The rock joint fissure slope in cold regions is prone to deformation and failure problems such as relaxation, tension and collapse under freeze-thaw (F-T) cycles. Based on the ideology of clean production and promoting the structural integrity of geotechnical projects in cold areas, this study designed and prepared aeolian-sand (AS) to replace part of river sand as a filling mortar material by taking advantage of the low cost and easy availability of AS. Investigations were carried out to determine the impact of varying proportions of AS in mortar on the microstructure and shear properties of the mortar-rock interface under F-T cycles. Therefore, F-T cycle testing, nuclear magnetic resonance (NMR) testing and shear testing were carried out on grout with different proportions of AS. The results show that the right proportion of AS replacement could enhance the shear deformation resistance and F-T resistance of the mortar-rock interface, and 30% proportion is the optimal proportion. By increasing of F-T cycles, the three types of specimens showed different degrees of particle spalling, shedding and cracking. The slurry-rock interface layer in the A (0%) group exhibited the most severe F-T deterioration, while the B (15%) group showed a lesser degree, and the C (30%) group performed the best. T2 spectrum curve and total spectrum area change law from the microscopic point of view to verify the 30% AS proportion mortar-rock interface F-T resistance is the strongest, followed by 15% AS proportion mortar, the weakest is ordinary mortar. The degradation of the mortar-rock bond is primarily due to the conversion of solid to liquid phases and the movement of internal water caused by fluctuating temperatures. The extent of F-T deterioration in the slurry-rock interface layer is greatly affected by the varying proportions of AS. The shear strength and shear stiffness of specific proportion of AS decreased with the increase of F-T cycles. For same F-T cycles, the shear strength and shear stiffness of group C (30%) were the highest, followed by group B (15%) and group A (0%). The grout material not only reinforces the F-T joint fissure slope, but also reduces the cost of grout reinforcement and promotes the clean production of geotechnical structures.

Considering the significance of thermodynamic cycles in the global energy system, it is necessary to develop new general classes of thermodynamic cycles to relieve current energy and environmental problems. Inspired by the relationship between power cycles and refrigeration cycles, we realize that general classes of thermodynamic cycles should occur in pairs with opposite functions. Here we reverse class 1 heating cycles to obtain another new general class of thermodynamic cycles named class 2 heating cycles (HC-2s). HC-2s have two basic forms, and each contains six thermodynamic processes. HC-2s present the simplest and most general approach to utilizing the temperature difference between a medium-temperature heat source and a low-temperature heat sink to achieve efficient high-temperature heating. HC-2s fill the gaps that have existed since the origin of thermal science, and they will play significant roles in the global sustainable energy system.

Thermodynamic cycles are not only the core concepts of thermal science, but also key approaches to energy conversion and utilization. So far, power cycles and refrigeration cycles have been the only two general classes of thermodynamic cycles. While diverse types of systems have been developed to perform thermodynamic cycles, no new general classes of thermodynamic cycles have been proposed. Based on the basic principles of thermodynamics, here we propose and analyze a new general class of thermodynamic cycles named class 1 heating cycles (HC-1s). Two basic forms of HC-1s are obtained by connecting six essential thermodynamic processes in the proper order and forming a thermodynamic cycle. HC-1s present the simplest and most general approach to utilizing the temperature difference between a high-temperature heat source and a medium-temperature heat sink to achieve efficient medium-temperature heating and/or low-temperature cooling. HC-1s fill the gaps that have existed since the origin of thermal science, and they will play significant roles in energy conservation and emission reduction.

Counting in terms of cycles allows modeling many processes of Nature. We make use of a slight numerical incongruence within the numbering system to find a translational mechanism which connects sequential ↔ commutative properties of assemblies. The algorithms allow picturing the logical syntax Nature uses when reading the DNA. Ordering a collection on two different properties of its members will impose two differing sequences on the members. The coordinates of a point on a plane of which the axes are the two sorting orders sidestep the logical contradiction arising from the different linear assignments. During a reorder, elements aggregate into cycles. Using an etalon collection of simple logical symbols (which are pairs of natural numbers), which we reorder, we see typical movement patterns along the path of the string of elements that are members of the same cycle. We split the {value, position} descriptions of a natural number and observe the places the unit occupies at specific instances of time among its peers, while being a member of a cycle, under different orders prevailing. Which places elements occupy among their peers, under specific order conditions, is determined by numeric properties of the natural numbers that make up the element. The model presented is therefore tautologic, and can be compared to a hybrid of sudokus with the ultimate form of Rubik‘s cube. It is necessary for the reader to do some self-education on the matter of cycles as a prerequisite to understanding the working principle of the model. The contraption being a new development, it can’t have references in literature.One cannot lose a bet on the idea that sorting and ordering a collection of elementary logical elements will turn up typical patterns and that these archetypes of patterns will be of interest to Theoretical Physics, Chemistry, Biology, Information Theory, and some other fields, too.

Immune checkpoint inhibitors (ICI) are a promising form of immunotherapy that has significantly changed the therapeutic landscape for many advanced cancers. They have shown unique clinical benefit against a broad range of tumour types and a strong overall impact on survival in studied patient populations. However, there are still many limitations holding back this immunotherapy from reaching its full potential as a possible curative option for advanced cancer patients. A great deal of research is being undertaken in the hope of driving advancements in this area, building a better understanding of the mechanisms behind immune checkpoint inhibition and ultimately developing more effective, safer, and wider-reaching agents. Taking into account the current literature on this topic, this review aims to explore in depth the basis of the use of ICIs in the treatment of advanced cancers, evaluate its efficacy and safety, consider its current limitations, and finally reflect on what the future holds for this very promising form of cancer immunotherapy.

In the century and a half since Maxwell first conjured his “finite being” which Lord Kelvin subsequently dubbed a “daemon”, researchers have explored the connections between non-equilibrium thermodynamics, entropy, and information theory. In recent years various Thermodynamic Uncertainty Relations (TURs) have been derived to inform upon the relationship between the entropy production and the precision possible in thermodynamic machines and processes. In this paper the recently derived TURs are applied to the hypothetical thermodynamic economy as described by Parker [1]. The TURs define the lower bound on the total entropy production of the economy. Changes in this entropy production rate has consequences on the stability of the economic system and plays a central role in the business cycle. This new perspective has important implications for policy makers, researchers, and other economic actors.

The historic view of metadata as “data about data” is expanding to include data about other items that must be created, used and understood throughout the data and project life cycles. In this context, metadata might better be defined as the structured and standard part of documentation and the metadata life cycle can be described as the metadata content that is required for documentation in each phase of the project and data life cycles. This incremental approach to metadata creation is similar to the spiral model used in software development. Each phase also has distinct users and specific questions they need answers to. In many cases, the metadata life cycle involves hierarchies where latter phases have increased numbers of items. The relationships between metadata in different phases can be captured through structure in the metadata standard or through conventions for identifiers. Metadata creation and management can be streamlined and simplified by re-using metadata across many records. Many of these ideas are being used in metadata for documenting the life cycle of research projects in the Arctic.

The study aimed to determine the effect of heat stress (HS) on reproductive parameters [calving to first service (CTFS) and first service conception rate (FSCR)] and general physiological responses [rectal temperature (RT) and respiratory rate (RR)] in tropical Holstein Friesian dairy cows raised in Ratchaburi province, Thailand. Cows were divided into a moderate HS (n = 22) and a mild HS (n = 22) group. Cycling cows were detected and injected with PGF2α at the beginning of the experimental period. Reproductive and physiological parameters were recorded. The average temperature humidity indices experienced by the cows were 80.67 ± 0.79 and 77.81 ± 1.09 for the moderate and mild HS groups, respectively. Cows showed significantly lower RT and RR in the mild (38.47 ± 0.21°C and 41.04 ± 4.55 bpm, respectively) than in the moderate HS group (38.87 ± 0.15°C and 51.17 ± 10.52 bpm). Under mild HS, cows showed a better response to injection of PGF2α than those under moderate HS. The percentage of cows that ovulated after being induced by PGF2α and showed estrus signs was higher in the mild than the moderate HS groups (54.55% versus 18.18%). Furthermore, the FSCR of cows under mild HS tended to be higher than in the moderate HS group (54.55 % and 42.11%, respectively), while the average CTFS interval was significantly shorter under mild than moderate HS (69.47 ± 18.18 and 84.60 ± 27.68, respectively). These results indicate that HS impairs reproductive performance in cross-bred Holstein cows, especially in moderate HS conditions.

Age-related diseases (ARDs) are the leading cause of death worldwide, and contribute to 90% of mortality in developed countries. Interestingly, the mortality rates of individual ARDs increase exponentially with age. Processes described by the exponential growth function typically involve a branching chain reaction or, more generally, a positive feedback loop. Here I propose that each ARD is mediated by one or several positive feedback loops (vicious cycles). I then identify critical vicious cycles in five major ARDs: atherosclerosis, hypertension, diabetes, Alzheimer’s and Parkinson’s. I also propose that the progression of ARDs can be halted by selectively interrupting the vicious cycles and suggest the most promising targets. An evolutionary perspective is also offered.

Natural cycles underpin the very stuff of life. In this commentary we consider unnatural cycles: that is, anthropogenic activities which have a circularity, but whose nature is to have a detrimental effect on human health, exacerbating existing problems. Natural cycles have feedback loops, some of which have recently come to light, with an understanding that everything is connected in some way. In health, feedback loops are imperative in homeostatic mechanisms. However, in the unnatural cycle the feedback loops serve to reinforce (and in some cases amplify) negative problems. We offer a commentary on an unnatural cycle moving from air quality to lung function and back to air quality; we call this the lung disease unnatural cycle. We suggest where links occur, and where wider consideration of interactions between various disciplines can lead to breaking this unnatural (or vicious) cycle, changing it to a healthy cycle where individual health can be improved, along with better global scale outcomes. We suggest that many activities within this unnatural cycle occur within silos. However, the improved cycle incorporates joint activities at geological, health, and financial levels, to the mutual benefit of all, breaking the unnatural cycle, and improving health, life and financial costs.

Cholera is an acute enteric infectious disease caused by the Gram-negative bacterium Vibrio Cholerae. Despite a huge body of research, the precise nature of its transmission dynamics has yet to be fully elucidated. Mathematical models can be useful to better understand how an infectious agent can spread and be properly controlled. We develop a compartmental model describing a Human population, a bacterial population as well as a phage population. We show that there might be eight equilibrium points; one of which is a disease free equilibrium point. We carry out numerical simulations and sensitivity analyses and we show that the presence of phage can reduce the number of infectious individuals. Moreover, we discuss the main implications in terms of public health management and control strategies.

Climate change is one of the main issues that humanity is currently facing due to carbon dioxide emissions caused by the use of fossil fuels. Organic Rankine cycles may play an important role in reducing these emissions since they can be operated by using industrial waste heat of renewable energies. The present study presents a comprehensive bibliographic review of organic Rankine cycles. The study not only actualizes previous reviews that mainly focused on basic cycles operating on subcritical or supercritical conditions but also includes the analysis of novel cycles such as two-stage and hybrid cycles and the used fluids. Recuperative and regenerative cycles are more efficient than reheated and basic single-stage cycles. The use of two-stage cycles makes it possible to achieve higher thermal efficiencies and net power outputs of up to 20% and 44%, respectively, compared with those obtained with single-stage cycles. Theoretical studies show that hybrid systems, including Brayton and organic Rankine cycles, are the most efficient; however, they require very high temperatures to operate. Most organic Rankine cycle plants produce net power outputs from 1 kW up to several tens of kW, mainly using microturbines and plate heat exchangers.

Gestational Diabetes Mellitus (GDM) is related with adverse outcomes for both the mother and the offspring. Immune and senescence play a crucial role in GDM progression. This study aims to explore the diagnostic significance of immune-related senescence (IRS) genes in GDM. We used weighted gene co-expression network analysis (WGCNA) and single sample gene set enrichment analysis (ssGSEA) to compute the immune score and aging score in control and GDM samples. Machine learning identified core IRS genes. Then we performed unsupervised cluster analysis in GDM patients to explore immune infiltration. Finally, we validated the core genes in clinical samples. We used the intersection of MEblack module from WGCNA and differentially expressed genes (DEGs) to obtain the potential genes. Next, a univariate logistic regression model including 23 potential genes were constructed, and these genes were filtered by least absolute shrinkage and selection operator (LASSO) algorithm. There were 5 potential genes (COX17, RRAS2, RRAGC, CECR1, and TACC2), which defined as biomarkers, remained eventually, and the efficacy of these biomarkers was evaluated by nomogram. Finally, the results from both qRT-PCR and western blot analyses demonstrated CECR1 was down-regulated, while TACC2 was up-regulated in GDM placental tissue. Our study identified CECR1 and TACC2 as diagnostic biomarkers for GDM associating with immune and senescence, providing a new perspective on GDM progression.

Immune checkpoint inhibitors (ICI’s) are in the forefront of advanced Non Small Cell Lung Cancer (NSCLC) treatment. Still, only 27- 46% of patients respond to initial therapy with ICI’s and of those, up to 65% develop resistance within four years. After disease progression (PD), treatment options are limited, with 10% Objective Response Rate (ORR) to second or third-line chemotherapy. In this context, ICI rechallenge is an appealing option for NSCLC. Most data on the efficacy of ICI rechallenge are based on retrospective real-world studies of small, heavily pretreated, and heterogeneous patient groups. Despite these limitations, these studies suggest that ICI monotherapy rechallenge in unselected NSCLC patient populations who discontinued initial ICI due to PD is generally ineffective, with a median Progression-Free Survival (PFS) of 1.6-3.1 months and a Disease Control Rate (DCR) of 21.4%-41.6%. However, there is a subpopulation that benefits from this strategy, and further characterization of this subgroup is essential. Furthermore, immunotherapy rechallenge in patients who discontinued initial immunotherapy following treatment protocol completion and progressed after an immunotherapy-free interval showed promising efficacy, with a DCR of 75-81%, according to post-hoc analyses of several clinical trials. Future research of ICI rechallenge for NSCLC should focus on better patient stratification, to reflect the underlying biology of immunotherapy resistance more accurately.

We search for limit cycles in the dynamical model of two-species chemical reactions that contain seven reaction rate coefficients as parameters and at least one third-order reaction step, that is, the induced kinetic differential equation of the reaction is a planar cubic differential system. Symbolic calculations were carried out using the Mathematica (or, Wolfram language) mathematical program package, and it was also used for the numerical verifications to show the following facts: the kinetic differential equations of these reactions each has two limit cycles surrounding the stationary point of focus type in the positive quadrant. In the case of Model 1, the outer limit cycle is stable and the inner one is unstable that appears in a supercritical Hopf bifurcation. Moreover, the oscillations in a neighborhood of the outer limit cycle are slow-fast oscillations. In the case of Model 2, the outer limit cycle is unstable and the inner one is stable. With another set of parameters, the outer limit cycle can be made stable and the inner one unstable.

This paper studies pandemic viruses that spread during the period (1759–2020) according to solar activity cycles. Our findings and results include the following: (1) The severity of a pandemic correlates negatively with the strength of solar activity; (2) Pandemic viruses are classified into three types based on their compatibility with solar activity associations. Most of them spread through the quiet Sun, where viruses survive better in cold and rainy weather, and in stable geomagnetic fields without strong disturbances; (3) The emergence of new strains of influenza viruses was manifested in two ways. First, the annual epidemics due to antigenic drift. Second, pandemics recur every 1–12 solar cycles (about 11–120 years) due to viral reassortment of new subtypes, which results in antigenic shifts; (4) Pandemic viruses have two groups according to their recurring period: first, recurring in nine solar cycles; second, recurring in twelve solar cycles. Furthermore, we reassort pandemic viruses from their previous spread in the same periodic classification. Moreover, we derive a periodicity formula for each subtype of the pandemic virus as a spread date.

In the author's opinion, many global problems that face humanity - in the fields of education, medicine, management etc can be tackled more effectively if the cyclic nature of self-reproducing systems – including living beings – is taken into account. Summarizing the main physiological findings of the last decades on "adaptation reactions", one can very roughly say that the way of action which is effective in the sense of productive activity of people happens at the same time to be healthy, and it gives the participants of the process the feeling of happiness. The present paper represents a very short overview of the contemporary concepts of the adaptation reactions based on the fundamental understanding of their cyclic nature due to general properties of self-reproducing systems. One interesting feature of self-reproduction cycles is its first "phase of orientation" which was not discussed in detail in the past but plays a key role in the whole cycle.

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.

Meningitis is a severe disease associated with death in children under five with highest rates of infections under age of one. Vaccines for Neisseria meningitides and Haemophilus influenza are used to prevent the main causative agents of meningitis. Administration of H. influenzae type b (Hib) vaccine is recommended at 2, 4 and 6 months with a booster dose at 18 months. N. meningitidis has two commercially available vaccines, the pure polysaccharide is recommended at 24 months meanwhile the protein-conjugated vaccines at 12 months. We sought in this study to examine if coadministering the vaccines for the two main meningitis causing bacteria might be synergistic as a preliminary step towards the possibility of shuffling immunization schedule. So, we coadministered Hib vaccine with commercially available vaccines either quadrate (ACWY) polysaccharide meningococcal (Men) or conjugated meningococcal (Nim) vaccines in Balb/C mice (n = 6/group) and compared to each vaccine administered separately and controls. Thirty-five days post immunization, we measured specific antibodies titers. Hib vaccine increased Men antibody titers significantly for serotypes Y and W. When Hib vaccine was coadministrated with Nim, antibody titer for Y, W and A significantly increased. For serotype C, there was no significant difference in antibody titers among immunized groups. As for effect of meningococcal vaccines on Hib, Men significantly increased Hib antibody titers while Nim had no effect. Collectively, our data suggested that coadministration of Hib and Men or Nim vaccines was safe and had synergistic effect on immune responses elicited to both vaccines. Further studies are needed before immunization schedule modifications. Such immunization schedule recommendation should provide better protection against this life-threatening disease in young children.

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are significantly changing treatment strategies for human malignant diseases including oral cancer. Cancer cells usually escape from immune system and acquire proliferative capacity and invasive/metastatic potential. We have focused on the two immune checkpoints, PD-1/PD-L1 and CD47/SIRPα in the tumor microenvironment of oral squamous cell carcinoma (OSCC), and performed a retrospective analysis of the expression of seven immune-related factors (PD-L1, PD-1, CD4, CD8, CD47, CD56 and CD11c), and examined their correlation with clinicopathological status. As a result, there were no significant findings relating seven immune-related factors and several clinicopathological statuses. However, the immune-checkpoint related factors (PD-1, PD-L1, CD47) were highly expressed in non-keratinized epithelium-originated tumors when compared to those in keratinized epithelium-originated tumors. It is of interest that immunoediting via immune checkpoint-related factors was facilitated in non-keratinized sites. Several researchers reported that keratinization of oral mucosal epithelia affected the immune response, but our present finding is the first study to show a difference of the tumor immunity in the originating-epithelium of OSCC, keratinized or non-keratinized. Tumor immunity, an immune escape status of OSCC might be different in the originating-epithelium, keratinized or non-keratinized.

Oncolytic virotherapy is a promising immunotherapy approach for cancer treatment, utilizing viruses to preferentially infect and eliminate cancer cells while stimulating immune responses. In this review we synthesize current literature on the molecular circuits of immune sensing and response to oncolytic virotherapy; focusing on viral DNA or RNA sensing by infected cells, cytokine and danger-associated signal sensing by neighboring cells, and subsequent downstream activation of immune pathways. The sequential sense-and-response mechanisms involve the triggering of molecular sensors by viruses or infected cells to activate transcription factors and related genes for a breadth of immune responses. We describe how molecular signals induced in the tumor upon virotherapy can trigger diverse immune signaling pathways, activating both antigen-presenting cell-based innate and T cell-based adaptive immune responses. Insights into these complex mechanisms provide valuable knowledge for enhancing oncolytic virotherapy strategies.

Response of tomato and eggplant to continuous lighting (CL) and abnormal light/dark (L/D) cycles was studied to elucidate the role of the absence of the dark period in the diurnal cycle in the development of leaf injuries under CL. Four light treatments were set: 16/8 h (control), 24/0 h (CL), 6/6 h, and 24/24 h (abnormal L/D cycles). These light treatments provided average daily light integrals of 17.3, 25.9, 13.0 and 13.0 mol m-2 day-1, respectively. Results of this work have shown that in both tomato and eggplant abnormal L/D cycles caused photoinhibition and leaf injuries similar to those in CL-grown plants. Induced defense mechanisms were not strong enough to contend against oxidative stress caused by light treatments that provided plants with even smaller DLI than 16/8 h photoperiod did. Half time during abnormal L/D cycles were dark periods. Despite these facts, abnormal L/D cycles were injurious. It is concluded that photooxidative stress induced by CL can not be attributed to excessive DLI or the continuity of light itself (the absence of dark periods). Therefore, we believe that the hypothesis suggesting circadian asynchrony to be the main triggering factor of CL-induced leaf injuries is the most plausible among many others proposed.

Thermal-based actuators are known for generating large force and displacement strokes at mesoscale (millimeter) regime. In particular, two-phase thermal actuators are found to benefit from the scaling laws of physics at mesoscale to offer large force and displacement strokes; but they have low thermal efficiencies. As an alternative, a combustion-based thermal actuator is proposed and its performance is studied in both open and closed cycle operations. Through a physics-based lumped-parameter model, we investigate the behavior and performance of the actuator using a spring-mass-damper analogy and taking an air standard cycle approach. Three observations are reported: (1) the mesoscale actuator can generate peak forces of up to 400 N and displacement strokes of about 16 cm suitable for practical applications; (2) an increase in heat input to the actuator results in increasing the thermal efficiency of the actuator for both open and closed cycles; and (3) for a specific heat input, both the open and closed cycle operations respond differently \textemdash different stroke lengths, peak pressures, and thermal efficiencies.

Fermented foods have long been known to have immunomodulatory capabilities and fermentates derived from the lactic acid bacteria of dairy products can modulate the immune system. We have used skimmed milk powder to generate novel fermentates using Lb. helveticus strains SC234 and SC232 and we demonstrate here that these fermentates can enhance key immune mechanisms that are critical to the immune response to viruses. We show that our novel fermentates SC234 and SC232 can positively impact on cytokine and chemokine secretion, nitric oxide (NO) production, cell surface marker expression, and phagocytosis in macrophage models. We demonstrate that fermentates SC234 and SC232 increase the secretion of cytokines IL-1β, IL-6, TNF-α, IL-27, and IL-10, promote an M1 proinflammatory phenotype for viral immunity via NO induction, decreases chemokine expression of Monocyte Chemoattractant Protein (MCP), increasing cell surface marker expression, and enhance phagocytosis in comparison to their starting material. These data suggest that these novel fermentates have potential as novel functional food ingredients for the treatment, management and control of viral infection.

Antler is the fastest growing tissue. Because is based on proto-oncogenes, to avoid the risk of cancer, antlers evolved strong anticancer mechanisms, and thus its extract (DVA) is effective also against the few human tumours studied so far. We assessed whether DVA is a general anticancer compound testing direct effects in cells of different tumours: glioblastoma (GBM), colorectal and breast cancer, and leukaemia. DVA reduced viability of tumour but not healthy cells. Mobility decreased at least at the longest test (72 h). Intraperitoneal/oral 200 mg DVA/kg administration in GBM xenograft mice for 28 d reduced tumour weight 66.3% and 61.4% respectively, and also spleen weight. In addition, tumours treated with DVA showed symptoms of liquefactive necrosis. Serum cytokines showed DVA up-regulated factors related with tumour fighting and down-regulated those related with inducing immune tolerance to the tumour. DVA shows general anticancer effects in the lines tested and, in GBM mice, also strong indirect effects apparently mediated by the immune system.

Abstract: Lipidic carriers employed for the entrapment, encapsulation and precise targeting the bioactive compounds offer significant advantages to the biomedical, pharmaceutical, nutraceutical and cosmeceutical industries. These lipid and phospholipid-based vesicles can improve the solubility, permeation, pharmacokinetics, pharmacodynamics and bioavailability of the encapsulated material. As a matter of fact, nano-sized phospholipid vesicles have attained the highest success rate in commercialization among the available drug encapsulation technologies. Nevertheless, developing industrially acceptable products still remains a challenge. Among the main disadvantages of conventional lipidic carriers are their instability in the biological environments, and their sensitivity to changes in the pH, temperature and enzymes. To overcome these problems, the new generation of phospho/lipid-based carrier systems was developed using ingredients from microorganisms living in extremely harsh environments (i.e., archeaeobacteria). The present entry aims to review unique features of archaeolipids and recent developments in their application for the encapsulation of genetic material as well as their role and function as adjuvants and vaccine candidates.

Fowlpox virus (FPV) has been used as a vector for many years. To date, surprisingly, very little data exist on the persistence of fowlpox vaccines in chicken tissues, or what kind of immune cells respond to the vaccination at the site of inoculation. Although both humoral and cellular mediated immunity (CMI) play a part in overall immunity against FPV, little is known regarding the cell-mediated immune responses to FPV infection. The main aim of this paper was to measure persistence of the recombinant fowlpox vaccine in the skin tissues following vaccination. The results showed that the recombinant FPVs do not persist for long, and are cleared by 6 days post-vaccination (dpv). The response of immune cells (macrophages, B cells, CD4+ and CD8+ T cells) that infiltrating the site of vaccination was estimated.

Wireless Sensor Network (WSN) and the sensing devices are considered part of the core components of the Internet of Things (IoT). Hence, the modeling of IoT-WSNs is fundamental to having a better understanding, management, and deployment of this kind of technology. A fundamental issue in WSN is energy consumption due to the inherent limitations of this resource in the sensor devices. On the other hand, several issues arise in heterogeneous scenarios due to the coexistence of different sensor devices. Therefore, the modeling process becomes challenging and must consider the different transmission and operation cycles and modes that the transmission protocol implements to assure successful functioning in terms of transmission, synchronization, and energy savings. A duty-cycled MAC WSN protocol (PSA-MAC) has been modeled based on a pair of two-dimensional Discrete-Time Markov Chain (2D-DTMC), whose solution in terms of stationary probability distribution is used by expressions that have been derived to evaluate the energy consumption of sensor devices that could be used for WSN-based IoT applications. Analytical results of average energy consumption are obtained, where the synchronization, data, and sleep periods of a full transmission cycle are considered in a heterogeneous scenario with different node classes and priority assignments. Also, the normal and awake operation cycles are considered to assure synchronization and energy savings. Moreover, the transmission schemes of SPT (transmission of single packets) and APT (transmission of packets in aggregation) are also considered in the model. These results are validated through discrete event-based simulations, and the obtained results are accurate.

This study aims to better understand students who attend the Basic Vocational Training Cycles (FPB) regarding the measures to ensure diversity. This quantitative research project approximates the perception of students concerning their passage through their previous studies and their satisfaction and goals after finishing the school year. The sample con-sists of 352 students from Cordoba (Spain). A questionnaire has been used which follows the CIPP model. After the exploratory factor analysis was completed with the different groups of items and their descriptive analysis, various tests were carried out to consider the hypotheses (Pearson's correlation (r), one-factor analysis of variance and repeated ANOVA measures). The results indicate that the educational interest of the students is ac-ademic and professional. Likewise, there is no relationship detected between the appear-ance of socio-professional goals and average academic levels and the attributions with re-spect to repetitions of previous courses, although these goals vary depending on the satis-faction shown by the students with respect to the cycles. We conclude that the course of the FPB influences the adoption of decisions regarding academic-professional projects.

One of society’s greatest challenges is sequestering vast amounts of carbon to avoid dangerous climate change without driving competition for land and resources. Here we assess the potential of an integrated approach based on enhancement of natural biogeochemical cycles in agro-ecosystems that stimulate carbon capture and storage while increasing resilience and long-term productivity. The method integrates plant photosynthesis in the form of (cover) crops and agroforestry which drives carbon capture. Belowground plant-carbon is efficiently stored as stable soil organic carbon (SOC). Aboveground crop and tree residues are pyrolyzed into biochar, which is applied to the soil reducing carbon release through decomposition. Enhanced weathering of basalt powder worked into the soil further captures and stores carbon, while releasing nutrients and alkalinity. The integrated system is regenerative, through enhanced virtuous cycles that lead to improved plant capture, biomass storage and crop yield, the prerequisites for large-scale carbon sequestration along with food security.

In February 2004, the Food and Drug Administration (FDA) was the first to approve the combination of cisplatin (CDDP) and pemetrexed (PEM) as standard first-line chemotherapy for untreated, unresectable malignant pleural mesothelioma (MPM). However, after that approval, no progress was made in the standard first-line treatment of MPM for almost 15 years. Positive results from a phase 3 study (Mesothelioma Avastin Cisplatin Pemetrexed Study: MAPS) verifying the effect of bevacizumab, an anti-angiogenesis agent added to CDDP/PEM for unresectable MPM, were published in The Lancet in December 2015; however, this did not lead to approval by national drug regulatory agencies. Furthermore, no second-line treatment was established for cases refractory to CDDP/PEM. In August 2018, the Pharmaceuticals and Medical Devices Agency of Japan was the first in the world to approve monotherapy with nivolumab, an immune checkpoint inhibitor (ICI), for previously unresectable, advanced, or recurrent MPM. Following Japan, in October 2020, the FDA approved the combination of nivolumab and ipilimumab for the treatment of previously untreated, unresectable MPM. In this article, we review the transition of drug treatment for MPM, in light of the historical background, focusing on the benefits of ICIs.

This article explores the geothermal resources of Kazakhstan's Zharkent Basin, with a specific focus on the high-temperature geothermal sources in the Almaty region of Southern Kazakhstan. The research aims to analyze the energy characteristics of the Organic Rankine Cycle (ORC) for harnessing low-enthalpy geothermal energy for small-scale electricity generation. A detailed thermodynamic model was developed, employing R134a as the working fluid. An in-depth analysis of the Zharkunak field (Zharkent, Almaty region) revealed that well 5539, with its notably high temperatures, offers the highest potential for geothermal electricity production, achieving an annual output of approximately 10,371 MWh. The total electric power output from the studied wells in the region is estimated at 20,111 MWh annually, representing a significant contribution towards sustainable energy production and reducing reliance on traditional coal-fired power plants. The study concludes that the Organic Rankine Cycle is not only a viable and efficient technology for utilizing low-enthalpy geothermal resources to generate electricity on a small scale, but also a key player in enhancing energy independence. By leveraging local geothermal energy, the Almaty region can significantly reduce its reliance on external energy sources, thereby fostering sustainable development and reducing environmental impacts.

This article explores the important role of traditional shipyards in the global maritime industry, covering aspects of construction, repair, and maintenance. With the advent of faster manufacturing techniques, traditional shipyards face important challenges such as planning errors, coordination problems, delivery delays, and underutilization of technology, which results in high costs, reduced productivity, and prolonged projects. The application of Manufacturing Cycle Efficiency (MCE) emerged as an important solution to significantly increase production efficiency. MCE empowers shipyards to deal effectively with waste, bottlenecks, and disruptions, thereby increasing performance, competitiveness, and profitability. Using a comprehensive approach that uses both qualitative and quantitative methods, including field surveys, and in-depth interviews in the traditional shipyards industry, this research identifies Non-Value-Added (NVA) processes, conducts process mapping, and calculates MCE. The findings reported in this article underscore the significant wastage in the production process, indicating an urgent need for improvement, given the current average MCE value of 67.08%, indicating considerable room for improvement. This article provides innovative perspectives on optimizing the traditional shipyards industry through production cycle efficiencies while offering actionable recommendations. Key focus areas include integrating management systems, adopting advanced technologies, and implementing sustainable strategies to improve MCE, especially by reducing non-value-added time wastage, such as inspection and storage. By implementing strategies that optimize production, minimize waste, and overcome the challenges of global competition, this research contributes to improving MCE. In conclusion, this study is an invaluable guide for industry stakeholders, enabling them to enhance their competitiveness and adapt effectively to a dynamic business environment.

The response of carbon fixation in C3 plants to elevated CO2 is relatively larger when photosynthesis is limited by carboxylation capacity (VC) than when limited by electron transport (J). Recent experiments under controlled, steady-state conditions have shown that photosynthesis at elevated CO2 may be limited by VC even at limiting PPFD. These experiments were designed to test whether this also occurs in dynamic field environments. Leaf gas exchange was recorded every 5 minutes using two identical instruments both attached to the same leaf. The CO2 concentration in one instrument was controlled at 400 mol mol-1 and one at 600 mol mol-1. Leaves were exposed to ambient sunlight outdoors, and cuvette air temperatures tracked ambient outside air temperature. The water content of air in the leaf cuvettes was kept close to that of the ambient air. These measurements were conducted on multiple, mostly clear days for each of three species, Glycine max, Lablab purpureus, and Hemerocallis fulva. The results indicated that in all species, photosynthesis was limited by VC rather than J at both ambient and elevated CO2 both at high midday PPFDs and also at limiting PPFDs in the early morning and late afternoon. During brief reductions in PPFD due to midday clouds, photosynthesis became limited by J, The net result of the apparent deactivation of Rubisco at low PPFD was that the relative stimulation of diurnal carbon fixation at elevated CO2 was larger than would be predicted when assuming limitation of photosynthesis by J at low PPFD.

Fibrosis is an important health problem and its pathogenetic activation is still largely unknown. It can develop either spontaneously or, more frequently, as a consequence of various underlying diseases, such as chronic inflammatory autoimmune diseases. Fibrotic tissue is always characterized by mononuclear immune cells infiltration. The cytokine profile of these cells shows clear proinflammatory and profibrotic characteristics. Furthermore, the production of inflammatory mediators by non-immune cells, in response to several stimuli, can be involved in the fibrotic process. It is now established that defects in the abilities of non-immune cells to mediate immune regulation may be involved in the pathogenicity of a series of inflammatory diseases. The convergence of several, not yet well identified, factors results in the aberrant activation of non-immune cells, such as epithelial cells, endothelial cells and fibroblasts, that producing pro-inflammatory molecules, exacerbate the inflammatory condition leading to the excessive and chaotic secretion of extracellular matrix proteins. However, the precise cellular mechanisms involved in this process have not yet been fully elucidated. In this review we explore the latest discoveries on the mechanisms that initiate and perpetuate the vicious circle of abnormal communications between immune and non-immune cells, responsible for fibrotic evolution of inflammatory autoimmune diseases.

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

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Opossums, native to the Americas, are unique marsupials with over 100 species. The Common Opossum and Virginia Opossum are notable species. They are nocturnal, omnivorous, and adapt to various habitats. Their reproduction involves a short gestation and marsupial pouch development. Despite their ecological benefits like seed dispersal and insect control, their proximity to human habitats exposes them to pathogens, posing public health risks. These include protozoa, helminths, and arthropods that can spread zoonotic parasites and vector-borne diseases. The marsupial immune system, including opossums, is complex, rivaling eutherian mammals. Key immune genes were identified in the grey short-tailed opossum genome. CD1 protein and VpreB surrogate light chain were also found. Marsupials are proposed as ideal models for studying developmental immunology. A West Indian opossum (Didelphis marsupialis) was found and examined. Blood tests revealed abnormalities, including a low white blood cell count and signs of anemia. The results contribute to understanding the species’ health and adaptability in the wild.

In light of the recent pandemic, several COVID-19 vaccines were developed, tested and approved in a very short time, a process that otherwise takes many years. Above all, these efforts have also unmistakably revealed the capacity limits and potential for improvement in vaccine production. This review aims to emphasize recent approaches for targeted rapid adaptation and production of vaccines from an interdisciplinary multifaceted perspective. Using literature research, stakeholder analysis and a value proposition canvas, we reviewed technological innovations on the pharmacological level, formulation, validation and resilient vaccine production to supply bottlenecks and logistic networks. We identified four main drivers to accelerate the vaccine product life cycle: computerized candidate screening, modular production, digitized quality management and a resilient business model with corresponding transparent supply chains. In summary, the results presented here can serve as a guide and implementation tool for flexible, scalable vaccine production to respond swiftly to pandemic situations in the future.

Due to slow progression and susceptibility to radical forms of treatment low-grade PC is associ-ated with high overall survival (OS). With the clinical progression of PC the therapy is getting more complex. The immunosuppressive tumor microenvironment (TME) makes PC a difficult target for most immunotherapeutics. Its general immune resistance is established by i.e. immune evasion through Treg cells, synthesis of immunosuppressive mediators, and defective expression of surface neoantigens. The success of sipuleucel-T in clinical trials initiated several other clinical studies that specifically target the immune escape of the tumor and eliminate the immunosuppres-sive properties of TME. In the settings of PC treatment, this can be commonly achieved with radi-ation therapy (RT). Also, focal therapies usually applied for localized PC, such as high-intensity focused ultrasound (HIFU) therapy, cryotherapy, photodynamic therapy (PDT), or irreversible electroporation (IRE) were shown to boost anti-cancer response. Nevertheless, the present guide-lines restrict their application to localized and low-grade PC. This review explains how RT and focal therapies enhance the immune response. We also provide data supporting the combination of RT and focal treatments with immune therapies.

A portable, electrical impedance spectroscopy device to monitor the bioimpedance’s resistive component of beef meat by injecting a sinusoidal current of 1mA at 65.5 kHz was developed. In 4 slaughtered beef both right and left longissimus dorsi muscles where trimmed and left muscle portion was frozen to -18° C up to 7^th day while right one was meantime maintained at 5° C. Median value of specific resistivity of not-frozen sample was about twice Ω cm^-1 with respect of that of frozen-thawed sample (P = 0.004). It was concluded that the device is reliable to monitoring the ripening of beef meat in situ.

The study investigates the evolution of soil pore structure and shear strength deterioration in compacted clayey soil under controlled wetting and drying (wd) cycles, which are expected to become more frequent due to climate change. Thirty soil samples were compacted at optimal moisture content and 90% of maximum dry density. These samples were then subjected to 0, 1, 5, 10, and 15 controlled wd cycles from saturation to the wilting point, and volumetric changes were recorded during each cycle. After the wd treatment, the soil samples were scanned using X-ray Computed Tomography (CT) at 50 μm resolution and then sheared under unconsolidated-undrained and consolidated-undrained conditions in a triaxial test. Significant shrinkage and swelling of soil samples were observed during wd cycles, with average volumetric strain fluctuating between +12% at saturation and -5% at the wilting point. X-ray CT visualisation and analysis revealed higher porosity, more prominent pores and increased pore length in soil samples with increasing wd cycles. Both undrained and effective soil shear strength markedly decreased with increasing wd cycles. CT-derived macroporosity and pore length were significant predictors of the soil's undrained and effective shear strength when exposed to wd cycles. The findings emphasise the considerable impact of climate change, specifically wd cycles, on clayey soil, highlighting the need for consideration in the design of earth-based infrastructure.

Predominantly antibody deficiencies (PAD) represent the most common type of primary immu-nodeficiencies in humans, characterized by a wide variation in disease onset, clinical manifesta-tions, complications and outcome. Considering that the prevalence of PAD in Greece is unknown and there is limited knowledge on clinical and laboratory characteristics of affected patients, we conducted a nationwide study, including 153 patients (male/female: 66/87; median age: 43.0 years; range: 7.0-77.0) diagnosed and/or followed-up between April 2007 to September 2023. Furthermore, we classified our cohort into five Groups according to their medical history, im-munoglobulin levels, and CTLA4-mutational status: 123 had common variable immunodeficien-cy (CVID), 12 with CVID-like disease (with a history of a previous B-cell depletion immunother-apy for autoimmune or malignant disease), seven with combined IgA and IgG subclass deficien-cies, five with immune dysregulation syndrome and CTLA4 defects, and six with unclassified hypogammaglobulinemia. We demonstrated a remarkable delay of PAD diagnosis, several years after the onset of related symptoms (median: 9.0 years, range: 0-43.0). Family history of PAD was only 11.8%, with the majority of patients considered sporadic cases. Most patients were diag-nosed in the context of a diagnostic work-up for recurrent infections, or recurrent/resistant auto-immune cytopenias. Interestingly, ten patients (5.6%) had no history of infection, diagnosed due to either recurrent/resistant autoimmunity, or during a work-up of their medical/family history. Remarkable findings included an increased prevalence of lymphoproliferation (60.1%) and atopy (24.2%), while 39 patients (25.5%) developed bronchiectasis and 16 (10.5%) granulomatous dis-ease. Patients with CTLA4 defects displayed a variable clinical phenotype at diagnosis, with four patients diagnosed during a work-up of re-current infections, while one also displayed a massive splenomegaly. Cancer was a common complication in our cohort (25 patients, 16.3%), with B-cell malignancies representing the most common neoplasms (56.7%). Our findings indicate the necessity of awareness about PAD and their complications, aiming for early diagnosis and appropriate management of affected patients

Increasing evidence points to host Th17 inflammatory responses as contributing to the severe lung pathology and mortality of lower respiratory tract infections from coronaviruses. This includes host inflammatory and cytokine responses to COVID-19 caused by the SARS-2 coronavirus (SARS CoV2). From studies conducted in laboratory animals, there are additional concerns about immune enhancement and the role of potential host immunopathology resulting from experimental human COVID-19 vaccines. Here we summarize evidence suggesting there may be partial overlap between the underlying immunopathologic processes linked to both coronavirus infection and vaccination, and a role for Th17 in immune enhancement and eosinophilic pulmonary immunopathology. Such findings help explain the link between viral-vectored coronavirus vaccines and immune enhancement and its reduction through alum adjuvants. Additional research may also clarify links between COVID-19 pulmonary immunopathology and heart disease.

Extracellular vesicles (EV) released by tumor cells are a major aspect of the resistance-associated secretory phenotype (RASP), by which immune evasion can be established. Heat shock proteins (HSPs) are an evolutionarily conserved family of molecular chaperones, which stabilize proteins, minimize protein misfolding and aggregation within the cell, besides facilitating protein translocation, refolding and degradation. (i) Releases of extracellular HSPs (ex-HSP) and EV-associated HSPs (EV-HSP) are essential in RASP, by which molecular cotransfer of HSPs with oncogenic factors into recipient cells can promote cancer progression and resistance against stress such as hypoxia, radiation, chemicals, and immune system. (ii) RASP of tumor cells can eject anticancer drugs, molecularly targeted therapeutics, and immune checkpoint inhibitors with EVs. (iii) Cytotoxic lipids can be also released from tumor cells as RASP. Nevertheless, ex-HSP and EV-HSP can play immunostimulatory and immunosuppressive roles by binding to receptors such as LRP1/CD91/A2MR, scavenger receptors, and toll-like receptors expressed on recipient cells. Liquid biopsy of HSPs in body fluids may be useful in diagnosis, prognosis, and treatment in cancer. Regarding HSP90-targeted therapeutics, we summarize the pros, cons, and problem solutions in this review. Although production of HSPs are canonically induced by heat shock factor 1 (HSF1) and hypoxia-inducible factor 1 (HIF-1), recent studies discovered that production of HSPs is also regulated by matrix metalloproteinase 3 (MMP3) and heterochromatin protein 1 (HP1) and production of cochaperone CDC37 is reciprocally regulated by myeloid zinc finger 1 (MZF1) and SCAN-D1.

Fermented foods and ingredients, including fermentates derived from lactic acid bacteria (LAB) in dairy products, can modulate the immune system. Here we describe the use of reconstituted skimmed milk powder to generate novel fermentates from Lactobacillus helveticus strains SC232, SC234, SC212, and SC210, and from Lacticaseibacillus casei strains SC209 and SC229, and demonstrate using in vitro assays that these fermentates can differentially modulate cytokine secretion by bone marrow derived dendritic cells (BMDCs) when activated with either the viral ligand, loxoribine, or an inflammatory stimulus, lipopolysaccharide. Specifically, we demonstrate that SC232 and SC234 increase cytokines IL-6, TNF-α, IL-12p40, IL-23, IL-27 and IL-10, and decreased IL-1β in primary bone marrow derived dendritic cell (BMDCs) stimulated with a viral ligand. In contrast exposure of these cells to SC212 and SC210 resulted in increased IL-10, IL-1β, IL-23, and decreased IL-12p40 following activation of the cells with the inflammatory stimulus LPS. Interestingly SC209 and SC229 had little or no effect on cytokine secretion by BMDCs. Overall, our data demonstrates that these novel fermentates have specific effects and can differentially enhance key immune mechanisms that are critical to viral immune responses, or can suppress responses involved in chronic inflammatory conditions, such as Ulcerative Colitis (UC), and Crohn’s disease (CD).

This paper presents some aspects of command and control of the new generation of machines-tools with numerical control. A problem faced by numerical control programmers is related to the length (relatively long) of the programs, with implications in the costs and duration of the manufacturing preparation. A method of reducing the main program and other redundant expenses is the introduction and use of processing cycles and subroutines for automatic calculation of the cutting tool trajectory, a fact that also allows the optimization and simplification of numerical control programming on flexible order manufacturing systems numeric. The method involves the use of predefined cycles and appropriate subroutines in order to improve the efficiency of the programming activity in a balanced way. It is a new and rapid method for optimize the structure of program using the numerical subroutine for command the movement of tool, in our case, with application for turning and milling.

Exposure of experimental rodents to controlled cycles of light, food, and temperature is important when investigating alterations in circadian cycles that profoundly influence health and disease. However, applying such stimuli simultaneously is difficult in practice. Our aim was to design, build, test, and open-source describe a simple device that subjects a conventional mouse cage to independent cycles of physiologically relevant environmental variables. The device is based on a box enclosing the rodent cage to modify the light, feeding, and temperature environments. The device provides temperature-controlled air conditioning (heating or cooling) by a Peltier module and includes programmable feeding and illumination. All functions are set by a user-friendly front panel for independent cycle programming. Bench testing with a model simulating the CO2 production of mice in the cage showed: a) suitable air renewal (by measuring actual ambient CO2), b) controlled realistic illumination at the mouse enclosure (measured by a photometer), c) stable temperature control, and d) correct cycling of light, feeding, and temperature. The cost of all the supplies (retail purchased by e-commerce) was < 300 US$). Detailed technical information is open-source provided, allowing for any user to reliably reproduce or modify the device. This approach can considerably facilitate circadian research since using one of the described low-cost devices for any mouse group with a given light-food-temperature paradigm allows for all the experiments to be performed simultaneously, thereby requiring no changes in the light/temperature of a general-use laboratory.

In order to study the acoustic emission characteristics of sandstone under the action of the high temperature-water cooling cycle, the RMT-150B electro-hydraulic servo rock test system and the DS-5 acoustic emission detection and analysis system were used to conduct a single analysis of the sandstone after the high temperature-water cooling cycle. Experimental study on acoustic emission characteristics under axial compression, analyzing the deformation, strength and acoustic emission characteristics of sandstone under different temperatures and cycles. The results of the study show that the high temperature-water cooling action causes changes in the physical properties of the sandstone. The expansion rate of the rock sample decreases first and then increases when the temperature rises, and the strength first increases and then decreases. The number of cycles has little effect on the physical properties of the rock sample; sandstone acoustic emission ringing count increases with the increase of temperature and cycle times, acoustic emission activities become more frequent with the loading process; with the increase of cycle times and temperature, acoustic emission ringing counts and accumulative acoustic emission energy appear earlier The rock sample enters the elastic deformation stage ahead of schedule, the yielding period increases, and the rock sample presents a trend of transition from brittle failure to ductile failure; the ringing count and cumulative energy increase with the increase in temperature and cycle times, and the high-energy ringing count and cumulative energy increase. The simultaneous sharp increase of the rock sample is the harbinger of the failure and instability of the rock sample.

This paper develops a chemical model for a closed constant volume combustion of gaseous mixtures of methane and hydrogen. Since the combustion is strongly depending on temperature, pressure and fuel composition, they were chosen the actual corresponding thermodynamic systems using this kind of combustion, respectively the spark ignition reciprocating engines in order to evaluate the combustion parameters and exhaust flue gases composition. The actual cycles impose extra restrictive operational conditions through the engine volumetric compression ratio, the geometry of combustion volume, the mode to prepare the mixture of methane and hydrogen, the cooling system and the delivered power. The chemical model avoided the unknown influences in order to explain accurately the influence of hydrogen upon the constant volume combustion and flue gases composition. The model adopted simplifying hypotheses, respectively isentropic compression and expansion processes, closed constant volume combustion developed by two successive steps obeying to the energy and mass conservation laws and, flue gases exhaust described also by two steps, i.e. an isentropic expansion through the flow section of exhaust valves followed by a constant pressure stagnation (this succession is corresponding in fact to a throttling direct process). The chemical model supposed the homogeneous mixtures of gases with variable heat capacities function of temperatures, the Mendeleev - Clapeyron ideal gas state equation and, the variable chemical equilibrium constants for chosen chemical reactions. It was assumed that the flue gases chemistry is prevailing during the isentropic expansion and flue gases exhaust and has mainly a thermal ground. The chemical model allowed evaluation of flue gasses composition and of noxious emissions.

Cancer-associated cachexia (CAC) is a debilitating condition marked by muscle and fat loss, unresponsive to nutritional support, and contributes significantly to morbidity and mortality in patients with cancer. Immune dysfunction, driven by cytokine imbalance, contributes to CAC progression. This review explores the potential relationship between CAC and anti-cancer immune response in pre-clinical and clinical studies. Pre-clinical studies showcase the involvement of cytokines like IL-1β, IL-6, IL-8, IFN-γ, TNF-α, and TGF-β, in CAC. IL-6 and TNF-α, interacting with muscle and adipose tissues, induce wasting through JAK/STAT and NF-κB pathways. Myeloid-derived suppressor cells (MDSCs) exacerbate CAC by promoting inflammation. Clinical studies confirm elevated pro-inflammatory cytokines (IL-6, IL-8, TNFα) and immune markers like neutrophil-to-lymphocyte ratio (NLR) in patients with CAC. Thus, immunomodulatory mechanisms involved in CAC may impact the anti-neoplastic immune response. Inhibiting CAC mechanisms could enhance anti-cancer therapies, notably immunotherapy. R-ketorolac, a new immunomodulator, reversed weight loss and increased survival in mice. Combining these agents with immunotherapy may benefit patients with cancer experiencing CAC. Further research is vital to understand the complex interplay between tumor-induced immune dysregulation and CAC during immunotherapy.

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

Studies on the characteristics of hazardous air pollutants (HAPs) in the emissions of medium-duty diesel trucks are significantly insufficient compared to that on heavy-duty trucks. This study investigates the characteristics of regulated pollutants and HAPs such as volatile organic compounds (VOCs), aldehydes, and polycyclic aromatic hydrocarbons (PAHs), and estimates non-methane hydrocarbon (NMHC) speciation in the emissions of medium-duty diesel trucks. Ten medium-duty diesel trucks conforming to Euros 5 and 6 were tested for worldwide harmonized light duty driving test cycle (WLTC), new European driving cycle (NEDC), constant volume sampler (CVS)-75, and National Institute of Environmental Research (NIER)-9 using a chassis dynamometer. CO and NMHC emissions were the highest in the NEDC because of its longer low-speed driving time. NOx emissions were the highest in WLTC owing to the influence of thermal NOx in the high-speed phase. Alkanes dominated non-methane volatile compound (NMVOC) emissions owing to the low reaction of the diesel oxidation catalyst. After-treatment system, driving, and engine conditions influenced the individual components of NMVOC emissions. Formaldehyde emissions were the highest among aldehydes irrespective of driving cycles. By sampling the particle-phase of PAHs, we detected benzo(k)fluoranthene and benzo(a)pyrene and estimated the concentrations of the gas-phase PAHs with models to obtain the total PAH concentrations. The toxic equivalency quantities of benzo(k)fluoranthene and benzo(a)pyrene from NIER-9 (cold) for both Euro 5 and Euro 6 vehicles were more than five times higher than that of NIER (hot) and NEDC. In the case of NMHC speciation, formaldehyde emissions were the highest in all the driving cycles. Formaldehyde and benzene must be controlled in the emissions of medium-duty diesel trucks to reduce their health threats. The results of this study will aid in establishing a national emission inventory system for HAPs of mobile sources in Korea.

Development of non-conventional hybrids (NCHs) responds to the demand for the Elotes Occidentales 'EO' race for production of pozole. The effect of: crop cycle (2019, 2020 and 2021) on physical characteristics, flowered grain quality and phytochemical content of two HNC (Pz1 and Pz2) of pozolero maize, as well as the effect of the presence or absence of pedicel, type of pollination (open and controlled, 2019), and progenitor lines (female and male, 2020) on flowered grain quality and content of phytochemical compounds were evaluated. Size, hardness, color, total phenols and anthocyanins in unprocessed grain were determined, and yield, volume and puncture strength in flowered grain. Results were analyzed with a factorial arrangement in a completely randomized design. There were significant differences (p≤0.05) in most of the variables studied by effect of crop cycle and genotype. NCHs had large grains (40 g 100 grains-1), soft endosperm (IF> 60), pink-purple color, and phenol and anthocyanin contents similar to those reported for the 'EO' race. The presence or absence of the pedicel did not affect flowered grain quality. Controlled pollination favored anthocyanin synthesis. The anthocyanin content of NCHs was determined by the female line. Thermal processing reduced anthocyanins by 60%; however, they leached into the flowering broth, so that the pozole made from NCHs improves the nutraceutical value of the pozole, relative to that of pozole made with Cacahuacintle maize.

Microbial populations involved in forming the distinctive precipitates of the S, Fe, Mn, and Ca cycles in the San Diego River watershed reflect an interplay between mineralogy of the rocks in the watershed, sparse rainfall, ground- and surface-water anoxia, and runoff of high sulfate, treated imported water. In the less developed headwaters, Temescal Creek tributary emerges from pyrite-bearing metamorphic rocks, and thus exhibits both an oxidized Fe and reduced S cycle. In the middle reaches, the river moves through developed land where treated, imported high sulfate Colorado River water enters from urban runoff. Mast Park surrounded by caliche-bearing sedimentary rocks is a site where marl is precipitating. Cobbles in riffles in the river are coated black with Mn oxide. When the river encounters deep-seated volcanic bedrock, it wells up to precipitate both Fe and Mn oxides at Old Mission Dam. Then, directly flowing through caliche-laced sedimentary rocks, Birchcreek tributary precipitates tufa. Further downstream, at a site that periodically receives full sunlight, a sulfuretum sets up during the summer when the river is deoxygenated. Such a rich geochemistry results in activity of iron and manganese oxidizing bacteria, sulfur oxidizers and reducers, and cyanobacteria precipitating calcareous marl and tufa.

Glutamine is the most abundant and versatile amino acid in the body. In health and disease, the rate of glutamine consumption by immune cells is similar or greater than glucose. For instance, in vitro and in vivo studies have determined that glutamine is an essential nutrient for lymphocyte proliferation and cytokine production, macrophage phagocytic plus secretory activities and neutrophil bacterial killing. Glutamine release to the circulation and availability is mainly controlled by key metabolic organs, such as the gut, liver and skeletal muscles. During catabolic/hypercatabolic situations glutamine can become essential for metabolic function, but its availability may be compromised due to impairment of homeostasis in the inter-tissue metabolism of amino acids. For this reason, glutamine is currently part of clinical nutrition supplementation protocols and/or recommended for immune suppressed individuals. However, in a wide range of catabolic/hypercatabolic situations (e.g. ill/critically ill, post-trauma, sepsis, exhausted athletes) it is currently difficult to determine whether glutamine parenteral or enteral supplementation should be recommended based on the amino acid plasma concentration (glutaminemia). Although the beneficial immune based effects of glutamine supplementation is already established, many questions and evidence for positive in vivo outcomes still remain to be presented. Therefore, this paper provides an integrated review on how glutamine metabolism in key organs is important to cells of the immune system. We also discuss glutamine metabolism, action and important issues related to the effects of glutamine supplementation in catabolic situations.

Under the dual erosion conditions of the dry-wet cycle, which is caused by the high chloride salt concentrations in mine water and fluctuations in mine water level, cemented paste backfill (CPB) suffers serious damage and deterioration. To discuss the mechanical properties and permeability characteristics of CPB under erosion, this study designs an immersion experiment for CPB under chloride salt and dry-wet cycle conditions. Through a uniaxial compressive strength (UCS) test, the change law for the mechanical parameters of the CPB was explored, strength constitutive equation of the CPB was constructed, and the process of deterioration of the CPB was analyzed. Through the penetration test, the diffusion characteristics of packing under chloride salt and dry-wet cycle conditions were explored. The results demonstrated that the strength and elastic modulus of the CPB first increased and then decreased rapidly, with maximum decrease rates of 32.2% and 38.2%, respectively. The CPB structure presents an initial non-damage stage, initial damage stage, damage development stage, damage destruction, and residual damage stage. The chloride ion penetration depth gradually increased with an increase in the number of dry-wet cycles, with a maximum diffusion depth of 20.5 mm. The maximum apparent diffusion coefficient of chloride ion was 18.99×10-10m2/s, and the maximum concentration was 0.303 mol/L. Under the double erosion conditions due to chloride salt and dry-wet cycle, the CPB structure is seriously damaged.

Type2 diabetes(T2D) is a pervasive modern disease, classified as a metabolic disorder marked by hyperglycemia, hyperinsulinemia, and life-long threatening cardiovascular morbidities. Subclinical inflammation stands as the primary pathogenetic factor propelling T2D progression, correlated with heightened levels of proinflammatory cytokines. Immune cells serve as the prominent sources of cytokine production, and under diabetic conditions, they tend toward a proinflammatory phenotype, fostering chronic inflammation. This review zeroes in on the disrupted homeostasis characteristic of diabetic conditions, encompassing cytokines, hormones, and their interplay with altered immune function, all contributing to the onset of diabetic cardiovascular complications.

Intratumoral immune cytolytic activity (CYT), measured as the geometric mean of the expression of Granzyme-A (GZMA) and Perforin-1 (PRF1), has emerged as a critical factor in cancer immunotherapy, with significant implications for patient prognosis and treatment outcomes. Here, we review how different immune checkpoint pathways, the composition of Tumor Microenvironment (TME), antigen presentation and metabolic pathways, all regulate CYT. We also discuss the various methods through which CYT can be assessed. The detection and analysis of tumor-infiltrating lymphocytes using flow cytometry or immunohistochemistry provide important information on the immune cell populations within the TME. Gene expression profiling and spatial analysis techniques, such as multiplex immunofluorescence and imaging mass cytometry, allow researchers to study CYT in the context of the TME. We further report the significant clinical implications that CYT has, as its increased levels are associated with positive clinical outcomes and a favorable prognosis. Moreover, CYT can be used as a prognostic biomarker and aid in patient stratification. Measuring CYT through different methods offers promising paths for improving treatment responses. Overall, we highlight that the understanding and modulation of CYT levels is critical for improving cancer immunotherapy. Research into CYT and the factors that influence it has the potential to transform cancer treatment and improve patient outcomes.

Polyphenols, long-used components of medicinal plants, have drawn great interest in recent years as potential therapeutic agents because of their safety, efficacy, and wide range of biological effects. Approximately 74% of the world's population still uses plant-based medicines, indicating the ongoing significance of phytochemicals for human health. The study emphasizes the growing body of research examining the role of polyphenols in uncovering their anti-adipogenic and anti-obesity properties. Functions of polyphenols including phenylpropanoids, flavonoids, terpenoids, alkaloids, glycosides, and phenolic acids are distinct due to changes in chemical diversity, and structural characteristics. This review methodically investigates the mechanism of how naturally occurring polyphenols mediate obesity and metabolic function. To this end, hormonal control of hunger has the potential to inhibit pro-obesity enzymes such as pancreatic lipase, the promotion of energy expenditure, and the modulation of adipocytokine production. Specifically, polyphenols affect insulin, a hormone that is essential for regulating blood sugar, and they also play a role in part in a complex web of factors that affect the progression of obesity. This review also explores the immunomodulatory properties of polyphenols, providing insight into their ability to improve immune function. The effects of polyphenols on gut health, improving the number of commensal bacteria, cytokine production suppression, and immune cell mediation, including natural killer cells and macrophages. Taken together, continuous studies are required for prudent and precise mechanisms underlying polyphenols' therapeutic potential in obesity and immunomodulation. In the interim, this review emphasizes the holistic approach to health and promotes the consumption of a wide range of foods and drinks high in polyphenols. This review lays the groundwork for future developments, indicating that the components of polyphenols and their derivatives may provide the answer to urgent worldwide health issues. This compilation of the body of knowledge paves the way for future discoveries in the global treatment of pressing health concerns in obesity and metabolic diseases.

COVID-19 is characterized by a heterogeneous clinical presentation and prognosis. Risk factors contributing to the development of severe disease include old age and the presence of comorbidities. However, the genetic background of the host has also been recognized as an important determinant of disease prognosis. Considering the pivotal role of innate immunity in the control of SARS-CoV-2 infection, we analyzed the possible contribution of several innate immune gene polymorphisms (including TLR2-rs5743708, TLR4-rs4986790, TLR4-rs4986791, CD14-rs2569190, CARD8-rs1834481, IL18-rs2043211 and CD40-rs1883832) in disease severity and prognosis. A total of 249 individuals were enrolled and further divided into five (5) groups, according to the clinical progression scale provided by the World Health Organization (WHO) (asymptomatic, mild, moderate, severe and critical). We identified that elderly patients with obesity and/or diabetes mellitus were more susceptible to developing pneumonia and respiratory distress syndrome after SARS-CoV-2 infection, while the IL18-rs1834481 polymorphism was an independent risk factor for developing pneumonia. Moreover, individuals carrying either the TLR2-rs5743708 or the TLR4-rs4986791 polymorphisms exhibited a 3.6- and 2.5-fold increased probability for developing pneumonia and a more severe disease, respectively. Our data supports the notion that the host’s genetic background can significantly affect COVID-19 clinical phenotype, also suggesting that the IL18-rs1834481, TLR2-rs5743708 and TLR4-rs4986791 polymorphisms may be used as molecular predictors of COVID-19 clinical phenotype.

Dendritic cells (DCs) are the professional antigen-presenting cells that recognize and present antigens to naïve T cells to induce antigen-specific adaptive immunity. Among the T-cell subsets, T helper type 2 (Th2) cells produce the humoral immune responses required for protection against helminthic disease by activating B cells. DCs induce a Th2 immune response at a certain immune environment. Basophil, eosinophil, mast cells, and type 2 innate lymphoid cells also induce Th2 immunity. However, in the case of DCs, controversy remains regarding which subsets of DCs induce Th2 immunity, which genes in DCs are directly or indirectly involved in inducing Th2 immunity, and the detailed mechanisms underlying induction, regulation, or maintenance of the DC-mediated Th2 immunity against allergic environments and parasite infection. A recent study has shown that a genetic defect in DCs causes an enhanced Th2 immunity leading to a severe atopic dermatitis. We summarize the Th2 immune-inducing DC subsets, the genetic and environmental factors which involved in DC-mediated Th2 immunity, and current therapeutic approaches for Th2-mediated immune disorders. This review is to provide an improved understanding of DC-mediated Th2 immunity and Th1/Th2 immune balancing, leading to control over their adverse consequences.

A parallel between defense powers of sovereign nations and effective immunity that guards health is relevant to demonstrate vulnerability of immune system under external forces (vaccines, drugs). History demonstrated that sovereignty (power within) of small nations often threatened or destroyed by military might of powerful nations (power without) who use false-flags and propaganda for motives that are financial-control-driven. Similarly, we propose that body’s complex immune neuroplasticity (power within, adaptive, horizontal) is stretched-thin and weakened by the external forces, particularly by vaccination of the unborn/newborn or immune-compromised individuals. Validity of genomics (innate, perpendicular) as origins of ‘hereditary’ diseases (eg, allergies, diabetes, cancers) that for a century dominated research and treatment is also challenged. In conclusion, we propose that the pressure/power from within creates life with potential to sustain health, while the pressure/power from without, weaken and destroy life.

Industrial data scarcity is one of the largest factors holding back the widespread use of machine learning in manufacturing. To overcome this problem, the concept of transfer learning was developed and it achieved high attention in recent industrial research. Our paper focuses on the problem of time series segmentation and presents the first in-depth research about transfer learning for deep-learning based time series segmentation on the example of industrial end-of-line pump testing. In particularly, we investigate if the performance of deep learning models can be increased by pretraining the network with data from other domains. Three different scenarios are analyzed: source and target data being closely related, source and target data being distantly related, and source and target data being non-related. The results demonstrate that transfer learning can enhance the performance of time series segmentation models in respect to accuracy and training speed. The benefit is most clearly seen in scenarios where source and training data are closely related and the number of target training data samples is lowest. However, in the scenario of non-related datasets, cases of negative Transfer Learning were observed as well. Thus, the research emphasizes the potential, but also the challenges of industrial Transfer Learning.

Strong numerical and functional response of owls to voles in cyclic environments is well known, but there is insufficient knowledge from boreonemoral region, in particular, with depleted populations of the small mammals. In this study we describe the dynamics of the small mammal population in Latvia from 1991 to 2016 and link them to owl population characteristics. We used food niche breadth, number of fledglings and population trends to describe the numerical response of six owl species to dampened small mammal population cycles. We found temporarily in-creasing food niche breadth in tawny and Ural owls. There were no other responses in tawny owl, whereas the breeding performance of three forest specialist species – pygmy, Tengmalm`s and Ural owls – were similar to vole crash years in Fennoscandia. Moreover, the populations of forest specialist owls are decreasing and the change in Ural owl can be attributed to the depletion of small mammal populations. We found evidence of carry-over effect in eagle owl arising from strong correlation of declining breeding performance with the small mammal abundance indices in previous autumn. We conclude that dampening of the small mammal population cycles is an important covariate to overwhelming impacts of habitat destruction with stronger response in more specialized (to prey or habitat) species.

Planktonic foraminiferal biomineralization intensity, reflected by their shell calcite mass, affects global carbonate deposition and is known to follow the climate cycles by being increased during glacial stages and decreased during interglacial ones. Here we measure the dissolution state and the mass of the shells of the planktonic foraminifera species Globigerina bulloides from a Tropical Eastern North Atlantic site over the last two glacial-interglacial climatic transitions and we report no major changes in plankton calcite production with the atmospheric pCO2 variations. We attribute this consistency in foraminifera calcification to the climatic and hydrological stability of the tropical regions. We however recorded increased shell masses midway through the penultimate deglaciation (Termination II). In order to elucidate the cause of the increased shell weights we performed δ18O, Mg/Ca and μCT measurements on the same shells from a number of samples surrounding this event. We find that shells of increased mass are internally contaminated by sediment infilling and that shell weights are responding to local hydrographic changes.

Abstract: The SARS-CoV-2 pandemic has reemphasized the urgent need for broad-spectrum antiviral therapies. We developed a computational workflow using scRNA-Seq data to assess cellular metabolism during viral infection. With this workflow we predicted the capacity of cells to sustain SARS-CoV-2 virion production in patients and found a tissue-wide induction of metabolic pathways that support viral replication. Expanding our analysis to influenza A and dengue viruses, we identified metabolic targets and inhibitors for potential broad-45 spectrum antiviral treatment. These targets were highly enriched for known interaction partners of all analyzed viruses. Indeed, phenformin, an NADH:ubiquinone oxidoreductase inhibitor, suppressed SARS-CoV-2 and dengue virus replication. Atpenin A5, blocking succinate dehydrogenase, inhibited SARS-CoV-2, dengue virus, respiratory syncytial virus, and influenza A with high selectivity indices. In vivo, phenformin showed antiviral activity against SARS-CoV-2 in a Syrian hamster model. Our work establishes host metabolism as druggable for broad-spectrum antiviral strategies, providing invaluable tools for pandemic preparedness.

Many estuarine ecosystems and the fish communities that inhabit them have undergone substantial changes in the past several decades, largely due to multiple interacting stressors that are often of anthropogenic origin. Few are more impactful than droughts, which are predicted to increase in both frequency and severity with climate change. In this study, we examined over five decades of fish monitoring data from the San Francisco Estuary, California, U.S.A, to evaluate the resistance and resilience of fish communities to disturbance from prolonged drought events. High resistance was defined by the lack of decline in species occurrence from a wet to a subsequent drought period, while high resilience was defined by the increase in species occurrence from a drought to a subsequent wet period. We found some unifying themes connecting the multiple drought events over the fifty-year period. Pelagic fishes consistently declined during droughts (low resistance), but exhibit a considerable amount of resiliency and often rebound in the subsequent wet years. However, full recovery does not occur in all wet years following droughts, leading to permanently lower baseline numbers for some pelagic fishes over time. In contrast, littoral fishes seem to be more resistant to drought and may even increase in occurrence during dry years. Based on the consistent detrimental effects of drought on pelagic fishes within the San Francisco Estuary and the inability of these fish populations to recover in some years, we conclude that freshwater flow remains a crucial but not sufficient management tool for the conservation of estuarine biodiversity.

Solar power innately has issues with weather, grid demand and time of day, which for the case of concentrating solar power (CSP) can be mitigated through use of thermal energy storage. Nuclear reactors, including lead-cooled fast reactors (LFRs), can load follow, but have high fixed and low operating costs which can make this economically unattractive. We investigate potential synergies through coupling CSP and LFR together in a single supercritical CO$_2$ Brayton cycle and/or using the same thermal energy storage. Combining these cycles allows for the LFR to thermally charge the salt storage in the CSP cycle during low demand periods to be dispatched when grid demand increases. The LFR/CSP coupling into one cycle is modeled to find the preferred location of the LFR heat exchanger, CSP heat exchanger, sCO$_2$-to-salt heat exchanger (C2S), turbines, and recuperators within the supercritical CO$_2$ Brayton cycle. Three cycle configurations have been studied: two-cycle configuration, which uses CSP and LFR heat for dedicated turbocompressors, has the highest efficiencies but with less component synergies; a combined cycle with CSP and LFR heat sources in parallel is the simplest with the lowest efficiencies; and a combined cycle with separate high temperature recuperators for both the CSP and LFR is a compromise between efficiency and component synergies. Additionally, four thermal energy storage charging techniques are studied: the turbine positioned before C2S, requiring a high LFR outlet temperature for viability; the turbine after the C2S, reducing turbine inlet temperature and therefore power; the turbine parallel to the C2S producing moderate efficiency; and a dedicated circulator loop. While all configurations have pros and cons, use of a single cycle offers component synergies with limited efficiency penalty. Using a turbine in parallel with the C2S heat exchanger is feasible but results in a low charging efficiency, while a dedicated circulator loop offers flexibility and near perfect heat storage efficiency but increasing cost with additional cycle components.

Immune checkpoint inhibition therapy (ICIT) is an emerging field in oncology especially opening new horizons to chemotherapy refractory patients. This paper provides deep insight into immune related adverse events (irAEs) posing a major challenge and drawback to ICIT, and presents right management strategies for very complex complications. Moreover, for the first time in literature, a non-linear mathematical model is introduced to measure the ICIT success rate and to decide about the optimum ICIT duration. Furthermore, a strategy is presented to overcome or to delay the progression after initial good response in a subset of patients.

Background: First episode psychosis (FEP), schizophrenia and affective disorders are accompanied by activation of the immune inflammatory response system (IRS). The compensatory immune-regulatory reflex system (CIRS) is a regulatory immune response that is induced by the IRS but exerts negative feedback through, for example, increased levels of anti-inflammatory cytokines such as IL-4, IL-13 and IL-10. Different phenotypes of schizophrenia may exhibit distinct IRS and CIRS immune profiles.Aims: This study aims to examine the IRS and CIRS components, including macrophagic M1, T-helper (Th)-1, Th-2, Th-17 and T-regulatory (Treg) phenotypes, in antipsychotic-naïve FEP patients before and after risperidone treatment.Methods: We included 31 antipsychotic-naïve FEP patients who had measurements of IRS and CIRS biomarkers before and after treatment with risperidone for 10 weeks, and 22 healthy controls.Results: Antipsychotic-naive FEP patients showed interrelated increments in M1, Th-1, Th-2, Th-17 and Treg phenotypes and a relatively greater IRS response (especially granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6 and IL-12) as compared with the CIRS response (IL-4, IL-13, IL-5 and IL-10). Inflammatory markers, especially IL-6 and IL-8, were significantly correlated with negative, psychotic, affective and excitation symptom dimensions. Treatment with risperidone significantly suppressed the IRS and CIRS. Baseline levels of CIRS biomarkers, especially higher soluble tumor necrosis factor receptor-1 and IL-10 predicted clinical improvement during treatment.Discussion: Our findings indicate that FEP is characterized by robust IRS (M1 + Th-1 + Th-17) and CIRS responses, suggesting that monocytes, macrophages, Th-1, Th-2, Th-17 and Treg cells are activated. The findings indicate that a) FEP patients are prone to the detrimental effects of M1, Th-1, Th-17 and Th-2 cells, which may contribute to long-lasting abnormalities in brain circuitry; and b) in FEP, the CIRS may contribute to recovery from the acute phase of illness. Enhancing the CIRS is a new drug target to treat FEP.

This overview initially describes insect immune reactions and then brings together present knowledge of the interactions of vector insects with their invading parasites and pathogens. It is a way of introducing this special issue with subsequent papers presenting the latest details of these interactions in each particular group of vectors. Hopefully, this paper will fill a void in the literature since brief descriptions of vector immunity have now been brought together in one publication and could form a starting point for those interested and new to this important area. Descriptions are given on the immune reactions of mosquitoes, blackflies, sandflies, tsetse flies, lice, fleas and triatomine bugs. Cellular and humoral defences are described separately but emphasis is made on the co-operation of these processes in the completed immune response. The paper also emphasises the need of great care in extracting haemocytes for subsequent study as appreciation of their fragile nature is sometimes overlooked with non-sterile media, smearing techniques and excessive centrifugation sometimes used. The potential vital role of eicosanoids in the instigation of many of the immune reactions described is also discussed. Finally, the priming of the immune system, mainly in mosquitoes, is considered and one possible mechanism is presented

The innate immune system is the first line of defense against pathogens. It’s composition includes barriers, mucus and other substances as well as phagocytic and other cells. The purpose of the paper is to analyze in general grounds the immune system and the body immunity to cancer. Simple ideas and the qualitative theory of differential equations are used along with general principles such as the minimization of the pathogen load and economy of resources. In the simplest linear model, the annihilation rate of pathogens in any tissue should be greater than the pathogen’s average rate of growth. When nonlinearities are added, a reference value for the number of pathogens is set, and a stability condition emerges, which relates strength of regular threats, barrier height and annihilation rate. On the other hand, in cancer immunity, the linear model leads to an expression for the lifetime risk, which accounts for both the effects of carcinogens (endogenous or external) and the immune response. The stability condition allows a comparison of immunity in different tissues. The way the tissue responds to an infection shows a correlation with the way it responds to cancer. These statements are formulated at the qualitative level, but may and deserve to be quantitatively checked.

Diabetes is a prevalent global health issue associated with significant morbidity and mortality. Diabetic retinopathy (DR) is a well-known inflammatory, neurovascular complication of diabetes and a leading cause of preventable blindness in developed countries among working-age adults. However, the ocular surface components of diabetic eyes are also at risk of damage due to uncontrolled diabetes, which is often overlooked. Inflammatory changes in the corneas of diabetic patients indicate that inflammation plays a significant role in diabetic complications, much like in DR. The eye´s immune privilege restricts immune and inflammatory responses, and the cornea and retina have a complex network of innate immune cells that maintain immune homeostasis. Nevertheless, low-grade inflammation in diabetes contributes to immune dysregulation. This article aims to provide an overview and discussion of how diabetes affects the ocular immune system’s main components, immune-competent cells, and inflammatory mediators. By understanding these effects, potential interventions and treatments may be developed to improve the ocular health of diabetic patients.

Extracellular vesicles (EV), including exosomes and microvesicles, are released from various cells and alter recipient cell phenotypes and fates by their biomolecules. Here we review current knowledge about tumor EVs and how they prompt malignant cell communication with tumor-associated cells, such as cancer-associated fibroblasts, tumor endothelial cells, and immune cells. We delineate the major pathways and molecular players that influence each step of cancer initiation, progression, and resistance. Of note, cancer exosomes involve immunosuppression by tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells. Moreover, tumor exosomes can induce the apoptosis of killer T cells and immune checkpoint of dendritic cells and attenuate natural killer cells. An in-depth understanding of EV biology is essential to ensure the clinical development of exosome/EV-based therapeutic products, which will be of benefit to exosome manipulation in cancer management.

Chronic inflammation, the activation of immune cells and their cross-talk with cardiomyocytes in the pathogenesis and progression of heart diseases has long been overlooked. However, with the latest research developments, it is increasingly accepted that a vicious cycle exists where cardiomyocytes release cardiocrine signaling molecules that spirals down to immune cell activation and chronic state of low‐level inflammation. For example, cardiocrine molecules released from injured or stressed cardiomyocytes can stimulate macrophages, dendritic cells, neutrophils and even T-cells, which then subsequently increase cardiac inflammation by co-stimulation and positive feedback-loops. One of the key proteins involved in stress-mediated cardiomyocyte signal transduction is a small GTPase RhoA. Importantly, the regulation of RhoA activation is critical for effective immune cell response and is being considered as one of the potential therapeutic targets in many immune-cell-mediated inflammatory diseases. In this review we provide an update on the role of RhoA at the juncture of immune cell activation, inflammation and cardiac disease.

Cancer risk is known to increase tremendously when the immune system is suppressed, e.g., as observed in young organ-transplant recipients and AIDS patients. Based on such data, it may be hypothesized that the main reason for the development of clinical cancer is the weakening or suppression of the immune system, and that uncontrolled multiplication of cancer cells occurs when some aspects of the immune system fall below certain critical levels. Therefore, cancer may be prevented and treated by boosting these critical aspects of the immune system so that they are maintained above the critical levels. If multiple immune system boosting interventions are utilized, more aspects of the immune system would be boosted, increasing the likelihood of enhancing the critical aspects of the immune system and generating a cancer preventive and/or therapeutic effect. Clinical trials are needed to validate this approach for cancer prevention and treatment. If validated, the proposed approach could result in a major reduction of the death and suffering caused by cancer in the world.

Phospholipases are a family of lipid altering enzymes that can either reduce or increase bioactive lipid levels. Bioactive lipids elicit signaling responses, activate transcription factors, promote g-coupled protein activity, and modulate membrane fluidity that mediate cellular function. Phospholipases and the bioactive lipids they produce are important regulators on immune cell activity, dictating both pro-inflammatory and pro-resolving activity. During atherosclerosis, pro-inflammatory and pro-resolving activities govern atherosclerosis progression and regression respectively. This review will look at the interface of phospholipase activity, immune cell function, and atherosclerosis.

The dominant paradigm holds that spontaneous and therapeutically induced anti-tumor responses are mediated mainly by CD8 T cells and directed against tumor-specific antigens (TSAs). The presence of specific TSAs on cancer cells can only be proven by mass spectrometry analyses. Bioinformatic predictions and reverse immunology studies cannot provide this type of conclusive evidence. Most TSAs are coded by unmutated non-canonical transcripts that arise from cancer-specific epigenetic and splicing aberrations. When searching for TSAs, mass spectrometry analyses must therefore interrogate not only the canonical reading frame of annotated exome but all reading frames of the entire translatome. The majority of aberrantly expressed TSAs (aeTSAs) derive from unstable short-lived proteins that are good substrates for direct MHC I presentation but poor substrates for cross-presentation. This is an important caveat because cancer cells are poor antigen-presenting cells and the immune system therefore depends on cross-presentation by dendritic cells (DCs) to detect the presence of TSAs. We therefore postulate that, in the untreated host, most aeTSAs are undetected by the immune system. We present evidence suggesting that vaccines inducing direct aeTSA presentation by DCs represent an attractive strategy for cancer treatment.

The paper outlines a methodology for developing a model to estimate energy consumption in electric vehicles (EVs). The most robust validation indicators were exhibited by an artificial intelligence method, specifically neural networks. Within this framework, two predictive models for EV energy consumption were developed for winter and summer conditions, based on actual driving cycles. Such models hold particular significance for microscale road analyses. The resultant model for test data in summer conditions demonstrates validation indicators with an R2 of 86% and an MSE of 1.4, while for winter conditions, the values are 89% and 2.8, respectively, confirming its high precision. The paper also presents exemplary applications of the developed models, utilizing both real and simulated microscale data. The results obtained and the presented methodology can be especially advantageous for decision-makers in city road management and infrastructure planners, aiding both cognitive understanding and better planning of charging infrastructure networks.

In this work, an evaluation and quantification of the impact of using mixtures based on Supercritical Carbon Dioxide "s-CO2" (s-CO2/COS, s-CO2/H2S, s-CO2/NH3, s-CO2/SO2) are made as a working fluid in simple and complex recompression Brayton s-CO2 power cycles configurations that have pressure drops in their components. These cycles are coupled to a solar thermal plant with parabolic-trough collector (PTC) technology. The methodology used in the calculation performance is to establish values of the heat recuperator total conductance (UAtotal) between 5 and 25 MW/K. The main conclusion of this work is that the cycle's efficiency has improved due to s-CO2 mixtures as working fluid; this is significant compared to that obtained using the standard fluid (pure s-CO2). Furthermore, a techno-economic analysis is carried out that compares each configuration's costs using pure s-CO2 and a mixture of s-CO2/COS with a molar fraction (70/30) respectively as working fluid where relevant results are obtained. These results show that the best configuration in terms of thermal efficiency and cost is the RCC-RH for pure sCO2 with values ​​of 41.25% and 2811 $/kWe, while for the mixture sCO2/COS, the RCC-2RH configuration with values ​​of 45, 05% and 2621 $/kWe is optimal. Using the mixture costs 6.75% less than if it is used the standard fluid (s-CO2).

This study investigated the effects of freeze-thaw cycles on the mechanical properties of hardened self-compacting concrete for varying column heights. A column (100×20×300 cm) was fabricated by C30 self-compacting concrete in the laboratory and 10 cube samples (10x10x10 cm) were taken from fresh concrete as the references. After a period of 28 days, 160 core specimens (Ø67 mm in diameter) were taken from different column heights. Unit weight, water absorption, compressive strength, and freeze-thaw tests were performed on these 170 (10 reference cubic and 160 core) samples. The mechanical properties of the core specimens before freeze-thaw and after 8-56 freeze-thaw cycles were reported for varying column heights. The average compressive strength value of the reference cubic samples was determined as 40.28 MPa, while the compressive strengths of the core specimens before freeze-thaw were ranged from 40.25 MPa to 49.62 MPa, impying an increase in compressive strength values up to 23.18% compared to the reference cubic samples. Compressive strengths of the specimens subjected to 8 and 56 freeze-thaw cycles varied between 38.71‒48.07 MPa and 31.72‒39.11 MPa, respectively. Statistical analysis revealed that the compressive strength of the concrete exposed to 56 freeze-thaw cycles was significantly different from that of the other specimens.

This study investigated the effects of freeze-thaw cycles on the mechanical properties of hardened self-compacting concrete for varying column heights. A column (100×20×300 cm) was fabricated by C30 self-compacting concrete in the laboratory and 10 cube samples (10x10x10 cm) were taken from fresh concrete as the references. After a period of 28 days, 160 core specimens (Ø67 mm in diameter) were taken from different column heights. Unit weight, water absorption, compressive strength, and freeze-thaw tests were performed on these 170 (10 reference cubic and 160 core) samples. The mechanical properties of the core specimens before freeze-thaw and after 8-56 freeze-thaw cycles were reported for varying column heights. The average compressive strength value of the reference cubic samples was determined as 40.28 MPa, while the compressive strengths of the core specimens before freeze-thaw were ranged from 40.25 MPa to 49.62 MPa, impying an increase in compressive strength values up to 23.18% compared to the reference cubic samples. Compressive strengths of the specimens subjected to 8 and 56 freeze-thaw cycles varied between 38.71‒48.07 MPa and 31.72‒39.11 MPa, respectively. Statistical analysis revealed that the compressive strength of the concrete exposed to 56 freeze-thaw cycles was significantly different from that of the other specimens.

In schizophrenia, a single latent trait underlies psychosis, hostility, excitation, mannerism, negative (PHEMN) symptoms, formal thought disorders (FTD) and psychomotor retardation (PMR). Schizophrenia is accompanied by a breakdown of gut and blood-brain-barrier (BBB) pathways, increased tryptophan catabolite (TRYCAT) levels, bacterial translocation, and lowered natural IgM and paraoxonase (PON)1 activity. The aim of this study was to examine the factor structure of schizophrenia symptom domains and the biomarker correlates of these factors. We recruited 80 patients with schizophrenia and 40 healthy subjects and assessed the IgA/IgM responses to paracellular/transcellular (PARA/TRANS) ratios, IgA responses to TRYCATs, natural IgM to malondialdehyde and Gram-negative bacteria, and PON1 enzymatic activity.Direct Hierarchical Exploratory Factor Analysis showed a bifactorial oblique model with a) a general factor which loaded highly on all symptom domains, named overall severity of schizophrenia (“OSOS”); and b) a single-group factor (SGF) loading on negative symptoms and PMR. We found that 40% of the variance in the OSOS score was explained by IgA/IgM to PARA/TRANS ratio, male sex and education while 36.9% of the variance in SGF score was explained by IgA to PARA/TRANS, IgM to Gram-negative bacteria, female sex (positively associated) and IgM to MDA, and PON1 activity (negatively associated). Schizophrenia phenomenology comprises two biologically-validated dimensions, namely a general OSOS dimension and a single-group negative symptom dimension, which are associated with a breakdown of gut/BBB barriers, increased bacterial translocation and lowered protection against oxidation, inflammation and bacterial infections through lowered PON1 and natural IgM.

The present study evaluates ratcheting response of notched and press-fitted Al 7075-T6 specimens under stress-controlled asymmetric cycles. The degree of interference fit (DIF) directly influenced progressive plastic strain magnitude and rate at notch root region. Local ratcheting at the hole-pin interference region was analyzed by means of two kinematic hardening rules of Ahmadzadeh-Varvani (A-V) and Chaboche coupled with the Neuber rule. Ratcheting strains at notch root of aluminum samples with DIF=0 (non-press-fitting samples) were measured to be highest in magnitude. For the press-fitted samples, however ratcheting strains dropped noticeably as DIF increased from 1% to 2%. Press-fitted samples plastically deformed the perimeter edge of notches and improved materials locally at the notch edge, resulting in a better resistance against ratcheting progress. Local ratcheting at different distances of 0.5, 1.3 and 3.0 mm from the notch root were evaluated for both pinned and unpinned samples through the hardening rules and compared with those of measured values. The predicted ratcheting curves by means of the A-V and Chaboche hardening rules closely agreed with experimental data and respectively positioned above and below the measured data.

Inflammation is the response of the innate immune system to any type of injury. Although acute inflammation is critical for survival, dysregulation of innate immune response leads to chronic in-flammation. Many synthetic anti-inflammatory drugs have side effects, and thus, natural an-ti-inflammatory compounds are still needed. Cannabis sativa L. may provide a good source of in-flammation-reducing molecules. Here, we tested the anti-inflammatory properties of cannabis ex-tracts and pure cannabinoids in lipopolysaccharide (LPS)-induced inflammation in human THP-1 macrophages. We found that pre-treatment with cannabidiol (CBD), delta-9-tetrahydrocannabinol (THC), or extracts containing high levels of CBD or THC reduce the level of induction of various cytokines. The CBD was more efficient than THC, and the extracts were more efficient than pure cannabinoids. Finally, IL-6, IL-10 and monocyte chemoattractant protein-1 (MCP-1) were most sensitive to pre-treatments with CBD and THC, while IL-1β, IL-8 and TNF-α were less responsive. Thus, our work demonstrates the potential of use of cannabinoids or/and cannabis extracts for the reduction of inflammation and establishes IL-6 and MCP-1 as the sensitive markers for the analysis of the effect of cannabinoids on inflammation in macrophages.

There has been no significant efficacy in treatment for osteosarcoma (OS) metastasis after nearly four decades of trials. This motivates us to elucidate OS therapies according to their four bidirectional mutation stages. To refresh the OS therapy status quo, the historical developments and clinical advancements are briefly described. However, the main issue of metastasis remains unresolved, accounting for 90% of pulmonary metastasis deaths. Thus, this metastasis problem is related to immune evasion and chemoresistance that are being induced after long-term treatment by the use of immunotherapy for tumorigenesis. Therefore, it is rationale to discuss the relationship cycles of mutation stages including tumorigenesis, metastasis, immune evasion, and chemoresistance. Even though many combinational and targeted therapies have been developed to intensify these mutation treatments, successful clinical translations with higher cure rates are still rare. Through this review, an in-depth understanding of the bidirectional relationship between the four OS mutation stages and their respective therapies is provided. Herein, we summarise the medicines used to treat tumorigenesis, including COLGALT2 inhibitors, Tra2B, and AGAP1, miR-148a and miR-21-5p EVs, and the lncRNA LIFR-AS1. Following the medicines used to treat metastasis are AXL, miR-135a-5p, mRNA BCL6, TGFβ1, Tim-3, SOCS5, CASC15, KLF3-AS1, PDCD4, ATG5, and Rab22a-NeoF1. Then the medicines used to treat immune evasion are N-cadherin, anti-IL-9, USP12 inhibitor, IgG-4+ B-cells, LAP inhibitor, anti-Wnt2 mAb, anti-αvβ8 integrin, HK2-mediated IκBα, IDO inhibitor with NO, and TGF-βRII with anti-IgG1. Finally, the medicines used to treat chemoresistance are DHFR, FPGS, HSP-90AA1, XCT-790, ATKI, and IGF1. As a result, this contribution is expected to serve as a reference and guide for scientists and clinicians.

The Bunyavirales order includes at least fourteen families with diverse but related viruses, which are transmitted to vertebrate hosts by arthropod or rodent vectors. These viruses are responsible for an increasing number of outbreaks worldwide and represent a threat to public health. Infection in humans can be asymptomatic, or it may present with a range of conditions from a mild, febrile illness to severe hemorrhagic syndromes and/or neurological complications. There is a need to develop safe and effective vaccines, a process requiring better understanding of the adaptive immune responses involved during infection. This review highlights the most recent findings regarding T cell and antibody responses to the five bunyavirus families with known human pathogens (Peribunyaviridae, Phenuiviridae, Hantaviridae, Nairoviridae, and Arenaviridae). Future studies that define and characterize mechanistic correlates of protection against bunyavirus infections or disease will help inform the development of effective vaccines.

Background: Probiotics can provide health benefits to an individual by regulation of the immune system. Many clinical trials have found that probiotics can prevent upper respiratory tracts infections. Aim: To perform a systematic review and meta-analysis of available trials to investigate the effectiveness of probiotics in the prevention of upper respiratory tract infections in individuals of all ages. Conclusion: Probiotics were found to be better in reducing the number of participants who experienced acute URTI, the average duration per episode of acute URTI, use of antibiotics in URTI related cases and absence due to URTI. Side effects were found to be minor, making probiotics a good candidate for clinical use. This shows that probiotics are effective in preventing acute URTIs. However, due to limited studies and small sample size, the results are subjected to bias and should be interpreted with care.

Like other organisms, fungi produce extracellular vesicles (EVs) that are involved in various biological processes, including intercellular communication and the transport of molecules between cells. These EVs can be applied in fungal pathogenesis, virulence, and interactions with other organisms, including host cells, in the case of fungal infections. While some types of mycoses are relatively common and easily treatable, certain neglected mycoses pose significant public health challenges, such as sporotrichosis, chromoblastomycosis, and paracoccidioidomycosis. These infectious diseases can cause significant morbidity and disability, leading to a reduced quality of life for the patients. So, research about the virulence factor is essential to understand how fungi escape the immune system. In this context, this manuscript reviews the study of fungi EVs, their cargo, their obtaining, and their role during the infectious process, which is extremely important for understanding this neglected mycosis.

Kidney disease is a significant health problem worldwide, affecting an estimated 10% of the global population. Kidney disease encompasses a diverse group of disorders that vary in their underlying pathophysiology, clinical presentation, and outcomes. These disorders include acute kidney injury (AKI), chronic kidney disease (CKD), glomerulonephritis, nephrotic syndrome, polycystic kidney disease, diabetic kidney disease, and many others. Despite their distinct etiologies, these disorders share a common feature of immune system dysregulation and metabolic disturbances. The immune system and metabolic pathways are intimately connected and interact to modulate the pathogenesis of kidney diseases. The dysregulation of immune responses in kidney diseases includes a complex interplay between various immune cell types, including resident and infiltrating immune cells, cytokines, chemokines, and complement factors. These immune factors can trigger and perpetuate kidney inflammation, causing renal tissue injury and progressive fibrosis. In addition, metabolic pathways play critical roles in the pathogenesis of kidney diseases, including glucose and lipid metabolism, oxidative stress, mitochondrial dysfunction, and altered nutrient sensing. Dysregulation of these metabolic pathways contributes to the progression of kidney disease by inducing renal tubular injury, apoptosis, and fibrosis. Recent studies have provided insights into the intricate interplay between immune and metabolic pathways in kidney diseases, revealing novel therapeutic targets for the prevention and treatment of kidney diseases. Potential therapeutic strategies include modulating immune responses through targeting key immune factors or inhibiting pro-inflammatory signaling pathways, improving mitochondrial function, and targeting nutrient-sensing pathways such as mTOR, AMPK, and SIRT1. This review highlights the importance of the interplay between immune and metabolic pathways in kidney diseases and the potential therapeutic implications of targeting these pathways.

The role of innate immunity in neutralization of viral infections (including COVID-19) and forming long-lasting and specific immune memory is considered. It is assumed that antiviral protection is generated by the mechanism of RNA interference (RNAi) and is based on the presence of specific viral patterns in the DNA library of the host cells.

Osteoimmunology was coined about twenty years ago to identify a strict cross talk between bone niche and immune system both in physiological and pathological activities, including cancer. Several molecules are involved in the complex interaction between bone niche, immune and cancer cells. The Receptor Activator ok NF-kB (RANK)/RANK Ligand (RANKL/Osteoprotegerin (OPG) pathway plays a crucial role in bone cells/cancer interactions with subsequently immune system control failure, bone destruction, inhibition of effect and metastasis outcome. The bidirectional cross talk between bone and immune system could became a potential target for anticancer drugs. Several studies evidenced a direct anticancer role with improved survival of bone-targeted therapies such as bisphosphonates and RANKL antagonist Denosumab. Conversely, initial data evidenced a possible anti-bone resorption effect of systemic anticancer drugs through and immunomodulation activity, i.e. new generation antiandrogens (Abiraterone) in prostate cancer. All data could open a future rationale of combined bone, immunologic and targeted therapies in cancer treatment.

Autophagy is a highly conserved catabolic mechanism that mediates the degradation of damaged cellular components by inducing their fusion with lysosomes. This process provides cells with an alternative source of energy for the synthesis of new proteins and the maintenance of metabolic homeostasis in stressful environments. Numerous studies have demonstrated beneficial roles for the induction as well as the suppression of autophagy in cancer cells. Autophagy may induce either survival or death depending on the cell/tissue type. Radiation therapy is widely used therapeutic option to treat cancer, and it induces autophagy in human cancer cell line. Also, melatonin seems to affect cancer cell death via regulation of programmed cell death. In this review, we summarize the current understanding of autophagy and its regulation in cancer.

Acute respiratory distress syndrome (ARDS) is caused by infectious insults, such as pneumonia from various pathogens or related to other noninfectious events. Clinical and histopathologic characteristics are similar across severely affected patients, suggesting that a common mode of immune reaction may be involved in the immunopathogenesis of ARDS. There may be etiologic substances that have an affinity for respiratory cells and induce lung cell injury in cases of ARDS. These substances originate not only from pathogens, but also from injured host cells. At the molecular level, these substances have various sizes and biochemical characteristics, classifying them as protein substances and non-protein substances. Immune cells and immune proteins may recognize and act on these substances, including pathogenic proteins and peptides, depending upon the size and biochemical properties of the substances (this theory is known as the protein-homeostasis-system hypothesis). The severity or chronicity of ARDS depends on the amount of etiologic substances with corresponding immune reactions, the duration of the appearance of specific immune cells, or the repertoire of specific immune cells that control the substances. Therefore, treatment with early systemic immune modulators (corticosteroids and/or intravenous immunoglobulin) as soon as possible may reduce aberrant immune responses in the potential stage of ARDS.

Sulfate attack is one of the main factors affecting the durability of concrete structures. In recent years, multi-walled carbon nanotubes (MWCNTs) have attracted the attention of scholars for their excellent mechanical properties and durability performance. In this paper, the influence of sulfate attack and dry-wet cycles on the performance of multi-walled carbon nanotube-lithium slag concrete (MWCNTs-LSC) with varied MWCNTs content (0wt%, 0.05wt%, 0.10wt% and 0.15wt%) and varied water-cement ratios (0.35, 0.40 and 0.45) were investigated. Besides, scanning electron microscopy (SEM) and X-ray computed tomography (CT) tests were conducted to analyze the microstructure and pore structure of the concrete. The results show that concrete incorporated with MWCNTs could effectively mitigate sulfate attack The resistance to sulfate attack of concrete is negatively related to the water-cement ratio when the dry-wet cycle is fixed. The MWCNTs-LSC showed the best compressive strength at the water-cement ratio of 0.35 and 0.10 wt% MWCNTs. The SEM test results showed that the MWCNTs both filled the pores and cracks within the specimen and formed bridges between the cracks, enhancing the resistance to sulfate attack. The CT test results also showed that the addition of MWCNTs could reduce the porosity of concrete, refine the pore size and inhibit the generation and development of cracks, thus optimizing the internal structure of concrete and improving its resistance to sulfate attack.

The mechanism of immune activation and de-activation is very important. Host should trigger effective immunity against pathogen infection. And, host cannot trigger immunity against self-antigens that will lead to detrimental autoimmune disorders. Spleen and liver have opposite roles in mediating immune responses. Spleen is the organ involving in immune activation, and liver is the organ involving in immune de-activation. Sympathetic nerve system and parasympathetic nerve system have opposite roles in mediating immune responses. Sympathetic nerve system is involving in pro-inflammatory, and parasympathetic nerve system is involving in anti-inflammatory. ACTH and glucocorticosteroid have opposite roles in mediating immune responses. ACTH is involving in activating adaptive immunity with inhibiting innate immunity, and glucocorticosteroid is involving in activating innate immunity with inhibiting adaptive immunity. The molecular chaperons, heat shock proteins, which are induced by fever, have the vital roles in immune activation. On the contrary, IgD B cells and gamma-delta T cells are causing immune de-activation via the mechanism of clonal anergy. These mechanism can help us the know the work of immunological pathways better for better control of infectious diseases and autoimmune disorders.

Keywords: COVID-19, severity, influenza, serum antibodies, blood tests

Influenza is an acute respiratory illness caused by influenza virus infection, which is managed using vaccines and antiviral drugs. Recently, the antiviral effects of plants and foods have gained attention. This review summarizes the therapeutic properties of Euglena against influenza from a functional food viewpoint. While it has been reported that Euglena contributes to suppressing blood sugar levels and ameliorates symptoms caused by stress by acting on the autonomic nervous system, the immunostimulatory and antiviral activities of Euglena have also been reported. In this review, I focused on the immunostimulation of antiviral activity via the intestinal environment and the suppression of viral replication in infected cells. The functions of specific components of Euglena, which also serve as a source of a wide range of nutrients such as vitamins, minerals, amino acids, unsaturated fatty acids, and β-1,3-glucan (paramylon), are also reviewed. Euglena has animal and plant properties and natural compounds with a wide range of functions, providing crucial information for improved antiviral strategies.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer care and shown remarkable efficacy clinically. This efficacy is, however, limited to subsets of patients with significant infiltration of lymphocytes into the tumor microenvironment. To extend their efficacy to patients who fail to respond or achieve durable responses, it is now becoming evident that complex combinations of immunomodulatory agents may be required to extend efficacy to patients with immunologically “cold” tumours. Oncolytic viruses (OVs) have the capacity to selectively replicate within and kill tumour cells resulting in the induction of immunogenic cell death and the augmentation of anti-tumour immunity and have emerged as a promising modality for combination therapy to overcome the limitations seen with ICIs. Pre-clinical and clinical data has demonstrated that OVs can increase immune cell infiltration into the tumour and induce anti-tumour immunity, thus changing a “cold” tumour microenvironment that is commonly associated with poor response to ICIs, to a “hot” microenvironment which can render patients more susceptible to ICIs. Here, we review the major viral vector platforms used in OV clinical trials, their success when used as a monotherapy and when combined with adjuvant ICIs, as well as pre-clinical studies looking at the effectiveness of encoding OVs to deliver ICIs locally to the tumour microenvironment through transgene expression.