Registry and survey data gave an opportunity to compare possible roles of social attitudes and social values in control and limit the COVID-19 pandemic. We analysed social values and time series of daily R0 (reproduction rate) estimates for 27 European countries. Embedded and affective autonomy are significantly negatively associated (p-Value<0.05) with controlled R0. It could mean that well interconnected societies with high attention to maximize utilities are more likely to couple with COVID-19. Hierarchy is significantly positively associated (p-Value<0.05) with controlled R0. Thus, hierarchical structures could inhibits control of COVID-19. The results emphasize the need to pay more attention to social values context in evaluating the effectiveness of mitigation strategies internationally.

There is tremendous interest, in the economic literature, for the determinants of firms’ capital structure decisions. A rich body of empirical works now exists that purports to identify firm- and country-level factors affecting firms’ financing patterns. In addition, more recently, a new stream of studies has emerged that investigates cross-regional variation in small firms’ capital structure. While small firms’ leverage does seem to vary across regions, at least in countries where significant regional differences in economic and financial development and in the quality of institutions exist, not much yet is known about variation in debt maturity, in debt in relation to equity, and between different types of small firms. The present paper aims to fill this gap through an empirical analysis of cross-regional variation in the capital structure of a sample of about 30,000 Italian small firms over a 13-year period, including the aftermath of the credit crunch that followed the 2007-8 global financial crisis. The findings confirm the view that small firms in underdeveloped regions are more financially constrained, but also amend some of the results shown in the literature, in particular by showing how small firms in Italy’s Southern regions have higher levels of equity and fixed assets than small firms in other regions.

The p53 tumor suppressor protein shows antiviral activity. The replication of viruses is also antagonized by interferons (IFNs) – cytokines, which control immunity genes by the STAT transcription factors. The best studied interferons belong to type I (e.g. IFNα) and type II (IFNγ) groups. IFNα and IFNγ both induce activating phosphorylation of STAT1 on Tyr701. Previously, we noticed that p53 activates SOCS1, which is a negative regulator of STAT1 phosphorylation. Thus, we hypothesized that p53 by activating SOCS1 expression reduces phosphorylation of STAT1 and attenuates activation of genes stimulated either by IFNα or IFNγ. To test this hypothesis, we exposed p53-proficient and p53-deficient cells to strong p53 activators, and either to IFNα or IFNγ. Subsequently, we estimated the phosphorylation status of STAT1 and the expression of genes regulated by either of these cytokines. Strong activation of p53 reduced the phosphorylation of STAT1 on Tyr701, however surprisingly it did not lead to reduced expression of most tested interferon-stimulated genes. On contrary, p53 and IFNγ synergized in the activation of CASP1, IFIT1 and IFIT3 genes. We conclude that the interactions between p53 and interferon-activated pathways are more complicated than initially expected, but the apparent cooperation between p53 and IFNγ deserves further studies.

An entomopathogenic nematode, Oscheius tipulae, was isolated from a soil sample. The identification of this species was supported by morphological and molecular markers. The nematode isolate exhibited pathogenicity against different target insects including lepidopteran, coleopteran, and dipteran insects. The virulence of this nematode was similar to that of a well-known entomopathogenic nematode, Steinernema carpocapsae, against the same insect targets. A comparative metagenomics analysis of these two nematode species predicted the existence of a combined total of 272 bacterial species in their intestines, of which 51 bacterial species were shared between the two nematode species. In particular, the common gut bacteria included several entomopathogenic bacteria including Xenorhabdus nematophila, which is known as a symbiotic bacterium to S. carpocapsae. The nematode virulence of O. tipulae to insects was enhanced by an addition of dexamethasone but suppressed by an addition of arachidonic acid, suggesting that the immune defenses of the target insects against the nematode infection is mediated by eicosanoids, which would be manipulated by the symbiotic bacteria of the nematode. Unlike S. carpocapsae, O. tipulae showed high virulence against dipteran insects including fruit flies, onion flies, and mosquitoes. O. tipulae showed particularly high control efficacies against the onion maggot, Delia platura, infesting the Welsh onion in the rhizosphere in both pot and field assays.

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.

Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are multi-targeted and variable over time. Multiplex quantitative serological assays are needed to provide accurate and robust seropositivity data for establishment of serological signatures during vaccination and or infection. We describe here, validation and evaluation of an electro-chemiluminescence (ECL) based Mesoscale Discovery assays (MSD), for estimation of total and functional IgG to SARS-CoV-2 spike, nucleocapsid, and receptor binding (RBD) proteins in human serum samples to establish serological signatures of SARS-CoV-2 natural infection and breakthrough cases. The 9-PLEX assay was validated as per ICH, EMA and US FDA guidelines using a panel of sera samples including the NIBSC/WHO international reference panel (20/268). Assay demonstrated high specificity and selectivity in inhibition assays, wherein the homologous inhibition was more than 85% and heterologous inhibition was below 10 %. Assay also met predetermined acceptance criteria for precision (CV < 30 %), accuracy (70-130 %) and dilutional linearity. Method applicability to serological signatures was demonstrated using sera samples (N=45) representing vaccinated, infected and breakthrough cases. The method was able to establish distinct serological signatures and thus provide potential tool for seroprevalence of SARS-COV-2 during vaccination or infection.

In the past decade, it has been discovered that intestinal flora can influence various organ-specific cancers by altering the body's energy balance, increasing obesity, synthesizing genetic toxins and small signaling molecules, initiating and modulating immune responses, and metabolizing indigestible dietary components, exogenous substances, and drugs. In this review, we will focus on elucidating the role of gut flora based on its molecular mechanisms and its potential therapeutic implications in head and neck tumors in the near future.

The Golgi apparatus, long known for protein processing and vesicular trafficking, has recently emerged as an essential player in innate immune signaling pathways. This review article discusses our growing understanding of Golgi cells' roles in initiating and activating innate immunity pathways. We elaborate on the relevance of membrane connections between Golgi organelles and other organelles such as endoplasmic reticulum, mitochondria, endosomes, and autophagosomes that facilitate efficient access to innate immune signal transduction and subsequent effector responses. Additionally, we discuss microbial strategies that exploit the Golgi while diminishing its associated innate immune responses. By providing greater illumination of its multiple functions and mechanisms of operation, this article offers invaluable insight into how protein processing impacts innate immunity and vice versa.

Poplar (Populus) is a genus of woody plants of value for the pulp industry, green energy, urban landscaping, soil phytoremediation and as an ornamental plant. Due to the increasing economic importance of poplar, there is a need to ensure its stable growth by increasing its resistance to pathogens, as one of the main problems in poplar cultivation is its susceptibility to numerous diseases. Currently, breeding poplars with reduced susceptibility to infections is receiving increasing attention. Genetic engineering can produce organisms with improved traits faster than traditional methods, and with the development of CRISPR/Cas-based genome editing systems, scientists have a new highly efficient tool at their disposal to create valuable genotypes. In this review, we summarize recent research data on poplar diseases, the biology of their pathogens, and how these plants resist pathogens. In the final section, we discuss genetic engineering, genome editing, and microbiome strategies that we believe are suitable for obtaining new improved poplar lines.

The coronavirus disease 2019 (COVID-19) pandemic clearly has had a great influence on the lifestyle of the population, especially on patients with type 2 diabetes mellitus. During the COVID-19 outbreak, many countries/regions implemented social isolation measures, leading to an increase in negative behaviors and impairing the capability of diabetic patients to resist the COVID-19, ultimately causing a severe prognosis. Moreover, multiple studies have emphasized the significance of physical exercise in the management of type 2 diabetic patients infected with COVID-19 as the epidemic progressed. In our study, we selected research focusing on COVID-19-infected diabetic patients from Dec 1, 2019 to Aug 9, 2023 and sought to investigate the impact of type 2 diabetes on the immune function, inflammation factor levels, lung injury and mental disorders of patients, as well as to assess the risk of novel coronavirus pneumonia in these patients. And we also summarized the effects of high-intensity, moderate-intensity and low-intensity exercise on novel coronavirus pneumonia infection in type 2 diabetic patients and the mechanisms of their effects. Finally, diabetic patients with COVID-19 are suggested to perform low-intensity exercise to facilitate their recovery. Our study offers guidance for a proper understanding of the dangers of diabetes and the use of appropriate measures to reduce the risk of novel coronavirus pneumonia infections in type 2 diabetic patients.

Abstract: A multitude of biotic and abiotic stress factors do harm to plants by bringing about diseases and inhibiting normal growth and development. As an omnipotent signaling molecule, salicylic acid (SA) plays crucial roles in plants' tolerance responses to both biotic and abiotic stresses, thereby maintaining plants’ normal growth and improving yields under stresses. In view of this, this paper mainly discusses the role of SA in both biotic stresses, and abiotic stresses of plants. SA regulates the expression of genes involved in defense signaling pathways, thus enhancing plants’ immunity. In addition, SA mitigates the negative effects of abiotic stresses, and acts as a signaling molecule to induce the expression of stress-responsive genes and the synthesis of stress-related proteins. In addition, SA also improves certain yield-related photosynthetic indexes, thereby enhancing crop yield under stresses. On the other hand, SA acts with other signaling molecules in regulating plants’ growth and improving tolerances under stresses. This paper reviews recent advances in SA’s roles in plant stress tolerances, so as to provide theoretical references for further studies concerning the decryption of molecular mechanisms for SA’s roles and the improvement of crop management under stresses.

In this article, we first assessment of peste des petits ruminants (PPR) antibodies in vaccinated pregnant ewes of Kazakh breed fine-fleeced immunized with the PPR vaccine and the duration of maternal immunity in their lambs. Ewes in the last trimester of pregnancy of gestation were immunized with a vaccine from the Nigeria 75/1 strain of the PPR virus (PPRV) produced by the Research Institute of Biological Safety Problems (RIBSP), Kazakhstan. Serum samples from lambs born from vaccinated and unvaccinated ewes were collected a week after birth and at intervals of 7 days for 18 weeks after birth. Serum samples collected from lambs were tested for PPR antibodies using competitive ELISA and Virus neutralization test (VNT). Maternal antibodies (MAs) in lambs born from vaccinated ewes were detected up to 18 weeks with a tendency to decrease starting at week 14 and by the end of the experiment receded below the protective level (&lt;1:8). In the blood serum of a 14-week-old lamb with MAs (1:8), post vaccination with a field dose (103 TCID50) of the vaccine against PPR, the titers of protective antibodies to the PPRV increased to 1:16 on 14 day post vaccination and lamb protected from infection upon field PPRV. A lamb of the same age with MAs in the 1:8 titer was 100% protected from infection with the field PPRV. Therefore, it is recommended that lambs of the Kazakh fine-wool breed be immunized from the age of 14 weeks or older to avoid a period of susceptibility.

Bone Morphogenetic Proteins (BMPs) are a group of structurally and functionally related signaling molecules that comprise a subfamily, belonging to the TGF-β superfamily. Most BMPs play roles in the regulation of embryonic development, stem cell differentiation, tumor growth and some cardiovascular and cerebrovascular diseases. Although evidences are emerging for the antiviral immunity of a few BMPs, more BMPs are needed to determine whether this function is universal. Here we identified the zebrafish bmp4 ortholog, whose expression is up-regulated by challenge with virus or its mimic poly(I:C). Overexpression of bmp4 in EPC cells significantly decreased the viral titer of GCRV-infected cells. Moreover, compared to wild type zebrafish, viral load and mortality were significantly increased in both larvae and adults of bmp4-/- mutant zebrafish infected with GCRV virus. We further demonstrated that Bmp4 promotes the phosphorylation of Tbk1 and Irf3 through p38 MAPK pathway, thereby inducing the production of type I IFNs in response to virus infection. These data suggest that Bmp4 runs an important role in the host defense against virus infection. Our study expands the understanding of BMP protein functions and opens up new targets for the control of viral infection.

CD4+ T cells orchestrate and regulate immunity within jawed vertebrates, yet our understanding of their evolution, development, and cellular physiology has only begun to be unearthed in the past few decades. Discoveries of genetic diseases that ablate this cellular population have provided insight into their critical functions while transcriptomics, proteomics, and highresolution microscopy have recently revealed new insights into CD4+ T cell anatomy and physiology. This article compiles historical, microscopic, and multi omics data which can be used as a reference atlas to dissect cellular physiology within these influential cells and further understand pathologies like HIV infection that inflict human CD4+ T cells.

Osteoarthritis (OA) is the most common degenerative joint disease that causes chronic pain and disability. Different innate immune components, including macrophages, T cells, and neutrophils, participate in osteoarthritis pathophysiology. Neutrophils are the most abundant circulating leukocytes with multiple specialized functions contributing to innate and adaptive immune functions. Although neutrophils produce proinflammatory cytokines and chemokines, reactive oxygen species (ROS), matrix-degrading enzymes, and neutrophil extracellular traps (NET) that promote joint degradation as the first recruit cells in an inflamed joint, these cells also play an important role in joint repair by regulating the immune response, releasing anti-inflammatory factors, and activating some protective genes. In this review, various aspects of neutrophil biology, their role in inflammation and its association with osteoarthritis, and possible therapeutic approaches to target neutrophils for the treatment of osteoarthritis are described. Understanding neutrophil heterogeneity and their mechanisms of action in joint inflammation, provides a potential strategy for OA management.

Tropical corals construct the three-dimensional framework for one of the most diverse ecosystems on the planet, providing habitat to a plethora of species across taxa. However, these ecosystem engineers are facing unprecedented challenges, such as increasing disease prevalence and marine heatwaves associated with anthropogenic global change. As a result, major declines in coral cover and health are being observed across the world's oceans, often due to the breakdown of coral-associated symbioses. Here, we review the interactions between the major symbiotic partners of the coral holobiont – the cnidarian host, algae in the family Symbiodiniaceae, and the microbiome – that influence trait variation, including the molecular mechanisms that underlie symbiosis and the resulting physiological benefits of different microbial partnerships. In doing so, we highlight the current framework for the formation and maintenance of cnidarian-Symbiodiniaceae symbiosis, and the role that immunity pathways play in this relationship. We emphasize that understanding these complex interactions is challenging when you consider the vast genetic variation of the cnidarian host and algal symbiont, as well as their highly diverse microbiome, which is also an important player in coral holobiont health. Given the complex interactions between and among symbiotic partners, we propose several research directions and approaches focused on symbiosis model systems and emerging technologies that will broaden our understanding of how these partner interactions may facilitate the prediction of coral holobiont phenotype, especially under rapid environmental change.

To date, viruses closely related to SARS-CoV-2 have been reported in four bat species: Rhinolophus acuminatus, Rhinolophus affinis, Rhinolophus malayanus, and Rhinolophus shameli. Here, we analysed 343 sequences of the mitochondrial cytochrome c oxidase subunit 1 gene (CO1) from georeferenced bats of the four Rhinolophus species identified as reservoirs of SARS-CoV-2-like viruses. Haplotype networks were constructed in order to investigate patterns of genetic diversity among bat populations of Southeast Asia. No strong geographic structure was found for the four Rhinolophus species, suggesting high dispersal capacity. The ecological niche of SARS-CoV-2 like viruses was predicted using the four localities of bat SARS-CoV-2-like viruses and the localities where bats showed identical or very similar CO1 haplotypes than virus-positive bats. The ecological niche of SARS-CoV-like viruses was deduced from the localities where bat SARS-CoV-like viruses were previously detected. The results show that the ecological niche of SARS-CoV2-like viruses includes several regions of mainland Southeast Asia whereas that of SARS-CoV-like viruses is mainly restricted to China. In agreement with these results, human populations in Laos, Vietnam, Cambodia, and Thailand appear to be much less affected by the Covid-19 pandemic than other countries of Southeast Asia. In the climatic transitional zone between the two ecological niches (southern Yunnan, northern Laos, northern Vietnam, and possibly Hainan and Taiwan), genomic recombination between highly divergent viruses is more likely to occur. Since recombinant viruses can threaten the benefit of vaccination campaigns, these regions should be under surveillance.

The novel coronavirus diseases 2019 (COVID-19) has unfolded an unprecedented worldwide public health emergency with disastrous economic consequences. Around 12 million coronavirus cases have already been identified with over half a million deaths. Despite numerous efforts by the government as well as international organizations, these numbers are still increasing with a surprising rate. Although urgent and absolutely necessary, a reliable therapeutic or vaccine is still elusive and this status quo may remain for an uncertain period of time. Taken that into account, boosting up adaptive immunity through nutritional interventions may help subside this epidemic and save many lives. This review focuses on the nexus between a balanced diet and adaptive immunity, particularly, how a poor diet may lead to compromised immunity resulting in susceptibility to viral infections. Additionally, we discuss how nutrients (vitamins, minerals, trace elements) could be used as a tool to modulate immune response and thus impede viral infections. The study also summarized nutritional recommendations to combat COVID-19 in different countries and territories and dietary sources of those key nutrients. Moreover, different nutritional intervention strategies based on different age groups, physiological and medical conditions were also included, and the challenges of nutritional interventions towards the care of COVID-19 patients were also discussed. Since the availability of a drug or vaccine is still uncertain, a balanced diet or nutrient therapy could be used as a robust strategy to combat COVID-19. Thus, we hope this review may help to make an informed decision with regard to diet choice both at individual level as well as clinical settings.

In humans, coronaviruses can cause infections of the respiratory system, with damage of varying severity depending on the virus examined: ranging from mild or moderate upper respiratory tract diseases, such as the common cold, to pneumonia, severe acute respiratory syndrome, kidney failure and even death. Human coronaviruses known to date, common throughout the world, are seven. The most common - and least harmful - ones were discovered in the 1960s and cause a common cold. Others, more dangerous, were identified in the early 2000s and cause more severe respiratory tract infections. Among these the SARS-CoV, isolated in 2003 and responsible for the Severe Acute Respiratory Syndrome (the so-called SARS), which appeared in China in November 2002, the Coronavirus 2012 (2012-nCoV) cause of the Middle Eastern Respiratory Syndrome from Coronavirus (MERS), which exploded in June 2012 in Saudi Arabia, and actually SARS-CoV-2. On December 31, 2019, a new Coronavirus strain was reported in Wuhan, China, identified as a new Coronavirus beta strain ß-CoV from Group 2B, with a genetic similarity of approximately 70% to SARS-CoV, the virus responsible. of SARS. In the first half of February, the International Committee on Taxonomy of Viruses (ICTV), in charge of the designation and naming of the viruses (i.e., species, genus, family, etc.), thus definitively named the new coronavirus as SARS-CoV-2. This article highlights the main knowledge we have about the biomolecular and pathophysiologic mechanisms of SARS-CoV-2.

COVID-19 is fast spreading around the globe in a highly contagious manner. The results from our study showed that after intervention with successive Lockdowns, there was marked decrease in the rate of COVID-19 cases, though there was sporadic volatility in number of COVID-19 cases due to some extrinsic factors. Concomitant with reduction in rate of COVID-19 there was gradual increase in doubling time of COVID-19, steady increase in number of discharged/recovered patients from COVID-19 reaching to ≥ 58% taking the entire Indian population into consideration. Another important aspect was consistent low mortality rate was accompanied by gradual increase in recovery rate of COVID-19 in the population. The possible implication of these results in the development of protective immunity in the population has been discussed.

Hepatitis C virus (HCV) represents a challenging global health threat in ~200 million infected individuals. Clinical data suggests that only ~10-15% of acutely HCV-infected individuals will achieve spontaneous viral clearance despite exuberant virus-specific immune responses, which is largely attributed to difficulties in recognizing the pathognomonic symptoms during the initial stages of exposure to the virus. Given the paucity of a suitable small animal model, it is also equally challenging to study the early phases of viral establishment. Further, the host factors contributing to HCV chronicity in a vast majority of acutely HCV-infected individuals largely remain unexplored. The last few years have witnessed a surge in studies showing that HCV adopts a myriad mechanisms to disconcert virus-specific immune responses in the host to establish persistence that includes, but not limited to viral escape mutations, viral growth at privileged sites, and antagonism. Here, we discussed a few hitherto poorly explained mechanisms employed by HCV that are believed to lead to chronicity in infected individuals. A better understanding of these mechanisms would aid the design of improved therapeutic targets against viral establishment in susceptible individuals.

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

The microstructure evolution during the cold rolling and subsequent annealing of Alloy 800H was investigated. Two distinct rolling methods, unidirectional rolling and cross-rolling, were intro-duced. Results show that better ductility was observed in the unidirectional rolling than in cross-rolling, whilst a higher volume fraction of large deformed grains was observed in the cross-rolled plates than in the unidirectionally rolled plates. Recrystallization occurred faster in plates from unidirectional rolling than from cross-rolling.

Bismaleimide (BMI) is a high-performance thermosetting resin widely used in the aerospace, automotive, and mechanical and electronics industries due to its chemical and mechanical stability. It also has the capability of being used as an ink in polyjets used for 3D printing evident from thinner mellamide FTIR bands and faster curing rates as observed from TGA-DSC studies.

Classical Hodgkin lymphoma (cHL) is a highly curable disease (70-80%), even though long-term toxicities, drug resistance, and predicting clinical responses to therapy are major challenges in cHL treatment. To solve these problems, we characterized two cHL cell lines with acquired resistance to doxorubicin, KM-H2dx and HDLM-2dx (HRSdx), generated from KM-H2 and HDLM-2 cells, respectively. HRSdx cells developed cross-resistance to vinblastine, bendamustin, cisplatin, dacarbazine, gem-citabine, brentuximab vedotin (BV), and γ-radiation. Both HDLM-2 and HDLM-2dx cells had an intrinsic resistance to BV but not to the drug MMAE. HDLM-2dx acquired cross-resistance to caelyx. HRSdx cells had in common: decreased CD71, CD80, CD54, cyt-ROS, HLA-DR, DDR1, CD44; increased Bcl-2, CD58, COX2, CD26, CCR5, invasive capability; increased CCL5, TARC, PGE2, TGF-β, and capability to hijack monocytes. In HRSdx cells, less sensitive to DNA damage and oxidative stress, the efflux drug transporters MDR1 and MRP1 were not up-regulated, and doxorubicin accumulated in cytoplasm rather than in nucleus. Both autophagy inhibitor chloroquine and extracellular vesicles (EVs) release inhibitor GW4869 enhanced doxorubicin activity and counteracted doxorubicin resistance. In conclusion, this study identifies common modulated antigens in HRSdx cells, the associated cross-resistance patterns, and new potential therapeutic options to enhance doxorubicin activity and overcome resistance.

The need for cross-modal retrieval (CMR) among users is growing because of the swift advancements in computer vision and natural language processing. Promoting home operating systems is greatly aided by the openKylin home operating system. It is focused on enhancing the functionality of the operating system with safe and dependable operating technologies. Practical implications abound for integrating computer vision research into home operating systems. A multimodal retrieval approach based on openKylin is presented to improve the usability of text search graphs, audio, and video. The overview of pertinent domestic and international research is the main topic of this article. This technological advancement. It then offers details on the design, implementation procedure, and final implementation outcomes for demonstration. The works of natural operations show that this strategy has excellent accuracy and performance.

Aryl chlorides and bromides in the presence of NHC palladium hydroxo dimers of the type [{Pd(µ-OH)Cl(NHC)}2] (where NHC = IPr, SIPr, IMes, SIMes) undergo an efficient and selective Sonogashira cross-coupling with terminal acetylenes. For the coupling of 4-chlorotoluene with phenylacetylene TON = 560000 was observed. The procedure enables high-throughput and selective synthesis of a broad spectrum of unsymmetrically substituted 1,2-diarylacetylenes. Nearly a quantitative amount of HCl was detected within cross-coupling products. Water plays the role of the base and is regenerated in the process so that it does not have to be used in stoichiometric amounts (relative to the limiting reactant). Generation of the active Pd(0) complex proceeds via ethanol oxidation.

For a long time, the transition to adulthood was seen as a troubled period where good development was synonymous with the absence of problems. Positive Youth Development (PYD) emerged as a holistic and strength-based perspective that focuses on the fact that young people may have the internal and external resources for healthy and successful development through five dimensions (5C’s) that empower them: Perceived Competence, Confidence, Character, Connection, and Caring. The aim of this study was to examine the relationship between the global PYD factor (and the 5C’s) and risk behaviors, in addition to analyzing gender differences. This study showed the results of a cross-sectional study of 1044 emerging adults from 11 Spanish universities in 2021. Data collection was performed by applying an online self-report measure. The results showed that the Character was protective against substance abuse, mainly in women, while the connection was related to the participation of betting money and online betting in men. Caring was protective against money bets in the men’s sample. However, controversial results were found regarding Perceived competence, which had a positive association with substance abuse, money bets, and drunk driving. It seems that high levels of Perceived competence, rather than objective competence, were associated with engagement in various risk behaviors, especially in the absence of other C´s. These results are discussed regarding the promotion of PYD to improve successful development and may suggest the need to foster healthy lifestyles and prevent risky behaviors in youth through the 5C's promotion programs within the university context.

The pion-argon cross-section measurement is crucial to understand effects such as final-state interactions, which account for a large source of systematic uncertainty in neutrino oscillation experiments. ProtoDUNE-SP, with its charged particle beam data, can provide such experimental constraints. This paper elaborates the methodology to measure the cross-section on large-scale LArTPCs like ProtoDUNE-SP. We use the 1 GeV MC sample to demonstrate the analysis procedures. The cross-sections for pion kinetic energy ranging from 350 MeV to 950 MeV are measured on the MC. The consistency of the MC results with its input values serves as validation of the method and the procedures, which we will later use to perform measurements on the data sample.

Economic globalisation has promoted the extensive circulation of commodities around the world, and international trade has increasingly been a strong booster for economic growth in China. As an foundation for national economy, the shift of agricultural products (AP) from production to distribution has become the focus of agricultural development, and in recent years, the international trade of agricultural products in China has been the highest in the world. While, cross-border e-commerce (CBE), as one of the important modes of agricultural products circulation, has brought new opportunities for China's fresh agricultural products to carry out online import and export trade under the favourable policies continuously introduced internationally. This research analyses status of APCBE in Yunnan Province, China, and propose strategies for developing CBE of Yunnan AP.

In the field of vision-based robot grasping, effectively leveraging RGB and depth information to accurately determine the position and pose of a target is a critical issue. To address this challenge, we propose a tri-stream cross-modal fusion architecture for 2-DoF visual grasp detection. This architecture facilitates the interaction of RGB and depth bilateral information and is designed to efficiently aggregate multiscale information. Our novel modal interaction module (MIM) with spatial-wise cross-attention algorithm adaptively captures cross-modal feature information. Meanwhile, the channel interaction modules (CIM) further enhance the aggregation of different modal streams. In addition, we efficiently aggregate global multiscale information through a hierarchical structure with skipping connections. To evaluate the performance of our proposed method, we conduct validation experiments on standard public datasets and real robot grasping experiments. We achieve the image-wise detection accuracy of 99.4% and 96.7% on Cornell and Jacquard datasets respectively. The object-wise detection accuracy reaches 97.8% and 94.6% on the same datasets. Furthermore, physical experiments using the 6-DoF Elite robot demonstrate a success rate of 94.5%. These experiments highlight the superior accuracy of our proposed method.

Background: Cardiovascular disease (CVD) has been one of the leading causes of death and disability-adjusted life years lost worldwide. Blood pressure, lipid, and cholesterol are good predictors of CVD risk and correspond upon age and physical fitness. However, few studies have explored the variation trend of CVD risk factors across different populations upon age and their muscle strength. Objective: to analysis the variation tendency of CVD risk factors in blood according to age and relative grip strength among different populations. Method: 25363 participants were recruited in this cross-sectional study and 24709 were included in the analysis. A logistic regression and a Bayesian probabilistic analysis based on Markov Chain Monte Carlo (MCMC) Modeling is conducted to build probability prediction models of hypertension, hyperlipidemia, and hypercholesterolemia according to age, relative grip strength, body weight conditions, and physical activity levels. Results: 1) age might be the main influence factor of hypertension, which is regarded as one of the primary CVD risk factors. However, although keeping a high level of physical activity might have positive effect on preventing hypertension because that individuals with normal body weight and higher physical activity shows a lower probability of being diagnosed with hypertension, it might could not prevent individuals from getting hypertension with age. 2) After 60, individuals of normal body weight seem more likely to have hyperlipidemia than those are overweight or obese. 3) Larger relative grip strength might not be able to offset the negative effects of obesity, overweight and physical inactivity on hyperlipidemia. 4) The probability of getting hypercholesterolemia varies less with age and relative grip strength. Conclusion: Body weight management and keeping high levels of physical activity are recommended at any age. It might benefit to increase some bodyweight after 60 years old.

Background: New insecticides with novel modes of action such as neonicotinoids have recently been recommended for public health use by WHO. Resistance monitoring of such novel insecticides requires a robust protocol to monitor the development of resistance in natural populations. In this study, we comparatively used three different solvents to assess the susceptibility of malaria vectors to neonicotinoids across Africa.Methods: Mosquitoes were collected from May to July 2021 from three agricultural settings in Cameroon (Njombe-Penja, Nkolondom, and Mangoum), the Democratic Republic of Congo (Ndjili-Brasserie), Ghana (Atatam), and Uganda (Mayuge). Using the CDC bottle test, we compared the effect of three different solvents (ethanol, acetone, acetone+MERO) on the efficacy of neonicotinoids against Anopheles gambiae s.l. In addition, TaqMan assays were used to genotype key pyrethroid-resistant markers in An. gambiae and to evaluate potential cross-resistance between pyrethroids and clothianidin.Results: Lower mortalities were observed for all populations when using absolute ethanol or acetone alone as solvent (11.4- 51.9% mortality for Nkolondom, 31.7- 48.2% for Mangoum, 34.6- 56.1% for Mayuge, 39.4- 45.6% for Atatam, 83.7- 89.3% for Congo and 71.05- 95.9% for Njombe pendja) compared to acetone + MERO for which 100% mortality was observed for all the populations. Synergist assays (PBO, DEM and DEF) revealed a significant increase of mortality suggesting that metabolic resistance mechanisms are contributing to the reduced susceptibility. A negative association was observed between the L1014F-kdr mutation and clothianidin resistance with a greater frequency of homozygote resistant mosquitoes among the dead than among survivors (OR=0.5; P=0.02). However, the I114T-GSTe2 was in contrast significantly associated with a greater ability to survive clothianidin with a higher frequency of homozygote resistant among survivors than other genotypes (OR=2.10; P=0.013). Conclusions: This study revealed a contrasted susceptibility pattern depending on the solvents with ethanol/acetone resulting in lower mortality, thus possibly overestimating resistance, whereas the addition of MERO consistently increased the efficacy of neonicotinoids in terms of percentage mortalities and time to final mortality. The addition of MERO could however prevent the early detection of resistance development. We therefore recommend monitoring susceptibility using both acetone alone and acetone+MERO (8-10µg/ml for clothianidin) to capture the accurate resistance profile of the mosquito populations.

The vibrational excitation cross section of a diatomic molecule by positron impact is obtained using wavepacket propagation techniques. The dynamics was carried on a two-dimensional potential energy surface which couples a hydrogen-like harmonic oscillator to a positron via a spherically symmetric correlation polarization potential. The cross section for the excitation of the first vibrational mode is in good agreement with previous reports. Our model suggests that a positron couples to the target vibration by responding instantly to an interaction potential which depends on the target vibrational coordinate.

This paper presents a study on the development of the cross-curricular learning outcome (CCLO) "Ethical, environmental and professional responsibility" by the students of different Bache-lor’sDegrees taught at Universitat Politècnica de València. The work and development of this learning outcome entails great complexity, given the double dimension of responsibility that it involves. At the end of their training at the university, students are expected to show ethical, en-vironmental, and professional responsibility towards themselves and others. Interviews have been conducted with lecturers who work and assess this outcome in their subjects, most/all of them related to science and engineering. The objective was to identify the learning approach used at the different subjects to guarantee the acquisition of this CCLO by the students. A focus group has also been carried out with students to determine the importance they give to this learning outcome, and to know their degree of satisfaction with the training received. The methodology used to obtain the data from lecturers and students and to process the information to get a precise diagnosis is fully described in the paper. Results are satisfactory to some extent: most of the lecturers carry out appropriate activities and most of students achieve the expected proficiency level. Finally, recommendations are given to improve the development of this cross-curricular learning outcome.

Light absorption in single nanowires (NWs) is one of the most crucial factors for photovoltaic applications. In this paper, we carried out a detailed investigation of light absorption in single rectangular NWs (RNWs). We show that the RNWs exhibit improved light absorption compared with the square NWs (SNWs), which can be attributed to the symmetry-breaking structure that can increase the light path length by increasing the vertical side and the enhanced leaky mode resonances (LMRs) by decreasing the horizontal side. We found that the light absorption in silicon RNWs can be enhanced by engineering the horizontal and vertical sides, the photocurrent is significantly increased by 276.5% or 82.9% compared with that of the SNWs with the same side length as the horizontal side of 100 nm or the vertical side of 1000 nm, respectively. This work provides an effective way for designing high-efficiency single NW photovoltaic devices based on the symmetry breaking from the SNWs to RNWs.

Background: Physical activity is recommended to mitigate the incidence of obesity, but delivery of community wide initiatives is cumbersome. The challenges met by such programs are magnified when implementation transpires in the remote villages of Alaska. To overcome the difficulty of this challenge in the Arctic, the Skiku/AK Nordic cross-country skiing program was developed. The objective of this study was to evaluate whether access to Skiku/AK Nordic program would promote physical activity levels that met the daily recommendations for physical activity in Alaska Native children. Methods: Eight children (4 females and 4 males; 10±2 years/age) were recruited from Kaktovik, Alaska for participation in this study. Expert coaches and staff provided one week of cross-country ski instruction and access to ski equipment. Physical activity was monitored using ActiGraph GT3X+ accelerometers. Data collected from the devices was then downloaded and analyzed using ActiLife software. Results: The participants expended ~586 calories/day devoted to physical activity. Light and moderate physical activity was 68±38 minutes/day and 447±248 minutes/day, respectively. Conclusions: Delivery of the Skiku/AK Nordic program promoted favorable levels of physical activity in Alaska Native children. Further research is needed to assess the longitudinal and seasonal effectiveness of the Skiku/AK Nordic program.

Light trapping in single nanowires (NWs) are of vital importance for photovoltaic applications. However, circular NWs (CNWs) can limit its light-trapping ability due to high geometrical symmetry. In this work, we present a detailed study of light trapping in single NWs with an elliptical cross-section (ENWs). We demonstrate that the ENWs exhibit significantly enhanced light trapping compared with the CNWs, which can be ascribed to the symmetry-broken structure that can orthogonalize the direction of light illumination and the leaky mode resonances (LMRs). That is, the elliptical cross-section can simultaneously increase the light path length by increasing the vertical axis and reshape the LMR modes by decreasing the horizontal axis. We found that the light absorption can be engineered via tuning the horizontal and vertical axes, the photocurrent is significantly enhanced by 374.0% (150.3%, 74.1%) or 146.1% (61.0%, 35.3%) in comparison with that of the CNWs with the same diameter as the horizontal axis of 100 (200, 400) nm or the vertical axis of 1000 nm, respectively. This work advances our understanding of how to improve light trapping based on the symmetry breaking from the CNWs to ENWs and provides a rational way for designing high-efficiency single or self-assembled NW photovoltaic devices.

Purinergic receptors (P2X) are ATP-gated ion channels with an elusive role in the CNS. While the P2X2 and P2X4 subtypes are widely expressed in most neurons (i.e. at the edge of the postsynaptic densities of excitatory synapses), the direct contribution of P2X to synaptic transmission is uncertain. Several P2X have been shown to participate in receptor cross-talk: an interaction where one receptor (e.g. P2X2) influences the activity of another (e.g. GABA or AMPA receptors.) In this study, we tested for interactions between P2X2 or P2X4 and N-methyl-D-aspartate receptors (NMDARs). Using two-electrode voltage-clamp electrophysiology experiments in X. laevis oocytes, we demonstrate that both P2X2 and P2X4 interact with NMDARs in an inhibitory manner. When investigating the molecular domains responsible for this phenomenon, we found that the P2X2 c-terminus (CT) could interfere with P2X2 and P2X4 interactions with NMDARs. We also report that 11 distal CT residues on the P2X4 facilitate the P2X4-NMDAR interaction, and that a peptide consisting of these P2X4 CT residues (11C) can disrupt the interaction between NMDARs and P2X2 or P2X4. Collectively, these results provide new evidence for the modulatory nature of P2X2 and P2X4, suggesting they might play a more nuanced role in the CNS.

In wideband radar systems, the performance of motion parameters estimation can significantly affect the performance of object detection and the quality of inverse synthetic aperture radar (ISAR) imaging. Although the traditional motion parameters estimation methods can reduce the range migration (RM) and Doppler frequency migration (DFM) effects in ISAR imaging, the computational complexity is high. In this paper, we propose a new fast non-searching motion parameters estimation method based on cross-correlation of adjacent echoes (CCAE) for wideband LFM signals. A cross-correlation operation is carried out for two adjacent echo signals, then the motion parameters can be calculated by estimating the frequency of the correlation result. The proposed CCAE method can be applied directly to the stretching system, which is commonly adopted in wideband radar systems. Simulational results demonstrate that the new method can achieve better estimation performances, with much lower computational cost, compared with existing methods. The experimental results on real radar data sets are also evaluated to verify the effectiveness and superiority of the proposed method compared to the state-of-the-art existing methods.

The increase in hypoxia events, a result of climate change in coastal and fjord ecosystems, impacts the health and survival of mussels. These organisms deploy physiological and molecular responses as an adaptive mechanism to maintain cellular homeostasis under environmental stress. However, the specific effects of hypoxia on mussels of socioeconomic interest, such as Mytilus chilensis, are unknown. Using RNA-seq, we investigated the transcriptomic profiles of the gills, digestive gland, and adductor muscle of M. chilensis under hypoxia (10 days at 2 mg L-1) and reoxygenation (10 days at 6 mg L-1). There were 15,056 differentially expressed transcripts identified in gills, 11,864 in the digestive gland, and 9,862 in the adductor muscle. The response varied among tissues, showing chromosomal changes in Chr1, Chr9, and Chr10 during hypoxia. Hypoxia regulated signaling genes in the Toll-Like, mTOR, citrate cycle, and apoptosis pathways in gills, indicating metabolic and immunological alterations. These changes suggest that hypoxia-induced a metabolic shift in mussels, reducing reliance on aerobic respiration and increasing reliance on anaerobic metabolism. Furthermore, hypoxia appeared to suppress the immune response, potentially increasing disease susceptibility, with negative implications for the mussel culture industry and natural bed populations. This study provides pivotal insights into metabolic and immunological adaptations to hypoxia in M. chilensis, offering candidate genes for adaptive traits.

This review highlights the potential and limitations of mRNA vaccines with a particular focus on mucosal delivery as an alternative to parenteral administration. The strengths of mRNA vaccines are: a) Versatility: they can be adapted to target a wide range of pathogens; b) Faster development: designed and produced more quickly than traditional vaccines; c) High efficacy: effective in preventing severe disease, as demonstrated during the COVID-19 pandemic. Current challenges: a) Delivery: current methods (mainly intramuscular injection) may not be optimal for inducing mucosal immunity; b) Stability: mRNA is fragile and needs to be protected from degradation; c) Safety: potential side effects, including myocarditis, blood clotting, allergic reactions need further investigation. Mucosal delivery could be more effective in preventing the transmission of pathogens and is generally better accepted by the population. Pros: offers the potential to induce local immunity at the site of pathogen entry, potentially providing broader protection; Cons: developing effective delivery systems and adjuvants for mucosal delivery is difficult. Extracellular vesicles as a mucosal delivery system are promising and offer a potentially safe, scalable, and needle-free approach. Future directions: a) Optimizing mRNA constructs: strategies like codon optimization and self-amplifying RNA can improve stability and translation efficiency; b) Rigorous pre-clinical studies are essential before human trials.

Selenium nanoparticles (SeNPs) has higher bioavailability and safety than inorganic selenium, and was widely used in medical, agricultural, nutritional supplements, and antibacterial fields. The present study screened a strain L11 producing SeNPs from a selenium rich dairy cow breeding base in Hubei Province, China. The strain was identified as Bacillus subtilis through physiological, biochemical, and molecular biology analysis. Through optimization of cultivation conditions, the optimal cultivation parameters for L11 to produce SeNPs were pH=6, cultivation temperature of 37 °C, 4 mmol/L Na2SeO3, and cultivation for 48 hours. XPS, SEM-EDS, and TEM were used to verify that the Se particles produced by L11 are SeNPs with diameters ranging from 50 to 200 nm. The combination of protein analysis of different cell components and TEM analysis showed that L11 mainly produces SeNPs through the transformation of the cell's periplasmic space, cell membrane, and cell wall. Adding L11 SeNPs complex to sheep feed can significantly enhance the antioxidant activity and immunity of sheep, and increase the Se content in the neck muscles, liver, and spleen tissues.

Lipid nanoparticles (LNPs) have attracted extensive attention in tumor immunotherapy in recent years. The strategy of targeting immune cells in cancer therapy has become a research area of great interest. mRNA vaccines are a potential choice for tumor immunotherapy due to their ability to directly encode antigen proteins and stimulate a strong immune response. However, the mode of delivery and lack of stability of mRNA are key issues limiting its application. LNPs are an excellent mRNA delivery vector, and their structural stability and biocompatibility make them an effective means to deliver mRNA to specific targets. This study summarizes the research progress in LNP delivery vector-assisted targeted controlled release mRNA vaccines in tumor immunity. The role of LNPs in improving mRNA stability, immunogenicity and targeting is discussed. In addition, combined with the cutting-edge research results, the potential mechanisms and application prospects of LNP-mRNA vaccines in tumor immunotherapy were further analyzed. This review aims to systematically summarize the latest research progress in LNP delivery carrier-assisted targeted controlled-release mRNA vaccines in tumor immunity to provide new ideas and strategies for tumor immunotherapy and provide more effective treatment plans for patients.

Background Recent studies indicate that donor innate immune responses participate in initiating and accelerating innate responses and allorecognition in the recipient. These immune responses negatively affect recipient outcomes and predispose recipients to allograft coronary artery vasculopathy (CAV). We hypothesized that donor cause of death (COD) associated with higher levels of innate immune response would predispose recipients to more adverse outcomes post-transplant, including CAV. Methods We performed a single-institution retrospective analysis comparing donor characteristics and COD to recipient adverse cardiovascular outcomes. We analyzed the medical records of local adult donors (age 18-64) in a database of donors where adequate data was available. We linked donor characteristics and COD to recipient adverse cardiac outcomes after transplant, including cardiovascular (CV) death and incidence of significant antibody-mediated rejection (pAMR) after transplant (>2 episodes of pAMR within 90 days post-transplant). The data were analyzed using logistic regression, log-rank test of differences, and Tukey Contrast. Results Donor advanced age, female sex, and CODs of motor vehicle accident and intracranial hemorrhage were significantly associated with a higher incidence of recipient CV death and early pAMR compared to other donor characteristics and CODs. Conclusions In this single institution study, we found that recipients with hearts from donors over 40 years, donors who were female, or donors who died with a COD of motor vehicle accidents or intracranial hemorrhage had a higher frequency of CV related deaths and early pAMR. Donor monitoring and potential treatment of innate immune activation may decrease subsequent recipient innate responses and allorecognition stimulated by donor derived inflammatory signaling which lead to adverse outcomes.

Background: The molecular domestication of the gag gene of retrotransposons and retroviruses gave rise to the Gagr gene in the genome of Drosophila. The Gagr protein has a conservative structure in all Drosophila species, suggesting an essential function. As we previously shown, the Gagr gene may play a part in immune response and processes linked to stress reactions. Methods: Tub-GAL4&gt;UAS-Gagr flies, which had the Gagr gene knockdown in all tissues, were compared with the control hybrid Tub-GAL4&gt;w1118. Gagr gene function was verified by RNA-sequencing followed by RT-PCR and physiological tests. Results: In contrast to the control strain, we observed that flies with the Gagr gene knockdown had a shorter lifespan, but the mutant strain was more resistant to heat stress. Also, the Gagr knockdown strain had higher level of transcription of the immune response genes, according to a transcriptome analysis. It has been shown that the ammonium persulfate used to induce stress causes the Toll, Jal-STAT, and Jnk/MAPK signaling pathways to become activated, which results in a systemic response in numerus tissues in the control strain. Conversely, the Gagr gene mutant strain exhibits low expression of the stress response. Enrichment of the molecular function of genes overexpressed under ammonium persulfate stress in the control strain, but not in the Gagr knockdown mutant, revealed a category with 19 transcription factors involved in the control of organism development, morphogenesis and the functioning of the central nervous system. Their expression pattern and the Gagr gene's expression pattern match. The data obtained demonstrates the importance Gagr is to maintaining both the body's immune system and homeostasis.

Black Knot (BK) is a deadly disease of European (Prunus domestics) and Japanese (Prunus salicina) plums caused by the hemibiotrophic fungus Apiosporina morbosa. After infection, the appearance of warty black knots indicates a phytohormonal imbalance in infected tissues. Based on this hypothesis, we quantified phytohormones such as indole-3-acetic acid, tryptophan, indoleamines (N-acetylserotonin, serotonin, and melatonin), and cytokinins (zeatin, 6-benzyladenine, and 2-isopentenyladenine) in temporally collected tissues of susceptible and resistant genotypes belonging to European and Japanese plums during of BK progression. The results suggested auxin-cytokinins interplay driven by A. morbosa appears to be vital in disease progression by hampering the plant defense system. Taken together, our results indicate the possibility of using the phytohormone profile as a biomarker for BK resistance in plums.

The study investigated the effect of a multi-strain probiotic compound containing Bacillus coagulans, Enterococcus faecalis, Clostridium butyricum and Bacillus mesentericus as in-feed zinc oxide (ZnO) alterna-tive on growth performance, diarrhea incidence, antioxidant status, lipid profile, stress and immunity in weaned piglets. A total of 72 piglets were randomly divided into 3 groups with four replicates of six piglets each. The details of the groups were as follows; (i) weaned control group (WC) received basal diet, (ii) weaned probiotic group (WB) received basal diet and probiotics and (iii) positive control (PC) group received basal diet with 2500 mg/kg ZnO. The experiment lasted for 28 days. Probiotic supple-mentation improved growth performance and reduced diarrhea rate. Probiotics supplementation im-proved lipid profile; significantly lower levels of total cholesterol and low-density lipoprotein cholesterol and higher level of high-density lipoprotein cholesterol in WB group as compared to those of the control group (WC) were recorded. Probiotic supplementation stimulated antioxidant defense system by in-creasing total antioxidant capacity and decreasing lipid peroxidation. Probiotic supplementation down-regulated the stress biomarkers like serum cortisol and serum heat shock proteins. WB group showed higher serum levels of IgG and IgM throughout the study period and higher IgA at day 28 as compared to WC. These data suggest that supplementation of the probiotic minimizes the weaning stress, thereby improves the growth performance, lipid profile, antioxidant status and systemic as well as mucosal immunity. Therefore, the multi-strain probiotic compound may be used to replace ZnO in weaned piglets.

The newly emerged variants of SARS-CoV-2 created a potential threat among societies and highlighted one of the significant concerns in facing the pandemic. SARS-CoV-2 variants harboring mutations in the structural protein, especially in the RBD domain of spike protein, have raised concern about potential immune escape. The spike protein of SARS-CoV-2 play a vital role in infection and is an important target for neutralizing antibodies. The mutations that occur in the structural proteins, especially in the spike protein, lead to changes in the virus attributes of transmissibility, an increase in disease severity, a notable reduction in neutralizing antibodies generated, and thus a decreased response to vaccines and therapy. The immune response against SARS-CoV-2 has been reported mainly through innate immune responses rather than adaptive immune responses. SARS-CoV-2 invades the host's innate immunity, possibly through inducing cytokine storm, impairing type I IFN responses, and suppressing antigens presentation to T cells. Therefore, the adaptive immune response is required to combat SARS-CoV-2 infection. The SARS-CoV-2 infections activated both arms of adaptive immunity; humoral and cell-mediated immunity. The observed multiple mutations in the RBD domain of the spike protein compromised the adaptive immune response and showed immune escape because it increases the affinity of spike protein binding with the ACE-2 receptor of host cells and increases resistance to neutralizing antibodies. Cytotoxic T-cell responses are crucial in controlling SARS-CoV-2 infections from the infected tissues and clearing them from circulation. CD8+cytotoxic T cells identify and directly kill the infected cells by releasing soluble mediators perforin and granzymes. The functional exhaustion of cytotoxic T cells may increase the severity of the disease. The expression of activation markers of T cells could indicate hyperactivation or functional exhaustion; the exact implication is not yet understood in SARS-CoV-2 infections. These mutations at critical residues influence the antigenic profile of SARS-CoV-2, which may evade the immune responses and thus reduce the immunogenicity and efficacy of vaccines. Therefore, the spike protein may be recognized as a primary target for vaccines and drugs. This review article summarizes the impact of mutations in the spike protein of SARS-CoV-2, especially mutations of RBD, on immunogenicity, immune escape, and vaccine-induced immunity, which could potentially contribute to future studies focusing on vaccine design and immunotherapy.

Vaccination has proven highly effective against severe acute res-piratory syndrome coronavirus 2 (SARS-CoV-2), but the long-term immunogenicity and the functional preserved im-mune responses of vaccines are needed to inform evolving evi-dence-based guidelines for boosting schedules. We enrolled 205 healthcare workers into a cohort study; all had received three doses of BBIBP-CorV (China Sinopharm Bio-Beijing Company) inactivated vaccine. We assessed SARS-CoV-2 specific binding antibodies, neutralizing antibody, and peripheral T and B cell responses. We demonstrated that more robust antibody re-sponses to SARS-CoV-2 were elicited by booster immunization compared to primary vaccination. Neutralizing antibody titers to SARS-CoV-2 Omicron variant were also efficiently elevated post homologous vaccine booster despite in a lower titer compared to the prototype stain. In addition to S specific humoral and cellular immunity, BBIBP-CorV also induced N-specific antibody and ef-fector T cell responses. The third-dose vaccination led to further expansion of critical polyfunctional T cell responses, likely an essential element for vaccine protection. In particular, a func-tional role for Tfh cell subsets in immunity was suggested by the correlation between both CD4+Tfh and CD8+Tfh with total anti-body, IgG, B cell responses and neutralizing antibodies. Our study details the humoral and cellular responses generated by the BBIBP-CorV booster vaccination in a seven-month follow up study. There is a clear immunologic boosting value of homolo-gous inactivated SARS-CoV-2 vaccine boosters, a consideration for future vaccine strategies.

Glycans play important roles as recognition molecules on cell surfaces in living organisms due to their remarkable structural diversity. Carbohydrates exist in numerous isomeric forms and can adopt diverse structures through various branching patterns. Despite their relatively small molecular weights, they exhibit extensive structural diversity. On the other hand, lectins, also known as carbohydrate-binding proteins, not only recognize and bind to the diverse structures of glycans but also induce various biological reactions based on structural differences. Initially discovered as hemagglutinins in plant seeds, lectins have been found to play significant roles in cell recognition processes in higher vertebrates. However, our understanding of lectins in marine animals, particularly marine invertebrates, remains limited. Recent studies have revealed that marine animals possess novel lectins with unique structures and glycan recognition mechanisms not observed in known lectins. Of particular interest is their role as pattern recognition receptors in the innate immune system, where they recognize glycan structures of pathogens. Furthermore, lectins serve as toxins for self-defense against foreign enemies. Recent discoveries have identified various pore-forming proteins containing lectin domains in fish venoms and skins. These proteins utilize lectin domains to bind target cells, triggering oligomerization and pore formation in the cell membrane. These findings have spurred research into the new functions of lectins and lectin domains. In this review, we present recent findings on the diverse structures and functions of lectins in marine animals.

Over the past decade, studies have demonstrated the importance of bioactive metabolites derived from the microbiota in the regulation of physiological processes essential for homeostasis and the maintenance of human health. Strategies to modulate the production of these metabolites in the gastrointestinal tract hold promise for combating dysbiosis or inflammatory bowel disease. Metabolic engineering of probiotics could be one of these solutions. In this work, we engineered Escherichia coli Nissle 1917 (EcN) to overproduce spermidine, a metabolite known for its anti-immunosenescence and anti-inflammatory properties. Using a rational synthetic biology approach coupled with analysis by high resolution mass spectrometry, we designed in several steps and validated engineered probiotics overproducing and excreting spermidine. Based on our results, we first added the enzyme substrate putrescine and showed the overproduction of spermidine and decided to add a transporter limiting the production of the acetylated form of spermidine. Next, we used untargeted metabolomics to study the impact of engineering on the central metabolism of E. coli Nissle. Untargeted metabolomics appears to be a good strategy to optimize the metabolic engineering of probiotic strains and thus accelerate their development for personalized medicine.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has caused more than 600 million cases and over 6 million deaths worldwide. Vaccination has been the main strategy used to contain the spread of the virus, and to avoid hospitalizations and deaths. Currently, there are two mRNA-based and one adenovirus vectored vaccines approved and available for use in the U.S. population. The versatility, low cost and rapid-to-manufacture attributes of DNA vaccines are important advantages over other platforms. However, DNA vaccination must meet higher efficiency levels for use in humans. Importantly, in vivo DNA delivery combined with electroporation (EP) has been successfully used in the veterinary field. Here we evaluated the safety, immunogenicity and protective efficacy of a novel linear SARS-CoV-2 DNA vaccine candidate for delivered by intramuscular injection followed by electroporation (Vet-ePorator™) in ferrets. The results demonstrated that the linear SARS-CoV-2 DNA vaccine candidate did not cause unexpected side effects, and was able to elicit neutralizing antibodies and T cell responses using a low dose of the linear DNA construct in prime-boost regimen, and significantly reduced shedding of infectious SARS-CoV-2 through oral and nasal secretions in a ferret model.

Mast cells (MCs) are best known as key effector cells of immediate type allergic reactions that may even culminate in life-threatening anaphylactic shock syndromes. However, strategically positioned at host-environment interfaces and equipped with a plethora of receptors, MCs also play an important role in the first line defense against pathogens. Their main characteristic, the huge amount of preformed pro-inflammatory mediators embedded in secretory granules, allow for a rapid response and initiation of further immune effector cell recruitment. The same mechanism, however, may account for detrimental overshooting responses. MCs are not only detrimental in MC-driven diseases, but also responsible for disease exacerbation in other inflammatory disorders. Focusing on the skin as the largest immune organ, we herein review both beneficial and detrimental functions of skin MCs all the way from skin barrier integrity via host defense mechanisms to MC-driven inflammatory skin disorders. Moreover, we emphasize the importance of IgE-independent pathways of MC activation and their role in sustained chronic skin inflammation and disease exacerbation.

Herd immunity happens when a relatively large proportion of a population becomes infected by an agent, subsequently recovers, and attains immunity against the same agent. That proportion thus indirectly protects the naïve population by preventing the spread of the infection. Herd immunity has been suggested to interrupt and control the COVID-19 pandemic. However, relying on establishing herd immunity can be catastrophic considering the virulence and lethality of SARS-CoV-2. Meanwhile our understanding of the pathogenesis, case-fatality rate, transmission routes, and antiviral therapy for COVID-19 remains limited now. Interrupting or slowing the COVID-19 transmission seems more opportune than vaccination, antiviral therapy, or herd immunity, all of which will take some time to yield. Thus, social distancing, face-masking, and hygiene are the most appropriate immediate countermeasures. Because the social fabrics, economic implications, and local demands of various nations are unique, early relaxation of restrictions may seem hasty particularly when fatality rates are high, or when the healthcare systems could be inadequate or become inundated. Conclusively, avoiding any overwhelmingly risky approach in fighting the pandemic is prudent.

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.

Currently, with a large number of fatality rates, coronavirus disease-2019 (COVID-19) has emerged as a potential threat to human health worldwide. It has been well-known that severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is responsible for COVID-19 and World Health Organization (WHO) proclaimed the contagious disease as a global pandemic. Researchers from different parts of the world amalgamate together inquest of remedies for this deadly virus. Recently, it has been demonstrated that the spike glycoprotein (SGP) of SARS-CoV-2 is the mediator behind the entrance into the host cells. Our group has comprehensibly analyzed the SGP of SARS-CoV-2 through multiple sequence analysis along with the phylogenetic analysis. Further, this research work predicted the most immunogenic epitopes for both B-cell and T-cell. Notably, we focused mainly on major histocompatibility complex (MHC) class I potential peptides and predicted two epitopes; WTAGAAAYY and GAAAYYVGY, that bind with the MHC class I alleles which are further validated by molecular docking analysis. Furthermore, this study also proposed that the selected epitopes were shown availability in a greater range of the population. Hence, our study comes up with a strong base for the implementation of designing novel vaccine candidates against SARS-CoV-2, however adequate laboratory works will need to be conducted for the appropriate application.

The Bacillus Calmette-Guerin vaccine (BCG vaccine) designed to prevent tuberculosis in children has been shown to induce a trained immune response in the body to fight against bacteria as well as other parasites and viruses. This knowledge has been reciprocated to generate the idea that this vaccine can also offer protection against severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). Some recent pre-print articles have highlighted that countries with mass BCG immunizations seems to have a lower incidence of coronavirus disease 2019 (COVID-19) compared to those without BCG immunization. There are yet no experimental proof of any such association and the world health organisation (WHO) is currently testing the theory with clinical trials on selected cohorts. Epidemiologists and other scientific experts has expressed both their hope and concern simultaneously regarding the success theory of BCG vaccination to prevent COVID-19. Though its still not verified in any way whether the BCG vaccination can actually prevent COVID-19 or not but we believe a thorough analytical research in this regard is indeed worth a shot.

The recognition of (1→3)-β-D-glucans (BGs) by β-1,3-D-glucan recognition protein (BGRP) found in invertebrates plays a significant role in the activation of toll pathway and pro-phenol oxidase system in insect host defense against fungal invasion. To examine the structural diversity of BGs in BGRP interaction, the binding specificity of BGRPs cloned from four different insectswas characterized using ELISA. Recombinant BGRPs expressed as Fc-fusion proteins of human IgG1 bound to solid phase BGs. Because of the binding specificities, the BGRPs were categorized into two different ultrastructure- binding characters. The BGRPs from Silkworm and Indian meal moth bound to BGs containing triple-helical structure. Other BGRPs from red flour beetle and yellow mealworm beetle showed no binding to triple-helical BGs, but to alkaline-treated BGs, which have partially opened helical conformation. These evidences suggest that the innate immune system distinguishes different BG conformations and it is equipped for the diversity of BG structures.

Suppressors of cytokine signaling (SOCS) influence cytokine and growth factor signaling by negatively regulating the JAK-STAT pathway. This maintains homeostasis during host immune response. However, functional characterization of SOCS family members in invertebrates is limited. In this study, we discovered the Type-I subfamily of the SOCS genes in the mealworm beetle, T. molitor. The full-length ORFs of TmSOCS5, TmSOCS6, and TmSOCS7 consisted of 1,389, 897 and 1,458 nucleotides, encoding polypeptides of 462, 297 and 485 amino acids, respectively, The C-terminal region of TmSOCS was highly conserved in the SH2 and SOCS box domains. Phylogenetic analysis revealed that the three SOCS genes clustered within the same sub-family and the highest amino acid identity was with the Tribolium castaneum SOCS genes (TcSOCS). While the expression of TmSOCS5 and TmSOCS6 was low in larval, pupal, and adult stages of the insect, TmSOCS7 showed higher expression. The expression of TmSOCS5 and TmSOCS6 was higher in larval hemocytes and adult ovary. The microbes expressed the three TmSOCS genes to varying degrees. C. albicans elicited the strongest response in the host with highest 15-fold expression in TmSOCS7 3 h post-inoculation. Collectively, these data suggest that the Type I TmSOCS could play a role in eliciting host immunity.

Our goal was to determine the cellular immune response (CIR) among a random sample of the Borriana COVID-19 cohort (Spain) to identify its associated factors and their relationship with infection, reinfection and sequelae. We conducted a nested case-control study using a randomly selected sample of 225 individuals age 18 and older, including 36 individual naïve to SARS-CoV-2 infection, and 189 infected patients. We employed flow cytometry-based immunoassays for intracellular cytokine staining, utilizing Wuhan and BA.2 antigens and chemoluminescence microparticle immunoassay for detection SARS-CoV-2 antibodies. Logistic regression models were used. A total of 215 (95.6%) participants exhibited T-cell response (TCR) to at least one antigen. Positive responses of CD4+ and CD8+ T cells were 89.8% and 85.3% respectively. No difference in CIR was found for naïve and infected patients. Patients who experienced sequelae exhibited higher CIR than those without. A positive correlation was observed between TCR and Anti-Spike IgG levels. Factors positive associated with TCR included A-blood group, number of SARS-CoV-2 vaccine doses received, and Anti-N IgM; factors inversely related were the time elapsed since the last vaccine dose or infection, and B-blood group. These findings contribute valuable insights into the nuance immune landscape shaped by SARS-CoV-2 infection and vaccination.

Background/Objectives: Population aging is rapidly increasing, and the importance of preventive medicine has been stressed. Health checkup, diet, and exercise are of paramount importance. This study aimed to evaluate the effectiveness of a personalized dual-task intervention that combined exercise with cognitive tasks in improving physical and cognitive functions among independently living elderly individuals. Methods: Participants were aged &gt;65 years who were mostly independent in their activities of daily living, divided into 2 groups. The group receiving the 20-min robot-assisted session was compared to the group receiving traditional functional restoration training. This randomized trial assessed the impact of this intervention on the 30-s chair stand test score and Montreal Cognitive Assessment-Japanese version score of the participants. Results: Both scores significantly improved in the intervention group, indicating enhanced lower-limb function and cognitive capabilities. Conclusions: These findings suggest that integrating cognitive tasks with physical exercise can be a potent strategy to improve overall well-being in the elderly, offering valuable insights for designing comprehensive preventive health programs tailored to this demographic.

Opportunistic networks, an evolution of mobile Ad Hoc networks (MANETs), offer decentralized communication without relying on preinstalled infrastructure, enabling nodes to route packets through different mobile nodes dynamically. However, due to the absence of complete paths and rapidly changing connectivity, routing in opportunistic networks presents unique challenges. This paper proposes a novel probabilistic routing model for opportunistic networks, leveraging nodes' meeting probabilities to route packets towards their destinations. The model dynamically builds routes based on the likelihood of encountering the destination node, considering factors such as last meeting time and acknowledgment tables to manage network overload. Additionally, an efficient message detection scheme is introduced to alleviate high overhead by selectively deleting messages from buffers during congestion. Furthermore, the proposed model incorporates cross-layer optimization techniques, integrating optimization strategies across multiple protocol layers to maximize energy efficiency, adaptability, and message delivery reliability. Through extensive simulations, the effectiveness of the proposed model is demonstrated, showing improved message delivery probability while maintaining reasonable overhead and latency. This research contributes to the advancement of opportunistic networks, particularly in enhancing connectivity and efficiency for Internet of Things (IoT) applications deployed in challenging environments.

The satellite Earth observation (EO) sector is burgeoning with hundreds of commercial satellites being launched each year, delivering a rich source of data that could be exploited for societal benefit. Data streams from the growing constellation of commercial satellites are of variable quality, limiting the potential for their combined use in science applications that need long time-series data from multiple sources. The quality of calibration performed on optical sensors onboard many satellite systems is highly variable due to calibration methods, sensor design, mission objective, budget, or other operational constraints. A small number of currently operating well-characterised satellite systems with onboard calibration, such as Landsat-8/9, Sentinel-2, and planned future missions like the NASA Climate Absolute Radiance and Refractivity Observatory (CLARREO) Pathfinder, the European Space Agency (ESA) Traceable Radiometry Underpinning Terrestrial and Helio Studies (TRUTHS), and LIBRA from China, are considered benchmarks for optical data quality due to their traceability to international measurement standards. This paper describes the concept of a space-based transfer calibration radiometer called the Satellite Cross-Calibration Radiometer (SCR) that would enable the calibration parameters from satellites such as Landsat-8/9, Sentinel-2, or other benchmark systems to be transferred to a range of commercial optical EO satellite systems while in orbit. A description of the key characteristics of the SCR to successfully operate in orbit and transfer calibration from Reference systems to Client systems is presented. A system like the SCR in orbit could complement SI-Traceable satellites (SITSats) to improve data quality and consistency and facilitate the interoperable use of data from multiple optical sensor systems for delivering higher returns on the global investment in EO.

Financial stress can have significant implications for individuals, businesses, asset prices and the economy as a whole. This study examines the nonlinear structure and dynamic changes in the multifractal behavior of cross-correlation between the financial stress index (FSI) and four well-known commodity indices, namely Commodity Research Bureau Index (CRBI), Baltic Dry Index (BDI), London Metal Index (LME) and Brent Oil prices (BROIL), using multifractal detrended cross correlation analysis (MFDCCA). For analysis, we utilized daily values of FSI and commodity index prices from 16th June 2016 to 9th July 2023. The following are the most important empirical findings: (I) All of the chosen commodity market indices show cross correlations with the FSI and have notable multifractal characteristics. (II) The presence of power law cross-correlation implies that a noteworthy shift in FSI is likely to coincide with a considerable shift in the commodity indices. (III) The multifractal cross-correlation is highest between FSI and Brent Oil (BROIL) and lowest with LME. (IV) The rolling windows analysis reveals a varying degree of persistency between FSI and commodity markets. The findings of this study have a number of important implications for commodity market investors and policymakers.

The cost effective design of tidal turbines requires a good estimation of the loading cycles and their extrema that are related to the unsteady fluctuations of the current velocity. Apart from the ambient turbulence, the main source of velocity fluctuations is the presence of surface waves. In the present study, we analyse the effect of waves propagating against the current on the performance and the loads of a twin vertical axis tidal turbine by an experimental approach at a 1/20 scale. Overall, the results show little or no effect of the waves on the average power and loads compared to the condition with current only, but a significant impact on their standard deviation that rises linearly with the waves amplitude. The drag, lift and pitching moment show extended ranges up to 7.5 times higher and extreme values exceedance by 60 to 100 % with irregular waves compared to the condition without waves. Those load and power fluctuation increase are fully due to the presence of waves as the coherence function between the rotor torque or the loads and the velocity spectra exceed 0.5 on the whole wave frequency bandwidth. The results also reveal a rotational sampling of the waves by the rotors that had also been observed on horizontal axis turbines. From a structural design point of view, the authors recommand to conduct tests in irregular wave conditions as the loads range and extreme values are 1.5 to 2 times higher than those encountered with regular waves of the same significant height and period.

(1) Background: We aimed to identify factors associated with the presence of apical lesions (AL) on panoramic radiographs and to evaluate the predictive value of the identified factors. (2) Methodology: Panoramic radiographs from 1071 patients (age: 11-93 a, mean: 50.6 a ± 19.7 a) with 27532 teeth were included. Each radiograph was independently assessed by five experienced dentists for AL. A range of shallow machine learning algorithms (logistic regression, k-nearest neighbor, decision tree, random forest, support vector machine, adaptive and gradient boosting) were employed to identify factors on patient and tooth level associated with AL and to predict AL. (3) Results: AL were detected in 522 patients (48.7%) and 1133 teeth (4.1%), whereas males showed a significantly higher prevalence than females (52.5%/44.8%; p<0.05). Logistic regression found that an existing root canal treatment was the most important risk factor (adjusted Odds Ratio 16.89; 95% CI: 13.98-20.41), followed by the tooth type ‘molar’ (2.54; 2.1-3.08) and the restoration with a crown (2.1; 1.67-2.63). Associations between factors and AL were stronger and accuracy higher when using less complex models like decision tree (F1 score: 0.9 (0.89-0.9)). (4) Conclusions: The presence of AL was higher in root-canal treated teeth, those with crowns and molars. More complex machine learning models did not outperform less complex ones.

Chaphamaparvovirus (ChPV) is an ancient virus that has been detected in a variety of hosts. In this study, based on the phylogenetic analysis and the adaptability of ChPV to multiple hosts, we evaluated the potential of feline (FeChPV) and canine ChPV (CaChPV) for cross-species transmis-sion. Phylogenetic analysis showed that FeChPV and CaChPV were closely related. Notably, two strains of ChPVs isolated from domestic cats and 2 from dogs clustered together with CaChPVs and FeChPVs, respectively, suggesting the stringent boundaries between canine and feline ChPV may be broken. Further analysis revealed that CaChPV and FeChPV were more adapted to dogs than to cats, strongly suggesting the possibility of unidirectional or bidirectional transmission be-tween dogs and cats. Mutation analysis identified several shared mutations in cross-species-transmissible strains that were not located within immune epitopes. Furthermore, the VP struc-tures of FeChPV and CaChPV exhibited a high degree of similarity across both cross-species-transmissible and non-cross-species-transmissible strains. However, definitive experimental evi-dence is lacking, and its capacity for cross-species transmission should be approached with cau-tion and elucidated in further studies.

In today's world, news events are emerging incessantly. Classifying the same event reported by different countries is of significant importance for public opinion control and intelligence gathering. Due to the diverse types of news, relying solely on translators would be costly and inefficient, while depending solely on translation systems would incur considerable performance overheads in invoking translation interfaces and storing translated texts. To address this issue, we mainly focus on the clustering problem of cross-lingual news. To be specific, we use a combination of sentence vector representations of news headlines in a mixed semantic space and the topic probability distributions of news content to represent a news article. In the training of cross-lingual models, we employ knowledge distillation techniques to fit two semantic spaces into a mixed semantic space. We abandon traditional static clustering methods like K-Means and AGNES in favor of the incremental clustering algorithm Single-Pass, which we further modify to better suit cross-lingual news clustering scenarios. Our main contributions are as follows: (1) We adopt the English standard BERT as the teacher model and XLM-Roberta as the student model, training a cross-lingual model through knowledge distillation that can represent sentence-level bilingual texts in both Chinese and English. (2) We use the LDA topic model to represent news as a combination of cross-lingual vectors for headlines and topic probability distributions for content, introducing concepts such as topic similarity to address the cross-lingual issue in news content representation. (3) We adapt the Single-Pass clustering algorithm for the news context to make it more applicable. Our optimizations of Single-Pass include adjusting the distance algorithm between samples and clusters, adding cluster merging operations, and incorporating a news time parameter.

This study investigates the applications of reconfigurable intelligent surfaces (RIS) in heterogeneous downlink networks (HetNet). Due to the network densification, the small cell base station (SBS) interferes with the macrocell users (MUE). In this paper, we utilize RIS to mitigate cross-tier interference in an HetNet via directional beamforming by adjusting the phase shift of the RIS. We consider an RIS-assisted HetNet consisting of multiple SBS nodes and MUEs that utilize both direct paths and reflected paths. Therefore, the aim of this study is to maximize the sum rate of all MUEs by jointly optimizing the transmit beamforming of the macrocell base station (MBS) and the phase shift of the RIS. An efficient RIS reflecting coefficients-based optimization (RCO) is proposed based on a successive convex approximation approach. Simulation results are provided to show the effectiveness of the proposed scheme in terms of its sum rate in comparison with the scheme HetNet without RIS and the scheme HetNet with RIS but with random phase shifts.

This research was conducted with the aim of knowing how to compare the financial performance of the oil and gas trading industry with cross-sectional analysis techniques. The type of research conducted in this research is qualitative research with research objects at several companies, namely PT Radiant Utama Interinsco Tbk, PT Elnusa Tbk, PT AKR Corporindo Tbk, and PT Aneka Gas Industri Tbk. The data used in this study comes from secondary data, namely the internet in the form of company financial reports for the 2019-2021 period obtained from the Indonesia Stock Exchange. The results of this study indicate that PT Radiant Utama Interinsco Tbk has the best financial performance on inventory turnover ratio and average age, PT Elnusa Tbk has good inventory performance on current ratio, quick ratio, DAR, and DER., PT AKR. Corporindo Tbk has performed well on the ratios of TIE, FCC, Dividend Payout, Dividend Yield, and PER. PT Aneka Gas Industri Tbk has performed well on the ratio of Receivables Turnover Ratio and Average Age of Receivables.

Introduction: This study explores exposure to misinformation, COVID-19 risk perception, and confidence towards the government as predictors to negative attitudes toward the COVID-19 vaccine. Methods: A cross-sectional survey was carried out from 30 June to 30 August 2021 involving 775 respondents. The survey instrument for the questionnaire is an adaptation from various different studies consisting of five main variables: 1) misinformation about vaccination; 2) risk perception toward COVID-19; 3) attitudes toward the vaccination programme; 4) intention to get vaccinated; and 5) public confidence in the government in executing the vaccination programme. Results: The results of this study indicate that higher exposure to misinformation led to higher levels of negative attitudes toward the COVID-19 vaccine. When the perceived risk of COVID-19 infection was high, mistrust of vaccine benefits was low but there were also higher worries about the future effects of the vaccine. Confidence in government was associated with lower negative attitudes toward the COVID-19 vaccine. Conclusion: The results of this study may help develop an understanding of negative attitudes toward vaccinations in Malaysia and its contributing factors.

Objective: The aim of this study was to provide a new machine learning method to determine temporal events and inner-cycle parameters (e.g., cycle, poles and skis contact and swing time) in cross-country roller ski skating on the field, using a single deported inertial measurement unit (IMU). Methods: The developed method is based on long short-term memory neural networks to detect poles and skis initial and final contact with the ground during the cyclic movements. Eleven athletes skied four laps of 2.5 km at low and high intensity using skis with two different rolling coefficients. They were equipped with IMUs attached to the upper back, lower back and to the sternum. Data from force insoles and force poles were used as reference system. Results: The IMU placed on the upper back provided the best results, as the LSTM network was able to determine the temporal events with an accuracy ranging from 49 to 55 ms and the corresponding inner-cycles parameters were calculated with a precision of 63 to 68 ms. The method detected 95% of the events for the poles and 87% of the events for the skis. Conclusion: The proposed LSTM method provides a promising tool for assessing temporal events and inner-cycle phases in roller ski skating showing the potential of using a deported IMU to estimate different spatio-temporal parameters of human locomotion.

This article aims to identify the current development of cross-border tourism between Vietnam and China. The paper analyzes the perception and strategy of cross-border tourism development in the two countries, especially in the context of China’s implementation of the “Belt and Road Initiative” (BRI). The article emphasizes that Vietnam and China have recently made efforts to promote cross-border tourism development. At the same time, Vietnam and China see cross-border tourism development as a significant part of comprehensive border cooperation between the two countries. However, the development plans for cross-border tourism between the two countries are still mainly on the desk, not yet implemented effectively. Thus, its achievements are relatively modest. Besides, the article emphasizes that the interests of the people living in the border area, especially the Vietnam side, are almost “forgotten” in the development of cross-border travel between the two countries. Besides, the article also analyzes the challenges that the two sides are facing, especially the Vietnam side, in promoting the development of cross-border tourism between the two countries.

Having valid and reliable tools that help health professionals to assess fear in children undergoing medical procedures is essential to offer humanized and quality of care in the paediatric population. The aim of this study was to develop the cross-cultural adaptation and the evaluation of the psychometric properties of the Spanish version of the “Child Medical Fear Scale” in its shortened version (CMFS-R). The design consisted of two phases, first of cross-cultural adaptation and second of the psychometric validation of the CMFS-R with a sample of 262 children from Spain. Confirmatory factor analysis was conducted to assess construct validity and the Cronbach alpha and the adjusted item-total score correlation coefficients were performed to study reliability. The results confirmed internal consistency and construct validity of the Spanish version of the CMFS-R, indicating that the scale has an acceptable level of validity and reliability. Therefore, this study brings a new version of the scale to assess fear related to medical procedures for use in the Spanish paediatric population.

The uptake of buildings employing cross-laminated timber (CLT) assemblies and designed to Passivhaus standard has accelerated internationally over the past two decades due to several factors including design responses to the climate crisis by decarbonising the building stock. Structural CLT technology and the voluntary Passivhaus certification both show measurable benefits in reducing energy consumption, while contributing to durability and indoor comfort. However, there is a general lack of evidence to support a fast uptake of these technologies in Australia. This paper responds to the compelling need of providing quantitative data and adoption strategies, it explores their combined application as a potential pathway for climate-appropriate design of energy-efficient and durable mass timber envelope solutions for subtropical and tropical Australian climates. Hygrothermal risk assessments of interstitial condensation and mould growth of CLT wall assemblies inform best-practice design of mass timber buildings in hot and humid climates. This research found that the durability of mass timber buildings located in hot and humid climates may benefit from implementing the Passivhaus standard to manage interior conditions. The findings also suggested that climate-specific design of the wall assembly is critical for mass timber buildings, in conjunction with excellent stormwater management practices during construction and corrosion protection for metallic fasteners.

Two ligands, 1, 3-bis(4-carboxyphenyl)imidazolium chloride and 4, 4՛-bipyridine, were employed to prepare nickel and zinc azolium based MOFs, 1 and 2 by the mixed ligand solvothermal approach. The positively charged azolium moieties in the imidazolium linker resulted in a charged environment in the as-synthesized frameworks. As a result, 1 and 2 demonstrated preferential adsorption of CO2 over methane molecules in the gas phase adsorption due to the higher quadruple moment of CO2, which interacts more with the positively charged frameworks. Besides, in aqueous media, 1 and 2 exhibited incredible adsorption efficiency for anionic dyes. In the following, MOF 1 was metallated at the carbene site of the azolium linker to generate the novel heterogeneous catalyst 1-Pd, which was successfully applied for Sonogashira and Suzuki-Miyaura coupling reactions without losing its activity after three cycles.

We report on the successful preparation of wet dressings hydrogels based on Chitosan-Poly(N-Vinyl-Pyrrolidone)-Poly(ethylene glycol)-Poly(acrylic acid) and Poly(ethylene oxide) by e-beam cross-linking in weakly acidic media, to be used for rapid healing and pain release of infected skin wounds. The structure and compositions of hydrogels investigated according to sol-gel and swelling studies, network parameters, as well as FTIR and XPS analyses showed the efficient interaction of the hydrogel components upon irradiation, maintaining the bonding environment while the cross-linking degree increasing with the irradiation dose and the formation of a structure with the mesh size in the range 11-67 nm. Hydrogels with gel fraction above 85% and the best-swelling properties in different pH solutions were obtained for hydrogels produced with 15 kGy. The hydrogels are stable in the simulated physiological condition of an infected wound and show appropriate moisture retention capability and the water vapor transmission rate up to 272.67 g m-2 day-1, to ensure fast healing. The hydrogels proved to have a significant loading capacity of ibuprofen (IBU), being able to incorporate a therapeutic dose for the treatment of severe pains. Simultaneously, IBU was released up to 25% in the first 2h, having a release maximum after 8h.

Mass crises are disruptive to people's mental health. The study aimed to explore mental distress during COVID-19 quarantine in a sample of university workers in Brazil. The survey included sets of questions about demographics, health, and support, an open question about major concerns, and the Clinical Outcome Routine Evaluation (CORE-OM), a measure of mental distress. 407 professionals participated in the study: mean age of 40 years (SD = 11.2), mostly female (67.8%), married (64.8%) and fulfilling social distancing to avoid COVID-19 infection (99%). Using the Consensual Qualitative Research for simple qualitative data (CQR-M) the main areas of concern were grouped into six domains, as follows: Work, Health, Isolation, Personal life and routine, Social environment, and Future. Many responses were multiple. They form categories indicating specific concerns within these domains. Quantitative data were analyzed by identifying the simple effects of potential predictors of mental distress. The results indicated medium effects of help with household chores, psychiatric treatment, age and physical exercise. Having someone available to listen was the only variable with a large effect in reducing mental suffering. The hybrid approach showed that the psychological experience during the pandemic is quite multifaceted and complex pointing new clues for public mental health.

This paper examined the multifractal properties of six acknowledged agro-meteorological parameters, such as reference evapotranspiration (ET0), wind speed (U), incoming solar radiation (SR), air temperature (T), air pressure (P), and relative air humidity (RH) of five stations in California, USA. The investigation of multifractality of datasets from stations with differing terrain conditions: Dagget, Bakersfield, Santa Maria, Los Angeles and San Diego using the Multifractal Detrended Fluctuation Analysis showed the existence of a long term persistence and multifractality irrespective of the location. The scaling exponents of SR and ET0 time series are found to be higher for stations with higher altitudes. Subsequently, this study proposed using the novel multifractal cross correlation (MFCCA) method to examine the multiscale-multifractal correlations properties between ET0 and other investigated variables. MFCCA could successfully capture the scale dependent association of different variables and the dynamics in the nature of their associations from seasonal to multi-annual time scale. The multifractal exponents of pressure and relative air humidity are consistently lower than the exponents of ET0, irrespective of station location. This study found that joint scaling exponent was nearly the average of scaling exponents of individual series in different pairs of variables. Additionally, the α-values of joint multifractal spectrum were lower than the α values of both of the individual spectra, validating two universal properties in the mutifractal cross correlation studies for agro-meteorological time series. The temporal evolution of cross-correlation showed similar pattern for all pair-wise associations involving ET0, except for the RH-ET0 link.

In this project, we use a statistical multiple regression to study the impact of eight various predictors (relative compactness, surface area, wall area, roof area, overall height, orientation, glazing area, glazing area distribution) to estimate the cooling load energy efficiency of residential buildings. We try to analyze and visualize the effect of each predictor with each of the response variable using different classical statistical analysis tools used in describing linear models, in such a way so that we can find out the most strongly related predictor variables. Before starting all of this, we use the idea of model selection by stepwise regression technique and compare the AIC of these models and identified a better model between all of them. Then, we compare a classical linear regression approach by simulations on 768 diverse residential buildings show that we can predict CL with low mean absolute error. By using ANOVA we determine variation in the different residuals. Also, we use non constant variance test to verify it. Furthermore, we check leverage and influence points as well as outliers as well as determined cook distance for influential points. By taking box cox transformation and weights, we also introduce WLS technique to fit the model for better results and did all type of important analysis to understand the energy efficiency. Finally, we show 5-fold cross validation to verify our model.

Recently deep cross-modal hashing networks have received increasing interests due to its superior query efficiency and low storage cost. However, most of existing methods concentrate less on hash representations learning part, which means the semantic information of data cannot be fully used. Furthermore, they may neglect the high-ranking relevance and consistency of hash codes. To solve these problems, we propose a Self-Attention and Adversary Guided Hashing Network (SAAGHN). Specifically, it employs self-attention mechanism in hash representations learning part to extract rich semantic relevance information. Meanwhile, in order to keep invariability of hash codes, adversarial learning is adopted in the hash codes learning part. In addition, to generate higher-ranking hash codes and avoid local minima early, a new batch semi-hard cosine triplet loss and a cosine quantization loss are proposed. Extensive experiments on two benchmark datasets have shown that SAAGHN outperforms other baselines and achieves the state-of-the-art performance.

Zika virus (ZIKV) is a flavivirus that originated in Africa but emerged in Latin America in 2015. In this region, other flaviviruses such as Dengue (DENV), West Nile, and Yellow Fever Virus (YFV) also circulate, allowing for possible antigenic cross-reactivity to impact viral infections and immune responses. Studies have found antibody mediated enhancement between DENV and ZIKV, but the impact of YFV antibodies on ZIKV infection has not been fully explored. ZIKV infections cause congenital syndromes, such as microcephaly, necessitating further research into ZIKV vertical transmission through the placental barrier. Recent advancements in biomedical engineering have generated co-culture methods that allow for in vitro recapitulation of the maternal: fetal interface. This study utilized a transwell assay, which is a co-culture model utilizing human placental syncytiotrophoblasts, fetal umbilical cells, and a differentiating embryoid body to replicate the maternal: fetal axis. To determine if cross reactive YFV vaccine antibodies impact the pathogenesis of ZIKV across the maternal fetal axis, maternal syncytiotrophoblasts were inoculated with ZIKV or ZIKV incubated with YFV vaccine anti-sera, and viral load was measured 72 hours post inoculation. The data show that the impact of YFV on ZIKV replication is cell line dependent. In differentiating embryoids, the presence of YFV antibodies enhanced ZIKV infection. Since viral pathogenesis, and the impact of antigenic cross-reactive antibodies, is cell line specific at the maternal-fetal axis, this suggests there may be discreet mechanisms that impact congenital ZIKV infections.

Background: Public misconception and demand for the indication of antibiotics could lead to inappropriate prescribing and consumption. Successful treatment can only be achieved when the public and industrial users have knowledge on antibiotic use and resistance. This survey is aimed to assess antibiotic usage and knowledge regarding antibiotics and antimicrobial resistance (AMR) among undergraduate students of Universiti Brunei Darussalam (UBD), public university located in Brunei Darussalam. Methods: A cross-sectional study was performed using a self-administered questionnaire. The questionnaire was adapted from the World Health Organization (WHO) Antibiotic Resistance, Multi-country public awareness survey distributed online. Students at UBD were invited to participate in the online survey through internal email. The questionnaire consisted of 5 sections: demographic information, antibiotic usage, knowledge on antibiotics, antibiotic resistance (AMR) and use of antibiotics in agriculture. Data were analyzed descriptively and appropriate inferential statistics was used accordingly. Cronbach’s alpha was also done to determine the internal consistency. The section on antibiotic use and knowledge showed good internal consistency of Cronbach’s alpha 0.66 and 0.86 respectively. Research ethics approval was obtained from the PAPRSB Institute of Health Sciences, Universiti Brunei Darussalam (UBD). Results: A total of 145 students returned the complete questionnaire. The result of the study found that 50% of the students had good level of knowledge of antibiotic and antimicrobial resistance with a mean total knowledge score of 11.4 out of 14. Respondents reported the use of antibiotic in the past (69%). Many of the students could identify the use of antibiotics for the treatment of bacterial infection. However, there were also students who incorrectly thought that antibiotics can be used for cold and flu (43%) and fever (41%). Moreover, 76% of the respondents mistakenly believed that antibiotic resistance is the result of the body becoming resistant to antibiotics. Only 12% of the respondents were found to have poor knowledge in the study. Conclusions: Misconceptions in regards to the use of antibiotics for conditions related to viral illnesses was noticed among the respondents in our study. Thus, improving knowledge on antibiotics is crucial to address those beliefs.

Since the COVID-19 caused by SARS-CoV-2 break out in Wuhan China from Dec. 2019, it has spread to hundreds of countries up to now. Scientists from all over the world have paid tremendous efforts to research and try to control the disease. Previous studies suggested that some of the wild animals could be intermediate hosts between humans and origination of SARS-CoV-2, and some companion animals of humans can be infected by SARS-CoV-2, which raised our curiosity about cross-infection of SARS-CoV-2 between animals and humans. Thus, we select some kinds of animals that might have contact with humans to estimate the susceptibility to SARS-CoV-2 in different animals by evolutionary analysis of their receptors for SARS-CoV-2. The results show that some companion animals of the Felidae family like the cat has a higher infection possibility while the species of the Rodent family like the rat and mouse having close contact with humans show an opposite result, which consist with recent animal experiments and researches. These should raise concerns about cross-infection between human and companion animals or animals having close contact with humans which might turn animals into depositaries of the coronavirus even after control of SARS-CoV-2 spreading and cause second or more waves of infections after social reopening. Another side of our results stands by the opinion that bioinformatic analysis can be consistent with experiments in some respects so that we can prevent unnecessary sacrifice of laboratory animals in future experiments.

With the rapid development of Internet and the widely usage of smart devices, massive multimedia data are generated, collected, stored and shared on the Internet. This trend makes cross-modal retrieval problem become a hot issue in this years. Many existing works pay attentions on correlation learning to generate a common subspace for cross-modal correlation measurement, and others uses adversarial learning technique to abate the heterogeneity of multi-modal data. However, very few works combine correlation learning and adversarial learning to bridge the inter-modal semantic gap and diminish cross-modal heterogeneity. This paper propose a novel cross-modal retrieval method, named ALSCOR, which is an end-to-end framework to integrate cross-modal representation learning, correlation learning and adversarial. CCA model, accompanied by two representation model, VisNet and TxtNet is proposed to capture non-linear correlation. Beside, intra-modal classifier and modality classifier are used to learn intra-modal discrimination and minimize the inter-modal heterogeneity. Comprehensive experiments are conducted on three benchmark datasets. The results demonstrate that the proposed ALSCOR has better performance than the state-of-the-arts.

An appearance model plays a crucial rule in multi-target tracking. In traditional approaches, the two steps of appearance modeling i.e visual representation and statistically similarity measure are modeled separately. Visual representation is achieved either through hand-crafted features or deep features and statically similarity is measure through a cross entropy loss function. A loss function based on cross-entropy (KL-divergence, mutual information) find closely related probability distribution for the targets. However, if the targets have similar visual representation, it ends up mixing the targets. To tackle this problem, we come up with a synergetic appearance model named Single Shot Appearance Model based on Siamese neural network. The network is trained with a contrastive loss function for finding the similarity between different targets in a single shot. The input to the network is two target patches and based on their similarity, a contrastive score is output by the network. The proposed model is evaluated on accumulative dissimilarity metric on three datasets. Quantitatively, promising results are achieved against three baseline methods.

Abstract Optimal targeting of nanoparticles (NP) to dendritic cells (DCs) receptors to deliver cancer-specific antigens is key to an efficient induction of anti-tumor immune responses. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles containing tètanus toxoid and gp100 melanoma-associated antigen, toll-like receptor adjuvants were targeted to the DC-SIGN receptor in DCs by specific humanized antibodies or by ICAM3-Fc fusion proteins mimicking natural ligand. Despite higher binding and uptake efficacy of anti-DC-SIGN antibody-targeted NP vaccines than ICAM3-Fc ligand, no difference were observed in DC activation markers CD80, CD83, CD86 and CCR7 induced. DCs loaded with NP coated with ICAM3-Fc appeared more potent in activating T cells via cross-presentation than antibody-coated NP vaccines. This fact could be very crucial in the design of new cancer vaccines.

Multi-task Gaussian processes (MTGPs) are a powerful approach for modeling structured dependencies among multiple tasks. Researchers on MTGPs have contributed to enhance this approach in various ways. Current MTGP methods, however, cannot model nonlinear task correlations in a general way. In this paper we address this problem. We focus on spectral mixture (SM) based kernels and propose an enhancement of this type of kernels, called multi-task generalized convolution spectral mixture (MT-GCSM) kernel. The MT-GCSM kernel can model nonlinear task correlations and mixtures dependency, including time and phase delay, not only between different tasks but also within a task at the spectral mixture level. Each task in MT-GCSM has its own generalized convolution spectral mixture kernel (GCSM) with a different number of convolution structures and all spectral mixtures from different tasks are dependent. Furthermore, the proposed kernel uses inner and outer full cross convolution between base spectral mixtures, so that the base spectral mixtures in the tasks are not necessarily aligned. Extensive experiments on synthetic and real-life datasets illustrate the difference between MT-GCSM and other kernels as well as the practical effectiveness of MT-GCSM.

Background: In rheumatoid arthritis (RA), anti-citrullinated protein/peptide antibodies (ACPAs) are responsible for disease onset and progression, however, our knowledge is limited on ligand binding affinities of autoantibodies with different citrulline-peptide specificity. Methods: Citrulline-peptide specific ACPA IgGs were affinity purified and tested by ELISA. Binding affinities of ACPA IgGs and serum antibodies were compared by surface plasmon resonance (SPR) analysis. Bifunctional nanoparticles harboring a multi-epitope citrulline-peptide and a complement activating peptide were used to induce selective depletion of ACPA producing B cells. Results: KD values of affinity purified ACPA IgGs varies between 10-6-10-8 M and inversely correlate with disease activity. Based on their cross-reaction with citrulline-peptides we designed a novel multi-epitope peptide, containing Cit-Gly and Ala-Cit motifs in two-two copies, separated with a short, neutral spacer. This peptide detects antibodies in RA sera with 66 % sensitivity and 98 % specificity in ELISA and is recognized by 90% of RA sera, while none of the healthy samples in SPR. When coupled to nanoparticles, the multi-epitope peptide specifically targets and depletes ACPA producing B cells ex vivo. Conclusions: The unique multi-epitope peptide designed on the basis of ACPA cross-reactivity might be suitable to develop better diagnostics and novel therapies for RA.

New class of biologically active and non-active compounds can be synthesized via transition metal mediated Suzuki cross coupling reaction that has a great impact on the advancement of organic chemistry. These resulted products can lend a helping hand in pharmaceutical and polymer chemistry for the betterment of mankind. Suzuki-Miyaura cross coupling reaction is one of the best tools through which many natural and non-natural compounds can be synthesized.

The stiffness of the myosin cross-bridges is a key factor in analysing possible scenarios to explain myosin head changes during force generation in active muscles. The seminal study of Huxley and Simmons (1971: Nature 233: 533) suggested that most of the observed half-sarcomere instantaneous compliance (=1/stiffness) resides in the myosin heads. They showed with a so-called T₁ plot that, after a very fast release, the half-sarcomere tension reduced to zero after a step size of about 60Å (later with improved experiments reduced to 40Å). However, later X-ray diffraction studies showed that myosin and actin filaments themselves stretch slightly under tension, which means that most (at least two-thirds) of the half sarcomere compliance comes from the filaments and not from cross-bridges. Here we have used a different approach, namely to model the compliances in a virtual half sarcomere structure in silico. We confirm that the T₁ curve comes almost entirely from length changes in the myosin and actin filaments, because the calculated cross-bridge stiffness (probably greater than 0.4 pN/Å) is higher than previous studies have suggested. In the light of this, we present a plausible modified scenario to describe aspects of the myosin cross-bridge cycle in active muscle. In particular, we suggest that, apart from the filament compliances, most of the cross-bridge contribution to the instantaneous T₁ response comes from weakly-bound myosin heads, not myosin heads in strongly attached states. The strongly attached heads would still contribute to the T₁ curve, but only in a very minor way, with a stiffness that we postulate could be around 0.1 pN/Å, a value which would generate a working stroke close to 100 Å from the hydrolysis of one ATP molecule. The new program can serve as a tool to calculate sarcomere elastic properties for any vertebrate striated muscle once various parameters have been determined (e.g. tension, T₁ intercept, temperature, X-ray diffraction spacing results).

Tobamoviruses are a group of plant viruses posing a significant threat to agricultural crops worldwide. In this review, we focus on plant immunity against tobamoviruses, including pattern-triggered immunity (PTI), effector-triggered immunity (ETI), RNA-targeting pathway, hormones and reactive oxygen species (ROS). Further, we highlight genetic resources for resistance against tobamoviruses in plant breeding and discuss future directions on plant protection against tobamoviruses.

The new class of mRNA vaccines is studied extensively, leading to many novel prospects based on the pivotal success of vaccines against the SARS-Cov-2 virus. Many novel mechanisms of immune response discovered have led to the possibility of mutation-resistant vaccines by combining multiple conserved epitopes as antigens to manipulate the T-cell and B-cell responses; these antigens can also come from different organisms, providing protection against numerous diseases and of most tremendous significance is the utility of mRNA vaccines in preventing and treating more than 100 autoimmune disorders. This is a significant humanitarian breakthrough given the ease and faster and low cost of mRNA vaccines, being a chemical entity. This paper provides a prospective analysis of mRNA vaccines with much broader applications than anticipated when these vaccines entered treating SARS-Cov-2 infections.

Current COVID-19 vaccines can effectively reduce disease severity and hospitalisation; however, they are not considerably effective in preventing infection and transmission. In this context, mucosal vaccines are pertinent to prevent SARS-CoV-2 infection and spread. In this study, we generated a replication-competent recombinant chimeric influenza A virus (IAV) expressing the receptor-binding domain (RBD) of SARS-CoV-2 prototype in the C-terminus of the neuraminidase (NA) of A/Puerto Rico/08/1934 H1N1 (PR8). The remaining seven segments from A/WSN/1933 H1N1 (WSN) were named PR8NARBD/WSN. We observed that the recombinant virus with the WSN backbone demonstrated improved expression of NA and RBD. A single intranasal dose of PR8NARBD/WSN in mice generated robust mucosal immunity, neutralising antibodies, cellular immunity, and tissue-resident memory T cells specific to SARS-CoV-2 and IAV. Importantly, immunisation with PR8NARBD/WSN viruses effectively protected mice against lethal challenges with H1N1, H3N2 IAV, and SARS-CoV-2 Beta variant and significantly reduced lung viral loads. Overall, our research demonstrates the promising potential of PR8NARBD/WSN as an attractive vaccine against emerging SARS-CoV-2 variants and influenza A virus infections.

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 enters the host by infecting nasal ciliated cells. Then, the virus can spread towards the oropharyngeal cavity and the pulmonary tissues. The antiviral adaptive immunity is promptly induced in response to virus detection, with virus-specific T lymphocytes appearing before antiviral antibodies. Both breadth and potency of the antiviral CD8+ T cell immunity have a key role in containing viral spread and disease severity. Current anti-SARS-CoV-2 vaccines do not impede the virus replication in the upper respiratory tract, and there is consensus on the fact that the best potency of the antiviral immune response in both blood and upper respiratory tract can be reached upon infection in vaccinees (i.e., breakthrough infection). However, whether the antiviral CD8+ T cells developing in response to the breakthrough infection in the upper respiratory tract diffuse to the lungs also is still largely unknown. To fill the gap, we checked the CD8+ T cell immunity elicited after infection of K18-hACE2 transgenic mice both 3 weeks and 3 months after anti-Spike vaccination. The virus-specific CD8+ T cell immunity was monitored in both blood and the lungs before and after infection. By investigating the de novo generation of CD8+ T cells specific for SARS-CoV-2 viral proteins, we found that both membrane (M) and/or nucleocapsid (N)-specific CD8+ T cells were induced at comparable levels in blood of both unvaccinated and vaccinated mice. Conversely, N-specific CD8+ T cells were readily found in the lungs of control mice, but were either rare or absent in those of vaccinated mice. These results support the idea that the hybrid cell immunity developing after asymptomatic/mild breakthrough infection strengthens the antiviral cell immunity at lungs only marginally, implying that the direct exposition of the viral antigens is required for the induction of an efficient antiviral cell immunity in the lungs.

The risks for complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection are higher in obese individuals. Obesity is a state of chronic low-grade inflammation, with high leptin levels due to leptin resistance, high basal levels of other pro-inflammatory cytokines such as TNF-alpha, MCP-I and IL-6, and low adiponectin levels, thus contributing to a state of defective innate immunity as well as impaired B and T cell responses. Obesity is a risk factor for metabolic syndrome, diabetes, cardiovascular disease and hypertension. It has been observed that pre-existence of these diseases confers a higher risk of severe SARS CoV2 infection as well as the need for intensive care; even below the age of 60 years if their body mass index (BMI) is greater than 30 kg/m2, and even more so if it is > 35 kg/m2. The metabolic factors contributing to the changes in altering the immune mechanisms in obese individuals and how this enhances the susceptibility to infection and development of serious SARS-CoV2 infection have been the subject of many debates. Future development of targeted therapy and guidelines will be benefited by greater understanding into these metabolic pathways.

Chronic kidney disease (CKD) is actually considered a public health priority according to the increasing number of patients affected by this condition: this casuistry is not only related to specific glomerular, tubular or autoimmune diseases or a consequence of acute kidney injury (AKI) episodes leading to organ failure, but it is tied to the progression of life expectancy and the impact of comorbidities such as cardiovascular disease, diabetes and cancer. CKD and its comorbidities promote low grade inflammatory status with an impact on patients’ clinical conditions, reducing their possibility for kidney transplantation or graft survival and their survival when receiving renal replacement therapies such as hemodialysis (HD) or peritoneal dialysis (PD). CKD is often referred to as an ageing accelerator: innate immune system dysregulation, in the uraemic proinflammatory milieu, is involved in this accelerated senescence phenomena and pentraxins, particularly Pentraxin-3 (PTX-3), are of particular interest in the development of kidney disease. A complete understanding of the mechanism of CKD progression, innate immune system involvement and a proper definition of PTX-3 role in kidney disease, could redefine the approach for diagnosis and a more centered patients’ management to slow down CKD progression over time and reduce its clinical and social impact.

Mass cells (MCs) are tissue cells that are derived from bone marrow stem cells that contribute to allergic reactions, inflammatory diseases, innate and adaptive immunity, autoimmunity, and mental disorders. MCs located near the meninges communicate with microglia through the production of mediators such as histamine and tryptase, but also through the secretion of IL-1, IL-6 and TNF, which can create pathological effects in the brain. Preformed chemical mediators of inflammation and tumor necrosis factor (TNF) are rapidly released from the granules of MCs, the only immune cells capable of storing the cytokine TNF, although it can also be produced later through mRNA. The role of MCs in nervous system diseases has been extensively studied and reported in scientific literature and is of great clinical interest. However, many of the published articles concern studies on animals (mainly rats or mice) and not on humans. MCs are known to interact with neuropeptides that mediate endothelial cell activation, resulting in central nervous system (CNS) inflammatory disorders. In the brain, MCs interact with neurons causing neuronal excitation with the production of neuropeptides and the release of inflammatory mediators such as cytokines and chemokines. This article explores the current understanding of MC activation by neuropeptides and the role of pro-inflammatory cytokines, suggesting a therapeutic effect of the anti-inflammatory cytokines IL-37 and IL-38.

Immune checkpoint inhibitors (ICI) are currently use in a wide range of tumors, but only 20-40% of patients achieve clinical benefit. Aim of our study was to find predictive biomarkers of ICI treatment. We analyzed by immunohistochemistry various cell subsets, including CD3+ cells, CD8+ cells, CD68+ cells, CD20+ cells, FoxP3+ cells, and molecules as LAG-3, IDO1, TGfβ. Comprehensive genomic profiles were analyzed. Correlation of various biomarkers with efficacy of ICI treatment in patients with advanced solid tumors was evaluated. We evaluated 56 patients treated with ICI monotherapy. Longer median progression-free survival (PFS) was found in tumors negative for nuclear FoxP3 (P = 0.002, HR 0.14) and in TMB-high tumors (P = 0.024, HR 0.38). Longer overall survival (OS) was found in patient with intraepithelial CD8 negativity (P = 0.045, HR 0.47). In malignant melanoma CD68 negativity, FoxP3 negativity and PDL TPS ≥ 1 was associated with longer PFS. In NSCLC FoxP3 was associated with longer PFS and OS. We found that absence of expression of several biomarkers such as CD68 and FoxP3 is associated with better survival. TMB-high and PD-L1 expression not universally but in certain disease could predict response.