In chronic myeloid leukemia (CML), a clonal proliferative disorder of granulocytic lineage, the 90%‐95% of cases are characterized by t(9;22) (q34.1;q11.2) translocation, leading to the Philadelphia chromosome (1). Rarely, CML patients directly present a blast crisis, mostly of myeloid origin (2, 3). Herein, we describe one rare CML case, showing an unusual early T lymphoid blastic crisis.

We propose that the coexistence of gapless Fermi arcs with the metal-insulator crossover of in-plane resistivity in strongly underdoped cuprates can be explained by the FL* fractionalized Fermi liquid nature of these systems and it is not due simply to disorder effects. The particle excitations of this FL* system derived from variants of the t-J model are: the gapless holon carrying charge with small Fermi momentum proportional to the doping, the gapful spinon carrying spin 1/2, gauge fluctuations coupling them and the hole as a spinon-holon bound state or resonance due to gauge binding with a Fermi surface respecting the topological Luttinger theorem. In our proposal Fermi arcs are determined by the hole resonance, whereas the metal-insulator crossover is dominated by spinon-spinon (with subleading holon-holon) gauge interactions and this dichotomy is able to explain their coexistence.

Radiotherapy for cancer has been known to affect the responses of immune cells, especially those of CD8+ T cells that play a pivotal role in anti-tumor immunity. Clinical success of immune checkpoint inhibitors led to an increasing interest into the ability of radiation to modulate CD8+ T cell responses. Recent studies that carefully analyzed the CD8+ T cell responses following radiotherapy suggest the beneficial roles of radiotherapy on anti-tumor immunity. In addition, numerous clinical trials that evaluate the efficacy of combining radiotherapy with immune checkpoint inhibitors are undergoing. In this review, we summarize the current status of knowledge regarding the changes of CD8+ T cells following radiotherapy from various preclinical and clinical studies. Furthermore, key biologic mechanisms that underlie such modulation, including both direct and indirect effects, are described. Lastly, we discuss the current evidence and essential considerations for harnessing radiotherapy as a combination partner for immune checkpoint inhibitors.

The oncogenicity of the human cytomegalovirus (CMV) is debated to this day. In recent years, mounting evidence addresses an anti-cancer effect via T cell-mediated CMV-targeted tumor de-struction. However, the data mostly comes from single-center studies and in vitro experiments. Broad geographic coverage is required to offer a global perspective. This study examined the correlation between country-specific CMV seroprevalence (n=73) and age-standardized inci-dence rates for 34 tumors using data obtained from the International Agency for Research on Cancer of the World Health Organization. The association between CMV and cancer incidences in 10-year age increments was also analyzed. The study revealed a worldwide inverse correlation between CMV seroprevalence and incidences of 88.2% tumors. Notably, this inverse link persists for all cancers combined (Spearman’s ρ= -0.732, p= 0.001). An antithetical and significant correlation is also observed in particular age groups for the vast majority of tumors. Our results corroborate the conclusions of previous studies and indicate that this phenomenon holds true on a global scale. It applies to a wide spectrum of cancer histologies, suggesting a common under-lying mechanism – CMV-stimulated T cell tumor targeting. Although these results further advance the notion of CMV-based therapies, further in-depth investigation of host-virus interactions is warranted.

The aim of our study was to evaluate the impact of T. gondii status on eosinophils count (PNE), eosinophil to lymphocyte ratio (ELR) and eosinophil to neutrophil to lymphocytes ratio (ENLR) before and after can-nabis cessation in patients with psychiatric disorders. One hundred and eighty-eight patients were includ-ed in the study. T. gondii, PNE, ELR, ENLR, and urinary cannabis were measured at baseline and after 4 weeks of cannabis cessation. Highest PNE (p = .02), ELR (p = .03) and ENLR levels (p = .031) and highest increase of PNE (p = .044), and ENLR (p = .036) levels were found in patients after cannabis cessation only in the Toxo+ group. At four weeks, significant interactions between cannabis and T. gondii status for PNE (p = .038), and for ENLR (p = .043) levels were found, as well as for the evolution between baseline and 4 weeks for ENLR level (p = .049). After cannabis cessation, we found a positive correlation between negative symptoms and PNE levels at 4 weeks in the Toxo+ group. This study shows that the increase of inflammation after cannabis cessation might be modulated by T. gondii seropositivity status in patient after cannabis cessation.

Human Rhinovirus (HRV) is the most common cause of upper respiratory infections and exacerbations of asthma. In this work, we selected 14 peptides (6 from HRV A and 8 from HRV C) encompassing potential CD4 T cell epitopes. Peptides were selected for being highly conserved in HRV A and C serotypes and predicted to bind to multiple HLA II molecules. We found positive T cell recall responses by IFNγ-ELISPOT assays to 8 peptides, validating 7 of them (3 from HRV A and 4 from HRV C) as CD4 T cell epitopes through intracellular cytokine staining assays. Additionally, we verified their promiscuous binding to multiple HLA II molecules by quantitative binding assays. According to their experimental HLA II binding profile, the combination of all these 7 epitopes could be presented and recognized by > 95 % of the world population. We actually determined IFNγ responses to a pool encompassing these CD4 T cell epitopes by intracellular cytokine staining, finding positive responses in 29 out of 30 donors. The CD4 T cell epitopes identified in this study could be key to monitor HRV infections and to develop peptide-based vaccines against most HRV A and C serotypes.

When swine flu vaccines and circulating influenza A virus (IAV) strains are poorly matched, vaccine-induced antibodies may not protect from infection. Highly conserved T cell epitopes may, however, have a disease-mitigating effect. The degree of T cell epitope conservation among circulating strains and vaccine strains can vary, which may also explain differences in vaccine efficacy. Here, we evaluate a previously developed conserved T cell epitope-based vaccine and determine the persistence of T cell epitope conservation over time. We used a pair-wise homology score to define conservation between the vaccine’s swine leukocyte antigen (SLA) class I and II-restricted epitopes and T cell epitopes found in 1,272 swine IAV strains sequenced between 2013 and 2017. Twenty-four of the 48 total T cell epitopes included in the epitope-based vaccine were highly conserved and found in >1,000 circulating swine IAV strains over the five-year period. In contrast, commercial swine IAV vaccines developed in 2013 exhibited declining conservation with the circulating IAV strains over the same five-year period. Conserved T cell epitope vaccines may be useful adjunct for commercial swine flu vaccines and to improve protection against influenza when antibodies are not cross-reactive.

For several years, drugs bearing reactive electrophilic appendages have been developed. These units typically confer prolonged residence time of the drugs on their protein targets, and may assist targeting shallow binding sites and/or improving drug-protein target spectrum. Studies on natural electrophilic molecules have indicated that in many instances natural electrophiles use similar mechanisms to alter signaling pathways. However, natural reactive species are also endowed with other important mechanisms to hone signaling properties that are uncommon in drug design. These include ability to be active at low occupancy and elevated inhibitor kinetics. Here we discuss how we have begun to harness these properties in inhibitor design.

Chimeric antigen receptors (CARs) is one of the curative immunotherapeutic approaches that exploit the antigen specificity and cytotoxicity function of potent immune cells against cancers. Neuroblastoma, the most common extracranial pediatric solid tumors with diverse comportment, could be a promising candidate for using CARs therapies. Several methods harness CARs modified cells in neuroblastoma to increase therapeutic efficiency, albeit the assessment has still been less successful. Regarding the improvement of CARs, various trials have been launched to overcome insufficient capacity. However, the reason behind the inadequate response against neuroblastoma of CARs modified cells are still not well understood. It is essential to update the present reveal of comprehension of CARs to improve the efficiency of CARs therapies. This review summarizes the crucial features of CARs and its design for neuroblastoma, discusses challenges that impact the outcomes of the immunotherapeutic competence, and focuses on devising strategies currently investigated to improve the efficacy of CARs for neuroblastoma immunotherapy.

Despite advances in the understanding of its molecular pathophysiology, prostate cancer remains largely incurable, highlighting the need for novel therapies. We developed a chimeric antigen receptor (CAR) specific for prostate specific membrane antigen (PSMA), a glycoprotein that is overexpressed in prostate cancer, which expression involves neovasculature of several tumor entities, thus envisaging an additional antiangiogenic effect. To optimize the CAR design, we compared two CARs with signaling domains containing one or two T cell costimulatory elements, in addition to CD3ζ. Conversely, what has been described for other CARs, a third-generation CAR (containing CD28 and 41BB co-signaling domains) induced a potent antitumor effect similar to a second-generation CAR (containing CD28 co-signaling domain), though we observed a detrimental effect of the additional costimulatory domain that was attributed to increased activation-induced cell death (AICD). This “super-stimulation” resulted in exhaustion of cells, higher frequencies of cell death and, more importantly, the impossibility of sufficiently expanding the CAR cells to obtain the minimum number of cells requested for in vivo therapies. While the superiority of 2nd and 3rd generation over 1st generation CAR T cells has been clearly shown in both preclinical and clinical studies, the optimal combination of costimulatory domains for 3rd generation CAR-T cells must still be defined and should be evaluated case-by-case in order to fine-tune immunotherapy approaches.

The study was done to determine the effect of supplementing different forms of L-methionine (L-Met) and acetate on protein synthesis in immortalized bovine mammary epithelial cell line (MAC-T Cell): Control, L-Met, conjugated L-Met and acetate (CMA), and non-conjugated L-Met and Acetate (NMA). Protein synthesis mechanism was determined by omics method. NMA group had the highest protein content in the media and β-casein mRNA expression levels (P < 0.05). The number of upregulated and downregulated proteins observed were 77 and 62 in CMA group and 50 and 81 in NMA group from 448 proteins, respectively (P < 0.05). NMA and CMA treatments stimulated pathways related to protein and energy metabolism (P < 0.05). Metabolomic analysis also revealed CMA and NMA treatments resulted in increases of several metabolites (P < 0.05). In conclusion, NMA treatment increased protein concentration and expression level of β-casein mRNA in MAC-T cells compared to CMA.

The article presents tests aimed to verify the possibility of making T-joints in TMCP steel using laser. The tests involved the use of 10 mm thick high yield point steel S700MC obtained in an industrial manufacturing process. The joints made in the tests were single and double-sided. Subsequent non-destructive tests revealed that the joints obtained in the tests represented quality level B in accordance with PN-EN ISO 13919-1. Single-sided welding performed using the laser beam having a power of 11 kW enabled the obtainment of 8 mm deep penetration without visibly deforming the web of the joint. The double-sided welded joints were characterised by proper geometry and the presence of gas pores in the welds not compromising the requirements of quality level B (strict requirements). The weld structure was bainitic-ferritic. The weld hardness was by approximately 60 HV1 higher than that of the base material (280 HV1). The HAZ area was slightly softer than the base material. The tests of thin foils performed using a high-resolution scanning transmission electron microscope revealed that, during welding, an increase in the content of the base material in the weld was accompanied by an increase in contents of alloying microagents Ti and Nb, particularly near the fusion line. The above-named alloying microagents, in the form of fine-dispersive (Ti,Nb)(C,N) type precipitates, could reduce plastic properties of joints.

Spinors are used for the computation of probability in quantum mechanics. They are treated as elements of a complex vector space in contrast to a real vector space. Spinor theory is abstract mathematics with an ambiguous interpretation. The overall phase of spinors does not affect the computation of probability in quantum mechanics. If two spinors have an overall phase of imaginary number i, then they can be treated like vectors in a real vector space. The square of the magnitude of the number, which is the sum of dot product and the term having basis vector i of cross product of two such vectors, is equal to the probability computed using the corresponding spinors. Therefore, the geometry of such spinors can be easily depicted in a three-dimensional space like vectors in a real vector space. Spinors are not isotropic vectors in Hilbert space. The sum of dot product and cross product of two complex numbers is equivalent to the quotient of the division of one complex number by another. Similarly, the sum of dot product and cross product of two vectors is the quotient of the division of one vector by another. Using the rules of division of vectors, we can find the rules of multiplication of vectors. The rules of multiplication and division of basis vector i match the rules of multiplication and division of imaginary number i. Therefore, basis vector i is nothing but imaginary number i. Multiplication of dot and cross product of two vectors to the second vector will give us the components of the first vector that are parallel and orthogonal to the second vector. Vectors are also made up of complex numbers like spinors. The reason for finding dot product of complex numbers in the process of computing the probability is to ignore the overall phase in contrast to the phase difference. This is misconstrued as complex vector space in quantum mechanics. 3-D number which is nothing but a spinor with new notation is an extension of vector algebra. It can have a real number as a term in addition to the terms i, j and k. In all other respects, it is a vector. 3-D numbers are part of the number system like real numbers and complex numbers. The real numbers are one dimensional numbers, the complex numbers are two-dimensional numbers and the 3-D numbers as well as vectors and spinors are three-dimensional numbers. As polarisation and spin are one and the same, we can straight away apply 3-D numbers to polarisation of light. 3-D numbers will greatly simplify the study of areas of science where three-dimensional space is involved.

The enhancement of early diagnosis of lung cancer is mandatory to improve prognosis. We observed the increase cancer stem cells (CSC) and circulating tumor cells (CTC) in blood of mice on d3 after Lewis lung carcinoma (LLC) cell implantation before disease symptom. Besides we have developed an approach to reprogramming immune cells by inhibiting the MAPK/ERK pathway through MEKi and the PD-1/PD-L1 immune checkpoint signaling pathway. We hypothesized that reprogramming of spleen CD8+ T-cells could also create a population of immune cells with high antitumor activity. We reprogrammed CD8+ T-cells derived from the spleen of C57BL/6 mice (rsCD8+T-cells). The rsCD8+T-cells were able to migrate to lung and were more resistant after the exhaustion in vitro in comparison with naïve sCD8+T-cells. In the orthotopic LLC model, the rsCD8+T-cells therapy increased the amount of proliferating CD8+ and CD4+ T-cells in blood and lung from mice. The amount of CSC decreased in the blood and lung of mice treated with rsCD8+ T-cells. A morphological study revealed a decrease in the number of metastases in lung tissue. The antitumor effects of rsCD8+T-cells are based on the activation of the host immune response by increasing the populations of CD8+ and CD4+ T-cells and apoptosis of CSCs.

Triple-negative breast cancer (TNBC) is an aggressive and highly metastatic type of tumor. TNBC is often enriched in tumor-infiltrating neutrophils (TINs), which support cancer growth in part by counteracting tumor-infiltrating lymphocytes (TILs). Prior studies identified the enhancer of zeste homolog 2 (EZH2) as a pro-tumor methyltransferase in primary and metastatic TNBC. We hypothesized that EZH2 inhibition in TNBC cells per se would exert anti-tumor activity by altering the tumor immune microenvironment. To test this hypothesis, we used CRISPR to generate EZH2-knockout (KO) and overexpressing lines from parent (wild-type -WT) 4T1 cells, an established murine TNBC model. In vitro, EZH2 KO and OE cells showed little change in replicative capacity and invasiveness, but marked changes in surface marker profile and cytokine/chemokine secretion compared to WT cells. On in vivo injection, EZH2 KO cells showed significantly reduced primary tumor growth and a 10-fold decrease in lung metastasis compared to WT cells, while EZH2 OE cells were unchanged. Compared to WT tumors, TIN:TIL ratios were greatly reduced in EZH2 KO tumors but unchanged in EZH2 OE tumors. Our findings show a tumor-intrinsic role of EZH2 in the 4T1 TNBC model in regulating TIN/TIL poise, primary tumor progression and lung metastasis in vivo.

Keywords: Agrobacterium 1; Xenorhabdus 2; NR-AMP 3 T-DNA keyword 4; TI-plasmid 5; Intact/Cured/T-DNA Deleted 6 Sensitive/Resistant 7; EMA_PF2 8; HPLC 9

By conjugating a radioantigen (o-quinone) with a protein - Esherichia coli endotoxin, a stable polyantigen complex-protein-quinoid radioantigen (BChA) - o-quinone imine (C6H10O-NH - protein) was obtained, including haptenic (o-quinone) and protein part of the antigenic complex (Esherichia coli endotoxin). Using the above components (hyperimmune antiradiotoxic serum, ethanol extract of the Vita-Force apiphitopreparation, metabolic products of Bifidobacterium bifidum, Bacillus subtilis and a highly dispersed fraction of bentonite), a polyfunctional composition «Polyapisogen» was compiled, including polyglobulins (500 cm3 per 1 L),500 cm3 of 4% ethanol extract of the Vita-Force apiphitopreparation, in which a highly dispersed fraction of bentonite (20 g), metabolism products (2 g powder) and Bacillus subtilis metabolism products (4 g) are dissolved. The polyfunctional preparation obtained by the above-described technology is used as an activator of the immune system against the background of its imbalance induced by agents of a radiogenic nature. It was found that a single subcutaneous injection of the drug at a dose of 25 mg / kg of live weight (dry matter basis) had a radioprotective effect increasing the survival rate of affected animals upto 75%. The studies carried out can serve as a basis for the creation of polyfunctional radioprotective, immunoprotective and bioprotective agents not only for isolated, but also for combined lesions of the body by agents of radiogenic and non-radiogenic nature using polyglobulins, convalescent serums, bee products, metabolic products of probiotic microorganisms and mineral sorbents.

The high level of dengue virus (DENV) seroprevalence in areas where Zika virus (ZIKV) is circulating and the cross-reactivity between these two viruses have raised concerns on the risk of increased ZIKV disease severity for patients with a history of previous DENV infection. To determine the role of DENV pre-immunity in ZIKV infection, we analysed the T and B cell responses against ZIKV in donors with or without previous DENV infection. Using PBMCs from donors living in an endemic area in Colombia, we have identified, by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay, most of the immunodominant ZIKV T-cell epitopes in the non-structural proteins NS1, NS3 and NS5. Analyses of the T and B-cell responses in the same donors revealed a stronger T-cell response against peptides conserved between DENV and ZIKV, with a higher level of ZIKV-neutralizing antibodies in DENV-immune donors, in comparison with DENV-naïve donors. Strikingly, the potential for antibody mediated enhancement of ZIKV infection was reduced in donors with sequential DENV and ZIKV infection in comparison with donors with DENV infection only. Altogether, these data suggest that individuals with DENV immunity present improved immune responses against ZIKV.

The aim of this article is introduced the concept of double framed T-soft fuzzy set (DFT-soft fuzzy set) which is the combination of soft set and fuzzy set. We also defined the notions and apply this concept in BCK/BCI-algebras. By using example, we also discussed the concept of double framed T-soft fuzzy algebra (DFT-soft fuzzy algebra) and double framed B-soft fuzzy algebra (DFB-soft fuzzy algebra) and also investigated their properties. Each double framed T-soft fuzzy algebra is double framed B-soft fuzzy algebra but by using example, we proved that converse may or may not be possible.

LCK, a member of the Scr kinase family, is a non-receptor tyrosine kinase involved in immune cell activation, antigen recognition, tumor growth, and cytotoxic response. The enzyme has usually been linked to T lymphocyte activation upon antigen recognition. Lck activation is central to CD4, CD8, and NK activation. However, recently, it has become clearer that activating the enzyme in CD8 cells can be independent of antigen presentation and enhance cytotoxic response. The role of Lck in NK cytotoxic function has been controversial in a similar fashion as the role of the enzyme in CAR T cells. Inhibition of Lck has been mainly to treat hematologic malignancies with a high rate of success. They may be useful in treating other tumor types, and they may be useful to prevent cell exhaustion. New, more selective inhibitors have been documented, and they have shown inter-esting activities not only in tumor growth but in the treatment of autoimmune diseases, asthma, and graft vs host disease. Drug repurposing and bioinformatics can aid in solving several unsolved is-sues on the role of Lck in cancer. In summary, the role of Lck in immune response and tumor growth is not a simple event and requires more research.

Despite advances in our knowledge of systemic lupus erythematosus (SLE) has increased over time, there are still many challenges in deciphering the precise mechanisms involved in the development and progression of the disease. Recent evidence has raised questions about the effectiveness of the programmed cell death protein 1 (PD-1) in suppressing autoreactive CD4+ T cells during the autoimmune response. Research has ventured into investigate the potential impact of PD-1 on various CD4+ T cell subpopulations, including T follicular helper (Tfh) cells, circulating Tfh (cTfh) cells, and T peripheral helper (Tph) cells, all of which exhibit substantial PD-1 expression and have been closely related with several autoimmune disorders including SLE. This review aims to highlight the complex role of PD-1 in autoimmunity and emphasizes the imperative for further research to elucidate its functions during autoreactive T-cell response. Additionally, we address the potential of PD-1 or its ligands as a possible therapeutic target in SLE.

Anti-CD19 chimeric antigen receptor (CAR) T-cells represent a novel immunotherapy that has shown remarkable success in the treatment of adult relapsed or refractory (R/R) B-cell non-Hodgkin's lymphoma, adult R/R mantle cell lymphoma, and R/R acute paediatric lymphoblastic leukaemia. One barrier to the widespread use of CAR T-cell therapy is toxicity, primarily cytokine release syndrome (CRS) with a variable grade of severity. The main manifestations of CRS are fever, hypotension, cytopenia, organ dysfunction among others. Neurological toxicities vary widely and range from headaches to encephalopathy. In addition, anti-CD19 CAR T-cell therapy provokes an array of less frequent events, such as coagulopathies, delayed cytopenia, and cardiovascular toxicities. In general, toxicities are usually reversible and resolve on their own in most cases, though severe cases may require intensive care and immunosuppressive therapy. Deaths due to CRS, neurologic toxicity and infectious complications have been reported, which highlights the gravity of these syndromes and the critical nature of appropriate intervention. In this paper, we look at all available FDA- and EMA-approved information about the pathophysiology, clinical manifestations, risk factor reviews of existing toxicity grading systems, current management strategies, and guidelines for anti-CD19 CAR T-cell toxicities. We also present new approaches, which are under investigation, to mitigate these adverse events.

The integration of Artificial Intelligence (AI) in the FinTech industry has substantially reshaped operational workflows, product innovation, and risk management, all of which influence company valuation. This study investigates the impact of AI-enhanced multilayer networks on FinTech valuation. Utilizing a novel scalable multilayer network model with AI-driven Copula Nodes, the research reveals that operational efficiency is a significant driver of market value. However, the findings emphasize the necessity of a balanced strategy that integrates AI across all operational layers, particularly in risk management and product innovation, to maximize valuation. This study offers a comprehensive framework that enhances understanding of AI’s complex role in FinTech valuation, providing critical insights for industry stakeholders.

This paper focuses on studying the mapping properties of singular integral operators on product spaces. The boundedness of such operators is established on Triebel-Lizorkin spaces whenever their kernel functions belong to Grafakos and Stefanov class. Our results generalize and improve some previously known results.

This paper investigates the possible failure modes of the product development process in production companies that are active in the B2C markets with a focus on household products. Since these cases require short lead times and are difficult to differentiate, in many instances the end result will not be the desired one and could affect profitability for a season or for good. A model of these possibilities is created and an approach to plan contingencies for their solutioning is proposed in the article. The main guideline is to switch from failure probability determination to accepting failure as inevitable and using digital solutions to reinforce the development process in order to offset its impact. For this goal, an Industry 5.0 Abatement Factor (abbreviated IFAF) is introduced in the contingency planning approach, that factors in the evaluation the low cost of digital instruments and the proper mix of Technology, Humans and AI (abbreviated THAI). The new working procedure based on these concepts and their interlinkages is discussed based on specific examples.

Nowadays circular economy trend drives researchers in the recovery of various bioactive compounds from agri-food by-products. Enzyme-assisted extraction (EAE) is shown as an innovative green technology for the effective extraction of various phytochemicals from agri-food section by-products, therefore this study aimed to evaluate the application of EAE as green technology to obtain extracts from olive leaves (Olea europaea) for potential industrial production. EAE was conducted under various enzyme dose combinations, and incubation time (120 min). Obtained extracts were characterized in terms of total polyphenols (TP) and Total Antioxidant Activity (AA). Firstly, the enzyme synergistic effect in enzymatic extraction of polyphenols was evaluated. TP optimal extraction conditions (468.19 mg GAE/L) were achieved after EAE (50-50%) and for AA (69.85 AA%). According to the above results, a second experimental part occurred for the incubation time (min.) and enzyme dose (mL) of optimal extraction conditions of olive leaves. Results indicated EAE as an excellent choice for green extraction of polyphenols from the olive leaves.

Although Lov\'{a}sz introduced the graph exponential $G^K$ in 1967, this product has received little attention. This paper focuses on the number of components in $G^K$ when exponent $K$ is a complete graph $K_n$. For a connected bipartite $G$, when $K$ is $K_2$, $G^{K_2}$ has three components; and when $K$ is $K_n$ with $n>2$, $G^{K_n}$ produces $\lceil\frac{n+1}{2}\rceil$ components. A connected $G$ with an odd cycle produces one component in $G^{K_n}$.

ABSTRACT Lubricants play a crucial role in reducing friction and wear between surfaces in relative motion. Engine oil, as a lubricant, is specifically designed to minimize friction and wear between the moving parts of different equipment and machinery. Engine oil blending serves the purpose of adjusting the variety of lubricants available to meet specific performance requirements. Through blending, it is possible to tailor the characteristics of the lubricating oil, such as viscosity, stability, and additive content, to optimize its effectiveness in reducing friction, protecting engine components, and enhancing overall equipment performance. By customizing lubricant formulations through blending, manufacturers can address the diverse lubrication needs of modern engines and machinery, ensuring smooth operation, longevity, and efficiency.To enhance the quality of the lubricant and achieve the desired high-performance multi-grade engine oil, a systematic approach was followed. The process began with testing the specific gravity of the oil using a hydrometer and thermometer to ensure accurate measurements. Subsequently, 5 liters of base oil were carefully measured and poured into a stainless steel reactor pot to serve as the blending vessel. Following this, 1 liter of paraffin oil (100N) was added to the base oil to introduce specific properties to the blend. To further optimize the formulation, 0.42 kg (7% of the total blend) of additives, including a selection of specific performance-enhancing compounds, was incorporated. These additives, such as Aspen, Tackifier, and other essential components like anti-wear, corrosion inhibitors, detergents, dispersants, and antioxidants, were meticulously measured and added to the mix. Through this precise blending process, the goal was to craft a high-quality multi-grade engine oil that meets the stringent performance requirements for various operating conditions and equipment types. After the melted Aspen and dissolved tackifier were added to the mixture, thorough stirring was carried out to ensure uniform distribution until a homogeneous blend was achieved. The mixture was then exposed to heat to facilitate the reaction between the base oil and additives, reaching a temperature of 70°C for optimal blending. Subsequently, 0.5 kg of viscosity index improver was introduced into the mixture and stirred continuously for a period of 5 minutes to ensure proper integration. Following this step, 5 grams of dye were carefully added to the mixture, and stirring was continued to evenly disperse the coloring agent throughout the blend. This meticulous process aimed to ensure that all components were effectively incorporated, facilitating the production of a high-quality, customized multi-grade engine oil with enhanced performance characteristics and optimal lubricating properties. After subjecting the mixture to a temperature of 70°C, the heat source was removed, allowing the product to gradually cool down to room temperature, which was estimated to be around 30°C. Following this cooling process, the product underwent a filtration step to remove any residual impurities present in the mixture. A sample of the purified product was then extracted for further analysis. Quality control tests were meticulously carried out on the sample to ensure that the product met the rigorous standards set by the Standard Organization of Nigeria (SON). The results obtained from the quality control tests were highly promising, indicating that the product indeed complied with the stringent specifications outlined by the regulatory body. This adherence to quality standards is essential in ensuring the product's reliability and performance in various applications. The successful outcome of the quality control test underscores the meticulous attention to detail and commitment to excellence in the production process. The rigorous quality control procedures implemented in the analysis of the product highlight the commitment to upholding high standards of quality and safety in the manufacturing process. By consistently meeting and exceeding industry regulations and standards, the product not only demonstrates its reliability but also reflects a dedication to customer satisfaction and product excellence. The adherence to the SON standards showcases a commitment to producing top-quality products that meet the needs and expectations of consumers and industry stakeholders alike.

Recent technological advancements such as IoT and Big Data have granted industries extensive access to data, opening up new opportunities for integrating Artificial Intelligence (AI) across various applications to enhance production processes. We can cite two critical areas where AI can play a key role in industry such as product quality control and predictive maintenance. This paper presents a survey of AI applications in the domain of Industry 4.0, with a specific focus on product quality control and predictive maintenance. Experiments were conducted using two datasets, incorporating different machine learning and deep learning models from the literature. Furthermore, this paper provides an overview of the AI solution development approach for product quality control and predictive maintenance. This approach includes several key steps, such as data collection, data analysis, model development, model explanation, and model deployment.

Concern for global health security and the environment due to the emergence of antibiotic-resistant bacteria and antibiotic residues in meat and other livestock products has led many countries to restrict the use of antibiotics in animal feed. This experiment was performed to assess the impact of dietary supplementation with a probiotic (Bacillus subtilis) and a postbiotic (Saccharomyces cerevisiae fermentation product) on growth performance, carcass traits, blood haemato-biochemical profile, gut microbiome, gut morphology, and immune response in broilers as an alternative to antimicrobials in poultry production system to minimize the effect on global health security. A total of 324-day-old Ven Cobb 400 broiler chicks were randomly divided into three dietary groups, each containing 12 replicated pens (n = 12), .and each replicate contained nine broiler chickens. The dietary groups consisted of 1) a basal diet without any growth promoting (T1), 2) the basal diet augmented with Bacillus subtilis at 200 g/MT feed (T2), and 3) the basal diet supplemented with Saccharomyces cerevisiae fermentation product at 1.25 kg/MT feed (T3). To calculate body weight gain, all birds and residual feed were weighed on a replicated basis over days 0, 7, 14, 21, 28, 35, and 42; mortality was recorded daily. Each replicate's mortality percentage was calculated and used to adjust BW, ADFI, and FCR calculations at the trial's end. At the end of the trial (42 d), two chickens from each replicate (24 chickens per group) were slaughtered for carcass traits, gut microbiome, and morphology measurements. Blood samples were collected for the haemato-biochemical profile on 35d and antibody titer on 28d and 35d.Feeding with SCFP (T3 group) significantly improved average daily feed intake (ADFI) and average daily gain (ADG) of chickens compared to the T1 (control) and T2 (probiotic) groups from 1 to 14 days of age. FCR was significantly improved (P<0.05) in SCFP-fed birds (T3) relative to the control (T1)over the entire experimental period (1-42 days). Carcass traits and blood haemato-biochemical parameters remained unaffected (P>0.05) by any diets. However, cholesterol levels and concentrations of corticosterone were significantly lower (P<0.05) in SCFP-fed birds (T3) compared to those of the probiotic (T2) and control (T1) groups. Total E. coli, Enterohaemorrhagic E. coli, ESBL-producing Enterobacteriaceae, and Salmonella counts were significantly higher in the T1group compared to T3 and T2 groups (P<0.05) and Salmonella counts were lower in T3 when compared to T2 (P<0.05). However, there was no significant difference in Lactobacillus count among treatment groups. PCR based characterization of ESBL- producing Enterobacteriaceae revealed maximum presence of blaCTX-M-Type (6/15, 40%), followed by blaSHV-Type (5/15, 33.3%) and blaTEM-Type (4/15, 26.6%). No variation in the occurrence pattern of ESBL/beta-lactamase associated genes in the studied ESBL- producing Enterobacteriaceae isolates was observed between the treatment groups. A significant increase in villi height and villi height to crypt depth ratio (VH: CD) (P<0.05) was observed in both T3 and T2 groups. Contrarily, villi widths did not vary across the dietary groups (P>0.05). The control group (T1) displayed a notable deeper in crypts when compared to the T3 and T2 groups (P<0.05). On day 28, the SCFP-fed birds (T3) and those fed the probiotics (T2) exhibited a significant increase (P<0.05) in antibody titers against Newcastle disease virus and Infectious bursal disease virus. Increase in antibody titre against IBDV in birds with the addition of SCFP in the diet was detected for the first time. However, there were no significant differences observed on day 35. The phagocytic activity of neutrophils and lymphocytes in broiler chickens did not show any noticeable variations among the different groups at day 35(P>0.05).It can be concluded that Saccharomyces cerevisiae fermentation product and Bacillus subtilis probiotic could be viable alternatives to antimicrobials in poultry production considering beneficial impacts in broilers fed antibiotic-free diet.

Synthesis of natural products with complicated architecture often requires segments having the functional groups that can be structurally transformed with the desired stereogenic centers. Bicyclic ?-lactones have a great potential for a suitable segment for natural product synthesis. However, the stereoselective construction of such functionalized bicyclic ?-lactones is not as straightforward as one might expect. On the other hand, the Lewis acid template-mediated Diels-Alder reaction is one of the most powerful and versatile methods for providing bicyclic ?-lactones with high regioselectivity and stereoselectivity. In this reaction, the Lewis acid template activates the dienophile as well as linking the diene and dienophile by a temporary tether. Therefore, Diels-Alder reaction smoothly proceeds in a stereocontrolled manner, allowing a simple access to bicyclic ?-lactone as a valuable building block for the synthesis of complicated natural products. In this review, some highlights of the Lewis acid-mediated Diels-Alder reaction, along with its application to the synthesis of biologically active compounds are discussed.

Handwriting abnormalities in children with attention deficit hyperactivity disorder (ADHD) have sometimes been reported both (i) at product level (i.e., quality/legibility of the written trace and speed of writing) and (ii) at process level (i.e., dynamic and kinematic features such as on-paper and in-air durations, pen pressure and velocity peaks, etc.). Conversely, other works have failed to reveal any differences between ADHD and typically developing children. The question of the presence and nature of handwriting disorders in ADHD remains open and merits an in-depth examination. The aim of this systematic review was therefore to identify studies investigating the product and/or process of handwriting in children with ADHD compared with typically developing individuals. This review was conducted and reported in accordance with the PRISMA statement. A literature search was carried out using three electronic databases. The methodological quality of the studies was systematically assessed using Critical Appraisal Skills Program (CASP) criteria. Twenty-one articles were identified. Of these, 17 described handwriting quality/legibility, 12 focused on speed and 14 analyzed the handwriting process. All studies (100%) with satisfactory methodology procedures reported impaired product and process in children with ADHD while 25% evidenced difference in speed of production. Most importantly, the studies differed widely in their methodological approach. Substantial gaps remain, particularly with regard to ascertaining comorbidities, ADHD subtypes and the medical status of included children. The lack of overall homogeneity in samples calls for higher quality studies. We conclude with recommendations for further studies.

Enzymes used in the synthesis of natural products are potent catalysts, capable of efficient and stereoselective chemical transformations. Lsd18 catalyzes two sequential epoxidations during the biosynthesis of lasalocid A, a polyether polyketide natural product. We performed protein engineering on Lsd18 to improve its thermostability and catalytic activity. Utilizing structure-guided methods of FoldX and Rosetta-ddG, we designed 15 mutants of Lsd18. Screening of these mutants using thermal shift assay identified stabilized variants Lsd18-T189M, Lsd18-S195M, and the double mutant Lsd18-T189M-S195M. Trypsin digestion, molecular dynamic simulation, circular dichroism (CD) spectroscopy, and X-ray crystallography provided insights into the molecular basis for the improved enzyme properties. Notably, enhanced hydrophobic interaction within the enzyme core and interaction of the protein with the FAD cofactor appear to be responsible for better thermostability.

Thin-film lithium niobate has gained significant attention in photonics due to its broad optical transparency, high refractive index, nonlinear coefficient, and substantial electro-optic coefficient. It holds great promise for developing electro-optic modulators with low loss, a compact size, and wide bandwidth. This study focuses on a meticulous investigation utilizing microwave photonics to establish a high-performance electro-optic modulator. Specifically, we analyze the optical mode field distribution and traveling wave electrode structure of lithium niobate thin-film materials. The proposed modulator achieves an impressive half-wave voltage-length product of 1.69 V·cm, a negligible metal loss of 0.01 dB/cm, and a substantial 3dB electro-optic bandwidth of 50 GHz. This research successfully realizes low-loss, high-efficiency LNOI electro-optical modulators, providing a strong foundation for large-scale integrated optoelectronic systems.

Plant-derived diterpene synthases (PdiTPSs) play a critical role in the formation of structurally and functionally diverse diterpenoids. However, the specificity or promiscuity of PdiTPSs remains unclear. In order to gain more understanding of this, the sequences of 199 functionally characterized PdiTPSs and their corresponding 3D structures were collected and manually corrected. Then, the correlations among sequences, domains, structures and their corresponding products were comprehensively analyzed. However, those features alone was insufficient for ef-fective product-specific classification of PdiTPSs as these methods could not establish a clear mapping between the enzymes and products. Nevertheless, local structural analysis can identify residues that have been experimentally proven to influence product outcomes through mutagenesis, and these residues exhibit conservation in spatial positioning and physicochemical properties. And aromatic residues surrounding the substrate exhibited selectivity towards its chemical structure. Specifically, tryptophan (W) was preferentially located around the linear substrate geranylgeranyl pyrophosphate (GGPP), while phenylalanine (F) and tyrosine (Y) were preferentially located around the initial cyclized diterpene intermediate. This analysis revealed the functional space of residues surrounding the substrate of PdiTPSs, most of which have not been experimentally explored. These findings provide guidance for screening specific residues for mutation studies to change the catalytic products of PdiTPSs.

Cashew (Anacardium occidentale) processing generates a by-product (CB) with potential for health benefits and could be a favorable ingredient to be added to a probiotic food matrix. This study aimed to assess the functional attributes of CB in fermented milk with a probiotic and a starter culture using in vitro- gastrointestinal conditions. Using a standardized fermentability assay, two strains more adapted to the dehydrated CB were chosen and applied in: Test Formulation (TF, with CB) and Control Formulation (CF, without CB). TF and CF were fermented by the probiotic strain Lacticaseibacillus paracasei subsp. paracasei F19® and the starter Streptococcus thermophilus ST-M6®. During a 28-day refrigerated (6-8 °C) shelf-life study, both strains used in CF and TF were resistant and maintained a population above 8.0 log CFU/mL in the fermented milk. TF had significant increase in total phenolic compounds and greater antioxidant potential during shelf life, along with improved survival of F19® after in vitro-simulated gastrointestinal conditions. The cashew by-product revealed to be promising as a substrate for the strains studied and the presence of CB increased the content of phenolics and antioxidant activity during storage, as well as the gastric resistance to the probiotic., leading to a promising healthy product.

Acute myeloid leukemia (AML) is the most common and incurable leukemia subtype. Despite extensive research into the disease's intricate molecular mechanisms, AML have not yet identified effective treatments or expanded diagnostic or prognostic markers. The morphological, immunophenotypic, cytogenetic, biomolecular, and clinical characteristics of AML patients are extensive and complex. Leukemia stem cells (LSC) consist of hematopoietic stem cells (HSC) and cancer cells transformed by the complex, finely-tuned interaction that causes the complexity of AML. Microenvironmental regulation of LSC dormancy, its diagnostic and therapeutic implications for identifying and targeting LSCs due to their significance in the pathogenesis of AML were discussed in this review. It is essential to perceive the relationship between the niche for LSCs and HSC, which together cause the progression of AML. Notably, methylation is a well-known epigenetic change that is significant in AML, and our data also reveals that microRNAs are a unique factor for LSC. Furthermore, multiple-targeted approaches to reduce the risk of epigenetic factors, such as the administration of natural compounds for the elimination of local LSC, may prevent potentially fatal relapses. Furthermore, the survival analysis of overlapping genes revealed that specific targets had significant effects on the survival and prognosis of patients. We predicted that the multiple-targeted effects of herbal products on epigenetic modification are governed by different mechanisms in AML and prevent potentially fatal relapses. Thus, these strategies can facilitate the incorporation of herbal medicine and natural compounds into the advanced drug discovery and development processes enabled achievable by Network Pharmacology research.

Background: the nature of alpha-D-mannose - natural aldohexose sugar, C-2 glucose epimer, whose intended use is for preventing urinary tract infections - in the interaction with E. coli is addressed in order to drive the issue of its regulatory classification as a medicinal product or medical device. Methods: PRISMA systematic review approach was applied; Delphi Panel method used to target consensus on statements retrieved from evidence. Results: Based of regulatory definitions and research evidences, the mechanism of D-mannose does not involve a metabolic or immunological action while there is an uncertainty regarding the pharmacological action. Specific interaction between the product and the bacteria within the body occurs, but its nature is inert: it does not induce a direct response activating or inhibiting body processes. Moreover, the action of D-mannose takes place, even if inside the bladder, outside the epithelium on bacteria that have not yet invaded the urothelial tissue. Therefore, its mechanism of action is not directed to host structures but to structures (bacteria) external to the host's tissues. Conclusions: From a regulatory perspective, D-mannose maintains the current medical device classification: new regulations and legal judgments can add further considerations. From a pharmacological perspective, research is driven versus synthetic mannosides: no further considerations are expected on alpha-D-mannose.

Water is essential for all living things however its pain has become serious. Many industrial activities cause its pollution by the release of polluting byproduct. Waste water treatment is hence necessary. In this context, the waste water of the textile industry containing Red Acid 52 was treated by the solid waste of the washed natural phosphate byproduct. Natural phosphate was also studied. The solid materials were first characterized by chemical analysis, Fourier Transform Infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The phosphate materials were after that, tested in the adsorption of the Red Acid 52. The experimental data indicated that the phosphate waste rock allowed the removal of Red Acid 52. Its maximum retention capacity attained 18.4 mg.g-1. Calcinations of materials inhibits the removal capacity found reduced by 60 to 70%. The adsorption kinetics of the Red Acid 52 on the material is well described by the pseudo second order model while the adsorption isotherms are identified by the Langmuir model. Hereafter, the thermodynamic study revealed that the adsorption process is spontaneous and exothermic. Keywords: Waste water, Phosphate co-product, Adsorption, Red Acid 52.

Objective: To investigate the use of blood levels of N-(2 cyanoethyl)valine (CEVal), a haemoglobin adduct of acrylonitrile, to assess lack of compliance with smoking cessation. Methods: We report CEVal concentrations and percentiles over time for 2 cessation groups, compliance was established using NNAL concentrations. CEVal half-life was estimated. Optimal thresholds were calculated based on receiver operating characteristics analysis. Results: At 180 days, among 67 participants in the continued smoking group and 159 assigned to smoking cessation or sole THP use. CEVal half-life was estimated to be approximately 30 days and the optimal thresholds were for NNAL at 40 pg/mL and CEVal at 35 pmol/g globin (81% sensitivity and specificity). Conclusions: A new generation of biomarkers of compliance is required, specific to the new generation of nicotine products. Methodological validation and standardisation could allow robust assessment of effects across clinical and observational studies while promoting comparability between studies. CEVal could play an important role as biomarker of compliance for smoking cessation and switching studies.

This manuscript critically reviews the design and delivery of spray-dried particles for the achievement of high total lung doses (TLD) with a portable dry powder inhaler. We introduce a new metric termed the product density, which is simply the TLD of a drug divided by the volume of the receptacle it is contained within. The product density is given by the product of three terms: the packing density (the mass of powder divided by the volume of the receptacle), the drug loading (the mass of drug divided by the mass of powder), and the aerosol performance (the TLD divided by the mass of drug). This manuscript discusses strategies for maximizing each of these terms. Spray drying at low drying rates with small amounts of a shell-forming excipient (low Peclet Number) leads to formation of higher density particles with high packing densities. This enables ultrahigh TLD (>100 mg of drug) to be achieved from a single receptacle. Emptying of powder from capsules is directly proportional to the mass of powder in the receptacle, requiring an inhaled volume of about 1 L for fill masses between 40 and 50 mg and up to 3.2 L for a fill mass of 150 mg.

A selection of 36 commercial probiotic fermented dairy products from UK and Europe markets were evaluated for the numbers, types and viability of Lactobacillus strains against the stated information on their packages. A comparative study was carried out on selectivity of MRS-Clindamycin, MRS-Sorbitol and MRS-IM Maltose, to select the right medium for enumeration of probiotic Lactobacillus. Based on selectivity of medium for recovery of the targeted lactobacilli and also simplicity of preparation, MRS-Clindamycin was chosen as the best medium for enumeration of probiotic Lactobacillus in fermented milks. The results of enumeration of lactobacilli showed that 22 out of a total 36 tested products contained more than 106 colony forming units/g at the end of their shelf- life, which comply with the recommended minimum therapeutic level for probiotics. Rep-PCR using primer GTG-5 was applied for initial discrimination of isolated strains, and isolates, which presented different band profile, were placed in different groups. The isolated Lactobacillus spp. were identified mainly as Lactobacillus acidophilus, Lactobacillus casei and Lactobacillus paracasei by analysis of partial sequences of the 16S ribosomal RNA and rpoA genes. In conclusion, it is unknown to recommend the adequate number of probiotic bacteria to be consumed to ensure the beneficial properties.

Numerous studies in the literature have investigated the effect of financial development on poverty, and tend to report a poverty reduction effect of financial development. The present paper considers the issue in the other way around, by examining the effect of poverty on financial development. In particular, it has investigated the financial development effect of poverty that passes through three main channels, including the education level, the level of trade openness, and the degree of export product concentration. The analysis is carried out using a sample of 97 developing countries over the period 1980-2017, and the two-step Generalized Methods of Moments (GMM). Results have shown that poverty genuinely affects financial development through these three channels. Specially, lower poverty rates induce greater financial development in countries that experience higher education levels. Similarly, a rise in poverty rates in the context of restrictive trade policies (that eventually result in lower levels of trade openness) undermines the development of the financial sector. Finally, higher poverty levels adversely affect financial development in countries that experience an increase in the level of export product concentration.

This paper is devoted to the study of reproducing kernels on 2-inner product Hilbert spaces. We focus on a new structure to produce reproducing kernel Hilbert and Banach spaces. According to multi-variable computing, this structures can be useful in electrocardiographs, machine learning and economy

Mill scale is the by-product of iron and steel industry. It can be recycled via sinter plant or solid as sinter feed materials. 85 to 90% of the constituent particles are more than 0.008 inches. The iron content is near around 70 %, with a very small amount of alkaline compounds and non-ferrous metals. Mill scale is polluted and contaminated with lubricants, oils and greases from the equipment. In this experiment for recovering of oil from mill scale, it is treated with three different methods. Then all methods were compared according to the ability of oil elimination and iron recovered. After washing and boiling with surfactants, large amount of polluted waste water becomes a problem for environment so this wastewater was utilized for making of Microbial Fuel Cells (MFCs), production of electricity in MFC depends on the biodegradation of organic materials, so different waste were added in wastewater for making MFC. The remaining of MFC was converted in bioethanol, biodiesel and biofertilizer. So this research is economical and environmentally friendly and fulfilled the important aspect of green environment with zero waste. It will be a mile stone in the research of metallurgy, environmental engineering, recycling technology and zero waste management.

Cigarette butts, also known as tobacco product waste (TPW), are the single most collected item in environmental trash cleanups worldwide. This study used an online survey tool (Qualtrics) to assess knowledge, attitudes, and perceptions about this issue among individuals representing the Framework Convention Alliance (FCA). The FCA has about 683 members on its listserv, including non-governmental tobacco control advocacy groups that support implementation of the World Health Organization’s (WHO) Framework Convention on Tobacco Control (FCTC). Respondents (n = 65) represented countries from all six WHO regions. The majority (82%) had heard the term TPW, and all considered TPW as an environmental harm at some level. Additionally, 29% of respondents failed to identify that “cigarette filters make smoking easier.” Most (73%) correctly identified TPW components; however, fewer (60%) correctly identified the composition of cigarette butts. The majority (57%) were unfamiliar with Extended Producer Responsibility (EPR) and Product Stewardship (PS) as possible environmental intervention strategies. Respondents expressing opinions concurred that adding a litter fee to fund TPW programs will aid in reducing tobacco use and reduce the environmental impacts of TPW (100%); that prevention, reduction, and mitigation of TPW could be an important part of international tobacco control programs (98%); and that banning smoking in outdoor venues could reduce TPW (95%). Only 16% reported effective prevention or clean-up efforts in their countries. Weighted rankings revealed that respondents’ saw the national government, the tobacco industry, and state governments as most important in addressing TPW. The results of this research will inform continuing international discussions by the FCTC Conference of the Parties (COP) regarding environmental policies that may be addressed within FCTC obligations.

Idiopathic pulmonary fibrosis [IPF] is a chronic progressive disease characterised by the accumulation of scar tissue in the lung parenchyma. It primarily occurs in middle-aged and elderly adults and results in significant morbidity and mortality worldwide. The disease occurs due to repetitive lung epithelial injury, subsequent fibroblast activation and myofibroblast differentiation, resulting in excessive extracellular matrix deposition. This leads to scar formation and subsequent loss of lung function. Current treatment options for patients with IPF include the two anti-fibrotic drugs, pirfenidone and nintedanib, which can slow disease progression; however, there are currently no known cures for the disease. As such, novel methods and drug targets are warranted. In this review, we provide an up-to-date account of the importance of specific cytokines and the potential role of regulatory immune cells. We discuss their role in the pathogenesis of IPF and address some of the key gaps in knowledge.

Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of T-cell lymphomas characterised by high relapse rates and no curative treatments unless the allogeneic stem cell transplantation. The main complication in the management of this kind of malignancy is the variability that characterises the genetic and clinical features among the CTCL subtypes. JAK/STAT, MAPK/ERK, PI3K/Akt, and NF-kB are those signalling pathways that are found altered in CTCL and that are responsible for promoting both T-cell malignancy and the pro-tumorigenic microenvironment. Thus, targeting key players of these pathways can be an advantageous therapeutic option for CTCL. In this review, we aim to summarise the different approaches that precisely inhibit the kinases of each cited signalling. JAK inhibitors seem to be the most promising kinase inhibitors for CTCL. However, adverse events have been reported especially in patients with immunosuppression or an underlying autoimmune disease. More studies are needed, especially clinical trials, to investigate the benefits of these drugs for the treatment of cutaneous T-cell lymphomas.

Pathogenic adenovirus (Ad) infections are widespread but typically mild and transient, except in the immunocompromised. As vectors for gene therapy, vaccine and oncology applications, Ad based platforms offer advantages including ease of genetic manipulation, scale of production and well established safety profiles, making them attractive tools for therapeutic development. However, the immune system often poses a significant challenge that may need to be overcome for adenovirus based therapies to be truly efficacious. Both pre-existing anti-Ad immunity in the population as well as the rapid development of an immune response against engineered adenoviral vectors can have detrimental effects upon the downstream impact of an adenovirus-based therapeutic. This review focusses on the different challenges posed, including pre-existing natural immunity and anti-vector immunity induced by a therapeutic, both in context of the innate and adaptive immune responses. We summarize different approaches developed with the aim of tackling these problems, as well as their outcomes and potential future applications.

To elucidate the cellular immune response to coronavirus disease (COVID-19) among children, we assessed cellular immunity in 8 children post-vaccination for COVID-19 and 11 children after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, using the T-SPOT®.COVID assay for both the spike (S) and nucleocapsid (N) proteins. In the vaccinated group, the T-SPOT®.COVID assay for the S protein yielded positive results in all eight children. In contrast, in the post-infection group, the assay for the N protein was positive in 5 of 11 children, with 3 of these 5 children requiring hospital admission, including 2 who needed mechanical ventilation. Therefore, the T-SPOT®.COVID assay is valuable for assessing cellular immunity against COVID-19, and most children infected with COVID-19 may not develop such immunity unless the disease severity is significant.

A Friedmann-Lemaitre-Robertson-Walker space-time model with all curvatures k=0,±1 is explored in f(R,T) gravity. The solutions are obtained via the parametrization of the scale factor that leads to a model transiting from a decelerated universe to an accelerating one. The physical features of the model are discussed and analysed.

Oak woodlands are a keystone ecosystem that may not be sustainable under ongoing fire management regimes and climate change. For example, in 2014, sassafras saplings started to emerge in degraded woodlands at the 1200 ha Drury Conservation Area as part of research at the Bull Shoals Field Station in Taney County, Missouri where burning was initiated in 1999. After Spring (March) 2021 burnt, we examined trend in the potential community and ecosystem effects, we assessed sapling density, height, and specific leave weigh (SLW) of white oak and sassafras (<1.0 m) from fall 2021 through fall 2022. In fall 2021, sassafras density was 560/0.1ha with mean height of 25.42cm and SLW of 0.00436g/cm² while white Oak density was 171/0.1ha with mean height of 10.2cm and SLW of 0.00680g/cm. However, in fall 2022, Sassafras density was 582/0.1ha with mean height of 71.689cm and SLW of 0.00366 g/cm² meanwhile, white Oak density was 213/0.1ha with mean height of 50.544cm and SLW of 0.00563 g/cm². We analyzed mass loss for sassafras and white oak after buried for 198 days. The weight loss for sassafras was 0.857g while oak was 0.790g for 61 days of buried. Subsequent sassafras weight loss was 1.942g, 3.343g, 4.222g and 4.82g while that of white Oak was 1.877g, 2.862g, 3.344g and 4.28g for day 105, 153 and 198 respectively. The nutrients composition and carbon sequestration of sassafras and white oak species need to be determined to better understand the effect of their dominance in fire management regime of degraded oak woodland in Southwest Missouri Ozarks.

The solar heat pump system based on photovoltaic photothermal (PV/T) modules is a new technology that integrates photovoltaics and heat reutilization. It can improve the efficiency of photovoltaic conversion and recovery the remaining heat generated during the photoelectric conversion process, thereby improving the comprehensive efficiency of the whole system. Simulink software is a visual simulation tool, which has the advantages of strong applicability, clear simulation structure and calculation process. The design of its graphical programming greatly simplifies the user modeling process and allows for direct viewing of results, therefore improving the simulation efficiency. At present, there is little research on simulation of solar heat pump systems with PV/T modules based on Simulink software. In this paper, the mathematical models of each component contained in the PV/T solar heat pump system were established based on the system working principle, energy conservation equations and some empirical formulas, and then the operation of the system was simulated by the Simulink software. Due to the operation characteristic of PV/T modules is the key influencing factor for the whole system performance, the model and simulation process for PV/T modules were introduced in detail. The results showed that the surface temperature of PV/T modules under different operating conditions was significantly lower than that of ordinary photovoltaic panels, and the temperature change amplitude was lower. As results, the power generation and photovoltaic conversion efficiency were significantly improved.

CD8 T cells and Natural Killer (NK) cells are cytotoxic lymphocytes important in the response to intracellular pathogens and cancer. Their activity depends on the integration of a large set of intracellular and environmental cues, including antigenic signal, cytokine stimulation and nutrients availability. This integration is achieved by signaling hubs such as the mechanistic target of Rapamycin (mTOR). mTOR is a conserved protein kinase, controlling cellular growth and metabolism in eukaryotic cells and therefore is essential for lymphocyte development and maturation. However, our current understanding of mTOR signaling comes mostly from studies performed in transformed cell lines, which constitute a poor model to comprehend metabolic pathway regulation. Therefore, it is only quite recently that the regulation of mTOR in primary cells has been assessed. Here we review the signaling pathways leading to mTOR activation in CD8 T and NK cells, focusing on activation by cytokines. We also discussed how this knowledge can contribute to immunotherapy development for intracellular pathogen and cancer treatment.

Energy is needed by cancer cells to stay alive and communicate with their surroundings. The primary organelles for cellular metabolism and energy synthesis are mitochondria. Researchers recently proved that cancer cells can steal immune cells' mitochondria using nanoscale tubes. This finding demonstrates the dependence of cancer cells on normal cells for their living and function. It also denotes the importance of mitochondria in cancer cells’ biology. Emerging evidence has demonstrated how mitochondria are essential for cancer cells to survive in the harsh tumor microenvironment, evade the immune system, obtain more aggressive features, and resist treatments. For instance, functional mitochondria can improve cancer resistance against radiotherapy by scavenging the released reactive oxygen species. Therefore, targeting mitochondria can potentially enhance oncological outcomes, according to this notion. The patients' reactions to radiation are varied, ranging from a complete response to even cancer progression during treatment. This concept illustrates how different levels of mitochondrial metabolism might contribute to this heterogeneity. Considering this notion can help to improve personalized oncological treatments. This article outlines the importance of mitochondrial metabolism in cancer biology and personalized treatments.

In this paper, the concept of fuzzy locally convex spaces generated by a family of fuzzy seminorms is introduced. We prove that a Minkowski functional of zero neighborhoods generates a seminorm and finally deduce that the topology generated by the family of seminorms coincides with that of the Minkowski functional.

Chimeric antigen receptor and T-cell receptor (CAR-T/TCR) cellular immunotherapies have shown remarkable success in the treatment of some refractory B-cell malignancies, with potential to provide durable clinical response for other types of cancer. In this paper, we look at all available FDA CAR-T/TCR clinical trials for the treatment of cancer, and analyze them with respect to different disease tissues, targeted antigens, products, and originator locations. We found that 627 of 1,007 registered are currently active and of those 273 (44%) originated in China and 280 (45%) in the US. Our analysis suggests that the rapid increase in the number of clinical trials is driven by the development of different CAR-T products that use a similar therapeutic approach. We coin the term bioparallels to describe such products. Our results suggest that one feature of the CAR-T/TCR industry may be a robust response to success and failure of competitor products.

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

Prostaglandin E2 (PGE2) is an important biological mediator involved in the defense against Mycobacterium tuberculosis (Mtb) infection. Currently, there are no reports on the mycobacterial components that regulate PGE2 production. Previously, we have reported that RpfE-treated dendritic cells (DCs) effectively expanded the Th1 and Th17 cell responses simultaneously; however, the mechanism underlying Th1 and Th17 cell differentiation is unclear. Here, we show that PGE2 produced by RpfE-activated DCs via the MAPK and cyclooxygenase 2 signaling pathways induces Th1 and Th17 cell responses mainly via the EP4 receptor. Furthermore, mice administered intranasally with PGE2 displayed RpfE-induced antigen-specific Th1 and Th17 responses with a significant reduction in bacterial load in the lungs. Furthermore, the addition of optimal PGE2 amount to IL-2-IL-6-IL-23p19-IL-1β was essential for promoting differentiation into Th1/Th17 cells with strong bactericidal activity. These results suggest that RpfE-matured DCs produce PGE2 that induces Th1 and Th17 cell differentiation with potent anti-mycobacterial activity.

During their complex life cycles, the Apicomplexan parasites, Plasmodium falciparum and Toxoplasma gondii employ several genetic switches to regulate their gene expression. One such switch is mediated at the level of translation through upstream Open Reading Frames (uORFs). As uORFs are found in the upstream regions of a majority of genes in both the parasites, it is essential that their roles in translational regulation be appreciated to a greater extent. This review provides a comprehensive summary of studies that show uORF-mediated gene regulation in these parasites and highlights examples of clinically and physiologically relevant proteins that exhibit uORF-mediated regulation. In addition to these examples, several studies that use bioinformatics, transcriptomics, proteomics, and ribosome profiling also indicate the possibility of widespread translational regulation by uORFs. Further analysis of genome-wide datasets will reveal novel genes involved in key biological pathways such as cell-cycle progression, stress-response, and pathogenicity. The cumulative evidence from studies presented in this review suggests that uORFs will play crucial roles in regulating gene expression during clinical disease caused by these important human pathogens.

Synthesis of zeolite T with a variety of desired characteristics necessitate extensive work in the formulation and practical experiments either by conventional hydrothermal methods or aided with different approaches and synthesis techniques such as secondary growth or microwave irradiation. The objectives of this review are to adduce the potential work in zeolite T (Offretite-Erionite) synthesis evaluating determining factors affecting the synthesis and quality of the zeolite T crystals. Attention is given to the extensive studies that interconnect with other significant findings.

It was once thought that high QoS (Quality of Service) performance solves recurrent problems of low-quality multimedia services. Since then, solutions have been proposed to ensure a high level of QoE (Quality of Experience). In this document, the authors attempt to outline their understanding of an accurate meaning of quality of multimedia services. Starting from QoS and passing through generalised QoE, the authors focus on aspects of subjective and objective quality modelling and optimisation of visual performance for TRV (Target Recognition Video) applications (such as video surveillance), outlining the path of ITU-T standardisation in this area. The authors revised the ITU-T Recommendation P.912 to reflect improved subjective test techniques developed since this Recommendation was approved. The authors also attempt to predict at least some existing errors of reasoning, which are likely to become evident for the industry in the next decade.

Although Mast cells are known as key drivers of type I allergic reactions, there is increasing evidence for their critical role in host defense. MCs do not only play an important role in initiating innate immune responses, but also influence the onset, kinetic and amplitude of the adaptive arm of immunity, or fine-tune the mode of the adaptive reaction. Intriguingly, MCs have been shown to affect T cell activation by direct interaction or indirectly by modifying properties of antigen-presenting cells, and can even modulate lymph node-borne adaptive responses remotely from the periphery. In this review, we provide a summary of recent findings that explain how MCs act as a link between the innate and the adaptive immunity, all the way from sensing inflammatory insult to orchestrating the final outcome of the immune response.

The advent of the genome editing era brings forth the promise of adoptive cell transfer using engineered chimeric antigen receptor (CAR) T-cells for targeted cancer therapy. CAR T-cell immunotherapy is probably one of the most encouraging developments for the treatment of hematological malignancies. In 2017, two CAR T-cell therapies were approved by the U. S Food and Drug Administration; one for the treatment of pediatric Acute Lymphoblastic Leukemia (ALL), the other for adult patients with advanced lymphomas. However, despite significant progress in the area, CAR T-cell therapy is still in its early days and faces significant challenges, including the complexity and costs associated with the technology. B-cell lymphoma is the most common hematopoietic cancer in dogs, with an incidence approaching 0.1% and a total of 20-100 cases per 100,000 individuals. It is a widely accepted naturally occurring model for human non-Hodgkin’s lymphoma. Current treatment is with combination chemotherapy protocols, which prolong life for less than a year in canines and are associated with severe dose-limiting side effects, such as gastrointestinal and bone marrow toxicity. To date, one canine study generated CAR T-cells by transfection of mRNA for CAR domain expression. While this was shown to provide a transient anti-tumor activity, results were modest, indicating that stable, genomic integration of CAR modules is required in order to achieve lasting therapeutic benefit. This Commentary summarizes the current state of knowledge on CAR T-cell immunotherapy in human medicine and its potential applications in animal health, while discussing the potential of the canine model as a translational system for immuno-oncology research.

Inflammatory bowel disease (IBD) has evoked a significant interest in human immunobiology given its tactical immune evasion methodologies resulting in acute immune destabilization. IBD comprising of Crohn’s disease and Ulcerative colitis manifest as chronic inflammation in the gut mucosa, leading to complexities involving immune dysregulation in the T helper lymphocyte arm effecting disease pathogenicity. The mucosa of the alimentary canal is constantly exposed to a myriad of food antigens and luminal microorganisms for which a consistent host-protective mechanism is operative in healthy people. Lowered mucosal immune expression which allows penetration of the epithelial barrier by infective pathogenic microbes, elicits both innate and adaptive immune responses in the gut culminating in aberrant intestinal inflammation. Interestingly, IBD leukocyte repertoire is significantly entwined with chemokine assisted chemotactic navigation into the sites of inflammation which is also thought to generate favourable immune suppressive responses. The functions of the cognate chemokine receptor, CCR6, which binds with its unique ligand CCL20, are expected to tilt the balance between upregulation of homeostatic tolerance and inflammatory pathophysiology. This review aims at critically examining the CCR6 driven immune pathways; T_H1/T_H2, T_H1/T_H17, T_H17/ T_reg, IL-23/IL-17, Akt/ERK-1 /2, ILC3 for systematic investigation of its underlying mechanisms in the future and to underpin its importance in resolving IBD aetiopathology. Thus, CCR6 occupies an exclusive position in gut immunology which renders it an invaluable therapeutic tool for the production of novel medicaments to treat IBD.

During the past two decades there has been a major shift in the choice of agents to treat multiple myeloma, whether newly diagnosed or in the relapsed/refractory stage. The introduction of new drug classes, such as proteasome inhibitors, immunomodulators, and anti-CD38 and anti-SLAMF7 monoclonal antibodies, coupled with autologous stem cell transplantation, have approximately doubled the disease’s five-year survival rate. However, this positive news is tempered by the realization that these measures are not curative and patients eventually relapse and/or become resistant to the drug’s effects. Thus, there is a need to discover newer myeloma-driving molecular markers and develop innovative drugs designed to precisely regulate the actions of such putative targets. B cell maturation antigen (BCMA), which is found almost exclusively on the surfaces of malignant plasma cells to the exclusion of other cell types, including their normal counterparts, has emerged as a specific target of interest in this regard. Immunotherapeutic agents have been at the forefront of research designed to block BCMA activity. These agents encompass monoclonal antibodies, such as the drug conjugate belantamab mafodotin; bispecific T-cell engager strategies exemplified by AMG 420; and chimeric antigen receptor (CAR) T-cell therapeutics that include idecabtagene vicleucel (bb2121) and JNJ-68284528.

Background: Nodal peripheral T-cell lymphomas (nPTCLs) encompass a heterogeneous group of mature and aggressive lymphoid malignancies, including peripheral T-cell lymphoma, not otherwise specified (PTCL/NOS), angioimmunoblastic T-cell lymphoma (AITL) and anaplastic large cell lymphoma (ALCL) ALK-positive and ALK-negative. Their differential diagnosis and prognosis are an issue in the clinical practice. Accurate biomarkers to refine the different subtypes of nPTCLs and to stratify their prognosis are essential to improve their treatment approach. The aim of this study was to test the prognostic impact of GATA3 gene expression, and its capability to discriminate the different subtypes of nPTCLs. Patients and Methods: From 2000 to 2017, 80 patients with nPTCLs were eligible for GATA3 gene expression analysis that was assessed retrospectively by quantitative real time PCR (qRT-PCR) of neoplastic biopsies in Formalin-Fixed Paraffin-Embedded samples (FFPE). Results: Median age was 49 years old (IqR 34-59), 43/80 (53.7%) were male. Median follow-up was 1.72 years. Of them, 36.3% were classified as PTCL/NOS, 31.2% ALK-negative ALCL, 21.2% ALK-positive ALCL and 11.3% AITL. The majority of cases had advanced stage (III/IV). Two-year estimated overall survival (OS) and progression-free survival (PFS) were 52.2% and 39.5%, respectively. The median GATA3 gene expression level was 0.49% (range 0 – 7.07) in all cohort, it was 0.11% for ALK-positive ALCL, 0.46% for ALK-negative ALCL, 0.86% for PTCL/NOS and 0.67% for AITL. The difference of GATA3 gene expression among distinct variants of nPTCLs was statistically significant (p < 0.001). GATA3 gene expression levels ≥ 0.71% discriminate PTCL/NOS from ALK-negative ALCL and AITL with sensitivity of 62% and specificity of 80.3%. GATA3 gene expression levels ≥ median was associated with poor 2-year OS for PTCL/NOS (46.7% x 21.4%, p=0.04) and for ALK-negative ALCL (85.7% x 54.5%, p=0.04). Conclusion: Despite the relative small and heterogeneous group of patients with nPTCLs, GATA3 gene overexpression may be an important biomarker associated with poor prognosis in PTCL/NOS and ALK-negative ALCL. Moreover it may also discriminate different subtypes of nPTCLs. Further studies with larger series of patients should confirm our findings.

CRCMSS/pMMR contain a significantly increased fraction of TREM2+ macrophages (TAMs) and CD66+ neutrophils (TANs) together with decrease of CD4-CD8-CD3+ double negative T lymphocytes (DNTs); no differences were revealed by the analysis of myeloid and plasmacytoid dendritic cell populations. A fraction of tumor-infiltrating T-cells display an exhausted phenotype, co-expressing PD-1 and TIM-3. Remarkably, expression of PD-L1 on fresh tumor cells and TAMs was undetectable even after in vitro stimulation with interferon-γ. These findings confirm the immune suppressive microenvironment of CRCMSS/pMMR characterized by dense infiltration of TAMs, occurrence of TANs, lack of DNTs, T-cell exhaustion and interferon-γ unresponsiveness by host and tumor cells. Appropriate bypass strategies should consider these combinations of immune escape mechanisms in CRCMSS/pMMR.

Over the last decades, cellular immunotherapy has revealed its curative potential. However, the inherent physiological characteristics of immune cells can limit the potency of this approach. Best defined in T cells, dysfunction associated with terminal differentiation, exhaustion, senescence, and activation-induced cell death undermine adoptive cell therapies. In this review, we concentrate on how the multiple mechanisms that articulate the various forms of immune dysfunction impact cellular therapies primarily involving conventional T cells, but also other lymphoid subtypes, in addition to the various strategies put in place to circumvent these effects. The repercussions of immune cell dysfunction across the full life cycle of cell therapy, from the source material, during manufacturing, and after adoptive transfer are discussed. Applicable to cellular products prepared from native and unmodified immune cells, as well as genetically engineered therapeutics, the understanding and potential modulation of dysfunctional features is key to the development of improved cellular immunotherapies.

The enzyme-coupled transient receptor potential channel subfamily M member 7, TRPM7, has been associated with immunity and immune cell signalling. Here, we review the role of this remarkable signalling protein in lymphocyte proliferation, differentiation, activation and survival. We also discuss its role in mast cell, neutrophil and macrophage function and highlight the potential of TRPM7 to regulate immune system homeostasis. Further, we shed light on how the cellular signalling cascades involving TRPM7 channel and/or kinase activity culminate in pathologies as diverse as allergic hypersensitivity, arterial thrombosis, and graft versus host disease (GVHD), stressing the need for TRPM7 specific pharmacological modulators.

Freeze drying (FD) is a technique used to preserve the bioactive content and flavor of samples. Foods with a short shelf life due to nature have been preserved by FD in recent years. The success of the drying technique is thanks to the high retention ability of the bioactive compounds and the flavor of the sample. However, the high cost and energy consumption of the FD limit its usage in several fields. Freezing, primary drying, and secondary drying, which take place in the same device, are the stages of the FD. In addition, several parameters, including pretreatment, size, temperature, sample species, time, and pressure, affect the FD process. These parameters are controlled to increase the effectiveness of the FD on the samples. Moreover, FD was compared with other drying techniques including hot-air drying, microwave drying, vacuum drying, and solar drying to determine its protective capability. It has also been applied to the valorization of waste products, which is a common problem worldwide. For valorization, microencapsulation and powder production have been achieved by FD. In recent years, studies on the effects and use of the FD on various materials increased, providing new aspects for the future of science and food industry.

Prime numbers are the building blocks of number theory, and their properties have intrigued mathematicians for centuries. In this paper, we explore a specific categorization of primes, which we refer to as "twin primes", “cousin primes” and "sexy primes". We begin by examining the form of prime numbers greater than 7 and analyze their potential to be expressed in terms of $6n + 5$ or $6n + 7$. This investigation leads to the identification of conditions under which prime numbers can form twin, cousin and sexy pairs. We further develop a general framework to characterize the product of all twin (except 15), cousin (except 21) and sexy primes, providing insights into their algebraic structure.

The paper considers two models of queuing with a varying structure based on the introduction of additional transient intensities into known models or their combinations, which create stationary distributions convenient for calculation. In the first model, it is a probabilistic mixture of known stationary distributions with given weights. In the second model, this uniform distribution is repeatedly used in physical statistics. Both models are based on the selection of states, between which additional transient intensities are introduced. The algorithms used in the paper for introducing new transient intensities are closely related to the concept of flow in a deterministic transport network. The introduced controls are selected so that the marginal distribution of the combined system is a mixture of the marginal distributions of the combined systems with different weights determined by the introduced transient intensities. As a result, the process of functioning of the combined system is obtained by switching processes corresponding to different combined systems at certain points in time.

The Riemann Hypothesis (RH) is proved based on a new absolutely convergent expression of $\xi(s)$, which was obtained from the Hadamard product, through paring $\rho_i$ and $\bar{\rho}_i$, and taking the possible multiple zeros into consideration with their real (unique and unchangeable) multiplicities, i.e. $$\xi(s)=\xi(0)\prod_{\rho}(1-\frac{s}{\rho})=\xi(0)\prod_{i=1}^{\infty}(1-\frac{s}{\rho_i})(1-\frac{s}{\bar{\rho}_i})=\xi(0)\prod_{i=1}^{\infty}\Big{(}\frac{\beta_i^2}{\alpha_i^2+\beta_i^2}+\frac{(s-\alpha_i)^2}{\alpha_i^2+\beta_i^2}\Big{)}^{m_{i}}$$ where $\xi(0)=\frac{1}{2}$, $\rho_i=\alpha_i+j\beta_i$ and $\bar{\rho}_i=\alpha_i-j\beta_i$ are the complex conjugate zeros of $\xi(s)$, $0<\alpha_i<1$ and $\beta_i\neq 0$ are real numbers, $m_i\geq 1$ is the real multiplicity of $\rho_i$, $0<|\beta_1|\leq|\beta_2|\leq|\beta_3|\leq \cdots$. Then, according to the functional equation $\xi(s)=\xi(1-s)$, we have $$\prod_{i=1}^{\infty}\Big{(}1+\frac{(s-\alpha_i)^2}{\beta_i^2}\Big{)}^{m_{i}}=\prod_{i=1}^{\infty}\Big{(}1+\frac{(1-s-\alpha_i)^2}{\beta_i^2}\Big{)}^{m_{i}}$$ which, owing to the uniqueness and unchangeableness of $m_i$, is finally equivalent to (for more details, see the proof of Lemma 3.) $$\Big{(}1+\frac{(s-\alpha_i)^2}{\beta_i^2}\Big{)}^{m_{i}}=\Big{(}1+\frac{(1-s-\alpha_i)^2}{\beta_i^2}\Big{)}^{m_{i}} \Leftrightarrow \alpha_i=\frac{1}{2}, 0<|\beta_1|<|\beta_2|<|\beta_3|<\cdots$$ Thus, we conclude that the RH is true.

Introduced in 1967 by Lov\'{a}sz, graph exponentiation has received little attention over the past several decades. Since graph exponentiation produces large graphs and any graph can be constructed utilizing its adjacency matrix, we provide a four step linear construction algorithm that generates the adjacency matrix for the graph exponential.

Abstract: Steamed ginseng water (SGW), the by-product generated from the heated processing of red ginseng, with high content of active substances, better skincare activities, and large amount output ineffective utilization, resulted in environmental pollution and resource waste. In current study, UHPLC-Q-Exactive-MS/MS liquid chromatography-mass spectrometry and multivariate statistical analysis were conducted to characterize the compositional features of the repeated thermal-treated SGW. The total sugar content, total sugar content, total reducing sugar content, total non-reducing sugar content, DPPH, ABTS+, Fe3+ reducing capacity, and the hydroxyl radical scavenging abilities were employed to evaluate the gross contents variation connect with anti-oxidant activities during heat processes. The result revealed the SGW content and antioxidant activity were highly correlated, the 7th SGW sample showed the highest content and the strongest ability on anti-aging capacities. 38 significant common differential markers were screened, by the four compared SGW groups (1- and 3-, 1- and 5-, 1- and 7-, and 1- and 9) through OPLS-DA analysis. The current study showed that the thermal proceeding times could be a vital index value during the recycling operation quality control of SGW, which has a huge potential in anti-aging cosmetic raw materials, In the meanwhile, our results provided a green, sustainable, low-cost thinking of rational application on ginseng resource.

Due to the recent trend of unmanned economy, retail stores have gradually reduced their service and cashier manpower. The retail product recognition becomes one of key issues for unmanned shopping. Although the success of deep neural networks has made object recognition feasible in a variety of applications, it still struggles to perform well on a large number of classes of retail products. In this paper, we propose an improved ensemble learning-based approach for retail product recognition. In the proposed approach, the object classification network is first improved through feature extraction and block attention. An ensemble model is then built by integrating multiple network models and using loss selection as model weights. In the experiments, the feasibility of our ensemble learning-based approach has been evaluated through many production items. The results demonstrate the effectiveness of the proposed approach compared with previous retail product recognition methods.

In order to meet the diversified rehabilitation needs of people, it is necessary to design a product for active rehabilitation of patients. Existing rehabilitation chairs use intelligent massage, which can cause problems such as large massage area, inability to local massage, large chair size, and inability to meet the continuous use of the damaged parts. In this paper, modular design method and multi-layer evaluation method are used to solve the problems related to rehabilitation chairs. The authors use the questionnaire survey method and the functional technology matrix method to determine the functional requirements of the rehabilitation chair, and then use the multilevel evaluation methods, including the AHP method, entropy weight method main and grey correlation analysis, to optimize the functional solutions of the rehabilitation chair, and finally obtain a chair for the rehabilitation of patients with upper and lower limb disorders. Problems such as generalisation of rehabilitation scope and non-durable use of components were solved, and the purpose of active exercise was achieved. This study verifies that the use of multilevel decision evaluation method can effectively improve the efficiency of programme decision-making, and provides theoretical and practical basis for the design of similar products.

Given a fuzzy normed space $ \left( X,N \right) $‎, ‎we will introduce the notion of fuzzy near best approximation within a relative distance $ \rho \geq 0 $‎. ‎Some basic properties are characterized and also many examples for illustration are presented‎.

In this paper, we establish certain Lp bounds for several classes of rough Marcinkiewicz integrals over surfaces of revolution on product spaces. By using these bounds and using an extrapolation argument, we obtain the Lp boundedness of these Marcinkiewicz integrals under very weak conditions on the kernel functions. Several previous results on Marcinkiewicz operators are essentially extended or improved. Our results represent natural extensions and improvements of several known results on Marcinkiewicz integrals over symmetric spaces.

Chronic stress in dairy cattle industry has negative impacts on animal health, productivity, and welfare. It has been confirmed that cortisol transfers to milk and resists the high temperature during milk processing. This study evaluated the relationship between milk cortisol concentration (MCC) in commercial milk products and the temperature-humidity index (THI) at time of milk production. Eleven commercially produced pasteurized and sterilized milk products, purchased in Chuncheon, Korea, with production dates ranging from July to October 2021 were analyzed. The MCC was extracted using diethyl ether and analyzed using enzyme immunoassay. Average THI values based on microclimate data provided by the Korea Meteorological Administration were 77±0.8, 75±1.4, 69±1.4, and 58±1.8, in July, August, September, and October, respectively. The average MCC levels were 211.9±95.1, 173.5±63.8, 109.6±53.2, and 106.7±33.7 pg/mL in July, August, September, and October, respectively. MCC in July was higher than in August, September and October (p<0.05), while it was lower in September and October than in August (p<0.05). Significant variations in MCC were observed in commercial milk products across the four production months (p<0.05), except for two milk products. Overall, monitoring cortisol residue in commercial dairy milk products can be an alternative indicator of stress in dairy cattle of farms.

Extracts of Cordyceps militaris which possess the bioactive capacity such as antimicrobial activity and DPPH-free radical scavenging capacity, are applied to the serum product. This finished serum product has been evaluated the in vitro bioactivity and the stability with expect to find out a good extract with a suitable percentage used for serum product as natural materials on preservatives and antioxidation.

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

A simple undirected graph $\Gamma=(V_\Gamma,E_\Gamma)$ admits an $H$-covering if every edge in $E_\Gamma$ belongs to at least one subgraph of $\Gamma$ that isomorphic to a graph $H$. For any graph $\Gamma$ admitting $H$-covering, a total Labelling $\beta: V_\Gamma \cup E_\Gamma \longrightarrow \{1,2,\dots,p\}$ is called an $H$-irregular total $p$-labelling of $\Gamma$ if every two different subgraphs $H_1$ and $H_2$ of $\Gamma$ isomorphic to $H$ have distinct weights where the weight $w_\beta(K)$ of subgraph $K$ of $\Gamma$ is defined as $w_f(K):=\displaystyle \sum_{v\in V_K} f(v) + \sum_{e\in E_K} f(e)$. The smallest number $p$ for which a graph $\Gamma$ admits an $H$-irregular total $p$-labelling is called the total $H$-irregularity strength of $\Gamma$ and is denoted by $ths(\Gamma)$. In this paper, we determine the total $H$-irregularity strength of edge comb product of two graphs.

This study introduces and demonstrates a comprehensive, accurate, unbiased approach to robust quantitative comparison of Electronic Nicotine Delivery Systems (ENDS) appropriate for establishing substantial equivalence (or lack thereof) between tobacco products. The approach is demonstrated across a family of thirteen pen- and pod-style ENDS products. Methods employed consist of formulating a robust emissions surface regression model, quantifying the empirical accuracy of the model as applied to each product, evaluating relationships between product design characteristics and maximum emissions characteristics, and presenting results in formats useful to researchers, regulators, and consumers. Results provide a response surface to characterize emissions (total particulate matter and constituents thereof) from each ENDS appropriate for use in a computer model and for conducting quantitative exposure comparisons between products. Results demonstrate that emissions vary as a function of puff duration, flow rate, E-Liquid composition, and device operating power. Further, results indicate that regulating design characteristics of ENDS devices and consumables may not achieve desired public health outcomes; it is more effective to regulate maximum permissible emissions directly. Three emissions outcome measures (yield per puff, mass concentration and constituent mass ratio) are recommended for adoption as standard quantities for reporting by manufacturers and research laboratories. The approach provides a means of (a) quantifying and comparing maximal emissions from ENDS products spanning their entire operating envelope, (b) comparative evaluation of ENDS devices and consumable design characteristics, and (c) establishing comparative equivalence of maximal emissions from ENDS. A consumer-oriented product emissions dashboard is proposed for comparative evaluation of ENDS exposure potential. Maximum achievable power dissipated in the coil of ENDS is identified as a potentially effective regulatory parameter.

Factorization reduces computational complexity and is therefore an important tool in statistical machine learning of high dimensional systems. Conventional molecular modeling, including molecular dynamics and Monte Carlo simulations of molecular systems, is a large research field based on approximate factorization of molecular interactions. Recently, the local distribution theory was proposed to factorize global joint distribution of a given molecular system into trainable local distributions. Belief propagation algorithms are a family of exact factorization algorithms for trees and are extended to approximate loopy belief propagation algorithms for graphs with loops. Despite the fact that factorization of probability distribution is their common foundation, computational research in molecular systems and machine learning studies utilizing belief propagation algorithms have been carried out independently with respective track of algorithm development. The connection and differences among these factorization algorithms are briefly presented in this perspective, with the hope to intrigue further development in factorization algorithms for physical modeling of complex molecular systems.

The article is devoted to the new results of the author, which add his previously published ones, of studying hidden rules and symmetries in structures of long single-stranded DNA sequences in eukaryotic and prokaryotic genomes. The author uses the existence of different alphabets of n-plets in DNA: the alphabet of 4 nucleotides, the alphabet of 16 douplets, the alphabet of 64 triplets, etc. Each of such DNA alphabets of n-plets can serve for constructing a text as a chain of these n-plets. Using this possibility, the author represents any long DNA nucleotide sequence as a bunch of many so-called n-texts, each of which is written on the basis of one of these alphabets of n-plets. Each of such n-texts has its individual percents of different n-plets in its genomic DNA. But it turns out that in such multi-alphabetical or multilayer presentation of each of many genomic DNA, analyzed by the author, universal rules of probabilities and symmetry exist in interrelations of its different n-texts regarding their percents of n-plets. In this study, the tensor product of matrices and vectors is used as an effective analytical tool borrowed from the arsenal of quantum mechanics. Some additions to the topic of algebra-holographic principles in genetics are also presented. Taking into account the described genomic rules of probability, the author puts also forward a concept of the important role of stochastic resonances in genetic informatics.

This note addresses a fundamental problem in matrix theory on establishing and characterizing range equalities for matrix expressions that involve generalized inverses. We first establish a group of necessary and sufficient conditions for the matrix range equality ${\rm range}(D_1 - C_1A_1^{\dag}B_1) = {\rm range}(D_2 - C_2A_2^{\dag}B_2)$ to hold, where $(\cdot)^{\dag}$ denotes the Moore--Penrose inverse of matrix. We then give several groups of range equalities with extrusion properties for multiple matrix products associated with two matrices and their conjugate transposes and Moore--Penrose inverses.

The current work aimed to screen the ruminal cyanide-utilizing bacteria and evaluate the influence of fresh cassava root (FCR) and pellets containing high sulfur (PELFUR) on cyanide content, kinetics of gas, in vitro degradability, and ruminal fermentation. The experiment was conducted in a Completely randomized design (CRD) for a screening of cyanide-utilizing bacteria and the dietary treatments were the level of cyanide at 0, 150, 300, and 450 ppm. A 5 × 3 factorial arrangement in a Completely randomized design was used for in vitro study. Factor A was the level of FCR at 0, 260, 350, 440, and 530 g/kg of 0.5 g dry matter (DM) substrate, and factor B was the level of PELFUR at 0, 15, and 30 g/kg DM substrate. Adding different doses of cyanide significantly affected cyanide-utilizing rumen bacterial growth (p < 0.05). Increasing the concentration of cyanide from 0 to 150 and 150 to 300 ppm, resulted in an increase in cyanide-utilizing rumen bacteria of 38.2% and 15.0%, respectively. Increasing the FCR level to more than 260 g/kg of 0.5 g substrate could increase cumulative gas production (p < 0.05), whereas increasing doses of PELFUR from 15 to 30 g/kg increased the cumulative gas production when compared with that of 0 g/kg PELFUR (p < 0.05). Cyanide concentration in rumen fluid decreased with PELFUR (p < 0.05) supplementation. Degradability of in vitro dry matter and organic matter following incubation increased at 12 and 24 h due to PELFUR supplementation with FCR and increased additionally with 15 g/kg PELFUR (p < 0.05) in 440 g/kg FCR. Proportions of the total volatile fatty acids, acetic acid (C2), propionic acid (C3), and butyric acid, as well as the ratio of C2 to C3 among supplementations with FCR (p < 0.05) were significantly different. As the proportion of FCR increased to 530 g/kg of the substrate, the volume of C3 increased by 14.6%. This is the first finding of bacteria in the rumen capable of utilizing cyanide, and cyanide might function as a nitrogen source for bacterial cell synthesis. Inclusion of FCR of 530 g/kg with 30 g/kg PELFUR could increase the cumulative gas production, the bacterial population, the in vitro degradability, the proportion of C3, and the rate of the disappearance of cyanide.

This note shows that the well-known reverse order law $(AB)^{\dag} = B^{\dag}A^{\dag}$ for the Moore--Penrose inverse of matrix product is equivalent to many other equalities for that are composed of multiple products $(AB)^{\dag}$ and $B^{\dag}A^{\dag}$ by means of the definition of the Moore--Penrose inverse and orthogonal projector theory.

This paper investigates and explores the minor crops production in Pakistan and its association with the agricultural gross domestic product. The agriculture sector of Pakistan has a rich contribution to the economic growth and development. Like major crops; minor crops also have a vital role to boost up the agriculture sector. Time span data was used in this study and it was collected from the Economy Survey of Pakistan annual reports. Augmented Dickey-Fuller (ADF) unit root test and Ordinary Least Square (OLS) method was used to analyze the data and results were interpreted by employing the Johansen co-integration test. Study results reveal that bajra, barely and jowar has a significant impact on the agricultural gross domestic product, while the total cropped area has a negative impact on AGDP. On the basis of the study results, we recommend the policy implications.

Product introductions play a pivotal role in the success and competitiveness of manufacturing, particularly in the context of new product development. Low-volume manufacturing companies exhibit distinct characteristics that significantly influence the product introduction process. Notably, the quality of information exchange between product design and production interfaces becomes paramount in this high-mix and low-volume industry. Consequently, there exists a pressing need to explore various methods for adapting and customizing management mechanisms and strategies to align with the unique requirements and characteristics of low-volume manufacturing and its associated product introduction processes. While the need for this knowledge is critical in the context of low-volume manufacturing, a majority of existing studies predominantly focus on the management aspects within high-volume manufacturing. Therefore, the primary aim of this study is to investigate the customization of product introduction management strategies to enhance the quality of information content within the realm of low-volume manufacturing. Drawing upon a longitudinal analysis of new product introductions within a low-volume manufacturing company, this study narratively elucidates how the examined company implemented product introduction management strategies to facilitate the enhancement of information content quality during the product introduction phase. The study presents its findings on management strategies across three key stages: pre-implementation, post-implementation, and subsequent modification and refinement of strategies following the initial round of implementation. By shedding light on these strategies, this study offers a comprehensive understanding of management approaches in the context of low-volume product introduction. As a result, it makes a valuable contribution to the discourse on information management and interface management in the high-mix, low-volume manufacturing literature.

Streptomyces, being one of the most promising genera due to its ability to synthesize a variety of bioactive secondary metabolites of pharmaceutical interest, here studied in relation to its genomic and metabolomic potential. Coinciding with the increase in sequenced data, mining of bacterial genomes for biosynthetic gene clusters (BGCs) has become a routine component of natural product discovery. Herein, we describe the isolation and characterization of a Streptomyces tendae VITAKN with quorum sensing inhibitory activity (QSI) that was isolated from southern coastal parts of India. The nearly complete genome consists of 8,621,231bp with a GC content of 72.2%. Utilizing the BiG-SCAPE-CORASON platform, a sequence similarity network predicted from this strain was evaluated through sequence similarity analysis with the MIBiG database and existing 3,365 BGCs predicted by antiSMASH analysis of publicly available complete Streptomyces genomes. Crude extract analyzed on LC-HRMS/MS and Global Natural Product Social Molecular Networking (GNPS) online workflow using dereplication resulted in the identification of cyclic dipeptides (2,5-diketopiperazines, DKPs) in the extract, which are known to possess QSI activity. Our results highlight the potential use of genomic mining coupled with LC-HRMS/MS and bionformatic tools (GNPS) as a potent approach for metabolome studies in discovering novel QSI lead compounds. This study also provides the biosynthetic diversity of these BGCs and an assessment of the predicted chemical space yet to be discovered.

Advanced chronic lymphocytic leukemia (CLL) is accompanied by increased circulating regula-tory T cells (Tregs) and increased susceptibility to severe infections, which were also shown to en-tail a striking induction of FOXP3 expression in Tregs. As homeostasis of the most suppressive CD45RA-FOXP3high activated Treg (aTreg) subset differs, it is critical to analyse homeostatic sig-naling in Treg subsets. Therefore, in this study, by using conventional and imaging flow cytome-try, we monitored STAT5 signaling/phosphorylation (pSTAT5) and investigated Treg subsets in relation to the Binet stage, the total tumor mass score (TTM) and disease course during follow-up of 37 patients with CLL. aTreg percentage was significantly increased among CD4+ T cells from patients with advanced disease and significantly correlated with the TTM. A subgroup of patients with higher aTreg percentages among CD4+FOXP3+ T cells at the start of therapy was character-ized by more frequent episodes of severe infections during follow-up, suggesting that aTreg frac-tion could represent a possible marker of severe disease course with infectious complications. Augmented homeostatic STAT5 signaling could support aTreg expansion, as higher pSTAT5 lev-els were significantly corelated with increased aTreg frequency among CD4+FOXP3+ T cells during follow-up of patients on therapy as well as following SARS-CoV-2 antigen-specific stimulation in vitro.

Epidermodysplasia verruciformis (EV) is a rare genodermatosis caused by β-human papillomaviruses (HPV) in immunodeficient patients. EV is characterized by flat warts and pityriasis-like lesions and might be isolated or syndromic, associated with some other infectious manifestations. We report here three patients from 2 independent families with syndromic EV for 2 of them. By whole exome sequencing, we found that patients carry new homozygous variants in STK4, both leading to a premature stop codon. STK4 deficiency causes a combined immunodeficiency characterized by a broad infectious susceptibility to bacteria, viruses and fungi. Auto-immune manifestations were also reported. Deep immunophenotyping revealed multiple cytopenia in the three affected patients, in particular deep CD4+ T cells deficiency. We report here the fourth and the fifth cases of syndromic EV due to STK4 deficiency.

We present a case of adult-onset systemic chronic active EBV disease (CAEBV) in a 40-year-old woman with chronic HBV hepatitis. Initial symptoms resembled a viral illness, progressing to recurrent fever, transaminitis, and anasarca. Investigations revealed high-level EBV viremia and an abnormal T-cell population in liver and bone marrow, indicative of CAEBV. Liver biopsy showed CD3+ T-cells lacking TCRbeta and displaying dim/negative CD5, with elevated EBV-infected T-cells. Next-generation sequencing identified rare variants in CREBBP, SPEN, TP73, and PLCG2, suggesting potential contributions to disease pathogenesis. This case underscores diagnostic challenges and management complexities of adult-onset CAEBV, particularly with underlying chronic HBV infection. Genomic profiling offers crucial insights into the molecular landscape of rare lymphoid malignancies, highlighting the importance of personalized treatment strategies. The distinct immunophenotypic features underscore the heterogeneity in EBV-associated T-cell LPDs, urging further research for optimized clinical management

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

Purpose: Pancreatic cancer (PAAD) is one of the most lethal malignancies. Immunotherapy is largely ineffective in PAAD. T-cell exhaustion contributes to the resistance for immunotherapies. We investigated the prognostic potential of T cell exhaustion-related genes (TEXGs). Methods: Single-cell RNA (scRNA) sequencing dataset from TISCH, and bulk sequencing datasets from TCGA and GTEx were applied to screen differently expressed TEXGs. Kaplan-Meier survival, LASSO regression, and Univariate/Multivariate Cox regression analysis were performed to construct TEXGs risk model. This model was used to predict the prognosis, tumor immune microenvironment, and immunotherapy response. PAAD cohorts from ICGC and GSE71729 datasets were used to validate this risk model. Pan-cancer expression of SPOCK2 was performed in TISCH database. Results: A six-gene (SPOCK2, MT1X, LIPH, RARRES3, EMP1, and MEG3) risk model was constructed. Low-risk PAAD patients had longer survival time in both training dataset (TCGA-PAAD, n=178) and validation datasets (ICGC-PACA-CA, ICGC-PAAD-US, and GSE71729, n=412). Multivariate Cox regression analysis demonstrated that the risk score was an independent prognostic variable for PAAD. High-risk patients correlated with cancer-related KEGG pathway enrichment, higher mutation frequency of KRAS and TP53 genes, and immunosuppressive status. Immunohistochemistry staining confirmed the changes of TEXGs in clinical samples. Moreover, pan-cancer scRNA sequencing datasets from TISCH analysis indicated that SPOCK2 might be a novel marker of exhausted CD8+ T cells. Conclusion: In conclusion, we established and validated a T cell exhaustion-related prognostic signature for PAAD patients. Moreover, our study suggests that SPOCK2 may be a novel marker of exhausted CD8+ T cells.

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

Co-inhibitory receptors (Co-IRs) are essential in controlling the progression of immunopathology in rheumatoid arthritis (RA) by limiting T cell activation. The objective of this investigation was to determine the phenotypic expression of Co-IRs T cells and to assess the levels of serum soluble PD-1, PDL-2, and Tim3 in Taiwanese RA patients. Co-IRs T cells were immunophenotyped employing multicolor flow cytometry, and ELISA was utilized for measuring soluble PD-1, PDL-2, and Tim3. Correlations have been detected across the percentage of T cells expressing Co-IRs (MFI) and different indicators in the blood, including ESR, high sensitivity CRP (hsCRP), 28 joint disease activity scores (DAS28), and soluble PD-1/PDL-2/Tim3. In RA patients, we recognized elevated levels of PD-1 (CD279), CTLA-4, and TIGIT on CD4+ T cells; TIGIT, HLA-DR, TIM3, and LAG3 on CD8+ T cells; and CD8+CD279+TIM3+, CD8+HLA-DR+CD38+ T cells. The following tests proved to be correlated with hsCRP: CD4/CD279 MFI, CD4/CD279%, CD4/TIM3%, CD8/TIM3%, CD8/TIM3 MFI, CD8/LAG3%, and CD8+HLA-DR+CD38+%. CD8/LAG3 and CD8/TIM3 MFIs are linked to ESR. DAS28-ESR and DAS28-CRP exhibited relationships with CD4/CD127 MFI, CD8/CD279%, and CD8/CD127 MFI, respectively. CD4+CD279+TIM3+% was correlated with DAS28-ESR (p=0.0084, N=46), DAS28-CRP (p=0.007, N=47), and hsCRP (p=0.002, N=56), respectively. In the serum of patients with RA, levels of soluble PD-1, PDL-2, and Tim3 were extremely elevated. CD4+ TIM3+% (p=0.0089, N=46) and CD8+ TIM3+% (p=0.0305, N=46) were correlated with sTIM3 levels; sPD1 levels were correlated with CD4+CD279+% (p<0.0001, N=31) and CD3+CD279+% (p=0.0084, N=30). Co-IRs expressions on CD4+ and CD8+ T cells, as well as soluble PD-1, PDL-2, and Tim3 levels, could function as indicators of disease activity and potentially play crucial roles in the pathogenesis of RA, in accordance to our findings.