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.

Cotton is a potential and excellent candidate to balance both agricultural production and reme-diation of mercury-contained soil, as its main production fiber hardly involve into food chains. However, there is known rarely about the tolerance and response to Hg environments in cotton. In this study, The biochemical and physiological damages, in response to mercury (Hg), were investigated in upland cotton seedlings. The results on cottonseeds germination, indicated the germination rate were suppressed by high Hg levels, as the decrease of percentage was more than 10% at 1000 µM Hg. Shoots and roots’ growth were significantly inhibited above 10 µM Hg. The inhibitor rates (IR) in fresh weight were close between shoots and roots, whereas that in dry weight the root growth was more obviously influenced by Hg. In comparison of organs, the growth inhibition ranked as root > leaf > stem. The declining of translocation factor (TF) op-posed the Hg level even as low to 0.05 at 50 µM Hg. The assimilation of cotton plants was af-fected negatively by Hg toxicity, as evidenced from the performances on photosynthesis pig-ments (chlorophyll a and b) and gas exchange (Intercellular CO2 concentration (Ci), CO2 assimila-tion rate (Pn) and stomatal conductance (Gs)). Sick phenotypes on leaf surface included small white zone, shrinking and necrosis. Membrane lipid peroxidation and leakage were Hg dose-dependent as indicated by malondialdehyde (MDA) content and relative conductivity (RC) values in leaves and roots. More than 10 µM Hg damaged antioxidant enzyme system in both leaves and roots (P<0.05). Concludingly, 10 µM Hg post negative consequences to upland cotton plants in growth, physiology and biochemistry, whereas high phytotoxicity and damage ap-peared at more than 50 µM Hg concentration.

The comparison of group means in item response models constitutes an important issue in empirical research. The present article discusses an extension of Haebara linking by proposing a flexible class of robust linking functions for comparisons of many groups. These robust linking functions are particularly suited to item response data that are generated under partial invariance. In a simulation study, it is shown that the newly proposed robust Haebara linking approach outperforms existing approaches of Haebara linking. In an empirical application using PISA data, it is illustrated that country means can be sensitive to the choice of linking functions.

Early stable deep molecular response (DMR) of nilotinib is associated with goal of treatment-free remission (TFR) for patients with chronic-phase chronic myeloid leukemia (CML-CP). It is significant to early distinguish patients who can obtain DMR and fit for TFR. We performed a multicenter study to explore early cumulative MR4.5 rate by 18 months with nilotinib in patients with newly diagnosed CML-CP (ND-CML-CP) in China. From 29 institutes, 106 ND-CML-CP patients received nilotinib (300mg BID). The cumulative MR4.5 rate of nilotinib by 18 months was 69.8% (74/106). The cumulative MMR and MR4.0 rates of nilotinib by 18 months were 94.3% (100/106) and 84.9% (90/106), respectively. Patients with ultra-early molecular response (u-EMR) at 6 weeks were not significantly different to obtain DMR or MMR by 24 months compared to those without u-EMR (P=0.7584, P=0.9543, respectively). Our study demonstrated that treatment with nilotinib in patients with ND-CML-CP contributed to obtain high early MR4.5.

Anticipating future successional forest trends in the face of ongoing global change is an essential conservation target. Mountain forests are especially sensitive to environmental shifts, and their past responses to climatic and anthropogenic (external) drivers may provide a basis for improving predictions of future developments. This paper uses independent high-resolution palynological and paleoclimatic reconstructions to statistically analyze the long-term effects of external drivers on regional forest succession in the central Iberian Pyrenees during the last 500 years. The dominant taxa of these forests (Quercus, Betula, Pinus) showed significant relationships with summer temperature, summer drought and autumn precipitation. Immediate and delayed (by two or more decades) responses of these trees to climatic drivers were identified. Regional succession showed a closed path, starting at the end points around the attraction domain of pine-dominated forests. This trajectory was determined by a trend toward anthropogenic forest clearing (16th to 18th centuries) and a reverse trend of natural forest recovery (18th to 20th centuries). Forest clearing was due to burning, facilitated by drought, and was followed by the expansion of cropping and grazing lands. Forest recovery was fostered by reduced human pressure and rising temperatures. The statistical approach used in this work has unraveled ecological relationships that remained unnoticed in previous works and would be important for predicting future successional trends under changing climates. The reported response lags of individual taxa to climatic drivers may complicate the establishment of reliable ecological relationships and should be addressed in future studies.

It has been more than three decades since the discovery of multifunctional factors, Non-POU Domain-Containing Octamer-Binding Protein, NonO and Splicing Factor, Proline-and Glutamine-Rich, SFPQ. Some of their functions, including their participations in transcriptional and posttranscriptional regulation as well as their contribution to paraspeckle subnuclear body organization have been well-documented. In this review, we focus on the roles of NonO and SFPQ in cell cycle with particular attention to their participation in nonhomologous end joining (NHEJ) and homologous recombination (HR) of DNA damage responses induced by irradiation. In these contexts, absence or malfunction of either or both lead to genome instability and ultimately to apoptosis, cellular senescence, and tumor development. This review also will shed light on NonO and SFPQ function in DNA/RNA/protein binding and their association with Ku heterodimer of the NHEJ pathway required for repair of DNA double-strand breaks (DSBs).

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.

The molecular mechanisms underlying heat stress tolerance in animals to high temperatures remain unclear. This experiment was performed with Sprague-Dawley rats housed at 22 ℃ (control group; CT), and 42 ℃ for 30 min (H30), 60 min (H60), and 120 min (H120). Transcriptomic analysis using RNA-Sequencing (RNA-Seq) from blood (CT and H120), liver (CT, H30, H60, and H120), and adrenal glands (CT, H30, H60, and H120) was performed. The differentially expressed mRNA isoforms (DEIs) were identified and annotated by the CLC Genomics Workbench. Biological process and metabolic pathway analyses were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. A total of 225, 5,764, and 4,988 DEIs in the blood, liver, and adrenal glands were observed. Furthermore, the number of novel differentially expressed transcript lengths with annotated genes and the novel differentially expressed transcript with non-annotated genes were 136 and 8 in blood, 3,549 and 120 in the liver, as well as 3,078 and 220 in adrenal glands, respectively. A total of 35 genes were involved in the heat stress response, out of which Dnaja1, LOC680121, Chordc1, AABR07011951.1, Hsp90aa1, Hspa1b, Cdkn1a, Hmox1, Bag3 and Dnaja4 were commonly identified in the liver and adrenal glands, suggesting that these genes may regulate heat stress response through interactions between liver and adrenal glands. The results suggest that the identified mRNA isoforms could be considered as potential candidates for selecting mammals to improve thermotolerance.

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.

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.

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.

This paper presents a novel approach for individual design perception modeling using the YUKI-trained Fuzzy Inference System. The study focuses on understanding how individuals perceive design based on personality traits, particularly openness to experience. The proposed YUKI algorithm optimizes the FCM clustering algorithm, enhancing its ability to handle uncertain and imprecise data. The YUKI-trained FIS generates several Sugeno-type FIS models to predict design perception, to minimize the Root Mean Squared Error between the model prediction and the actual design perception of participants. The results demonstrate that the YUKI-trained FIS offers more accurate predictions compared to the traditional FCM-trained FIS, and the RMSE values for individual design perceptions fall within a satisfactory range of 0.84 to 1.32. The YUKI-trained FIS proves effective in clustering individuals based on their level of openness, providing insights into how personality traits influence design perception.

Studies evaluating candidate tick-derived proteins as anti-tick vaccines in natural hosts have been limited due to high costs. To overcome this problem, animal models are used in immunization tests. The aim of this article was to review the use of rabbits as an experimental model for the evaluation of tick-derived proteins as vaccines. A total of 57 tick proteins have been tested for their immunogenic potential using rabbit as model for vaccination. The most commonly used rabbit breeds were New Zealand (73.8%), Japanese white (19%), Californians (4.8%) and Flemish lop-eared rabbit (2.4%). Anti-tick vaccines efficacy resulted in up to 99.9%. Haemaphysalis longicornis (17.9%) and Ornithodoros moubata (12.8%) were the most common tick model in vaccination trials. Experiments in rabbits have revealed that some proteins (CoAQP, OeAQP, OeAQP1, Bm86, GST-Hl, 64TRP, serpins and voraxin) can induce immune responses against various tick species. In addition, in some cases it was possible to determine that the vaccine efficacy in rabbits was similar to experiments performed in natural hosts (e.g. Bm86, IrFER2, RmFER2, serpins and serine protease inhibitor). In conclusion, results have shown that prior to performing anti-tick vaccination trials using natural hosts, rabbits can be used as suitable experimental models for these studies

Antimicrobial peptides (AMPs) can directly kill Gram-positive bacteria, Gram-negative bacteria, mycobacteria, fungi, enveloped viruses and parasites. At sublethal concentrations some AMPs and also conventional antibiotics can stimulate bacteria response to increase their resilience, also called the hormetic response. That can include stimulation of growth, mobility, and biofilm production. Here, we have discovered AMPs that stimulate the growth of certain mycobacteria. Peptide 14 for example showed growth stimulating effect on M. tuberculosis, M. bovis, M. avium subsp. paratuberculosis (MAP), M. marinum, M. avium-intracellulare, M. celatum and M. abscessus. The effect was more pronounced at low bacterial inocula. The peptides induce a faster transition from the lag phase to the log phase and keep the bacteria longer in the log phase before entering the stationary phase compared to non treated control. In some cases, an increase in the division rate was observed. An initial screen using MAP and a collection of 75 peptides revealed 13 peptides with a hormetic effect. For M. tuberculosis a collection of 25 artificial peptides were screened and 9 were found to reduce the time to positivity (TTP), improving growth. A screen of 43 naturally occurring peptides, 11 fragments of naturally occurring peptides and 5 designed peptides, all taken from the APD3, identified a further 44 peptides that also lowered TTP by at least 5%. Lasioglossin LL-III (Bee) and Ranacyclin E (Frog) were the most active natural peptides, the human cathelicidin LL37 fragment GF-17 and a porcine cathelicidin protegrin-1 fragment was the most active fragment of naturally occurring peptides. Peptide 14 showed growth-stimulating activity between 50 ng/ml and 10 µg/ml whereas the stability-optimised peptide 14D had a narrow activity range of 0.1 - 1 µg/ml. Peptides identified in this study are now part of novel products improving the diagnosis of mycobacteria in humans and animals.

Electricity generation from renewable energy sources is emerging as a result of global carbon emission reduction policies. However, most renewable energy sources are non-dispatchable and cannot be adjusted to meet the fluctuating electricity demands of society. A flexible operation process has been proposed as an effective solution to compensate for the unstable nature of renewable energy sources. Thermal load fluctuations during flexible operation may cause creep-fatigue damage to the high-temperature components of thermal power plants, as they are designed with a focus on creep damage under a constant power level. This study investigated the residual life of high-temperature components, such as a superheater tube and a reheater header, to failure under flexible operation conditions using finite element analysis and empirical models. First, we determine an analytical solution for the straightened superheater tube under thermal conditions and compare it with the numerical solution to verify the numerical models. Through the verified finite element model, the creep-fatigue life of the reheater header is estimated by considering flexible operation factors and employing the Coffin-Manson and Larson-Miller models. Although fatigue damage increases with decreasing minimum load and ramp rate, we confirmed that creep damage significantly affects the residual life during flexible operation. In addition, a surrogate model was proposed to evaluate the residual life of the reheater as a function of the flexible operation factors using the machine learning methodology, based on the results of finite element methods. It can be used to predict its residual life without performing complex thermal-structure analysis and relying on empirical models for fatigue and creep life. We expect our findings to contribute to the efficient operation of thermal power plants by optimizing the flexible operation factors.

Minute Virus of Mice (MVM) is an autonomous parvovirus of the Parvovirus family that replicates in mouse cells and transformed human cells. MVM genomes localize to cellular sites of DNA damage with the help of their essential non-structural phosphoprotein NS1 to establish viral replication centers. MVM replication induces a cellular DNA damage response that is mediated by signaling through the ATM kinase pathway, while inhibiting induction of the ATR kinase signaling pathway. However, the cellular signals regulating virus localization to cellular DNA damage response sites has remained unknown. Using chemical inhibitors to DNA damage response proteins, we have discovered that NS1 locallization to cellular DDR sites is independent of ATM or DNA-PK signaling, but is dependent on ATR signaling. Pulsing cells with an ATR inhibitor after S-phase entry leads to attenuated MVM replication. These observations suggest that the initial localization of MVM to cellular DDR sites depends on ATR signaling before it is inactivated by vigorous virus replication.

When exposed to a viral infection, the attacked cells promptly set up defence mechanisms. Part of antiviral responses, the innate immune interferon pathway and associated interferon stimulated genes are notably allowing the production of proteins bearing an antiviral activity. Numerous viruses are able to evade the interferon response, highlighting the importance of controlling this pathway to ensure their efficient replication. Several viruses are also known to manipulate the metabolism of infected cells to optimize the availability of amino acids, nucleotides and lipids. They then benefit from a reprogramming of the metabolism that favours glycolysis instead of mitochondrial respiration. Given the increasingly discussed crosstalk between metabolism and innate immunity, we wondered whether this switch from glycolysis to mitochondrial respiration would be beneficial or deleterious for an efficient antiviral response. We used a cell based model of metabolic reprogramming. Interestingly, we showed that increased mitochondrial respiration was associated with an enhanced interferon response following poly:IC stimulation. This suggests that during viral infection, the metabolic reprogramming towards glycolysis is also part of the virus' strategies to inhibit the antiviral response.

Background: In long-term care facilities, there are many residents who do not have the ability to seek shelter by themselves in the case of an emergency. Thus, it is extremely important that the staff of nursing homes are equipped with correct disaster prevention concepts, emergency survival responses, and hazard mitigation measures. Purpose: Discuss the intervention effectiveness of different fire prevention and emergency response trainings at nursing homes and the relationship and predictivity of awareness to self-efficacy. Method: Recruit staff from two nursing homes through purposive sampling, using a two-team pre-and post-test design to collect results from 41 individuals in the experiment group and 40 individuals in the control group. The research tool is the “Nursing Home Fire Prevention and Emergency Response Awareness and Self-Efficacy Scale,” to compare the effectiveness of advanced and general fire safety trainings. Result: After receiving improved advanced fire safety training, the total score and the result of the experiment group on fire prevention and emergency response awareness and self-efficacy had both performed better than the control group who received general fire safety training (p < .001); fire prevention and emergency response awareness has significant and positive correlation with self-efficacy (r=.601, p < .001), and awareness is a significant predictor variable to self-efficacy (p < .001). Conclusion/Practical Application: This study finds that the key to improving learning effectiveness includes adding fire science concept chapter when creating fire safety training material in order to strengthen basic awareness; fire safety training should comprehensively introduce all related duty responsibilities of staff fire defense formation, in turn enabling mutual responsive support for the needs of the site; also, to become familiarized with the knowledge requires appropriate frequency of training and enhancing the staff’s awareness to fire prevention and emergency response, which is the most important key of learning effectiveness.

Based on the textured controllable interface effect, the dynamic performances of the textured and ordinary pilot valve are analyzed experimentally, and the influence of the textured controllable interface on the response of pilot valve is studied. Results show that when Pin is small, the textured surface shortens the reciprocating time of valve core, increasing the flow rate, and speeds up the piston stroke of oil cylinder. The valve core actions much more stable and sensitivity. Meanwhile, combined with the theoretical calculation, the operation mechanism of texturing the pilot valve is analyzed. It is concluded that the stress of textured valve core sealing surface is greater than that of ordinary one, and the pressure difference gradually decreases with the increase of Pin, and the flow difference is basically the same as the force on the sealing surface. This indicates that the textured surface improves lubrication characteristics, reduces the friction between components. The textured valve makes the velocity changes gently, and enhances the responsiveness and stability of the valve. Those related results provide a new idea for enhancing the response design of the pilot valve.

Here we draw insights from the latest serendipitous findings made on the opposing roles of a validated drug-target protein Keap1. We weigh up how natural reactive electrophiles and electrophilic small-molecule drugs in clinical use directly impinge on seemingly conflicting, yet both Keap1-electrophile-modification-dependent, cell-survival- vs. cell-death-promoting behaviors. In the process, we convey how understanding reactive chemical-signal regulation at a single-protein-specific level is an enabling necessity in deconstructing otherwise intricate reactive-small-molecule-responsive cellular pathways. We hope this opinion piece further spurs the broader interests of basic and pharmaceutical research communities toward better understanding of molecular mechanisms underpinning reactive small-molecule-regulated signaling subsystems.

Featured Application: Bio-electronic devices take advantages of some specific duties of biological matter. The specific ability of some proteins to use sunlight is considered for the realization of photo-electronic devices . Here the focus is on the role of the pH, whose variations seem to affect the protein conductance

Emergency Management has not developed in a cohesive or comprehensive manner. Differing terms are used to name identical concepts. A standard comprehensive doctrine for the important development of emergency management is needed. In this paper I explain a doctrinal framework for emergency management. The paper states a clear identification of the five dimensions, and each of their components, necessary to the informed practice of Emergency Management. Although emergencies vary in cause and severity, the process of Emergency Management necessary for optimal handling of these emergencies varies little. The “All Hazards Approach” to emergency management establishes and reinforces commonality in processes, procedures, planning templates and organizational structure. The three types of agencies associated with emergency management activities are discussed, including the subject matter agency, coordinating agency, and supporting agency. The four critical functions of emergency management are detailed, and include mitigation, preparedness, response, and recovery, often all carried out concurrently. The ten activities, and seven resources of emergency management are highlighted. There are many ways to represent the integration of these five dimensions, to ensure completeness, while ensuring clarity; the two most common are described. When experts in Emergency Management follow the doctrine, they can coordinate all those involved to be sure that all aspects of any hazard are considered, and that all organizations/agencies, functions, activities, and resources of Emergency Management are coordinated and optimally active. Following this process is the only way to ensure the best outcomes from any emergency.

Staphylococcus aureus mastitis remains a major challenge for dairy farming. Here, 24 mice were immunized and divided into four groups: G1: control; G2: Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) DNA vaccine; G3: F0F1 ATP synthase subunit α (SAS), succinyl-diaminopimelate (SDD), and cysteinyl-tRNA synthetase (CTS) recombinant proteins; and G4: SAS+SDD+CTS plus GM-CSF DNA vaccine. The lymphocyte subpopulations and the intracellular interleukin-17A (IL-17A) and interferon-γ production in the draining lymph node cells were immunophenotyped by flow cytometry. The immunophenotyping and lymphocyte proliferation was determined in spleen cells cultured with and without S. aureus stimulus. Immunization with S. aureus recombinant proteins generated memory cells in draining lymph nodes. Immunization with the three recombinant proteins plus GM-CSF DNA led to an increase in the percentage of IL-17A+ cells among overall CD44+ (memory), T CD4+, CD4+ T CD44+ CD27-, γδ TCR, γδ TCR+ CD44+ CD27+ and TCRVγ4+ cells. Vaccination with S. aureus recombinant proteins associated with GM-CSF DNA vaccine downregulates TH2 immunity. Immunization with the three recombinant proteins plus the GM-CSF DNA led to a proliferation of overall memory T, CD4+ and CD4+ TEM cells upon S. aureus stimulus. This approach fostered type 3 immunity, suggesting the development of a protective immune response against S. aureus.

Background: Molecular nuclear medicine, due to hybrid imaging camera systems and new tailored radiopharmaceuticals, has been gained a clinical relevance for diagnosis, therapy and follow-up of solid tumors. Despite numerous literature studies, many new radiopharmaceuticals for imaging tumor microenvironment, have not yet been used, routinely, in oncological clinical practice to monitor treatments. This is due to poor comparability of published studies, due to poor design and methodology, heterogeneous population and prevalence of preclinical studies. Methods: In this systematic review, we described the use of radiopharmaceuticals for evaluation of tumor treatment response by targeting microenvironment. We reviewed studies published from 2000 to 2020, to provide an updated status of research in this topic. Results: There is a growing role of radiopharmaceuticals and nuclear medicine imaging techniques in the management of cancer treatments, especially immunotherapy. Of the 24 papers included, 16 were preclinical studies. Conclusions: New radiopharmaceuticals could have an excellent impact in molecular imaging, leading to better diagnosis and important clinical information for therapy decision making and follow-up of cancer treatments in different solid tumors. Recently developed radiopharmaceuticals may provide great advantage to improve personalized medicine for patients with a great cost-effectiveness ratio.

Seroprevalence studies suggest that the number of PCR-confirmed COVID-19 cases is significantly smaller than the true number of infections. I study logintidual seroprevalence data from 7 sites across the US, from early April 2020 to June 27. I show that not only COVID-19 seroprevalence does not seem to increase over time, there is no clear association between the number of cases reported during a period and the change in seroprevalence during the same time. I conclude that as they are, seroprevalence studies can only be used in the qualitative sense and distinguish between populations with no COVID-19 exposure, to those populations where the virus had already started spreading.

SARS-CoV-2 is a novel coronavirus that is the causative agent of Coronavirus infectious disease 2019 (COVD-19). As of the 17^th April 2020, it has infected 2 114 269 people resulting in 145 144 deaths. The timing, magnitude and longevity of humoral immunity is not yet understood for SARS-CoV-2. Nevertheless, understanding this is urgently required to inform the likely future dynamics of the pandemic, to guide strategies to allow relaxation of social distancing measures and to understand how to deploy limiting vaccine doses when they become available to achieve maximum impact. SARS-CoV-2 is the seventh human coronavirus to be described. Four human coronaviruses circulate seasonally and cause common colds. Two other coronaviruses, SARS and MERS, have crossed from animal sources into humans but have not become endemic. Here we review what is known about the human humoral immune response to epidemic SARS CoV and MERS CoV and to the seasonal, endemic coronaviruses. Then we summarize recent, mostly non-peer reviewed studies into SARS-CoV-2 serology and reinfection in humans and non-human primates and summarize current pressing research needs.

Flaviviruses replicate in membranous factories associated with the endoplasmic reticulum (ER). The replication rate generates a high polyprotein integration that can contribute to ER stress. Therefore, the host cell can develop an Unfolded Protein Response (UPR) to this protein accumulation which will stimulate appropriate cellular responses in the infectious context (Adaptation, autophagy or cell death). These different stress responses can help to overcome the virus and usually support antiviral strategies initiated by infected cells. In the present study, we investigated the capacity of ZIKA virus (ZIKV) to induce ER stress in epithelial A549 cells with a special focus on the causal factors behind it. We observed that the cells respond to ZIKV infection by implementing an UPR through activation of the IRE1 and PERK pathway but surprisingly without activation of the ATF6 branch. When we examined the effects of modulating the ER stress response we found that UPR inducers significantly inhibit ZIKV replication. Interestingly, our findings provide evidence that ZIKV can altered the UPR in order to escape to the host cell defense system.

Boiler efficiency is called to some extent of total thermal energy which can be recovered from the fuel. Boiler efficiency losses are due to four major factors: the dry gas flux, the latent heat of steam in the flue gas, the combustion loss or the loss of unburned fuel, radiation and convection losses. In this research, the thermal behavior of boilers in gas refinery facilities is studied and their efficiency and their losses are calculated. The main part of this research is comprised of analyzing the effect of various parameters on efficiency such as excess air, fuel moisture, air humidity, fuel and air temperature, the temperature of combustion gases, and thermal value of the fuel. Based on the obtained results, it is possible to analyze and make recommendations for optimizing boilers in the gas refinery complex using response-surface method (RSM).

The new WHO Environmental Noise Guidelines for the European Region have recommendations for limiting noise exposure associated with adverse health effects. The limits are said to be based on a systematic review of existing evidence. This paper gives a systematic assessment of the presented evidence with respect to aircraft noise annoyance and demonstrates that the new guidelines are based on an arbitrary selection of existing studies comprising an imperfect and faulty set of data not representative for the general airport population.

Novel multifunctional fluorescent chemosensors composed of electrospun (ES) nanofibers with high sensitivity toward pH, mercury ions (Hg²⁺), and temperature were prepared from poly(N-Isopropylacrylamide-co-N-methylolacrylamide-co-rhodamine derivative) (poly(NIPAAm-co-NMA-co-RhBN2AM)) by employing electrospinning process. NIPAAm and NMA moieties provide hydrophilic and thermo-responsive properties (absorption of Hg²⁺ in aqueous solutions), and chemical cross-linking sites (stabilization of the fibrous structure in aqueous solutions), respectively. The fluorescent probe, RhBN2AM is highly sensitive toward pH and Hg²⁺. Synthesis of poly(NIPAAm-co-NMA-co-RhBN2AM) with different compositions were carried on via free-radical polymerization. ES nanofibers prepared from sensory copolymers with a 71.1:28.4:0.5 NIPAAm: NMA: RhBN2AM ratio (P3 ES nanofibers) exhibited significant color change from nonfluorescent to red fluorescence while sensing pH or Hg²⁺, and high reversibility of on/off switchable fluorescence emission when Hg²⁺ and ethylenediaminetetraacetic acid (EDTA) were sequentially added. The P3 ES nanofibrous membranes had a higher surface-to-volume ratio to enhance their performance than did the corresponding thin films. In addition, the fluorescence emission of P3 ES nanofibrous membranes exhibited second enhancement above the lower critical solution temperature. Thus, the ES nanofibrous membranes prepared from P3 with on/off switchable capacity and thermo-responsive characteristics can be used as multifunctional sensory devise for specific heavy transition metal (HTM) in aqueous solutions.

This paper presents performed Ansys numerical simulation on WindFloat structures. It contributes to the methodology of calculation based on CFD instruments to study the movements of the waves on semi-submersible stationary structures and highlights the importance of using RAO functions. RAO numerical approach developed can be applied to design semisubmersible WindFloat structures in order to fulfill essential requirements regarding operational safety and design. Numerical methodology was designed in accordance marine loads and the I.T.T.C. recommendations. The numerical RAO results for regular wave movements include many elements for the semi-submergible structure. Close results to open sea operation can be achieved by constant improvement in numerical simulation methodologies. The work opens the way for further hydrodynamic development on irregular waves for realistic hydrodynamic and structural response of the actual semi-submersibles at sea. The results demonstrate the accuracy of RAO function approach for specific WindFloat in Jonswap spectrum.

Background. Adhesives and sealants can be used to repair and preserve solid damaged organs. This study explores the activity of different matrix metalloproteinases (MMP) during the healing of liver injuries treated with two biological adhesives (Tachosil and GelitaSpon) and a new synthetic elastic cyanoacrylate (Adhflex®). Methods. Liver traumatic injuries were experimentally induced in 90 male Wistar rats using a Stiefel biopsy punch in the liver. Wound healing was evaluated 2, 6, and 18 days after injury by determining MMP1, 2, 8, 9, and 13 expression. The histopathological repair was assessed by hematoxylin-eosin, Masson’s trichrome, and Periodic Acid Schiff (PAS) staining. The three sealants used supported complete healing of the liver lesions. Both histopathology and MMP findings indicate that the degradation process of Adhflex® is slower and produces a strong initial inflammatory reaction. Results. All the MMPs measured disclosed higher values at early stage of the healing process in animals treated with Adhflex® and Tachosil, being the expression of for MMP2 and MMP9 significantly higher in the Adhflex-treated group. Animals treated with Tachosil had significant higher values of MMP8 and MPP13 than the Adhflex-treated group. Animals treated with Adhflex® showed a maintained overexpression in all the MMPs tested even at the latest wound healing stages. Conclusion. Notably, this MMPs overexpression did not influence negatively the histological healing process of the hepatic injuries. Given that all hepatic trauma injuries should be considered emergencies, any easy-to-use and rapid sealant, such as Adhflex®, could be considered as a suitable treatment option.

With the rapid development of wind power generations, the inertial response of wind turbines (WTs) are widely concerned recently, which is important for grid frequency dynamic and stability. This paper recognizes and understands the inertial response of type-3 and type-4 WTs from the view of equivalent internal voltage, in analogy with typical synchronous generators (SGs). Due to the dynamic of the equivalent inertial voltage different from SGs, the electromechanical inertia of WTs is completely hidden. The rapid power control loop and synchronization control loop is the main reasons that the WT's inertial response is disenabled. On the basis of the equivalent internal voltage's dynamic, the existing inertia control method for WTs are reviewed and summarized as three approaches from the view of WT's control, i.e. optimizing the power control or synchronization control or both. At last, the main challenges and issues of these inertia controls are attempted to explain and address.

During meat processing, lactic acid bacteria (LAB) have to competitively adapt to the hostile en-vironment produced by curing additives (CA). The objective of this study was to investigate the ability of Latilactobacillus curvatus CRL 705, a bioprotective strain of meat origin, to adapt to CA. A physiological and proteomic approach was performed. CRL 705 was grown in a chemically de-fined medium (CDM) containing specific concentrations of CA (NaCl, nitrite, sucrose and ascor-bic acid). The results showed minor differences in growth kinetics in the presence of CA. Glucose consumption, present in CDM, and production of lactic acid and bacteriocins were not signifi-cantly affected. Proteomic analyses indicated that most of the identified proteins (36 out of 39) mainly related to carbohydrate metabolism (18%), posttranslational modifications (15.6%), energy production and conversion (11.1%), translation (11.1%) and nucleotide metabolism (8.9%), were under expressed. In response to the studied CA, CRL 705 slowed down its general metabolism, achieving slight changes in physiological and proteomic parameters. The observed performance is another characteristic that extends the well-known competitive profile of CRL 705 as a meat starter- and -bioprotective culture. This is the first report dealing with the impact of CA on LAB proteomics.

The appearance of brain metastasis is the most serious complication of breast cancer with mostly fatal outcomes. To reach the brain, tumor cells need to pass the blood-brain barrier (BBB). The molecular mechanisms underlying penetration of the BBB are largely unknown. Previously we found that tumor-infiltrating T lymphocytes enhance the development of brain metastasis of estrogen receptor-negative (ER-) breast cancer. In the current study, we investigate the contribution of T lymphocytes and the IFN- pathway in enabling breast cancer cells to pass the in vitro BBB. CD8+ cells display the strongest stimulatory effect on breast cancer cell passage. We show that inhibition of the IFN- receptor in MDA-MB-231 breast cancer cells, or neutralization of soluble IFN-, impairs the in vitro trespassing of breast cancer cells. Importantly, we validated our findings using gene expression data of breast cancer patients. CXCL-9,-10,-11/CXCR3 axis, dependent on IFN- signaling activity, was overexpressed in primary breast cancer samples of patients who developed brain metastasis. The data support a role for T-lymphocytes and the IFN- pathway in the formation of brain metastasis of ER- breast cancer, and offer targets to design future therapies for preventing breast cancer cells to cross the BBB.

Mahanadi is one of the major inter-state east flowing perennial rivers in peninsular India. Hamp watershed of Seonath Sub-basin of upper Mahanadi basin was considered for the study to estimate the sediment yield and nutrient loss-based identification of critical agricultural sub-watershed and its critical Hydrological Response Unit (HRU) using Soil and Water Assessment Tool (SWAT) in-terfaced with GIS i.e., ArcSWAT. The study area was divided into 14 sub-watersheds considering topographical parameters derived from DEM and drainage network. The land cover, soil layers, and DEM were used to generate 207 HRUs for analysis of annual runoff, sediment yield and nu-trient loss for 2004-2008 (calibration period) and 2010-2013 (validation period). The sediment yield, runoff estimation and nutrient loss matched consistently well with the monthly and seasonal measured values. On the basis of average annual sediment yield (18.18 t/ha), runoff (245.97 mm) and nutrient loss NO3-N (1.62 kg/ha), respectively, sub-watershed WS4 was categorized under high priority for critical are identification. The sub watershed WS4 comprises of 15 HRUs (No. 36 - 50) with four kharif crops viz rice, soybean, maize and sugarcane. Results showed that the crops soy-bean, maize and sugarcane reduced the average annual runoff by 18.1, 31.4 and 18.0 per cent, respectively whereas the sediment yield was increased drastically by 104.5, 37.5 and 5.7 per cent, respectively as compared to rice. Soybean and maize crops HRU generate significant amount of soil and nutrient loss and were found to be as the critical HRUs for the upper Mahanadi River basin

Resistant cancer often shows a particular secretory trait such as heat shock proteins (HSPs) and extracellular vesicles (EVs), including exosomes and oncosomes surrounded by lipid bilayers. Lipoproteins are biochemical assemblies that transport hydrophobic lipid (a.k.a. fat) molecules in body fluid and are composed of a single-layer phospholipid and cholesterol outer shell, lipids molecules within the particles, and apolipoproteins embedded in the membrane. However, lipoprotein storage and secretion by cancer cells have not well-investigated yet. We found lipoproteins were stored and abundantly secreted by neuroendocrine, castration-resistant prostate cancer (NEPC / CRPC) cells but barely secreted by colon cancer cells and oral squamous cell carcinoma (OSCC) cells. In addition, large EVs (approx. 300 nm diameter) and potential oncosomes were released by CRPC and OSCC cells. Proteomics revealed that CRPC cells secreted EVs enriched with tetraspanins and extracellular matrices which were reduced upon heat shock stress and alternatively lipoproteins and HSPs were secreted upon stress. Heat shock stress triggered secretion of lipoprotein-EV complexes that contained apolipoprotein A, B, C and E. These data suggested that vesicular assembly composed of EVs and lipoproteins enriched with cholesterols and phospholipids may be stored in resistant cancer cells but released upon cell stress that is increased in cancer therapies.

A steel damper column is an energy-dissipating member that is suitable for reinforced concrete (RC) buildings and multistory housing. To assess the seismic performance of buildings with steel damper columns, the peak displacement of the whole building and the energy dissipation demand of the dampers must be evaluated. This article proposes an energy-based prediction procedure for the peak and cumulative response of an RC frame building with steel damper columns. The proposed procedure considers two energy-related seismic intensity parameters, namely the maximum momentary input energy and the total input energy. The peak displacement is predicted considering the energy balance during a half cycle of the structural response, using the maximum momentary input energy. The energy dissipation demand of the dampers is then predicted considering the energy balance during a whole response cycle using the total input energy. The local responses (e.g., peak drift, maximum plastic rotation of beams, maximum shear strain, and energy dissipation demand of dampers) are predicted using pushover analysis. Numerical analysis results for 8- and 16-story RC buildings show that the proposed prediction method achieves satisfactory accuracy.

Mitochondrial functions are essential for life, critical for development, maintenance of stem cells, adaptation to physiological changes, responses to stress and aging. The complexity of mitochondrial biogenesis requires coordinated nuclear and mitochondrial gene expression, owing to the need of stoichiometrically assemble the OXPHOS system for ATP production. It requires, in addition, the import of thousands of proteins from the cytosol to keep optimal mitochondrial function and metabolism. Moreover, mitochondria require lipid supply for membrane biogenesis, while it is itself essential for the synthesis of membrane lipids. To achieve mitochondrial homeostasis, multiple mechanisms of quality control have evolved to ensure that mitochondrial function meets cell, tissue and organismal demands. Herein, we give an overview of mitochondrial mechanisms that are activated in response to stress, including mitochondrial dynamics, mitophagy and the mitochondrial unfolded protein response (UPR^mt). We then discuss the role of these stress responses in aging, with particular focus on Caenorhabditis elegans. Finally, we review observations that point to the mitochondrial PHB (prohibitin) complex as a key player in mitochondrial homeostasis, being essential for mitochondrial biogenesis and degradation, and responding to mitochondrial stress. Understanding how mitochondria responds to stress and how such responses are regulated is pivotal to combat aging and disease.

Respiratory tract epithelium infection plays a primary role in Nipah virus (NiV) pathogenesis and transmission. Knowledge about infection dynamics and host responses to NiV infection in respir-atory tract epithelia is scarce. Studies in non-differentiated primary respiratory tract cells or cell lines indicate insufficient interferon (IFN) responses. However, studies are lacking to determin-ing complex host response patterns in differentiated respiratory tract epithelia to understand NiV replication and spread in swine. Here we characterized infection and spread of NiV in differenti-ated primary porcine bronchial epithelial cells (PBEC) cultivated at the air-liquid-interface (ALI). After the initial infection of only a few apical cells, lateral spread for 12 days with epithelium disruption was observed without releasing substantial amounts of infectious virus from the api-cal or basal sides. Deep time course proteomics revealed pronounced upregulation of genes re-lated to type I/II- IFN, immunoproteasomal subunits, TAP-mediated peptide transport and MHC I antigen presentation. Spliceosomal factors were downregulated. We propose a model in which NiV replication in PBEC is slowed by a potent and broad type I/II-IFN host response with con-version from 26S proteasomes to immunoproteasomal antigen processing and improved MHC I presentation for adaptive immunity priming. NiV induced cytopathic effects could reflect the focal release of cell-associated NiV, which may contribute to efficient airborne viral spread between pigs.

Considering the increasing rate of energy consumption and its environmental detrimental effects, as well as considering the use of non-renewable energy sources such as fossil fuels, energy management issues have become more important. Given the 40% share of the building industry's total energy consumption, as well as the 80% share of energy consumed during the operation period, attention to the areas of energy management and optimization during the operation period of the buildings can have a major impact on buildings’ energy performance. In this research, through identifying building energy management tools and studying previous studies and assessing the effects of building energy management systems, the economic and environmental impacts of using building energy management systems on the annual energy consumption in an office building in Tehran as a case study has been investigated. The results indicate a 32 percent reduction in energy consumption and a significant reduction in the release of the environmental pollutants in smart mode compared to the base mode. Moreover, considering the social costs associated with the emitted pollutants as well as the return period, it has been attempted to identify the factors contributing to the economic justification of using smart heating and cooling systems. According to the results, the use of smart energy management systems can be considered as an effective step in optimizing and managing energy consumption in the construction sector.

The outbreak of COVID-19 is a public health emergency that caused disastrous results in many countries. The global aim is to stop transmission and prevent the spread of the disease. To achieve it, every country needs to scale up emergency response mechanisms, educate and actively communicate with the public, intensify infected case finding, contact tracing, monitoring, quarantine of contacts, and isolation of cases. Responding to an emergency requires efficient collaboration and a multi-skilled approach (medical, information, statistical, political, social, and other expertise), which makes it hard to define one interface for all. As actors from different perspectives and domain backgrounds need to address diverse functions, the possibility to exchange available information quickly would be desirable. Geoportal provides an entry point to access a variety of data (geospatial data, epidemiological data) and could be used for data discovery, view, download, and transformation. It helps to deal with challenges like data analysis, confirmed cases geocoding, recognition of disease dynamics, vulnerable groups identification, and capacity mapping. Predicting and modeling the spread of infection, along with application support for communication and collaboration, are the biggest challenges. In response to all these challenges, we have established the Epidemic Location Intelligence System (ELIS) using open-source software components in the cloud, as a working platform with all the required functionalities.

Complete pathologic response (pCR) predicts the long-term outcome of neoadjuvant treated (NAC) breast cancer (BC) but is reached in <10% of hormone-receptor-positive patients. Biomarkers able to guide adjustment or interruption of an ineffective therapy are desired. Here, we evaluated whether shifts in the serum concentration of thymidine kinase 1 (sTK1) during NAC could be utilized as a biomarker. In the PROMIX trial, women with localized HER2- BC received neoadjuvant epirubicin/docetaxel in six cycles. sTK1 was measured with an ELISA in 54 patients at cycles 1-4 and in a total of 131 patients before and 48h after cycle 1. The prognostic significance of the results was evaluated by log-rank tests of Kaplan–Meier estimates. Treatment resulted in a 2-fold increase of sTK1 before and 3-fold increase 48h after the cycles, except for the first cycle, where half of patients reacted with a decrease (post/pre sTK1- ratio <1.12) and the other half reacted with an increase (ratio >1.12). OS rates in ER+ patients with ratios of >1.12 and <1.12 were 97.7% and 78% (p=0.005), respectively, and DFS rates were 90.7% and 68% (p=0.006), respectively. Thus, response of sTK1 at the first cycle of chemotherapy could be used both as an early biomarker for guidance of chemotherapy and for the study of inherent tumor chemo-sensitivity, which could predict long-term outcome prior to therapy.

Since the recent legalization of medical and recreational use of cannabis (Cannabis sativa L.) in many regions worldwide, there has been high demand for research to improve yield and quality. With the paucity of scientific literature on the topic, this study investigated the relationships between light intensity (LI) and photosynthesis, inflorescence yield, and inflorescence quality of cannabis grown in an indoor environment. After growing vegetatively for 2 weeks under a canopy-level photosynthetic photon flux density (PPFD) of ≈ 425 μmol·m-2·s-1 and an 18-h light/6-h dark photoperiod, plants were grown for 12 weeks in a 12-h light/12-h dark ‘flowering’ photoperiod under canopy-level PPFDs ranging from 120 to 1800 μmol·m-2·s-1 provided by light emitting diodes. Leaf light response curves varied both with localized (i.e., leaf-level) PPFD and temporally, throughout the flowering cycle. Therefore, it was concluded that the leaf light response is not a reliable predictor of whole- plant responses to LI, particularly crop yield. This may be especially evident given that dry inflorescence yield increased linearly with increasing canopy-level PPFD up to 1800 μmol·m-2·s-1, while leaf-level photosynthesis saturated well below 1800 μmol·m-2·s-1. The density of the apical inflorescence and harvest index also increased linearly with increasing LI, resulting in higher-quality marketable tissues and less superfluous tissue to dispose of. There were no LI treatment effects on cannabinoid potency, while there were minor LI treatment effects on terpene potency. Commercial cannabis growers can use these light response models to determine the optimum LI for their production environment to achieve the best economic return; balancing input costs with the commercial value of their cannabis products.

Some studies have demonstrated that in vivo degradation processes are influenced by the material’s physico-chemical properties. The present study compares two hydroxyapatites manufactured on an industrial scale, deproteinized at low and high temperatures, and how physico-chemical properties can influence the mineral degradation process of material performance in bone biopsies retrieved 6 months after maxillary sinus augmentation. Residual biomaterial particles were examined by field scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) to determine the composition and degree of degradation of the bone graft substitute material. According to the EDX analysis, the Ca/P ratio significantly lowered in the residual biomaterial (1.08±0.32) compared to the initial composition (2.22±0.08) for the low-temperature sintered group, which also presented high porosity, low crystallinity, low density, a large surface area, and poor stability and a high resorption rate compared to the high-temperature sintered material. This demonstrates that variations in the physico-chemical properties of bone substitute material clearly influence the degradation process. Further studies are needed to determine whether the resorption of deproteinized bone particles proceeds slowly enough to allow sufficient time for bone maturation to occur.

Climate change has a inevitable impacts on tree radial growth, particularly at mountain timeberlines. To understand climate effects on conifer radial growth in the central Hengduan Mountains and potential impacts of future climate change on conifer forest, we studied growth responses to climate variables in Abies georgei, the major tree species of conifer forest in Hengduan Mountains. We collected tree ring samples from four sites near the timberlines and analyzed the relationship between principle components (PC#1) of four chronologies and climatic variables by using response function analysis (RFA), redundancy analysis (RDA) and moving interval analysis (MIA). A. georgei growth was affected by both temperature (positive effects) and precipitation (negative effects). Specifically, the radial growth of A. georgei was significantly and positively correlated with current July and previous November temperature (detected by both RFA and RDA), while precipitation of current June and September inhibited tree growth (detected by RDA). More rapid warming in recent 20 years (1990–2010) clearly enhanced growth responses to July and November temperature, whereas the relationship was weaken for June and September precipitation according to MIA. Under the climate trend of the study area, if the increasing temperature could offset the negative effects of excessive precipitation, A. georgei radial growth would likely benefit from warming, the dynamics of conifer forest should also consider indirect impacts of climate change.

Previous studies investigated the effects of seed rates and seed recycling practices on the yield and yield related variables. However, higher yield does not always guarantee cost-efficiency. This study aimed at investigating the yield effects of plot-level seed rate along with the cost-benefit analysis of seed recycling practices. This study has introduced the dose-response model to the existing analytical methods used in analyzing the effect of different agrochemicals on crop yield. A multi-stage stratified sampling technique was used to select a total of 450 sample respondents. Data was gathered using a mix of data collection tools. Descriptive statistics along with the dose-response model have been applied for data analysis. Farmers of the study were found to be dissimilar in terms of their seed rate application. The dose-response analysis indicated that the highest average wheat yield has been associated with a seed rate of 50 kg ha-1 above what is recommended. The yield effect of seed recycling has also been assessed and a one-time seed recycling has caused a yield decline of 665 kg ha-1 as compared to the non-recycled seeds. The cost reduced by using recycled seed is by far lower than the economic gains associated with using unrecycled and fresh seeds. The cost-benefit analysis made clear that farmers can reduce their seed costs through seed recycling but their yields and net income can be best improved by using unrecycled CBWS. Thus, farmers must be encouraged to make use of unrecycled seed by establishing agricultural credit schemes geared towards seed procurement and seed price subsidy as key strategies to reduce economically wasteful seed recycling practices.

Following legalization, cannabis has quickly become an important horticultural crop in Canada and increasingly so in other parts of the world. However, due to previous legal restrictions on cannabis research there are limited scientific data on the relationship between nitrogen (N), phosphorus (P), and potassium (K) supply (collectively: NPK) and the crop yield and quality. This study examined the response of a high delta-9-tetrahydrocannabinol (THC) Cannabis sativa cultivar grown in deep-water culture with different nutrient solution treatments varying in their concentrations (mg L^-1) of N (70, 120, 180, 250, 290), P (20, 40, 60, 80, 100) and K (60, 120, 200, 280, 340) according to a central composite design. Results demonstrated that inflorescence yield responded quadratically to N and P, with the optimal concentrations predicted to be 194 and 59 mg L^-1, respectively. Inflorescence yield did not respond to K in the tested range. These results can provide guidance to cultivators when formulating nutrient solutions for soilless cannabis production and demonstrates the utility of surface response design for efficient multi-nutrient optimization.

Deep neural networks (DNNs) have gained prominence in addressing regression problems, offering versatile architectural designs that cater to various applications. In the field of earthquake engineering, seismic response prediction is a critical area of study. Simplified models such as single-degree-of-freedom (SDOF) and multi-degree-of-freedom (MDOF) systems have traditionally provided valuable insights into structural behavior, known for their computational efficiency facilitating faster simulations. However, these models have notable limitations in capturing the nuanced nonlinear behavior of structures and the spatial variability of ground motions. This study focuses on leveraging ambient vibration (AV) measurements of buildings, combined with earthquake (EQ) time-history data, to create a predictive model using a neural network (NN) in image format. The primary objective is to predict a specific building's earthquake response accurately. The training dataset consists of 1,197 MDOF 2D shear models, generating a total of 32,319 training samples. To evaluate the performance of the proposed model, termed MLPER (Machine Learning based Prediction of building structures' Earthquake Response), several metrics are employed. These include mean absolute percentage error (MAPE) and mean deviation angle (MDA) for comparisons in the time domain. Additionally, we assess magnitude-squared coherence values and phase differences (Δφ) for comparisons in the frequency domain. This study underscores the potential of MLPER as a reliable tool for predicting building earthquake response, addressing the limitations of simplified models. By integrating AV measurements and EQ time-history data into a neural network framework, MLPER offers a promising avenue for enhancing our understanding of structural behavior during seismic events, ultimately contributing to improved earthquake resilience in building design and engineering.

Cytokines are mediators of inflammation that could lead to fibrosis. The aim was to monitor cytokine levels in saliva and serum after locally fractionated radiotherapy of the head and neck in mice and investigate associations with salivary gland fibrosis and hyposalivation. C57BL/6 mice were randomized to sham or X-ray irradiation of 66 Gy in 10 fractions over 5 days. Blood and saliva were collected on day -7, 5, 35, 80 and 105 with following cytokine analysis. The harvested submandibular salivary gland was assessed for presence of fibrosis. Decision tree regression analysis was used to investigate whether cytokine levels could predict late endpoints in terms of hyposalivation or fibrosis. Significant formation of fibrosis in gland tissue and reduced saliva production was found after irradiation. The pro-inflammatory cytokines IL-1α, TNF, TIMP1, G-CSF, KC and MIP-1α showed increased levels in saliva in irradiated mice and strong correlation with late endpoints. The decision tree analysis largely separated controls from irradiated animals with IL-1α being the strongest predictor. Pro-inflammatory cytokines in saliva, but not in serum, were associated with late endpoints. This indicates that cytokine expression in saliva is a good biomarker for local salivary gland damage with IL-1α as the strongest single predictor.

Multiple lines of evidence indicate that CD8$^+$ T cells are important in the control of HIV-1 (HIV) replication. However, CD8$^+$ T cells induced by natural infection cannot eliminate the virus or reduce viral loads to acceptably low levels in most infected individuals. Understanding the basic quantitative features of CD8$^+$ T-cell responses induced during the course of HIV infection may therefore inform us about the limits that HIV vaccines, which aim to induce protective CD8$^+$ T-cell responses, must exceed. Using previously published experimental data from a cohort of HIV-infected individuals with sampling times from acute to chronic infection we defined the quantitative properties of CD8$^+$ T-cell responses to the whole HIV proteome. In contrast with a commonly held view, we found that the relative number of HIV-specific CD8$^+$ T-cell responses (response breadth) changed little over the course of infection (first 400 days post-infection), with moderate but statistically significant changes occurring only during the first 35 symptomatic days. This challenges the idea that a change in the T-cell response breadth over time is responsible for the slow speed of viral escape from CD8$^+$ T cells in the chronic infection. The breadth of HIV-specific CD8$^+$ T-cell responses was not correlated with the average viral load for our small cohort of patients. Metrics of relative immunodominance of HIV-specific CD8$^+$ T-cell responses such as Shannon entropy or the Evenness index were also not significantly correlated with the average viral load. Our mathematical-model-driven analysis suggested extremely slow expansion kinetics for the majority of HIV-specific CD8$^+$ T-cell responses and the presence of intra- and interclonal competition between multiple CD8$^+$ T-cell responses; such competition may limit the magnitude of CD8$^+$ T-cell responses, specific to different epitopes, and the overall number of T-cell responses induced by vaccination. Further understanding of mechanisms underlying interactions between the virus and virus-specific CD8$^+$ T-cell response will be instrumental in determining which T-cell-based vaccines will induce T-cell responses providing durable protection against HIV infection.

Specific nutrients including n-3 long chain polyunsaturated fatty acids (LCPUFAs), flavonoids, vitamin A, D and E are considered to possess protective properties on human health by impacting on immunological reactions. An ‘inflammation-suppressive’ effect appears to be the common denominator of the beneficial effects of most of these dietary components which may protect against the development of chronic immune disorders such as allergy. However, the majority of these promising data are from preclinical studies such as animal disease models, as the majority of clinical studies only indicate associations. PUFAs, especially n-3 LCPUFAs, have been shown to interact with both the sensitization as well as the effector phase in food allergy. However, it should be noted and realised that PUFAs are highly susceptible to lipid oxidation. Flavonoids and fat-soluble vitamins both contain anti-inflammatory properties and are able to act as anti-oxidants as well. Here, we explore the anti-allergic properties of PUFAs, flavonoids and fat-soluble vitamins in order to create an overview and, more importantly, suggest a strategy to target food allergies using these components and combinations thereof. Dietary n-3 LCPUFAs and the above mentioned micronutrients are promising anti‐allergy agents capable of influencing the allergic immune response through multiple and different biological pathways.

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.

Abstract: Polylactic acid (PLA) is brittle in nature with extensive deformation property. For improvement of the end-use quality, it is of significant importance to enhance the producibility of fused deposition modeling (FDM)-printed objects in PLA. The purpose of this investigation is to boost toughness and to reduce the production cost of the FDM-printed tensile test samples with the desired part thickness. To attain the research purpose number of experiments are designed and analyzed by the Response Surface Method (RSM). The statistical analysis is performed to deal with this concern considering layer thickness, infill percentage, and extruder temperature as controlled factors. The tensile test specimens are printed based on the designed experiments, and the tensile strength tests are conducted by SANTAM 150 universal testing machine based on ASTM D638. The honeycomb internal fill pattern is applied for the production of light-weight and high-strength specimens. The area under Force- Extension curve up to fracture is acquired as the toughness of the printed specimens. This study also developed a modeling process using ANN and ANN-GA techniques for developing an accurate estimation for toughness, part thickness, and production cost as dependant variables. Results were evaluated by correlation coefficient and RMSE values. According to the modeling results, ANN-GA as a hybrid ML technique could successfully improve the accuracy of modeling about 7.5, 11.5 and 4.5 % for toughness, part thickness, and production cost, respectively, in comparison with those for the single ANN method. In the other side, the optimization results confirm that the optimized specimen is cost-effective and able to comparatively undergo deformation, which develops the usability of printed PLA objects. The research is accomplished under the constraints of PLA compatibility with existing fused deposition modeling setup without changing the functional hardware/software of the machine. Although the mechanical properties and dimensional accuracy of PLA have already been studied, there is little literature on the toughness of the printed PLA with honeycomb internal fill pattern.

Highly-resolved data on water balance components (like runoff or storage) are crucial to improve water management, e.g., in drought or flood situations. Because regional observations of these components cannot be acquired adequately, applying water balance models is a feasible solution. We developed an innovative approach using the physically-based lumped-parameter water balance model BROOK90 (R version) integrated into a sensor network platform to derive daily water budget components for catchments in the Free State of Saxony. The model is not calibrated but rather uses available information on soil, land use and precipitation only. We applied the hydro response units (HRUs) approach for 6175 small and medium-sized catchments. For the evaluation, model output was cross-evaluated in ten selected head catchments in a low mountain range in Saxony. The mean values of Kling-Gupta efficiency (KGE) for the period 2005-2019 to these catchments are 0.63 and 0.75 for daily and monthly discharge simulations, respectively. The simulated evapotranspiration and soil wetness are in good agreement with the SMAP_L4_GPH product in April 2015-2018. The study can be enhanced by using different data platforms as well as available information on study sites.

MRI is the gold standard for treatment response assessment in glioblastoma. However, there is no consensus regarding the optimal interval for MRI follow-up during standard treatment. Moreover, reliable assessment of treatment response is hindered by the occurrence of pseudoprogression. It is unknown if a radiological follow-up strategy with 2-3 months intervals actually benefits patients and how it influences clinical decision making about continuation or discontinuation of treatment. This study assessed the consequences of scheduled follow-up scans (post-chemoradiotherapy [post-CCRT], after 3 cycles of adjuvant chemotherapy [TMZ3/6], after completion of treatment [TMZ6/6]) and unscheduled scans on treatment decisions during standard concomitant and adjuvant treatment in glioblastoma patients. Additionally, we evaluated how often follow-up scans resulted in diagnostic uncertainty (tumor progression versus pseudoprogression), and whether perfusion MRI improved clinical decision making. Scheduled follow-up scans during standard treatment in glioblastoma patients rarely resulted in early termination of treatment (2.3% post-CCRT, 3.2% TMZ3/6, and 7.8% TMZ6/6), but introduced diagnostic uncertainty in 27.7% of cases. Unscheduled scans resulted in more major treatment consequences (30%; p&lt;0.001). Perfusion MRI caused less diagnostic uncertainty (p=0.021) but did not influence treatment consequences (p=0.871). This study does not support the current pragmatic follow-up strategy and suggests a more tailored follow-up approach.

Plants harbor a large diversity of endophytic microbes. Meadow fescue (Festuca pratensis) is a cool-season grass known for its symbiotic relationship to the systemic and vertically- via seeds - transmitted fungal endophyte Epichloë uncinata but the effect of the endophyte on the microbial endophyte community and phytohormones is largely unexplored. Here, we sequenced the endophytic bacterial and fungal communities in the leaves and roots, analyzed phytohormone concentrations and plant performance parameters in Epichloë-symbiotic (E+) and Epichloë-free (E-) individuals of two meadow fescue cultivars. The endophytic leaf microbial community differed between leaf and root tissues independent of endophyte symbiosis while the fungal community was different in leaves of Epichloë-symbiotic and Epichloë-free plants in both cultivars. At the same time, endophyte symbiosis decreased salicylic acid and increased auxin concentrations in leaves. Epichloë-symbiotic plants showed a higher biomass, chlorophyll content (SPAD) and higher seed mass at the end of the season. Our results demonstrate that Epichloë-symbiosis alters the leaf fungal microbiome, which coincides with changes in phytohormone concentrations, indicating that Epichloë endophytes affect both, plant immune responses and other fungal endophytes. Whether the effect of Epichloë endophytes on other fungal endophytes is connected to changes in the phytohormone concentrations remains to be elucidated.

Immune response stimulation may be an adjuvant to antimicrobial treatment. Here, we evaluated the impact of immune response modification by lysophosphatidylcholine (LPC) combined with imipenem or ceftazidime in murine models of peritoneal sepsis (PS) and pneumonia by Pseudomonas aeruginosa. Imipenem and ceftazidime-susceptible strain (Pa39), and imipenem and ceftazidime-resistant strain (Pa238) were used. Ceftazidime pharmacokinetic and pharmacodynamic parameters were determined. Therapeutic efficacy, and TNF-α and IL-10 levels were determined in murine models of PS and pneumonia by Pa39 and Pa238 treated with LPC, imipenem or ceftazidime, alone or in combination. In PS model, LPC+ceftazidime reduced spleen and lungs Pa238 concentrations (-3.45 and -3.56 log10 CFU/g; P<0.05) than ceftazidime monotherapy, while LPC+imipenem maintained the imipenem efficacy (-1.66 and -1.45 log10 CFU/g; P>0.05). In pneumonia model, LPC+ceftazidime or LPC+imipenem reduced lungs Pa238 concentrations (-2.37 log10 CFU/g, P=0.1, or -1.35 log10 CFU/g, P=0.75). For Pa39 no statistically significant difference has been observed in PS and pneumonia models between combined therapy and monotherapy. Moreover, LPC+imipenem and LPC+ceftazidime decreased and increased significantly TNF-α and IL-10 levels, respectively, in comparison with untreated controls and monotherapies. These results demonstrate the impact of immune response modification by LPC plus antibiotics on the prognosis of infections by ceftazidime-resistant P. aeruginosa.

Depending on human body conditions and environmental conditions, it is sometimes difficult to conduct subject experiments. In such cases, it is effective to use a thermal manikin. There are few studies that investigate the effect of the non-uniform and asymmetric outdoor thermal environment on the mean skin temperature. The purpose of this study is to clarify the influence of the non-uniform and asymmetric thermal radiation of short-wavelength solar radiation in an outdoor environment on the calculation of the mean skin temperature. The skin temperature of the front of the coronal surface, which was facing the sun and where the body received direct short-wavelength solar radiation, and the skin temperature of the rear of the coronal surface, which was in the shadow and did not receive direct short-wavelength solar radiation were respectively measured. The feet, upper arm, forearm, hand and lower leg, which are susceptible to short-wavelength solar radiation in a standing posture, had a noticeable difference in skin temperature between sites in the sun and in shade. The mean skin temperature of sites facing the sun was significantly higher than the mean skin temperature of those in the shade.

Salmonid alphavirus strain 3 is responsible for outbreaks of pancreas disease in salmon and rainbow trout in Norway. Although the extensive amount of research on SAV3 focused mainly on the heart and pancreas (of clinical importance), tropism and pathogenesis studies of the virus in other salmon tissues are limited. Here, we used a combination of RT-qPCR (Q_nsp1 gene) and in situ hybridization (RNAscope®) to demonstrate the tropism of SAV3 in situ in tissues of Atlantic salmon, employing a challenge model (by cohabitation). In addition, as previous results suggested that pseudobranch may harbor the virus, the change in the expression of different immune genes upon SAV3 infection (RT-qPCR) was focused on the pseudobranch in the current study. In situ hybridization detected SAV3 in the heart, pseudobranch, gills, pyloric caeca, and pancreas after virus infection, with the heart ventricle showing the most extensive infection. Furthermore, the detection of the virus at different adipose tissues associated with the internal organs of the salmon, suggests a specific affinity of SAV3 to adipocyte’s components. The innate immune response to SAV3 in the pseudobranch after infection dominated over the adaptive responses, yet it did not mitigate the infection in that tissue. The early detection of SAV3 in the pseudobranch after infection, along with the persistent low infection over the experimental course, suggests a pivotal role of the pseudobranch in SAV3 pathogenesis in Atlantic salmon.

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.

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.

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.

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.

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.

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.

Soil transverse isotropy results in different stiffness characteristics in the horizontal and vertical directions. However, the effect is usually neglected in the seismic motion analysis. In this study, an equivalent linear anisotropic soil model was established based on the finite element method and investigated the impact of anisotropic parameters on ground motion at the site under various seismic wave inputs. It is found that the anisotropic parameters have a more significant effect for the seismic waves with the dominant frequency closer to the fundamental frequency of the site. As an example, the soil dynamic parameters in Shanghai Yangshan Port were calibrated by a series of bending elements, resonance columns, and cyclic triaxial tests. The influences of anisotropy on the peak ground acceleration (PGA) and response spectrum are studied for Yangshan Port. Addi-tionally, the standard design response spectra considering the soil anisotropy were provided. A comparison reveals that the existing isotropic design response spectrum may lead to dangerous seismic design for the structures at Yangshan port.

Cellular aging has drawn the attention of researchers, scientists, and biotech businesses for the treatment of a number of medical conditions. Cellular aging is primarily defined by consistent cessation of proliferative development in response to internal and external stressors, including DNA damage, telomere shortening, mitochondrial dysfunction, and regulation of the senescence-associated secretory phenotype (SASP). Disturbances involving these factors may contribute to age-related disease development. Therefore, the current review aims to explore anti-aging factors targeting DNA damage response and SASP regulation and their detailed signaling networks. In addition, it provides an opportunity for researchers to identify not only anti-aging targets, but also anti-aging therapeutic strategies based on identified and non-identified targets.

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

High mobility group box 1 (HMGB1) is secreted from activated immune cells, necrotic cells, and certain cancers. Previous studies have reported that different patterns of post-translational modification, particularly acetylation and oxidation, mediate HMGB1 release and confer distinct extracellular HMGB1 signaling activity. Here we report that cisplatin but not carboplatin induces secretion of HMGB1 from human A549 non-small cell lung cancer (NSCLC) cells. Cisplatin-mediated HMGB1 secretion was dose-dependent and was regulated by nuclear exportin 1 (XPO1) also known as chromosomal maintenance 1 (CRM1) rather than adenosine diphosphate (ADP)-ribosylation, acetylation, or oxidation. HMGB1, as well as lysine acetylation and cysteine disulfide oxidation of secreted HMGB1, were monitored by sensitive and specific assays using immunoprecipitation, stable isotope dilution, differential alkylation, and nano liquid chromatography parallel reaction monitoring/high-resolution mass spectrometry (nano-LC-PRM/HRMS). A major fraction of the HMGB1 secreted by low dose cisplatin treatment of A549 NSCLC cells was found to be in the fully reduced form. In contrast, mainly oxidized forms of HMGB1 were secreted by dimethyl sulfoxide (DMSO)-mediated apoptosis. These findings suggest that inhibition of XPO1 could potentiate the anti-tumor activity of cisplatin by increasing the nuclear accumulation of HMGB1 protein, an inhibitor of cisplatin DNA-adduct repair. Furthermore, low-dose cisplatin therapy could modulate the immune response in NSCLC through the established chemokine activity of extracellular reduced HMGB1. This could potentially enhance the efficacy of subsequent immunotherapy treatment.

The 2019 COVID-19 pandemic caused by SARS-CoV-2 has resulted in many fatalities worldwide. Despite various types of supportive care, mortality rates for patients with comorbidities remain high. To explore alternative treatment options, interferons (IFNs) have emerged as promising therapeutic drugs for SARS-CoV-2. This review aims to investigate the potential of IFNs as a drug with details on their mechanisms of action, and available data on their use with ongoing clinical trials, results, potential limitations, and challenges. Recently published research articles, which were systematically searched through online databases, have been selected and found that IFNs have colossal potential in treating SARS-CoV-2 infection by modulating the host's immune response and inhibiting viral replication and decreasing the severity of disease and hospitalization (p = 0.03, ±0.05) and (p = 0.04, ±0.05) respectively. However, due to less available data, more controlled and randomized trials are needed to confirm the efficacy and safety of IFN therapy. The optimal dosing and duration of IFN therapy also remain to be determined. Although further research is needed the wait for ongoing clinical trial results under investigation is also important for a better understanding of IFN therapy.

The synthesis 2-tert-butyl-4-methylphenol is of great significance because of its widely application in industry, and the development of highly efficient catalyst is necessary to the alkylation of p-cresol and tert-butyl alcohol. Here, an efficient and mild method was established, caprolactam was chosen as hydrogen-bonding acceptor, p-toluenesulfonic acid was employed as hydrogen-bonding donor, and deep eutectic solvent (DES) was prepared to catalyze the alkylation reaction. The structure of the DES catalyst was characterized by 1H NMR spectra, thermogravimetric analysis and fourier transform infrared spectra (FT-IR). In addition, response surface design based on Box-Behnken method was employed to optimize the alkylation reaction process parameters, the study of reaction kinetics was also carried out subsequently. The recycle performance of the catalyst was evaluated by recovery experiments, and a good result was obtained. Comparing with the literature reported, we here provide a mild method to the synthesis of 2-tert-butyl-4-methylphenol.

The present research was titled “A Study on Dark Triad Personality and Emergency Response and Psychological Adaptation among Young Adults during Pandemic.” The purpose of the study was to explore the association between the dimensions of dark triad personality namely narcissism, psychopathy, Machiavellianism and the dimensions of emergency response and psychological adaptation namely worry, agitation, awareness, prosociality, perceived self-efficacy. The correlation between the dimensions of dark triad personality and the dimensions of emergency response and psychological adaptation. Gender differences were also studied for the dimension dark triad personality. The results showed that a strong positive correlation existed between narcissism and agitation, Machiavellianism and worry and Machiavellianism and agitation. Narcissism and psychopathy were found to be strong predictors of agitation. Significant Gender differences were noted on the dimensions of psychopathy and Machiavellianism where males scored higher than females.

In 1948, Skinner described the behavior of pigeons under response-independent schedules as “superstitious,” and proposed that the responses were reinforced by contiguous, adventitious food deliveries. Subsequently, response-independent schedules have been of interest to both basic and applied researchers, first to understand the mechanisms involved, and later, as “noncontingent reinforcement” (NCR) to reduce undesirable behavior. However, the potential superstitious effects produced by these schedules have been challenged, with some researchers arguing that antecedent variables play a significant role. This paper examines the evidence for adventitious reinforcement from both laboratory and applied research, the results of which suggest that antecedent, non-operant functions may be important in fully understanding the effects of NCR. We propose an applied-basic research synthesis, in which attention to potential non-operant functions could provide a more complete understanding of response-independent schedules. We conclude with a summary of the applied implications of the non-operant functions of NCR schedules.

Coronavirus disease 2019 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To contain the virus, numerous preventive measures have been taken including isolation of patients, careful infection control, social distancing, and taking vaccine. So far, new confirmed and death cases are still increasing. SARS-CoV-2 invades cells by using the angiotensin converting enzyme 2 (ACE2). ACE2 is an essential enzyme of the renin-angiotensin system (RAS) which converts angiotensin II (Ang II) to angiotensin (1-7). ACE2 is expressed in different organs, including lung, heart, and kidney. A high number of COVID-19 patients developed kidney injury has been reported. Renal impairment and acute injury are associated with mortality of COVID-19, which is 14-16 times higher than other general patients. Acute Kidney Injury has been occured in 2.9 up to 43% of intensive care unit patients. The increasing evidence show that the components of RAS can activate the complement cascade, and cytokines production. Kidney injury caused by SARS-CoV-2 is related mainly to systemic and local inflammation. Moreover, the uncontrolled immune responses mediated by SARS-CoV-2 including hypercytokinaemia, secondary hemophagocytic lymphohistiocytosis, antibody dependent enhancement, complement system, and phagocytic cells activation can contribute in the virus pathogenesis leading to associated renal dysfunction. However, the role and crosstalk between of RAS components and immune response in mediating kidney injury remain undefined. In this review, we focus on the recent studies to provide the pathogenesis of SARS-CoV-2 interacting with RAS and immune responses to mediate kidney injury.

An immune-inflammatory response is accompanied by increased nitro-oxidative stress. The aims of this mechanistic review are to review: a) the role of redox sensitive transcription factors and enzymes, ROS/RNS production and the activity of cellular antioxidants on the activation and performance of macrophages, dendritic cells, neutrophils, T cells, B cells and natural killer cells; b) the involvement of high-density lipoprotein (HDL), apolipoprotein (Apo)A1, paraoxonase (PON)-1, and oxidized phospholipids in the regulation of the immune response; and c) the detrimental effects of hypernitrosylation and chronic nitro-oxidative stress on the immune response. The redox changes during immune-inflammatory responses are orchestrated by the actions of nuclear factor (NF)-κB, HIF1alpha, the mechanistic target of rapamycin (mTor), the phosphatidylinositol 3‑kinase (PI3K) / protein kinase B (AKT) signalling pathway, mitogen-activated protein (MAP) kinases, 5' AMP-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor (PPAR). The performance and survival of individual immune cells is under redox control and sensitive to intracellular and extracellular levels of ROS/RNS and is heavily influenced by cellular anti-oxidants including the glutathione and thioredoxin systems, nuclear factor erythroid 2-related factor 2 (Nrf-2), and the HDL complex. Chronic nitro-oxidative stress and hypernitrosylation inhibit the activity of those antioxidant systems, the tricarboxylic acid cycle, mitochondrial functions, and the metabolism of immune cells. In conclusion, those redox-associated mechanisms modulate metabolic reprogramming of immune cells, macrophage and T helper cell polarization, phagocytosis, production of pro- versus anti-inflammatory cytokines, immune training and tolerance, chemotaxis, pathogen sensing, antiviral and antibacterial effects, Toll-like receptor activity, and endotoxin tolerance.

Using the above results from RMS analysis the optimum values were predicted for the independent significant variables (Figure 3) the optimized levels of these variables in combination with other media variables the maximum production was predicted to be 199.90 U/mL. The predicted data were validated through confirmatory experiments performed in triplicates. A 1.29-fold increase in amylase activity against un-optimized (OVAT) medium was achieved in the present study authenticating the efficacy of RSM in process optimization (Figure 4). 2.6 Model validation and scale-up at laboratory scale (5L) bioreactor Once the parameters were standardized in the shake-flasks culture, the experiment was scaled-up to a laboratory-scale bioreactor (5 L). The yield of amylase increased by 1.01 fold (205.69 U/mL), it could be possible because the enzyme production in a bioreactor is higher than in shake-flasks culture as the various critical variable factors such as the dissolved oxygen (DO) and the pH can be optimally controlled at the desired levels [22].

The effect of CO2 pre-treatments on tomato quality prior to cold storage was investigated using physiochemical and transcriptome changes. Three hours CO2 treated fruits were firmer than untreated fruits and had a good appearance even after being transferred from 4°C storage to 20°C for 8 d. CO2 pretreatment with cold storage showed a synergistic effect on delayed ripening through reduced respiration; these tomatoes exhibited a lower lycopene content than untreated fruit under cold storage. Tomatoes treated with 30% CO2 had fewer pits than untreated fruits subjected to chilling temperatures, even after being transferred to 20°C for 8 d. Functional enrichment analyses from transcriptome and metabolome commonly showed that CO2-responsive genes or metabolites were involved in the sucrose and starch and biosynthesis of secondary metabolisms. The most frequently detected domain, ethylene-responsive factor domain and reduced glycolysis provide insights into the mechanism that CO2 regulates tomato quality.

The ongoing crisis of COVID-19 pandemic that swept across the world, poses serious challenges on health delivery systems particularly in developing countries. In Africa however, the crisis rather inspires and sparks creativity and innovation at the national, institutional, organizational, and individual levels. This paper unravels Africa’s response mechanisms to the virus that might have relatively contributed to the low infection rate of the pandemic within the continent. Some criteria are adopted to assess and assemble the most influential government policies and home-grown innovations from various African countries and territories within the continent. It is found that, some of the innovations do not only help in combating the virus, but also have socio-economic benefits as they substantially complement government efforts in easing the burden of the citizenry as they cope with preventive protocols imposed on them. This study will be helpful in identifying the most significant home-based innovations that can be improved and used to reduce health delivery crises within the continent even after COVID-19.

Due to the high solar irradiance or energy price, certain regions in the U.S. may reach 100% PV penetration and experience degradation of frequency response greater than the interconnection as a whole. Therefore, in this section, the 100% PV penetration region in each interconnection is simulated to study the local high PV penetration effects. The study was performed by quantifying RoCoF, frequency nadir, and settling frequency at different regional PV penetration levels. The impact of high regional PV penetration on the compliance of grid code on frequency response is also studied.

Microalgal harvesting is one of the most challenging processes in the development of algal research and development. Several methods, such as centrifugation, flocculation, and filtration, are available at the laboratory scale. However, the requirement of expensive pieces of equipment and the possibility of biomass contamination are recurring gaps that hinder the development of microalgae I+D in different parts of the world. Recently, the electroflotation has been proved as a suitable method for the harvesting of different species of microalgae and cyanobacteria. To this day, there are no companies that sell laboratory-scale electroflotation equipment; this is mainly due to the gap in the knowledge on which factors (time, mixing rate, number of electrodes, and others) will affect the efficiency of concentration without reducing the biomass quality. This paper aims to build an innovative low-cost electroflotation system under 300 USD with cheap and resistant materials. To achieve our goal, we test the interaction of three variables (time, mixing rate, and amount of electrodes) were evaluated. Results showed that an efficiency closer to 100% could be achieved under 20 minutes using >10 electrodes and 150 rpm. We hope this innovative approach can be used by different researchers to improve our knowledge of the concentration and harvesting of algae and cyanobacteria.

The endoplasmic reticulum (ER) comprises a network of tubules and vesicles that constitutes the largest organelle of the eukaryotic cell. Being the location where most proteins are synthesized and folded, it is crucial for the upkeep of cellular homeostasis. In addition, it is the largest ionic calcium reservoir in cells, tightly regulating the levels of this second messenger according to cellular necessities. Disturbed ER homeostasis triggers the activation of an intricate and conserved molecular machinery, termed the unfolded protein response (UPR). Given the impact of this signaling network upon an extensive list of cellular processes, ER stress is involved in the onset and progression of multiple diseases, including cancer and neurodegenerative disorders. There is, for this reason, an increasing number of publications focused on characterizing and/or modulating ER stress, which have resulted in a wide array of techniques employed to study ER-related molecular events. This review aims to sum up the tools available design a study of this nature.

XGBoost is recognized as an algorithm with exceptional predictive capacity. Models for a binary response indicating the existence of accident claims vs. no claims can be used to identify the determinants of traffic accidents. We compare the relative performances of logistic regression and XGBoost approaches for predicting the existence of accident claims using telematics data. The dataset contains information from an insurance company about individuals’ driving patterns – including total annual distance driven and percentage of total distance driven in urban areas. Our findings show that logistic regression is a suitable model given its interpretability and good predictive capacity. XGBoost requires numerous model-tuning procedures to match the predictive performance of the logistic regression model and greater effort as regards interpretation.

The process of preparing anti-glare thin films by spray-coating silica sol-gel to soda-lime glass was exclusively and statistically studied in this paper. The effects of sol-gel deliver pressure, air transport pressure, and spray gun displacement speed on the gloss, haze, arithmetic mean surface roughness, and total transmittance light were analyzed. The experimental results indicate that the factors of sol-gel deliver pressure, air transport pressure, and displacement speed exhibit significant effect on the haze, gloss, and Ra. In contrast, the variation of total transmittance light with these three factors are insignificant. Because the anti-glare property is predominantly determined by low gloss and high haze, therefore, we aim to minimize gloss and maximize haze to achieve high anti-glare. Central composite design and response rurface methodology are employed to analyze the main and interaction effects of the three factors through quadratic polynomial equations, which are confirmed by the analysis of variance and R². The response surface methodology predict the lowest gloss and highest haze are 9.2 GU and 57.0%, corresponding to the sol-gel deliver pressure, air-transport pressure, and displacement speed of 250 kPa, 560 kPa, and 140 mm/s, and 340 kPa, 620 kPa, and 20 mm/s, respectively. Comparing the predicted optimal data with the real experimental results validates the applicability of the mathematical model. This study provides an important basis for the subsequent production of anti-glare glass with different specifications to satisfy the market demand.

The design of curved surface sliders (CSS) based on the elastic response spectrum is done by iteration to find the combination of friction coefficient and displacement capacity which satisfies the condition that the maximum horizontal CSS force is equal to the horizontal force of the structure. Although this CSS design is valid it does not necessarily minimize structural acceleration. This paper therefore describes the optimum CSS design for minimum structural acceleration. All valid CSS designs and the optimum CSS design are represented by their associated trajectory in the elastic response spectrum plane which visualizes the optimization problem. The results demonstrate that the optimum CSS design is not obtained at maximum tolerated effective damping ratio. The subsequent sensitivity analysis describes how much the structural acceleration increases if the actual friction coefficient of the real CSS deviates from its optimum design value. The analysis points out that the increase in structural acceleration is approximately one order of magnitude smaller than the deviation in friction. The sensitivity data may be used by structural engineer to determine tolerable deviations in friction coefficient which still results in acceptable structural accelerations.

Human influenza A viruses (IAVs) cause global pandemics and epidemics, which remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral outbreaks, new treatments are urgently needed. Developing new virus control modalities requires better understanding of virus-host interactions. Here we describe how IAV infection triggers cellular apoptosis, and how this process can be exploited towards development of new therapeutics, which might be more effective than the currently available anti-influenza drugs.

The steel damper column is an energy-dissipating member that is suitable for reinforced concrete (RC) buildings, and those used for multistory housing in particular. However, the effectiveness of steel damper columns may be affected by the behavior of surrounding members, and this effect can be severe in the case of seismic sequences. This article investigates the nonlinear response of building models having an RC moment-resisting frame (MRF) with and without steel damper columns under seismic sequences. The applicability of the concept of the momentary energy input to the prediction of the peak response of RC MRFs with damper columns under seismic sequences is also investigated. The main findings of the study are summarized as follows. (1) The peak response of RC MRFs with damper columns subjected to sequential accelerations is similar to the peak response obtained considering only the mainshock, whereas the cumulative strain energy of RC MRFs accumulates more for sequential accelerations. (2) The steel damper column is effective in reducing the peak and cumulative responses of RC MRFs in the case of sequential seismic input. (3) The relation of the hysteretic dissipated energy during a half cycle of the structural response and the peak displacement of the first modal response can be properly evaluated using the simple model proposed in this study.

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.

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.

Unlike plants which have special gravity-sensing cells, such special cells in animals are yet to be discovered. However, microgravity, the condition of apparent weightlessness, causes bone, muscular and immune system dysfunctions in astronauts following spaceflights. Decades of investigations show correlations between these organ and system-level dysfunctions with changes induced at the cellular level both by simulated microgravity as well as microgravity conditions in outer space. Changes in single bone, muscle and immune cells include morphological abnormalities, altered gene expression, protein expression, metabolic pathways and signaling pathways. These suggest that human cells mount some response to microgravity. However, the implications of such adjustments on many cellular functions and responses are not clear. Here, we addressed the question whether microgravity induces alterations to drug response in cancer cells. We used both adherent cancer cells (T98G) and cancer cells in suspension (K562) to confirm known effects of microgravity and then treated the K562 cells with common cancer drugs (hydroxyurea and paclitaxel) following 48 hours of exposure to microgravity via a NASA-developed rotary cell culture system. Fluorescence-guided morphometry revealed microgravity-induced loss of the significant reduction (p &lt; 0.0l) to the nuclear to cytoplasm ratio of cancer cells treated with hydroxyurea. Our results call for more studies on impact of microgravity on cellular drug-response, in view of the growing need for space medicine, as space exploration grows.

The aim of this study was to identify the differentially expressed genes (DEG) from the skeletal muscle and liver samples of animal model for metabolic diseases in human. To perform the study, the fatty acid (FA) profile and RNA sequencing (RNA-Seq) data of 35 samples of liver tissue (SOY1.5, n=17 and SOY3.0, n=18) and 36 samples of skeletal muscle (SOY1.5, n=18 and SOY3.0, n=18) of Large White pigs were analyzed. The FA profile of the tissues was modified by the diet, mainly those related to monounsaturated (MUFA) and polyunsaturated (PUFA) FA. The skeletal muscle transcriptome analysis revealed 45 DEG (FDR 10%), and the functional enrichment analysis identified network maps related to inflammation, immune process, and pathways associated with the oxidative stress, type 2 diabetes and metabolic dysfunction. For the liver tissue, the transcriptome profile analysis revealed 281 DEG, which participate in network maps related to neurodegenerative diseases. With this nutrigenomics study, we verified that different levels of soybean oil in the pig diet, an animal model for metabolic diseases in humans, affected the transcriptome profile of skeletal muscle and liver tissue. These findings may help to better understand the biological mechanisms that can be modulated by the diet.

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.

Catalase, an antioxidant enzyme widely produced in mammalian cells and bacteria, is crucial in mitigating oxidative stress in a hostile environment. This function enhances the intracellular survivability of various intracellular growth pathogens, including Brucella abortus. In this study, to determine whether the inhibition of catalase can inhibit the intracellular growth of Brucella (B.) abortus, we employed 3-amino-1,2,4-triazole (3-AT), a catalase inhibitor, in both RAW 264.7 macrophage cells and an ICR mouse model during Brucella infection. The intracellular growth assay indicated that 3-AT exerts growth-inhibitory effects on B. abortus within macrophages. Aside from that, it contributes to the accumulation of reactive oxygen species and the formation of nitric oxide. Notably, 3-AT diminishes the activation of the nucleus transcription factor (NF-κB) and modulates cytokine secretion within infected cells. In our mouse model, the administration of 3-AT reduced B. abortus proliferation within the spleen and liver of infected mice. This reduction was accompanied by a diminished immune response to infection, as indicated by lowered levels of TNF-α, IL-6, IL-10, and altered CD4+/CD8+ T-cell ratio. These results suggest the protective and immunomodulatory effects of 3-AT treatment against Brucella infection.

In swarm-robotics foraging, the purpose of task allocation is to adjust the number of active foraging robots dynamically based on the task demands and changing environment. It is a difficult challenge to generate self-organized foraging behavior in which each robot can adapt to environmental changes. To complete the foraging task efficiently, this paper presents a novel self-organized task allocation strategy known as the dynamic response threshold model (DRTM). To adjust the behavior of the active foraging robots, the proposed DRTM newly introduces the traffic flow density, which can be used to evaluate the robot density. First, the traffic flow density and the amount of obstacle avoidance are used to adjust the threshold which determines the tendency of a robot to respond to a stimulus in the environment. Then, each individual robot uses the threshold and external stimulus to calculate the foraging probability that determines whether or not to go foraging. Simulation and physical experiments are carried out to evaluate the performance of the proposed method. The experimental results show that the DRTM is superior to and more efficient than the adaptive response threshold model (ARTM) in swarm foraging.

In contrast to normal cells, tumor cells of multiple entities overexpress the Heat Shock Protein 70 (Hsp70) not only in the cytosol, but also present it on their plasma membrane in a tumor-specific manner. Furthermore, membrane-Hsp70 positive tumor cells actively release Hsp70 into lipid microvesicles termed exosomes into the blood. Due to conformational changes of Hsp70 in the lipid environment, most commercially available antibodies fail to detect membrane-bound and exosomal Hsp70. To fill this gap and to assess the role of exosomal Hsp70 in the circulation as a potential tumor biomarker, we established the novel complete Hsp70 (compHsp70) sandwich ELISA using two monoclonal antibodies (mAbs) that are able to recognize both, free and lipid-associated Hsp70 on the cell surface of viable tumor cells and exosomes. The epitopes of the mAbs cmHsp70.1 (aa 451-461) and cmHsp70.2 (aa 614-623) that are conserved among different species reside in the substrate-binding domain of Hsp70, with measured affinities of 0.42 nM and 0.44 nM, respectively. Validation of the compHsp70 ELISA revealed a high intra- and inter-assay precision, linearity in a concentration range of 1.56 to 25 ng/ml, high recovery rates of ‘spiked’ liposomal Hsp70 (>84%), comparable values between human serum and plasma samples, and no interference by food intake or age of the donors. Hsp70 concentrations in the circulation of patients with glioblastoma, squamous cell or adeno non-small cell lung carcinoma (NSCLC) at diagnosis were significantly higher than those of healthy volunteers. Hsp70 concentrations dropped concomitantly with the decrease in viable tumor mass on irradiation of patients with approximately 20 Gy (range 18 – 22.5 Gy) or after completion of radiotherapy (60 - 70 Gy). In summary, the compHsp70 ELISA presented herein provides a highly sensitive and reliable tool for measuring free and exosomal Hsp70 in liquid biopsies of tumor patients, levels of which can be used as a predictive tumor-specific biomarker, risk assessment and for monitoring therapeutic outcome.

Spatial Data Infrastructures (SDI) support the harvesting, curating, storage, and sharing of data along with providing access to development, analytic, and visualization tools that enable the building of innovative applications to address broad or specific challenges. SDIs can be especially powerful in bringing together data and tools supporting a particular theme – and this paper discusses and demonstrates the value of an SDI focused on Health. Many potential benefits of a Health SDI are proposed, and the case of supporting emergency response efforts is developed in detail. Leveraging a Health SDI, a Health Risk Index was created that provides emergency response personnel (both Emergency Operations Managers and Emergency Medical Responders) key insights into the unique health risks the impacted population faces due to the disaster. In order to establish the Health Risk Index, datasets from multiple national and global sources representing health data and social data that influences health outcomes – typically called social determinants of health – are harvested, merged, and republished to support further efforts at advancing the Health Risk Index. Visualizations of the Health Risk Index at the global, national, and sub-national levels down to the address level are presented along with demonstrations of its use.

Artificial intelligence methods may help in unveliling information hidden in high-dimensional oncological data. Flow cytometry studies of haematological malignancies provide quantitative data with the potential to be used for the construction of response biomarkers. Many computational methods from the bioinformatics toolbox can be applied to these data but have not been exploited in their full potential in leukaemias, specifically for the case of childhood B-cell acute lymphoblastic leukemia. In this paper we analysed flow cytometry data obtained on diagnosis from 54 paediatric B-cell acute lymphoblastic leukemia patients from two local institutions. We constructed classifiers based on the Fisher’s Ratio to quantify differences in expression levels of immunophenotypical markers between patients with relapsing and non-relapsing disease. The distribution of the marker CD38 was found and validated to have a strong discriminating power between both patient cohorts, thus providing a classifier.

Plants attained cellular homeostasis of phosphate (Pi) through an integrated response pathway regulated by different families of transcription factors including MYB, WRKY, bHLH and ZFP. The systemic response to Pi limitation showed the critical role played by inositol pyrophosphate (PP-InsPs) as signaling molecule and SPX (SYG1/PHO81/XPR1) domain proteins as sensor of cellular Pi status. Binding of SPX to PP-InsPs regulates the transcriptional activity of the MYB-CC proteins, phosphate starvation response factors (PHR/PHL) as the central regulator of Pi-deficiency response in plants. Vacuolar phosphate transporter, VPT may sense the cellular Pi status by its SPX domain, and vacuolar sequestration is activated under Pi replete condition and the stored Pi is an important resource to be mobilized under Pi deficiency. Proteomic approaches led to new discoveries of proteins associated with Pi-deficient response pathways and post-translational events that may influence plants in achieving Pi homeostasis. This review provides current understanding on the molecular mechanisms at the transcriptional and translational levels for achieving Pi homeostasis in plants highlighting the importance of DNA-protein and protein-protein interactions. The potential strategies for employing the CRISPR technology to modify the gene sequences of key regulatory and response proteins for attaining plant Pi homeostasis are discussed.

Following the development of tyrosine kinase inhibitors (TKI), the survival of patients with chronic myeloid leukaemia (CML) drastically improved. With the introduction of these agents, CML is now considered a chronic disease, for some patients. Taking into consideration the side effects, toxicity, and high cost, discontinuing TKIs became a goal for patients with chronic phase CML. Patients who achieved deep molecular response (DMR) and discontinued TKI, remained in treatment-free remission (TFR). Currently, the data from the published literature demonstrate that 40-60% of patients achieve TFR, with relapses occurring within the first six months. In addition, almost all patients who relapsed regained a molecular response upon re-treatment, indicating TKI discontinuation is safe. However, there is still a gap in the understanding the mechanisms behind TFR, and whether there are prognostic factors that can predict the best candidates who qualify for TKI discontinuation with a view to keeping them in TFR. Furthermore, the information about a second TFR attempt and the role of gradual de-escalation of TKI before complete cessation is limited. This review highlights the factors predicting success or failure of TFR. In addition, it ex-amines the feasibility of a second TFR attempt after the failure of the first one, and the current guidelines concerning TFR in clinical practice.

Motorcycles can be considered a new form of smart vehicle when taking into account their small and modern structure and due to the fact that nowadays they are used in the new role of ambu-lance to rapidly reach emergency patients in large cities with traffic congestion. However, there is no study regarding the measuring of access time for motorcycle ambulances in large cities of Thailand. Therefore, this study aims to compare access times to patients between motorcycle ambulances and conventional ambulances, including analysis of the use of AED installed on motorcycle ambulances to contribute to the sustainable development of public health policies. In two hundred and seventy-one operations, it was found that the times from dispatch to vehicle (ambulance and motorlance) being en route and times from the 1669 center (center for com-mand-and-control EMS in Thailand) call receipt to arrival on scene (response time) of motorcycle ambulances was shorter than that of a conventional ambulance and the use of AED on a motor-cycle ambulance can increase the chances of survival for patients with cardiac arrest outside the hospital in public places where AEDs are not available and in all cases where access to an AED was less than eight minutes.