This study investigates the effectiveness of a range of timber-based solutions for seismic and energy retrofitting of existing masonry buildings. These solutions are designed not only to prevent structural collapse during earthquakes but also to create integrated interventions that enhance thermo-physical performance and reduce emissions in existing buildings. Various case scenarios were considered and both mechanical and energetic behavior post-intervention were evaluated. Timber-engineered products serve as foundational components for the retrofit approach, encompassing one-dimensional vertical elements (strong-backs) and various types of panels (cross-laminated timber panels, laminated veneer lumber panels, and oriented strand board panels). The analyzed retrofit techniques share a common principle, involving the attachment of these timber-based elements to the building's wall surfaces through mechanical point-to-point connections. The proposed solutions integrate strong-backs and timber panels with membranes and insulation layers, yielding cohesive and highly effective interventions. Finite element modeling was employed to analyze the mechanical and thermal responses of the retrofitted walls. A comprehensive comparative analysis of various techniques was conducted to determine the most effective solution for each specific scenario.

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

Little is known about the long-term durability of the induced immune response in subjects af-fected by obesity, particularly in those with an abdominal distribution of adipose tissue. We evaluated SARS-CoV-2-specific antibody response after BNT162b2 vaccine booster dose, com-paring individuals with abdominal obesity (AO) with those without, discerning between indi-viduals previously infected or not. IgG-TrimericS were measured in 511 subjects at baseline, 21 days after vaccine dose-1 and at one, three, six and nine months after dose-2 and at one and three months after booster dose. Nucleocapsid antibodies were assessed at baseline and at the end of the study to detect SARS-CoV-2 infection. To evaluate the three-months difference in absolute variation of IgG-TrmicericS levels from booster dose we used multivariable linear regression that showed interaction between AO and SARS-CoV-2 infection status (p=0.016). AO is associated with higher absolute IgG-TrimericS variation in prior infected individuals, regardless of possi-ble confounders and IgG-TrimericS levels at booster dose (p=0.0125). No interaction was evinced using BMI in the same regression model (p=0.418). The robust response in the development of antibodies after booster dose, observed in people with OA and previous infection, may support the recommendations to undergo the booster dose also in this population group.

Background: The effect of rice bran arabinoxylan compound (RBAC), a plant-based immunomodulator, on the quality of life (QoL) in cancer patients and underlying physiological pathways remains unclear. Trial design: The RBAC-QoL study is a double-blind, randomised, controlled pilot feasibility study. The aim is to determine RBAC’s effects on QoL and the associated action mechanisms. Primary outcomes are the EORTC QLQ-C30 functional, symptom, and global QoL scores with inflammatory, nutritional, and cytokine parameters as secondary and exploratory outcomes. Methods: Recruitment targets adults diagnosed with solid organ tumours (≥ stage II) undergoing active treatment in several outpatient centres in New South Wales, Australia. Interventions are RBAC or matched placebo at 3g/day for 24 weeks allocated through stratified randomisation with participants, oncologists, and data collectors blinded. Data is collected from five study visits six weeks apart. The trial is ongoing. An interim intention-to-treat analysis was performed using repeated measure ANOVA with pairwise comparisons where statistical significance is observed and adjusted with covariates. Results: Global QoL scores from currently available data (n = 16; RBAC = 7, placebo = 9) were statistically different between groups (F[1,8] = 8.6, p = 0.019, eta2[g] = 0.267). Pairwise comparisons found significant differences at week 6 (p = 0.032, Cohen’s d = 1.454) and marginally at week 12 (p = 0.069, d = 1.427). Age-adjusted analysis showed a continuous upward trend in QoL improvement over time with RBAC, while the placebo group did not deviate from baseline QoL. Significant elevations of serum white blood cell count (week 18) and total protein (weeks 12 and 18) were detected in the RBAC group compared to placebo. The total protein levels correlated highly with white blood cell count (Pearson’s r = 0.539, p < 0.001) and moderately with the global QoL scores (r = 0.338, p = 0.01). No intervention-related adverse events were reported in both groups. Conclusions: RBAC improves QoL beyond placebo during active cancer treatment, possibly through the immuno-nutritional pathway. These findings are preliminary but valuable for future research. Funding and registration: Daiwa Pharmaceutical Co., Ltd, Japan; BioMedica Nutraceuticals Pty Ltd., Australia. ANZCTR Reg No: ACTRN12619000562178p.

Atopic dermatitis (AD), a T2 inflammatory skin condition, is widely recognized as one of the most prevalent chronic and recurrent skin disorders. One of the most effective therapy for treating moderate-to-severe AD is Dupilumab, a monoclonal antibody that blocks both IL-4 and IL-13 signaling. At the same time, no comprehensive analysis of cytokines profile was made in AD patients undergoing Dupilumab therapy. The primary objective of our research was to examine the levels of main cytokines to better understanding systemic immune response in AD and to identify potential biomarkers of the effectiveness of Dupilumab treatment. AD patients demonstrated significant clinical improvements one year after initializing of Dupilumab therapy. We identified 16 cytokines that showed major difference between Dupilumab-treated patients and patients without Dupilumab therapy. Six cytokines showed correlation with AD severity and the efficacy of Dupilumab therapy. Jointly revealed cytokines could potentially predict the effectiveness of Dupilumab treatment and help to choose the precision target therapy in AD patients as well.

Autosselecionar a intensidade do treinamento aeróbico é uma perspectiva que permite aos praticantes desenvolver autonomia (escolha do ritmo), melhorar a aptidão física e alcançar a perda de peso. Comparar o efeito de quatro protocolos de treinamento aeróbico nas respostas cardiometabólicas e psicofisiológicas em homens e mulheres adultos fisicamente inativos. A amostra foi composta por 11 indivíduos com idade entre 56 ± 10 anos e IMC 29,2 ± 2,4 kg/m2 que realizaram quatro diferentes protocolos de treinamento aeróbio em esteira, sendo: 1-indivíduo com intensidade autosselecionada (ISS), 2-indivíduo com intensidade prescrita (IPI) (64-76% da FC máx), grupo 3 pequeno com autosseleção. intensidade selecionada (SGS) e intensidade prescrita em 4 pequenos grupos (SGP) (64-76% da FC máx). Foram analisados ​​frequência cardíaca, lactato, percepção subjetiva de esforço, resposta afetiva, escala de ativação, prazer, intenção de repetir a sessão, velocidade da esteira e distância total do protocolo. A análise estatística utilizou ANOVA com teste post hoc de Tukey (p<0,05). As análises de frequência cardíaca, lactato, percepção subjetiva de esforço, escala de ativação, prazer, velocidade média e distância total não apresentaram diferenças significativas entre os protocolos. A resposta afetiva apresentou menor declínio no protocolo ISS (p<0,05), e a intenção de repetir a sessão de treinamento foi maior no protocolo ISS (p<0,05). Conclusão: Os dados permitem concluir que o protocolo de treino ISS produziu resultados superiores na resposta afetiva e na intenção de repetir a sessão.

To study the fermentation process of biocatalyzing decanoic acid to synthesize trans-2-decenoic acid, this study was based on the engineering E.coli constructed in the laboratory in the early stage and studied the effect of seed liquid culture time, culture temperature, inoculum amount, induction temperature, dissolution effects of substrate solvent, metal ions, and substrate loading on the yield of trans-2-decenoic acid. Based on single-factor experimental optimization, the Box–Behnken design was used to conduct response surface testing using the substrate feeding concentration, inducer concentration, and MnCl2 concentration as response variables and trans-2-decenoic acid production as the response value. The optimal fermentation process was determined through experiments: seed culture time 20 h, culture temperature 37°C, inoculation amount 1%, induction temperature 30°C, substrate flow amount 0.15 g/L, inducer concentration 5.60 g/L, MnCl2 concentration was 0.10 mM. Under these conditions, the average production of trans-2-decenoic acid was 1.982 ± 0.110 g/L. Compared with the basic LB medium, the production of trans-2-decenoic acid increased by 1.042 g/L; compared with the previous period, the yield of trans-2-decenoic acid studied increased by 1.501 ± 0.110 g/L, which provides a reliable basis for further research on the fermentation process of biocatalytic decanoic acid synthesis of trans-2-decenoic acid.

The study of coordination practices in health policy and, especially in emergency situations is a central aspect. The COVID-19 pandemic has highlighted the need for further research on such practices, especially those that are deployed in complex and unforeseen situations to respond quickly while minimising errors. These dialogic coordination practices (DP) have been identified through case studies but have not been validated. The purpose of this study is to develop and validate a DP questionnaire for healthcare teams. The development of the items was based on a literature review and the content validation was carried out by means of a Delphi study. A total of 10 experts assessed the clarity and appropriateness of the items and their corresponding measurement scales. Consensus was reached after the second round, with a percentage of agreement greater than or equal to 90% for all items. The validation of these items constitutes a methodological innovation that responds to the call in the literature to open up new avenues for comparative studies, the possibility of generalising the findings obtained and the possibility of bringing together different approaches to the problem of coordination, key in health policy.

Heat shock factor 1 (HSF1) is a transcription factor crucial for regulating heat shock response (HSR), one of the significant cellular protective mechanisms. When cells are exposed to proteotoxic stress, HSF1 induces the expression of heat shock proteins (HSPs) to act as chaperones, correcting the protein-folding process and maintaining proteostasis. In addition to its role in HSR, HSF1 is overexpressed in multiple cancer cells, where its activation promotes malignancy and leads to poor prognosis. The mechanisms of HSF1-induced tumorigenesis are complex and involve diverse signaling pathways, dependent on cancer type. With its important roles in tumorigenesis and tumor progression, targeting HSF1 offers a novel cancer treatment strategy. In this article, we examine the basic function of HSF1 and its regulatory mechanisms, focus on the mechanisms involved in HSF1’s roles in different cancer types, and examine current HSF1 inhibitors as novel therapeutics to treat cancers.

Background: We investigated the tumor immune response in gastric cancer patients receiving third line nivolumab monotherapy to identify immune-related biomarkers for better patient se-lection. Methods: Nineteen patients (10 males, median age 67 years) who received nivolumab as a third or later line therapy were enrolled. We analyzed the tumor immune response in durable clinical benefit (DCB) and non-DCB patients. Pre-treatment and early-on-treatment tumor transcriptomes were examined, and gene expression profiles, immunograms, and T cell receptor (TCR) repertoire were analyzed. Results: DCB was observed in 15.8% of patients, with comparable secondary endpoints (ORR, OS, PFS) to previous trials. Individual immunograms showed no significant changes before and ear-ly-on-treatment, nor consistent alterations among DCB cases. The intratumoral immune response was suppressed by previous treatments in most third or later line nivolumab recipients. TCR repertoire analysis revealed newly emerged clonotypes in on-treatment tumors, but clonal re-placement did not impact efficacy. High T cells/Tregs ratios and a low UV radiation response gene signature were linked to DCB and treatment response. Conclusions: This study emphasizes the tumor immune response's importance in nivolumab ef-ficacy for gastric cancer. High T cells/Tregs ratios and specific gene expression signatures show promise as potential biomarkers for treatment response. Larger cohort validation is crucial to optimize immune checkpoint inhibitors in gastric cancer treatment.

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

Natural products, especially biologically active compounds derived from plants, have been and continue to be invaluable in anticancer research and therapeutic discoveries. Rice bran arabinoxylan compound (RBAC) is a heteropolysaccharide extract of defatted rice bran obtained through enzymatic treatment with Lentinus Edodes mycelium. RBAC exhibited antitumour properties by arresting in vivo tumour growth in several murine models. In vitro experiments showed RBAC to promote apoptosis in cancer cells by increasing the susceptibility of CD95 (Fas/APO-1) ligands and downregulating Bcl-2 proteins to trigger the permeabilisation of the mitochondrial membrane. RBAC may restore immune dysfunction in cancer patients, most notably by upregulating natural killer cell activity and modulating cytokine production to enhance inflammatory and cytotoxic responses. As such, RBAC acts on the immune system to enhance chemopreventative activity and block tumourigenesis. In treatment, RBAC works synergistically with other natural products and chemotherapeutic agents, such as daunorubicin and paclitaxel, by enhancing drug transport to increase DNA damage in tumours and reduce proliferation. In a clinical trial, combining RBAC with chemoembolization in treating liver cancer showed improved response, reduced recurrence, and prolonged survival time. RBAC has been shown to augment the endogenous antioxidant system to prevent oxidative stress and thus protect against the harmful side effects of radiation therapy. RBAC also has chemoprotective effects, with animal and human studies showing reduced toxicity and side effects from chemotherapy, leading to improved health-related quality of life. Meta-analysing the best available evidence indicates that RBAC treatment increases the odds of survival among cancer patients by 4.02 times (95% CI: 1.67, 9.69) in the first year and 2.89 (95% CI: 1.56, 5.35) times in the second year after commencing treatment, compared to those not treated with RBAC. Notwithstanding, additional research is needed to characterise, quantify, and standardise the active ingredients in RBAC responsible for the anticancer effects. More well-designed, large-scale clinical trials are required to further substantiate the treatment efficacies.

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

Food allergies are a growing public health concern worldwide, especially in children and young adults. Allergen-specific IgE plays a central role in the pathogenesis of food allergies, but their titers poorly correlate with allergy development. Host immune systems yield allergen-specific immunoglobulin (Ig)A, IgE and IgG subclasses with low or high affinities and differential Fc N-glycosylation patterns that can affect the allergic reaction to food in multiple ways. High affinity IgE is required to induce strong mast cell activation eventually leading to allergic anaphylaxis while low affinity IgE can even inhibit the development of clinically relevant allergic symptoms. IgA and IgG antibodies can inhibit IgE-mediated mast cell activation through various mechanisms, thereby protecting IgE-positive individuals from allergy development. The production of IgE and IgG with differential allergenic potential seems to be affected by the signaling strength of individual B cell receptors, and by cytokines from T cells. This review provides an overview of the diversity of the B cell response and the diverse roles of antibodies in food allergy.

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

In the dairy cattle sector, the evaluation of the effects induced by heat stress is still one of the most impactful and investigated aspects as it is strongly connected to both sustainability of the production and animal welfare. On the other hand, more recently, the possibility of collecting large dataset made available by the increasing technology diffusion is paving the way for the application of advanced numerical techniques based on machine learning or big data approaches. In this scenario driven by rapid change there could be the risk of dispersing the relevant information represented by the physiological animal component, which should maintain the central role in the development of numerical models and tools. In the light of this, the present literature review aims to consolidate and synthesize existing research on the physiological consequences of heat stress in dairy cattle. The present review provides, in a single document, an overview as complete as possible of the heat stress-induced responses in dairy cattle with the intent of filling the existing research gap for extracting the veterinary knowledge present in the literature and make it available to those who are developing numerical models and tools.

Radiotherapy is the primary treatment modality for non-metastatic nasopharyngeal carcinoma (NPC) across all TNM-stages. Locoregional control rates have been impressive even from the 2D-radiotherapy (RT) era, except when the ability to deliver optimal dose coverage to the tumor is compromised. However, short- and long-term complications following head and neck RT are potentially debilitating, and thus, there had been much research investigating technological advances in RT delivery over the past decades, with the primary goal of limiting normal tissue damage. On this note, with a plateau in gains of therapeutic ratio by modern RT techniques, future advances have to be focused on individualization of RT, both in terms of dose prescription and delineation of target volumes. In this review, we analyzed the guidelines and evidence related to contouring methods, and dose prescription for early and locoregionally-advanced (LA-) NPC. Next, with the preference for induction chemotherapy (IC) in patients with LA-NPC, we assessed the evidence concerning radiotherapy adaptations guided by IC response, as well as functional imaging and contour changes during treatment. Finally, we discussed on RT individualization that is guided by EBV DNA assessment, and its importance in the era of combinatorial immune checkpoint blockade therapy with RT.

COVID-19 pandemic outbreak challenged the global public health in last couple of years. Throughout the pandemic period, numbers of mutant strains of SARS- CoV-2 created challenges for the infected patients with diverse pathophysiology and immune response. Variant of Concern (VOC) alpha (B.1.1.7), delta (B.1.617.2) and omicron (B.1.1.529) grew most notable for causing the epidemiological manifestations, which eventually caused elevated infectivity resulting in significant mortality. This review indicates the comparative analysis of the immune-pathophysiological mechanisms in respect to the aforementioned strains of SARS-CoV-2.

This study examined infants' neural responses to emotional prosody in natural speech. A multi-feature oddball paradigm was used with 34 3~11 month-old infants. Results showed distinct early (100-200 ms) and late (300-500 ms) mismatch responses to different emotional prosodies. Older infants had more negative early responses with happy and angry prosodies evoking stronger responses compared to sad prosody while younger infants showed a clearer distinction between angry and sad prosodies. In the late time window, angry prosody elicited more negative responses than sad prosody with younger infants showing more distinct responses between these two prosodies. Males exhibited stronger early mismatch responses than females. These findings call for further research on the implications for socio-emotional and language development.

This paper investigates the hydroelastic responses of offshore floating solar photovoltaic farms (OFPVs) to minimize structural motion. The OFPV usually occupies a large sea space in the order of hectares and due to its huge structural length-to-thickness ratio, the structural deformation under wave action has to be taken into consideration. The flexible deformation of the structure under hydrodynamic loading is termed the hydroelastic response. Due to the relatively long structural length with respect to the encountering wavelength, the diffraction and radiation of waves have to be taken into account to accurately represent the hydrodynamic loadings on the floating platform. The numerical model is first validated by comparing the eigenvalues and eigenvectors of the OFPV obtained from the proposed numerical scheme with their counterparts obtained from an established finite element software. This is followed by the investigation of the hydroelastic response of various OFPVs designed in varying layout configurations. The various layout configurations are obtained by altering the floating modular units’ dimensions as well as the spacing of the OFPVs when deployed adjacent to each other. The optimal configuration that gives the best performance in terms of the overall smallest response, known as compliance, is then suggested. The results suggest that a longish OFPV layout has a lower hydroelastic response and the motion could be further reduced by increasing the global flexural stiffness via layout arrangement.

Photosynthesis response curves were carried out using different light intensities in 14 olive cultivars subjected to moderate and severe water deficits. For each cultivar, the electronic transfer ratio in response to light was also obtained. The mathematical adjustment of these response curves allowed calculating, with a correlation coefficient above 0.95, parameters such as photosynthetic efficiency, the slope of the curves, the number of electrons required to fix a CO2 molecule, and the number of photons to assimilate a molecule of CO2, among others, as well as their variation with the lack of water. This work represents the first contribution of the response of photosynthesis in olive cultivars to different light intensities in moderate and severe drought conditions for a considerable number of cultivars. The parameters described, and the results provided, pave the road for subsequent work related to plant physiology and other areas of science and technology, and allow the tolerance to water stress to be objectively compared in these fourteen olive cultivars.

Salmonella is the intracellular pathogen and etiological known for the cause of asymptomatic carriage, gastroenteritis, systemic disease (typhoid fever), in severe cases death may also occur. Altered function of mitochondria due to Salmonella infection impacts the immune response. Mitochondria which are recognized as the “powerhouse” of the cells are also know to play central role in the immune metabolism. Mitochondrial dynamics such as fusion, fission, signaling, transport and mitophagy influences the immune system and also maintains the cellular integrity. Mitochondrial DNA and Reactive oxygen species formation also elicits the inflammatory responses. This review discusses the immune metabolism and effect of altered mitochondrial dynamics in case of Salmonella infection.

Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic infection by HCV can lead to liver cirrhosis or cancer. Although some immune-competent individuals can clear the virus, others develop chronic HCV disease due to viral mutations or an impaired immune response. IFNs type I and III and the signal transduction induced by them are essential for a proper antiviral effect. Research on the viral cycle and immune escape mechanisms have generated the basis of therapeutic strategies to achieve a sustained virological response (SVR). The first therapies were based on IFN-, then IFN-α plus ribavirin (IFN-RBV); then, pegylated-IFN--RBV (PEGIFNα-RIV) to improve cytokine pharmacokinetics. However, the maximum SVR was 60%, and several significant side effects were observed, decreasing the patients' treatment adherence. The development of direct-acting antivirals (DAAs) significantly enhanced SVR (&gt; 90%); the compounds were able to inhibit HCV replication without significant side effects, even in pediatric populations. The management of coinfected patients HBV-HCV and HCV-HIV has also improved based on DAA and PEG-IFNα-RBV (HBV-HCV). CD4 cells are crucial for an effective antiviral response. IFNλ3, IL28B, TNF-α, IL-10, TLR-3, and TLR-9 gene polymorphisms are involved in viral clearance, therapeutic responses, and hepatic pathologies. Future research focuses on searching for strategies to circumvent resistance-associated substitution (RAS) to DAAs, develop new therapeutic schemes for different medical conditions, including organ transplant, and develop vaccines for long-lasting cellular and humoral responses with cross-protection to different HCV genotypes. The goal is to minimise the probability of HCV infection, HCV chronicity and hepatic carcinoma.

Avian necrotic enteritis is an enteric disease of broiler chickens caused by certain pathogenic strains of Clostridium perfringens in combination with predisposing factors. A vaccine offering complete protection against the disease has not yet been commercialized. In a previous study, we produced five recombinant proteins predicted to be surface-exposed and unique to necrotic enteritis-causing C. perfringens and the immunogenicity of these potential vaccine candidates was assessed in broiler chickens. In the current work, the relative contribution of the antibodies raised by these putative antigens to protect broiler chickens was evaluated using an experimental necrotic enteritis induction model. Additionally, the link between the immune response elicited and the gut microbiota profiles in immunized birds subjected to infection with virulent C. perfringens was studied. ELISA results showed that the IgY antibody titers in vaccinated birds on days 21 and 33 were significantly higher than those on days 7 and 14 and those in birds receiving the adjuvant alone, while the relative contribution of the specific immunity attributed to these antibodies could not be precisely determined using this experimental NE induction model. Besides, 16S rRNA gene amplicon sequencing showed that immunization of birds with recombinant proteins had a low impact on the chicken caecal microbiota.

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

Cloud computing is a strong and efficient technology facing some efficiency challenges attributable to its decentralized nature. The emergence of fog computing has subdivided the expansive cloud into numerous smaller units known as "cloudlets." Fog computing is one of the most recent advancements in today’s cloud computing landscape. Each cloudlet is a novel and diminutive architectural element extending the contemporary cloud computing infrastructure. The term "cloudlets" has been integrated with fog computing due to its augmenting impact on the attributes of cloud computing. F fog computing is a significant foundation and an indispensable cloud component. Consequently, this technology holds the potential to address efficiency concerns effectively. As a result, this paper focuses on enhancing the efficiency of the cloud computing environment by fine-tuning the efficiency parameters derived from fog computing. These parameters encompass response time, latency, and network utilization. The proposed solution involves developing a simulation system to minimize task redundancy and increase performance levels in the healthcare environment. The outcomes manifest a substantial improvement in the performance of the suggested system, with a clear increase depending on the three key parameters (response time, network utilization, and latency). Therefore, these findings are encouraging and carry significant implications, promoting the application of the proposed system in the real healthcare environment.

The clinical relationship between diabetes and inflammation is well-established. Various branches of science independently have confirmed that disrupting oxidant-antioxidant equilibrium and elevated lipid peroxidation could be a potential mechanism for chronic kidney disease associated with Type 2 diabetes mellitus (T2DM). Under diabetic condition, hyperglycemia, especially inflammation, and increased reactive oxygen species generation are bidirectionally associated. Inflammation, oxidative stress and tissue damage are believed to have a role in the development of diabetes. Although the exact mechanism underlying the oxidative stress and its impact on diabetes progression remains uncertain, the hyperglycemia-inflammation-oxidative stress interaction clearly plays a significant role in onset and progression of vascular disease, kidney disease, hepatic injury, pancreas damage and, therefore holds promise as a therapeutic target. Evidence strongly indicates that the use of multiple antidiabetic medications therapy fails to achieve the normal range for glycated hemoglobin target, signifying treatment resistant diabetes. Antioxidants with polyphenols are considered useful as adjuvant therapy for their potential anti-inflammatory effect and antioxidant activity. We aimed to analyze the current major points reported in preclinical in vivo and clinical studies of antioxidants in the prevention or treatment of inflammation in T2DM. Then, we will share our speculative vision of the future diabetes clinical trials.

In the land use planning framework in the neighbourhood of industrial facilities, the current approach to predicting the consequences of massive toxic gas releases is generally based on Gaussian or integral models. For many years, CFD models have been more and more used in this context, in accordance with the development of High-Performance Computing (HPC). The present paper focuses on harmonizing input data for Atmospheric Transport and Dispersion (AT&amp;D) modelling between the widely used approaches. First, a synthesis of the practice’s harmonization for atmospheric dispersion modelling within the framework of risk assessment is presented. Then, these practices are applied to a large-scale INERIS ammonia experimental release. For illustration purposes, the impact of the proposed harmonization will be evaluated using different approaches: the SLAB model, the FDS model and the Code_Saturne model. The two main focuses of this paper are the adaptation of the source term dealing with a massive release and the wind flow modelling performance using an experimental signal for CFD models inflow. Finally, comparisons between the modelling and experimental results enable checking the consistency of these approaches and reinforce the importance of the input data harmonization for each AT&amp;D modelling approach.

This study continued the analysis of immunization with the receptor binding domain (RBD) associated with the adjuvants Dimethyldioctadecylammonium bromide (DDA) and Saponin (Sap) (RBD+DDA/Sap) or Aluminum hydroxide (AH) and outer membrane vesicles (OMVs) of Neisseria meningitidis (RBD+AH/OMV); from adult to old age and assessed maternal-fetal transference of antibodies. Outbred Swiss mice were immunized with 2 intramuscular (IM) doses with the antigenic preparations RBD+DDA/Sap, RBD+AH/OMV or RBD alone. The humoral immune response was evaluated using ELISA, avidity-ELISA, Immunoblotting and a Omicron-surrogate-neutralization assay (BA.1), while the cellular immune response was analyzed by ELISpot. Our previous work studied the IgG response; here, we verified that IgM levels were higher right after the immunization doses, but, as IgG, it persisted until 368 days after the immunization. The avidity of IgM increased from low to intermediate-to-high after the booster dose. RBD+DDA/Sap presented neutralizing indexes against Omicron at days 47 and 176, while RBD+AH/OMV showed neutralization on days 21, 47 and 176. Cellular response, measured 465 days after immunization, revealed IFN-Y and IL-4 secretion. The offspring of RBD+DDA/Sap had detectable antibodies, which decreased around 45 days after birth, the last point we analyzed. The results suggested that DDA/Sap is a promising adjuvant mixture to enhance humoral and cellular immune response against SARS-CoV-2, improving maternal-fetal transference of antibodies; cross-reactivity with Omicron variant; and the maintenance of antibodies for a long period.

Faced with difficulties stemming from the complex interactions between tight gas sand bodies and fractures when describing and identifying reservoirs, a composite reservoir model was established. By setting the supply boundary to characterize the superposition characteristics of sand bodies, a mathematical model of unstable seepage in fractured vertical wells in tight sandstone gas reservoirs was constructed considering the factors such as stress sensitivity, fracture density and fracture symmetry. The seepage law and pressure response characteristics of gas well in tight sandstone discontinuous reservoir with stress sensitivity, semi-permeable supply boundary and complex fracture topology were determined, and the reliability of the model was verified. The research results more accurately depict the pressure characteristic curve of the superposed sand body complex fracture vertical well, and provide a more comprehensive model for tight gas production dynamic analysis and well test data analysis, which can more accurately guide the dynamic inversion of reservoir and fracture parameters.

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

Lutein, a plant-derived xanthophyl-carotenoid, is an exceptional antioxidant and anti-inflammatory constituent found in food. Elevated concentrations of lutein found in human blood and plasma, due to high dietary intake, are beneficial against eye disease and improve cardiometabolic health. Lutein plays an important protective role against the development of neurological disorders, including Alzheimer’s disease (AD), multiple sclerosis (MS) and Parkinson’s disease (PD). It has also been shown to be beneficial for liver, kidney and respiratory health. Lutein, acting as a very strong antioxidant, can alleviate oxidative stress and downgrade reactive oxygen species (ROS). Oxidative stress is one of the key pathogenic mechanisms in post-COVID and mRNA vaccine injury syndromes. Recent in silico studies suggest that lutein and other naturally derived antioxidants, by docking at the site where the SARS-CoV-2 spike protein (SP) binds to the angiotensin enzyme type 2 (ACE2) receptor, may neutralize the SP-ACE2 interactions. Lutein can be added to a detoxification regimen to aid in clearing Spike protein and relieving symptoms. In agreement with Hippocrates’ dictum to “Let food be thy medicine,” this review establishes dietary lutein as a valuable therapy in the treatment of post-COVID syndrome, mRNA vaccine injury syndromes, and a wide range of other chronic illnesses.

Frontotemporal lobar degeneration (FTLD) belongs to a heterogeneous group of highly complex neurodegenerative diseases and represents the second cause of presenile dementia in individuals under 65. Frontotemporal-TDP is a subgroup of frontotemporal dementia characterized by the aggregation of abnormal protein deposits, predominantly transactive response DNA-binding protein 43 (TDP-43), in the frontal and temporal brain regions. These deposits lead to progressive degeneration of neurons resulting in cognitive and behavioral impairments. Limbic age-related encephalopathy (LATE) pertains to age-related cognitive decline primarily affecting the limbic system which is crucial for memory, emotions, and learning. Though distinct, emerging research suggests a potential overlap in pathogenic processes, with some cases of limbic encephalopathy displaying TDP-43 pathology. Genetic factors play a pivotal role in both disorders. Mutations in various genes, such as progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72), have been identified as causative in frontotemporal-TDP. Similarly, specific genetic variants have been associated with an increased risk of developing LATE. Understanding these genetic links provides crucial insights into disease mechanisms and the potential for targeted therapies.

Abstract: With the continuous integration of various energy systems and the reform of energy trading marketization, the traditional power demand response can no longer meet the needs of multi-energy coupling. For the joint response problem of multi-energy, this paper proposes a comprehensive demand response optimization incentive model considering the user response characteristics, with the complete energy service providers and multiple users as the participants of the comprehensive demand response, to solve the response strategy for the optimal goal of all parties. The implementation architecture of integrated demand response and the electrothermal energy hub model is introduced first. Secondly, the integrated demand response collaborative optimization strategy of the integrated energy service providers and users is established, and the existence and uniqueness of the optimal solution are proved. Finally, the example analysis demonstrates that the proposed strategy can reduce the integrated energy service providers' response cost and user dissatisfaction under multiple scenarios.

With more and more transportation tunnels have been and will be constructed in loess areas in Northwest China with high earthquake potential, the overall stability of portal section under earthquakes actions and the related aseismic countermeasures attracted the attentions from both the scholars and engineers, especially the tunnels in the upper slope connecting the high bridges crossing rivers or valleys. In order to study the dynamic response characteristics and damage evolution of steep loess slope with a tunnel under the earthquake actions, a large-scale shaking table tests were performed on steep loess slope with a tunnel. Wenchuan-tangyu (WT) wave and El Centro (El) wave records were applied on the model to investigate the displacement response and acceleration response of loess slope with a tunnel under the horizontal (X) and the combined action of horizontal and vertical (X-Z) seismic loads, respectively. In particular, three-dimensional non-contact optical measurement techniques were used to obtain the slope surface displacements. The results showed that the main deformation pattern of the slope was horizontal movement and settlement when the seismic wave input was in the X and X-Z directions, respectively. However, the X direction seismic wave had a greater impact on the deformation of the slope, and the tunnel portal slope was destroyed under the action of a large horizontal seismic acceleration finally. Slope failure ahead of a tunnel could be divided into four stages, i.e. elastic deformation stage, plastic deformation accumulation stage, local failure stage, and overall failure stage. The peak ground displacement of X direction (PGDX) and peak ground displacement of Z direction (PGDZ) of the slope surface increased with the increasing of the input peak ground acceleration (PGA) when the input wave was same waveform and same direction. The existence of the tunnel had a great influence on the PGA and the PGA amplification factor (PGAAF) of the soil mass surrounding it. This was because the seismic waves encounter a tunnel surface with clear differences in the physical properties of the medium during their propagation in the slope, thereby forming a strong reflection and refraction effect, and the amplitude changed significantly. Numerical simulation results were basically consistent with the experimental results.

Spectral calibration consists of the calibration of wavelengths and the measurement of the instrument's spectral response function (SRF). Unlike conventional slits, the absorbed aerosol sensors (AAS) are used as a slit homogenizer, in which the spectral response function (SRF) is not a conventional Gaussian curve. To be more precise, the SRF is the convolution of the slit function of the spectrometer, the line spread function of the optical system, and the detector response function. The SRF of the slit homogenizer is a flat-topped multi-Gaussian function. Considering the convenience of fitting, a super-Gaussian function, which looks like a similar distribution to the flat-topped multi-Gaussian function, is used to fit the measured data in a spectral calibration. According to the results, the SRF’s shapes, due to the Earth port, resemble a Gaussian curve with a flatted top could be concluded, which contains an FWHM of 1.78–1.82 nm for the AAS. The results show that the correlation coefficients are about 0.99, which proves that the fitting function could better characterize the SRF of the instrument.

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

Rhabdomyosarcoma is a rare cancer arising in skeletal muscle that typically impacts children and young adults. It is a worldwide challenge in child health as treatment outcomes for metastatic and recurrent disease still pose a major concern for both basic and clinical scientists. The treatment strategies for rhabdomyosarcoma include multi-agent chemotherapies after surgical resection with or without ionization radiotherapy. In this comprehensive review, we first provide a detailed clinical understanding of rhabdomyosarcoma including its classification and subtypes, diagnosis, and treatment strategies. Later we focus on chemotherapy strategies for this childhood sarcoma and discuss the impact of three mechanisms that are involved in chemotherapy response including apoptosis, macro-autophagy, and the unfolded protein response. Finally, we discuss in vivo mouse and zebrafish models, and in vitro 3-dimensional bioengineering models of Rhabdomyosarcoma to screen future therapeutic approaches and promote muscle regeneration.

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

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

The ubiquitin proteasome system (UPS) utilizes an orchestrated enzymatic cascade of E1, E2, and E3 ligases to add single or multiple ubiquitin-like molecules as post-translational modification (PTM) to proteins. Ubiquitination can alter protein functions and/ or marks ubiquitinated proteins for proteasomal degradation but deubiquitinases (DUBs) can reverse protein ubiquitination. While the importance of DUBs as regulatory factors in the UPS is undisputed, many questions remain on DUB selectivity for protein targeting, their mechanism of action, and the impact of DUBs on the regulation of diverse biological processes. Furthermore, little is known about the expression and role of DUBs in tumors of the human central nervous system (CNS). In this comprehensive review, we have used publicly available transcriptional datasets to determine the gene expression profiles of 99 deubiquitinases (DUBs) from five major DUB families in seven primary pediatric and adult CNS tumor entities. Our analysis identified selected DUBs as potential new functional players and biomarkers with prognostic value in specific subtypes of primary CNS tumors. Collectively, our analysis highlights an emerging role for DUBs in regulating CNS tumor cell biology and offers a rationale for future therapeutic targeting of DUBs in CNS tumors.

The purpose of this research work was to synthesis bio-derived nanocomposite films by incorporating Na0.5Bi0.5TiO3 (NBT) nanoparticles into Chitosan matrix. The NBT nanoparticles were synthesized using a traditional solid-state technique. Then, through a solution casting approach, flexible composite films were fabricated using Chitosan polymer. The morphology and structural assessments were carried out utilizing scanning electron microscopy (SEM), X-ray diffraction and fourier transform infrared technique. The SEM micrographs showed that NBT nanoparticles were randomly distributed and interconnected with other particles, forming interconnected grains with substantial interspaces within the matrix. The spectral response between 300 and 800 nm of the composites is mainly governed by light scattering of NBT particles with diameter sizes in the 100 - 400 nm range and the bandgap of the NBT phase. The dielectric studies demonstrated that the composite films exhibited higher dielectric values compared to the pure Chitosan film. Besides, the increase of NBT amount was found to increase the dielectric values. Additionally, local piezoelectric measurements reveal the expected piezoelectric and ferroelectric behavior for the NBT particles dispersed into the polymer matrix, as locally probed by Piezoresponse Force Microscopy. The studied system bears interest for advanced biocompatible opto- and piezo-electric materials.

In their natural environment, bacteria are exposed to various stresses. The stress-response sigma factor SigB of gram-positive Bacillus subtilis is the best-characterized example. Unlike Bacillus subtilis, the gram-positive bacterium Streptomyces coelicolor A3(2) contains nine SigB homologues (SigBFGHIKLMN) with a major role in differentiation and response to osmotic stress. We previously constructed a two-plasmid system to identify promoters recognized by these sigma factors. Interestingly, almost all identified promoters were recognized by two or more SigB homologues. However, no specific sequences characteristic for these recognition groups were found. To examine this cross-recognition in vivo in S. coelicolor A3 (2), one of these promoters was cho-sen, which drives the expression of the sporulation-specific gene ssgB. The ssgBp promoter was inserted into a luciferase reporter plasmid and conjugated to S. coelicolor M145 and nine mutant strains containing deleted individual sigB homologous genes. Luciferase reporter activity indi-cated differential activity of this promoter in these mutant strains, suggesting overlapping pro-moter recognition by these SigB homologues. To determine which nucleotides in the ̶ 10 re-gion are responsible for the selection of a specific SigB homologue, several mutant promoters with altered last three nucleotides in this region were prepared and tested in the two-plasmid system. Some mutant promoters were specifically recognized by some SigB homologues. Mutant promoters were inserted into a luciferase reporter plasmid and conjugated to S. coelicolor A3(2) and these nine mutant strains. Luciferase reporter activity indicated differential activity of these ssgBp mutant promoters, indicating overlapping promoter recognition by these SigB homologues in S. coelicolor A3(2).

Preterm birth (PB) is a leading cause of perinatal morbidity and mortality. PB prediction is per-formed by measuring cervical length, with a detection rate of around 70%. Although it is known that a cytokine-mediated inflammatory process is involved in the pathophysiology of PB, no screening method implemented in clinical practice includes cytokine levels as a predictor varia-ble. Here, we quantified cytokines in cervical-vaginal mucus of pregnant women (18-23.6 weeks of gestation) with high- or low-risk for PB determined by cervical length, collecting relevant obstetric information. IL-2, IL-6, IFN-γ, IL-4, and IL-10 were significantly higher in the high-risk group, while IL-1ra was lower. Two different models for PB prediction were created using the Random Forest machine-learning algorithm: the full model with 12 clinical variables and cyto-kine values, and the adjusted model, including the most significant variables -maternal age, IL-2, and cervical length- (detection rate 66 vs 87%, false positive rate 12 vs 3.33%, false negative rate 28 vs 6.66%, and area under the curve 0.722 vs 0.875, respectively). The adjusted model integrat-ing cytokines showed a detection rate 8 points higher than the gold standard calculator, which may allow us to identify PB risk more accurately and implement strategies for preventive in-terventions

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

Human T-cell leukemia virus type-1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATL). HTLV-1 carriers have a life-long asymptomatic balance between infected cells and host antiviral immunity, but 5–10% of carriers lose this balance and develop ATL. Coinfection with Strongyloides also promotes ATL development, suggesting that the immunological status of infected individuals is a determinant of viral pathogenicity. As CD4+ T cells play a central role in host immunity, deregulation of their function and differentiation by HTLV-1 promotes the immune evasion of infected T cells. During ATL development, the accumulation of genetic and epigenetic alterations in key host immunity-related genes further disturbs immunological conditions. Various therapeutic approaches have been developed to treat these abnormalities. Allogeneic hematopoietic stem cell transplantation is currently the only treatment with the potential to cure ATL; however, the patient's immune state may also contribute to its outcome. Additionally, the activity of the anti-CC chemokine receptor 4 antibody, mogamulizumab, also depends on immune functions, such as antibody-dependent cytotoxicity. In this review, we comprehensively summarize the immunological pathogenesis of HTLV-1 infection in ATL and integrate clinical findings to determine the factors to be considered for developing treatment strategies for ATL.

Intergenerational integration has given rise to a novel aging paradigm known as all-age communities, which is garnering international attention. In China, the aging population and the implementation of the three-child policy have resulted in increased demand for retirement and childcare services among residents in older neighborhoods. Consequently, there is a pressing need to retrofit these older neighborhoods to accommodate all-age living arrangements given the high demand they generate. Therefore, this study undertakes research interviews with residents and constructs an exploratory theoretical model rooted in established theory. To assess the significance of our model, we employ Smart PLS 3.0 based on 297 empirical data points. Our findings indicate that anxiety has a significant negative effect on payment behavior; objective perception, willingness to pay, and government assistance exert significant positive effects on payment behavior. By comprehensively analyzing the mechanisms underlying residents’ payment behavior, this study provides valuable insights to the government for promoting the aging process within communities and formulating effective transformation policies.

Purpose of the study: to reveal how the transfusion and the refraining from it affects the neuro-vascular unit in the congenital heart defects correction with cardiopulmonary bypass. Materials and methods: in vitro research, we formed a model of a neurovascular unit, which contains neu-rons, astrocytes and endothelial cells. This cellular model was cultivated in hypoxia conditions with the oxygen saturation levels of 1, 2, 3, 4%. In addition, this unit was cultivated with the pa-tient's serum adding in two different groups - with minimal and maximal levels of system in-flammatory response that we estimated by IL-6 level. Results: We found that during incubation in hypoxic conditions, the level of transendothelial resistance changed in groups with oxygen levels of 1% and 2% only after 4 hours. When we cultivated neurovascular unit cells with patients' sera, we found a minimal level of transendothelial resistance at 4 hours that increased after 24 hours. Permeability analysis showed that its level significantly decreased in the 1% and 2% oxygen group at 60- and 90-minutes relative to the control group. Conclusion: the system inflammatory response has more expressed but less long effect on the neurovascular unit model than hypoxia.

The integrated stress response is a signaling network comprised of four branches, each of which senses different cellular stressors, converging on the phosphorylation of eIF2α to depress global translation and initiate recovery. One of these branches is composed of GCN2, which senses cellular amino acid insufficiency and participates in the maintenance of amino acid homeostasis. Previous studies have shown that GCN2 is a viable cancer target when amino acid stress is provoked by inhibiting an additional target. In this light, we screened a combination of drugs to identify biologically active compounds which synergize with the GCN2 inhibitor TAP20. First, a panel of 25 compounds was assayed in six cancer cell lines for drug sensitivity. Each compound was then combined with TAP20 at concentrations below their IC50, and the impact on cell growth was assessed. Selected strongly synergistic combinations were further characterised using synergy analyses and matrix-dependent invasion assays. Inhibitors of proteostasis, of the MEK-ERK pathway and pan-CDK inhibitors flavopiridol and seliciclib were found to potently synergize with TAP20 in two of the tested cell lines. Among their common CDK targets is CDK7, which was selectively targeted with THZ-1 and found to synergize with TAP20. Finally, these combinations were found to be partially synergistic when assessed using matrix-dependent invasion assays. However, we found that TAP20 alone was sufficient to restrict invasion at concentrations well below its growth-inhibitory IC50. We conclude that GCN2 can be targeted for treating cancers by polytherapy or even monotherapy.

Sporothrix brasiliensis is the most pathogenic species, responsible for the Brazilian cat-transmitted sporotrichosis hyperendemics. In this scenario, investigation of pathogen-host interaction can provide relevant information for future treatment strategies. To this end, the invertebrate Galleria mellonella has proven to be a suitable alternative to evaluate the virulence of pathogenic fungi since the insect immune system is similar to the mammalian innate immune response. The aim of this work was to investigate phenotypic and molecular aspects of the immune response of G. mellonella throughout the S. brasiliensis infection. Hemocyte density and the evolution of the fungal load were evaluated. In parallel, RT- qPCR expression analysis of genes encoding antimicrobial peptides (Gallerimycin and Galiomycin) and stress management genes (C7 Contig 15362 and C8 Contig 1910) was conducted. Fungal load and hemocyte densities were proportionally increasing simultaneously to the deleterious morphological events and larvae mortality. Gallerimycin, C7 Contig 15362, and C8 Contig 19101 genes were positively regulated (p&lt;0.05) at distinct moments of S. brasiliensis infection, characterizing a time-dependent and alternately modulated profile. Galiomycin gene expression remained unchanged. Our results contribute to the future proposal of potential alternative pathways to treat and, consequently, control S. brasiliensis zoonosis, a major public Health in Latin America.

The focus of recent research shifts towards complex ‘whole organism’ responses (i.e., in multiple functional traits) in adaptation to or to defend against stressors under complex environmental conditions. This increasing complexity is challenging to analyse and demands sophisticated tools to drive meaningful conclusions from those data. Trait-based regression models, multivariate analyses, like principal component analyses, and plasticity indices can be used to tackle challenges with those complex investigations. But those methods have substantial limitations, like the need for high sample size, multi-dimensionality of results or the need for trait coordination in high-dimensional space, or the calculation on the population level, which might buffer or cover the de facto occurring individual effects. To improve and simplify studies on ‘whole organism’ responses, analyses, and their interpretation, we developed the Index for Adaptive Responses. This straightforward framework can unite all traits of an organism in one number. A newly developed transformation method, included in this framework, comprises a normalisation and standardisation to a baseline or control without changing the data or variance structure of the original data. We assessed the performance and accuracy of the framework with an application in an extensive predator-prey case study, with simulations and application examples using literature data. We show that the Index for Adaptive Responses respects adaptations as well as maladaptations and outperforms established approaches. The framework is robust against outliers and non-gaussian distribution. We further show that the qualitative prediction of the adaptiveness of included traits is highly accurate, even under challenging conditions, e.g., low replicate numbers. Functions and algorithms of the framework are provided with an R package but can easily be translated into other programming languages. The Index for Adaptive Responses will simplify future research on complex adaptive responses and improves our understanding of these responses’ ecological as well as evolutionary implications.

Bioactive lipids are involved in cellular signalling events with links to human disease. Many of these are involved in inflammation under normal and pathological conditions. Despite being attractive molecules from a pharmacological point of view, detection and quantification of lipids has been a major challenge. Here, we have optimised a liquid chromatography dynamic multiple reaction monitoring targeted mass spectrometry (LC-dMRM-MS) approach to profile eicosanoids and fatty acids in biological samples. In particular, by applying this analytic workflow to study a cellular model of Chronic Myeloid Leukaemia (CML), we found that intra- and extra-cellular 2-Arachidonoylglycerol (2-AG), intracellular Arachidonic Acid (AA), and extracellular Prostaglandin F_2α (PGF_2α), 5-Hydroxyeicosatetraenoic acid (5-HETE), Palmitic acid (PA, C16:0) and Stearic acid (SA, C18:0) were altered in response to immunomodulation by type I Interferon (IFN-I), a currently approved treatment for CML. Our observations indicate changes in eicosanoid and fatty acid metabolism with potential relevance in the context of cancer inflammation and CML.

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.

Syphilis continues to be a significant global health concern, and understanding the latest advancements in immunology and pharmacological treatment is crucial for effective disease management. This review article provides an in-depth exploration of these advancements, aiming to contribute to the growing body of knowledge on syphilis research. The epidemiology of syphilis sets the stage for this review, highlighting the persistent burden of the disease worldwide. Current trends and challenges in disease control are discussed, shedding light on the need for comprehensive prevention strategies and improved surveillance systems. The immunological aspects of syphilis are the focus of this review. The intricate interplay between the host immune response and the evasive strategies employed by Treponema pallidum, the causative agent of syphilis, are explored. These include the mechanisms of immune evasion, the role of adaptive and innate immunity, and the development of immune-mediated tissue damage. The article also highlights advancements in diagnostic methods, with emphasis on the importance of accurate and timely detection. From traditional serological tests to the emergence of novel molecular and point-of-care assays, these developments have significantly improved the efficiency and accuracy of syphilis diagnosis. In terms of pharmacological treatment, the review covers the current recommendations and emerging strategies for managing syphilis infections. The challenges posed by antimicrobial resistance are addressed, emphasizing the importance of appropriate treatment regimens and close monitoring of therapeutic efficacy. Looking to the future, this review highlights the potential of vaccine development as a preventive measure against syphilis. Promising vaccine candidates and ongoing research efforts are discussed, offering hope for an effective means of disease prevention. In conclusion, this comprehensive review explores the advancements in syphilis research, from the understanding of immunological complexities to the development of innovative treatment strategies. By collectively advancing our knowledge, we can strive towards better disease management and minimize the impact of syphilis on global public health.

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

Biomimetics, which are similar to natural compounds that play an important role in the metabolism, manifestation of functional activity and reproduction of various fungi, have a pronounced attrac-tion in the current search for new effective antifungals. Actual trends in the development of this area of research indicate that unnatural amino acids can be used as such biomimetics, including those containing halogen atoms; compounds similar to nitrogenous bases embedded in the nucleic acids synthesized by fungi; peptides imitating fungal analogues; molecules similar to natural sub-strates of numerous fungal enzymes and Quorum Sensing signaling molecules of fungi and yeast; etc. Most part of the review is devoted to the analysis of semi-synthetic and synthetic antifungal peptides and their targets of action. This review is aimed at combining and systematizing the cur-rent scientific information accumulating in this area of research, developing various antifungals with an assessment of the effectiveness of the created biomimetics and the possibility of combining them with other antimicrobial substances to reduce cell resistance and improve antifungal effects.

The influence of four levels of dietary supplementation on the development of the immune response and on the biology of Haemonchus contortus and Trichostrongylus colubriformis was evaluated in Dorper lambs under serial artificial mixed-infections with 1000 infective larvae (L3) of each species, given every three days for 12 weeks. For each of the four diets formulated, one infected group (n=7) and one control group (n=4) were set up. Diets 1, 2, 3 and 4 contained 0%, 25%, 50% and 75% of concentrate, respectively. There was an evident immune response to infection in all groups, manifested through eosinophilia and production of anti-L3 immunoglobulins. There was a significant inverse relationship between the levels of nutrients in the diets and the numbers of late fourth-stage larvae, early fifth-stage larvae and adults of H. contortus. Most of the H. contortus parasite population was in hypobiosis at the early-fourth stage, representing 59.5%, 75.8%, 83.3% and 86.3% of the total Haemonchus worm burden, respectively, in the Diets 1, 2, 3 and 4. In the case of T. colubriformis, hypobiosis was not observed and the diet had no influence on establishment of the parasite.

Supercritical fluid extraction (SFE) is an innovative green technology for the extraction of phytochemicals from plants. Therefore, this study aimed to evaluate the application of SFE and to optimize the extraction condition of the Thai herbal formula, Kleeb Bua Daeng (KBD). A Box-Behnken design (BBD) with response surface methodology was used to determine the effect of extraction time, temperature, and pressure on response variables including extraction yield, total phenolic content (TPC), total flavonoid content (TFC), total carotenoid content (TCC) and total anthocyanin content (TAC) of KBD formula. The highest percentage extraction yield, TPC, TFC, and TCC of the extracts were 3.81%, 464.56 mg gallic acid equivalents/g extract, 217.19 mg quercetin equivalents/g extract, and 22.26 mg β-carotene equivalents/g extract, respectively. The results indicated that SFE is a suitable method of extraction for green recovery of some phytochemicals from the KBD formula.

The advancement of technology and the availability of specialized digital signal processing chips have made digital filter design and implementation more feasible in a variety of fields, including biomedical engineering. This paper makes two key contributions. First, it uses a genetic algorithm to optimize the coefficients of Finite Impulse Response (FIR) filters. Second, it conducts a case study on using genetic algorithms to optimize FIR filters for electrocardiogram (ECG) biomedical signal noise removal. The goal of the proposed filter design approach is to achieve the desired signal bandwidth while minimizing the side lobe level and eliminating unwanted signals using a genetic algorithm. The results of the comprehensive analysis of the impact of different genetic operators show that the genetic algorithm-based filter outperforms conventional filter designs.

: Ovarian cancer has a dismal prognosis. Standard treatment following surgery relies on platinum-based chemotherapy. However, sizeable percentages of patients are unresponsive. Identification of markers predicting response to chemotherapy might help select eligible patients while sparing unresponsive ones treatment-associated toxicity. Cancer/testis antigens (CTA) are expressed by healthy germ cells and malignant cells of diverse histological origin. This expression profile identifies them as attractive targets of cancer immunotherapies. We analyzed correlations between expression of MAGE-A10 and New York esophageal-1 cancer (NY-ESO-1) CTAs at protein level and effectiveness of platinum-based chemotherapy in patients with advanced-stage high-grade serous ovarian carcinoma (HGSOC). MAGE-A10 and NY-ESO-1 protein expression was analyzed by immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded samples from 93 patients with advanced-stage HGSOC treated at our institutions between January 1996 and December 2013. Correlation between expression of these markers and response to platinum-based chemotherapy, evaluated according to RECIST 1.1 criteria, platinum sensitivity, measured as platinum free interval (PFI), progression free (PFS) and overall survival (OS) was explored. MAGE-A10 protein expression predicts unresponsiveness to platinum-based chemotherapy (p=0.005), poor platinum sensitivity (p<0.001), and poor PFS (p<0.001) and OS (p<0.001). Multiva-riate analysis identifies MAGE-A10 protein expression as independent predictor of poor platinum sensitivity (p=0.005) and shorter OS (p<0.001). Instead, no correlation was observed between NY-ESO-1 protein expression and response to platinum-based chemotherapy (p=0.832), platinum sensitivity (p= 0.168), PFS (p=0.126) and OS (p=0.335). MAGE-A10 protein expression reliably identifies advanced-stage HGSOC unresponsive to platinum-based chemotherapy. Targeted im-munotherapy could represent an important alternative therapeutic option in these cancers.

Abstract Plant uptake and assimilation of essential nitrogen compounds from the soil are mainly in the form of nitrate and ammonium ions. Plant nitrate transporters (NRTs) play a crucial role in nitrate uptake from the soil into the roots. NRT structural analysis reveals the mechanisms by which these transporters function. Similarly, plant ammonium transporters (AMTs) mediate the uptake of ammonium ions, and their structural analysis has provided valuable information on their mechanisms. After nitrogen uptake by plant roots, the nitrogen metabolism pathway involves the incorporation of nitrogen into organic compounds. Glutamine synthetase (GS) and glutamate synthase (GoGAT) are the master players in this pathway. They work together to convert ammonium ions into glutamine and glutamate, respectively. Different isoforms of GS and GoGAT exist, enabling plants to fine-tune nitrogen metabolism based on environmental cues. Under severe abiotic stress conditions, nitric oxide (NO) has been found to enhance plant survival under drought. Furthermore, the interaction between salinity stress and nitrogen availability in plants has been studied, with NO identified as a potential mediator of responses to salt stress. On the other hand, excessive use of nitrate fertilizers can lead to health and environmental issues. Therefore, alternative strategies, such as establishing nitrogen fixation in plants through diazotrophic microbiota, have been explored to reduce reliance on synthetic fertilizers. Ultimately, genomics can identify new genes related to nitrogen fixation, which could be harnessed to improve plant productivity. By deciphering the genetic basis of nitrogen-fixing traits, researchers aim to develop crops that efficiently utilize nitrogen from the environment.

Tumour microenvironment, composed of pro- and anti-tumour immune cells, affects cancer cells behaviour. We aimed to evaluate if tumour-infiltrating lymphocyte (TIL) density and TILs subtypes in core biopsies at diagnosis of breast cancer patients could predict pathologic complete response (pCR; ypT0/is ypN0) from neoadjuvant systemic therapy (NST). The TIL subtypes were determined based on the proportions of presumably anti-tumour (CD8+, CXCL13+) and pro-tumour (PD-1+, FOXP3+) immune cells. A prospective, non-interventional study including 171 participants undergoing NST was performed. The median TIL density for the entire cohort was 10% (IQR: 3.5-23.8), and 59 (35%) patients achieved pCR. TIL density was positively associated with pCR (univariately and multivariably). In the multivariable logistic regression model, TIL density was an independent predictor of pCR (p=0.012, OR 1.27; 95% CI 1.05-1.54) when controlled for age (p=0.232), Ki-67 (p=0.001), node-negative status (p=0.024), and HER2+/triple negative vs luminal B-like subtype (p&lt;0.001). In our sample, higher proportions of PD-1+ TILs and FOXP3+ TILs were associated with a higher probability of pCR but the association was not statistically significant. In the exploratory multivariable analysis, we showed that only higher CD8+ TILs were associated with pCR. In conclusion, TIL density and its subtypes are associated with pCR.

We here investigate the dynamical behavior of a fractional-order predator-prey system with anti-predator behavior and Holling IV type functional response. First we study the non-negativity, existence, uniqueness, and boundedness of solutions to the system from a mathematical analysis perspective. Then, we analyze the stability of its equilibrium points and the possibility of bifurcations using stability analysis methods and bifurcation theory, and prove the existence of a supercritical Hopf bifurcation in the system. After providing numerical simulations to illustrate the conclusions theoretically derived, by summarizing those various analytical results obtained, we finally present three interesting conclusions that can contribute to better understanding and preservation of ecological systems.

Food and drinks can be contaminated with pollutants such as lead and strontium and this poses a serious danger to human health. For this reason, a number of effective sensors have been developed for the rapid and highly selective detection of such contaminants. TBA, a well-known aptamer developed to selectively target and thereby inhibit the protein of clinical interest -thrombin, is receiving increasing attention for sensing applications, particularly for the sensing of different cations. Indeed, TBA, in the presence of these cations, folds into the stable G-quadruplex structure. Furthermore, different cations produce small but significant changes in this structure that result in changes in the electrical responses that TBA can produce. In this article we produce an overview of the expected data regarding the use of TBA in the detection of lead and strontium, calculating the expected electrical response using different measurement techniques. Finally, we conclude that the TBA should perform better as a detector of strontium rather than lead.

Hepatitis B Virus (HBV) is a challenge for global health services, affecting millions and leading hundreds to end-stage liver disease each year. This comprehensive review explores the interactions between HBV and the host, examining their impact on clinical outcomes. HBV infection encompasses a spectrum of severity, ranging from acute hepatitis B to chronic hepatitis B, which can potentially progress to cirrhosis and hepatocellular carcinoma (HCC). Occult hepatitis B infection (OBI), characterized by low HBV DNA levels in hepatitis B surface antigen-negative individuals, can reactivate and cause acute hepatitis B. The identification of diverse HBV genotypes reveals distinct geographical distributions and associations with clinical outcomes. Moreover, single nucleotide polymorphisms (SNPs) within the host genome have been linked to several clinical outcomes, including cirrhosis, HCC, OBI, hepatitis B reactivation, and spontaneous clearance. The immune response plays a key role in controlling HBV infection by eliminating infected cells and neutralizing HBV in the bloodstream. Furthermore, HBV can modulate host metabolic pathways involved in glucose and lipid metabolism and bile acid absorption, further influencing disease progression. HBV clinical outcomes correlate with three levels of viral adaptation. In conclusion, the clinical outcomes of HBV infection could result from complex immune and metabolic interactions between the host and HBV. These outcomes can vary among populations and are influenced by HBV genotypes, host genetics, environmental factors, and lifestyle. Understanding the degrees of HBV adaptation is essential for developing region-specific control and prevention measures.

Multiple sclerosis (MS) is a chronic and demyelinating disease with an autoimmune origin, in which inflammation and demyelination lead to neurodegeneration and progressive disability. The treatment target is slowing down the disease course and mitigating the symptoms. Approximately 30 to 50% of patients do not respond optimally to Disease Modifying Therapies (DMTs), in which therapeutic response may be influenced by genetic factors such as genetic variants. Therefore, our study aimed to investigate the association of HLA DRB1*0403 genetic variant and therapeutic response to DMTs in MS. We included 105 patients with MS diagnosis. No evidence of disease activity based on the absence of clinical relapse, disability progression or radiological activity (NEDA-3), was used to classify therapeutic response. Patients were classified as follows: a) control: patients who achieved NEDA-3 b) case: patients who did not achieve NEDA-3. DNA was extracted from peripheral blood leukocytes. HLA DRB1*0403 genetic variant was analyzed by quantitative polymerase chain reaction (qPCR) using TaqMan probes. NEDA-3 was achieved in 86.7% of MS patients treated with DMTs. Genotype frequencies were: GG 50.5%, GA 34.3% and AA 15.2%. No differences were observed in the genetic variant AA between patients who achieved NEDA-3 versus patients who did not achieve NEDA-3 (48.7% vs. 43.1%, p=0.6). We concluded that in Mexican patients with MS, HLA DRB1*0403 was not associated with therapeutic response to DMTs.

Chronic kidney disease (CKD) is a progressive condition of kidney dysfunction due to diverse causes of injury. In healthy kidneys, protein-bound uremic toxins (PBUTs) are cleared from the systemic circulation by proximal tubule cells through the concerted action of plasma membrane transporters that facilitate their urinary excretion, but the endogenous metabolites are hardly removed with kidney dysfunction and may contribute to CKD progression. Accumulating evidence suggests that senescence of kidney tubule cells influences kidney fibrosis, the common endpoint for CKD with an excessive accumulation of extracellular matrix (ECM). Senescence is a special state of cells characterized by permanent cell cycle arrest and limitation of proliferation, which promotes fibrosis by releasing senescence-associated secretory phenotype (SASP) factors. The accumulation of PBUTs in CKD causes oxidative stress and increases the production of inflammatory (SASP) factors that could trigger fibrosis. Recent studies provide some clues that PBUTs may also promote senescence in kidney tubular cells. This review provides an overview on how senescence contributes to CKD and the involvement of PBUTs in this process, and how kidney senescence can be studied, Finally, some suggestions for future therapeutic options for CKD while targeting senescence are given.

The SARS-CoV-2 virus, which is responsible for the COVID-19 pandemic which emerged and spread, has sparked intense research on its spike protein, which is essential for viral entrance into host cells. Viral reproduction and transmission, host immune response regulation, receptor recognition and host cell entrance mechanisms, as well as structural and functional effects have all been linked to mutations in the spike protein. Spike protein mutations can also result in immune evasion mechanisms that impair vaccine effectiveness and escape, and they are linked to illness severity and clinical consequences. Numerous studies have been conducted to determine the effects of these mutations on the spike protein structure and how it interacts with host factors. These results have important implications for the design and development of medicines and vaccines based on spike proteins as well as for the assessment of those products' efficiency against newly discovered spike protein mutations. The paper gives a general overview of how spike protein mutations are categorized and named, as well as the genomic and phylogenetic techniques that have been used to track their genesis and dissemination. Additionally, it looks at the links between spike protein mutations and clinical outcomes, illness severity, unanswered problems, and future research prospects. Additionally, explored are the effects of these mutations on vaccine effectiveness as well as the possible therapeutic targeting of spike protein mutations.

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

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

Covid-19 has had a significant impact on the lives of populations across the world. Since the first reported case of the coronavirus in Wuhan, China, the world faced a situation of dealing with a novel virus. While the physical health effects of the coronavirus was the center of focus for much of the pandemic, Covid-19 was accompanied with significant social and psychological consequences on the world populations. In this review, we aim to assess how the coronavirus pandemic has affected the African continent at large, highlighting the socio-psychological consequences. Through citing some examples of a few countries in Sub-Saharan Africa, the review will detail the experiences of the populations within this region which remain plagued with economic and health vulnerabilities that were further exposed by the pandemic.

A novel approach based on response surface methodology (RSM) was developed to predict and apply the best extraction conditions for the isolation of various-type polyphenolic antioxidants from the dried flower buds of Magnolia x soulangeana Soul.-Bod. var. ‘Lennei’ (Magnoliaceae). As a method of choice, ultrasound-assisted extraction was used and the optimized extraction parameters (temperature, time of extraction, the composition of aqueous-ethanolic extractants and solvent to solid ratio) have been determined using a central composite design factorial analysis, followed by appropriate spectrophotometric methods (with Folin–Ciocalteu and 2,2-diphenyl-1-picrylhydrazyl reagents) to determine the antioxidant and antiradical potential of extracts, respectively. The use of 66.8% (V/V) ethanol, as the extraction solvent during the 55.2 min extraction protocol, and the ratio of extractant volume to herbal substance of 46.8 mL/g gave the highest total yield of bioactive antioxidant phenolics in the extract obtained. For this herbal preparation, qualitative and quantitative analysis was performed using combined chromatographic (LC), spectroscopic (PDA) and tandem mass spectrometric (ESI-QTOF–MS/MS) techniques. A detailed phytochemical profiling, conducted for the first time, documented substantial amounts of polyphenolic antioxidants, especially phenylethanoids and flavonoids in the flower buds of M. soulangeana ‘Lennei’. Their average total content exceeded 30.3 and 36.5 mg/g dry weight, respectively.

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a high rate of mortality in kidney transplant recipients (KTRs). The current vaccine strategy for KTRs seems to be unable to provide effective protection against coronavirus disease 2019 (COVID-19) [2] and the occurrence of severe COVID-19 in some vaccinated KTRs suggested a lack of immunity. We analized here the antibody response in a group of 32 kidney transplant recipients (KTR) followed at the Nephrology and Dialysis unit of the Hospital Pio XI of Desio, Italy, compared with a group of 23 healthy workers classified as Late responders (HCW-LR) (10 males age 27-62) and 13 females (age 46-64). We observed that the patients need additional vaccine boosters due to their immunocompromised status and therapy to protect them from infections related to viral variants, in accordance with the literature.

Due to the non-degradability of petroleum-based packaging materials, serious environmental pollution and the depletion of non-renewable resources have become pressing issues. In order to actively promote green production and address these concerns, there is an urgent need for new packaging materials to replace traditional plastic products. Starch-based packaging materials, composed of starch, fiber, and plasticizers, offer a degradable and environmentally friendly alternative. Starch alone cannot undergo thermoplastic processing due to its inherent structural characteristics. Therefore, researchers have explored modifications by incorporating plasticizers to create processable thermoplastic starch (TPS). However, there are challenges related to the high crystallinity and poor compatibility between TPS and fibers, resulting in decreased mechanical properties. To address these challenges, a novel approach combining plasticizer optimization and response surface method (RSM) optimization has been proposed to enhance the mechanical properties of starch-based packaging materials. This method leverages the advantages of composite plasticizers and process parameters. The findings demonstrate that the composite plasticizer effectively disrupt the hydrogen bonding and granule morphology of starch, leading to a significant reduction in crystallinity. Based on these findings, the optimal process parameters are determined using the RSM, resulting in a forming temperature of 198 °C, forming time of 5.4 minutes, and AC content of 0.84 grams. Compared with the non-optimized values, the tensile strength increases by 12.2% and the rebound rate increases by 8.1%.

The objective of this study was to evaluate the glycemic index and the satiety response of three Mexican kinds of honey. The values of fructose ranged from 272.40-395.10 g/kg, while the glucose value ringed 232.20-355.50 g/kg. The ratio F/G of sample honey was 1.45, 1.00, and 1.17 for Highland, Multifloral, and Avocado honey, respectively. Twenty-six participants completed this study, which was previously approved by the ethics committee of the Facultad de Salud Pública y Nutrición (CE 2/2018-19). Highland and Avocado honey is classified as medium-GI (69.204.07 and 66.365.74, respectively), while Multifloral honey is classified as high-GI (74.245.98). The Highland honey presented the best satiety response. The difference in IG values and the effect of the satiety response of Highland honey could be explained by the different fractions of carbohydrates in samples and other components such as phytochemicals.

The COVID-19 pandemic cost 7-8 million deaths worldwide, creating an unprecedented health and economic crisis. Affecting 700 million people globally, the magnitude of this pandemic is far from anything that humanity has encountered in recent times. A detailed investigation revealed that more than the SARS-CoV2 virus, the hyperactive immune system mediated injury as the real cause of mortality. Cytokine storm following viral infection leads to the surge of proinflammatory cytokines resulting in ARDS and lung injury. Anti-inflammatory intervention with anti-IL6 (anti-IL-6 receptor monoclonal antibodies (mAbs) (e.g., sarilumab, tocilizumab) and anti-IL-6 mAbs (i.e., siltuximab) and /or steroid-based approach lead to substantial protection and prevent death thereby implying the role of inflammation in COVID-19. In this short review, we summarized the dysregulated immune system in COVID-19 infection, investigating in detail the virus–host immune cross talks and presenting the possibilities of therapeutic intervention.

DNA damage response (DDR) pathways in keto-enol genotoxicity have not been characterized, and few studies have reported genotoxic effects in non-target organisms. The present study shows that concentrations of 11.2, 22.4, 37.3 mg/L of Movento® 240SC and 12.3, 24.6, 41.1 mg/L of Envidor® 240SC for 72 h oral exposure induced DSBs by significantly increasing the percentage of γH2AV expression in regions 2b and 3 from the germarium of wildtype females of Drosophila melanogaster Oregon R, compared to the control group (0.0 mg/L of insecticides), by confocal immunofluorescence microscopy. The comparison between both insecticides’ revels that only the Envidor® 240SC induces concentration-dependent DNA damage, as well as structural changes in the germarium. We determined that the DDR induced by Movento® 240SC depends on the activation of the ATMtefu, Chk1grp and Chk2lok kinases by significantly increasing the percentage of expression of γH2AX in regions 2b and 3 of the germarium, and that ATRmei-29D and p53dp53 kinases only respond at the highest concentration of 37.3 mg/L of Movento® 240SC. With the Envidor® 240SC insecticide, we determined that the DDR depends on the activation of the ATRmei-29D/Chk1grp and ATMtefu/Chk2lok kinases, and p53dp53 by significantly increasing the percentage of expression of γH2AX in the germarium.

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

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

The papaya mealybug Paracoccus marginatus is an invasive, polyphagous pest and poses a quarantine threat to tropical and subtropical countries. Infested commodity internationally should be undergoing phytosanitary treatment, while irradiation is recommended to replace methyl bromide fumigation. Dose-response tests were conducted on the 2-, 4-, and 6-d-old eggs and gravid females of P. marginatus using the X-ray radiation doses of 15–105 Gy with an interval of 15 Gy, respectively. Radiotolerance was compared using fiducial overlapping and lethal dose ratio (LDR) test, resulting in insignificant difference except for LDR test at LD90 (leading 90% mortality at 95% confidence level (CL)); the estimated dose for 99.9968% mortality at 95% CL was 176.5–185.2 Gy, which was validated in the confirmatory tests using gamma irradiation because gammy and X-rays have equal biological effect on pests. Therefore, a total of estimating 60,386 gravid females of papaya mealybug irradiated with 146.8–185.0 Gy resulted in no F1 nymphs developing. Eggs can therefore be used as an alternative to gravid females for dose-response tests; the recommended minimum dose for phytosanitary treatment of P. marginatus on infested commodity is 185 Gy, with treatment efficacy ≥ 99.9950% at 95% CL.

The response of plasmonic metal particles to an electromagnetic wave undergoes significant features at the nanoscale level. Different properties of the internal composition of a metal, such as its ionic background and the free electron gas, begin to manifest more prominently. As the dimensions of the nanostructures decrease, the classical local theory gradually becomes inadequate. Therefore, Maxwellʹs equations need to be supplemented with a relationship determining the dynamics of current density which is the essence of nonlocal plasmonic models. In this field of physics, the standard (linearized) hydrodynamic model (HDM) has been widely adopted with great success, serving as the basis for a variety of simulation methods. However, ongoing efforts are also being made to expand and refine it. Recently, the GNOR (general nonlocal optical response) modification of the HDM has been used, with the intention of incorporating the influence of electron gas diffusion. Clearly, from the classical description of fluid dynamics, a close relationship between viscosive damping and diffusion arises. This offers a relevant motivation for introducing the GNOR modification in an alternative manner. The standard HDM and its existing GNOR modification also do not include the influence of interband electron transitions in the conduction band and other phenomena that are part of many refining modifications of the Drude‐Lorentz and other models of metal permittivity. In this article, we present a modified version of GNOR‐HDM that incorporates the viscosive damping of the electron gas and a generalized Drude‐Lorentz term. In the selected simulations, we also introduce Landau damping which corrects the magnitude of the standard damping constant of the electron gas based on the size of the nanoparticle. We have chosen a spherical particle as a suitable object for testing and comparing HD models and their modifications because it allows finding precise analytical solutions for the interaction and, simultaneously, it is a relatively easily fabricable nanostructure in practice. Our contribution also includes our own analytical method for solving the HDM interaction of a plane wave with a spherical particle. This method forms the core of calculations of the characteristic quantities, such as the extinction cross‐sections and the corresponding components of electric fields and current densities.

Citrus peels are considered as a rich source of valuable biomolecules like pectin as polymer of polysaccharide acid. In this study, response surface methodology was used to optimize pectin extraction from Citrus clementina peels using citric acid as extraction solvent. The effect of parameters conditioning the extraction process and pectin yield (pH, temperature, extraction time, solid/liquid ratio, and raw material particle size) was investigated using a Box-Behnken design. The quality of the extracted pectin was assessed both chemically (moisture, ash, protein, and sugar content) and functionally (gelling power and emulsifying activity). According to the screening experiment, the factors pH, temperature, and particle size were the main factors influencing the pectin yield. The adjusted mathematical model enabled us to plot response surfaces in order to determine optimal extraction conditions. The highest production yield of pectin (26.6%) was obtained at the optimal conditions of: pH = 1.5; temperature 100 °C and particle size = 0.1 mm for an extraction time of 30min. Compared to the predicted value of 26.6%, the experimental extraction yield was about 21.4% of pectin. Concerning the functional properties, the extracted pectin has a high gelling power of 164°SAG and an emulsifying activity of 38.5%.

Abstract: This study aims to analyze the physico-mechanical properties and dynamic models of tissue-simulating hydrogels, specifically the photoacoustic (PA) response signals, by varying the concentrations of polyvinyl alcohol (PVA) and molecular weight (MW). A state space model (SSM) is proposed to study the PVA hydrogels to retrieve the PA-related signal's damping ratio and nat-ural frequency. Nine box-shaped PVA hydrogels containing saline solution were used, with five concentrations of PVA (7, 9, 12, 15, 20%) for MW1 and four for MW2. The results indicated that the concentration of PVA and MW played an important role in the PA wave's amplitude, arrival time, and speed of sound over the hydrogels. The SSM parameters showed that increasing PVA and MW concentrations improved the hydrogels' ability to absorb and transfer energy under the PA effect. These parameters were also found to be correlated with density and modulus of elasticity. Addi-tionally, the concentrations of PVA and MW affected the absorption and optical scattering coeffi-cients. The physical-mechanical properties, including porosity, density, and modulus of elasticity, improved as the concentration of PVA and MW increased. The ultimate goal of this study is to develop hydrogels as phantoms that can be used for tissue simulation and imaging.

We have much to learn from historic buildings. The fact that they are still standing is obvious, but unfortunately often not appreciated. In this paper the results obtained from a series of parametric analyses, where the influence that geometric and mechanical parameters have in the structural response of existing cob walls within an Irish context, are presented. A design of experiments using central composite designs was implemented along with analysis of variance following two computational approaches, namely, finite element method and kinematic limit analysis. As results, a series of response surfaces and parametric equations with which it is possible to compute safety factors and collapse multipliers (within the range of values studied) are provided. Based on the results obtained, it could be concluded that traditional cob walls in Ireland are very robust. Relatively high acceleration values, unlikely to happen in a low seismic hazard region such as Ireland, would be needed to start the collapse mechanisms studied or cause yielding in typical vernacular cob walls. Furthermore, the equations generated with the refined regression models, can be used by practitioners as a first approach to estimate the safety levels of existing cob buildings with similar characteristics.

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

The noncoding RNAs (ncRNAs) are small transcript sequences that do not encode proteins but participate in the regulation of gene expression at the post-transcriptional level playing important biological roles such as proliferation and differentiation. In the tumor microenvironment, the dysregulated immunological response can participate in the progression and negative phenotype of cancer, the variability of switch cell differentiation and activation of the different immune cell lineages showed differential regulation by the type of cancer. Recent evidence showed that the upregulation of lncRNA can be used as a biomarker and predictive indicator for cancer progression. The use of lncRNA to turn off the tumor immune response and activate the anti-tumoral immune response is day by day a promising reality for the control of cancer. However, is imperatively elucidated the role of each ncRNA identified as well as its respective molecular pathways regulated, including the immune checkpoints, before its application at the clinical level. The correct delivery of lncRNA or mimics to inhibit its expression using the most efficient carriers to the cell or cellular organelle is a science that should continue to be developed.

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

Production of biofuel from lignocellulosic biomass is relatively low due to the limited knowledge about natural cell wall loosening and cellulolytic processes in plants. Industrial separation of cellulose fiber mass from lignin, its saccharification and alcoholic fermentation is still cost-ineffective and environmental unfriendly. Assuming that the green transformation is inevitable and that the new sources of raw materials for biofuels are needed, we decided to study cell death - a natural process occurring in plants in a context of reducing the recalcitrance of lignocellulose for production of second generation bioethanol. “members of the enzyme families responsible for lysigenous aerenchyma formation were identified during the root hypoxia stress in Arabidopsis thaliana cell death mutants. The cell death regulatory genes, LESION SIMULATING DISEASE 1 (LSD1), PHYTOALEXIN DEFICIENT 4 (PAD4) and ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) conditionally regulate the cell wall when suppressed in transgenic aspen. During four years of growth in the field the following effects were observed: lignin content was reduced, the cellulose fiber polymerization degree increased and the growth itself was unaffected. The wood of transgenic trees was more efficient as a substrate for saccharification, alcoholic fermentation and bioethanol production. The presented results may trigger the development of novel biotechnologies in the biofuel industry.

To ensure high-quality care, operationalize resilience and fill the knowledge gap regarding how to improve the prerequisites for resilient performance, it is necessary to understand how adaptive capacity unfolds in practice. Coronavirus 2019 stress-tested complex healthcare systems, and intensive care was driven to an unprecedented escalation. The main aim of this research was to explain the escalation process of intensive care from a microlevel perspective, including expressions of resilient performance, intervening conditions at the micro-meso-macrolevels and short- and long-term consequences. A secondary aim was to provide clinical recommendations regarding how to optimize the prerequisites for resilient performance in intensive care. A grounded theory methodology was used. First-person stories from different healthcare professionals (n70) in two Swedish regions were analyzed using the constant comparative method. A novel conceptual model of the escalation process of intensive care emerged, and 41 clinical recommendations concerning the optimal prerequisites for resilient performance were identified. Escalation was conceptualized as a transition from threatening chaos to temporary order through a complex process of adaptation. To prepare for the future, the components space, stuff, staff, system and science with associated continuity plans must be implemented, anchored and communicated to actors at all levels of the system.

Salvia hispanica (chia) is a highly nutritious food source and has gained popularity due to its high omega-3 fatty acid content. Red spider mites are a serious problem in the production of S. hispanica. However, no study has been conducted to analyse the defensive response to the infestation of red spider mites in S. hispanica. To elucidate the molecular mechanisms of the defensive response of S. hispanica to red spider mites, we performed a transcriptomic analysis of S. hispanica when infested by red spider mites. In the comparative assessment of leaf transcriptomes, a total of 1743 differentially expressed genes (DEGs) were identified between control and mite-infested S. hispanica. From these, 1208 (69%) transcripts were up-regulated and 535 (31%) were down-regulated. The DEGs included transcription factors, defense hormones, and secondary metabolites that were either suppressed or activated in response to spider mite herbivory. Gene Ontology (GO) enrichment analysis revealed that plant secondary metabolites such as glucosinolates, and signalling pathways, including the jasmonic acid signalling pathway, may play an important role in the defence against red spider mites. This study provides novel insights into the defence response of S. hispanica in response to insect herbivory and could be a resource for the improvement of pest resistance in the chia.

Ship pilots and maritime safety administration have an urgent need for more accurate and earlier warnings on strong wind gusts. This study firstly investigates the “Oriental Star” cruise ship cap-sizing event in 2015, one of the deadliest shipwreck events in recent years, and explores all related hydro-meteorological components in a global mesoscale model. It is found that, rather than the missing signal in raw surface wind prediction, the cumulus precipitation variable (CP) increases dramatically during the accident occurrence, which significantly corresponds to the sub-grid strong wind gust. The effective lead-time can be extended from 24hr (deterministic model) to 48hr (en-semble model). This finding is then verified in another two recent deadly cruise boat accidents. The introduction of the new variable is bearing the hope of improvement to the current maritime safeguard system, on predicting sub-grid strong wind gusts for small-size cruise boats in offshore and inland rivers. Finally, an automatic-response system is developed to provide economical con-vection prediction via Inmarsat email communication, aiming to explore operational severe con-vective gust early-warning and appropriate numerical mesoscale model application.

Gastric cancer is among the top 5 causes of cancer-related death worldwide. Preoperative chemotherapy has been established as an option in patients with locally advanced gastric cancer. However, chemotherapy yields variable results, owing to the cellular and molecular heterogeneity of this disease. Identifying patients who did or did not respond to preoperative therapy can allow clinicians to alter treatment modalities and provide important information related to prognostication. Pathologic response to preoperative therapies, called Tumor Response Grade (TRG), has been evaluated to quantify treatment response. Multiple systems for TRG have been established. However, literature has demonstrated inconsistent results for TGR systems and prognosis, possibly due to variability in interpretation of tumor response between systems and interobserver variability. Radiographic response to preoperative therapies using RECIST 1.1 criteria and endoscopically-assessed tumor response have demonstrated association with survival; however their use in gastric cancer remains challenging given the inability to accurately and consistently identify and measure the tumor, especially in the setting of neoadjuvant therapy where treatment-related changes can obscure the gastric wall layers. This review is focused on summarizing the available literature related to evaluating TRG in gastric cancer, as well as providing a brief overview on the use of radiographic and endoscopic methods to assess response to preoperative therapies. Lastly, we outline future directions regarding the use of a universal TRG system to guide care and assist with prognosis.

The present study employed a modifed QuEChERS method to systematically analyze the presence of fifteen Quinolones and seven Tetracyclines antibiotic residues in local animal food. Additionally, a multi-level-four-factor Box-Behnken design (BBD) within the framework of Response surface methodology (RSM) was utilized to evaluate the various factors affecting the detection efficiency of the sample pretreament procedure. The optimization was performed by Design Expert®, the factors including volume of the acetonitrle, the addition of formic acid, the duration of extract and the addition of EDTA were combined to experiment design until reach an optimal solution. Finally, the sample test was conducted by ultra-high performance liquid chromatography-quadrupole-linear ion trap mass spectrometry in both multiple reaction monitoring (MRM) and enhanced product ion (EPI) scan modes on a QTRAP® 5500 instrument. The overall average recoveries from actual samples fortified with 22 antibiotics at three levels ranged from 74.7 to 122.6% based on the use of matrix-fortified calibration with the variation ranging from 2.1 to 18.2% (n=6). The limits of detection and quantification were 0.3 μg kg-1 and 1.0 μg kg-1, respectively.

Hemifacial spasm (HFS) is a rare disorder characterized by involuntary facial muscle contractions. The primary cause is mechanical compression of the facial nerve by nearby structures. Lateral spread response (LSR) is an abnormal muscle response observed during electromyogram (EMG) testing and is associated with HFS. Intraoperative monitoring of LSR is crucial during surgery to confirm successful decompression. Proper anesthesia and electrode positioning are important for accurate LSR monitoring. Stimulation parameters should be carefully adjusted to avoid artifacts. The disappearance of LSR during surgery is associated with short-term outcomes, but its persistence does not necessarily indicate poor long-term outcomes. LSR monitoring has both positive and negative prognostic value, and its predictive ability varies across studies. Early disappearance of LSR can occur before decompression and may indicate better clinical outcomes. Further research is needed to fully understand the implications of LSR monitoring in HFS surgery.

Introduction: The primary objective of researchers in the biology of ageing is to gain a comprehensive understanding of the ageing process while developing practical solutions that can enhance the quality of life for older individuals. This involves a continuous effort to bridge the gap between fundamental biological research and its real-world applications. Purpose: In this narrative review, we attempt to link research findings concerning the hormetic relationship between neurons and germ cells, and translate these findings into clinically relevant concepts. Methods: We conducted a literature search using PubMed, Embase, PLOS, Digital Commons Network, Google Scholar and Cochrane Library from 2000 to 2023, analyzing studies dealing with the relationship between hormetic, cognitive, and reproductive aspects of human ageing. Results: The process of hormesis serves as a bridge between the biology of neuron-germ cell interactions on one hand, and the clinical relevance of these interactions on the other. Details concerning these processes are discussed here, emphasizing new research which strengthens the overall concept. Conclusions: This review presents a scientifically and clinically relevant argument, claiming that maintaining a cognitively active lifestyle may decrease age-related degeneration, and improve overall health in ageing.

Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the Nairoviridae family and Bunyavirales order, is transmitted to humans via tick bites or contact with the blood of infected animals. It can cause severe symptoms, including hemorrhagic fever, with a mortality rate between 5 to 30%. CCHFV is classified as a high-priority pathogen by the World Health Organization (WHO) due to its high fatality rate and the absence of effective medical countermeasures. CCHFV is endemic in several regions across the world, including Africa, Europe, the Middle East, and Asia, and has the potential for global spread. The emergence of the disease in new areas, as well as the presence of the tick vector in countries without reported cases, emphasizes the need for preventive measures should be taken. In the past, the lack of a suitable animal model susceptible to CCHFV infection has been a major obstacle in the development of vaccines and treatments. However, recent advances in biotechnology and the availability of suitable animal models have significantly expedited the development of vaccines against CCHF. These advancements have not only contributed to an enhanced understanding of the pathogenesis of CCHF but have also facilitated the evaluation of potential vaccine candidates. This review outlines of the immune response to CCHFV and animal models utilized for the study of CCHFV and highlights the progress made in CCHFV vaccine studies. Despite remarkable advancements in vaccine development for CCHFV, it remains crucial to prioritize continued research, collaboration, and investment in this field.

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

In response to the structural optimization problem of PCB stator coreless disc motors, the orthogonal response surface method was used to optimize the motor structure, determine the basic parameters of the motor preliminarily, and conduct orthogonal experiments on the motor parameters based on the optimization design objectives, The optimization factors were the quantity of magnetic pole of the motor rotor, the ratio of main/auxiliary pole size, the thicknessof the permanent magnet, and the air gap length.The motor torque，the amplitude of magnetic density of the air gap and waveform distortion rateare used as optimization objectives. The motor parameters that make the motor torque reach the maximum, the air gap magnetic density maximum, and the waveform distortion rate minimum. Due to the use of PCB plates instead of motor stator cores in PCB coreless disc motors,The service life of the PCB board during motor operation will be reduced with the temperature rise generated by the stator winding To solve this problem, the response surface analysis of the motor is carried out to reduce the temperature rise of the stator windings during the operation of the motor. PCB board and stator winding are the main factors affecting the temperature rise of the motor.Taking the thickness of the PCB board, the hole diameter on the board, and the uneven width of the stator winding as optimization factors, the motor parameters with the lowest temperature rise of the motor winding are obtained. Simulation analysis is conducted using Ansys/Maxwell software, and the results prove the feasibility of optimization.

Objectives: The aim of this study is to evaluate some mechanisms of the immune response of people infected with SARS-CoV-2 in both acute infection and early and late convalescence phases. Methods: This is a cohort study of 70 cases of COVID-19, confirmed by RT-PCR, followed up to 60 days. Plasma Samples and clinical data were. Viral load, blood count, indicators inflammation were the parameters evaluated. Cellular immune response was evaluated by flow cytometry and Luminex immunoassays. Results: In the severe group, hypertension was the only reported comorbidity. Non severe patients have activated memory naive CD4+ T cells. Critically ill patients have central memory CD4+ T cell activation. Severe COVIS-19 patients have both central memory TCD8+ T cells and activated effector TCD8+ cells. Non-severe COVID-19 cases showed an increase in IL1β, IL-6, IL-10 and TNF and severely ill patients had higher levels of the cytokines IL-6, IL-10 and CXCL8.Conclusion: The present work showed that different cellular responses are observed according to the COVID-19 severity in patients from Brazil an epicenter the pandemic in South America. Also, we notice that some cytokines can be used as predictive markers for the disease outcome, possibility implementation of strategies effective by health managers.

Fanconi anemia (FA) develops due to a mutation in one of the FANC genes that are involved in repair of interstrand crosslinks (ICLs). FANCG, a member of the FA core complex, is essential for ICL repair. Previous FANCG-deficient mouse models were generated with drug-based selection cassettes in mixed mice backgrounds, leading to a disparity in interpretation of genotype-related phenotype. To exclude these confounders, we created a Fancg-KO (KO) mouse model using CRISPR/Cas9. The entire Fancg locus was targeted and maintained on the immunological well-characterized C57BL/6J background. Intercrossing of heterozygous mice resulted in sub-Mendelian numbers of homozygous mice, suggesting loss of FANCG can be embryonic lethal. KO mice displayed infertility, hypogonadism but no other developmental problems. Bone marrow analysis revealed a defect in various hematopoietic stem and progenitor subsets with a bias towards myelopoiesis. Cell lines derived from Fancg-KO mice were hypersensitive to crosslinking agents-cisplatin and Mitomycin C, and Fancg-KO mouse embryonic fibroblasts (MEFs) displayed increased γ-H2AX upon cisplatin treatment. Reconstitution of these MEFs with Fancg cDNA corrected for the ICL hypersensitivity. Collectively, this project provides a new, genetically and immunologically well-defined Fancg-KO mouse model for further in vivo and in vitro studies on FANCG and ICL repair.