Background: Long COVID, characterized by a persistent symptom spectrum following SARS-CoV-2 infection, poses significant health, social, and economic challenges. This review aims to consolidate knowledge on its epidemiology, clinical features, and underlying mechanisms to guide global responses; Methods: We conducted a systematic literature review, analyzing peer-reviewed articles and reports to gather comprehensive data on long COVID’s epidemiology, symptomatology, and management approaches; Results: Our analysis revealed a wide array of long COVID symptoms and risk factors, with notable demographic variability. The current understanding of its pathophysiology suggests a multifactorial origin yet remains partially understood. Emerging diagnostic criteria and potential therapeutic strategies were identified, highlighting advancements in long COVID management.; Conclusion: This review highlights the multifaceted nature of long COVID, revealing a broad spectrum of symptoms, diverse risk factors, and the complex interplay of physiological mechanisms underpinning the condition. Long COVID symptoms and disorders will continue to weigh on healthcare systems in years to come. Ad-dressing long COVID requires a holistic management strategy that integrates clinical care, social support, and policy initiatives. The findings underscore the need for increased international cooperation in research and health planning to address the complex challenges of long COVID. There is a call for continued refinement of diagnostic and treatment modalities, emphasizing a multidisciplinary approach to manage the ongoing and evolving impacts of the condition.

The ground consists of many layers of soil with different properties. The propagation speed and path of seismic waves are affected by different soil layers. It is necessary to understand that layered soil exhibits different dynamic behaviors and responses under the action of seismic waves. This study utilized weathered soil and silica sand as materials to create multi-layered soil conditions with varying degrees of compaction. By conducting 1 g shaking table test on multi-layered soil, the interaction and influence between different soil layers under different earthquake conditions were observed. The approach of numerical analysis aims to validate the experimental results and provide an in-depth understanding of the dynamic behaviors of multi-layered soil grounds during seismic events. The results of this study show that the amplification effect of seismic waves is related to the number of soil layers and the degree of compaction of the soil layers. This indicates that the multi-layered soil ground and the behavior of the soil layers play an important role in the propagation and impact of seismic waves, and this amplification effect is of great significance in actual seismic disaster risk assessment and design.

Mastitis-causing bacteria can establish persistent infections in the mammary gland of commercially important dairy animals despite the presence of strong specific humoral and cellular immune mechanisms. The aim of this study was to encapsulate vitamin D3 by complex coacervation with sulfur-saturated bovine lactoferrin-alginate using microbial transglutaminase-catalyzed crosslinking and investigate the oral administration of encapsulated vitamin D3 in blood serum biomarkers of the immune response in late-lactating dairy goats. Dairy goats (n = 18) in late lactation were randomly assigned to three experimental groups (n = 6), after balancing weight. Dairy goats were orally administered with 0.35 mg vitamin D3/day in the unencapsulated form and 0.35 mg vitamin D3/day in the encapsulated powder form. Another group received the basal diet. The experimental period lasted 6 weeks. The blood serum concentrations of 25-hydroxyvitamin D3 [25-(OH)-D3], lactoferrin, immunoglobulin A (IgA), and interferon-gamma (INF-γ) were measured. The delivery of vitamin D3 to dairy goats resulted in a marked increase of 25-(OH)-D3 concentration in serum while the serum level of lactoferrin also increased. Alternatively, the serum levels of IgA and the immunomodulatory cytokine INF-γ were elevated following supplementation with the encapsulated vitamin D3. Overall, the capsules in the powder form used in this study kept vitamin D3 highly bioavailable.

The predatory mirids Macrolophus pygmaeus Ramber and Nesidiocoris tenuis Reuter (Heteroptera: Miridae) are used for the biological control of Tuta absoluta Meyrick (Lep.: Gelechiidae) and other pests in tomato greenhouses. The functional response of 1 (young) and 10 (old) days old adult females and males of M. pygmaeus and N. tenuis on eggs of T. absoluta, was determined on tomato at two temperatures (20° and 25°C) and LD 16:8 and found to be Type II. M. pygmaeus females exhibited higher predation efficiency, than males at both tested temperatures. Young M. pygmaeus females had a higher efficiency than old ones, whereas males had a low efficiency irrespective of age. The predation efficiency of N. tenuis was high (but lower than M. pygmaeus) in both young females and males, although old females had a higher efficiency than the respective males. Our results show that the two predatory species have different functional response characteristics to their prey depending mainly on sex and age which may affect their role as biological control agents.

A finite element model of 100m X-BOW polar exploration cruise is established. The entire ship frequency response analysis was carried out, comparing the simulated values with the test values, the maximum error is 22%, but only 0.24mm/s difference, the error can be ignored from the perspective of comfort, therefore, the simulation results meet the requirements of engineering accuracy and verify the effectiveness of the model. According to the solution method for global modal equivalent mass, combing the spatial distribution principle of local modal mass, the method for solving the equivalent mass of a single local mode in mixed mode is proposed, the equivalent mass of the local vibration region of 100m X-BOW polar exploration cruise ship is solved by this method, tuned mass dampers mass ratio parameters are calculated using the equivalent mass. According to the analysis, tuned mass dampers has 31dB vibration absorption effect at 13.4Hz when the mass ratio is 0.05, it also has certain control effect at 10Hz and 18.8Hz, the control effect is 3dB and 2dB respectively, the overall control frequency band is flat and robust.

The prevailing challenge in our current era is climate change, a crisis recognized by the global community that has prompted immediate actions to confront and mitigate its consequences. There is a consensus among scientists that human activities, driven by developmental ambitions, are the driving force behind the ongoing climate crisis. “The well-documented aftermath, including the rise in sea levels, coastal erosion, reduced agricultural yields, compromised access to clean water, and health implications, emphasizes the intricate and wide-ranging effects of climate change.” Furthermore, there is an increasing recognition that climate change gives rise to distinct social, economic, and divergent consequences. “Although all countries worldwide will undergo the impacts of climate change, the distribution of these effects will differ among regions, generations, age groups, income levels, occupations, and genders.” Notably, the adverse consequences will disproportionately impact the impoverished, predominantly situated in developing nations. “This paper explores the effects of climate change on displacement and the ensuing refugee dilemma.” It aims to scrutinize the inclusion of climate-induced displacement in the present international framework, encompassing both climate change and refugee regimes. The paper promotes a human rights-centred approach to tackling displacement stemming from climate change.

Diabetes mellitus (DM) poses a significant challenge to global health, with its prevalence projected to rise dramatically by 2045. This narrative review explores the bidirectional relationship between periodontitis (PD) and type 1 diabetes mellitus (T1DM), focusing on cellular and molecular mechanisms derived by the interplay between oral microbiota and the host immune response. A comprehensive search of literature published between 2008 and 2023 was conducted to elucidate the association between these two diseases. Preclinical and clinical evidence suggests a bidirectional relationship, with individuals with T1DM exhibiting heightened susceptibility to periodontitis, and vice versa. The review includes recent findings from human clinical studies, revealing variations in oral microbiota composition in T1DM patients, including increases in certain pathogenic species such as Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans, along with shifts in microbial diversity and abundance. Molecular mechanisms underlying this association involve oxidative stress and dysregulated host immune responses, mediated by inflammatory cytokines such as IL-6, IL-8, and MMPs. Furthermore, disruptions in bone turnover markers, such as RANKL and OPG, contribute to periodontal complications in T1DM patients. While preventive measures to manage periodontal complications in T1DM patients may improve overall health outcomes, further research is needed to understand the intricate interactions between oral microbiota, host response, periodontal disease, and systemic health in this population.

Pancreatic cancer (PC) has a poor prognosis and displays resistance to immunotherapy. A better understanding of tumor-derived extracellular vesicles (EVs) effects on immune responses might contribute to improved immunotherapy. EVs derived from Capan-2 and BxPC-3 PC cells isolated by ultracentrifugation were characterized by atomic force microscopy, western blot (WB), nanoparticle tracking analysis and label-free proteomics. Fresh PBMCs from healthy donors were treated with PC- or control-derived heterologous EVs followed by flow cytometry analysis of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated, or -untreated PBMCs was performed and IFN-γ concentration was measured by ELISA. Notably, most of the proteins identified in Capan-2 and BxPC-3 EVs by proteomic analysis were connected in a single functional network (p=1x10-16) and were involved in “Immune System” (FDR: 1.10x10-24 and 3.69x10-19, respectively). Interestingly, treatment of healthy donor-derived PBMCs with Capan-2 EVs, but not with BxPC-3 EVs or heterologous control EVs induced early activation of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated PBMCs was consistent with their activation by Capan-2 EVs, indicating IFN-γ among major upstream regulators, as confirmed by ELISA. Proteomic and functional analyses indicate that PC-EVs have pleiotropic effects, and some may activate early immune response, which might be relevant for the development of highly needed immunotherapeutic strategies in this immune-cold tumor.

This general review assesses the impact of physical exercise on oxidative and nitrosative stress and the counteractive role of antioxidants, drawing from a systematic literature search up to March 2024 in databases like PubMed and Web of Science. The review highlights studies on the effect of exercise on the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and antioxidant responses in both human and animal models based on rigorous inclusion and exclusion criteria. Due to the variety of exercise types and participants' characteristics, a narrative synthesis approach was adopted. The findings indicate that moderate exercise boosts antioxidant defenses, known as hormesis, whereas excessive physical activity may increase oxidative and nitrosative damage. The review also explores the complex effects of antioxidant supplementation, revealing that while natural dietary antioxidants support health, high-dose supplements could potentially hinder positive adaptations to exercise. Recommendations for athletes and the general active population highlight the importance of balancing exercise and dietary intake to optimize health benefits. The review concludes with a call for more detailed research on tailored exercise and nutrition plans to dissect these intricate relationships further.

Buckypaper (BP), a flexible and porous material, exhibits photovoltaic properties when exposed to light. In this study, we have employed Radio Frequency (RF) Sputtering of Zinc Oxide (ZnO) followed by rapid thermal annealing to enhance the photovoltaic response of BP. We investigated the impact of various sputtering parameters, such as the gas flow ratio of argon to oxygen and deposition time, on the morphology, composition, resistivity, and photovoltaic characteristics of ZnO-modified BP. Additionally, the photovoltaic performance of the samples under different illumination modes and wavelengths was compared. It was found that optimal sputtering conditions—argon to oxygen flow ratio of 1:2, deposition time of 20 minutes, and power of 100 watts—resulted in a ZnO film thickness of approximately 45 nanometers. After annealing at 400°C for 10 minutes, the ZnO-modified BP demonstrated a significant increase in photocurrent and photovoltage, along with a reduction in resistivity, compared to unmodified BP. Moreover, under gradient illumination, the ZnO-modified BP exhibited a photovoltage enhancement of 14.70 times and a photocurrent increase of 13.86 times, compared to uniform illumination. Under blue light, it showed a higher photovoltaic response than under other colors. The enhancement in photovoltaic response is attributed to the formation of a Schottky junction between ZnO and BP, an increased carrier concentration gradient, and an expanded light absorption spectrum. Our results validate that ZnO sputtering followed by annealing is an effective method for modifying BP for photovoltaic applications such as solar cells and photodetectors.

Microencapsulation by atomization can be used to minimize the loss of bioactive compounds, improving the characteristics and applicability of the powdered product. This study evaluates the effect of different encapsulating agents (maltodextrin, gum arabic, and chitosan) and three spray nozzle diameters (1.0, 1.2, and 1.5 mm) on the atomization of guavira (Campomanesia adamantium) pulp with added 6% bocaiuva (Acrocomia aculeata) dehydrated pulp in the green maturation stage. The experiment followed a simplex-centroid mixed design, with carrier agent concentrations and spray nozzle diameters as independent variables and powder yield, solubility, hygroscopicity, and vitamin C content as dependent variables. The results show that gum arabica increased powder yield and vitamin C retention. The addition of maltodextrin resulted in powders with increased solubility and low hygroscopicity. Furthermore, the optimization tool indicated that the best process conditions were achieved with the addition of gum arabic (10.8%) and chitosan (7.2%), resulting in powders with 29.48% yield, 82.96% solubility, 15.90% hygroscopicity and 741.11 mg/100g vitamin C. Furthermore, the 1.0 mm diameter spray nozzle was considered the most suitable for obtaining guavira pulp microparticles with higher ascorbic acid content.

Huanglongbing (HLB), or citrus greening, is a devastating disease impacting citrus trees worldwide, with severe effects particularly noted in Florida. Current strategies to combat HLB have focused on aggressive replanting despite the high susceptibility of young trees to infection. In this context, it is critical to explore agronomic practices that can enhance the health and resistance of young citrus trees to HLB. Here, we demonstrate that treatment with homobrassinolide (HBr), a type of brassinosteroid, on newly planted citrus trees can delay HLB infection and improve tree health amidst the high psyllid pressure conditions endemic to Florida. Our study reveals a significant reduction in HLB infection rates in HBr-treated trees compared to control trees, with only 25% of treated trees testing positive for HLB by six months, in contrast to 100% infection in untreated trees. This delay in infection may be attributed to HBr inducing an immune response and negatively impacting psyllid performance, as subsequently demonstrated in a greenhouse experiment. Our findings suggest that HBr applications could serve as a viable strategy to enhance the resilience of citrus production against HLB, underscoring the need for further investigation into their mechanisms of action and potential role in a comprehensive pest and disease management strategy.

Viral co-infections, where a host is infected by multiple viruses simultaneously, are common in the human population. Human viral co-infections can lead to complex interactions between viruses and the host immune system, affecting the clinical outcome and posing challenges for treatment. Understanding the types, mechanisms, impacts, and identification methods of human viral co-infections is crucial for the prevention and control of viral diseases. In this review, we first introduce the significance of studying human viral co-infections and summarize the current research progress and gaps in this field. We then classify human viral co-infections into four types based on the pathogenic properties and species of the viruses involved. Next, we discuss the molecular mechanisms of viral co-infections, focusing on virus-virus interactions, host immune responses, and clinical manifestations. We also summarize the experimental and computational methods for identifying viral co-infections, emphasizing the latest advances in high-throughput sequencing and bioinformatics approaches. Finally, we highlight the challenges and future directions in human viral co-infection research, aiming to provide new insights and strategies for the prevention, control, diagnosis, and treatment of viral diseases. This review provides a comprehensive overview of the current knowledge and future perspectives on human viral co-infections, and underscores the need for interdisciplinary collaborations to address this complex and important topic.

This paper presents the results of investigations into the pyrolysis of waste polypropylene in a laboratory fixed-bed batch reactor. The experiments were designed and verified in such a way as to allow the application of the Response Surface Methodology (RSM) in the development of an empirical mathematical model that quantifies the impacts mentioned above. The influence of the mass of the raw material (50, 100 and 150 g), together with the reactor temperature (450, 475 and 500 °C) and the reaction time (45, 50 and 75 min) was examined. It has been shown that the mass of the raw material, i.e. the filling volume of the reactor, has a significant influence on the pyrolysis oil yield. This influence exceeds the influence of reactor temperature and reaction time. This was explained by observing the temperature change inside the reactor at three different spots at the bottom, middle and top of the reactor. Recorded temperature diagrams show that with greater masses of feedstock, local overheating occurs in the middle part of the reactor, which leads to overcracking of vapor products, and from there to an increased formation of non-condensable gases, i.e. reduced yield of pyrolytic oil.

Dynamic time history analysis is a powerful and effective method to study the seismic response of tunnels, the dynamic time history to analyze the seismic response of the tunnel in the typical subway in this paper. The analysis results show that the overall levelling of the tunnel will not affect the tunnel too much, and the seismic response of the tunnel is mainly related to the relative displacement of the ground around the tunnel. The analysis results show that the internal force of the tunnel and the tunnel inclination have a good linear relationship, and the tunnel inclination can be used to measure the magnitude of the seismic response of the tunnel.

In spite of prevalence gaps in several micronutrients supporting immune function, significance of their deficits/supplementation for efficacy of vaccines is underinvestigated. Thus, influence of supplementation combining vitamins C and D, zinc, selenium and manganese, and N-acetyl-cysteine on mouse IgG responses and underlying mechanisms to seasonal quadrivalent influenza vaccine (QIV) was investigated. QIV was given in two doses (28 days apart). The supplementation starting 5 days before the first injection increased the total serum IgG titre, through stimulation of germinal centre (GC) reaction in secondary lymphoid organs (SLOs), as indicated by increase in the frequency of GC B cells and follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells. Additionally, the supplementation “optimized” IgG response following the second QIV injection by supporting more favorable (in respect to virus clearance) IgG2a response through favoring Th1 differentiation as indicating by Th1 (INF-γ) /Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely reflected partly their antioxidant action (as indicated by redox status analyses) on Th cell differentiation. Thus, the study forms solid base for further research aimed at repurposing use this safe and inexpensive micronutrient combination as an adjuvant for virus influenza vaccine.

A number of studies suggested that influenza vaccination can provide protection against COVID-19 but the underlying mechanisms that could explain this association is still unclear. In this study, the effect of the 2021/2022 seasonal influenza vaccination on the immune response to the booster dose of anti-SARS-CoV-2 vaccination was evaluated in a cohort of healthy individuals. One hundred and thirteen participants were enrolled, and 74 of them with no prior COVID-19 diagnosis or significant co-morbidities were considered for the analysis. Participants received the anti-influenza tetravalent vaccine and the booster dose of the anti-SARS-CoV-2 vaccine or the anti-SARS-CoV-2 vaccine alone. Blood was collected before and 4 weeks after each vaccination and 12 weeks after SARSCoV2 vaccination and analyzed for anti-flu and anti-spike-specific antibody titers and for in vitro influenza and SARS-CoV-2 neutralization capacity. Results indicated an increased reactivity in subjects who received both influenza and SARSCoV2 vaccinations, as compared to those who received only the SARS-CoV-2 vaccine, with sustained anti-spike antibody titers up to 12 weeks post-vaccination. Immune response to influenza vaccine was evaluated and individuals were stratified as high or low responders. High responders showed increased antibody titers against SARSCoV2 vaccine both after 4- and 12-weeks post-vaccination. On the contrary, the individuals classified as low responders were less responsive to the SARS-CoV-2 vaccine. These data indicate that both external stimuli, such as influenza vaccination, and the host's intrinsic ability to respond to stimuli play a role in the response to vaccine.

With the rapid development of tumor immunotherapy, nanoparticle vaccines have attracted much attention as a potential therapeutic strategy. The potential role of the mannose-modified lipid calcium phosphate nanoparticle vaccine in enhancing the anti-tumor immune response was investigated. The aim of this study was to investigate the effect of mannose modification on the immune response of nanoparticles in regulating the tumor microenvironment through systematic review and analysis and to explore its potential clinical application in tumor therapy. Currently, despite the potential advantages of nanoparticle vaccines in immunotherapy, achieving an effective immune response in the tumor microenvironment remains a challenge. Tumor immune escape and overexpression of immunosuppressive factors limit its clinical application. Therefore, this study will explore how to intervene in the immunosuppressive mechanism in the tumor microenvironment through mannose-modified lipid calcium phosphate nanoparticle vaccines so as to improve the immunotherapy effect of tumor patients and provide new ideas and strategies for the field of tumor therapy.

(1) Background: The proportion of fully mechanized harvesting systems in Austria is constantly increasing especially because of the technological development of the machines, which allows them to drive on increasingly steep terrain. This leads to additional challenges and potential hazards for the operators, which may also cause higher stress levels. The purpose of this study is to develop and debate a new set of methodologies for determining time and space resolved psychophysiology data to analyze stressful and non-stressful work situations for harvester and forwarder operators; (2) Methods: we suggest a study protocol to analyze a) tasks performed by the driver, b) environmental factors, like slope gradient, c) the psychophysiological response of experts during these tasks, and d) evaluate the worker´s subjective stress and fatigue before and after a harvest operation. (3) Results: Within this manuscript we present a study protocol based on quantitative and qualitative methods, like time and space resolved psychophysiology, questionnaires, qualitative interviews, as well as video and sensor-based analysis of environmental and machine data. The first results from real measurements of a forwarder driver are presented; (4) Conclusions: This multimodal research protocol serves to explore the relationship between stress, fatigue, and performed tasks. Through our quantitative and qualitative methodology, researchers can improve the health and safety of forest workers at work, improve their productivity and reduce damage to remaining trees.

This study explores the significance of active suspension systems for vehicles with lower chassis compared to conventional ones, aiming at the development of future automobiles. Conventional linear MR (Magneto-Rheological) dampers were found inadequate in ensuring sufficient vibration control because the vehicle's chassis becomes lowered in the unmanned vehicles or purposed based vehicles. As an alternative, a rotary type of MR damper is proposed in this work. The proposed damper is designed based on pre-specified design parameters through mathematical modeling and magnetic field analyses. Subsequently, a prototype of the rotary MR damper identical to the design is fabricated, and effectiveness is shown through experimental investigations. In configuring the experiments, a proportional-integral (PI) controller is employed for current control to reduce the response time of the damper. The results presented in this work provides useful guidelines to develop a new type of MR damper applicable to various types of future vehicles’ suspension systems with low distance from the tire to the body floor.

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Despite new methods of diagnostics and treatment as well as extensive biological and immunosuppressive treatment, the etiology of RA is not fully understood. Moreover, the problem of diagnosis and treatment of RA patients is still current and affects a large group of patients. It is suggested that these ER-related features may impair adaptation to chronic stress, inferring the risk of rheumatoid arthritis. The main goal in this study was evaluation of changes in mRNA translation to determine chronic ER stress conditions in rheumatoid arthritis patients. The study group consist of 86 individuals including total 56 rheumatoid arthritis patients and 30 healthy controls. The expression level of mRNA form blood samples of RA patients as well as controls of the PERK-UPR associated genes: p-eIF2, BCL-2, PERK, ATF4, BAX were investigated by Real-Time qPCR. GAPDH expression was used as a standard control. Considering the median, the expression of PERK, BCL-2, p-eIF2, ATF4, BAX was found to be significantly increased in the blood of RA patients compared with the control group. The p-value for the PERK gene was 0.0000000036, the p-value for the BCL-2 gene was 0.000000014, the p-value for the p-eIF2 gene was 0.006948, the p-value for the ATF4 gene was 0.0000056 and the p-value for the BAX gene was 0.00019, respectively. Thus, it can be concluded that targeting of the components of the PERK-dependent UPR signaling pathway via small-molecule PERK inhibitors, may contribute to the development of novel, innovative treatment strategies against rheumatoid arthritis.

Friction stir welding (FSW) is a solid state welding process for joining metallic alloys and dissimilar metals. It has emerged as an alternative technology for welding high strength alloys that are difficult to join with conventional techniques. FSW is used to produce products with better mechanical properties. Now a days aluminum alloys have been widely used in several industrial applications such as aerospace, marine, automobile and commercial applications due to their light weight structure, better mechanical properties and high corrosion resistance.In this work, three welding parameters such as spindle speed, welding speed and plunge depth were considered for friction stir welding. FSW was carried out between dissimilar aluminum alloy plates (AA6061 and AA 8011) to produce butt joint.A Box-Behnken design with three factors and three levels was chosen to minimize the number of experimental conditions .The tensile strength and hardness of the welded regions were evaluated. The optimum level settings and the major parameters that influence the joint strength were obtained by Box-Behnken design.

In this study, we investigated the role of Giardia EVs in cellular communication and their potential as vaccine candidates. Our findings revealed that Giardia EVs activate pro-inflammatory signalling cascades, including SAPK/JNK and ERK1/ERK2, as well as the NF-kB pathway, resulting in IκB-α degradation and p65 translocation to the nucleus, in mouse macrophages. Moreover, Giardia EVs increased the expression of genes encoding pro-inflammatory molecules, such as Il1β, Il6, Il4, Ptgs2, Nos2, and Tnf. Interestingly, Giardia EVs enhanced the maturation status of human Mo-DCs and significantly increased T-cell proliferation with a Th1 profile. Immunization studies demonstrated that Giardia EVs elicited antigen-specific antibodies, with IgG subclasses indicating a balance Th1/ Th2 response. Mass spectrometry analysis identified EV proteins (22 KDa and 50 KDa) that bind to serum antibodies of immunized mice including elongation factor 1-alpha, Alpha-7.3 giardin, tubulin, and Variant Surface Proteins (VSP), known antigenic proteins in Giardia infections. Overall, our results indicated that Giardia EVs modulate innate immune cells in vitro, induce antibody-based immune response in vivo, and contain conserved immunogenic proteins. Consequently, Giardia EVs hold promise as a cell-free vaccine candidate for giardiasis.

Brushless Direct Current Motors are significantly improved for using many electrical applications. The design investigation is increased year by year and most of the motor design researchers find out the superior efficiency of the BLDC motor. The traditional motor consumed more electrical power than BLDC motor. The design of BLDC motors that are compact, small, easy to control, save energy and light weight. Due to this fact, the design of BLDC motor should be analyzed to improve the motor characteristics performance. The research focuses on the design of BLDC motor performance using Taguchi Method and Response Surface Methodology (RSM) for Finite Element Method (FEM). Firstly, the Taguchi Method is applied to identify the optimization point of design parameters and consider using the reference model of actual BLDC electric fan motor with a rated power of 26Watts design. Based on the Taguchi Method to create the RSM is used to two-step optimization design performance using in FEM analysis. The performances of motor design proposed approach to provide the effeteness for motor design investigator. In this investigation aims the better structural performances in output power, torque, efficiency and torque ripple. The final design of proposed model achieved an energy efficiency is 10% higher than the reference design of prototype modes, the output power result is 10W higher this reference design. We can reduce the loss of the proposed motor design. Furthermore, the maximum torque can also increase the 0.032Nm of that design. The design simulation results were produced and studied by the FEM analysis of JMAG software. From the evaluation results, the configurations of reference model design are compared with the proposed design by using the three methods of motor design optimization showed the best characteristics for performance of motor investigation design.

To satisfy the interests of multiple agents and those of comprehensive indicators such as peak-to-valley differences and load fluctuations occurring on the network side, this paper presents a flexible load demand-side response optimization method that considers the benefits of peak-to-valley smoothing. First, load aggregation modelling of air conditioning and electric vehicles was conducted, and the complementarity of the power consumption behaviour of different types of flexible loads was used to improve the responsiveness of the load aggregator. Second, considering demand-side responses and taking into account the interests of both supply and demand, the load fluctuation and peak-to-valley difference on the network side are reduced, and a flexible load double-layer optimization model incorporating the peak-to-valley smoothing benefit is established. Finally, the effectiveness of the proposed optimization model is verified by using the KKT condition and the big M method to evaluate this two-layer optimization problem as a single-layer optimization problem. Comparative examples demonstrate that the proposed two-layer optimization method can improve the revenue of the distribution network operators and the load aggregators by using the complementary nature of the load response characteristics of electric vehicles and air conditioners. Moreover, the proposed method can effectively reduce the load peak-to-valley difference and load fluctuation of the distribution network by introducing the peak-to-valley smoothing benefit model.

While the underwater submersible encounters internal solitary wave (ISW), its loadings and motions would be seriously disturbed. To investigate the interaction effect between the suspended submersible and ISW, a three dimensional ISW-submersible interaction numerical model was established based on the Computational Fluid Dynamics (CFD) method. The generation and propagation of ISW was simulated in a two-layer fluid numerical wave tank according to the eKdV theory. The standard operation equation of submersible was introduced to simulate the six degree of freedom (6DoF) motions of submersible combined with the overset dynamic mesh method. The motion simulation method of submersible was effectively validated by comparing with published experimental results on the motion responses of the slender body under the ISW. Based on the constructed numerical model, the dynamic mechanism between the suspended submersible and ISW were studied, and the effects of the initial submerged depths and the ISW amplitudes on the dynamic responses of the submersible were revealed. According to the numerical results, the motions of the submersible have been significantly determined by its initial submerged depths. The submersible located above the ISW interface has a significant motion along the propagation direction of ISW and its motion trajectory resembles a counterclockwise semi ellipse. The motions of the submersible located below the ISW interface follows with the trace of the lower layer fluid which presented as an unclosed clockwise ellipse. The corresponding motions of the submersible would be increased as the increase of the ISW amplitudes.

Candidate vaccines against African swine fever virus (ASFV) based on naturally attenuated or genetically modified viruses have the potential to generate protective immune responses, although there is no consensus on what defines a protective immune response against ASFV. Studies, espe-cially in sensible host species, focused on unravelling protective mechanisms will contribute to the development of safer and more effective vaccines. The present study provides a detailed analysis of phenotypic and functional data on cellular responses induced by intradermal immunization and subsequent boosting of domestic pigs with the naturally attenuated field strain Lv17/WB/Rie1, as well as the mechanisms underlying protection against intramuscular challenge with the virulent genotype II Armenia/07 strain. The transient mild to moderate increase of IL-8 and IL-10 in serum observed after immunization might be directly correlated with survival. Protection was also associated with a robust ASFV-specific polyfunctional memory T cell response, where CD4CD8 and CD8 T cells were identified as the main cellular sources of virus-specific IFNγ and TNFα. In parallel to cytokine response, these T-cell subsets also showed specific cytotoxic activity as evidenced by the increased expression of the CD107a degranulation marker. Along with virus-specific multifunctional CD4CD8 and CD8 T responses, the increased levels of antigen experienced cytotoxic CD4 T cells observed after challenge in immunized pigs might also contribute to control virulent infection by killing mechanisms targeting infected antigen-presenting cells. Future studies should elucidate whether the memory T-cell responses evidenced in the present study persist and provide long-term protection against further ASFV infections.

Abstract Background In tumors, somatic mutagenesis presumably drives DNA damage response (DDR) via altered regulatory pathways increasing genomic instability and proliferative activity. These considerations led to the standard therapeutic strategy against cancer: the disruption of mutation activated DNA repair pathways of tumors. Purpose Justifying that cancer cells are not enemies to be killed, but rather they are ill human cells having the remnants of physiologic regulatory pathways. Results 1. Genomic instability and cancer development may be originated from the flaw of estrogen signal rather than excessive estrogen signaling. 2. Healthy cells with genomic instability exhibit somatic mutations helping DNA restitution. 3. Somatic mutations in tumor cells aim the restoration of DNA damage rather than further genomic derangement. 4. In tumors, estrogen signal drives the pathways of DNA stabilization leading to apoptotic death. 5. In the peritumoral cellular infiltration, the genomic damage of tumor induces inflammatory cytokine secretion and increased estrogen synthesis. In the inflammatory cells, increased growth factor receptor (GFR) signal confers unliganded activation of estrogen receptors (ERs). 6. In tumor cells responsive to genotoxic therapy, constitutive mutations help the upregulation of estrogen signal and consequential apoptosis. In tumors non responsive to genotoxic therapy, the possibilities for ER activation via either liganded or unliganded pathway, are exhausted leading to farther genomic instability and unrestrained proliferation. Conclusion Understanding the real character and behavior of human tumors at molecular level suggests that we should learn the genome repairing methods of tumors and follow them by supportive therapy rather than provoking additional genomic damages.

Abstract: Toxicity of emerging organic pollutants to photosystems of aquatic plants are still not well clarified. This study aimed to develop a novel ecotoxicological experimental protocol based on nanoscale electrochemical mapping of photosynthetic oxygen evolution of aquatic plants by SECM (scanning electrochemical microscopy). The protocol was also checked by confocal laser scanning microscopy (CLSM), the traditional Clark oxygen electrode method and chlorophyll fluorescence technique. The typical persistent organic pollutant 2,4-dichlorophenol (2,4-DCP) in water environment and the common aquatic Microsorium pteropus (M. pteropus) were chosen as the model organic pollutant and tested plant, respectively. It was found that the SECM method could well discriminated the responses of stoma micromorphology and spatial pattens of photosynthetic oxygen evolution on single stoma. The shape of stoma blurred with increasing 2,4-DCP concentration, which was in good agreement with the CLSM images. The dose-response curves and IC50 values obtained from the SECM data were verified by the data measured by the traditional Clark oxygen electrode method and chlorophyll fluorescence test. The IC50 value of single stoma oxygen emission of 24 h exposed plant leave, which was derived from the SECM current data (32535 μg L-1), was close to those calculated from the maximum photosynthetic efficiency (Fv/Fm) measured by chlorophyll fluorescence test (33963 μg L-1), and the Clark oxygen electrode method photosynthetic oxygen evolution rate (32375 μg L-1). The 72 h and 96 h 2,4-DCP exposure data further confirmed the reliability of the nanoscale stoma oxygen emission mapping methodology for ecotoxicological assessment. In this protocol, the procedures for how to collect effective electrochemical data and how to extract useful information from the single stoma oxygen emission pattern were well established. This study showed that SECM is a feasible and reliable ecotoxicological tool for evaluation of toxicity of organic pollutants to higher plants with unique nanoscale visualization advantage over the conventional methods.

For marine vessels, a propeller shaft system, also known as a propulsion shaft system, is an essential changer in engine torque and propeller thrust. The propeller shaft system is subjected to transverse, longitudinal, and torsional excitations during operation. These sources of excitations originate from alternating thrust generated by the propeller, operation of a propeller in a stern flow field which is non-uniform in time and space, misalignment of components such as shafts, bearings, and keyholes in the assembly, excitations in the form of rotational motion, and the whirling motion of the shafts. These dynamic excitations posed a challenging issue for the integrity and reliability of a marine vehicle. Thus, it is crucial to analyze the dynamic response of the propulsion shaft system. The dynamic analysis of the propulsion shaft system is typically conducted using numerical /analytical models. At present, Finite Element Model (FEM) as a numerical model plays a vital role in analyzing the dynamic response of the structure. The computed response and the modal parameters from the FE model are reliable only if accurate boundary conditions, such as stiffness, can be imposed on the model. However, the numerical FE model deviates from the experimental results because of uncertainties in the stiffness values of the bearings and other connectors. This paper uses the Response Surface Optimization (RSO) technique to estimate the unknown stiffness of the bearings used in the propulsion shaft system. The experimental model of the propeller shaft system is constructed from the steady-state response of the system using the step sine excitation. The natural frequencies and the amplitude of vibrations in the FE model are updated using the parametric RSO technique. The updated model shows that the difference in natural frequencies and vibration amplitude is less than 10% between the optimized and experimental models. Propeller Shaft, Vibrations, Optimization, Response Surface

The recent availability of commercial platforms for behavioral analysis in zebrafish larvae based on video-tracking technologies has exponentially increased the number of studies analyzing different behaviors in this model organism to assess neurotoxicity. Among the most commonly used assays in zebrafish larvae are basal locomotor activity (BLA) and visual motor response (VMR). However, the effect of different intrinsic and extrinsic factors that can significantly alter the outcome of these assays is still not well understood. In this work we have analyzed in 143 larvae the influence of age (5-8 days post-fertilization), time of day (8:00, 10:00, 12:00, 14:00; 16:00, 18:00, and 20:00 h), and experiment (three experiments performed at different days) on BLA and VMR results (4,004 analyses for each behavior). Results from both behaviors were adjusted to a Random-Effects linear regression model using generalized least squares (GLS), including in the model the effect of the three variables, the second-way interactions between them and the three-way interaction. The results presented in this manuscript show a specific effect of all three intrinsic factors and their interactions on both behaviors, supporting the view that the most stable time period for performing these behavioral assays is from 10:00 am to 04:00 pm, with some differences depending on age of the larva and the behavioral test.

This is a brief critique of the functions—particularly olfactory functions—specified for the “Chemosensory Protein” (CSPs) molecule family. On the basis of these proteins’ presence in the sensory antennal lymph of locusts, odor chemosensory ligand binding functions have been hypothesized. According to this hypothesis, the entire protein molecule superfamily is referred to as “CSPs”. However, new information and developments in the field of CSP molecular research, such as the expression of CSP genes in the gut, brain, fat body, wings, epidermis, and pheromone gland, as well as gene expression profiling from most early developmental stages—that is, CSP expression well in advance of the appearance of chemical sense nerve cells—strongly suggest that the protein molecule has other roles that are unrelated to chemosensing. Moreover, CSPs are found in bacterial microbial prokaryote organisms in addition to insects and all other arthropods. Thus, we examine the molecule’s name, definition, RNA editing, protein structure, lipid binding properties, DNA interaction, and evolutionary characteristics in brief before referring to this protein family as “Chemosensory Proteins”. As a means of renaming this protein family, this review article discusses the latest findings (“CSP” is attached to the tail of bigger intracellular proteins) and attempts to compel all the data. Because of its highly conserved molecular distinctive feature (four adjacent cysteines), we propose renaming “CSPs” as “4CSPs” (4 Cysteines Soluble Proteins) and use at least for abbreviations for distinctive animal proteins the common peptide 5-letter code, such as “Bommo-4CSPs”.

Buckling defect will appear on the outer surface of the deformed ring during constrained ring rolling (CRR) of aluminum alloy thin wall conical ring with inner high ribs (AATWCRIHR), if the geometrical dimension of the ribs doesn't match the wall thickness. To avoid the buckling defect, a quantitative method for characterizing the degree of the buckling defect is proposed using the area of buckling profile. Then an orthogonal experimental scheme was designed taking the width of the middle rib, thickness of wall, and height of the middle rib as design variables and defining the area of buckling profile as optimization objective. Subsequently, a quadratic polynomial response surface model was established by combining the optimization algorithm with the finite element method (FEM), and the geometrical dimension of the middle ribs of the deformed AATWCRIHR is optimized. Also the optimal parameter combination to minimize the area of buckling profile is obtained and verified using FE simulation. Results show that the AATWCRIHR after optimization doesn’t generate the buckling defect during constrained ring rolling, and it is proved that the quantitative buckling defect representation method and the optimization design method based on the response surface model and the finite element simulation results are feasible for the constrained ring rolling process of the AATWCRIHR.

In the context of carbon neutrality and carbon peaking, in order to achieve low carbon emissions and promote the efficient utilization of wind energy, hydrogen energy as an important energy carrier is proposed to mix hydrogen and natural gas to form hydrogen enriched compressed natu-ral gas (HCNG). It is also injected into the natural gas pipeline network to realize the transmission and utilization of hydrogen energy. At the same time, the participation of demand response is considered, the load peak and trough period is adjusted, and large-scale consumption of renewa-ble energy and the reduction of carbon emissions are realized. First of all, a fine model of hydro-gen production and hydrogen use equipment is established to analyze the impact of adding hy-drogen mixing on the economy and low-carbon of the system. With green certificates and demand response, the utilization rate of hydrogen energy is improved to further explore the energy utiliza-tion rate and emission reduction capacity of the system. Secondly, on the basis of modeling, the optimal scheduling strategy is proposed with the sum of energy purchase cost, equipment opera-tion cost, carbon emission cost, wind curtailment cost and green certificate income as the lowest objective function. Considering the constraints such as hydrogen blending ratio and flexible load ratio of the pipeline network, a low-carbon economic scheduling model of hydrogen mixed natu-ral gas was established. The model was linearized and solved by using MATLAB and CPLEX solver. By comparing different scenarios, the superiority of the model and the effectiveness of the strategy are verified.

Green synthesis of silver nanoparticles (AgNPs) using raw Whey has never been reported. Silver nanoparticle formation involves a reduction reaction of silver salt solution with Whey extract. Extract and metal salt concentrations, and temperature can control this reaction. In this work, incubation period, extract, AgNO3, and NaOH concentrations were used as the independent factors using central composite design under response surface methodology. The aim was to elucidate the influence these factors have on the measured UV-Vis absorption spectra fitted with a Voigt function, and to optimize the conditions for nanoparticle formation. The fitting parameters, peak wavelength (λ0), peak area (A), and Full Width at Half Maximum (FWHM), were the responses. Silver nanoparticle formation was only possible in an alkaline environment (pH 10). The peak wavelength and the FWHM are influenced mainly by extract and AgNO3 concentrations. In contrast, the peak area is influenced by a total of 33.54 % from the interaction terms of AgNO3 and extract concentrations with NaOH. Metallic AgNPs were formed for the following parameter ranges: a) Whey (0.4 – 1.6 % v/v), b) AgNO3 (0.15 – 0.6 mM), c) NaOH (10 – 50 mM), and d) Time (20 – 60 min). Silver oxide nanoparticles were also observed.

To facilitate the computation of the uniaxial compressive strength value of the cemented paste backfill under the condition of high sand-cement ratio, and to analyze the size effect of the cemented paste backfill with high sand-cement ratio under varied aspect ratios, the cemented paste backfill specimens with sand-cement ratios of 8:1-24:1 and aspect ratios of 0.5, 1, and 2 were prepared. Through response surface experiments and finite element analysis, the influence of three aspect ratios on the cemented paste backfill strength was explored, and the failure characteristics and size effect mechanisms of cemented paste backfill with various aspect ratios were analyzed. The model of strength conversion between cemented paste backfill with different aspect ratios was established. The results show that the compressive strength of the cemented paste backfill decreases with the increase of the aspect ratio under the same mass concentration and sand-cement ratio. When the aspect ratio is 0.5 and 1, the splitting failure is the main factor; when the aspect ratio is 2, the shearing failure is the main factor. The three-dimensional stress caused by the end effect of the cemented paste backfill is the main reason for the high strength when the aspect ratio is 0.5. Due to the one-dimensional stress zone generated in the middle of the cemented paste backfill with an aspect ratio of 2 in the laboratory, its strength value is closer to the actual uniaxial compressive strength value of the cemented paste backfill. The strength values of the cemented paste backfill with aspect ratios of 0.5 and 1 were higher than the actual uniaxial compressive strength values in the laboratory. The rationality of the theoretical analysis was verified by the ABAQUS analysis results. According to the experimental results, a strength conversion model between different aspect ratios is established, which can provide a reference for the design of the uniaxial compressive strength of the cemented paste backfill.

Among others, UWB-based multi anchor localization systems have been established for industrial indoor localization systems. However, multi anchor systems have high costs and installation effort. By exploiting the multipath propagation of the UWB signal, the infrastructure and thus the costs of conventional systems can be reduced. Our UWB Single Anchor Localization System (SALOS) successfully pursues this approach. The idea behind SALOS is to create a localization system with a sophisticated signal modeling. Therefore, neither measured reference like fingerprinting nor training is required for position estimation. Although SALOS has been implemented and tested successfully already in an outdoor scenario with multipath propagation, it has not yet been evaluated in indoor environment with challenging and hardly predictable multipath propagation. For this purpose, we have developed new algorithms for the existing hardware mainly a three-dimensional statistical multipath propagation model for arbitrary spatial geometries. The signal propagation between the anchor and predefined candidate points for the tag position is modeled in path length and complex-valued receive amplitudes. For position estimation, these modeled signals are combined to multiple sets and compared to UWB measurements via a similarity metric. In the end, a majority decision of multiple position estimates is performed. For evaluation, we implement SALOS in a modular fashion and install the system in a building. For a fixed grid of 20 positions, SALOS is evaluated in terms of position accuracy. The system results in correct position estimations for more than 73% of the measurements.

Social surveys are conducted to determine how annoyed people are in a certain noise situation. The results are typically presented as exposure-response curves showing the percentage of the area population that are highly annoyed as a function of the noise exposure level. It is a well-known fact that the survey results are not only dependent on the accumulated noise exposure, DNL, DENL, or similar, but also on various other factors such as maximum levels, exposure patterns, noise spectra, etc. A re-analysis of previously reported surveys shows that the results are also to a large extent dependent on survey-specific factors like wording of the annoyance questions, how the questionnaires are presented, response scales, methods of scoring highly annoyed, etc. This paper discusses and quantifies the influence of such factors and suggests ways of comparing results from surveys that have been conducted according to different protocols and different analysis methods.

The wave energy converter (WEC) technology constantly develops new designs and models. To encourage its development within the energy sector, research is required to improve current designs and create durable and effective devices. However, it is also crucial to investigate the suitability of a WEC to a site-specific sea condition as this can impact its optimal power absorption and constructability. This study evaluates and compares the efficiency of a heaving buoy with varied geometries in one of the most energetic places along the Mexican coast. A statistical analysis of the wave climate on the coast of Ensenada during the last 42 years is performed to define the conditions to which the device is subjected. The location of the WEC in shallow waters is chosen using a computational model which solves the modified mild slope equation in its elliptic shape. The heaving buoy floater is studied using three distinct geometries: a semi-sphere, a cylinder, and a proposed rounded semi-rectangle. The hydrodynamic response of the three geometries is then analysed in the frequency and time domain using ANSYS AQWA. The hydrodynamic study involves the assessment of the floating body dynamics, exerted forces, the power absorbed as well as the suitability of the proposed power take-off (PTO) system. Findings reveal that the proposed geometry absorbs the most energy, with an annual power of 135.11 MW, and that the transmission PTO design is appropriate for this type of technology.

Due to the long duration and high cost of traditional pumping tests, the response of well water level to seismic wave, earth tide, and barometric pressure provides a feasible method for determining continuous changes in aquifer hydraulic parameters. Aiming at the problem that the response phase shift of well BB water level to tidal tide M2 is greater than that of tide O1, this paper preferentially calculated the time series changes of S, Be, n and BKu based on the response mechanism of well water level to barometric pressure and earth tide and with the help of smooth moving method. Then by using the mixed flow model, the variation of transmissivity and leakage coefficient over time were simultaneously obtained, and the evolution process and characteristics of aquifer parameters near well BB caused by the Wenchuan earthquake were ultimately discussed. The calculation results are basically consistent with the previous pumping test, and have been verified and compared by using other scholars' methods. This solving process avoids the problems such as excessive dependence on initial values, multiple solutions, and unstable tide O1, which has a promoting effect on the study of the impact of seismic activity on aquifer systems.

This study investigated the inhibitory effect of Siegesbeckia orientalis ethanolic extract (SOE) on growth and metastasis of hepatic tumors in C57BL/6JNarl mice, which is the model of tumor-igenesis induced by subcutaneous injection of Hepa1-6 murine hepatoma cells on the back of mice. Feeding 25 mg SOE/kg BW daily for 14 days effectively reduced the hepatoma weight in tu-mor-bearing mice by 59.7%. SOE intervention reduced the expression of anti-apoptotic Bcl-2 gene in tumor tissue by 48.5% and down-regulated the antioxidant system, by reducing the gene ex-pression of catalase (48.0%), glutathione peroxidase (46.3%), and superoxide dismutase (32.0%). In addition, SOE intervention increased the production of ROS by 21.4%, and the gene expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 by 135.3%, 179.3% and 91.7%, respectively, indicating that SOE intervention promoted the acute inflammatory response. Results of H&E staining analysis showed that SOE had the ability to inhibit angiogenesis in tumor tissue. Fur-thermore, SOE treatment inhibited the expression of migration-related genes, such as MMP-2, MMP-7, MMP-9 and β-catenin, and the inhibition rates were 24.8%, 27.4%, 10.4% and 21.9%, respectively. These results imply that SOE had the ability to suppress tumor metastasis. On the other hand, SOE intervention decreased the serum contents of inflammatory cytokines, such as TNF-α, IL-1β and IL-6 by 27.4%, 30.4%, and 30.7%, respectively, indicating that SOE intervention has an anti-inflammatory effect on normal tissues of mice. Since SOE intervention had no signif-icant effect on liver and kidney weights, and no mice died throughout the experiment, it shows that it is safe to feed SOE under this experimental condition. Based on the above results, SOE has a great potential to be used in the treatment of hepatoma.

In order to improve the yield of the therapeutic agent N-methylsansalvamide (SA), optimization of stationary liquid fermentation conditions was carried out on an endophytic strain, Fusarium sp. R1, at flask level. Using a One-Factor-At-a-Time approach, the fermentation conditions for SA production were determined as follows: fermentation time of 13 d, 24 oC, initial pH of 6.5, seed age of 24 h, inoculum size of 5.0% (v/v), loading volume of 50% (v/v), 20.0 g/L salinity, and sucrose, tryptone, and yeast extract were found to be the best sources of carbon and nitrogen. Using response surface methodology, the optimal medium compositions consist of 22.5 g/L sucrose, 16.5 g/L tryptone, and 0.024 g/L yeast extract. Verification tests suggested that the SA yield under these optimal conditions reached up to 536.77 ± 2.67 mg/L, which was increased by almost ten times the initial yield (54.05 ± 3.45 mg/L). The findings indicate that a high SA production yield can be achieved by static culture of strain R1 under the proper fermentation conditions using a low-cost medium. This study paves the way towards industrial-scale SA production by strain R1 for new drug development.

Ralstonia solanacearum is the pathogen responsible for Ralstonia solanacearum, which is soil-borne, infests plant conduits to cause disease.They are not easy to control and are harmful.Therefore the development of a controlled-release agent responsive to the pathogen's soil temperature and moisture conditions could aid in its control. Corn kernel powder is used as a carrier for Tetramycin biopesticide, with various compounds tested for bonding.They were then made by extrusion moulding.Temperature and wetness responsive components, including Pentaerythritol Tetrastearate, Pentaerythritol Tetraoleate, Polyethylene Glycol Stearate, and Polyethylene Glycol Monooleate,are compounded and coated onto Tetramycin cores to form an intermediate shell layer. Finally, Ethyl cellulose(EC)and Hydroxypropyl methyl cellulose(HPMC) are dissolved and sprayed onto the outermost layer to complete the pellet's shell layer.After the evaluation of texture performance test,DSC analysis,TG test,temperature and humidity response performance test, as well as pellet cross-section SEM observation, field effectiveness test, etc., the preferred formulations were screened.The results showed that the preferred Core formulation:Corn kernel powder:Tetramycin aqueous:Xanthan gum mass ratio=13.5:23:2; Intermediate Shell layer:PETS: PETO: PEG400MO mass ratio=10:30:10; and Outer Shell layer: Ethyl cellulose (EC):Hydroxypropyl methyl cellulose (HPMC) mass ratio=5:1.Under soil conditions of high incidence of Ralstonia solanacearum, i.e., sustained warmth (30-35℃) and high humidity (30% moisture content), the formulated pills showed a release rate of 95.18% to 96.24% over a period of 35 days. Moreover, they showed a stepwise cyclic release process under alternating warm and humid-dry and cold conditions.In field tests on tobacco, a relative preventive efficacy of 54.74% was achieved 106 days post-transplanting. Soil bacterial community structure analysis revealed a significant decrease (2.28-2.84 times) in the abundance of Solanaceae Raelia under Tetramycin pellet treatment compared to the control. Additionally, fungal community structure showed highter consistency initially across various soil depths, with diversity differences between soil layers reestablished later (106 days), while the predominant categories of bacteria and fungi remained unchanged.In this study, we successfully developed a nucleoshell-type slow-controlled release pill embedded with Tetramycin. This pill effectively responded to temperature and humidity changes, resulting in high efficacy in disease prevention.This development holds significant promise for effectively improving drug utilization and easing application challenges, offering broad prospects for Ralstonia solanacearum prevention and control in agriculture.

Hiccups can significantly reduce the quality of life of patients and can occur as a drug side effect. Previous report using the Drug Adverse Event Database revealed sex-specific differences in the incidence of drug-induced hiccups. However, the pathogenesis of drug-induced hiccups remains unknown, and there is limited evidence on its treatment or prevention. This study examined molecular initiating events (MIEs), which are the starting point of adverse events, to investigate the drug-induced pathways of hiccups. We extracted drugs suspected to cause hiccups using FDA Adverse Event Reporting System, a large database on adverse drug reactions. Information on drugs suspected to be associated with hiccups were extracted from the overall population and sex-specific subgroups divided. In each data table, the predicted activity values of nuclear receptors (NRs) and stress response pathways (SPs) for each drug were calculated using the toxicity predictor, a machine-learning model. Univariate analysis extracted NRs and SPs associated with hiccups, and a multivariate analysis was performed to evaluate independent factors. Transforming growth factor-beta and antioxidant response element were considered an independent factor for hiccups in the male and female subgroups, respectively. This report first examined one of the mechanisms of drug-induced hiccups and identified MIEs associated with drug-induced hiccups.

In this study, we adopt a unique approach by utilizing the responses of human autonomic systems to gauge the abundance of pollutants in inhaled air. Air pollution has numerous impacts on human health on a variety of time scales. This study uses biometric observations of the human autonomic response on the second timescale to investigate how the human body autonomically responds to inhaled pollutants in microenvironments, including particulate matter. PM1 and PM2.5, carbon dioxide (CO2), nitrogen dioxide (NO2), and nitric oxide (NO) on small temporal and spatial scales. These pollutants are exemplars of the wider human exposome. We compare two experimental approaches that use a similar methodology, employing a biometric suite to capture the physiological responses of cyclists and sensors to monitor the pollutants in the air surrounding them. We employ machine learning algorithms to estimate the levels of these pollutants and decipher the body’s automatic reactions to them. We observed high precision in predicting PM1, PM2.5 and CO2 using a limited set of biometrics from participants. Although the predictions for NO2 and NO were reliable at lower concentrations, the precision varied throughout the data range. This discrepancy suggests the potential to improve our models with more comprehensive data collection or advanced machine learning techniques.

Glioblastoma, a deadly brain tumor, shows limited response to standard therapies like te-mozolomide (TMZ). Recent findings from the REGOMA trial underscore a significant survival improvement offered by regorafenib (REGO) in recurrent glioblastoma. Our study aimed to propose a 3D ex vivo drug response precision medicine approach to investigate recurrent glio-blastoma sensitivity to REGO and elucidate the underlying molecular mechanisms involved in tumor resistance or responsiveness to treatment. 3D glioblastoma organoids (GB-EXPs) obtained from 18 patients’ resected recurrent glioblastoma tumors were treated with TMZ and REGO. Drug responses were evaluated using NAD(P)H FLIM, stratifying tumors as responders (Resp) or non-responders (NR). Whole-exome sequencing was performed on 16 tissue samples, and whole-transcriptome analysis on 13 GB-EXPs treated and untreated. We found 35% (n=9) and 77% (n=20) of tumors responded to TMZ and REGO, respectively, with no instances of TMZ-Resp be-ing REGO-NR. Exome analysis revealed a unique mutational profile in REGO-Resp tumors compared to NR tumors. Transcriptome analysis identified distinct expression patterns in Resp and NR tumors, impacting Rho GTPase and NOTCH signaling, known to be involved in drug response. In conclusion, recurrent glioblastoma tumors were more responsive to REGO com-pared to TMZ treatment. Importantly, our approach enables a comprehensive longitudinal ex-ploration of the molecular changes induced by treatment, unveiling promising biomarkers in-dicative of drug response.

Conventional MRI sequences are standard methods to monitor patients with brain tumors but have significant limitations especially after irradiation. Currently, the role of FET-PET in radiotherapy of glioblastoma is emerging, starting from target definition, response assessment and in distinguishing progression from post-irradiation changes. Recently a PET RANO criteria have been published providing optimal strategy for treatment evaluation with amino-acid PET. Earlier, a PET/RANO group reported contribution of PET imaging to radiotherapy planning and monitoring in glioma patients. Also, increasing evidence have showed advantages of amino-acid PET vs. RANO MRI for prediction of overall survival. In this narrative review we aimed to summarize published data on FET-PET based treatment response assessment to radiotherapy and focused on details in protocols.

This report covers the analysis of Intrusion Detection Systems nowadays. Therefore, it focuses on the IDS classification, which includes not only a well-known explanation of Network/Host-Based IDS type but also cloud-based solutions. The paper explores ways of intrusion detection, providing examples of the best detecting tools (OSSEC, Snort or Bro (ZEEK)). Another aspect covered in this report is the juxtaposition of three systems: IDS, IPS and IRS and their response. Finally, there will be presented Intrusion Detection Systems' evasion techniques and challenges, followed by critical conclusions.

Avian Influenza viruses (AIVs) has posed a significant pandemic threat since their discovery. This review mainly focuses on the epidemiology, virology, and pathogenesis, and treatments of avian influenza viruses. We delve into the global spread, past pandemics, clinical symptoms, severity, and immune response related to AIVs. The review also discusses various control measures, including antiviral drugs, vaccines, and potential future directions in influenza treatment and prevention. Lastly, by summarizing the insights from the previous pandemic control, this review aims to direct effective strategies for managing future influenza pandemics.

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease caused by mutations to the dystrophin gene - resulting in deficiency of dystrophin protein, loss of myofiber integrity in skeletal and cardiac muscle, and eventual cell death and replacement with fibrotic tissue. Pathologic cardiac manifestations occur in nearly every DMD patient, with development of cardiomyopathy - the leading cause of death - inevitable by adulthood. As early cardiac abnormalities are difficult to detect, timely diagnosis and appropriate treatment modalities remain a challenge. There is no cure for DMD – treatment is aimed at delaying disorder progression and alleviating symptoms. A comprehensive understanding of the pathophysiological mechanisms is crucial to development of targeted treatments. While established hypotheses of underlying mechanisms include sarcolemmal weakening, upregulation of pro-inflammatory cytokines, and perturbed ion homeostasis, mitochondrial stress has recently come into focus as a potential key contributor. Several experimental compounds targeting the skeletal muscle pathology of DMD are in development, but effects of such agents on cardiac function remain unclear. Synergistic integration of small molecule- and gene-target-based drugs with metabolic, immune, or ion balance-enhancing compounds into a combinatorial therapy offers potential for treating dystrophin deficiency-induced cardiomyopathy, making it crucial to understand the underlying mechanisms driving the disorder.

Breast cancer is the most common cancer in women globally, often necessitating mastectomy and subsequent breast reconstruction. Silicone mammary implants (SMIs) play a pivotal role in breast reconstruction, yet their interaction with the host immune system and microbiome remains poorly understood. This study investigates the impact of SMI surface topography on host antimicrobial responses, wound proteome dynamics, and microbial colonization. Biological samples were col-lected from ten human patients undergoing breast reconstruction with SMIs. Mass spectrometry profiles were analyzed for acute and chronic wound proteomes, revealing a nuanced interplay between topography and antimicrobial respondseproteins. 16S rRNA sequencing assessed mi-crobiome dynamics, unveiling topography-specific variations in microbial composition. Surface topography alterations influenced wound proteome composition. Microbiome analysis revealed heightened diversity around rougher SMIs, emphasizing topography-dependent microbial inva-sion. In vitro experiments confirmed staphylococcal adhesion, growth, and biofilm formation on SMI surfaces, with increased texture correlating positively with bacterial colonization. This comprehensive investigation highlights the intricate interplay between SMI topography, wound proteome dynamics, and microbial transmission. The findings contribute to understanding host-microbe interactions on SMI surfaces, essential for optimizing clinical applications and minimizing complications in breast reconstruction.

Amidst escalating environmental concerns, short natural fiber thermoplastic (SNFT) biocomposites have emerged as sustainable materials for the eco-friendly production of mechanical components. However, their limited durability has prompted research into the experimental evaluation of the deterioration of the mechanical characteristics of SNFT biocomposites, particularly under the influence of ultraviolet rays. However, conducting tests to evaluate the mechanical properties can be time-consuming and expensive. In this study, an artificial neural network (ANN) model was employed to predict the mechanical properties (tensile strength) and the impact performance (resistance and absorbed energy) of polypropylene reinforced with 30 wt.% short flax or wood pine fibers (referred to as PP30-F or PP30-P, respectively). Eight parameters were collected from experimental studies. The ANN input parameters comprised nondestructive test results, including mass, hardness, roughness, and natural frequencies, while the output parameters were the tensile strength, the maximum impact load and absorbed energy. The model was developed using the ANN toolbox in MATLAB. The linear coefficient of correlation and mean squared error were selected as the metrics for evaluating the performance function and accuracy of the ANN model. They calculate the relationship and the average squared difference between the predicted and actual values. The data analysis conducted by the models demonstrated exceptional predictive capability, achieving an accuracy rate exceeding 96%, which was deemed satisfactory. For both the PP30-F and PP30-P biocomposites, the ANN predictions deviated from the experimental data by 3, 5, and 6% about the impact load, absorbed energy, and tensile strength, respectively.

Host immunological pathways have been proposed including TH1, TH2, TH3, TH9, TH17, TH22, TH1-like, and THαβ immune reactions. Besides TH2 and TH9 immune responses which are against multicellular parasites, host immunological pathways against viruses, intracellular micro-organisms (bacteria, protozoa, and fungi), and extracellular micro-organisms can use programmed cell death pathways to trigger immune reactions or to execute effective strategies to eliminate these pathogens. These programmed cell deaths include apoptosis, autophagic death, pyroptosis, ferroptosis, necroptosis, and NETosis. Apoptosis is related to host anti-virus eradicable THαβ immunity. Autophagic death is related to host anti-virus tolerable TH3 immunity. Pyroptosis is related to host anti-intracellular micro-organism eradicable TH1 immunity. Ferroptosis is related to host anti-intracellular micro-organism tolerable TH1-like immunity. Necroptosis is related to host anti-extracellular micro-organism eradicable TH22 immunity. NETosis is related to host anti-extracellular micro-organism tolerable TH17 immunity.

The DNA damage response (DDR) system is a complicated network of signaling pathways that detects and repairs DNA damage or induces apoptosis. Critical regulators of the DDR network include the DNA damage kinases ataxia telangiectasia mutated Rad3-related kinase (ATR) and ataxia-telangiectasia mutated (ATM). The ATR pathway coordinates processes such as replication stress response, stabilization of replication forks, cell cycle arrest, and DNA repair. ATR inhibition disrupts these functions, causing reduction of DNA repair, accumulation of DNA damage, replication fork collapse, inappropriate mitotic entry and mitotic catastrophe. Recent data have shown that the inhibition of ATR can lead to synthetic lethality in ATM-deficient malignancies. In addition, ATR inhibition plays a significant role in the activation of the immune system by increasing the tumor mutational burden and neoantigen load as well as by triggering the accumulation of cytosolic DNA and subsequently inducing the cGAS-STING pathway and the type I IFN response. Taken together, we review stimulating data showing that ATR kinase inhibition can alter the DDR network, the immune system and their interplay and therefore potentially provide a novel strategy to improve the efficacy of antitumor therapy, using ATR inhibitors as monotherapy or in combination with genotoxic drugs and/or immunomodulators.

Keywords: early childhood; education; quality; measurement; monitoring; majority world; Item Response Theory; psychometrics

Porcine epidemic diarrhea virus (PEDV) has affected the pork industry worldwide and during outbreaks the mortality of piglets has reached 100%. Lipid nanocarriers are commonly used in the development of immunostimulatory particles due to their biocompatibility and slow-release delivery properties. In this study, we developed a lipid nanoparticle (LNP) complex based on glycyrrhizinic acid (GA) and tested its efficacy as an adjuvant in mice immunized with the recombinant N-terminal domain (NTD) of porcine epidemic diarrhea virus (PEDV) spike (S) protein (rNTD-S). The dispersion stability analysis (Z-potential–27.6 mV) confirmed the size and charge stability of the LNP-GA, demonstrating that the particles were homogeneously dispersed and strongly anionic, that favors nanoparticles binding with the rNTD-S protein, which showed a slightly positive charge (2.11 mV) by in silico analysis. TEM image of LNP-GA revealed nanostructures with a spherical-bilayer lipid vesicle (⁓100 nm). The immunogenicity of the LNP-GA-rNTD-S complex induced an efficient humoral response 14 days after the first immunization (P < 0.05) as well as an influence on the cellular immune response by decreasing serum TNF-α and IL-1β concentrations, which was associated with an anti-inflammatory effect.

The recent outbreak of Nipah virus in India in 2023 had affected the Kozhikode district in Kerala, with a total of 6 confirmed cases and 2 deaths. The source of the outbreak was traced to fruit bats that contaminated date palm sap, a common drink in the region. The outbreak was contained by rapid detection, isolation, and contact tracing of the cases, as well as public health education and social distancing measures. It also highlighted the need for improved surveillance, diagnostics, and therapeutics for Nipah virus. This letter highlights the latest insights gained from the epidemiological, clinical, and laboratory investigations of the outbreak.

This study proposes a methodology for identifying time intervals in which time-of-use (ToU) energy tariffs can be set. This is achieved by analyzing the variability in electric power demand and esti-mating the potential for demand flexibility. The proposed methodology is as follows: first, data preprocessing is performed, focusing on the organization and cleaning of individual consumption records. Subsequently, the data are processed and classified by using consumption variability analysis and clustering techniques. Then, representative clusters are selected and time intervals are analyzed to identify periods of high electric power consumption variability. This methodology was tested with real data from smart meters in the Colombian electrical system, in which time intervals with potential for settinh ToU tariffs were ultimately identified. This work promotes the implementation of demand response strategies that enhance sustainability and facilitate the transition to a more resilient energy landscape both nationally and internationally. The findings are expected to contribute to the formulation of tariff schemes that encourage con-scious changes in electric energy consumption patterns.

Provenance trials provide a valuable opportunity to evaluate the impact of extreme events on growth and wood properties. In this study, we have evaluated 81 Norway spruce provenances, tested in three provenance trials established in the Romanian Carpathians in 1972. The response to drought of the Norway spruce provenances – resistance, recovery, resilience, and relative resilience, has been examined, as well as the relationship between climate and growth, and the correlations between wood traits, the coordinates of origin and drought resilience indices. In each provenance trial, there were significant differences between provenances and years regarding wood widths and latewood percentage (LWP). Regarding the drought extreme events, the years when it occurred in all three provenance trials were 2000 and 2003. Significant differences between provenances for at least one drought resilience index have been found in all provenance trials, for the year 2000. By using subperiods of 25 years, changes in the relationship between climate and growth have been observed. Several provenances with high radial growth and good resistance and/or recovery have been identified. Provenances that performed better in common garden experiments could be used in assisted migration even beyond the current natural range.

N6-methyladenosine (M6A) modification is the most abundant internal chemical modification on RNA molecules in eukaryotes and can affect mRNA metabolism and regulate RNA transcription, nuclear export, splicing, degradation, translation, ets, and has a significant impact on various aspects of physiology or pathobiology. Radiotherapy is the most common measure of tumor treatment, variety of cellular intrinsic mechanisms affect the responses of cells to ionizing radiation (IR) and effectiveness of cancer radiotherapy. In this review, we summarize and discuss the recent advances about the roles and mechanisms of RNA M6A methylation in cellular responses to radiation-induced DNA damage response, and outcomes of cancer radiotherapy. Insights into the RNA M6A methylation in radiation biology may facilitate the improvement of therapeutic strategies for cancer radiotherapy as well as radioprotection on normal tissues.

Background: To describe the effectiveness and safety of COVID-19 vaccine in a series of patients with rheumatoid arthritis (RA). Methods: Retrospective single-center study of RA patients, fulfilling the ACR 1987 or ACR/EULAR 2010 classification criteria, that received first COVID-19 vaccine between December 2020 and October 2021, had post-vaccination serology and subsequent follow-up of at least 6 months in a university hospital. Vaccine effectiveness was evaluated by the serological response and the incidence of post-vaccine COVID-19, and safety by the incidence of adverse events (AE) and RA flares. Adjusted logistic and linear multivariate regression analyses were carried out with Stata® to identify factors associated with vaccine response. Results: We included 118 patients with RA (87.2% women, age 65.4±11.6 years, evolution 12.0±9.6 years). 95.8% received complete vaccination schedule. Most patients (88.1%) developed adequate humoral immunogenicity, and the degree of serological response was significantly related to younger age and previous COVID-19 infection. After vaccination, 18.6% presented mild SARS-CoV-2 infection. Vaccine AE (19.5%) were mostly mild and inversely associated with age (OR 0.95). RA flares were anecdotal (1.7%) and inversely related to age (OR 0.95). Conclusion: Our results suggest that COVID-19 vaccine induces adequate humoral immunogenicity, with an acceptable safety profile in RA patients.

A Systemic Lupus Erythematosus (SLE) is a prototypical systemic autoimmune disease characterized by a complex interplay of genetic, molecular, and cellular factors. It is considered a multifactorial disorder influenced by genetic susceptibility, environmental triggers, and dysregulated immune responses. Understanding the molecular and cellular mechanisms driving SLE pathogenesis has been instrumental in developing targeted therapies to manage the disease and improve patient outcomes. In this essay, we will delve into the intricate molecular and cellular processes underlying SLE and examine the key lessons learned from human therapies.

This research aimed to assess the influence of red dragon fruit peels ratio (RDF-PR) from two species, Hylocereus hybridum (HH) and Hylocereus undatus (HU), and particle size (PS) on quality parameters of red dragon fruit peel powder (RDF-PP), and its further application in emulsified alpaca-based sausages as partial substitutes of pork-back fat. A three-level full factorial design (nine treatments) was employed to evaluate the effect of: (i) RDF-PR [HH(0%):HU(100%), HH(50%):HU(50%), and HH(100%):HU(0%)] and (ii) PS (499–297, 296–177, and <177 µm) on the dependent variables: L*, a*, b*, C, h°, water-holding capacity, oil-holding capacity, swelling capacity, pectin yield, degree of esterification (analysed through FT-IR), and crude fibre content. The data analysed through a response surface methodology showed that treatment one (T1) is the best with the optimised conditions at 100% HU RDF-PR and PS of <177 µm. The statistical validation of T1 exhibited the highest water holding capacity (32.1 g H2O/g peel), oil holding capacity (2.20 g oil/g peel), and pectin yield (27.1%). A completely randomised design (four formulations) was then used to assess the effect of partial replacement of pork-back fat by T1 in emulsified alpaca-based sausages. The results revealed that 65.7% of pork-back fat content was successfully replaced as compared with a control formulation.

This paper introduces the AltumView Sentinare smart activity sensor for senior care and patient monitoring. The sensor uses an AI chip and deep learning algorithms to monitor the activity of people, collect activity statistics, and notify caregivers when emergencies such as falls are detected. To protect privacy, only skeleton (stick figure) animations are transmitted instead of videos. The sensor is highly affordable, accessible, and versatile. It was a CES 2021 Innovation Award Honoree, and has been selected by Amazon as one of only three fall detection devices integrated into its Alexa Together urgent response service, and has received very positive reviews from Amazon customers. It has also been used in different senior care settings in about ten different countries. The paper presents the main features of the system, the evidences and lessons learned from its practical applications, and future directions.

Chemo-resistance is a substantial challenge in the realm of cancer treatment that requires exploring new therapeutic approaches for effective mitigation. Achieving this goal requires examination of the molecular mechanisms involved in both tumor growth and therapeutic interventions. The potential of NRF2 (Nuclear factor E2-related factor 2) in addressing resistance to chemotherapy across diverse cancer types highlights its value as a promising therapeutic approach based on cancer characteristics. Manipulating the NRF2 signaling pathway has a dual impact, offering promise for both preventing and treating cancer, as well as inhibiting carcinogenesis. The influence of the NRF2/KEAP1 pathway on the progression of tumor formation and resistance to drugs has been well-documented. The interplay between the NRF2 signaling pathway and processes such as endoplasmic reticulum (ER) stress, unfolded protein response (UPR), and autophagy plays a crucial protective role. A deeper understanding of NRF2's role in the modulating these pathways is necessary to develop novel approaches for improving chemotherapeutic efficacy. This article discusses the significance of the NRF2-KEAP1 pathway in preventing/promoting cancer and resistance mechanisms to various chemotherapeutic agents, with a focus on the complementary effects of antioxidants via NRF2-mediated signaling pathways. This study aims to provide a molecular basis for targeting NRF2 via inhibitors/activators as promising therapeutic strategies to overcome chemo-resistance.

In today's digital landscape, cybersecurity has become a priority, with attacks becoming increasingly sophisticated. Traditional security approaches are no longer enough, requiring a more dynamic and advanced response. In this context, integrating Artificial Intelligence (AI) and Machine Learning (ML) appears key to addressing this growing threat. However, despite their high effectiveness, there is a developed problem: the integration of various data sources and technologies for comprehensive protection. This article presents an in-depth review of integrating Artificial Intelligence and Machine Learning in cybersecurity, focusing particularly on Open Extended Detection and Response (Open XDR) technology. The literature review in this article was meticulously conducted with specific criteria in mind. It focused on sourcing peer-reviewed journals, authoritative cybersecurity publications, and recent conferences that primarily concentrate on the advancements in AI and ML within the cybersecurity domain, particularly from 2018 to 2023. This timeframe was chosen to ensure the inclusion of the most current and relevant developments in Open XDR technology, Intrusion Detection Systems, Endpoint Detection and Response, and Security Information and Event Management systems. Additionally, the review gave special attention to studies and reports highlighting practical implementations and real-world applications of these technologies, thereby ensuring a comprehensive understanding of their impact and effectiveness in enhancing cybersecurity resilience. The methodology used is a detailed literature review, examining how various cybersecurity components interact and function. These components include Intrusion Detection Systems (IDS), which monitor networks for malicious activities; Endpoint Detection and Response (EDR), which focuses on detecting and investigating security incidents on endpoints; and Security Information and Event Management (SIEM), systems that provide real-time analysis of security alerts. The review also considers the role of Active Directory, a directory service for Windows domain networks, and the process of log forwarding, where log files are transmitted to a central server for analysis, in the context of AI and ML. The paper delves into the development of AI and ML, underscoring their roles in cybersecurity for advanced data processing, pattern recognition, and predicting threats. It explores both supervised (where the model is trained on labeled data) and unsupervised learning (where the model learns from unlabeled data) in ML, and how these techniques bolster cybersecurity measures. The article highlights the significance of Open XDR as a critical innovation that integrates data from multiple sources for comprehensive security analysis. Further, the review discusses how the integration of AI and ML into various cybersecurity tools, such as IDS, EDR, and SIEM, augments capabilities in threat detection and response. It addresses the challenges and opportunities that AI and ML present in the cybersecurity domain, focusing on ethical issues, data privacy concerns, and the necessity for ongoing professional development in this rapidly advancing field. The paper concludes by affirming the effectiveness of merging AI and ML with these cybersecurity tools within the Open XDR framework.

Alginate, a biopolymer promising in food, biomedical, pharmaceutical, and electronic materials industries, is characterized by its biodegradability, biocompatibility, low toxicity, and gel-forming properties. It is most abundantly found in brown algae. However, conventional dilute acid and alkali extraction methods face limitations in commercialization due to their long processing time, low throughput, and high solvent requirements. In this study, a microwave-assisted extraction (MAE) process for sodium alginate was designed to improve extraction efficiency. Solid/liquid ratio, extraction temperature, and extraction solvent concentration were major variables affecting sodium alginate extraction from Undaria pinnatifida(sea mustard). They were then statistically optimized using response surface methodology. Under optimal conditions (13.27 g/L, 91.86 ℃, 2.51 %(w/v), and 15 min), the yield was 38.41 %, which was 93.43 % of the theoretical content of sodium alginate in Undaria pinnatifida. Our work has confirmed the productivity and industrial feasibility of efficient extraction of sodium alginate from marine biomass, and we hope that it will serve as an encouraging case for the application of biopolymers as one of the desirable options for alternative petrochemicals to construct a sustainable society.

Background: Pediatric Rapid Response Teams (RRTs) are expected to significantly lower pediatric mortality in healthcare settings. This study evaluates RRTs' effectiveness in decreasing cardiac arrests and unexpected Pediatric Intensive Care Unit (PICU) admissions. Methods: A quasi-experimental study (2014-2017) at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, involved 3,261 pediatric inpatients, split into pre-intervention (1,604) and post-intervention (1,657) groups. The intervention entailed pediatric specialists collaboratively managing acute decompensations following set protocols. Results: RRT was activated 471 times, primarily for respiratory distress (29.30%), sepsis (22.30%), clinical anxiety (13.80%), and hematological abnormalities (6.7%). Family concerns triggered 0.1% of activations. Post-RRT implementation, unplanned PICU admissions significantly reduced (RR = 0.552, 95% CI 0.485-0.628, P < 0.0001), and non-ICU cardiac arrests were eliminated (RR = 0). Patient care improvement was notable, with a -9.61 coefficient for PICU admissions (95% CI: -12.65 to -6.57, P < 0.001) and a -1.641 coefficient for non-ICU cardiac arrests (95% CI: -2.22 to -1.06, P < 0.001). Sensitivity analysis showed mixed results for PICU admissions, while zero-inflation Poisson analysis confirmed a reduction in non-ICU arrests. Conclusions: The deployment of pediatric RRTs is associated with fewer unexpected PICU admissions and non-ICU cardiopulmonary arrests, indicating improved PICU management. Further research using robust scientific methods is necessary to conclusively determine RRTs' clinical benefits.

Studies report variable effects of sex hormones on serious diseases. Severe disease and mortality rates in COVID-19 show marked gender differences that may be related to sex hormones. Sex hormones regulate the expression of the viral receptors ACE2 and TMPRSS2, which affect the extent of viral infection and consequently cause variable outcomes. In addition, sex hormones have complex regulatory mechanisms that affect the immune response to viruses. These hormones also affect metabolism through obesity, and severe disease can result from complications such as thrombosis. This review presents the latest research on the regulatory functions of hormones in viral receptors, immune responses, complications as well as their role in COVID-19 progression. It also discusses the therapeutical possibilities of these hormones by reviewing the recent findings of clinical and assay studies.

PURPOSE: Our research interrogates Professor Peter Doherty’s warning to Australians in April 2020 that ‘COVID-19 is just as lethal as the Spanish flu’. METHODS: We identified the epicentres of both pandemics, namely metropolitan Sydney in 1919 and metropolitan Melbourne in 2020. Using original sources, we compared the lethality of COVID-19 in these two cities. Lethality was measured by the number and rate of hospitalisations and deaths per 100,000 of population. Using these two measures, we diagnosed the waves of infection, their severity at various points in time and the cumulative impact of the viruses by the end of our in-depth study period, i.e. 30 September in 1919 and 2020. RESULTS: Spanish Flu in 1919 was more than 30 times more lethal than COVID-19 in 2020. The hospital admission and death rates of COVID-19 in Melbourne in 2020 constituted a small fraction of the devastation wrought by the Spanish Flu in Sydney in 1919. The patterns and lethality of the pandemic waves were also strikingly different. DISCUSSION AND CONCLUSION: Both pandemics broke out with the arrival of unknown pathogens against which vaccines and antivirals did not exist. Professor Doherty’s warning was perhaps taken seriously and that partly explains the findings of this study. Containing infection in 1919 and 2020 threw the burden on nonpharmaceutical interventions (NPIs) such as ‘protective sequestration’ (quarantine), contact tracing, lockdowns and masks. We discuss the effectiveness of these. Despite the failures of genomic analysis and the weaknesses of the contact tracing system due to mismanagement, it was persistent and detailed contact tracing that provided the best explanation for why NPIs in 2020 were more effective than in 1919 and therefore contributed to the lower lethality of the COVID-19 pandemic in its first year.

This is a brief critique of the functions—particularly olfactory functions—specified for the “Chemosensory Protein” (CSPs) molecule family. On the basis of these proteins’ presence in the sensory antennal lymph of locusts, odor chemosensory ligand binding functions have been hypothesized. According to this hypothesis, the entire protein molecule superfamily is referred to as “CSPs”. However, new information and developments in the field of CSP molecular research, such as the expression of CSP genes in the gut, brain, fat body, epidermis, and pheromone gland, as well as gene expression profiling from most early developmental stages—that is, CSP expression well in advance of the appearance of chemical sense nerve cells—strongly suggest that the protein molecule has other roles that are unrelated to chemosensing. Moreover, CSPs are found in bacterial microbial prokaryote organisms in addition to insects. Thus, we examine the molecule’s name, definition, RNA editing, protein structure, lipid binding properties, DNA interaction, and evolutionary characteristics in brief before referring to this protein family as “Chemosensory Proteins”. This article tries to compel and discuss the most recent information as a way to rename this protein family. Because of its highly conserved molecular distinctive feature (four adjacent cysteines), we propose renaming “CSPs” as “4CSPs” (4 Cysteines Soluble Proteins).

A wide variety of bioactive peptides have been identified in the central nervous system and several peripheral tissues in the ascidian Ciona intestinalis type A (Ciona robusta). However, hemocyte endocrine peptides have yet to be explored. Here, we report a novel 14-amino acid peptide, CiEMa, that is predominant in the granular hemocytes and unilocular refractile granulocytes of Ciona. RNA-seq and qRT-PCR revealed the high CiEma expression in the adult pharynx and stomach. Immunohistochemistry further revealed the highly concentrated CiEMa in the hemolymph of the pharynx and epithelial cells of the stomach, suggesting biological roles in the immune response. Notably, bacterial lipopolysaccharide stimulation of isolated hemocytes for 1-4 hours resulted in increased CiEMa secretion. Furthermore, CiEMa-stimulated pharynx exhibited mRNA upregulation of the growth factor (Fgf3/7/10/22), vanadium binding proteins (CiVanabin1 and CiVanabin3), and forkhead and homeobox transcription factors (Foxl2, Hox3, and Dbx), but not antimicrobial peptides (CrPap-a and CrMam-a) or immune-related genes (Tgfbtun3, Tnfa, and Il17-2). Collectively, these results suggest that CiEMa plays roles in signal transduction involving tissue development or repair in the immune response, rather than in the direct regulation of immune-response genes. The present study identified a novel Ciona hemocyte peptide, CiEMa, providing insights into the molecular and functional diversity of the immune response in chordates.

The pandemic SARS-CoV-2 continues to evolve to give rise to variants of concern that can escape vaccine-induced immunity. As such, more effective vaccines are urgently needed. In this study, we evaluated virus-like particle (VLP) as a vaccine platform for SAS-CoV-2. The spike, envelope, and membrane proteins of the SARS-CoV-2 Wuhan strain were expressed by a single recombinant baculovirus BacMam and assembled into VLPs in cell culture. The morphology and size of the SARS-CoV-2 VLP as shown by transmission electron microscopy was found to be similar to the authentic SARS-CoV-2 virus particle. In a mouse trial, two intramuscular immunizations of the VLP BacMam with no adjuvant elicited spike-specific binding antibodies in both sera and bronchoalveolar lavage fluids. Importantly, BacMam VLP -vaccinated mouse sera showed neutralization activity against SARS-CoV-2 spike pseudotyped lentivirus. Our results indicated that the SARS-CoV-2 VLP BacMam stimulated spike-specific immune responses with neutralization activity.

ADHD, one of the most prevalent diseases during childhood, we still do not know its precisely origin, although oxidative/nitrosative stress and the hypothalamic-pituitary-adrenal axis are suggested contributors. Methylphenidate, among others, is the main drug used in these patients, but its effects on relevant markers and structures remain unclear. This study, involving 59 patients diagnosed with ADHD according to DSM-5 criteria, aimed to assess changes in cortisol levels (using cortisol awakening response, CAR) and oxidative/nitrosative status with the treatment. Blood samples before and 3 months after treatment with methylphenidate were used to measure oxidative and inflammatory markers, and the endogenous antioxidant activity, while saliva samples tracked cortisol awakening response (CAR). The results show a treatment-related improvement in the redox profile, with the reduction of advanced oxidation protein products (AOPP), lipid peroxidation (LPO), and nitrite plus nitrate (NOx) levels, and the increase of the enzymatic activities of glutathione reductase (GRd) and catalase (CAT). Moreover, the area under the curve (AUC) of CAR increased significantly, indicating increased reactivity of the HPA axis. These result support by the first time the involvement of the endogenous antioxidant system in the pathophysiology of ADHD.

Abstract: To explore the interrelationship between groundwater microbial communities and hydrochemical characteristics in Mancheng district, Baoding city, samples from karst groundwater and porous groundwater were collected respectively. The hydrochemical analysis and 16s RNA gene V4-V5 region sequencing method were used to detail the water environmental characteristics and microbial community distribution pattern in the study area. The hydrochemical results reveal significant differences in major ion contents and other hydrochemical indices between karst water and porous water. Microbial community analysis demonstrates that Proteobacteria, Actinobacteria, and Firmicutes are the dominant taxa in both types of water bodies, but their proportions vary significantly in different water bodies. The difference in microbial communities between karst water and porous water reflects the influence of environmental factors such as ion concentration and pH on microbial distribution. Redundancy analysis (RDA) indicates significant associations between microbial community composition and environmental factors in both types of groundwater environments. Studying the distribution pattern of microbial communities and the connection with environmental factors in two types of groundwater provides important basis for interpreting the functional roles of microbes in groundwater ecosystems.

The retrieval of tree height percentiles with satellite lidar waveforms over the mountainous ar-eas is greatly challenged due to slanted and rugged topographic relief of underlying ground. A novel algorithm is proposed to extract the height percentiles based on the target response waveform (TRW) that is resolved by using a Richardson–Lucy deconvolution algorithm with an adaptive iterative time. The height metrics of the energy percentiles of 25%, 50%, 75% and 95% for the cumulative TRW distribution are determined by their vertical distances relative to the ground elevation in this study. To validate the proposed algorithm, we select the received waveforms of the Global Ecosystem Dynamics Investigation (GEDI) lidar over the Pahvant Mountains of central Utah, USA. The results reveal that the resolved TRWs resemble closely to the actual target response waveforms from the coincident airborne lidar data, with the mean values of the coefficient of correlation, total bias and root mean square error (RMSE) taking val-ue of 0.92, 0.0813 and 0.0016. In addition, the accuracies of the derived height percentiles from the proposed algorithm have been greatly improved compared with the conventional Gaussian de-composition method and the slope-adaptive waveform metrics method. The RMSE values de-crease by the mean values of 1.96 m and 2.72 m, respectively. It demonstrates that the proposed algorithm has good potential in the extraction of forest structure parameter over rugged moun-tainous areas.

Replication stress (RS) is a characteristic state of cancer cells as they tend to exchange precision of replication for fast proliferation and increased genomic instability. To overcome the consequences of improper replication control malignant cells frequently inactivate parts of their DNA damage response (DDR) pathways (the ATM-CHK2-p53 pathway), while relying on other pathways which help to maintain replication fork stability (ATR-CHK1). This creates a dependency on the remaining DDR pathways, vulnerability to further destabilization of replication and synthetic lethality of DDR inhibitors with common oncogenic alterations such as mutations of TP53, RB1, ATM, amplifications of MYC, CCNE1 and others. The response to RS is normally limited by coordination of cell cycle, transcription and replication. Inhibition of WEE1 and PKMYT1 kinases, which prevent unscheduled mitosis entry, leads to fragility of under-replicated sites. Recent evi-dence also shows that inhibition of Cyclin-dependent kinases (CDKs), such as CDK4/6, CDK2, CDK8/19 and CDK12/13 can contribute to RS through disruption of DNA repair and replication control. Here, we review the main causes of RS in cancers as well as main therapeutic targets – ATR, CHK1, PARP and their inhibitors.

Background and introduction: Lung cancer is a prevalent and deadly disease globally. Non-small cell lung cancer (NSCLC) is the most common subtype, comprising 85% of cases; Case report: A 65-year-old ex-smoker man presented to our facility with nocturnal cough. Various investigations revealed that he had metastatic NSCLC, for which he underwent chemotherapy with cisplatin and gemcitabine, followed by immunotherapy with Nivolumab. He achieved a complete response to the therapy and has remained free from recurrence for over 7 years since the initial diagnosis; Discussion and Conclusion: The treatment of metastatic NSCLC remains a significant therapeutic challenge, but the implementation of new therapeutic techniques has expanded the possibilities of achieving complete and durable eradication of the disease.

Ulcerative colitis is a chronic immune-mediated disease of unclear etiology, affecting people of different ages and significantly reducing the quality of life. Modern methods of therapy are mainly represented by anti-inflammatory drugs and are not aimed at a specific pathogenetic factor. In this study, we investigated the effect of transplantation of sterile stool filtrate from healthy donors on the induction of anti-inflammatory immune mechanisms. It was shown that performing such a procedure in patients with ulcerative colitis caused the appearance of T helper cells in the blood, which reacted to the content of sterile stool filtrates in an antigen-specific manner and produced IL10. At the same time, cells of the same patients before therapy in response to the addition of sterile stool filtrates were less reactive and predominantly produced IL4, indicating its pro-inflammatory skewing. The obtained data demonstrated the effect of an anti-inflammatory shift in the T-helper response after transplantation of sterile stool filtrate, which increased and persisted for at least three months after the procedure.

Chert rock is a by-product of sand quarrying (about 40% in the geological section). All attempts to use ordinary technologies for aggregate production from chert have been economically unsuccessful, resulting in significant chert "waste" accumulation covering vast quarry areas. This paper presents the study results of the effect of microwave irradiation on the mechanical properties of chert gravel, which is mineralogically relatively homogenous and consists of fine quartz grains. The results show that an increase in irradiation time decreases the strength of chert gravel (by a factor of 4-6 for the 2.5 min of irradiation), while the quenching changes the fractional content of the samples after the crushing test, decreasing the Gravel-to-Sand ratio.

: Alluvial soils naturally possess abundant soil nutrients. Nevertheless, excessive nitrogen addition and inappropriate use of nitrogen fertilizers lead to conditions where soil nutrients become immo-bilized, ultimately reducing productivity. This study investigates the potential of natural nano-material zeolite which is important land resources to improve nutrient utilization efficiency and mitigate the harmful effects of excessive fertilizer application. Specifically, the research ex-plores the incorporation of clinoptilolite zeolite and processed sewage sludge blends, alongside reduced recommended nitrogen fertilizer doses, to evaluate their impact on soil quality and plant growth. A greenhouse experiment was conducted (three-year study), comprising eight treatments with varying proportions of zeolite and sewage sludge. The efficacy of these treatments in en-hancing soil carbon pools, nutrient indices, and plant growth responses was assessed. Results in-dicate that a combination of 50% recommended fertilizer dose, 4-6% zeolite, and 5-10% sewage sludge significantly improved multiple aspects of plant growth, including leaves, tillers, culms, and panicles, leading to increased straw and grain yields. The addition of 6% zeolite in conjunc-tion with sewage sludge positively influenced plant tillering capacity. Certain treatment combina-tions exhibited a greater impact on plant height at different growth stages. For example, the treatment with 75% recommended fertilizer dose, 4% zeolite, and 5% sewage sludge significantly affected plant height at 40 and 55 days after treatment. Additionally, the combination of 50% recommended fertilizer dose, 6% zeolite, and 10% sewage sludge promoted plant height, carbon levels, and various yield parameters in later stages. Principal component analysis effectively dis-tinguished treatments incorporating zeolite and sewage sludge based on plant responses. The combination of 6% zeolite and 10% sewage sludge, along with a 50% recommended fertilizer dose, positively influenced soil carbon fractions, nutrient levels, and the growth response of rice plants.

Insect meal as a protein source has been considered a sustainable way to feed animals. H. illucens and T. molitor larvae meal are considered high protein sources for poultry, also presenting considerable amounts of fatty acids, vitamins, and minerals. However, other potential components in insect meal and insect oil have been more studied nowadays. Chitin, lauric acid, and antimicrobial peptides can present antimicrobial and prebiotic functions, indicating that low inclusions of insect meal can beneficially affect broilers` health and immune responses. This systematic review was developed to study the impact of insect products on health parameters of broilers, and a metanalysis was conducted to evaluate the effects on performance. A database was obtained based on a selection of manuscripts from 2016 to January 2023, following the mentioned parameters. There were positive effects of both H. illucens and T. molitor meal or oil products on poultry health status, especially in microbiota population, immune responses, and antimicrobial properties. The average daily gain was greater in broilers fed T. molitor meal compared to H. illucens meal (p = 0.002). The results suggest that low levels of insect meal were suitable for broilers, without result in negative effects on performance, while the insect oil can totally replace soybean oil without negative impacts.

The initiation of micro-cracks in concrete is primarily due to its brittleness, which causes severe impacts on the overall behavior of the concrete. However, incorporating fibers in concrete could significantly improve its mechanical properties. The current study demonstrates the influence of two types of fibers on the mechanical properties of concrete. Nylon Fiber Threads (NFT) and Nylon Fiber Strands (NFS) at a fiber content of 2.5 kg/m³ were incorporated in the concrete mix. Concrete with a compressive strength of 30 MPa and a water-cement ratio of 0.4 was produced to investigate the fresh and mechanical properties of conventional and nylon-fiber reinforced concrete (NFRC). The concrete prims and cylinders were tested for compressive, splitting, and flexural strength using ASTM standards (ASTM C-39, C-496, and D-790, respectively). It was found that NFT-reinforced samples achieved higher mechanical properties of concrete (13.05%) compared to NFS-reinforced samples. Test results showed that incorporation of nylon fibers (NF) in concrete decreased the compressive strength of cylindrical and cubical specimens by 0–10% and 5–15%, respectively. However, it increased the splitting tensile and flexural strengths by 0-15%, and 5-15% respectively. Furthermore, the incorporation of NF in concrete significantly improved the ductility and delayed the crack initiation in concrete.

Under high-frequency operating conditions, the high-speed solenoid valve (HSV) experiences energy loss and heat generation, which significantly impact its operational lifetime. Reducing the energy loss of HSV without compromising its opening response characteristics poses a significant challenge. To address this issue, a finite element simulation model of HSV coupled with a current feedback model is constructed to investigate the synergistic effects of dynamic response and energy loss. Predictive models for the opening response time, HSV driving energy, and Joule energy using Back Propagation neural network (BPNN) are established. Furthermore, a multi-objective optimization study on the current driving strategy using Non-dominated Sorting Genetic Algorithm II (NSGA-II) is conducted. After optimization, although there was a 6.24% increase in the opening response time, both HSV drive energy and Joule energy were significantly reduced by 15.67% and 22.49%, respectively. The proposed multi-objective optimization method for HSV driving strategy holds great significance in improving its working durability.

Abstract: The centrepiece of this analytical review is the metabolism of hydroxyapatite in its natural, bone, and synthetic forms, where the mitochondria-mediated mechanism may serve as the leading mechanism. The possibility that osteoblast mitochondria play an important role in the initial stages of bone mineralisation is discussed. Furthermore, the paper highlights the key role of mitochondria in the metabolism of synthetic hydroxyapatite.Differences between the results of in vivo and in vitro studies using synthetic hydroxyapatite of different morphologies are also detailed. It is noted that long-term infiltration with immune cells and in vivo studies are necessary to adequately evaluate hydroxyapatite as a bone-plastic material.Particular attention is given to the interaction of hydroxyapatite with immune cells and its ability to affect the ribosomes and mitochondria of cells. Due to its mechanical properties, scalability and potential use for the treatment of extensive bone defects of tumor origin, hydroxyapatite is a promising material.This study also highlights the importance of further development of in vitro research methods in the context of their biomimeticity. Overall, this work offers a theoretical direction for future studies of hydroxyapatite as a bone grafting material and emphasises the value of in vivo studies.

Micro/Nano Robot is an intelligent and efficient microrobot that can perform specific tasks under the influence of external stimuli. Depending on the application scenarios, the microrobot can adaptively transform into appropriate functional forms under different external stimuli, thus perfectly matching the needs. To date, microbots have been widely used in targeted therapy, drug delivery, tissue engineering, environmental remediation, and other fields. Although the applications of microrobots are promising, there are only a few reviews that can focus on the preparation methods and driving mechanisms. Therefore, it is necessary to outline the current status of the development of these microrobots in order to provide some new insights for the further development of the field. Therefore, this paper reviews the research progress of microrobots in terms of preparation methods, stimulus response mechanisms and applications, and highlights the applicability of different preparation methods and stimulus types. Finally, the current challenges faced by microrobots are highlighted and possible solutions are proposed to facilitate the practical application of microrobots.

SARS-CoV-2 infection can lead to life-threatening clinical manifestations. Patients with cardiovascular disease (CVD) are at higher risk for severe courses of COVID-19. However, strategies to predict the course of SARS-CoV-2 infection in CVD patients at the time of hospital admission are still missing. Here, we investigated whether this prediction is achievable by prospectively analysing the blood immunophenotype of 94 participants, including 20 uninfected and 37 acutely SARS-CoV-2-infected CVD patients and 37 healthy donors, using a 36-colour spectral flow cytometry panel. Unsupervised data analysis revealed little differences between healthy donors and CVD patients, whereas the distribution of the cell populations changed dramatically in SARS-CoV-2-infected CVD patients. The latter had more mature NK cells, activated monocyte subsets, central memory CD4+ T cells, and plasmablasts but fewer dendritic cells, CD16+ monocytes, innate lymphoid cells, and CD8+ T cell subsets. Moreover, we identified an immune signature characterised by mucosal-associated invariant T (MAIT) cells, intermediate effector CD8+ T cells, and natural killer T (NKT) cells that is predictive for CVD patients with a severe course of COVID-19. Thus, intensified immunophenotype analyses can help identify patients at risk of severe COVID-19 at hospital admission, improving clinical outcomes through specific treatment.

In recent years, the emergence of the concept of immunometabolism has shed light on the pivotal role that cellular metabolism plays in both the activation of immune cells and the development of immune programs. The antiviral response, a widely distributed defense mechanism used by infected cells, serves to not only control infections but also to attenuates their deleterious effects. The exploration of the role of metabolism in orchestrating the antiviral response represents a burgeoning area of research, especially considering the escalating incidence of viral outbreaks coupled with the increasing prevalence of metabolic diseases. Here, we present a review of current knowledge regarding immunometabolism and the antiviral response during viral infections. Initially, we delve into the concept of immunometabolism by examining its application in the field of cancer—a domain that has long spearheaded inquiries into this fascinating intersection of disciplines. Subsequently, we explore examples of immune cells whose activation is intricately regulated by metabolic processes. Progressing with a systematic and cellular approach, our aim is to unravel the potential role of metabolism in antiviral defense, placing significant emphasis on the innate and canonical interferon response.

The ADP-ribosylation factor 6 (Arf6), as the only member of the Arf family III protein, has been extensively studied for its diverse biological functions in animals. Previously, the Arf6 protein in Magnaporthe oryzae was found to be crucial for endocytosis and polarity establishment during asexual development. However, its role remains unclear in Sclerotinia sclerotiorum. Here, we identified and characterized SsArf6 in S. sclerotiorum using a reverse genetic approach. Deletion of SsArf6 impaired hyphal growth and development, and produced more branches. Interestingly, knockout of SsArf6 enhanced the tolerance of S. sclerotiorum to oxidative stress but the sensitivity to osmotic stress, and increased melanin accumulation, indicative of different roles of SsArf6 in various stress responses. Moreover, the appressorium formation was severely impaired, and fungal virulence to host plants was significantly reduced. Overall, our findings demonstrate the essential role of SsArf6 in hyphal development, stress responses, appressorium formation, and fungal virulence to host plants.

Cathinone is a natural stimulant found in Catha edulis and commonly used in new psychoactive substances. The objective of this study was to examine the disposition kinetics and metabolic profile of cathinone and its metabolite cathine through a single oral dose of cathinone administration in rats. Cathine and cathinone concentrations were identified and quantified using ion trap liquid chromatography (LC-IT/MS), while the metabolic profile was determined using the quadrupole time of flight UPLC-QTOF/MS method in the serum, brain, lung, liver, kidney, and heart over a period of 0, 0.5, 2.5, 6, 12, 24, 48, and 72 hours. The findings revealed a dynamic interplay between the pharmacokinetics of cathinone and its impact on organ-specific biomarkers. The distribution of cathinone and cathine was determined in serum, brain, heart, lung, kidney, and liver. The highest concentration of cathinone was found in the kidney at 1438.6 ug/L. It gradually decreased to 1.97 within 48 hours and disappeared after 72 hours. Within half an hour, cathinone levels in the lungs, liver, and heart were found to be 859, 798.9, and 385.8 ug/L, respectively. However, within 2.5 hours, these levels decreased to 608.1, 429.3, and 309.1 ug/L and kept decreasing until they became undetectable after 24 hours. The concentration of cathinone in the rat brain reduces quickly, dropping to undetectable levels within six hours, with levels decreasing from 712.7 ug/L after just 30 minutes. In the brain and serum, cathine reached its highest levels at 2.5 hours, while in other organs, it peaked at 0.5 hours. This indicates that the conversion of cathinone to cathine is slower in the brain and serum. The study found that cathinone's pharmacokinetics have a significant impact on organ-specific biomarkers. After administering the cathinone, there was a sharp change in biomarker levels, particularly in the liver and brain, during the initial hours. It is essential to investigate the correlation between the changes in biomarkers found in the brain and the levels of cathinone and cathine. The results have significant implications for drug development, pharmacovigilance, and clinical practices involving cathinone. In conclusion, this comprehensive analysis of cathinone's impact on organ-specific biomarkers provides a basis for informed decision-making in medical practices and further research into the cathinone's pharmacological properties.

This study compared cortical responses to speech in preschoolers with typical language development (TLD) and Developmental Language Disorder (DLD), and in adults. We investigated whether top-down language effects modulate speech perception in an adult-like manner. We compared cortical mismatch responses (MMR) during passive perception of speech differing in linguistic complexity in three groups of participants: preschoolers with TLD (n=11), preschoolers with DLD (n=16) and adults (n=20). We also measured children’s phonological skills and investigated if they are associated with the cortical responses. MMR results indicated top-down language effects in adults, with enhanced cortical discrimination of lexical stimuli but not of non-words. In preschoolers, the TLD and DLD groups did not differ on the MMR measures and no top-down effects were detected. Moreover, we found no association between MMRs and phonological awareness skills, even though the DLD group’s phonological skills were significantly lower. Our findings suggest that top-down language modulations on speech discrimination may not be present during early childhood, and that children with DLD may not exhibit cortical speech perception deficits. The lack of association between phonological and MMR measures indicates that further research is needed to understand the link between language skills and cortical activity in preschoolers.

This review compiles research findings pertaining to Nuclear Distribution C (NudC) genes and their involvement in various cellular processes, including nuclear migration, intracellular transport, nuclear positioning and cell cycle progression. Structural and functional similarities of NudC pro-teins across diverse organisms highlight their evolutionary conserved nature and pivotal roles in upholding cellular functions. Special attention is given to the growing importance of NudC family members in plants, elucidating their contributions to plant growth, development and responses to environmental challenges. Within this framework, we spotlight two Arabidopsis NudC genes, BOB1 and NMig1, for their indispensable roles in embryo and postembryonic development, and involvement in stress responses and tolerance mechanisms. Furthermore, we accentuate the chaperone activity of plant NudC family members, a crucial function in mitigating the adverse effects of stress and bolstering plant resilience in the face of environmental challenges. These insights underscore the promising potential of NudC members as valuable targets for enhancing crop performance, particularly when directed towards optimizing plant morphology and fortifying en-vironmental resistance to enhance overall crop productivity.

Ambient vibration energy is widely being harnessed as a source of electrical energy to drive low-power devices. The vibration energy harvester (VEH) of interest employs an electromagnetic transduction mechanism, whereby ambient mechanical vibration is converted to electrical energy. The limitations affecting the performance of VEHs, with an electromagnetic transduction structure, include its operational bandwidth as well as the enclosure-size constraint. In this study, an analysis and design of a nonlinear VEH system is conducted, using the Output Frequency Response Function (OFRF) representations of the actual system model. However, the OFRF representations are determined from the Generalised Associated Linear Equation (GALE) decompositions of the system of interest. The effect of both nonlinear damping and stiffness characteristics, to respectively extend the average power and operational bandwidth of the VEH device, is demonstrated.

Cut chrysanthemum, renowned as a highly favored floral choice globally, experiences a significant decline in production due to the practice of continuous cropping. The adverse physiological effects on cut chrysanthemums have been observed as a result of the degradation of soil physical and chemical properties, coupled with the proliferation of pathogens. It is noteworthy that the 'Guangyu' cultivar in Xinxiang, Henan province, China, has been specifically impacted by these effects. This study effectively identified and validated the precise pathogen accountable for wilt disease initially. Subsequently, an analysis was conducted to examine the invasion pattern of the pathogen and the physiological response of the chrysanthemum. Finally, PacBio platform was employed to investigate the dynamic alterations in the microbial community within the soil rhizosphere, comparing the effects of seven years of monocropping with the first year. The findings indicated that Fusarium solani was the primary causative agent responsible for wilt disease, as it possessed the ability to invade and establish colonies in plant roots, leading to alterations in various physiological parameters of the plants. Furthermore, the practice of continuous cropping had been observed to significantly disturb the microbial community composition, potentially acting as an additional influential factor in the advancement of wilt.

To address the problems of wind abandonment in the regional integrated energy system (RIES), which occurs when cogeneration unit operates in a heat-determined electricity operation mode, and the low efficiency of the energy storage system in a low-temperature environment, we propose an optimal scheduling method for RIES based on fine energy storage and wind power dissipation. First, a fine energy storage model is established on the source side and the conditional value at risk(CvaR) theory is used to quantify the uncertainty of wind power; then a combined heat and power demand response mechanism is introduced on the load side to reduce the peak-to-valley difference between heat and power loads, and to promote the consumption of wind power. Finally, with the objective of minimizing the total cost of RIES optimal dispatch, the example is solved on the MATLAB platform. The simulation results show that compared with the traditional model, the proposed model is not only more adaptable to the low-temperature environment, but also can effectively improve the system economy and wind power consumption.

In order to investigate both the physiological and molecular mechanisms underlying the impacts of organic selenium and nano-selenium on drought stress of Pak Choi (Brassica chinensis var. pekinensis. cv. ‘Suzhouqing’), we measured photosynthetic pigment, antioxidant, nutritional quality, and performed transcriptome sequencing of leaves using RNA-seq technology. Under drought conditions, the beneficial effects of organic selenium and nano-selenium on weight and quality of ‘Suzhouqing’ were primarily manifested in the following aspects. Firstly, there was an enhancement in photosynthetic capacity through upregulation of light-trapping pigment proteins: Lhca1, Lhca2, Lhca3, Lhca4, Lhcb1, Lhcb2, Lhcb3, Lhcb4 and Lhcb5. Secondly, effective regulation of reactive oxygen species homeostasis was achieved by activating the antioxidant system via up-regulation of glutathione S-transferase. Thirdly, water homeostasis was maintained through glutathione oxidase activity. Lastly, increased expression levels of ABC transporter, adenylate kinase and cysteine desulphurase contributed to elevated total selenium content. In addition, we screened hub core genes related to the above key metabolic pathways through Weighted Gene Co-expression Network Analysis. Since the results were consistent with the up-regulated genes identified in the Kyoto Encyclopedia of Genes and Genomes pathway of differentially expressed genes by transcriptome sequencing analysis, this confirms the accuracy and reliability of the transcriptome sequencing data.

Long-term health consequences are influenced by circumstances that occur during pregnancy. The confluence of the maternal and fetal circulations occurs at the placenta, which is the first or-gan to develop. Placental pathology can provide an accurate diagnosis of inflammation inside the amniotic sac. The pathological alterations of preterm placentas provide evidence for the causes of numerous perinatal pathologies, including spontaneous preterm births. This retrospec-tive study aimed to re-examine placentas regarded as normal by the Obstetrics and Gynecology Department in our institution so that grading and staging of any evident inflammatory response could be evaluated and associated with baby gender. Eighty-four full-term placentas were col-lected after delivery. Placentas that were considered normal and were not sent to the histo-pathology department were taken. Morphological examination of fresh placenta was conducted. Full thicknesses of placenta samples were taken from central and marginal regions of placental disc. Fetal and maternal inflammatory responses syndrome were assessed. Villitis of unknown etiology (VUE) and chronic deciduitis also were evaluated in the placenta. Immunohistochemis-try (IHC) was also performed to evaluate patterns of inflammation in the placenta using an-ti-CD8 and anti-CD68 antibodies. The correlation between the silent pathologies and clinical complications or involvement of developing fetal inflammatory response syndrome was meas-ured. In this study, seventeen (20%) maternal inflammatory samples and ten (12%) fetal inflam-matory samples showed inflammatory responses. The frequency of chronic deciduitis and villi-tis of unknown etiology was more remarkable among Saudi pregnant women than the previ-ously reported findings in the literature of placental pathology. The prevalence of fetal and ma-ternal inflammatory response was greater in the placentas of mothers of males than in placentas of female mothers. Grading placental inflammation usually predict the degree of maternal an-ti-fetal cellular rejection. Fetal inflammatory response syndrome usually goes unnoticed in Sau-di Arabia. There are differences in the inflammatory response in the placenta based on the sex of the newborn. Increasing the number of placental samples that must be sent for microscopic in-spection may be preferable due to their significance in identifying the causes of chronic disor-ders.

Rectal cancer presents significant diagnostic and therapeutic challenges, with neoadjuvant therapy playing a pivotal role in improving resectability and patient outcomes. MRI serves as a critical tool in assessing treatment response. However, differentiating viable tumor tissue from therapy-induced changes on MRI remains a complex task. In this comprehensive review, we explore treatment options for rectal cancer based on resectability status, focusing on the role of MRI in guiding therapeutic decisions. We delve into the nuances of MRI-based evaluation of treatment response following neoadjuvant therapy, with particular attention to emerging techniques like radiomics. Drawing from current literature and insights, we provide essential recommendations for post-neoadjuvant therapy management in rectal cancer, all within the context of MRI-based findings.

Introduction: Digitalis use in patients with severe heart failure is controversial. We assessed the effects of digitalis therapy on mortality in a large, observational study in recipients of cardiac resynchronization therapy (CRT). Methods: Consecutive patients receiving a CRT-defibrillator in three European tertiary referral centers were enrolled and followed for a median of 28 months. Digitalis use was assessed at the time of CRT implantation. Multivariate Cox-regression model and propensity score matching was used to determine all-cause mortality as primary endpoint. CRT-response (defined as improvement of ≥1 NYHA class), echocardiographic improvement (defined as improvement of LVEF of ≥ 5%), and ICD shocks were assessed as secondary endpoints. Results: The study comprised 552 CRT recipients with standard indications, including 219 patients (40%) treated with digitalis. Compared to patients without digitalis, they had more often atrial fibrillation, poorer LVEF and higher NYHA class (all p ≤ 0.002). Crude analysis of all-cause mortality demonstrated a similar relative risk of death for patients with and without digitalis (HR=1.14; 95% CI 0.88-1.5; p=0.40). After adjustment for independent predictors of mortality, digitalis therapy did not alter the risk for death (adjusted HR=1.04; 95% CI 0.75-1.45; p=0.82). Also, in comparison to 286 propensity score matched patients, mortality was not affected by digitalis intake (propensity adjusted HR=1.11; 95% CI 0.72-1.70; p=0.64). CRT response was predominant in digitalis non-users concerning both improvement of HF symptoms and LVEF (NYHA p<0.01; LVEF p<0.01) while patients on digitalis had more often ventricular tachyarrhythmias requiring ICD shock (p=0.01). Conclusions: Digitalis therapy had no effect on mortality but did negatively affect CRT response and susceptibility to ventricular arrhythmias requiring ICD shock treatment.

A capacity to reflect on experience and learn through it (reflective and reflexive practice) is deemed an essential part of ethical practice and research. Challenging traditional research approaches this arts-based, inter-disciplinary, Ph.D. project explores artistic practice as a research methodology, and how learning through experiences of ‘making’ things may enhance and amplify our understanding of the more affective aspects of human situations and experience. Grounded in the author’s artistic practice and learning through experiences of ‘making’, the author assembles and adapts frames from psychoanalysis, art (psycho)therapy, and the arts with/through which to observe and document their experience of an organisational situation. Describing the development of their method in three phases, analysis takes place through returning to revisit and rework artistic material produced, and engaging in conversation with the emergent material and others in response. Results take the form of artworks and artistic projects, including documentation of process. Emergent threads draw attention to the speculative, entangled, and affective nature of the research process, the reflexivity generated through moving and handling material, and the reflexive work of undergoing, foregrounding an ethics of responsibility, attention, and care for/of the body. As a space for imaginative encounter and performative enactment, and a site for reflexivity through which one may be pressed to notice and feel more acutely, the author argues that the research value resides in the capacity of this method to embrace complex relationalities, and engage our affective, ethical sensibilities in ways that may not emerge through more traditional approaches to reflective/reflexive practice(s). This has implications for both art therapy practice and research, amplifying the learning opportunities afforded by moving, modifying, and assembling things differently, the embodied ‘work’ of art as a method of enquiry, the cultural sensitivity of documentary fragments captured in/through various media and voices, and the value of collaborative endeavours where meaning is co-constructed in conversation.