plastics and has a good development prospect. This review provides a detailed overview of the current development of catalytic pyrolysis, catalytic hydrolysis, solvent decomposition and supercritical hydrothermal liquefaction for cracking plastics to make fuel oil. The reaction mechanism, influencing factors and promoting effects of catalysts in various degradation technologies are analyzed and summarized and the latest proposed tandem reaction for degrading plastics is briefly introduced. Finally, some optimization paths of waste plastic pyrolysis to fuel oil technology are proposed: synergies between mixed raw materials, in-depth exploration of catalysts, design and manufacture of reactors that match the pyrolysis technology. All these are important research directions for promoting the industrialization of plastic pyrolysis to fuel oil.

Employing remote sensing techniques to evaluate crop residue cover (CRC) enables rapid mapping of tillage practices over large cropland areas, which has significant practical implications for monitoring the implementation of conservation tillage practices. This research utilized Sentinel-2 MSI and Landsat-8 OLI remotely sensed data, various spectral indices were calculated and the datasets were correlated with the field-measured CRC data. Selected spectral indices, highly significantly correlated, were chosen to build a correlation model between the indices and the CRC. Considering Sentinel-2 MSI and Landsat 8 OLI remotely sensed data variations in spectral and spatial scales, the accuracy of CRC models was evaluated using R2 and RMSE values. From the results, it's evident that all six spectral indices, including STI, NDTI, SRNDR, NDI5, NDI7 and NDSVI, registered correlation coefficients with the CRC exceeded 0.3 in the study area. STI and NDTI showed a stronger correlation to CRC, with coefficients of 0.810 and 0.803, respectively. For the Landsat 8 data, the lowest correlation obtained was for NDSVI with the Landsat 8 data with a correlation coefficient of 0.358. Applying the linear regression technique, STI and NDTI obtained higher accuracy compared to other indices in the Sentinel-2 MSI data. For NDTI and STI, The R2 values were 0.650 and 0.665, respectively, while their corresponding RMSE values were 3.96% and 4.03%. The highest model accuracy was obtained for the STI and NDTI constructed from the Landsat 8 OLI data (R2 values 0.41 and 0.40; RMSE values 5.25% and 5.27%, respectively). The CRC model built using partial least squares regression (PLSR) exhibited greater precision when applied to the Sentinel-2 MSI data (R2 value 0.894; RMSE value 2.18%) in comparison to the Landsat 8 OLI data (R2 value 0.695; RMSE value 3.70%). PLSR has the potential to enhance the precision of the model. In addition, the study area shows that the estimation of the CRC is better in the one-dimensional linear regression model and the PLSR model created with the Sentinel-2 MSI optical data compared to the Landsat 8 OLI optical remotely sensed data. The validation suggests that the CRC estimation in the study area is more precise when using the model relying on Sentinel-2 satellite imagery rather than the Landsat 8 OLI imagery.

The Mara River basin (MRB) has a world-famous ecosystem, but the vegetation has been damaged due to economic development in recent years, and there is little known about the area that will experience severe vegetation damage in the future. Based on the vegetation vulnerability system, principal component analysis, and three CMIP6 scenarios (SSP1-2.6, SSP2-4.5, SSP5-8.5), vegetation vulnerability was calculated in the base period (2010-2019), near-term period (2020-2059) and long-term period (2060-2099) in the MRB. The spatial cluster of vegetation vulnerability was revealed by spatial correlation analysis, and the transition of vegetation vulnerability of different periods was analyzed by stochastic matrix. The results showed that in all periods, the vulnerability showed a high-high cluster in the east, and a low-low cluster midstream and downstream. From the stochastic matrix, the area of high vulnerability increased the least under the SSP1-2.6, while it increased the most under the SSP5-8.5. The vegetation vulnerability upstream increased the most from the base period to the near-term period and long-term period in the MRB. By comparing the vegetation vulnerability under different scenarios, and pointing out the areas with the highest vulnerability increase, this study can better provide comprehensive decision-making for vegetation protection in the MRB.

Chinese texts often feature a substantial volume of normative content, and their analysis has increasingly become a focal point in recent semantic analysis endeavors. Enhancing the effectiveness of text classification and clustering is pivotal in unveiling the intricate semantics within extensive textual data. Empirical research within the realm of computational social science has underscored the need for improved explanatory power when it comes to general text clustering methods applied to normative texts. This study introduces an innovative hierarchical clustering method that incorporates part-of-speech (POS) features and pioneers a novel semantic network model. It achieves this by amalgamating a POS-based feature weight calculation method with hierarchical clustering techniques. To assess its efficacy, the method is rigorously evaluated across three diverse text datasets, encompassing normative reports, news articles, and social media content. The experimental results unequivocally demonstrate the superior performance of the POS-HC method, surpassing the traditional TF and TF-IDF feature extraction methods in terms of clustering accuracy, and surpassing some existing clustering methods. Furthermore, its classification effectiveness exhibits notable advantages, particularly in the semantic classification of normative texts.

Dried blood spot (DBS) testing on confetti is one of the most common methods used to collect and extract DNA from field samples for molecular epidemiology of malaria studies. Here, we investigated whether ethanol or other solutions used to clean scissors are a source of sample contamination. DBS were prepared from 3 drops of blood from two Plasmodium falciparum cultures spotted on confetti, and 3 solutions (water, ethanol and DNase) were used to clean scissors between spots during DNA extraction. For each cleaning solution, two blank confetti were used as negative controls. Samples were analyzed by PCR-based genotyping of merozoite surface proteins 1 & 2 (msp-1 and msp-2), and P. falciparum chloroquine resistance transporter (Pfcrt). A total of 15 samples were analyzed. Based on msp-1 and msp-2 amplification, P. falciparum was detected on blank confetti when scissors were washed with ethanol. Based on Pfcrt amplification, DNA of P. falciparum was detected on blank confetti when scissors were cleaned with ethanol or water. No P. falciparum genes were detected on blank confetti when scissors were cleaned with DNase. Scissors cleaned with DNase prevented cross-contamination between samples during processing of dried blood spots, whereas ethanol (which is commonly used) fails to avert cross-contamination.

In pattern recognition domain, deep architectures are widely used nowadays and they have achieved fine grades. However, these deep architectures need special demands, especially big datasets and GPU. Aiming to gain better grades without deep networks, we propose a simplified algorithm framework using fusion features extracted from the salient areas of faces. Furthermore, the proposed algorithm has achieved a better result than some deep architectures. For extracting more effective features, this paper firstly defines the salient areas on the faces. This paper normalizes the salient areas of the same location in the faces to the same size, therefore it can gain more similar features from different subjects. LBP and HOG features are extracted from the salient areas, fusion features’ dimensions are reduced by Principal Component Analysis( PCA) and we apply softmax to classify the six basic expressions at once. This paper proposes a salient areas definitude method which uses peak expressions frames to compare with their neutral faces. This paper also proposes and applies the idea of normalizing the salient areas to align the specific areas which express the different expressions. This makes the salient areas found from different subjects have the same size. Besides, gamma correction method is firstly applied on LBP features in our algorithm framework which improves our recognition rates significantly. By applying this algorithm framework, our research has gained state-of-the-art performances on CK+ database and JAFFE database.

A portable laser photoacoustic sensor based on a Field-Programmable Gate Array (FPGA) is reported for methane detection. A tunable DFB diode laser in the 1654 nm wavelength range is used as an excitation source. The photoacoustic signal processing was implemented by a FPGA device. A small resonant photoacoustic cell is designed. The minimum detection limit (1σ) of 10 ppm for methane (CH₄) is demonstrated.

Quantifying the landscape pattern change can effectively demonstrate the ecological progresses and the consequences of urbanization. Based on remotely sensed land cover data in 1994, 2000, 2006 and a gradient analysis with landscape metrics at landscape- and class- level, we attempted to characterize the individual and entire landscape patterns of Shanghai metropolitan during the rapid urbanization. We highlighted that a roadscape transect approach that combined the buffer zone method and the transect-based approach was introduced to describe the urban-rural patterns of agricultural, residential, green, industrial, and public facilities land along the railway route. Our results of landscape metrics showed significant spatiotemporal patterns and gradient variations along the transect. The urban growth pattern in two time spans conform to the hypothesis for diffusion–coalescence processes, implying that the railway is adaptive as a gradient element to analyze the landscape patterns with urbanization. As the natural landscape was replaced by urban landscape gradually, the urban fringe expanded radically. The results also showed that the desakota region expanded its extent widely. Satellite towns witnessed the continual transformation from the predominantly rural landscape to peri-urban landscape. Furthermore, the gap between urban and rural areas remained large especially in public service. More reasonable urban plans and land use policies should push to make more of an effort to transition from the urban-rural separation to coordinated urban-rural development. This study is a meaningful trial in demonstrating a new form of urban–rural transects to study the landscape change of large cities from a strategic viewpoint. By combining gradient analysis with landscape metrics, we addressed the process of urbanization both spatially and temporally, and provided a more quantitative approach to urban studies.

The valorization of aquaculture/fisheries processing by-products, as well as unavoidable/unwanted catches and discards in Greece is currently an underutilized activity despite the fact that there are several best practices in Northern Europe and overseas. One of the main challenges is to determine whether the available quantities for processing are sufficient to warrant valorization of discards and fish side streams. This is the first attempt to systematically record and analyze the available quantities of fish by-products and discards in Greece in a spatial and temporal way in an effort to create a national exploitation Master Plan for the valorization of this unavoidable and unwanted biomass. A thorough survey conducted within the VIOAXIOPIO project unveiled a substantial biomass of around 19,000 tonnes annually that could be harnessed for valorization. Furthermore, the production of various High Added Value Biomolecules (HAVB) was investigated, and experimental trials were conducted to assess the potential yields and the collected data were used to formulate four valorization scenarios.

The social- and self-directed behaviours of two golden lion tamarins (Leontopithecus rosalia) was investigated while having residence in the tropical house of Aalborg Zoo, Denmark. The behaviour of the female had been distinct from the male since 2018. Despite several diagnostic examinations and medicinal treatments, the cause of the aberrant and apparently stereotypical behavioural patterns remained undetermined, which initiated this study. The pair were recorded throughout a predetermined observation period and these recordings were analysed to illuminate the behaviours of the individuals. The results showed that there were differences in the type, frequency, and durations of both social- and self-directed behaviours between the sick female and the healthy male. The female expressed both social- and self-directed behaviours more frequently and for longer durations, while the male were more socially reserved and did not engage in social behaviours as frequently. Furthermore, subsequent necropsy of the female revealed uro-genital disease.

The main goal was to investigate the ability of non-thermal plasma reactor with gliding arc discharge to remove the diesel exhaust particulates (DEPs). A conventional knifed-shaped LTP GA reactor was utilized. Three cases were studied: 140 L/min, 70 L/min and 14 L/min of air drawn through the reactor and diesel exhaust fumes were sampled continuously. They were assayed in terms of concentration and number particle size distribution. The higher the residence time’s, the higher the energy input that may be utilized for DEPs’ removal. Reactor’s performance definitely lowered the concentration of DEPs (250 - 580 nm) and altered their number size distribution. There was no effect on the number concentration, nor on the particle size distribution, of DEP particulates of 10 – 250 nm in size. The effectiveness of DEPs’ removal: Decreasing flow rate from 140 L/min to 70 L/min somehow altered the values. Achieving the airflow of 14 L/min led to a substantial improvement (even to a fourfold increase for 300 – 480 nm particles). Non-thermal plasma reactors with gliding arc discharge may be successfully adapted in the process of DEPs’ treatment. Their performance may be optimized by adjusting the airflow at the inlet of reactor to guarantee the longest aerosol residence times and the highest removal efficiency.

Wounds are an increasing global concern, mainly due to a sedentary lifestyle, frequently associated to the occidental way of life. The current prevalence of obesity in western societies, leading to an increase in type II diabetes, and an elderly population, are also a key factor associated to the problem of wounds healing. Therefore, it stands essential to find wound dressing systems allowing reestablishing the skin integrity in the shortest possible time and with the lowest cost, avoiding further damage and promoting patients´ well-being. Wounds can be classified into acute or chronic, depending essentially on the duration of the healing process, which is associated with. It depends on the extent and depth of wound, localization, level of infection and on the patient health status. For each kind of wound and respective healing stage there is a more suitable dressing. The aim of this review was to focus on the possible wound dressing management, aiming the more adequate healing approach for each kind of wound.

(1) Background: Depressional wetlands are highly vulnerable to changes in temperature and rainfall, affecting littoral vegetation, thus HydroGeoMorphic (HGM) wetland types. This study aimed to assess the utility of Sentinel-2A vegetation indices in enhancing delineation and sub-classify depressional HGM types. (2) Methods: We sampled 84 pairs of four vegetation indices from 10x10m plots along 14 belt transects in eight depressional wetlands in Mpumalanga, South Africa. We evaluated vegetation index differences between and within wetlands, focusing on lit-toral gradients. (3) Results: Significant differences (Bonferroni p

The climate crisis necessitates a global shift to achieve a secure, sustainable, and affordable energy system toward a green energy transition reaching climate neutrality by 2050. Because of this, renewable energy sources have come to the forefront and the research interest in microgrids which rely on distributed generation and storage systems has exploded. Furthermore, many new markets for energy trading, ancillary services, and frequency reserve markets have provided attractive investment opportunities in exchange for balancing the supply and demand of electricity. Artificial intelligence can be utilized to locally optimize energy consumption, trade energy with the main grid, and participate in these markets. Reinforcement learning (RL) is one of the most promising approaches to achieve this goal because it enables an agent to learn optimal behavior in a microgrid by executing specific actions that maximize the long-term reward signal/function. The study focuses on testing two optimization algorithms: logic-based optimization and reinforcement learning. This paper proposes an optimization algorithm based on reinforcement learning in an industrial microgrid that is capable of trading energy with the main grid, providing significant cost savings. The RL-based approach is implemented in Python based on real data from the site and in combination with MATLAB-Simulink to validate its results. The application of the RL algorithm achieved an average monthly cost saving of 20% compared to logic-based optimization and 86% savings compared to not using any optimization. These findings contribute to digitalization and decarbonization of energy technology and support fundamental goals and policies of the European Green Deal.

In this paper, we perform the neural cryptanalysis and comprehensively analyze five block ciphers, Data Encryption Standard (DES), Simplified DES (SDES), Advanced Encryption Standard (AES), Simplified AES (SAES), and SPECK. The vulnerability of the block ciphers is investigated in three different attacks, such as Encryption Emulation (EE), Plaintext Recovery (PR), Key Recovery (KR), and Ciphertext Classification (CC) attacks. For the plaintexts, randomly generated block-sized bit arrays and texts are used. The block ciphers apply different numbers of round functions in the encryption of the block-sized bit arrays, and they are investigated by using the deep learning models trained with different numbers of data in EE, PR, and KR attacks. Moreover, the block ciphers use two different text encryption methods, Word-based Text Encryption (WTE) and Sentence-based Text Encryption (STE), to encrypt the texts in various operation modes, and they are analyzed with deep learning models in EE, PR, and CC attacks. As a result, the block ciphers can be vulnerable to deep learning-based EE and PR attacks using a large amount of train data, and STE can improve the strength of the block ciphers, unlike WTE, which shows almost the same classification accuracy as the plaintexts, especially in CC attack. Additionally, when the keys that are the same as the plaintexts are used in encryption, the block ciphers can be perfectly broken in KR attack. Moreover, especially in KR attack, the RNN-based deep learning model shows higher average Bit Accuracy Probability (BAPavg) than the fully connected-based deep learning model, which is used more often in previous works of neural cryptanalysis. Furthermore, although the transformer-based deep learning model is a state-of-the-art model in Natural Language Processing (NLP), the RNN-based deep learning model is more suitable for CC attack and shows higher classification accuracy.

The amino acid proline accumulates in plants during abiotic stresses such as drought and salinity and is considered a reliable marker of environmental stress. While its accumulation is well established, its precise role in stress tolerance and its underlying molecular mechanism remain less clear. To address these issues, we performed a meta-analysis - a robust statistical technique that synthesizes results from multiple independent studies while accounting for experimental differences. We focused on 16 physiological and morphological parameters affected by drought and salt stress in transgenic plants expressing proline metabolic genes. For each parameter, we calculated the effect size as the response ratio (RR), which represents the logarithm of the mean value in the transgenic group over the mean value of the control group (lnRR). Under stress, most parameters exhibited significantly higher response ratios in the transgenic group, confirming the beneficial effects of proline during drought and salt stress. Surprisingly, under non-stressed conditions, most stress markers showed no significant differences between transgenic and non-transgenic plants, despite elevated proline levels in the former. These results suggest that the benefits of proline may be related to proline catabolism or may only become apparent during stress, possibly due to interactions with reactive oxygen species (ROS), which accumulate predominantly under stress conditions.

Incorporating renewables in the power grid presents challenges for stability, reliability, and operational efficiency. Integrating Energy Storage Systems (ESS) offers a solution by managing unpredictable loads, enhancing reliability, and serving the grid. Hybrid storage solutions have gained attention for specific applications, suggesting higher performance in some respects. This paper compares the performance of hybrid energy storage systems (HESS) to single battery, evaluating their energy supply cost and environmental impact through optimization problems. The model generates an optimized dispatch, minimizing cost or environmental impact of supplying energy to a generic load while considering battery degradation. Seven technologies are assessed, with an example applied to an industrial site contrasting vanadium redox flow (VRFB) and lithium batteries considering the demand of a local load (building). The results also indicates that efficiency and degradation curves have the highest impact in the final costs and environmental functions on the various storage technologies assessed. For the simulations of the example case, a single system only outperforms the hybrid system in cases where lithium efficiency is higher than approximately 87% and vanadium is lower approximately 82%.

This research focuses on the Hopf bifurcation occurring at a singular point with high-order degeneracy in a class of three-dimensional systems. Based on center manifold theorem, by expanding the technique for determining singular point values of degenerate singularities in two-dimensional systems, the formal series method to determine the singular point values at the high-order degenerate critical point is discussed. Furthermore, a class of specific three-dimensional differential systems with high-order degenerate singularities is explored. By computing the singular point values and determining center conditions, we proved that a minimum of 5 small-amplitude limit cycles in the vicinity of the origin. This research provides new perspectives on the center problem and limit cycle bifurcation in high-dimensional systems with high-order degenerate singular points.

The paper presents the prediction of hydrodynamic characteristics of different rudder -plane configurations behind a submarine in deep water through the Reynolds-Averaged Navier-Stokes method in Ansys Fluent Solver. The hydrodynamic force and moment acting on the Cross-plane, X-plane, and Y-plane rudder configurations are analyzed for estimating hydrodynamic coefficientsfor predicting the advantages of each configuration to control the ship. The obtained results show that X-force of the X-plane rudder configuration is larger than the force acting on the Cross-plane rudder and Y-plane rudder configurations. However, Y-force, and Z-force of the X-plane rudder configuration are significantly greater than the Y-force of the left configurations. The same tendency can be seen in the moment of the X-plane rudder about the y-axis and z-axis. The roll moment induced by the Y-plane and Cross-plane rudder configurations is significantly larger than the case of the X-plane rudder configuration.

Reducing GHG emissions is a crucial challenge in urban areas, characterized by high energy consumption and reduced exposure to nature. In this context, the urban green system could play a pivotal role. In the literature, scholars analyzed both the ability of species-specific and layout-specific green infrastructures to increase carbon sequestration and the best location sites of new green infrastructures, to increase the provision of overall ecosystem services. There is a lack of studies helping green urban planners and designers choose where and which green infrastructure to implement, based on vegetation species-specific performance and local carbon emissions of city components. This paper uses tree inventory data from a medium-sized city in central Italy (Perugia) to develop a spatial analysis of the urban parks' performance in carbon sequestration. Then, the method evaluates the carbon emission of a public city building to generate a spatialized balance between buildings’ demand and trees’ supply, to support local decisions about the best locations for new green infrastructures and the choice between species. The paper contributes to GIS-based tools that vary the recommended location sites and species for new green infrastructures based on the demanded ecosystem service.

This paper mainly explores the feasibility of using desert sand (DS) and recycled aggregate in cement stabilized base. Recycled coarse aggregate (RCA) and DS serve as the substitutes of natural coarse and fine aggregates, respectively, in cement stabilized base. A four-factor and four-level orthogonal test is designed to analyze the unconfined compressive strength, splitting tensile strength, and compressive resilient modulus. Furthermore, this paper investigates the effects of cement content, fly ash (FA) replacement rate, RCA replacement rate, and DS replacement rate on the road performance of cement stabilized base composing of RCA and DS. The test results reveal that the performance of cement stabilized base with partial RCA instead of natural coarse aggregate (NCA) and partial DS instead of natural fine aggregate satisfy the road use. Meanwhile, DS is beneficial to improve the strength of cement stabilized base. The correlation and microscopic analyses of the test results imply the feasibility of applying DS and recycled aggregate to cement stabilized base. It is hoped that this paper can offer a solid theoretical foundation for promoting the application of DS and recycled aggregate in road engineering.

From 2008 to 2024, the Newborn Screening Translational Research Network (NBSTRN), part of the National Institute of Child Health and Human Development (NICHD) Hunter Kelly Newborn Screening Program, served as a robust infrastructure to facilitate groundbreaking research in newborn screening (NBS), rare disease, and genomics. Over fifteen years, NBSTRN developed into a significant international network, supporting innovative research on novel technologies to screen, diagnose, treat, manage, and understand the natural history of more than 280 rare diseases. A key component of these efforts has been the development of resources and expertise for the newborn screening community in ethical, legal, and social issues (ELSI). This paper presents findings from a survey conducted by the NBSTRN team with input from one of theNBSTRN's expert workgroups, the Bioethics and Legal Workgroup. With responses from 88 members of the NBS community including researchers and state NBS programs, the survey found that individuals rely on internal and collegial ELSI resources and highlighted a substantial demand for structured, accessible training and resources. The survey’s insights emphasize the importance of privacy and informed consent in NBS research, and suggested a need for improved collaborative tools and educational programs focused on ELSI for the NBS community. The survey results may inform future efforts in ELSI and NBS research including the development of expanded ELSI tools that leverage digital platforms and consultative services.

Historically, urban development has always been centered on coastal areas – with access to waterbodies – seas, rivers and canals being a significant advantage for movement and trade. With most of the world’s megapolises located on coasts, land reclamation offers a solution for the expansion of city centers which are otherwise restricted by the coastline. The current understanding of urban regeneration and development on reclaimed lands is defined in this study, answering the basic questions of what, why and how. This study aims to assess the urban regeneration on reclaimed coastal land based on the principles of sustainable development defined by existing studies. The literature review establishes a theoretical framework and defines performance-based benchmarks identifying the spatial indicators of urban development. Composite indicators namely open space coverage, land use mix, percentage of coast for people, accessibility to public transportation and amenities, availability of pedestrian paths and cycling tracks and adequate road networks are considered for this framework. The conclusions are drawn based on the results of the analysis of spatial layout using GIS as a tool to map and empirically measure each indicator. The framework is validated using a major land reclamation project, West Bay, in the coastal urban area of ​​the city of Doha. The results determine that West Bay has achieved a good level of sustainability, although there are areas that could be enhanced to further improve the overall sustainability of urban development. These findings can serve as a guide for policymakers and various stakeholders for sustainable urban planning on reclaimed coastal lands.

In the last decades, the impacts of urbanization on the hydrological cycle have led to an increase in the frequency and magnitude of urban flooding events, also amplified by the effects of climate change. Sustainable Drainage Systems (SuDS) provide a revolutionary change in this field, improving the sustainability and resilience of cities. This research explores the integration of different SuDS with the aim of significantly reducing both flow volume and celerity of floods in a residual urban catchment area of metropolitan city of Querétaro (Mèxico), where extreme rainfall frequently occurs. This catchment is a representative suburb of urban pressure and environmental degradation problems. Currently, managing storm water under climate uncertainty through a multi-disciplinary approach is a major concern in this urban area. A 1D-2D coupling model of shallow water equations, finite volume method, unstructured meshing method, and hybrid parallel computing application defined the optimal configuration of SuDS at catchment scale to reduce the flood vulnerability in Querétaro. Specifically, in this paper we explore the management issues of the proposed SuDS configuration that acts as a water resource system with multiple purposes. A generic simulation model called MODSIM was applied to simulate the designed urban drainage system under a balanced IPCC future climate scenario in terms of reliability, resilience and vulnerability against water scarcity.

This study investigates the effects of Zinc (4wt.%) and severe plastic deformation on the mechanical properties of AZ61 magnesium alloy through the stir-casting process. The severe plastic deformation (equal channel angular pressing (ECAP)) has been done followed by T4 heat treatment. The microstructural examinations revealed that the addition of 4wt.%Zn enhances the uniform distribution of β-phase, contributing to a more uniformly corroded surface in corrosive environments. Additionally, dynamic recrystallization (DRX) significantly reduces the grain size of as-cast alloys after undergoing ECAP. The attained mechanical properties demonstrate that after a single ECAP pass, AZ61 + 4wt.%Zn alloy exhibits optimal yield strength (YS), ultimate compression strength (UCS), and hardness. This research highlights the promising potential of AZ61 + 4wt.%Zn alloy for enhanced mechanical and corrosion-resistant properties, offering valuable insights for applications in diverse engineering fields.

In 2023, the Bureau of Land Management (BLM) estimated that there were 68,928 mustangs living on United States public lands in 10 western states. The agency uses Appropriate Management Levels to determine the number of mustangs who need to be removed from the land. Once removed and processed, mustangs are sent to adoptions or sales events or retained in short-or long-term holding facilities. Adoptions and sales are the leading avenues for rehoming mustangs; however, the number of horses the BLM can place fluctuates annually and never approaches the greater number removed from the range. To explore opportunities for increasing the number of mustang adoptions, we conducted in-depth interviews with 23 horse trainers located on the U.S. East Coast, asking about participants’ training programs, relationships with horses, perceptions of mustangs, and challenges that mustangs face in the dressage and eventing industries. Participants had varying experiences with mustangs; however, all were willing to work with a mustang in some capacity. Participants voiced the need for more satellite adoption locations on the East Coast to decrease barriers to acquiring a mustang, notably cost and time, and for expanding existing training programs to include eventing and dressage.

Rebar cages form the skeletal framework of reinforced concrete structural members. They comprise longitudinal and transverse reinforcing bars, usually connected by tie wires. Past studies have identified tie-wire connections as the "weak links" in large, prefabricated rebar cages, leading to their failure during site handling and construction stages. Recent research has explored the use of mechanical U-bolt connectors to bolster stability and safety of rebar cages while reducing their vulnerability and risk of failure. This paper presents a comprehensive experimental and numerical investigation of a new type of mechanical connector, referred to as "Cage Clamp", to enhance rebar cage stability and safety. Component-level experimental tests are conducted to determine the force-displacement response of Cage Clamp connectors for crossbar connections in different degrees of freedom. The results highlight the remarkable strength and stiffness of Cage Clamp connectors, significantly outperforming traditional tie-wire connections. Furthermore, full-scale experimental tests are performed on a circular underground pile-shaft rebar cage with Cage Clamp connectors to assess its behavior under various site handling conditions. The data obtained from these experiments are used to construct and refine detailed 3D finite element models of the rebar cages, capable of capturing the complex behavior of rebar cages with Cage Clamp connectors. Using the numerical model, a sensitivity analysis is performed to assess the effect of the number of Cage Clamps on the deflection and stability of the rebar cage. The findings show that using cage clamps to connect pick-up rebar with lateral reinforcement at every 8 to 10 feet is sufficient to ensure the stability of the cage during typical site handling conditions. The results of this study serve as a basis for establishing analysis, design, fabrication, and handling guidelines for rebar cages, contributing to safe and efficient construction practices.

In steel structures, oblique thin steel plates serve as panel zones in structures spanning large spaces (e.g., warehouses and gymnasiums). Considerable research has been conducted on the shear buckling of panels due to seismic loads acting on a structure. Conversely, under snow or wind loads, the panel zone may experience compressive and tensile stresses simultaneously from two directions. Considering the economic preference for thin steel plates, evaluating the elastic critical local buckling stresses in the panel zone under biaxial normal stress may provide essential information to structural engineers. In this study, an elastic buckling analysis based on the energy method is performed to clarify the impact of panel geometry and boundary conditions on the elastic local buckling stresses of oblique panel zones. As confirmed, the buckling stresses derived from the energy method could simulate the local buckling stresses with accuracy comparable to that of finite element analysis, and an engineer-friendly design formula was proposed. Finally, we determined the correlation of the buckling stresses under biaxial stresses and presented a method for evaluating this correlation. Engineers can utilize the provided design equations to more efficiently and accurately calculate buckling loads, facilitating safer and more economical design of structures with oblique plates.

Domain generalization has led to remarkable achievements in Hyperspectral Image (HSI) classification. Inspired by contrastive language-image pre-training (CLIP), the language-aware domain generalization method has been explored to learn cross-domain-invariant representation. However, existing methods face some challenges: 1) The weak capacity to extract long-range contextual information and inter-class correlation. 2) Due to the inadequacies of the large-scale pre-training for HSI data, the spatial-spectral features of HSI and linguistic features can not be straightforwardly alignment. To address the above problems, a novel network has been proposed with a CLIP framework, which consists of an image encoder, based on an encoder-only transformer to obtain the global contextual information and inter-class correlation, a frozen text encoder, and a cross-attention mechanism, named Linguistic-Interact-with-Visual Engager (LIVE), enhances the interaction between two modalities. Extensive experiments demonstrating superior performance over state-of-the-art methods in HSI Domain Generalization with a CLIP framework.

This study delves into the dynamic field of medical education research, emphasizing the integration of research training within medical curricula. It seeks to understand the impact of such integration on the competencies of future medical professionals. The primary aim is to systematically categorize and analyze the current trends and future directions in medical education research. This involves assessing the influence of research training on medical students' skills and the methodologies used in such research. Methods: The research employs an extensive bibliographic literature review across multiple databases. It classifies studies into categories like experiential or case studies, editorials, and original research articles. This classification is based on criteria such as geographical location, research objectives, theoretical frameworks, and methodologies. Results: Findings reveal a diverse landscape in medical education research, with a significant emphasis on research training. The research showcases varying methodologies and approaches used globally, highlighting the thematic focus and geographical distribution of these studies. Conclusion: Medical education research is a globally expansive and evolving field. It underscores the importance of continuous investigation, particularly focusing on integrating research elements at curricular levels and exploring innovative educational strategies. The study also points out potential gaps in research, especially in underrepresented regions, indicating directions for future research efforts.

The concept of economic self-reliance, widely known by Thai people as the philosophy of sufficiency economy, has been widely promoted in rural Thai societies. By practicing this philosophy, it is expected that the citizens’ quality of life and local environments could be sustainably improved. This study aims to explore the contribution of the community practices of the sufficiency economy philosophy to rural villagers’ quality of life improvement, and to investigate potential factors that determine the trust of villagers in the philosophy. With the purpose to propose strategies which could enhance trust and promote villagers’ practices of the philosophy, the study investigated influences of three relevant factors on trust towards the philosophy. Those factors included factors related to cognitive-based trust, factors related to emotional-based trust, and factors related to demographic characteristics. Questionnaire surveys and in-depth interviews with community leaders and local villagers were conducted in the Ban Jamrung community, in Thailand’s Rayong province. The results of the statistical analysis revealed that the residents who applied the sufficiency economy philosophy in their daily lives experienced a relatively better quality of life. Additionally, it was found that trust in the philosophy could be predicted more by rational factors than by emotional factors. These findings could be utilized to develop strategies to maintain and enhance the trust of the people in the philosophy of sufficiency economy.

Purpose: This study aimed to identify the risk factors for acute pancreatitis (AP) and its impact on outcomes in Polish children treated for ALL. Methods: The study group included 2303 children who received intensive chemotherapy for ALL. The group was subdivided into patients with at least one episode of AP and those who did not develop AP following treatment for ALL. Results: The cumulative incidence of AP in the study group was 4.08%. Older age was an independent risk factor for AP development (OR 1.05; 95%CI: 1.006 – 1.098; p=0.03). The overall mortality related to AP was 2.13%. The probabilities of disease-free survival (p-DFS) and event-free survival (p-EFS) were 0.84 vs. 0.86, log-rank: p=0.65 and 0.75 vs. 0.80, log-rank: p=0.12, respectively in both subgroups. A total of 22 out of 94 patients (23.4%) with AP were re-exposed to asparaginase (ASP) during the subsequent phases of the treatment. Only one re-exposed to ASP patient (4.5%) developed a second episode of AP. There were no significant differences in p-DFS and p-EFS between patients re-exposed and not re-exposed to asparaginase (0.78 vs. 0.86, log-rank p=0.27 and 0.63 vs. 0.79, log-rank p=0.09 respectively). Conclusions: The incidence of AP in children with ALL is low and related to the patient’s age. AP development doesn’t seem to impact p-DFS and p-EFS in children with ALL. The recurrence of AP following re-exposure to asparaginase in patients with ALL and a history of AP is low (4.5%). Re-exposure to asparaginase after the first episode of AP doesn’t improve either p-DFS or p-EFS in children with ALL.

Dermatological consultations are a significant aspect of daily operations at small animal clinics, with atopic dermatitis (CAD) affecting almost 15% of the canine population. The ECS role in the skin reveals its direct action on homeostasis and deregulation, contributing to dermatopathies. It also details its presence in specialized skin cells, revealing a delicate and complex therapeutic potential. Due to the difficulties and the growing scientific evidence of the therapeutic benefits of cannabis, this work aimed to evaluate the anti-inflammatory effect of cannabis oil in treating CAD. Thus, canines diagnosed with CAD were divided into two groups: the group treated using full spectrum high cannabidiol (CBD) [cannabis oil orally] and the control group (olive oil). The evaluation methods for the effectiveness of the therapy were based on the measurement RNAm of interleukins 6, 10, and 31 and oxidative stress in the blood. Despite the theoretical basis, no significant results were obtained between the groups in this work. Thus, it is concluded that oral administration of full spectrum high CBD cannabis oil 2,5 mg/kg twice a day is not efficient in reducing IL and oxidative stress compared to placebo; nevertheless, it still presents a promising approach in the multi-target treatment of CAD.

Objective: Daratumumab (Dara) is the first-in-class human-specific anti-CD38 mAb approved for treating multiple myeloma (MM). However, DARA-induced depletion of CD38high natural killer (NK) cells results in crippled antibody-dependent cellular cytotoxicity (ADCC), which limits its clinical detection and prediction for Dara efficacy. Therefore, we aimed to explore new NK subsets that could predict Dara efficacy and the underlying mechanism in Dara development. Methods: Multicolour spectral flow cytometry monitored changes in the immune cells of 13 paired RRMM patients. We used machine learning-driven clustering, FlowSOM (Flow Self-Organizing Maps), and dimensional reduction with tSNE (t-distributed Stochastic Neighbour Embedding) to identify unique cell populations pre- and posttreatment. Then, in vitro, fratricide and proliferation assays were performed to explore the function of new NK subsets against MM under Dara treatment. Results: The NK cells were divided into 25 subsets, among which we found that the percentages of KIR-NKP46+ NK cells decreased in paired RRMM patients compared to healthy controls but increased significantly post-Dara treatment. The fold change in KIR-NKP46+ after one dose of Dara treatment can predict whether the best response could be achieved within one month (ROC=0.86, p=0.011). Further in vitro experiments showed that KIR-NKP46+ NK cells are superior to KIR+ NK cells, cooperatively acting with daratumumab to sustainably eradicate MM cells. Meanwhile, apoptosis was significantly decreased, and the proliferation ability was relatively increased post-Dara treatment. Conclusion: In conclusion, the fold change in KIR-NKP46+ NK cell subsets after one dose of Dara treatment can predict the outcome of the curative effect, indicating a putative role of KIR-NKP46+ subsets against MM cells. The mechanism attributed to a relative expansion of the subset due to decreased apoptosis and increased proliferation ability.

Combined radiation with hemorrhage (combined injury, CI), exacerbates hematopoietic acute radiation syndrome and mortality compared to radiation alone (RI). We evaluated the effects of RI or CI on blood cell depletion as a biomarker to differentiate the two. Male CD2F1 mice were exposed to 8.75 Gy γ- radiation (60Co). Within 2 h of RI, animals were bled under anesthesia 0% (RI) or 20% (CI) of total blood volume. Blood samples were collected at 4-5 h and days 1, 2, 3, 7, and 15 after RI. CI decreased WBC at 4-5 h and continued to decrease them until day 3; counts then stayed at the nadir up to day 15. CI decreased neutrophils, lymphocytes, monocytes, eosinophils and basophils more than RI on day 1 or day 2. CI decreased RBCs, hemoglobin and hematocrit on days 7 and 15 compared to RI, whereas Hemorrhage alone returned to the baseline on days 7 and 15. RBCs depleted after CI faster than post RI. Hemorrhage alone increased platelet counts on days 2, 3, and 7, which returned to the baseline on day 15. Our data suggest that WBC depletion may be a biomarker within 2 days post-CI and RBC depletion after 3 days post-CI.

Three different populations of sulfated polysaccharides can be found in the cell wall of the red alga Botryocladia occidentalis. In a previous work, the structures of the two more sulfated polysaccharides were revised. In this work, NMR-based structural analysis was performed on the least sulfated polysaccharide and its chemically modified derivatives. Results have revealed the presence of both 4-linked α- and 3-linked β-galactose units having the following chemical features: more than half of the total galactose units are not sulfated, the α-units occur primarily as 3,6-anhydro-galactose units either 2-O-methylated or 2-O-sulfated, and the β-galactose units can be 4-O-sulfated or 2,4-O-disulfated. SPR-based results indicated weaker binding of the least sulfated galactan to thrombin, factor Xa, and antithrombin, but stronger binding to heparin cofactor II than unfractionated heparin. This report together with our previous publication completes the structural characterization of the three polysaccharides found in the cell wall of the red alga B. occidentalis and correlates the impact of their composing chemical groups with the levels of interaction with the blood co-factors.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and a heterogeneous disease characterized by mature B-cell neoplasms. The standard immunochemotherapy for DLBCL is R-CHOP, which includes rituximab, cyclophosphamide, doxoru-bicin, vincristine, and prednisone. Up to 30-40% of patients with DLBCL either exhibit primary refractory disease to standard treatment or experience relapse after the initial response. A 72-year-old man diagnosed with DLBCL involving chromosomal translocations t(1;22)(q21;q11.2) and t(6;18)(p25;q21) showed primary refractory disease after the fourth cycle of R-CHOP. The patient ultimately experienced cardiac involvement by the lymphoma and received salvage chemotherapy. He passed away about 15 months away after the diagnosis of DLBCL. We conducted fluorescence in situ hybridization (FISH) for further analysis of the chromosomal translocations. The breakpoint of chromosome 1q21 was located at a distance of around 151 Mb from the telomeric end of chromosome 1p. The breakpoint in chromosome 22q11 contains the immunoglobulin lambda locus. Furthermore, the breakpoint of chromosome 6p was in the telomeric region of chromosome 6p21. The breakpoint of chromosome 18q21 contains BCL2. This case report presents the first documented co-occurrence of chromosomal translocations t(1;22)(q21;q11.2) and t(6;18)(p25;q21) in a patient with DLBCL. These chromosomal translocations may indicate a worse clinical outcome.

The sulfur-containing amino acids methionine (Met), cysteine (Cys) and taurine (Tau) are common dietary constituents with important cellular roles. Met restriction is already known to exert in vivo anticancer activity. However, since Met is a precursor of Cys, and Cys produces Tau, the role of Cys and Tau in the anticancer activity of Met-restricted diets is poorly understood. In this work, we screened the in vivo anticancer activity of several Met-deficient artificial diets supplemented with Cys, Tau or both. Diet B1 (6% casein, 2.5% leucine, 0.2% Cys and 1% lipids) and diet B2B (6% casein, 5% glutamine, 2.5% leucine, 0.2% Tau and 1% lipids) showed the highest activity and were selected for further studies. Both diets induced a marked anticancer activity in two animal models of metastatic colon cancer, which were established by injecting CT26.WT murine colon cancer cells in the tail vein or peritoneum of immunocompetent BALB/cAnNRj mice. Diets B1 and B2B also increased the survival of mice with disseminated ovarian cancer (intraperitoneal ID8 Tp53 -/- cells in C57BL/6JRj mice) and renal cell carcinoma (intraperitoneal Renca cells in BALB/cAnNRj mice). The high activity of diet B1 in mice with metastatic colon cancer may be useful in colon cancer therapy.

Small RNAs (sRNA) are epigenetic regulators of essential biological processes that have been linked to the onset and progression of leukemia, including acute adult T-cell leukemia-lymphoma (ATLL) caused by the retrovirus Human T-lymphotropic virus type 1. Here, we describe the sRNA profile of a 30-year-old female with ATLL at diagnosis and after maintenance therapy, with the goal of correlating their expression levels with response to therapy.

Trauma to the spinal cord causes extensive neuronal death contributing to the loss of sensory-motor and autonomic functions below the injury level. Apoptosis affects neurons after spinal cord injury (SCI) and is associated with increased caspase activity. Cleavage of X-linked inhibitor of apoptosis protein (XIAP) after SCI may contribute to this rise of caspase activity. Accordingly, we have shown that the elevation of XIAP resulted in increased neuronal survival after SCI and improved functional recovery. Therefore, we hypothesize that neuronal overexpression of XIAP can be neuroprotective after SCI with improved functional recovery. In line with this, studies of a transgenic mouse with overexpression of XIAP in neurons revealed that higher levels of XIAP after spinal cord trauma favours neuronal survival, tissue preservation, and motor recovery after the spinal cord trauma. Using the human SH-SY5Y cells overexpressing XIAP we show further that XIAP reduced caspase activity and apoptotic cell death after pro-apoptotic stimuli. In conclusion, this study shows that the levels of XIAP expression are an important factor for the outcome after spinal cord trauma and identifies XIAP as an important therapeutic target for alleviating the deleterious effects of SCI.

Introduction. Recent studies revealed that differentiation of valvular interstitial cell into myofibroblasts played an important role in pathological valve remodeling in rheumatic valvular disease. Objective. To investigate effects of atorvastatin, olmesartan, and resveratrol on Transforming Growth Factor β1-induced fibrosis. Methods. Valvular interstitial cell was isolated from 12-weeks male New Zealand rabbit (Oryctolagus cuniculus). Culture cells was divided into 4 groups, control group, group I (0.5 mg/mL Atorvastatin), group II (100 nmol/L Olmesartan), group III (50 μM/L Resveratrol) and group IV (combinations). All group were exposed to 100 nM Transforming Growth Factor β1 for 24 hours. Results. Immunochemical staining demonstrated that cells were completely differentiated into myofibroblasts with mean expression of α-smooth muscle actin 24522.64±4566.994. Atorvastatin, olmesartan, resveratrol, and its combination significantly reduced α-smooth muscle actin expression (6823±1735.3, 6942.7±2455.9, 14176.2±3343.3, 5051.8±1612.2 respectively (p<0.001). Conclusion. Our data showed atorvastatin, olmesartan, resveratrol, and its combination significantly reduce Transforming Growth Factor β1-induced valvular fibrosis.

Background: Acute hepatopancreatic necrosis disease (AHPND), is a bacterial disease of whiteleg shrimp, which has a high mortality rate (100%) and incurs economic losses. Our objective was to identify the genes which lead to cell and organ damage and investigate bioproducts to prevent and treat. Methods: Litopenaeus vannamei shrimp in Thua Thien Hue province, Vietnam were collected from an infected pond and analysed at the Institute of Biotechnology, Hue University. The PirA gene of Vibrio parahaemolyticus strain K5 was isolated and analyzed for nucleotide sequence and paired with the expression vector pQE30. The expression vector was transformed into E. coli strain M15, the PirA recombinant protein was expressed in the form of 6xHis-PirA fusion protein of about 15 kDa. PirA recombinant protein was purified and determined the PirAvp binding ratio, cloning and sequencing of PirA gene from Vibrio parahaemolyticus strain K5 causing AHPND by PCR method with specific primers and molecular weights of PirAvp and the PirAvp complex. Results: PirA gene from Vibrio parahaemolyticus strain K5 was cloned into pGEM-T easy vector (Promega, USA) and screened E. coli TOP10 colonies containing pGEM T easy/PirA recombinant plasmid on LB agar/ampicillin/IPTG/X-Gal medium. PCR showing a band of about 347 bp, matching the size of PirA gene and two nucleotide sequences (BamHI and HindIII). The results showed that PirA gene has a length of 336 bp and similar to PirA gene on GenBank (Code: KU556825.1). The results of protein extracted from E. coli M15 recombinant cells and 6xHis-PirA target protein was collected in elution fractions from EF2 to EF6, showed that the concentration of 6xHis-PirA protein and EF3 elution fraction collected a highest protein concentration (1,586.54 µg/ml). Conclusions: The purified PirA recombinant protein will provide materials for development research to create biological products to prevent and treat AHPND.

To characterize the mechanisms by which the highly-conserved exocyst trafficking complex regulates eye physiology in zebrafish and mice, we focused on exoc5 (aka sec10), a central exocyst component. We analyzed both exoc5 zebrafish mutants and retinal pigmented epithelium (RPE)-specific Exoc5 knockout mice. Exoc5 is present in both the non-pigmented epithelium of the ciliary body and in the RPE. In this study we set out to establish an animal model to study the mechanisms underlying the ocular phenotype and to establish if loss of visual function is induced by postnatal RPE Exoc5-deficiency. Exoc5-/- zebrafish showed smaller eyes, with decreased number of melanocytes in the RPE and shorter photoreceptor outer segments. At 3.5 days post fertilization, loss of rod and cone opsins were observed in zebrafish Tg:exoc5 mutants. Mice with postnatal RPE-specific loss of Exoc5 showed retinal thinning associated with compromised visual function, and loss of visual photoreceptor pigments. This retinal phenotype in Exoc5-/- mice was present at 20-weeks, and the phenotype was more severe at 27-weeks, indicating progressive disease phenotype. We previously showed that the exocyst is necessary for photoreceptor ciliogenesis and retinal development. Here, we report that exoc5 mutant zebrafish and mice with RPE-specific genetic ablation of Exoc5 develop abnormal RPE pigmentation, resulting in retinal cell dystrophy and loss of visual pigments associated with compromised vision. As RPE cells are “downstream” of photoreceptor cells in the visual process, these data suggest exocyst-mediated retrograde communication and dependence between the RPE and photoreceptors.

Stroke is one of the leading cause of adult disability and the second leading cause of death worldwide. The immune system actively participates in the pathobiological process of AIS, during the index event and during the repair process despite the limited attention drawn to this aspect in the existing stroke guidelines globally. The similar clinical course and similar circulating innate and adaptive immune cell counts in AIS and COVID-19 has created a renewed interest in these easily available biomarkers innate and adaptive immunological changes in AIS with potential diagnostic, prognostic, and therapeutic implications. The current scoping review aimed to assess the significance of circulating neutrophil and lymphocyte counts and their ratio (NLR) in AIS and explore their association with post-stroke recovery trajectory. The Arksey and O'Malley methodological framework was employed to review the published papers on the neutrophil-lymphocyte ratio (NLR) and AIS in late November 2020. Only studies published in English from 2000-2020 were included in this scoping review. Fifty-three published papers were reviewed. This review's key finding is that a canonical inflammatory response occurs in AIS just as in the case of COVID-19 and neurological involvements well described in the recent literature. An excessive circulating innate immune cells (neutrophils) and reduced circulating adaptive immune cells (lymphocytes ) are associated with poorer outcomes during the acute interventions ( reperfusion therapies) as well as the recovery trajectory. Main representatives of innate and adaptive immunity follow a canonical course in AIS and COVID-19. Exaggerated circulating innate ( elevated neutrophils and elevated NLR) and reduced adaptive immune response (lymphopenia) correlate with the worse outcome in AIS and COVID-19. This scoping review's findings make the strongest case for a systems biology-based approach to the standard operating procedures in stroke care urgently.

Oral cancer cells (TYS) and the signalling pathways involved in metastasis, in response to cancer-associated fibroblasts (CAFs, COM) and normal oral mucosal fibroblasts (MM1) was studied. Metastatic cell behaviour was observed by cell-scatter, 3D-collagen gel migration and 3D-spheroid invasion assays. Akt, MAPK, EGFR, TGFβRii and CXCR4 inhibitors were used to identify the signalling pathways involved. Signalling pathway protein expression and activation were assessed by SDS-PAGE and Western Blotting. COM-CM (conditioned medium) and MM1-CM stimulated cancer cell scattering, which was blocked only by the Akt inhibitor. COM-CM induced scattered cancer cells showed higher levels of Akt phosphorylation than the negative control and MM1-CM. Migration and invasion of TYS cells into the collagen gels from the spheroids was stimulated by CM from both sources, compared to the negative control. COM cells stimulated TYS, cancer cell invasion into the collagen more than MM1 and the control. Akt and EGFR inhibitors effectively blocked CM and COM cell-induced invasion. Akt-silenced cancer cells were not stimulated to migrate and invade by fibroblast-CM and did not survive addition of the EGFR inhibitor. This suggests that CAFs stimulate oral cancer cell migration and invasion in an Akt- dependent manner. EGFR and Akt are potential therapy targets in metastatic oral cancer.

Immunity against respiratory pathogens is often short-term, and consequently there is an unmet need for effective prevention of such infections. One such infectious disease is COVID-19, which is caused by the novel Beta coronavirus SARS-CoV-2 that emerged around the end of 2019. The World Health Organization declared the illness a pandemic on March 11, 2020, and since then it has killed or sickened millions of people globally. The development of COVID-19 systemic vaccines, which impressively led to a significant reduction in disease severity, hospitalization, and mortality, con-tained the pandemic's expansion. However, these vaccines have not been able to stop the virus from spreading because of the restricted development of mucosal immunity. As a result, breakthrough infections have frequently occurred and new strains of the virus have been emerging. Furthermore, SARS-CoV-2 will likely continue to circulate and, like the influenza virus, co-exist with humans. The upper respiratory tract and nasal cavity are the primary sites of SARS-CoV-2 infection and thus, a mucosal/nasal vaccination to induce a mucosal response and stop the virus transmission is warrant-ed. In this review, we present the status of the systemic vaccines, of the approved mucosal vaccines and those under evaluation in clinical trials. Furthermore, we present our approach of a B-cell pep-tide-based vaccination applied by prime-boost schedule for eliciting both systemic and mucosal immunity.

Despite chronic fibrosis and associated excess extracellular matrix (ECM) deposition and crosslinking occurring in many pathological conditions, few in vitro studies examine how fibrosis-induced ECM stiffening impacts lymphatic endothelial cells (LEC) behavior and subsequent new lymphatic vessel growth and function. This study examined the stiffening profile of PhotoCol®—commercially available methacrylated type I collagen—photo-crosslinked with photoinitiators Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), Irgacure 2959 (IRG), and Ruthenium/Sodium Persulfate (Ru/SPS) prior to evaluating PhotoCol® permeability and LEC response to PhotoCol® at low and high stiffness levels representing normal and fibrotic ECM stiffness. Ru/SPS produced the highest maximum stiffness for photo-crosslinked PhotoCol® hydrogels. While Ru/SPS stiffness values did not differ significantly with increased light exposure, permeability decreased significantly with increasing light exposure for 40 kDa dextran. Finally, LECs on softer PhotoCol® appeared smaller with less prominent VE-Cadherin (cell-cell junction) and F-actin expression compared to cells on stiffer PhotoCol®. Overall, PhotoCol® with Ru/SPS photoinitiator provides the fibrillar microstructure and dynamic stiffness range that enables systematic study of LEC stiffness responses relevant to the stiffened ECM observed in pathologies with significant fibrotic activity. Therefore, this study demonstrates the utility of PhotoCol® with Ru/SPS for disease modeling applications, particularly modeling lymphatic vascular growth and function during fibrosis.

Lung adenocarcinoma is the most prevalent form of lung cancer, and drug resistance is a significant obstacle in its treatment. This study aimed to investigate the overexpression of long non-coding RNAs (lncRNAs) as a mechanism that promotes intrinsic resistance in tumor cells from the onset of treatment. Drug-tolerant persister cells (DTP) are a subset of cancer cells that survive and proliferate after exposure to therapeutic drugs, making them an essential object of study for cancer treatment. The molecular mechanisms underlying DTP cell survival are not fully understood; however, long non-coding RNAs (lncRNAs) have been proposed to play a crucial role. DTP cells from lung adenocarcinoma cell lines were obtained after a single exposure to tyrosine kinase inhibitor TKIs (erlotinib or osimertinib). After establishing DTPs, RNA sequencing was performed to investigate the differential expression of the lncRNAs. Some lncRNAs and one mRNA were found to be overexpressed in DTP cells. The clinical relevance of lncRNAs was evaluated in a cohort of patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA). RT-qPCR validated the overexpression of lncRNAs and mRNA in residual DTP cells and LUAD biopsies. Knockdown of these lncRNAs increases the sensitivity of DTP cells to therapeutic drugs. This study provides an opportunity to investigate the involvement of lncRNAs in the genetic and epigenetic mechanisms underlying intrinsic resistance. The identified lncRNAs and CD74 mRNA may serve as potential prognostic markers or therapeutic targets to improve the overall survival of patients with lung cancer.

Infectivity assays are the key analytical technology for development of manufacturing processes for virus-based therapeutics. Here, we introduce a novel assay format that utilizes label-free bright field images to determine the kinetics of infection-dependent changes in cell morphology. In particular, cell rounding is directly proportional to the amount of infectious virus applied, enabling rapid determination of viral titers in relation to a standard curve. Our kinetic infectious virus titer (KIT) assay is stability-indicating and, due to its sensitive readout method, provides results within 24 hours post-infection. Compared to traditional infectivity assays, which depend on a single readout of an infection endpoint, cumulated analysis of kinetic data by a fit model results in precise results (CV &lt; 20%) based on only three wells per sample. This approach allows for a high throughput with ~400 samples processed by a single operator per week. We demonstrate the applicability of the KIT assay for VSV-GP and NDV, but it can potentially be extended to a wide range of viruses that induce morphological changes upon infection. The versatility of this assay, combined with its independence from specific instruments or software, makes it a promising solution to overcome the analytical bottleneck in infectivity assays within the pharmaceutical industry and as a routine method in academic research.

Nanoencapsulation has emerged as a recent improvement in the delivery of drugs, offering and improving stability and bioavailability, and allowing for the controlled and targeted delivery of substances to specific cells or tissues. However, traditional nanoparticle delivery faces challenges such as short circulation time and immune recognition. To address these issues, cell membrane-coated nanoparticles have been proposed as a promising alternative. The production of cell membrane-coated nanoparticles involves three key stages: cell lysis and membrane fragmentation, membrane isolation, and nanoparticle coating. Typically, cell membranes are fragmented using hypotonic lysis in combination with homogenization or sonication. Subsequent membrane fragments are isolated through multiple centrifugation steps. The coating of nanoparticles can be achieved through extrusion, sonication, or a combination of both methods. This analysis shows the absence of a universally applicable method for nanoparticle coating, as the three stages exhibit notable differences in their procedures. Here we review ongoing developments and approaches to cell membrane-coated nanoparticles that position this technology as a promising alternative for effective targeted drug delivery and many other therapeutic applications.

Cryptococcus neoformans is a fungus that mainly affects the respiratory system and the central nervous system. One of the main virulence factors is the capsule, constituted by the polysaccharides glucuronoxylomannan (GXM) and glucuronoxylomanogalactan (GXMGal). Polysaccharides are immunomodulators. One of the target cell populations for modulation are macrophages, part of the first line of defense, important for innate and adaptive immunity. It has been reported that macrophages can be modulated to act as a "Trojan horse" taking phagocytosed yeasts to strategic sites or having their machinery activation compromised. The scarcity of information on canine cryptococcosis led us to assess whether the purified capsular polysaccharides from C. neoformans would be able to modulate the microbicidal action of macrophages. In the present study, we observed that the capsular polysaccharides, GXM, GXMGal or capsule total did not present toxic effects for the DH82 macrophage cell line. However, it was possible to demonstrate that phagocytic activity was decreased after treatment with polysaccharides. In addition, yeasts recovered from macrophages treated with the polysaccharides, after phagocytosis, could be cultured, showing that their viability was not altered. The polysaccharides led to a reduction in ROS production and the expression of IL-12 and IL-6. We observed that GXMGal inhibits MHC class II expression and GXM reduces ERK phosphorylation. In contrast, GXMGal and GXM were able to increase the PPAR- expression. Furthermore, our data suggests that capsular polysaccharides can reduce the microbicidal activity of canine macrophages DH82.

Drug resistance in tumor cells is a significant roadblock in the clinical management of advanced or recurrent diseases in endometrial cancers. As a part of the tumor-stromal ecosystem, tumor cells are ecologically connected to the cancer-associated fibroblasts (CAFs), which form contributory elements of the tumor microenvironment (TME). We recently reported a novel model of patient-derived CAF-based 2-cell Hybrid Co-Culture (HyCC) to evaluate CAFs' role in developing drug resistance and understanding personalized tumor cell-CAF dialogue. Using our 2-cell HyCC model of patient-derived endometrial CAFs, we present data to demonstrate the direct counter-inhibitory effect of CAFs to combinations of cytotoxic and targeted drugs in developing drug resistance. CAFs derived from resected endometrial tumor samples were first passage-wise characterized before and after freeze-thaw for their positive and negative CAF markers expression pattern. Paclitaxel and its combination with copanlisib, TAK228, lenvatinib, and trametinib were used to test the 3D clonogenic growth of endometrial AN3CA cells on endometrial CAFs. We demonstrate that CAF-mediated resistance to antitumor drugs occurs via direct and indirect contact with CAFs in HyCC. Our data established the strength of the 2-cell HyCC model of patient-derived CAFs in solid tumors and provided a model of resistance to antitumor drugs tailored on a patient-to-patient basis.

Oral Squamous Cell Carcinoma is one among the most common cancer and early detection is the main key to avoid deaths. Automated diagnostic tools that process the histopathological images of a patient to detect abnormal oral lesions will be very much useful for the clinicians. A deep learning framework have been designed with an intermediate layer between feature extraction layers and classification layers for classifying the histopathological images into two categories, namely normal and oral squamous cell carcinoma. The intermediate layer is constructed using the proposed Swarm Intelligence technique called Modified Gorilla Troops Optimizer. Various optimization algorithms are implemented in literature for optimal parameter identification, weights updating and feature selection in deep learning models, but this work focuses on usage of optimization algorithm as intermediate layer that transforms the extracted features into the features that are more suitable for classification. Three datasets totally comprising 2784 normal and 3632 oral squamous cell carcinoma subjects are considered in this work. Three popular CNN architectures namely InceptionV2, MobileNetV3, and EfficientNetB3 are investigated as feature extraction layers. Two fully connected Neural Network layers along with batch normalization and dropout are used as classification layers. Among the investigated feature extraction models, MobileNetV3 performs well in all the three datasets with the highest accuracy of 0.89. Usage of the proposed Modified Gorilla Troops Optimizer as an intermediate layer boosts this accuracy to 0.95.

Background. Currently, most of the research in breast cancer has been carried out in conventional two-dimensional (2D) cell culture due to its practical benefits, however, the three-dimensional (3D) cell culture is becoming the model of choice in cancer research because it allows cell-cell and cell-extracellular matrix (ECM) interactions, mimicking the native microenvironment of tumors in vivo. Methods. in this work, we evaluated the effect of 3D cell organization on the expression pattern of miRNAs (by Small-RNAseq) and mRNAs (by microarrays) in the breast cancer SKBR3 cell line and analyzed the biological processes and signaling pathways regulated by the differ-entially expressed protein-coding genes (DE-mRNAs) and miRNAs (DE-microRNAs) found in the organoids. Results. We obtained well-defined cell-aggregated organoids with a grape cluster-like morphology with a size up to 9.2×105 μm3. The transcriptomic assays showed that cell growth in organoids significantly affected (all p < 0.01) the gene expression patterns of both, miRNAs and mRNAs, finding 20 upregulated and 19 downregulated DE-microRNAs, as well as 49 upregulated and 123 downregulated DE-mRNAs. In silico analysis showed that a subset of 11 upregulated DE-microRNAs target 70 downregulated DE-mRNAs. These genes are involved in 150 gene on-tology (GO) biological processes such as regulation of cell morphogenesis, regulation of cell shape, regulation of canonical Wnt signaling pathway, morphogenesis of epithelium, regulation of cy-toskeleton organization, as well as in the MAPK and AGE-RAGE signaling KEGG-pathways. In-terestingly, hsa-mir-122-5p (Fold Change (FC)=15.4), hsa-mir-369-3p (FC=11.4), and hsa-mir-10b-5p (FC=20.1) regulated up to the 81 % of the 70 downregulated DE-mRNAs. Conclu-sion, the organotypic 3D cell-organization architecture of breast cancer SKBR3 cells impacts the expression pattern of miRNAs-mRNAs network mainly through overexpression of hsa-mir-122-5p, hsa-mir-369-3p, and hsa-mir-10b-5p. All these findings suggest that the interaction between cell-cell and cell-ECM as well as the change in the culture architecture impacts gene ex-pression, and therefore, support the pertinence of migrating breast cancer research from conven-tional cultures to 3D models.

When oxidizing reduced sulfur compounds, the phototrophic sulfur bacterium Allochromatium vinosum forms spectacular sulfur globules as obligatory intracellular – but extracytoplasmic – intermediates. The globule envelope consists of three extremely hydrophobic proteins: SgpA and SgpB are very similar and can functionally replace each other. SgpC is involved in the expansion of the sulfur globules. The presence of a fourth protein, SgpD, has been suggested by comparative transcriptomics and proteomics of enriched sulfur globules. Here, we investigated the in vivo function of SgpD by coupling its carboxy-terminus to mCherry. This fluorescent protein requires oxygen for chromophore maturation, but we were able to use it in anaerobically growing A. vinosum provided the cells were exposed to oxygen for one hour prior to imaging. While mCherry lacking a signal peptide resulted in low fluorescence evenly distributed throughout the cell, fusion with SgpD carrying its original Sec-dependent signal peptide targeted mCherry to the periplasm and co-localized it exactly with the highly light-refractive sulfur deposits seen in sulfide-fed A. vinosum cells. Insertional inactivation of the sgpD gene showed that the protein is not essential for the formation and degradation of sulfur globules.

Previous research suggests that the senescence and death of the replaceable bud in chestnut cultivar (cv.) ‘Tima Zhenzhu’ involves programmed cell death (PCD). However, the molecular network responsible for regulating replaceable bud PCD is poorly characterized. Here, we performed transcriptomic profiling of the chestnut cv. ‘Tima Zhenzhu’ replaceable bud before (S20), during (S25), and after PCD (S30) to ascertain the molecular mechanism underlying the PCD process. A total of 5,779, 9,867, and 2,674 differentially expressed genes (DEGs) were discovered upon comparison of S20 vs. S25, S20 vs. S30, and S25 vs. S30, respectively. Approximately 6,137 DEGs common to at least two comparisons were selected for GO and KEGG enrichment analyses to interrogate the main corresponding biological functions and pathways. GO analysis showed that these common DEGs could be divided into three functional categories, including 15 cellular components, 14 molecular functions, and 19 biological processes. KEGG analysis found that “plant hormone signal transduction” included 93 DEGs. Overall, 441 DEGs were identified as related to the process of PCD. Most of these were found to be genes associated with ethylene signaling, as well as initiation and execution of various PCD processes. A hypothetical model, consisting of three overlapping processes, is proposed for the replaceable bud PCD: First, ethylene signaling is activated during preparation for PCD, in order to regulate the activity of downstream targets. Next, during PCD initiation, the up-regulation of several TFs (including MYB, MADS-box, bHLH, and NAC TFs) induces an increase in cytochrome c expression and in the cytosolic Ca2+ content, activating the Ca2+-dependent signaling cascade. Finally, during PCD execution, the process of autophagy and the activity of proteases (i.e., cysteine proteinases RD21A-like, metacaspase-9-like, vacuolar-processing enzyme-like, and senescence-associated proteins for hydrolysis) work synergistically to clear the cell of cellular components. When this process is complete, the replaceable bud senesces and dies.

Liver cancers give rise to a heavy burden of health care worldwide. Understanding the tumour microenvironment (TME) underpins the development of precision therapy. Single-cell RNA sequencing (scRNA-seq) technology has generated high-quality cell atlases of the TME, but its wider application faces enormous costs for various clinical circumstances. Fortunately, a variety of deconvolution algorithms can instead repurpose bulk RNA-seq data, alleviating the need for generating scRNA-seq datasets. In this study, we reviewed major public omics databases for relevance in this study and utilized 8 RNA-seq and 1 microarray datasets from clinical studies. To decipher the TME of liver cancer, we estimated the fractions of liver cell components by deconvoluting the samples with Cibersortx using three reference scRNA-seq atlases. We also confirmed that Cibersortx can accurately deconvolute cell types/subtypes of interest. Compared with non-tumorous liver, liver cancers showed multiple decreased cell types forming normal liver microarchitecture, as well as elevated cell types involved in fibrogenesis, abnormal angiogenesis and disturbed immune responses. Survival analysis shows that the fractions of five cell types/subtypes significantly correlated with patient outcomes, indicating potential therapeutic targets. Therefore, deconvolution of bulk RNA-seq data with scRNA-seq atlas references can be a useful tool to help understand the TME.

Standard cell culture is routinely performed at supraphysiological oxygen concentrations (~18% O2). Conversely, oxygen levels in most tissues range from 1%–6% (physioxia). Such hyperoxic conditions can alter reactive oxygen species (ROS) production, energy metabolism, mitochondrial network dynamics, and response to drugs and hormones. The aim of this project was to investigate the transcriptional response to different oxygen levels and whether it is similar across cell lines, or cell-line specific. Using RNA-seq, we performed differential gene expression and functional enrichment analyses in four human cancer cell lines, LNCaP, Huh-7, PC-3, and SH-SY5Y cultured at either 5% or 18% oxygen for 14 days. We found that oxygen levels affected transcript abundance of hundreds of genes, with the affected genes having little overlap between cell lines. Functional enrichment analysis also revealed different processes and pathways being affected in each cell line. Interestingly, we found that the top differentially expressed genes are involved in cancer biology. Further, we observed several hypoxia-inducible factor (HIF) targets upregulated at 5% oxygen, suggesting a role of HIF at physiological oxygen conditions. Finally, oxygen strongly induced transcription of mitochondrial genes in most cell lines, in a cell-type specific manner too. We conclude that cellular response to oxygen is widely cell-type specific, emphasizing the importance of maintaining physioxia in cell culture.

Targeted therapies with antiangiogenic drugs (e.g., sunitinib) and immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) are the standard of care for patients with metastatic renal cell carcinoma. Although these treatments improve patient survival, they are rarely curative. We previously hypothesized that advanced cancers might be treated without drugs by using artificial diets in which the levels of specific amino acids (AAs) are manipulated. In this work, after showing that AA manipulation induces selective anticancer activity in renal cell carcinoma cells in vitro, we evaluated the anticancer activity of 17 artificial diets in a challenging animal model of renal cell carcinoma. The model was stablished by injecting murine renal cell carcinoma (Renca) cells into the peritoneum of immunocompetent BALB/cAnNRj mice. Mice survival was markedly improved when their normal diet was replaced with our artificial diets. Mice fed a diet lacking six AAs (diet T2) lived longer than mice treated with sunitinib or anti-PD-1 immunotherapy; several animals lived very long or were cured. Controlling the levels of several AAs (e.g., cysteine, methionine and leucine) and lipids was important for the anticancer activity of the diets. Additional studies are needed to further evaluate the therapeutic potential of this simple and inexpensive anticancer strategy.

A clear relationship between the tau assemblies and toxicity has still to be established. To correlate the tau conformation with its proteotoxic effect in vivo we developed an innovative cell-worm-based approach. HEK293 cells expressing tau P301L under a tetracycline-inducible system (HEK T-Rex) were employed to produce different tau assemblies whose proteotoxic potential was evaluated using C. elegans. Lysates from cells induced for five days, significantly reduced the worm’s locomotor activity. This toxic effect was not related to the total amount of tau produced by cells or to its phosphorylation state but was related to the formation of multimeric tau assemblies, particularly tetrameric ones. We investigated the applicability of this approach for testing compounds acting against oligomeric tau toxicity, using doxycycline (Doxy) as prototype drug. Doxy affected the tau solubility and promoted the disassembly of already formed toxic aggregates in lysates of cells induced for five days. These effects translated into a dose-dependent protective action in C. elegans. These findings confirm the validity of the combined HEK T-Rex cells and C. elegans-based approach as a platform for pharmacological screening.

Circulating atypical cells (CAC) are released from a primary tumour site into peripheral blood and are indicators of cancer metastasis. CAC occur at very low frequency in circulating blood, and their detection remains challenging. Moreover, white blood cells (WBC) are the major contaminant in enriched CAC samples. Here, we developed matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) as a novel CAC characterization platform. Main spectra profiles (MSP) of normal and cancer cells were generated by MALDI-TOF MS, and a cell-main spectra database was then compiled and analysed using the MALDI Biotyper software. Logarithmic scores accurately predicted distinct cell types. The feasibility of this workflow was then validated using simulated samples, which were prepared by 5,000 WBC of three healthy individuals spiked with varying numbers (3, 6, 12, 25, 50 and 100) of lung, colon, or prostate cancer cells. MALDI-TOF MS was able to detect cancer cells down to six cells over the background noise of 5,000 WBC with significantly higher predictive scores as compared to WBC alone. Further development of cell-MSP database to cover all cancer types sourced from cell lines and patient tumours may enable the use of MALDI-TOF MS as a cancer-screening platform in clinical settings in the future.

Ongoing beta cell death in type 1 diabetes (T1D) can be detected using biomarkers selectively discharged by dying beta cells into plasma. MicroRNA-375 (miR-375) ranks among top biomarkers based on studies in animal models and human islet transplantation. Our objective was to identify additional microRNAs that are co-released with miR-375 proportionate to the amount of beta cell destruction. RT-PCR profiling of 733 microRNAs in a discovery cohort of T1D patients 1 hour before/after islet transplantation indicated increased plasma levels of 22 microRNAs. Sub-selection for beta cell selectivity resulted in 15 microRNAs that were subjected to double-blinded multicenter analysis. This led to identification of 8 microRNAs that were consistently increased during early graft destruction: besides miR-375, these included miR-132/204/410/200a/429/125b, microRNAs with known function and enrichment in beta cells. Their potential clinical translation was investigated in a third independent cohort of 46 transplant patients, by correlating post-transplant microRNA levels to C-peptide levels 2 months later. Only miR-375 and miR-132 had prognostic potential for graft outcome and none of the newly identified microRNAs outperformed miR-375 in multiple regression. In conclusion, this study reveals multiple beta cell-enriched microRNAs that are co-released with miR-375 and can be used as complementary biomarkers of beta cell death.

Pv11, an insect cell line established from the midge Polypedilum vanderplanki, is capable of ametabolic desiccation tolerance, so-called anhydrobiosis. We previously discovered that heat shock factor 1 (HSF1) contributes to the acquisition of desiccation tolerance by Pv11 cells, but the mechanistic details have yet to be elucidated. Here, by analyzing the gene expression profiles of newly established HSF1-knockout and -rescue cell lines, we show that HSF1 has a genome-wide effect on gene regulation in Pv11. HSF1-knockout cells exhibit a reduced desiccation survival rate, but this is completely restored in HSF1-rescue cells. By comparing mRNA profiles of the two cell lines, we reveal that HSF1 induces anhydrobiosis-related genes, especially genes encoding late embryogenesis abundant proteins and thioredoxins, but represses a group of genes involved in basal cellular processes, thus promoting an ametabolic state in the cell. In addition, HSF1 binding motifs are enriched in the promoters of anhydrobiosis-related genes and we demonstrate binding of HSF1 to these promoters by ChIP-qPCR. Thus, HSF1 directly regulates the transcription of anhydrobiosis-related genes and consequently plays a pivotal role in the induction of anhydrobiotic ability in Pv11 cells.

(1) Background: Overall survival of the patients with renal cell carcinoma (RCC) depends mostly on extra-renal extension, documented by the invasion of the pelvicalyceal system, or the perinephric/renal sinus fat or the renal vein/its segmental intraparenchymal branches. Staging may be challenging because of the high inter-observer variability. We have introduced a more accurate procedure to detect the extra-renal extension and, to possibly evaluate the impact of such more laborious approach, we have compared the RCC pathological staging obtained following both standard and modified procedures; (2) Methods: We selected 54 consecutive cases of RCC diagnosed 18 months before and 54 consecutive cases diagnosed 18 months after the introduction of the new method of sampling. Clinico-pathological characteristics have been statistically analyzed; (3) Results: Most of the features analyzed were non statistically significative, except the extra-renal invasion. More precisely, the occurrence of retrograde venous invasion was higher in the cases grossly approached with the more accurate method; (4) Conclusions: Extra-renal extension to intraparenchymal renal vein branches may be underestimated, leading to an inappropriate under-staging. Using more accurate staging procedures, to disclose the occurrence of intra-renal veins tumoral thrombosis, helps to better define the pathological stage, allowing patients to benefit of better fitting treatments.

Fanconi anemia (FA) patients have an exacerbated risk of head and neck squamous cell carcinoma (HNSCC). Treatment is challenging as FA patients display enhanced toxicity to standard treatments, including radio/chemotherapy. Therefore better therapies as well as new disease models are urgently needed. We have used CRISPR/Cas9 editing tools in order to interrupt the human FANCA gene by the generation of insertions/deletions (indels) in exon 4 in two cancer cell lines from sporadic HNSCC having no mutation in FA-genes: CAL27 and CAL33 cells. Our approach allowed efficient editing, subsequent purification of single-cell clones, and Sanger sequencing validation at the edited locus. Clones having frameshift indels in homozygosis did not express FANCA protein and were selected for further analysis. When compared with parental CAL27 and CAL33, FANCA-mutant cell clones displayed a FA-phenotype as they i) are highly sensitive to DNA interstrand crosslink (ICL) agents such as mitomycin C (MMC) or cisplatin, ii) do not monoubiquitinate FANCD2 upon MMC treatment and therefore iii) do not form FANCD2 nuclear foci, and iv) they display increased chromosome fragility and G2 arrest after diepoxybutane (DEB) treatment. These FANCA-mutant clones display similar growth rates as their parental cells. Interestingly, mutant cells acquire phenotypes associated with more aggressive disease, such as increased migration in wound healing assays. Therefore, CAL27 and CAL33 cells with FANCA mutations are phenocopies of FA-HNSCC cells.

Many species of the Asteraceae family are used in traditional Mexican medicine for possessing healing properties. Ageratina pichinchensis (Asteraceae) is a plant used for the treatment of gastric ulcers, deep wounds and for its antifungal effects. The aim of this study was to establish a cell suspension culture of A. pichinchensis, quantify the anti-inflammatory constituents 2,3-dihydrobenzofuran and 3-epilupeol, to evaluate the anti-inflammatory potential of its extracts and perform a phytochemical analysis. Cell suspension cultures were established in MS culture medium supplemented with 30 g L-1 sucrose and 1.0 g L-1 α-naphthaleneacetic acid (NAA) plus 0.1 mg L-1 6-furfurylaminopurine (KIN). The ethyl acetate extracts of cell suspension cultures analyzed by GC revealed that the maximum production of compounds The anti-inflammatory activity of these extracts exhibited significant inhibition of NO production. Furthermore, the phytochemical study of EtOAc and MeOH extracts of the biomass on day 20 led to the identification of 17 known compounds. The structures of compounds were assigned by analysis of 1D and 2D NMR data and the remainder by GC-MS. This is the first report of the production of the (-)-Artemesinol, (-)-Artemesinol glucoside, Encecalin and 3,5-diprenyl-acetophenone compounds by a cell suspension cultures of A. pichinchensis.

Photoelectrocatalytic water splitting by using various TiO₂ nanostructures is a promising approach to generate hydrogen without harmful byproducts. However, their effective performance is restricted by some drawbacks such as high rapid electron-hole pair recombination and backward reaction producing H₂O. Thus in this study, the probability of enhancing hydrogen generation rate by adding methanol as a sacrificial agent to the anodic chamber of a two-compartment photoelectrochemical cell is investigated. Herein, one-dimensional elongated TiO₂ nanorods that were fabricated via a facile one-pot hydrothermal method are utilized as potent photoanode. Voltammetric characterizations confirm that addition of alcoholic sacrificial agent has a significant effect on photoelectrochemical properties of TiO₂ nanorods which by adding 10 wt% of methanol, the photocurrent density and photoconversion efficiency increased from 0.8mA.cm^-2 to 1.5mA.cm^-2 and from 0.28% to 0.45%, respectively. The results of photoelectrocatalytic water splitting indicated that the hydrogen generation rate in the presence of methanol was about 1.2 times higher than that from pure water splitting. These enhancements can be attributed to the key role of methanol. Methanol molecules not only inhibit the electron-hole pair recombination but also accelerate the hydrogen generation rate by sharing their hydrogen atoms.

Background: Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is mainly associated with SDHB gene mutation and sometimes with SDHC or SDHD mutation. However, only three case of SDHA-deficient RCC have been reported, and the relation of SDHA mutation to RCC has not been clarified. Methods: We investigated SDHA/B/C/D gene mutations in 72 human RCCs by targeted next-generation sequencing, and also assessed SDHA and nuclear factor erythroid 2–related factor 2 (Nrf2) protein expression in 30 tumors. Results: NGS revealed SDHA gene mutations associated with amino acid sequence variations in 12 tumors, while no tumors had SDHB/C/D mutations. The SDHA gene mutations were identical in somatic and germline DNA of all 12 patients. Tumors with SDHA mutations showed a decrease of SDHA protein (p = 0.0177) and an increase of Nrf2 protein (p = 0.0120), with an inverse correlation between SDHA and Nrf2 protein expression (p = 0.0321). Tumor cells with SDHA mutations characteristically had eosinophilic cytoplasm and showed various patterns of proliferation. Conclusions: Our observations suggested that germline SDHA gene mutations might be linked to hereditary RCC associated with mitochondrial dysfunction.

Beta-thalassemia major (β-TM) is a severe form of thalassemia caused by mutations in the β-globin gene, resulting in partial or complete deficiency of β-globin chains. This deficiency results in oxidative stress, dyserythropoiesis, and chronic anemia. Cytokine dependent hematopoietic cell linker (CLNK) belongs to the adaptor protein family and has the capacity to interact with multiple signaling proteins thereby modulating signal transduction. The aim of the present study was to examine CLNK in sera of β-TM patients and examine its association with iron overload biomarkers. Sixty β-TM patients, aged 3–12 years old and undergoing blood transfusions, and 30 healthy control children were recruited and CLNK, ferritin and iron status parameters were measured. The results showed a significant increase (p < 0.001) in serum CLNK levels in β-TM patients as compared with normal controls. The increased levels of CLNK were significantly associated with increased ferritin levels. Increased CLNK levels in β-TM may be explained by reciprocal effects between immune signaling and immature erythrocytes, which, release soluble receptors and signaling molecules, including CLNK, in the blood.

The CCAAT/enhancer-binding protein β (C/EBPβ) is a transcription factor that regulates cellular proliferation, differentiation, apoptosis and tumorigenesis. Although the pro-oncogenic roles of C/EBPβ have been implicated in various human cancers, how it contributes to tumorigenesis or tumor progression has not been determined. Immunohistochemistry with human non-small cell lung cancer (NSCLC) tissues revealed that higher levels of C/EBPβ protein are expressed compared to normal lung tissues. Knockdown of C/EBPβ by siRNA reduced the proliferative capacity of NSCLC cells by delaying G₂/M transition of the cell cycle. In C/EBPβ-knockdown cells, a prolonged increase in phosphorylation of cyclin dependent kinase 1 at tyrosine 15 (Y15-pCDK1) was displayed with increased Wee1 and decreased Cdc25B expression, simultaneously. ChIP analysis showed that C/EBPβ bound to distal promoter regions of WEE1 and repressed WEE1 transcription through the interaction with histone deacetylase 2. Treatment of C/EBPβ-knockdown cells with a Wee1 inhibitor induced a decrease in Y15-pCDK1 and recovered cells from G₂/M arrest. In the xenograft tumors, the depletion of C/EBPβ significantly reduced tumor growth. Taken together, these results indicate that Wee1 is a novel transcription target of C/EBPβ that is required for the G₂/M phase of cell cycle progression, ultimately regulating proliferation of NSCLC cells.

In this study, a high energy conversion efficient dye-sensitized solar cells (DSSC) was successfully fabricated by attaching a double anti-reflection (AR) layer which is composed of a subwavelength moth-eye structured polymethyl methacrylate (PMMA) film and a polydimethylsiloxane (PDMS) film. The efficiency is up to 6.79%. The moth-eye structured PMMA film was fabricated by using anodic aluminum oxide (AAO) template which is simple, low-cost and scalable. The nano-pattern of AAO template has been precisely reproduced onto PMMA film. The photoanode is composed of Titanium dioxide (TiO₂) nanoparticles (NPs) with diameter of 25 nm deposited on the fluorine-doped tin oxide (FTO) glass substrate and the sensitizer N3. The double AR layer can effectively improve the short-circuit current density (JSC) and conversion efficiency from 14.77 to 15.79 mA/cm² and from 6.26% to 6.79%, respectively.

This study was conducted to evaluate the yield and quality parameters of milk from 60 indigenous South African goats of different genotypes namely Nguni, Boer and Non- descript reared under a free ranging system. Milk yield and quality parameters (milk fat, protein, lactose, solid non-fat and minerals) from Nguni (10), Boer (10) and Non-descript (10) goats was measured and analysed per week at each stage of lactation. Result showed that, Nguni goats produced (1.2±0.09, 1.3±0.11 and 1.2±0.07 litres per day) more milk (P ˂ 0.05) at early, mid and late stages of lactation than Boer (0.6±0.10, 1.0±0.17 and 0.6±0.09 litres per day) and Non-descript (0.3±0.10, 0.3±0.12 and 0.3±0.09 litres per day) goats, respectively. The mean value of milk fat, protein and lactose content from Nguni goat was (3.98, 3.54 and 5.31); Boer goat (2.9, 3.59 and 5.04) and Non-descript goat (4.05, 3.39 and 5.02), respectively. There was significant effect (P ˂ 0.05) of genotypes on milk fat, milk magnesium and sodium contents of Nguni, Boer and Non-descript goats. It could be concluded that, Nguni goat produced more milk than Boer and Non-descript goats, but the Non-descript goat had higher mean percentage of milk fat compared to Nguni and Boer goats.

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silencing a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)n (n = 1-4) peptides. The peptide:siRNA complexes were non-cytotoxic at N/P 40 (~20 μM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide:siRNA complexes showed serum stability at N/P ≥40. The synthesized conjugates, with a diameter of &lt;100 nm, formed nano complexes with siRNA and exhibited stable range of zeta potential values (13-18 mV at N/P 40). Confocal microscopy and flow cytometry analysis provided qualitative and quantitative evidence of successful cellular internalization of siRNA. Peptides oleyl-(WRH)3 and oleyl-(WRH)4 showed ~60% and ~75% cellular uptake of siRNA, respectively, in both MDA-MB-231 and SK-OV-3 cells. Western blot analysis of oleyl-(WRH)4 demonstrated effective silencing of the STAT-3 gene, with ~75% silencing in MDA-MB-231 cells and ~45% in SK-OV-3 cells.

This study investigated the development of novel probiotic formulations specifically designed for rainbow trout aquaculture. The project evaluated the effects of two formulations containing potential probiotic strains isolated from rainbow trout itself. These effects were assessed on various parameters including growth performance, immune response, liver enzyme activity, gene expression related to immunity, and the composition of the bacterial gut microbiota in rainbow trout (Oncorhynchus mykiss). In a completely randomized experimental design, a total of 450 rainbow trout were randomly divided into 70-liter fiberglass tank. The study included six treatments of three replicates (n=18 tanks). Six dietary treatments were included (A) and (B) containing three strains of Pediococcus sp P15, Lactococcus lactis ml3, Weissella cibaria ml6 at two dosages (300 and 500 mg/kg), treatments (C) and (D) containing five strains of P. sp P15, L. lactis ml3, W. cibaria ml6, Enterococcus faecium E10 and Lactobacillus curvatus 13A at two dosages (300 and 500 mg/kg), a commercial probiotic (E) at 300 mg/kg, and a control group (F) without probiotics. Treatments of (A), (B) and (E) resulted in the highest final weights in compared to control group. Fish fed treatments (A) and (B) had the lowest FCR than other groups. Treatments (A) and (D) showed a significant increase in immunoglobulin M (IgM) concentration compared to other groups. The expression of tumor necrosis factor (TNF) was significantly lower in group (A) than the control. In contrast, the expression of interleukin 6 (IL6) and immunoglobulin T (IgT) was increased 4.4-fold and 41-fold, respectively, in group (A) compared to control group. Among the probiotic fed treatments, group (A) showed a significant higher number of lactic acid bacteria compared to other groups during the experiment. This study highlights the significant role of treatment (A) containing three strains of P. sp P15, L. lactis ml3, and W. cibaria ml6 at a dosage of 300 mg/kg as a potential probiotic product for the rainbow trout industry.

Most of the mid-high permeability sandstone oilfields in China have entered the ultra-high water cut stage, accompanied with the highly-dispersed residual oil, and the control effect of mi-cro-heterogeneity on the residual oil is increasingly prominent. Understanding the microscopic characteristics of pore structural and its evolution during the long-term waterflooding is critical for enhancing the accuracy and efficiency of oil field exploitation. While the previous insights paid more attention to the geometrical and morphological features of pore structure and ignores the relation of pore structure with the fluid flow capacity. In this study, we propose a microscopic pore structure classification method considering pore size and local permeable capacity, which realizes the physical classification and quantitative evaluation of pore structure characteristics for different permeability rocks. The micro-pore structure is classified into 6 types based on the key evaluation parameters of pore diameter and flow flux area. By taking six mid-high permea-bility sandstone core samples from Daqing oilfield in China, a series of long-term waterflooding experiments are carried out and the interior pore structure was captured using high precision CT scanning technique. The results reveals that high-permeability reservoirs exhibit concentrated pores diameters and finer throats, whereas mid-permeability reservoirs exhibit smaller pores and throats in greater quantity. With the increase of water injection volumes, the permeable ca-pacity and connectivity of the high-connectivity pore space in ultra-high- and high-permeability reservoirs are enhanced, and in mid-permeability reservoirs, the micro-heterogeneity intensifies the increase in low-connectivity small pores. These findings provide new insights for the micro-scopic heterogeneity and a solid theoretical basis for investigating the occurrence of microscopic residual oil and optimising enhanced oil recovery strategies at the late stage of ultra-high water cut.

In this work, we introduce the first pipeline that combines a refraction-aware Structure-from-Motion (SfM) method with a deep learning model specifically designed for airborne bathymetry. We accurately estimate the 3D positions of the submerged points by integrating refraction geometry within the SfM optimization problem. This way, no refraction correction as post-processing is required. Experiments with simulated data that approach the real-world capturing conditions demonstrate that SfM with refraction correction is extremely accurate, with submillimeter errors. We integrate our refraction-aware SfM within a deep learning framework that also takes into account radiometrical information, developing a combined spectral and geometry-based approach, with further improvements on accuracy and robustness to different seafloor types, both textured and textureless. We conducted experiments with real-world data at 2 locations in the southern Mediterranean Sea, with varying seafloor types which demonstrate the benefits of refraction correction for the deep learning framework. We open-source our refraction-aware SfM, providing researchers in airborne bathymetry with a practical tool to apply SfM in shallow water areas.

This article presents the analysis of the allocation of important plant areas (IPA), which urgently identifies the most valuable sites for protecting plant objects. The study is based on a comprehensive inventory of the species composition of plants in the flora of the Western Karatau Ridge and the Mangyshlak Peninsula (arid regions)- key sites Akmysh, Samal, and Kogez, considered standard and the best preserved with natural vegetation cover. The flora of these critical sites was analysed using a combination of field surveys, herbarium studies, and a literature review. The results revealed a rich biodiversity, with 104 species from 82 genera and 33 families. Most species belong to 9 families, making up 60.6% of the total taxa. By the nature of life forms, perennial herbaceous plants dominate in all key sites (30 species, 50.0%). The eco-phylogenetic spectrum showed that a significant share of the flora of the studied IPAs is made up of xerophytes (21 species, 35%) and xeromesophytes (9 species, 15%); desert and mountain-steppe species prevail (53.0%). Rare, endangered and Red Book species account for 10-21.3% of those growing in the region. Regarding economic value, fodder, ornamental, honey, medicinal and food species dominate. The Shannon, Simpson, and Jaccard indices assessed alpha-beta and gamma diversity. The index showed that biodiversity in the Samal and Kogez sites is higher and more evenly distributed compared to the Akmysh site. The Whittaker, Harrison and Cody indices confirm significant differences in the species composition between the sites. In light of these compelling results, a clear and urgent call to action is proposed to allocate these areas to the IPA category, a crucial step towards ensuring the long-term existence of natural biocenoses.

Epirubicin, olaparib and ribociclib are three anti-tumoral molecules currently used in cancer therapy. Since serum levels of these drugs reveal a large inter-individual variability, validation of a fast, simple and reliable analytical method for quantitative determination of these molecules in human serum, with Therapeutic Drug Monitoring (TDM) purposes would be necessary. Papers in literature describe separation, identification and quantitation of the drugs in pharmaceutical formulas and biological matrices. The large majority of these approaches use protein precipitation for sample pre-treatment, followed by LC separation and tandem-mass-spectrometry (MS/MS) detection. We propose an alternative method using Solid Phase Extraction (SPE) with Oasis PRiME HLB® cartridges followed by high-performance liquid chromatography (HPLC) using a C18 (4.6 × 50 mm) column. A gradient mobile phase with 0.1% formic acid/acetonitrile was utilized. MS detection in single ion recording (SIR) mode was employed. A 13-minutes run-time analysis, including column re-equilibration was assessed. Data for all molecules were validated according to ICH Guidelines. Calibration curves for all analytes were linear with correlation coefficient larger than 0.997. Values for precision were less than 6%. The method was applied on serum samples from patients up-taking the drugs, proving its suitability in TDM assisted adjustment of doses in therapy.

Previous control methods developed by our research team cannot satisfy the high-accuracy requirements of unmanned surface vessel (USV) path-tracking during bathymetric mapping because of the excessive overshoot and slow convergence speed. For this reason, this study developed an adaptive fuzzy integral-derivative line-of-sight (AFIDLOS) guidance law for USV path-tracking control. Integral and derivative terms were added to counteract the effect of the sideslip angle, with which the USV could be quickly guided to converge to the planned path for bathymetric mapping. To obtain a high-accuracy of the look-ahead distance, a fuzzy control method was proposed. The proposed method was verified using simulations and outdoor experiments. The results demonstrate that the AFIDLOS guidance law can reduce the overshoot by 79.85%, shorten the settling time by 55.32% in simulation experiments, and reduce the average cross-track error by 10.91%, and can ensure a 30% overlap of neighboring strips of bathymetric LiDAR outdoor mapping when compared with the traditional method.

The increased prevalence of obesity worldwide has been implicated for the alarming rise of the incidence of gestational diabetes and preeclampsia as well, both considered as threatening conditions for both mother and fetus. We studied gene polymorphisms of the proinflammatory cytokine Interleukin 6 (IL-6) and the gene expression levels of VEGF and VEGF-receptor all known to be involved in pregnancy complications aiming to identify possible predisposing risk factors in pregnancies with obesity. G allele of IL-6 was found to correspond with an increased risk for gestational diabetes and preeclampsia occurrence. Furthermore, in obese pregnant mothers with either gestational diabetes or pre-existing type 2 diabetes and to those developed preeclampsia it was confirmed that gene expression levels of VEGF were reduced while they were increased for VEGF receptor. We conclude that the genetic profile of the obese pregnant woman shares a common background with that of a pre-existing type 2 diabetes mellitus and therefore predisposes to complications in pregnancy.

Cancer remains one of the main causes of death in the world due to its increasing incidence and treatment difficulties. Although several progresses have been done in this field, innovative approaches are needed to reduce tumor incidence, progression and spreading. In particular, the development of cancer vaccines is currently ongoing like both preventive and therapeutic strategy. This concept is not new, but few vaccines have been approved in oncology. Antigen-based vaccination emerges as a promising strategy, leveraging specific tumor antigens to activate the immune system response. However, challenges persist in finding suitable delivery systems and antigen preparation methods. Exosomes (EXs) are highly heterogeneous bilayered vesicles which carry several molecule types in the extracellular space. The peculiarity is that they may be released from different cells and may be able to induce a direct or indirect stimulation of immune system. In particular, EX-based vaccines may cause anti-tumor immune attack or produce memory cells recognizing cancer antigens and inhibit disease appearance. This review delves into EXs composition, biogenesis, and immune-modulating properties exploring their role as tool for prevention and therapy in solid tumors. Finally, here we describe future research directions to optimize vaccine efficacy and realize the full potential of EX-based cancer immunotherapy.

The study assessed the trapping efficacy of locally-modified 1) Gravid Aedes Trap(GAT) lined with insecticide-treated net (ITN) as a killing agent, 2) Autocidal Gravid Ovitrap(AGO) with sticky board in the semi-field system (SFS) and field setting. Fully-balanced Latin square experiments were conducted to compare GAT lined with ITN vs AGO, both with either yeast or grass infusion. Biogents-Sentinel (BGS) with BG-Lure and no CO2 was used as standard trap for Aedes mosquitoes. In the SFS, GAT outperformed AGO in collecting both nulliparous (65% vs 49%,OR=2.22,[95%CI:1.89-2.60],p

In an attempt to reuse fibrous textile waste and, at the same time, to address dye pollution in textile wastewater, waste cotton-based yarn was utilized as both a cheap and sustainable adsorbent and a precursor for carbon adsorbent production. Cotton and cotton/polyester yarn samples underwent thermal modification through carbonization followed by chemical activation with KOH. Various techniques including nitrogen adsorption-desorption isotherms, scanning electron microscopy, Fourier transform infrared spectroscopy, and surface charge determination were employed to analyze the morphological and surface properties of the cotton-based adsorbents. Adsorption properties were evaluated by testing the removal of selected cationic and anionic dyes from water. The impact of temperature, contact time, initial concentration, and pH of the adsorbate solution on adsorption was investigated, with experimental data analyzed using theoretical models. While carbonization alone did not significantly enhance adsorption properties, activated samples exhibited high efficacy in removing both cationic and anionic dyes from water. Despite the negative influence of the polyester component in the carbon precursor on the efficiency of activated samples in removing methyl orange, results indicated that activated cotton and cotton/polyester yarn could be used to prepare highly efficient adsorbents for the rapid removal of methylene blue from real wastewater samples.

(1) Background: Globally, about 600 million people are afflicted with diabetes, and one of its most prevalent complications is neuropathy, a debilitating condition. At present, the exploration of novel therapies for alleviating diabetic neuropathy-associated pain is genuinely captivating, considering that current therapeutic options are characterized by poor efficacy and significant risk of side effects. In the current research, we evaluated the antihyperalgesic effect of sildenafil (phosphodiesterase-5 inhibitor) – metformin (antihyperglycemic agent) combination and its impact on biochemical markers in alloxan-induced diabetic neuropathy in rats; (2) Methods: The study comprised a cohort of 70 diabetic rats and 10 non-diabetic rats which were submitted to hot, cold, and tactile stimulus tests. Morover, we investigated the influence of this combination on TNF-α, IL-6 nitrites and thiols levels in brain and liver tissues; (3) Results: The results demonstrated that all sildenafil-metformin combinations decreased the pain sensitivity in von Frey test, Hot-plate test and Cold-plate test. Furthermore, alterations in nitrites and thiols concentrations and pro-inflammatory cytokines (specifically TNF-α and IL-6) were noted following a 15-day regimen of various sildenafil-metformin combinations. (4) Conclusions: The combination of sildenafil and metformin has a synergistic effect in alleviating pain in alloxan-induced diabetic neuropathy rats. Additionally, the combination effectively decreased inflammation, inhibited the rise in NOS activity, and provided protection against glutathione depletion.

This research presents the creation of a Virtual Reality experience for the Balzi Rossi museum, commemorating the centenary of Prince Albert I Grimaldi's archaeological work at the site. The project, a collaboration between the University of Genoa's 3D Lab Factory, Eurodrone, and the Balzi Rossi archaeological museum, aims to preserve and convey the site's heritage through advanced VR technology. Initially employing Unreal Engine 4, the team used photogrammetry for 3D reconstruction of the "Caviglione" and "Florestano" caves, notable for their ancient rock engravings. This first VR model, despite hardware limitations, provided an interactive exploration of the site. The subsequent development phase utilized Unreal Engine 5, incorporating Nanite technology for enhanced visual fidelity. This advancement resulted in a more detailed and immersive VR experience, presenting the Balzi Rossi cliff across different historical periods, including the Würm glaciation. Key to this phase was optimizing the VR experience for performance, focusing on stable frame rates and minimizing motion sickness, and integrating a multi-lingual interface for broader accessibility. Since November 2023, the VR setup at the Balzi Rossi Museum has been an educational and interactive feature, enabling visitors to explore the site's history virtually. This research demonstrates the potential of VR in cultural heritage preservation and education, providing a foundation for future technological improvements in the field.

Background and Objectives: Knee osteoarthritis (KOA) is a degenerative disease that is targeting continuously people of different ages, but especially the elderly population, the number of which tends to increase continuously at the global level. Apart from age, excess weight can influence the evolution of the disease, with obesity being associated with a weak inflammation stage, and an imbalance between pro-inflammatory and anti-inflammatory cytokines. The present work aimed to identify specific biomarkers alike ACRP-30, IL-10, TNF-α, and IL-6 in synovial fluid and correlate them with patients’ clinical data. Materials and Methods: 24 subjects with KOA and over 50 years of age are involved in the present study. All patients performed a supine X-ray at the target knee. Ultrasound was performed using an ESAOTE MyLab Omega (ESAOTE Spa, Italy) ultrasound device and a 6-19 MHz linear array transducer. Results: The obtained results highlighted a significant correlation between age and adiponectin level (p=0.0451, r=-0.412). Also, the IL-10 values are lower in cases where the intensity of the pain is more pronounced (p=0.0405, r=-0.421). In addition, analyzing the data by gender, it was observed that in the case of males, stiffness is more related to age (p=0.0079, r=0.7993), compared to women (p=0.0203, r=0.6223). In the case of women, the progression of the disease tends to increase more intensively total WOMAC score’s values (p=0.00031, r=0.8342), compared with men (p=0.0289, r=7013). Regarding interleukins and BMI, significant correlations were observed only in the case of men. Conclusions: A significant correlation between age and adiponectin, and adiponectin and IL-6, suggests that advanced age may contribute to adiponectin reduction. Comparing men with women, it was observed that men's age is more related to rigidity, and IL-6 and IL-10 are directly correlated to BMI and women seem to be more sensitive to pain and stiffness.

The accumulation of brown algae from the genus Sargassum has been increasing over the years in coastal regions of the Caribbean, Africa, Brazil, and Mexico. This causes harmful effects to the ecosystem, health, economy, and climate due to gas emissions from its decomposition process. There is the possibility of this biomass being reused in civil construction, and few studies have been carried out on its application to common Portland cement mortar. As such, the objective of this study is to evaluate the potential of sargassum ash as a mineral addition to partial replacement of fine aggregates in Portland cement mortar. Characterizations of the raw materials were carried out through X-ray fluorescence spectroscopy, loss on ignition, particle size distribution, Brunauer–Emmett–Teller (BET), real density, X-ray diffraction, scanning electron microscopy, and dispersion spectroscopy of electrons. The mortars were prepared by partially replacing the fine aggregate (sand) with sargassum ash, at 0%, 5%, 10% and 20%. Mortar performance was evaluated through water absorption, apparent porosity, apparent specific mass, compressive strength after 7, 28, and 63 days after curing. Lastly, a life cycle assessment in accordance with ISO standards 14040:2006 and 14044:2006. The results showed that replacing sand with sargassum ash increases water absorption, apparent porosity, and decreases the apparent specific mass and compressive strength as replacement increases. Nevertheless, the compressive strength results after 63 days, for 5 and 10% replacement did not differ statistically from reference values. The life cycle assessment indicates that mortars with partial replacement of sand by sargassum ash showed positive environmental impacts when compared to reference values for most categories regardless of the scenario analyzed, especially for mortar with 10% replacement. As such, the use of sargassum ash at 10% does not alter compressive strength values after 63 days while reducing its environmental impact. The application of this biomass in civil construction materials provides a destination for this algae that has been causing several social, environmental, and economic problems.

Environmental monitoring programs rely on periodic spot sampling at specific locations, followed by laboratory analysis, aiming at the evaluation of water quality at a catchment scale. For this purpose, automatic telemetric stations for specific parameters have been installed by the Institute of Marine Biological Resources and Inland Waters of Hellenic Centre for Marine Research (IMBRIW-HCMR) within several Greek rivers and lakes, providing continuous and temporal monitoring possibilities. Nevertheless, the employment of unmanned surface vehicles (USV) equipped with integrated sensors represents a tool valuable to several monitoring strategies, offering enhanced temporal and spatial coverage over specific timeframes, allowing for targeted examination of sites or events of interest. The USVs have been deployed by Athens Water and Sewerage Company (EYDAP) as a cost-effective tool for the environmental monitoring of surface water bodies of interest, with emphasis on the spatial fluctuations of chlorophyllα, electrical conductivity, dissolved oxygen and pH, observed in Koumoundourou Lake and rivers Acheloos, Asopos and Kifissos. The effectiveness of an innovative heavy metal (HM) system installed in the USV for thein situ determination of copper and lead was also evaluated herewith. The results obtained demonstrate that both the timely detection of potential pollution from both anthropogenic activities and natural processes as well as the monitoring of inland waters are made feasible through the employment of USV.

Angiogenesis is a critical physiological response to ischemia but becomes pathological when dysregulated and driven excessively by inflammation. We recently identified a novel angiogenic role for tripartite-motif-containing protein 2 (TRIM2) whereby lentiviral shRNA-mediated TRIM2 knockdown impaired endothelial angiogenic functions in vitro. This study sought to determine whether these effects could be translated in vivo and to determine the molecular mechanisms involved. CRISPR/Cas9-generated Trim2–/– mice that underwent a periarterial collar model of inflammation-induced angiogenesis exhibited significantly less adventitial macrophage infiltration relative to wildtype (WT) littermates, concomitant with decreased mRNA expression of macrophage marker Cd68 and reduced adventitial proliferating neovessels. Mechanistically, TRIM2 knockdown in endothelial cells in vitro attenuated inflammation-driven induction of critical angiogenic mediators, including nuclear HIF-1α, and curbed the phosphorylation of downstream effector eNOS. Conversely, in a hindlimb ischemia model of hypoxia-mediated angiogenesis, there were no differences in blood flow reperfusion to the ischemic hindlimbs of Trim2–/– and WT mice despite a decrease in proliferating neovessels and arterioles. TRIM2 knockdown in vitro attenuated hypoxia-driven induction of nuclear HIF-1α but had no further downstream effects on other angiogenic proteins. Our study has implications for understanding the role of TRIM2 in the regulation of angiogenesis in both pathophysiological contexts.

Understanding the dynamics of Organic Carbon mineralization is fundamental in forecasting biosphere to atmosphere Net Carbon Ecosystem Exchange (NEE). With this perspective, we developed 3D-CMCC-PSM, a new version of the hybrid Process Based Model 3D‐CMCC FEM where also heterotrophic respiration (R_h) is explicitly simulated. The aim was to quantify NEE as a forward problem, by subtracting Ecosystem Respiration (R_eco) to Gross Primary Productivity (GPP). To do so, we developed a simplification of the Soil Carbon dynamics routine proposed in DNDC [1]. The method calculates decomposition as a function of soil moisture, temperature, state of the organic compartments, and relative abundance of microbial pools. Given the pulse dynamics of soil respiration, we introduced modifications in some of the principal constitutive relations involved in phenology and littering sub-routines. We quantified the model structure related uncertainty in NEE, by running our training simulations over 1000 random parameter-sets extracted from parameters distributions expected from literature. 3D-CMCC-PSM predictability was tested on independent time series for 6 Fluxnet sites. The model resulted in daily and monthly estimations highly consistent with the observed time series. It showed lower predictability in Mediterranean ecosystems, suggesting that it may need further improvements in addressing evapotranspiration and water dynamics.

Transition-metal-free synthesis of 4-pyrones via TfOH-promoted nucleophilic addition/cyclization of diynones and water has been developed. This transformation is simple, atom economical and environmentally benign, providing rapid and efficient access to substituted 4-pyrones.

Sustainable development and education in sustainable development (ESD) are crucial and interconnected topics under wide discussion today. Young adults need to be educated in how to help bring about change. Thus, the dynamic relationship between school and home is important. In education, use could be made of English language classes, especially since English is a global language that enables access to the sustainability literature and facilitates discussion in global conferences and meetings. Consequently, English as a foreign language (EFL) students could gain confidence from being able to understand and use the terminology of, for example, sustainability. In this paper, the use of competence-based language teaching (CBLT) is proposed as a means of introducing sustainability topics into EFL writing classes at a university in Saudi Arabia. Students’ competence in sustainable development is therefore considered based on their ability to write about suggested sustainable development topics, measured on a scale for five dimensions of ESD proposed by Michelsen and Fischer (2017). The results demonstrate that the students possessed competence in sustainable development and intended to participate in its implementation. Thus, recommendations are made for the stakeholders in the education sector to include sustainable development topics as an initial offering in the curricula of various specialties using the CBLT approach.

This paper presents a new semi-explicit algorithm for parameters estimation in a time-fractional generalization of dual-phase-lag heat conduction model with the Caputo fractional derivatives. It is shown that this model can be derived from a general linear constitutive relation for the heat transfer by conduction when the heat conduction relaxation kernel contains the Mittag-Leffler function. The model can be used to describe heat conduction phenomena in a material with power-law memory. The proposed algorithm of parameters estimation is based on the time integral characteristics method. The explicit representations of the thermal diffusivity and the fractional analogues of the thermal relaxation time and the thermal retardation are obtained via a Laplace transform of the temperature field and utilized in the algorithm. An implicit relation is derived for the order of fractional differentiation. In the algorithm, this relation is resolved numerically. An example illustrates the proposed technique.

ABSTRACT Background: To date, the COVID-19 pandemic has been the foremost health concern for humankind in the new millennia. This paper aims to describe the related hospitalizations in Italy during the first two years of the health emergency. Design and methods: This is a retrospective, population-based study of Italian hospitalizations for patients diagnosed with COVID-19 during the 2020-2021 period, extracted from the National Hospital Discharge Registry. The outcome variables considered include hospital admissions, costs, and length of stay, among other hospitalization-level variables. Costs were estimated through the charges associated with the Diagnosis-Related Group and Major Diagnostic Categories coding system, plus an additional cost attributed to COVID-19 admissions. To these charges was added an extra cost defined by the ministry of health. Results: In Italy, there were 357,354 hospitalizations for COVID-19 attributed to 298,856 patients in 2020 and 399,043 hospitalizations for COVID-19 attributed to 333,447 patients in 2021. COVID-19 patients faced a transfer rate thrice that of other patients. Hospitalizations were concentrated predominantly in the northern regions, particularly in the first year. Hospitalization rates varied by age in a sine wave pattern, peaking in the youngest and oldest age groups, with mortality rates escalating with age— tending to remain below 3% for those under 44 but surging to 40% in individuals over 75. The financial impact of COVID-19 hospitalizations was substantial, with total costs reaching €3.97 billion in 2020 and €4.99 billion in 2021. Costs per admission and per day also rose, from €11,112 and €807 in 2020 to €12,503 and €844 in 2021, respectively. Excluding the added financial burden of COVID-19, costs would have been notably lower. Hospitalizations involving continuous invasive mechanical ventilation were particularly costly (about 24.000 euros x admission), reflecting the significant resources required for these treatments. Conclusion: Implementing a protective pad around the entire health system that leverages networks of family doctors and nurses, connected in real time to the entire health system, can be crucial. Such a network, tasked with monitoring the local epidemiological situation, protecting vulnerable individuals also through telehealth visits, and establishing a triage system for infections in the initial phase, may effectively help in managing virus spread and protecting hospitals from unpredictable waves of admission demand. Strengthening primary health care could be a decisive factor for the future and enhance the system's resilience in facing new challenges.

The SK model proposed by Sherrington and Kirkpatrick is an important mean field model for spin glasses. The dependence structure of Hamiltonians of the SK model is considered in this paper. We have investigated the covariance matrix of Hamiltonians of the SK model, and establish a relationship between the rank of the corresponding covariance matrix and the dimension of the space spanned by the Hamiltonians. Finally, we also give an upper bound for the rank of the covariance matrix, which might be the best.

Short-range Internet of Things (IoT) sensor nodes operating at 2.4 GHz need to provide ubiquitous wireless sensor networks (WSNs) with energy-efficient, wide-range output power (POUT) and fully integrated on a single chip for wireless body area networks (WBANs) and wireless personal area networks (WPANs) using low-power Bluetooth (BLE) and Zigbee standards. The proposed fully integrated transmitter (TX) utilizes a digitally controllable current-mode class-D (CMCD) power amplifier (PA) with a second harmonic distortion (HD2) suppression to reduce VCO pulling in an integrated system while meeting harmonic limit regulations. The CMCD PA is divided into 7-bit slices that can be reconfigured between differential and single-ended topologies. Duty cycle distortion compensation is performed for HD2 suppression, and an HD2 rejection filter and a modified C-L-C low-pass filter (LPF) reduce HD2 further. Implemented in a 28 nm CMOS process, the TX achieves a wide POUT range of from 12.1 to -31 dBm and provides a maximum efficiency of 39.8% while consuming 41.1 mW at 12.1 dBm POUT. The calibrated HD2 level is -82.2 dBc at 9.93 dBm POUT, resulting in a transmitter figure of merit (TX_FoM) of -97.52 dB. Higher order harmonic levels remain below -41.2 dBm even at 12.1 dBm POUT, meeting regulatory requirements.

Background: Type 2 diabetes mellitus (T2DM) is associated with increased atherogenicity and inflammatory responses, which may be related to increased levels of high mobility group box 1 (HMGB1) and Dickkopf-related protein 1 (DKK1). Objective: The role of HMGB1 and DKK1 in T2DM is examined in association with lipid and insulin profiles. Methods: Serum HMGB1 and DKK1 were measured in T2DM with and without hypertension and compared with controls. Results: HMGB1 and DKK1 are significantly higher in T2DM irrespective of hypertension. T2DM was also accompanied by increased atherogenicity indices. HMGB1 and DKK1 are significantly correlated with HbA1c, glucose, indices of insulin resistance, β-cell function, and glucose toxicity, and different atherogenic indices. A large part of the variance in the β-cell index (30.5%) and glucose toxicity (34.8%) was explained by the combined effects of HMGB1 and DKK1 and hypertension. We found that 18.3% of the variance of the atherogenic index of plasma was explained by HMGB1 and DKK1 levels and that 31.2% was explained by glucose toxicity, HMGB1 and body weight. Conclusion: The higher serum HMGB1 and DKK1 levels in T2DM patients and the associations with atherogenicity indicate that low grade inflammation and disorders in the Wnt pathways are associated with T2DM and that both HMGB1 and DKK1 may contribute to increased atherogenicity in T2DM. Moreover, both biomarkers may cause more deficits in β-cell function and increase glucose toxicity leading to the development of more inflammation and diabetic complications. HMGB1 and the Wnt pathways are new drug targets in the treatment of T2DM.