Background: Diabetic patients are more likely to experience morbidity and mortality as a result of microvascular complications such as retinopathy, neuropathy, nephropathy, and stroke. There are many synthetic anti-diabetic agents available which are expensive and have undesirable pathological effects. Thus, it is essential to look for cost-effective, natural, and safe antidiabetic agents. The aim of this study was to screen phytoconstituent and evaluate the in-vitro and in-silico α-amylase inhibitory activity of ethanolic extract of Adhatoda vasica leaves. Method: The extraction of Adhatoda vasica leaves was performed with ethanol through Soxhlet extraction process. Different concentrations (0.1 mg/ml to 1 mg/ml) of ethanolic extract, Acarbose, and Sitagliptin, were prepared and all concentrations were evaluated for α-amylase inhibitory activity through the spectrophotometric method. Molecular docking (AutodockVina 1.2.0) and toxicity profiling (SToPToX web server) studies were performed. Results: The plant extract showed highest inhibition of α-amylase (56.763±0.0035) at a concentration of 1 mg/ml. This inhibitory activity was supported by the in-silico study. Vasicoline (C5) and quercetin (C9), active constitute of plant Adhatoda vasica, showed the best binding energy of 8.3 and 8.0 Kcal/mol respectively with α-amylase enzyme (PDBID: 4W93). Toxicity study revealed the safety profile of plant extract. Conclusion: It was concluded that Adhatoda vasica leaves possess some bioactive compounds which are responsible for controlling blood glucose levels and its identification, purification, and isolation may lead to the development of newer therapeutic agent with lesser side effects.

With reference to our 4G model of final unification, strong coupling constant and strong interaction charge of magnitude $e_s\cong 2.95e$, it is possible to understand the nuclear stability range with a simple power law of the form, $A_s\cong \left(Z+2.95\right)^{1.2\pm0.015}$

With the aim to develop novel scaffolds for sustained release of drugs, we initially developed an easy approach for the synthesis of α,ω-homobifunctional mercaptoacyl poly(alkyl oxide)s. This was based on the esterification of the terminal hydroxyl groups of poly(alkyl oxide)s with suitably S-4-methoxytrityl (Mmt) protected mercapto acids, followed by removal of the acid labile S-Mmt group. This method allowed the efficient synthesis of the title compounds in high yield and purity, which were further used in the development a thioether cross-linked liposome scaffold, by thia-Michael reaction of the terminal thiol groups with preformed nano-sized liposomes bearing maleimide groups on their surface. The reaction process was followed by 1H-NMR, using a Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion NMR experiment (1H-NMR CPMG), which allowed real-time monitoring and optimization of the reaction process. The thioether cross-linked liposomal scaffold that was synthesized was proven to preserve the nanosized characteristics of the initial liposomes and allowed sustained release of calcein (which was used as a chromophore), providing evidence for the efficient synthesis of a novel drug release scaffold consisted of nanoliposome building blocks.

As a result of scientific technological advancements in medical diagnostics, treatment modalities of non-communicable and communicable diseases, and palliative care approaches, the life expectancy of women is soaring than men across the globe, due to the longer telomere length and other protective factors. The main symptoms of menopause broadly be divided into psychological somatovegetative and urogenital. Neglected menopausal symptoms can lead to debilitating comorbidities which may end up in mortalities. Fortunately, modern treatment and therapeutic formalities based on pharmaceutical preparations, as well as lifestyle- modifications have provided long-lasting relief for the pre-menopausal woman. This can be done as per her preference if she is knowledgeable, resourceful, and cheerful. Menarchae is the “ alpha” and menopause is the “omega” phase in the reproductive lifecycle of any woman. Reproductive health is essentially an integral part of women’s health. In this 4^th industial revolution era information technology and digital science go hand in hand to improve the quality of life of populations across the globe irrespective of their educational and professional status. Health literacy among disadvantageous sub populations increased. Positive attitudes, perception and evidence-informed knowledge on adolesecent girls about not only ‘period pains’ but menopausal symptoms as an inevitable phase in a woman’s reproductive health may make a better sense at the dawn of evidence based medicine even in a low middle income country like Sri Lanka. Hence, this timely communication strengthens by, Do not fear when menopause is near: The Importance of a Preparatory Time and Space to face the consequences of Menopaus. How to forget the fact that alpha and the omega are inevitable phases in woman’s reproductive health trajectory. Moreover, the importance of a preparatory time and space well in advance preferably in peri-menopausal time to prevent and control the inevitable health consequences. Moreover, to invest in menopause for a brighter future in the modern personalized medicine era based on global scientific evidence.

Air pollution has been a major environmental issue worldwide from the last few decades. It is a man-made issue that has a serious harmful impact on the environment and the health of humans. There are different sources of emission, but industrial processes and motor vehicles contribute to a chief part of air pollution. It has acute as well as chronic effects on the health of humans and affects different organs. It is thought the main environmental risk factor in the incidence and progression of several diseases such as lung cancer, asthma, Alzheimer's and Parkinson's diseases. Long-term exposure to air pollution has different toxicological impacts on humans such as respiratory and cardiovascular diseases, neuropsychiatric complications, eye irritation and skin diseases. As per the study by the World Health Organization (WHO), nitrogen oxides (NOx), carbon monoxide (CO), ozone (O₃), sulfur dioxide (SO₂), volatile organic compounds (VOCs) and heavy metals are the major air contaminants. These pollutants are different in their properties, composition and time of disintegration. The aim of this study is to review the different sources, types, impacts, challenges and mitigation of air pollution in detail.

Parkinson’s disease and Alzheimer’s disease are the most commonly diagnosed neurodegenerative disorders. Though these disorders differ in terms of their underlying pathophysiology as well as in their clinical features and course, there is a certain degree of overlap between them. This overlap may be partly related to α-synuclein-mediated neuropathological changes. Recent evidence has found that depression is associated with an increased subsequent risk of both these neurological disorders, and that α-synuclein may also play a pathogenic role in depression. The current study examines epidemiological, population genetic and environmental exposure data in relation to the estimated prevalence of depressive disorders, Parkinson’s disease and Alzheimer’s disease using a cross-sectional, country-level analysis. The results of this study are consistent with a significant relationship between depressive disorders and neurodegenerative disorders, a possible shared genetic vulnerability related to functional polymorphisms of the α-synuclein gene SNCA, and potential gene-environment interactions involving fine particulate matter pollution. The significance of these results is discussed in the light of existing translational, clinical and epidemiological research on the links between these disorders.

We previously showed that mice with knockout in the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) gene encoding the PGC-1a protein and nuclear factor erythroid 2 like 2 (NFE2L2) gene, showed some features of the age-related macular degeneration (AMD) phenotype. To further explore the mechanism behind the involvement of PGC-1a in AMD pathogenesis we used young (3-month) and old (12-month) mice with knockout in the PPARGC1A gene and age-matched wild-type (WT) animals. An immunohistochemical analysis showed age-dependent different expression of markers of oxidative stress defense, senescence and autophagy in the retinal pigment epithelium of KO animals as compared with their WT counterparts. Multivariate inference testing showed that senescence and autophagy proteins had the greatest impact on the discrimination between KO and WT 3-month animals, but proteins of antioxidant defense also contributed to that discrimination. A bioinformatic analysis showed that PGC-1a might coordinate the interplay between genes encoding proteins involved in antioxidant defense, senescence and autophagy in the aging retina. These data support importance of PGC-1a in AMD pathogenesis and confirm the utility of mice with PGC-1a knockout as an animal model to study AMD pathogenesis.

Antimicrobial application of carbon nanomaterials such as carbon nanotubes (CNTs), capped CNT, C60 fullerene, and C70 fullerene are increasing owing to their low cytotoxicity properties compared to other nanomaterials such as metallic nanoparticles. Enhanced mechanical property and antibacterial activity can be caused by incorporation of CNTs in 3-dimentional (3D) printed nanocomposites (NCs). Interruption of bacterial membrane resulting from cylindrical shape and high aspect ratio properties has been found as the prominent antibacterial mechanism of CNTs. However, unraveling interaction of CNT, capped CNT, C60 fullerene, and C70 fullerene with virulence factors of the main bacterial pathogenesis has not yet been known. Therefore, in the present study, interactions of CNT, capped CNT, C60, and C70 with the eight virulence factors including protein kinase A and ESX-secreted protein B of Mycobacterium tuberculosis, pseudomonas elastase and exotoxin A of Pseudomonas aeruginosa, alpha-hemolysin and penicillin binding protein 2a of Staphylococcus aureus and shiga toxin 2a and heat-labile enterotoxin of Escherichia coli have been evaluated by molecular docking method of AutoDock Vina. This study disclosed the binding strength followed the sequence CNT > capped CNT > C70 > C60 towards alpha-hemolysin of S. aureus compared to other virulence factors with values of -19.6, -18.8, -13.6, and -12.8 kcal/mol, respectively. The lowest and highest binding affinity were found for CNT against 1TII and 1MWT by binding energy values of 97.4 and -20.1 kcal/mol. The stability of CNT-1MWT complex at the different times has resulted according to the normal mode analysis of elNémo and iMOD servers. Future studies should be focused on improving cellular uptake of CNTs, capped CNTs, C70, and C60 by surface functionalization for active targeting of bacteria.

Research for novel vaccine adjuvants remains a critical need to improve the immune responses to a recombinant vaccine antigen. Emulsion adjuvants such as AS03 and MF59, particularly in the area of Influenza vaccines, have shown antigen dose sparing and allowed reduced immunizations. It was previously demonstrated that these emulsion adjuvants can be formulated using a simpler, low shear process of self-emulsification. The role of alpha tocopherol as an immunomodulator in emulsion adjuvants is evident from the success of AS03 in the on-going covid-19 pandemic. Although, it was a challenge to formulate alpha tocopherol with a low shear process to get closer to the AS03 composition, the self-emulsified version referred as self-emulsifying adjuvant systems (SE-AS) showed comparable immune responses to AS03 when co-administered with a Quadrivalent influenza virus (QIV) vaccine. In this paper, we first optimized the SE-AS with alpha tocopherol referred to as SE-AS44 to allow sterile filtration. We compared the in vitro cytokine profile with self-emulsifying adjuvant 160 (SEA160), a squalene-only self-emulsified adjuvant with composition similar to MF59. We compared SE-AS44 and SEA160 co-administered with a recombinant cytomegalovirus (CMV) pentamer antigen, which is a less immunogenic antigen, in vivo to compare the antibody and T-cell responses, in different adjuvanted groups, in C57BL/6 mice.

Excessive neutrophil influx and activation in lungs during infections, such as manifest during the ongoing SARS CoV-2 pandemic, have brought neutrophil extracellular traps (NETs) and the con-comitant release of granule contents that damage surrounding tissues into sharp focus. Neutro-phil proteases, which are known to participate in NET release, also enable the binding of the viral spike protein to cellular receptors and assist in the spread of infection. Blood and tissue fluids normally also contain liver-derived protease inhibitors that balance the activity of proteases. In-terestingly, neutrophils themselves also express the protease inhibitor alpha-1-antitrypsin (AAT), the product of the SERPINA-1 gene, and store it in neutrophil cytoplasmic granules. The absence of AAT or mutations in the SERPINA-1 gene promote lung remodeling and fibrosis in diseases such as chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS) and increase the risk of allergic responses. Recent observations point to the fact that re-duced activity of AAT presents a major susceptibility factor for severe COVID-19. Here, we focus attention on the mechanism of neutrophil elastase (NE) in NET release and its inhibition by AAT as an additional factor that may determine the severity of COVID-19

Glutamate dehydrogenase (GDH) interconverts glutamate to a-ketoglutarate and ammonia, interconnecting amino acid and carbohydrate metabolism. In humans, two functional GDH genes, GLUD1 and GLUD2, encode for hGDH1 and hGDH2, respectively. GLUD2 evolved from retro-transponsition of the GLUD1 gene in the common ancestor of modern apes. These two isoenzymes are involved in the pathophysiology of neoplastic, neurodegenerative, and metabolic disorders. The 3D structures of hGDH1 and hGDH2 have been experimentally determined; however, no information is available about the path of GDH2 structure changes during primate evolution. Here, we compare the structures predicted by the AlphaFold Colab method for the GDH2 enzyme of modern apes and their extinct primate ancestors. Also, we analyze the individual effect of amino acid substitutions emerging during primate evolution. Our most important finding is that the predicted structure of GDH2 in the common ancestor of apes was the steppingstone for the structural evolution of primate GDH2s. Two changes with a strong functional impact occurring at the first evolutionary step, Arg443Ser and Gly456Ala, had a destabilizing and stabilizing effect, respectively, making this step the most important one. Subsequently, GDH2 underwent additional modifications that fine-tuned its enzymatic properties to adapt to the functional needs of modern-day primate tissues.

The 2022-2023 Mpox multi-country outbreak, identified in over 110 WHO Member States, revealed a predominant impact on cisgender men, particularly those engaging in sex with men, while less frequently affecting women. This disparity prompted a focused investigation into the gender-specific characteristics of Mpox infections, particularly among women, to address a notable knowledge gap. This review systematically gathers and analyzes scientific literature and case reports concerning Mpox infections in women, covering a broad geographical spectrum including regions such as Buenos Aires, Brazil, Northern California, Colombia, Nigeria, Europe, Vietnam, Spain, Switzerland, and the United States. The analysis delves into various aspects of Mpox in women, including clinical features, epidemiology, psychological impacts, preparedness strategies, and case studies, with particular attention to pregnant women and those with underlying health conditions. Empirical data from multiple studies underscore the unique epidemiological and clinical patterns of Mpox in women. In the United States, a small percentage of Mpox cases were reported among cisgender women, with a notable portion involving non-Hispanic Black or African American, non-Hispanic White, and Hispanic or Latino ethnicities. The primary transmission route was identified as sexual or close intimate contact, with the virus predominantly manifesting on the legs, arms, and genital areas. Further, a study in Spain highlighted significant disparities in diagnosis delays, transmission modes, and clinical manifestations between genders, indicating a different risk profile and disease progression in women. Additionally, a case from Vietnam linked to a new Mpox sublineage in women emphasizes the role of women in the transmission dynamics and the importance of genomic monitoring. This review emphasizes the necessity for inclusive surveillance and research to fully understand Mpox dynamics across diverse population groups, including women. Highlighting gender and sexual orientation in public health responses is crucial for an effective approach to managing the spread and impact of the disease. The findings advocate for a gender-diverse assessment in health services and further research to explore the nuances of Mpox transmission, behavior, and progression among different groups, thereby enhancing the global response to Mpox and similar public health challenges.

In an historic perspective on the development of the Standard Model of particle physics it is shown how mathematically driven axioms have masked the merits of a physically comprehensible structural view. It is concluded that the difference between the two approaches can be traced back to two major issues. Whereas in the Standard Model the quark is a Dirac particle with a single real dipole moment, the quark in the structural model, in confinement with other quarks, is a Dirac particle with two real dipole moments. The second issue is the view that empty space does not exist, but that space is filled with a polarisable energetic fluid. It is shown how recognition of these two issues pave a road to reconcile particle physics with gravity, in which the quark can be seen as a magnetic electron and in which the gluon, as the strong force carrier, can be seen as a massive photon.

Our knowledge of biology and mast cell (MC) function, as well as disorders associated with the pathologic activation of MCs has been evolving over the last few decades. Anaphylaxis, mast cell activation syndrome (MCAS) and mastocytosis are interrelated yet distinct conditions within the spectrum of mast cell activation disorders. Nevertheless, all three conditions can co-exist in one and same patient, as pathologic MC activation is the key finding in all three. When mediator release is excessive and involves multiple systems, anaphylaxis and MCAS may occur. Furthermore, mastocytosis is a clonal disorder of MCs and often presents with anaphylaxis and MCAS. Nevertheless, in some cases even proliferative and accumulative features of MCs in mastocytosis can account for symptoms and disease progression. In each case, diagnosis can be only made when diagnostic consensus criteria are fulfilled. The current article aims to provide a concise clinical update and pinpoint main difficulties in diagnosing these puzzling disorders of MCs in medical practice.

Coronavirus Disease-19 (COVID-19) is caused by the infection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The virus enters host cells through receptor-mediated endocytosis of angiotensin-converting enzyme-2 (ACE2), leading to systemic inflammation, also known as a “cytokine storm,” and neuroinflammation. COVID-19’s upstream regulator, interferon-gamma (IFNG), is downregulated upon the infection of SARS-CoV-2, which leads to the downregulation of ACE2. The neuroinflammation signaling pathway (NISP) can lead to neurodegenerative diseases, such as Parkinson's disease (PD), which is characterized by the formation of Lewy Bodies made of α-Synuclein protein encoded by synuclein alpha (SNCA). This study presents the pathways involved in the downregulation of ACE2 following SARS-CoV-2 infection and its effect on PD progression. Through QIAGEN’s Ingenuity Pathway Analysis, the study identifies the NISP as a top-five canonical pathway/signaling pathway and SNCA as a top-five upstream regulator. Core Analysis was also conducted on the associated molecules between COVID-19 and SNCA to construct a network connectivity map. The Molecule Activity Predictor tool was used to simulate the infection of SARS-CoV-2 by downregulating IFNG, which leads to the predicted activation of SNCA, and subsequently PD, through a dataset of intermediary molecules. Downstream Effect analysis was further used to quantify the downregulation of ACE2 on SNCA activation.

Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by resting tremor, bradykinesia, rigidity, postural instability, that also includes non-motor symptoms such as mood dysregulation. Dopamine (DA) is the primary neurotransmitter involved in this disease, but cholinergic imbalance has also been implicated. Current intervention in PD is focused on replenishing central DA, which provides remarkable temporary symptomatic relief but does not address the neuronal loss and the progression of the disease. It has been well established that neuronal nicotinic cholinergic receptors (nAChRs) can regulate DA release and that nicotine itself may have neuroprotective effects. Recent studies have identified nAChRs in nonneuronal cell types including glial cells, where they may regulate inflammatory responses. Given the crucial role of neuroinflammation in dopaminergic degeneration, and the involvement of microglia and astrocytes in this response, glial nAChRs may provide a novel therapeutic target in prevention and/or treatment of PD. In this review, following a brief discussion of PD, we focus on the role of glial cells and specifically their nAChRs in PD pathology and/or treatment.

Differential RNA editing by adenosine deaminases that act on RNA (ADARs) has been implicat-ed in several neurological disorders, including Parkinson’s disease (PD). Here, we report results of an RNAi screen of genes differentially regulated in adr-2 mutants, normally encoding the only catalytically active ADAR in Caenorhabditis elegans, ADR-2. Subsequent analysis of candidate genes that alter the misfolding of human α-synuclein (α-syn) and dopaminergic neurodegenera-tion, two PD pathologies, reveal that reduced expression of xdh-1, the ortholog of human xanthine dehydrogenase (XDH), is protective against α-synuclein-induced dopaminergic neurodegenera-tion. Further RNAi experiments show that WHT-2, the worm ortholog of the human ABCG2 transporter and a predicted interactor of XDH-1, is the rate-limiting factor in the ADR-2, XDH-1, WHT-2 system for dopaminergic neuroprotection. Proteomic analysis indicates that the editing of one nucleotide in wht-2 RNA leads to the substitution of threonine with alanine at residue 124 in the WHT-2 protein, changing its structure. Thus, we propose a model where wht-2, is edited by ADR-2 which promotes optimal export of uric acid, a known substrate of WHT-2 and a product of XDH-1 activity. In the absence of editing, uric acid export is limited provoking a reduction in xdh-1 transcription to limit uric acid production and maintain cellular homeostasis. In turn, ele-vation of uric acid is protective against dopaminergic neuronal cell death. These data indicate that modifying specific targets of RNA editing may represent a promising therapeutic strategy for PD.

We delve into the axion-dilaton model within the supergravity framework, with a specific focus on the intricacies of domain wall construction and stability. Employing holographic vitrification, we unravel the dynamics of domain wall formation in gauge theories featuring periodic vacuum structures. Our model, incorporating a QCD-like axion term and a stabilizing dilaton, undergoes scrutiny for conductivity variations under weak disorder. The investigation reveals the model's resilience, manifesting near-perfect conductivity under mild disorder conditions. However, the rigorous mathematical motivation for the holographic setup demands further elucidation. The scattered nature of our results prompts the necessity for a more systematic interpretation of QCD phenomena and conductivity transitions. This study contributes to the mathematical understanding of the axion-dilaton model's behavior, highlighting the imperative for a refined holographic framework and a more coherent interpretation of observed phenomena.

In this manuscript, we first introduce some properties of r-fuzzy soft α-open sets in fuzzy soft topological spaces based on the manuscript Aygunoglu et al. (Hacet. J. Math. Stat. 2014, 43, 193-208). In addition, we define the concepts of fuzzy soft α-closure (α-interior) operators, and investigate some properties of them. Furthermore, the concept of r-fuzzy soft α-connected sets is defined and characterized with help of fuzzy soft α-closure operators. Thereafter, we introduce and study the concepts of fuzzy soft almost (weakly) α-continuous mappings, which are weaker forms of fuzzy soft α-continuous mappings, and we discuss some properties of fuzzy soft α-continuity. Moreover, we establish that fuzzy soft α-continuity → fuzzy soft almost α-continuity → fuzzy soft weakly α-continuity, but the converse may not be true. It is also we show that the composition is fuzzy soft almost α-continuous mapping if, is fuzzy soft α-continuous mapping and is fuzzy soft almost continuous mapping. Finally, some new types of compactness via r-fuzzy soft α-open sets are defined, and the relationships between them are examined.

Breast cancer brain metastasis (BCBM) is a challenging condition with limited treatment options and poor prognosis. Understanding the interactions between tumor cells and the blood-brain barrier (BBB) is critical for developing novel therapeutic strategies. One promising target is estrogen receptor β (ERβ), which promotes the expression of key tight junction proteins, sealing the BBB and reducing its permeability. In this study, we investigated the effects of 17β-estradiol (E2) and the selective ERβ agonist diarylpropionitrile (DPN) on endothelial and cancer cells. Western blot analysis revealed the expression patterns of ERs in these cell lines, and estrogen treatment upregulated claudin-5 expression in brain endothelial cells. Using in vitro models of the BBB, we found that DPN treatment significantly increased BBB tightness about suppressed BBB transmigration activity of representative HER2-positive (BT-474) and triple-negative (MDA-MB-231) breast cancer cell lines. However, the efficacy of DPN treatment decreased when cancer cells were pre-differentiated in the presence of E2. Our results support ERβ as a potential target for the prevention and treatment of BCBM and suggest that targeted vector-based approaches may be effective for future preventive and therapeutic implications.

LC-SPIK is a liver cancer-specific isoform of Serine Protease Inhibitor Kazal and has been proposed as a new biomarker for the detection of HCC given its unique 3-D structure which differs from normal pancreatic SPIK. An ELISA technology based on its unique structure was developed to use LC-SPIK as an effective biomarker for the clinical diagnosis of HCC. AFP, the most widely used biomarker for HCC surveillance currently, suffers from poor clinical performance, especially in the detection of early-stage HCC. In one case-control study, which included 164 HCC patients and 324 controls, LC-SPIK had an AUC of 0.87 compared to only 0.70 for AFP in distinguishing HCC from liver disease controls (cirrhosis, HBV/HCV). LC-SPIK also performed significantly better than AFP for the 81 patients with early-stage HCC (BCLC stage 0 and A), with an AUC of 0.85 compared to only 0.61 for AFP. Cirrhosis is the major risk factor for HCC, about 80% of patients with newly diagnosed HCC have preexisting cirrhosis. LC-SPIK’s clinical performance was also studied in HCC patients with viral and non-viral cirrhosis including cirrhosis caused by nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). In a total of 163 viral cirrhosis patients with 93 HCC patients (50 early-stage), LC-SPIK had an AUC of 0.85, while AFP had an AUC of 0.70. For patients with early-stage HCC, LC-SPIK had a similar AUC of 0.83, while AFP had an AUC of only 0.60. For 120 patients with nonviral cirrhosis, including 62 HCC (23 early-stage) patients, LC-SPIK had an AUC of 0.84 while AFP had an AUC of only 0.72. For the 23 patients with early-stage HCC, LC-SPIK had a similar AUC of 0.83, while the AUC for AFP decreased to 0.65. All these results suggest that LC-SPIK has significantly better performance in the detection of HCC than AFP in all etiologies of liver diseases. In addition, LC-SPIK accurately detected the presence of HCC in 71%-91% of HCC patients with false-negative AFP test results in viral associated HCC and non-viral associated HCC.

In order for the body to function properly, it needs not only food, but also nutrients and non-nutritive bioactive compounds that have an immunomodulating effect. This applies not only to healthy people, but especially to people with accompanying chronic diseases, including type 2 diabetes. Unfortunately, the current food industry and the use of highly processed food promote nutritional deficiencies. Many studies confirm their occurrence in patients with type 2 diabetes. The article presents the influence of selected nutrients on the functioning of the immune system, which ensures homeostasis of the body, with particular emphasis on type 2 diabetes. The role of macroelements, microelements, vitamins and selected substances, such as omega-3 acids, coenzyme Q10 and alpha-lipoic acid. The minimum scope of tests that should be performed in patients to directly or indirectly determine the degree of malnutrition in this group of patients is presented.

The protection of first responders from radioactive contamination of alpha emitters that may result from a radiological accident is of great complexity due to the short range of the alpha particle in air of a few cm. To overcome this issue, for the first time a system for near real-time measuring alpha particles remotely mounted on a UAS has been developed, tested and calibrated. The new system, based on an optical system adapted to be installed on the UAS in order to measure the UV-C fluorescent emitting by the alpha particle in air, has been tested and calibrated carried out by laboratory and in field experiments using UV-C leds and ²⁴¹Am sources. In experimental flights, the probability of detecting a point source was determined to be approximately 60%. In case of a surface extended source, a detection efficiency per unit surface activity of ten counts per second per MBq cm^-2 are calculated. A background count rate of UV-C around 26 ± 28 s^-1 for an integration time of 0.1 s was measured during flights, which leads to a decision threshold surface activity of 5 MBq cm^-2.

The overcrowding of high-rise buildings in the city adversely affects the wind environment by changing the air currents in the surrounding areas. In particular, extreme climate phenomena caused by climate change are stronger and more frequent, causing social damages in cities. To comprehensively better understand the wind properties around high-rise buildings, actual filed measurement is necessary to determine the environment assessment of wind effect. We performed the on-site measurement on LCT residential complex regions (411.6m tall) with highly concentrated high-rise buildings in coastal city Busan, South Korea under extreme weather conditions such as typhoon invasions to determine wind fluid characteristics. In the field monitoring, five anemometers were installed to analyze the wind environment around high-rise buildings when typhoon 'Hinnamnor' invaded. Compared to the nearby weather station operated by KMA(Korea Meteorological Administration), the gust was 3.7 times stronger and the max 1 min-mean wind speed was 3.1 times stronger, and the characteristics of the downward wind and the canyon wind were shown depending on the location characteristics of the point. Turbulence intensity decreased as the wind speed increased and converged to a certain value. Likewise, the gust factor also decreased as the wind speed increased and converged to 2.0, which is considered to be the parameter that best represents the intensity of the instantaneous gust caused by the skyscraper wind effect.

Here we analyze three well-known conjectures: (i) the existence of infinitely-many twin primes, (ii) Goldbach’s strong conjecture, and (iii) Polignac’s conjecture. We show that the three conjectures are related to each other. In particular, we see that in analysing the validity of the Goldbach’s strong conjecture, one must consider also the existence of an infinite number of twin primes. As a consequence of how we approach this analysis, we also observe that if this conjecture is true, then so is Polignac’s conjecture. Our first step is an analysis of the existence of infinitely-many twin primes numbers. For this, using the formula 4((n−1)!+1) ≡ −n (mod n(n + 2)) – satisfied if and only if (n, n + 2) are twin primes –, together with Wilson’s theorem, we obtain conditions that must be met for two numbers to be twin primes. Our results, obtained from an analytic and functional study, lead us to conclude that there may exist infinitely-many twin primes. Next, we consider the validity of the Goldbach’s strong conjecture. After showing that the conjecture is true for the first even numbers, we notice a pattern that we analyze for any even number, reducing it to three cases: (i) when the even number 2n is two times a prime number n; (ii) when the even number 2n is such that n = 2m, with 2m − 1 and 2m + 1 twin primes; (iii) all other cases, i.e., for any 2n even number ∀n ∈ N with n > 1, n prime or not, with independence of n = 2m being 2m−1 and 2m+1 twin primes or not. In this last case we show that one can always find a certain r ∈ N such that 1 < r < n satisfying that n−r and n+r are primes, so that their sum is 2n. In this case we use the reduction to absurd method, and our results lead us to conclude that Goldbach’s strong conjecture is true to the best of our calculations, as well as the Polignac’s conjecture.

Cardiovascular diseases (CVDs) represent the leading cause of global mortality with 1,7 million deaths a year. One of the alternative systems to drug therapy to minimize the risk of CVDs is represented by alpha-linolenic acid (ALA), an essential fatty acid of the Omega-3 series, known for its cholesterol-lowering effect. The main purpose of this review is to analyze the effects of ALA and investigate the relevant n-6/n-3 ratio in order to maintain functionally beneficial effects. Concerning the lipid-lowering preventive effects, ALA may favorably affect the values of LDL-C and triglycerides in either adult and pediatric populations and it has a positive and protective effect against hypertension, suggesting that ALA is an useful diet-related antihypertensive compound. According to the 2009 EFSA statement, dietary ALA may contribute to reducing the risk of CVDs, thanks to anti-hypertensive, anti-atherosclerotic and cardio-protective effects.

The global textile sector, pivotal to economic development, significantly contributes to environmental degradation, prompting a shift towards sustainable raw material sources. Embracing circular economy principles, this industry is exploring the valorization of agricultural by-products. This study introduces an innovative approach to repurposing mango waste into valuable textile fibers, a byproduct of the fruit processing industry, predominantly generated during juice and jam production. The focus is on the lignocellulosic constituents of mango waste, specifically the peel, seed, and fibrous material, traditionally considered as refuse. Previous research has predominantly utilized mango peel in pectin extraction for food applications, whereas the potential of seed and fibrous content remains underexplored. This investigation endeavors to transform these fibrous by-products into high-value materials suitable for textile manufacturing. The process involved washing, drying, and comprehensive physicochemical characterization of mango fibers, emphasizing lignin quantification, revealing a composition of 12.2% lignin. An experimental design was employed to elucidate the impact of variables such as liquid-to-solid ratio, reaction duration, and sodium hydroxide concentration on lignin dissolution through alkaline hydrolysis. Optimal conditions—10% NaOH concentration, 30 mL/g liquid-to-solid ratio over six hours—achieved an 83% reduction in lignin content. The resulting fibers exhibited properties akin to conventional natural fibers, including a favorable aspect ratio indicative of their suitability for textile applications. A subsequent softening process using propylene glycol enhanced the fibers' spinability, producing a durable, textured fabric ideal for eco-conscious fashion applications, including bags, footwear, and accessories. This research demonstrates the feasibility of converting mango waste into a textile-worthy material and underscores the importance of waste revalorization in promoting sustainability within the circular economy framework.

Climate change will pose a challenge for the winemaking sector worldwide, bringing progressively drier and warmer conditions and increasing the frequency and intensity of weather extremes. The short-term adaptation strategy of applying biostimulants through foliar application serves as a crucial measure in mitigating the detrimental effects of environmental stresses on grapevine yield and berry quality. The aim of this study was to evaluate the effect of foliar application of a seaweed based biostimulant (A. nodosum – ANE) and glycine betaine (GB) on berry quality, bioactive compounds, antioxidant activity, and elucidated their action on the secondary metabolism. A trial was installed in a commercial vineyard (cv. ‘Touriga Franca’) in the Cima Corgo (Upper Corgo) sub-region of the Douro Demarcated Region. A total of four foliar sprayings were performed during the growing season: at flowering, pea size, bunch closer, and veraison. There was a positive effect of GB in the berry quality traits. Both ANE and GB increased the synthesis of anthocyanins and other phenolics in berries and influenced the expression of genes related to the synthesis and transport of anthocyanins (CHS, F3H, UFGT, MATE1 and GST). So, they have the potential to act as elicitors of secondary metabolism, leading to improved grape quality, but also sets the foundation for sustainable agricultural practices in the long run.

Background: Thyroid nodules are common, affecting nearly 65% of the general population. While they are widespread, it's crucial to recognize that the majority of these nodules are not cancerous and can be effectively managed through careful monitoring. Thyroid ultrasound is commonly used to evaluate thyroid nodules owing to its low cost, wide availability and technical ease of application. In sonography, it's crucial to assess characteristics and vascular flow. Yet, conventional color and power Doppler ultrasound may not always effectively capture small vessels and low velocities due to their limitations. Superior Microvascular Imaging can display the blood flow of small vessels and low-velocity blood flow, which is difficult to visualize with conventional Doppler ultrasound. Meanwhile other thyroid scans, that utilize either [99mTc] pertechnetate or (18)F-fluorodeoxyglucose, can categorize nodules as hyperactive ('hot'), exhibiting normal activity ('warm'), or having reduced/no activity ('cold'). Thus, the main goal of screening and tracking thyroid nodules is to improve the management of potentially worrisome thyroid malignancies. Methodology: The study was conducted within the structural framework of a network meta-analysis, with the index tests being - SMI, Radionuclide Scanning and Color Doppler, and the general link between them being the reference gold standard. The data collection involved searching for all pertinent literature using PubMed, Google Scholar, and the Cochrane Library databases. The essential data was extracted following the application of specific inclusion and exclusion criteria.This meta-analysis included 7 RCTs with 1,152 patients for Radionuclide Scanning, 10 RCTs with 1,847 patients for SMI and 8 RCTs with 4,480 patients for Color Doppler. They were analyzed using the QualSyst tool and the risk of bias was evaluated by using QUADAS-2 analysis.The statistical software packages MetaDiSc 1.4, RevMan (Review Manager, version 5.3), SPSS (Statistical Package for the Social Sciences, version 20) and Excel in Stata 14 were used to perform the statistical analyses. Result: According to the findings, the sensitivity for Radionuclide Scanning is calculated as 0.79 (range: 0.76 to 0.81) and specificity as 0.55 (range: 0.50 to 0.60) with a 95% confidence interval. The overall diagnostic odds ratio (DOR) for Radionuclide Scanning Is 10.54.Additionally, with a 95% confidence interval, SMI exhibits a sensitivity of 0.82 (with a range of 0.79 to 0.84) and a specificity of 0.86 (with a range of 0.84 to 0.88), while the overall DOR is approximately 25.73. Color Doppler demonstrates a calculated sensitivity of 0.71 (ranging from 0.69 to 0.74) and specificity of 0.81 (ranging from 0.79 to 0.83) with a 95% confidence interval, while its DOR is 13.48.Conclusion: As evidenced by this meta-analysis, blood flow dependent imaging techniques are superior in their abilities to be used as diagnostic tests, especially in conjunction with their use in detecting thyroid nodules. This study offers a starting point for delving deeper into the utilization of Radionuclide Imaging, Superior Microvascular Imaging and Color Doppler in diagnosing thyroid nodules in a clinical setting. Key Words: - Thyroid Nodule, Radionuclide Scanning, Superior Microvascular Imaging, Color Doppler Diagnosis, Sensitivity, Specificity, Diagnostic imaging

The inherited ‘EIA’ process at Brexit is based on a ‘Project’ period from Inception tothe start of construction works. The ‘Incompleteness’ of the process covers andidentifies stages that will impact on the environmental cycle: construction period,operational life, de-commissioning and a return to acceptable environmental footprint.A master environment structure-plan framework is required to commence with theupgrading of the complete ‘EIA’ process, embracing separate limbs for the UK’spriority environmental targets for climate change, and other major adverse effectswhich result in serious ‘harm’ to the UK environment. The identification of the processfor ‘incompleteness’ requires effective sustainability, and inclusion of effectivemanagement tools, for the essential ‘monitoring/control/recording’ proceduresthroughout the project life and the natural environmental cycle. This will allow theopportunity for a new approach to a structured ‘Suite of EIAR Directives’, to enable a‘EIAR’ regime that ‘will remain fit and proper for UK purpose’.

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

Parkinson’s Disease (PD) is a debilitating neurodegenerative disease, causing loss of motor function, and in some instances, cognitive decline and dementia, in those affected. The quality of life can be improved, and disease progression delayed through early interventions, however, current methods of confirming a PD diagnosis are extremely invasive. This prevents their use as a screening tool for the early onset stages of PD. We propose a surface imprinted polymer (SIP) electroimpedance spectroscopy (EIS) biosensor for detecting α-Synuclein (αSyn) and its aggregates, a biomarker that appears in saliva and blood during the early stages of PD as the blood brain barrier degrades. The surface imprinted polymer stamp is fabricated by low temperature melt stamping polycaprolactone (PCL) on interdigitated EIS electrodes. The result is a low-cost, small footprint biosensor that is highly suitable for non-invasive monitoring of the disease biomarker. The sensors were tested with αSyn dilutions in deionized water, and in constant ionic concentration matrix solutions with decreasing concentrations of αSyn to remove the background effects of concentration. The device response confirmed the specificity of these devices to the target protein of monomeric αSyn. The sensor limit of detection was measured to be 5 pg/L and its linear detection range was 5 pg/L – 5 µg/L. This covers the physiological range of αSyn in saliva and makes this a highly promising method of quantifying αSyn monomers for PD patients in the future. The SIP surface was regenerated, and the sensor reused to demonstrate its capability for repeat sensing as a potential continuous monitoring tool for the disease biomarker.

The aim of our study was to assess the relationship between the concentration/activity of salivary stress biomarkers (cortisol, α-amylase) and the psychological profile of patients with oral lichen planus (OLP) and primary burning mouth syndrome (BMS). A total of 160 subjects participated in this cross-sectional study: 60 patients with OLP; 60 patients with primary BMS; 40 control subjects. Unstimulated whole saliva (UWS) was collected between 9 and 10 am. Salivary biomarkers were analyzed by enzyme-linked immunosorbent assay (ELISA). Psychological assessment was evaluated with the Depression, Anxiety, and Stress Scale (DASS-21). Patients with primary BMS had higher salivary cortisol concentrations and α-amylase activity (0.52 vs. 0.44 µg/dl; 160531 vs. 145804 U/L) compared with patients with OLP. Patients with primary BMS had statistically significantly higher scores for depression, anxiety, and stress compared with patients with OLP and control subjects (p <0.001, Kruskal-Wallis test). There was a strong positive correlation between anxiety and depression, stress and depression, stress and anxiety in patients with OLP and BMS (p <0.001 and p <0.001, respectively). There was a good positive correlation between symptom intensity (pain/burning) and psychological profile (depression, anxiety, stress) in patients with primary BMS (r=0.373, p=0.003; r=0.515, p <0.001; r=0.365, p= 0.004, respectively). Patients with BMS show a stronger association with mental disorders compared to patients with OLP. However, an interdisciplinary psychoneuroimmunological approach is equally important in both patient groups (OLP and BMS), regardless of whether mental disorders are the cause or the consequence.

Microplastics and nanoplastics (MP/NPs) have been found everywhere they have been searched. On the top of Everest, in the Mariana Trench, on the clouds e recently, microplastics have been discovered in the human placenta, meconium and babies’ feces. In this review we explain what the consequences of the presence of these pollutants in fetuses and newborns are, with particular attention to human breastfeeding. Finally, we outline the possible political and social solutions to the problem of plastic overproduction that characterizes the modern world.

The mutton quality of Chinese Tan lambs (Ovis aries) has declined as feeding patterns have shifted from pasturing to pen rationing. Mutton quality is affected by fatty acids, and rumen microorganisms play a role in the synthesis of short-chain fatty acids, long-chain fatty acids, and conjugated linoleic acids. We used 16S rDNA sequencing to analyze the effects of two feeding patterns on the rumen bacteria of Tan lambs. In a randomized block design with 24 newborn Tan lambs, 12 lambs were fed by ewes in pasture and 12 were fed by pen-fed ewes. At 2 months, the biceps femoris and the longissimus dorsi were analyzed by gas chromatography for intramuscular fat content and fatty acid composition, and DNA in the rumen contents was extracted and used to analyze the structure of the bacterial community. Different feeding patterns had no significant effect on the intramuscular fat content of the biceps femoris and longissimus dorsi of the lambs, but there was a significant effect on fatty acid composition. Rumen bacteria were significantly more diverse in the pasture group than in the pen-ration group (P < 0.01). Twenty-one phyla were identified in the pasture group, and 14 phyla were identified in the pen-ration group. The dominant phyla in the pasture group were Bacteroidetes and Fibrobacteres; the dominant phyla in the pen-ration group were Proteobacteria and Bacteroidetes. The relative abundance of Proteobacteria was significantly higher in the pen-ration group than in the pasture group (P < 0.01). Diversity at the genus level was also higher in the pasture group, with 176 genera in the pasture group and 113 genera in the pen-ration group. The dominant genera in the pasture group were Prevotella_1, Rikenellaceae_RC9_gut_group, and Bacteroidales_BS11_gut_group_Na; the dominant genera in the pen-ration group were Prevotella_1, Prevotella_7, Succinivibrionaceae_UCG-001, and Succinivibrionaceae_NA.

The bioindicator potential of seagrass ecosystems in coastal trace metal monitoring is low for tropical island ecosystems. This study evaluated the bioindicator potential of six seagrass species exposed to anthropogenic trace metal pollution in the Andaman and Nicobar Islands (ANI) of India. Sediment and seagrass biomass, samples were analyzed for trace metals (Co, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Zn) from four locations of ANI exposed to anthropogenic contamination. Geo accumulation Index values indicated moderate trace metal contamination in seagrass sediment. Seagrass trace metal accumulation from sediment was both species-specific and location- specific for ANI. Small seagrass species such as H. ovalis, H. beccarii and H. uninervis accumulated the maximum concentration of six trace metals (Cr, Cu, Fe, Ni, Pb, Zn) in their tissues compared to big seagrass species like T. hemprichii and E. acoroides of ANI. This study indicates leaves of small seagrass and roots of big seagrass species can serve as short- and long-term bioindicators respectively, of coastal trace metal contamination in tropical islands of ANI.

A unique two-column ²³⁰U/²²⁶Th generator has been developed. The focus was hold on obtaining ²²⁶Th of high purity in a solution amenable to further labeling. The first column of the proposed generator filled with TEVA Resin held ²³⁰U, from which ²²⁶Th was eluted with 7 M HCl solution. UTEVA Resin pretreated with nitric acid solution was used as a sorbent for the second column for thorium retention. ²²⁶Th was extracted with 0.01-0.05 M citric buffer solution. One cycle of generator milking took 5-7 minutes and produced > 90% of ²²⁶Th in 1.5 ml of eluate, pH 4.5-5.0. The proposed two-column ²³⁰U/²²⁶Th generator was tested over two months including a second loading of ²³⁰U additionally accumulated from ²³⁰Pa. The ²³⁰U impurity in ²²⁶Th eluate was less than 0.01% allowing to use it directly in synthesis of radiopharmaceutical compounds.

Introduction: Despite great advances in the treatment of oncological diseases, the development of medical technologies to prevent or reduce complications of therapy, in particular, those associated with surgery and the introduction of antibiotics remains relevant. The aim of the study: to evaluate the effectiveness of the use of autoprobiotics based on indigenous non-pathogenic strains of Enterococcus faecium and Enterococcus hirae in the complex therapy of colorectal cancer (CRC) in the early postoperative period. Materials and methods: A total of 36 patients diagnosed with CRC were enrolled in the study. The study group (Group A) comprised 24 CRC patients who received autoprobiotic therapy in the early postoperative period, while the control group (Group C) included 12 CRC patients without autoprobiotic therapy.Prior to surgery and between days 14-16 post-surgery, comprehensive evaluations were conducted on all patients, encompassing the following: stool and gastroenterological complains analysis. examination of the gut microbiota (bacteriological study, quantitative polymerase chain reaction, metagenome analysis), analysis of interleukins in serum. Results: The use of autoprobiotics led to decrease dyspeptic complaints after surgery, was associated with absence of postoperative complications, did not cause side effects, led to a decrease in the level of pro-inflammatory cytokines (IL-6 and IL-18) in the blood serum. The use of autoprobiotics led to positive changes in the structure of escherichia and enterococci populations, the elimination of Parvomonas micra, Fusobacterium nucleatum, decrease in the quantitative content of Clostridium perfringens, Akkermansia muciniphila. Metagenomic analysis (16S rRNA) revealed an increase in alpha diversity. Conclusion: The administration of autoprobiotics in the postoperative period is highly effective and safe in the comprehensive treatment of colorectal cancer patients. Future studies will allow the discovery of additional fine mechanisms of autoprobiotic therapy and its impact on the digestive, immune, endocrine and neural systems.

Introduction: Flow-cytometry (FC) is a powerful tool that can assist in lymphoma diagnosis in lymph node (LN) specimens. Although lymphoma diagnosis and classification are mainly based on tumor cell characteristics, surrounding cells are less employed in this process.Methods: We retrospectively investigated alterations in the ploidy status, proliferative cell fraction (PF) and the percentages of surrounding immune cells in 62 consecutive LN specimens with B-Cell Non-Hodgkin Lymphoma (B-NHL) that were submitted for FC evaluation between 2019-2022.Results: Compared with indolent B-NHLs, aggressive B-NHLs show increased DNA aneuploidy and PF, increased monocytes, immature-granulocytes, mature granulocytes, CD8⁺ T-cells, Double-Negative-T-cells and Double-Positive-T-cells, and decreased total CD45⁺ cells, total lymphocytes, CD4⁺ T-cells and CD4/CD8 ratio. Receiver operating characteristic analysis determined PF > 6.8% and immature-granulocytes > 0.9% as optimal cutoffs with highest specificity and sensitivity in differentiating aggressive and indolent B-NHLs.Conclusions: These findings further strength the diagnostic value of DNA content analysis by FC and suggest the utilization of tumor surrounding immune cells in NHL diagnosis and classification.

Pathogenicity of many bacteria including Bacillus cereus and Staphylococcus aureus depends on pore-forming toxins (PFTs), which cause lysis of host cells by forming pores in membranes of eukaryotic cells. Bioinformatic analysis revealed in over 600 PFTs a region homologous to the Lys171-Gly250 sequence in hemolysin II (HlyII) from B. cereus, which we designated as “homologous peptide”. Three β-barrel PFTs were used for a detailed comparative analysis. Two of them –HlyII and cytotoxin K2 (CytK2), – are synthesized in Bacillus cereus sensu lato; the third – S. aureus α-toxin (Hla) – is the most investigated representative of the family. Protein modeling showed certain amino acids of homologous peptide to be located on the surface of the monomeric forms of these β-barrel PFTs. We obtained monoclonal antibodies against both a cloned homologous peptide and a 14-membered synthetic peptide DSFNTFYGNQLFMK as part of homologous peptide. The HlyII, CytK2 and Hla regions recognized by the obtained antibodies, as well as an antibody capable of suppressing the hemolytic activity of CytK2, were identified in the course of the work. Antibodies capable of recognizing PFTs of various origins can be useful tools for both identification and suppression of the cytolytic activity of PFTs.

This review provides an overview of the biotransformation of limonene and α-pinene, which are commonly found in wood residues and citrus fruit by-products, to produce high-value-added products. Essential oils derived from various plant parts contain monoterpene hydrocarbons, such as limonene and pinenes which are often considered waste due to their low sensory activity, poor water solubility, and tendency to autoxidize and polymerise. However, these terpene hydrocarbons serve as ideal starting materials for microbial transformations. Moreover, agro-industrial byproducts can be employed as nutrient and substrate sources, reducing fermentation costs, and enhancing industrial viability. Terpenes, being secondary metabolites of plants, are abundant in byproducts generated during fruit and plant processing. Microbial cells offer advantages over enzymes due to their higher stability, rapid growth rates, and genetic engineering potential. Fermentation parameters can be easily manipulated to enhance strain performance in large-scale processes. The economic advantages of biotransformation are highlighted by comparing the prices of substrates and products. For instance, R-limonene, priced at US$34/L, can be transformed into carveol, valued at around US$530/L. This review emphasises the potential of biotransformation to produce high-value products from limonene and α-pinene molecules, particularly present in wood residues and citrus fruit by-products. The utilisation of microbial transformations, along with agro-industrial byproducts, presents a promising approach to extract value from waste materials and enhance the sustainability of the antimicrobial, the fragrance and flavour industry.

Thyroid hormones are essential for regulating the metabolic rate, growth, development, and maintenance of many physiological processes in vertebrates. They are synthesized by the thyroid gland, which is an ancient organ that evolved early in vertebrate evolution. This study aims to characterize the evolutionary path of polymorphic variants associated with the hypothalamus-pituitary-thyroid (HPT) axis by comparing ancient DNA (aDNA) sequences of Late Pleistocene-Holocene hominin populations with those of modern humans. We evaluated the genetic sequences of several populations, including Neanderthals, Denisovans, Palaeolithic hunter-gatherers from European Russia and Sunghir, and Neolithic hunter-gatherers/farmers from Anatolia focusing on genes involved in the development of the thyroid gland and thyroid hormone (TH) biosynthesis, secretion, and transport. Results showed interesting variants in the DIO2 (rs225014), TPO (rs4927611), and TG (rs2069556 and rs1133076) genes. All SNPs seemed to confirm that Neanderthals, and in part Denisovas, were physiologically hypothyroidic. Probably they had lower T3 levels due to defective production or peripheral conversion. From the moment that the most favourable alleles in terms of T3 production appear during the Paleolithic, we are inclined to assume that their selection was linked to environmental pressure.Our study supports insight into the evolutionary history of the endocrine system and can help in providing understanding into the evolution of physiological systems and their adaptation to changing environments. Understanding the evolution of thyroid hormones can also shed light on the mechanisms underlying thyroid disorders in humans.

The TRPV3 calcium ion channel is vital for maintaining skin health and has been associated with various skin-related disorders. Since TRPV3 is involved in the development of skin inflammation, inhibiting TRPV3 could be a potential treatment strategy. Alpha-mangostin isolated from Garcinia mangostana L. extract exhibits diverse positive effects on skin health; however, the underlying mechanisms remain obscure. This study investigated the TRPV3-inhibitory properties of alpha-mangostin on TRPV3 hyperactive mutants associated with Olmsted syndrome and its impact on TRPV3-induced cytokine secretion and cell death. Our findings demonstrate that alpha-mangostin effectively inhibits TRPV3, with an IC50 of 0.077 ± 0.013 μM, showing inhibitory effects on both wild-type and mutant TRPV3. TRPV3 inhibition with alpha-mangostin decreased calcium influx and cytokine release, protecting cells from TRPV3-induced death. These results indicate that alpha-mangostin reduced inflammation in TRPV3-activated skin keratinocytes, suggesting that alpha-mangostin could be potentially used for improving inflammatory skin conditions such as dermatitis.

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown origin, with a median survival time of ~3 years after diagnosis without anti-fibrotic therapy. It is characterized by progressive fibrosis indicated by increased collagen deposition and high numbers of fibroblasts in the lung. It was demonstrated that CCL18 induces collagen and αSMA synthesis in fibroblasts. We aimed to identify the CCL18 receptor responsible for its pro-fibrotic activities. Methods: We used a random phage display library to screen for potential CCL18-binding peptides, demonstrated its expression in human lungs and fibroblast lines by PCR and immunostaining and verified its function in cell lines. Results: We identified CCR6 (CD196) as a CCL18 receptor and found its expression in fibrotic lung tissue and on lung fibroblast lines derived from fibrotic lungs but it is almost absent in control lines and tissue. CCL18 induces receptor-internalization in a CCR6-overexpressing cell line. CCR6 blockade in primary human lung fibroblasts reduces CCL18-induced FGF2 release as well as collagen-1 and αSMA expression. Knock-down of CCR6 in a mouse fibroblast cell line abolishes the induction of collagen and -smooth muscle actin expression. Conclusion: Our data indicate that CCL18 triggers pro-fibrotic processes via CCR6, highlighting its role in fibrogenesis.

The escalating demand for multifunctional and advanced materials for growing industries has turned scientific exploration to graphene-based hybrid filler polymer composites. The introduction of graphene with other fillers into polymer matrices results in astonishing properties and thus has gained significant attention in recent years. This study addresses the significance of graphene-based hybrid filler polymer composites in progressive materials science and engineering. The paper encloses some traditional and current preparation techniques employed in the fabrication of composites and a comprehensive review of successfully prepared graphene hybrid polymer composites with enhanced mechanical, thermal, and electrical properties reported in published research. The role of different factors, e.g., filler type, aspect ratios, filler-matrix compatibility, dispersion effects, homogeneity, filler orientation through polymer matrices, and curing conditions, are summarized. Finally, the applications in heavy industries, e.g., aerospace, electronics, energy storage, and automotive sectors were also analyzed. We hope this study will serve as a practical resource for new researchers and practitioners to understand and harness the full potential of these composites in various scientific and industrial fields.

BACE1 is involved in the production of beta-amyloid peptides, and inhibiting its activity is a potential therapeutic strategy for managing Alzheimer's disease, as excessive beta-amyloid accumulation is a characteristic feature of the disease.Computational results suggest that hypericin has the potential to act as an inhibitor of BACE1. The Molecular Docking results indicate a high binding affinity between hypericin and BACE1, with a notable binding energy score of -10.3 kcal/mol. Additionally, the formation of various chemical bonds, including hydrogen bonds and hydrophobic bonds, further supports the idea that hypericin may effectively interact with the active site of BACE1. It's important to note that while the in silico Molecular Docking results are promising, further in vitro and in vivo studies would be necessary to validate and better understand the inhibitory potential of hypericin against BACE1. Additionally, the practical application of hypericin as a BACE1 inhibitor in a therapeutic context would require careful consideration of factors such as bioavailability, safety, and efficacy.

This study centered on examining 60 different antibiotics by assessing their primary toxicity parameters through the pkCSM database. The parameters included Max. Tolerated Dose (Human) (log mg/kg/day), Oral Rat Acute Toxicity (LD50) (mol/kg), Oral Rat Chronic Toxicity (LOAEL) (log mg/kg_bw/day), and Minnow Toxicity (LC50) (log mM). The results highlight four potential antibiotics—cefotaxime, ceftriaxone, imipenem, and meropenem—that exhibited lower toxicity effects compared to other compounds. These findings imply a relatively favorable safety profile for these antibiotics concerning the specified toxicity parameters. However, it is crucial to interpret these outcomes within the context of the specific clinical application and to consider additional factors for a comprehensive safety assessment. It's essential to acknowledge that evaluating toxicity is intricate, and the determination of what is considered "less toxic" can rely on specific criteria and the context of use. Furthermore, individual responses to antibiotics may vary, and the selection of an antibiotic should be based on diverse factors, including the specific infection being treated, the patient's health, and potential side effects.

Abstract Introduction: Poor structural quality of health facilities for tuberculosis (TB) diagnosis and treatment contributes to unfavorable health outcomes among TB patients. Improving the quality of healthcare services helps to avert TB-related morbidity. Despite these facts, the level of structural quality of health facilitieSs to deliver TB services is not in line with what the national TB and leprosy program (NTLP) recommends. Hence, the present study was conducted to assess the structural quality of health facilities to deliver quality TB services to TB patients among public health facilities in the Sidama region.Objectives: To determine the quality of the structural domain of TB services at public health facilities in the Sidama region of southern Ethiopia.Methods: An institution-based cross-sectional study was conducted from June to July 2023 among randomly selected public health facilities in the Sidama region. We included 40 randomly selected public health facilities that delivered TB services in the study area. Data was collected by experienced data collectors using facility audits, clinical observation checklists, structured questionnaires, and in-depth interviews. An Open Kit Mobile (ODK) application was used to collect data and exported to SPSS version 26. All statistical analysis was done using SPSS version 26.Results: The overall mean quality score for the structural dimension was 50.25 among the 40 health facilities audited in the study area.Conclusion: The quality of TB services regarding structural dimensions was poor in the study area. Therefore, any strategies must give careful attention to increasing the comprehensive structural dimension of quality TB services.

The gold(I) N-heterocyclic carbene (NHC) complexes, containing a combination of 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (iPr) and the corresponding 7-azaindole derivative (HL1-4), were prepared and structurally characterized. The complexes of the composition of [Au(iPr)(HLn)], where n = 1–4 for 5-fluoro-7-azaindole (1), 5-bromo-7-azaindole (2), 3-chloro-7-azaindole (3) and 3-iodo-7-azaindole (4), were further evaluated for their in vitro anti-cancer and anti-inflammatory activities. The results showed that complexes (1–4) behave as considerably cytotoxic against human ovarian cancer cell line A2780 (with IC50 = 4–9 mircoM) and cisplatin-resistant cell line A2780R (with IC50 = 5–8 microM, except for 2 with IC50 > 25 microM), providing significantly higher cytotoxicity than anticancer drug cisplatin. Moreover, they also revealed a relatively good selectivity over normal cells (MRC-5), with the values of selectivity index, SI > 2.5. The complex 4 was further studied for its cellular effects in A2780 cells by cell cycle analysis, induction of apoptosis, intracellular ROS production, activation of caspases 3/7 and disruption of mitochondrial membrane potential. The ability of complexes (1–4) to influence the activity of pro-inflammatory transcription factor NF-κB and secretion of TNF-α were evaluated, showing that complex 4 reveals comparable effects as the inflammatory drug Auranofin.

To follow the growth and development of each tree (N = 1200) Pinus sylvestris L., var. Negorelskaya starting from the seed and continuing at the juvenile (or even generative) stage is the goal of an ambitious project to create a plant passport if possible. Five datasets of replenished empirical (tab-ular and file) and systematic data reflect the early results of a unique ongoing experiment conducted with families moved along a climatic gradient from the collection area (1731 degree days, 722 mm) to the experimental area (2326 degree days; 786 mm). Datasets of morphometric, VIS-spectrometric, and germination seed data, combined with the first results of biometric data (including the Dickson quality index) of seedlings produced from these seeds, will allow scientists in the future to conduct correlation and other statistical analysis, or train a neural network to determine the presence of connections between a seed and a plant. These data contribute to the early non-destructive diag-nosis and grading of seeds according to VIS-spectrometric properties. This dataset structure can complement the FLR-Library. In the future, by tracing seedlings in their early growth (for example, over three growing seasons at the site being restored), it will be possible to determine the degree of intensification of FRM production depending on the initial properties of the seed.

Stem cells can be used to treat diabetic mellitus and complications. ω3-docosahexaenoic acid (DHA) derived lipid mediators are inflammation-resolving and protective. This study found novel DHA-derived 7S,14R-dihydroxy-4Z,8E,10Z,12E,16Z,19Z-docosahexaenoic acid (7S,14R-diHDHA), a maresin-1 stereoisomer biosynthesized by leukocytes and related enzymes. Moreover, 7S,14R-diHDHA can enhance mesenchymal stem cell (MSC) functions in the amelioration of diabetic mellitus and retinal pericyte loss in diabetic db/db mice. MSCs treated with 7S,14R-diHDHA were delivered into db/db mice i.v. every 5 days for 35 days. Blood glucose levels in diabetic mice were lowered by 7S,14R-diHDHA-treated MSCs compared to control and untreated MSC groups, accompanied by improved glucose tolerance and higher blood insulin levels. 7S,14R-diHDHA-treated MSCs increased insulin+ β-cell ratio and decreased glucogan+ α-cell ratio in islets, as well as reduced macrophages in pancreas. 7S,14R-diHDHA induced MSC functions in promoting MIN6 β-cell viability and insulin secretion. 7S,14R-diHDHA induced MSC paracrine functions by increasing the generation of hepatocyte growth factor and vascular endothelial growth factor. Furthermore, 7S,14R-diHDHA enhanced MSC functions to ameliorate diabetes-caused pericyte loss in diabetic retinopathy by increasing their density in retina in db/db mice. Our findings provide a novel strategy for improving therapy for diabetes and diabetic retinopathy using 7S,14R-diHDHA-primed MSCs.

The aggregate aftermath of persistent inflammation in patients with inflammatory bowel disease (IBD) places them at increased risk for the advancement to colitis-associated colorectal cancer (CACRC). CACRC is preceded by IBD, the highly heterogenous, pharmacologically incurable, pertinacious, reverting/worsening, and immune-mediated inflammatory pathologies of the colon and rectum. The molecular and immunological basis of CACRC is highly correlated with the length/duration and stringency/severity of colon inflammation predisposed by the exogenous/free hemoglobin alpha chain (HbαC) the byproduct of infiltrating immune cells, extravasated erythrocytes, and macrophage erythrophagocytosis. The exogenous free HbαC prompts oxygen-free radical-arbitrated DNA damage (DNAD) through increased cellular reactive oxygen species (ROS) exacerbated by decreased tissue antioxidant defenses. Mitigation of Fenton reaction via pharmaceutical therapy would attenuate the ROS, promote apoptosis, DNAD repair, and subsequent prevent the incidence of CACRC. Three pharmaceutical options that attenuate hemoglobin toxicity include haptoglobin, deferoxamine, and flavonoids (vitamins C/E). Haptoglobin’s clearance rare from plasma is inversely correlated with its size; the smaller the size, the faster the clearance. Thus, the administration of Hp1-1 may prove to be beneficial. Furthermore, deferoxamine’s hydrophilic structure limits its ability to cross cell membranes. Thus, it may be beneficial if administered intracellularly to avoid the higher plasma concentrations and longer incubation periods associated with extracellular administration. Finally, the effectiveness of flavonoids and natural herb antioxidants is associated with high reactivity of hydroxyl substituents. Multiple analyses are currently underway to assess the clinical context of CACRC and outline the molecular basis of HbαC-induced ROS pathogenesis by exposing colonocytes and/or colonoids to HbαC. These cells are then treated with haptoglobin, deferoxamine (DFO), and flavonoids in order to separate free HbαC and measure their impact on hydroxyl radical formation therapies. The molecular pathogenesis of sporadic colorectal cancer (SCRC) i.e., “inflammation-dysplasia-carcinoma” progression sequence is well described, but the immunopathogenesis of CACRC herein reviewed is broadly still in prodromal stage/phase to be validated and understood. Therefore this timely review outlines the molecular and immunological basis of disease pathogenesis and the pharmaceutical intervention as a protective measure for CACRC.

To develop peptide drugs targeting integrin receptors, synthetic peptide ligands endowed with well-defined selective binding motifs are necessary. The snake venom KTS-containing disintegrins, that selectively block collagen α1β1 integrin, were used as lead compounds for the synthesis and structure-activity relationship of a series of linear peptides containing the KTS-pharmacophore and alternating natural amino acids and 3-aminobenzoic acid (MABA). To ensure a better stiffness and metabolic stability, one, two and three MABA residues, were introduced around the KTS pharmacophore motif. Molecular dynamics simulations have determined that the solution conformation of MABA peptide 4 is more compact, underwent larger conformational changes until convergence, and spent most of the time in a single cluster. The peptides’ binding affinity has been characterized by enzyme linked immunosorbent assay in which the most potent peptide 4 inhibited with IC50 of 324±8 µM and 550±45 µM the binding of GST-α1-A domain to collagen IV fragment CB3, and the cell adhesion to collagen IV using α1-overexpressor cells, respectively. Docking studies and MM-GBSA calculations confirmed that peptide 4 binds a smaller region of the integrin near the collagen- binding site and penetrated deeper into the binding site near Trp1. Peptide 4, inhibited tube formation by endothelial cell migration in the Matrigel angiogenesis in vitro assay. Peptide 4 was acutely tolerated by mice, showed stability in human serum, decreased tumor volume and angiogenesis, and significantly increased the survival of mice injected with B16 melanoma cells. These findings propose that MABA-peptide 4 can further serve as an α1β1-integrin antagonist lead compound for further drug-optimization in angiogenesis and cancer therapy.

Background: Autonomic balance measurement (ABM) is a valuable tool in clinical practice for assessing the functioning of the autonomic nervous system (ANS), which controls involuntary bodily functions. Here we summarize the current understanding of the utility of autonomic balance measurement in clinical practice. Methods: A narrative review of relevant literature was conducted, focusing on studies investigating the use of autonomic balance measures in various clinical settings. Results: ABM holds potential benefits in clinical practice, including aiding in diagnosing autonomic dysfunction, monitoring treatment efficacy, and predicting potential health complications. ABM can be crucial for diagnosing various conditions, including cardiovascular diseases (Heart failure, arrhythmias, and hypertension), neurological disorders (Parkinson's disease, Alzheimer's disease, and diabetic neuropathy), in sports medicine athletes can undergo ABM to optimize training regimens, enhance performance, assessing the impact of training stress, preventing overtraining, and promoting overall well-being and probably to assess potential health risks, in metabolic syndromes ABM can aid in the early detection of autonomic neuropathy, a diabetes-related complication, allowing for timely intervention and better management of the disease, and psychiatric disorders (Anxiety, depression, and post-traumatic stress disorder). In addition, ABM can be helpful in monitoring of treatment efficacy, by tracking changes in autonomic balance, clinicians can assess if treatments for conditions impacting the autonomic nervous system are effective. ABM can also be helpful in predicting outcomes by facilitating early recognition of future health complications in certain populations. However, limitations exist, including non-specificity, variability in measurements, and limited evidence for routine use in specific clinical settings. Conclusion: Incorporating autonomic balance measurement into routine clinical assessments provides a more comprehensive understanding of a patient's health. It complements traditional diagnostic methods, offering additional insights into the body's regulatory mechanisms. While autonomic balance measurement offers potential benefits, careful interpretation and consideration of its limitations are crucial for its effective use in clinical practice. ABM remains a valuable and versatile tool in clinical practice for a deeper understanding of the autonomic nervous system, enabling early detection, targeted interventions, and improved management of various medical conditions across different specialties.

O2 is essential for the life of eukaryotic cells. The ability to sense oxygen availability and initiate a response to adapt the cell to changes in O2 levels is a fundamental achievement of evolution. The key switch for adaptation consists of the transcription factors HIF1A, HIF2A and HIF3A. Their levels are tightly controlled by O2 through the involvement of the oxygen-dependent prolyl hydroxylase domain-containing enzymes (PHDs/EGNLs), the von Hippel-Lindau tumour suppressor protein (pVHL) and the ubiquitin-proteasome system. Furthermore, HIF1A and HIF2A are also under the control of additional post-translational modifications (PTMs) that positively or negatively regulate the activities of these transcription factors. This review focuses mainly on two PTMs of HIF1A and HIF2A: phosphorylation and acetylation.

Azobenzene photoswitches are fundamental components in contemporary approaches aimed at light-driven control of intelligent materials. Significant endeavors are directed towards enhancing the light-triggered reactivity of azobenzenes for such applications and obtaining water-soluble molecules able to act as crosslinkers in a hydrogel. Here, we report the rational design and the synthesis of azobenzene/alginate photoresponsive hydrogels endowed with fast reversible sol-gel transition. We started with the synthesis of three cationic azobenzenes (AZO A, B, and C) and then incorporated them in sodium alginate (SA) to obtain photoresponsive supramolecular hydrogels (SMHGs). The photoresponsive properties of the azobenzenes were investigated by UV-Vis and ¹H NMR spectroscopy. Upon irradiation with 365 nm UV light, the azobenzenes demonstrated efficient trans-to-cis isomerization, with complete isomerization occurring within seconds. The return to the trans form took several hours, with AZO C exhibiting the fastest return, possibly due to higher trans isomer stability. In the photoresponsive SMHGs, the minimum gelation concentration (MGC) of azobenzenes was determined for different compositions, indicating that small amounts of azobenzenes could induce gel formation, particularly in 5 wt% SA. Upon exposure to 365 nm UV light, the SMHGs exhibited reversible gel-sol transitions, underscoring their photoresponsive nature. This research offers valuable insights into the synthesis and photoresponsive properties of cationic, water-soluble azobenzenes, as well as their potential application in the development of photoresponsive hydrogels.

A series of alpha,omega-bis(o-methoxyphenyl)arenes were prepared through Suzuki-Miyaura coupling reactions of dibromoarenes with o-methoxyphenyl boronic acid. P2O5-CH3SO3H-mediated direct polycondensation of alpha,omega-bis(o-methoxyphenyl)arenes with trans-1,4-cyclohexanedicarboxylic acid proceeded regioselectively to afford 1,4-cyclohexanediyl-containing aromatic polyketones. The resulting aromatic polyketones have high Tg and excellent solubility in typical organic solvents. In addition, the polyketone films fabricated by solution casting method are more colorless and transparent than those without cyclohexanediyl units.

The development of integrated, compact, and multifunctional photonic circuits is crucial to increase the capacity of all-optical signal processing for communications, data management or microsystems. Plasmonics brings compactness to numerous photonic functions, but its integration into circuits in not straightforward due to insertion losses and poor modes matching. The purpose of this article is to detail the integration strategies of plasmonic structures on dielectric waveguides, and to show through some examples the variety and the application prospect of integrated plasmonic functions.

Liver fibrosis is a critical health issue with limited treatment options. This study investigates the potential of PGC-Sec, a secretome derived from PGC-1α-overexpressing adipose-derived stem cells (ASCs), as a novel therapeutic strategy for liver fibrosis. Upon achieving a cellular confluence of 70-80%, ASCs were transfected with pcDNA-PGC-1α. PGC-Sec, obtained through concentration of conditioned media using ultrafiltration units with a 3-kDa cutoff, was assessed through in vitro assays and in vivo mouse models. In vitro, PGC-Sec significantly reduced LX2 human hepatic stellate cell proliferation and mitigated mitochondrial oxidative stress compared to control-secretome (Ctrl-Sec). In an in vivo mouse model, PGC-Sec treatment led to notable reductions in hepatic enzyme activity, serum pro-inflammatory cytokine concentrations, and fibrosis-related marker expression. Histological analysis demonstrated improved liver histology and reduced fibrosis severity in PGC-Sec-treated mice. Immunohistochemical staining confirmed enhanced expression of PGC-1α, OPA1 (a mitochondrial function marker), and PPARα (an anti-fibrogenic marker) in the PGC-Sec-treated group, along with reduced Collagen 1A expression (a pro-fibrogenic marker). These findings highlight the therapeutic potential of PGC-Sec in combating liver fibrosis by enhancing mitochondrial biogenesis and function, and promoting antifibrotic processes. PGC-Sec holds promise as a novel treatment strategy for liver fibrosis.

Background: The Liver Imaging Reporting and Data System (LI-RADS) combines standardized terminology with a classification system for imaging findings in patients with HCC, therefore rendering diagnostic biopsy unnecessary in many cases. This retrospective study included 23 patients with a biopsy diagnosis of HCC, performed either before or after local interventional procedures, in order to evaluate the histopathologic changes induced by previous procedures and their potential influence on the response to immune therapy. Material and Methods: The study encompassed a cohort of patients diagnosed with Hepatocellular Carcinoma (HCC). Diagnosis was established through contrast-enhanced computer tomography or magnetic resonance imaging that identified LI-RADS-5 nodules in conjunction with historical liver disease and elevated alpha-fetoprotein (AFP) levels, or through histological examination confirming positivity for glypican3, heat shock protein70, and glutamine synthetase. The study detailed the liver disease etiology, LI-RADS scores, characteristics and dimensions of HCC nodules, serum AFP concentrations, Edmondson-Steiner grading, and the expression of programmed cell death ligand 1 (PD-L1) in the tumor cells. Results: Among the study's cohort of Hepatocellular Carcinoma (HCC) patients, a portion had not received any prior treatments, while the remainder experienced local HCC recurrence following trans-arterial chemoembolization or radiofrequency ablation. Observations indicated elevated alpha-fetoprotein (AFP) levels in those who had not undergone any previous interventions, showing statistical significance. The Edmondson-Steiner classification predominantly identified grade III differentiation across patients, irrespective of their treatment history. Furthermore, an increase in intra-tumoral programmed cell death ligand 1 (PD-L1) expression was noted in patients who had not been subjected to previous therapies. Conclusion: Liver biopsy offers valuable insights for patients with Hepatocellular Carcinoma (HCC), assisting in the tailoring of immune therapy strategies, particularly in cases of recurrence following prior local interventions.

A physical scrutiny of experimental results published in Physical Review Letters (December 2015, M. Giustina, et al., Phys. Rev. Lett. 115, 250401, and L. K. Shalm et al., Phys. Rev. Lett. 115, 250402) is undertaken. These articles reported that measured outcomes were fitted with quantum states possessing a dominant component of non-entangled photons, thereby contradicting their own claim of quantum nonlocality. With probabilities of photon detections lower than 0.1 %, the alleged quantum nonlocality cannot be classified as a resource for developing quantum computing devices, despite recent publicity. Experimental evidence of a feasible process for quantum-strong correlations has been identified (M. Iannuzzi, et al., Phys. Lett. A, 384 (9), 126200, 2020) in terms of correlations between independent and multi-photon states evaluated as Stokes vectors on the Poincaré sphere. As single-photon sources are not needed, the design and implementation of quantum computing operations will be significantly streamlined.

Current artificial intelligence (AI) technology is still considered weak AI. However, the progression towards strong AI unavoidably involves grappling with concerns surrounding consciousness, the mind, and creativity. This paper focuses on analyzing consciousness, creativity, and the generation of emotions to explore the possibility of machine-based consciousness, creativity, and emotion. We believe that the emergence of consciousness relies on the complex interplay at different layers within a complex system, rather than wholly relying on the underlying substrates of the system. Thus, it is plausible to consider the existence of machine-based consciousness, creativity, and emotion. Furthermore, swarm intelligence should be recognized as a distinct form of intelligence. Human individuals serve as the foundational substrate enabling the realization of swarm intelligence, with individual intelligence reflecting the projection of swarm intelligence at the individual level. The advanced state of human civilization is primarily attributable to the effect of swarm intelligence. Building upon basic emotions to adapt to environmental conditions, advanced human emotions are a product of the evolutionary process by swarm intelligence. Emotions serve as a pivotal impetus for the formation and development of societies grounded in swarm intelligence. In pursuit of super-AI that surpasses human civilization in the future, nurturing swarm intelligence represents an inevitable trajectory.

Some studies show that patients with mutations in the SNCA gene, which codifies for the alpha-synuclein protein, show a particular phenotype. The effects of SNCA Single Nucleotide Polymorphism (SNPs) in recently diagnosed, drug-naïve patients with PD have been less explored. Therefore, we set out to explore the differences in the clinical characteristics of recently diagnosed drug-naïve sporadic PD patients with or without SNCA rs3910105 or rs356181 SNPs. Patients with a clinical diagnosis of PD in the Parkinson’s Progression Markers Initiative (PPMI) database entered the study. We excluded those with missing data, dementia, psychiatric conditions, a diagnosis change over the first five years from the initial PD diagnosis, or with a familial history of PD. Subjects were evaluated with the MDS-Unified PD Rating Scale (MDS-UPDRS), DAT imaging, the Geriatric Depression Scale (GDS), the State-Trait Anxiety Inventory (STAI), the Montreal Cognitive Assessment (MoCA), the SCOPA-AUT for autonomic function, the Epworth Sleepiness Scale (ESS), the RBD Questionnaire, and the University of Pennsylvania Smell Identification Test (UPSIT). We included 308 PD patients fulfilling all inclusion and exclusion criteria. A logistic regression analysis and Machine-Learning models did not disclose any difference between patients either with or without the SNCA rs3910105 SNP or with or without the SNCA rs3910105 polymorphism. Our results suggest that the SNCA polymorphisms rs3910105 and rs356181 have no impact on the phenotype of idiopathic, sporadic, recently diagnosed, drug naïve PD patients.

Despite accumulating evidence that suggests a unique gut microbiota composition in athletes, a comprehensive understanding of this phenomenon is lacking. Furthermore, seasonal variation in the gut microbiota of athletes, particularly during the off-season, remains underexplored. This study aimed to compare the gut microbiotas between athletic subjects (AS) and non-athletic subjects (NS), and to investigate variations between athletic and off-season periods. The data were derived from an observational study involving Japanese male handball players. The results revealed a distinct gut microbiota composition in AS compared with NS, characterized by significantly higher alpha-diversity and a greater relative abundance of Faecalibacterium and Streptococcus. Moreover, a comparative analysis between athletic and off-season periods in AS demonstrated a significant change in alpha-diversity. Notably, AS exhibited significantly higher alpha-diversity than NS during the athletic season, but no significant difference was observed during the off-season. This study demonstrates the characteristics of the gut microbiota of Japanese handball players and highlights the potential for changes in alpha-diversity during the off-season. These findings contribute to our understanding of the dynamic nature of the gut microbiota of athletes throughout the season.

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

This article describes a novel electrochemical on-chip biosensor that utilizes anti-PSA antibody (Ab) and silver nanoparticles (AgNPs) to enhance the sensing and detection capability of prostate specific antigen (PSA) in the blood. The AgNPs are prepared, characterized, and applied onto a silicon photonic on-chip biosensing receptor platform designed to enhance the accurate detection of PSA. The AgNPs were synthesized by a chemical reduction method using silver nitrate (AgNO₃) as the precursor. Transmission electron microscopy (TEM), selected area electron diffraction (SAED), energy dispersion X-ray spectroscopy (EDS), small angle X-ray scattering (SAXS), X-ray diffraction (XRD), and light microscopy were among the methods used in the characterization and analysis of the AgNPs. Each stage of the immunosensor fabrication was characterized using cyclic voltammetry. The proposed immunosensor was applied in the detection of PSA, a prostate cancer biomarker, with a high sensitivity and a limit of detection of 0.17 ng/mL over a linear concentration range of 2.5 to 11.0 ng/mL. The immunosensor displayed good stability and was selective in the presence of interfering species like immunoglobulin (Ig) in human serum, ascorbic acid (AA), and diclofenac (Dic). The detectivity and sensitivity are significantly higher than previous reports on similar or related technologies.

This article is devoted to the problem of genetically coding of inherited cyclic structures in biological bodies, whose life activity is based on a great inherited set of mutually coordinated cyclic processes. The author puts forward and arguments the idea that the genetic coding system is capable of encoding inherited cyclic processes because it itself is a system of cyclic codes connected with Boolean algebra of logic. In other words, the physiological processes in question are cyclical because they are genetically encoded by cyclic codes. In support of this idea, the author presents a set of his results on the connection of the genetic coding system with cyclic Gray codes, which are one of many known types of cyclic codes. This opens up the possibility of using for modeling inherited cyclic biostructures those algebraic and logical theories and constructions that are associated with Gray codes and have long been used in engineering technologies: Karnaugh maps, Hilbert curve, Hadamard matrices, Walsh functions, dyadic analysis, etc. Additionally, the connections of these constructions with statistical rules of genomic DNAs and binary-genomic numbers are considered.

Background –The brinjal is of much importance in the warm areas of Far East, being grown extensively in India, Bangladesh, Pakistan, China and the Philippines. It is also popular in Egypt, France, Italy and United States. Preserving soil fertility throughout time by preserving organic matter and soil biological diversity, mechanical intervention, as well as exercise is highly needed in upcoming future. Effect of six different fertilizer, five organic and one synthetic fertilizers listing vermicompost, poultry manure, mustard cake, neem cake, bonemeal and N:P:K study were main concern of this investigation to find out the most suitable fertilizer for the brinjal.Result - the final growth and development through N:P:K @ 1.5%(19:19:19) outperformed all the organic fertilizers but when considering only organic fertilizer performance vermicompost@5 ton/ha was outperforming all the other organic fertilizers. Coming close to it, mustard cake@1.5ton/ha has shown its inheritance in providing nutrients. Use of other organic fertilizers are also effective use of poultry manure can provide nitrogen in higher amount in short time. Higher temperature above 25 degree Celsius cause slow growth, temperature range between 21 to 14 degrees Celsius was found better in terms of growth of flower and fruit formation.Conclusion – our experiment demonstrate specific organic fertilizer use over other fertilizers in terms of brinjal different developemental parameters and there is even comparision between synthetic fertilizer with organic fertilizer readily available in market. Vermicompost showed promising result followed by mustard cake for this specific brinjal genotype in northern plain of Indian subcontinent.

Psoriatic arthritis (PsA) is a persistent, inflammatory disease that affects individuals with psoriasis, arthritis, and enthesitis. Research has demonstrated that inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-23 (IL-23), and interleukin-17 (IL-17) play a pivotal role in both the onset and progression of PsA. These cytokines are generated by activated immune cells and stimulate the attraction of inflammatory cells to the synovium and joint tissues, resulting in the deterioration of cartilage and bone. The blocking of these cytokines has become a successful treatment strategy for PsA, as biological drugs that inhibit TNF-α, IL-23, and IL-17 have demonstrated notable clinical benefits. The association between PsA and other types of inflammatory cytokines or chemokines, excluding TNF-α, IL-23, and IL-17, has been extensively investigated in numerous studies. These findings may provide a chance for the discovery of novel therapeutic agents targeting other molecules, distinct from the currently approved biologics and targeted synthetic disease-modifying antirheumatic drugs. In this review, we discuss the current understanding of the role of inflammatory cytokines in PsA pathogenesis and clinical implications of targeting these cytokines for PsA treatment.

Stipa tenacissima (S. tenacissima), or esparto, is a perennial tussock grass that coexists with Pinus halepensis (P. halepensis) in semi-arid mediterranean woodlands. This research was carried out to explore diurnal transpiration at leaf level in esparto grass under different levels of pine-esparto competition and in contrasting environmental conditions of soil water. The measurements were spanned from the summer 2020 to spring 2021. The relationship between transpiration and competence was conducted in open and closed P. halepensis stands and taken into account the type of leave (green, senescent) and the maturity of the esparto grass. We observed a higher control of transpiration in green leaves, and correlations between transpiration and soil water were noted exclusively in this type of leaf. Our results substantiated a significant impact of pine competitors on transpiration of esparto grass, particularly during seasons characterized by high water-demand scenarios: the summer drought period and the commencement of the growing and flowering period (spring). Furthermore, our findings confirmed a greater response to transpiration in mature bushes compared to young ones under severe water stress, denoting higher adaptation to drought as esparto ages. Our results may have important implications for the dynamics and management of these semi-arid mixed woodlands, as well as the planning of reforestation programs aimed at restoring esparto grass steppes.

Alpha-B-Crystallin, a member of the small heat shock family of proteins, has been implicated in a variety of cardiomyopathies and in normal cardiac homeostasis. It is known to function as a molecular chaperone, particularly for desmin, but also interacts with a wide variety of additional proteins. The molecular chaperone function is also enhanced by signal-dependent phosphorylation at specific residues under stress conditions. Naturally occurring mutations in CRYAB, the gene that encodes alpha-B-crystallin, have been suggested to alter ionic intermolecular interactions that affect dimerization and affect chaperone function. These mutations have been associated with myofibrillar myopathy, restrictive cardiomyopathy, and hypertrophic cardiomyopathy, and promote pathological hypertrophy through different mechanisms such as desmin aggregation, increased reductive stress or activation of calcineurin-NFAT signaling. This review will discuss the known mechanisms by which alpha-B-crystallin functions in cardiac homeostasis and the pathogenesis of cardiomyopathies and provide insight into potential future areas of exploration.

Background: Mounting evidence supports the role of the endocannabinoid system in neurophysiology, includ-ing blood-brain barrier (BBB) function. Recent work has demonstrated that activation of endocannabinoid re-ceptors can mitigate insults to the BBB during neurological disorders, like traumatic brain injury, cortical spreading depression and stroke. As alterations to the BBB are associated with worsening clinical outcomes in these conditions, studies herein sought to examine the impact of endocannabinoid depletion on BBB integrity. Methods: Barrier integrity was investigated in vitro via bEnd.3 cell monolayers to assess endocannabinoid syn-thesis, barrier function, calcium influx, junctional protein expression, and proteome-wide changes. Results: In-hibition of 2-AG synthesis using DAGLα inhibition and siRNA inhibition of DAGLα led to loss of barrier in-tegrity via altered expression of VE-cadherin, which could be partially rescued by exogenous application of 2-AG. Moreover, the deleterious effects of DAGLα inhibition on BBB integrity showed both calcium and PKC (protein kinase C)-dependency. Conclusions: These data indicate that disruption of 2-AG homeostasis in brain endothelial cells, in the absence of insult, is sufficient to disrupt BBB integrity thus supporting the role of the endocannabinoid system in neurovascular disorders.

GvHD still remains, despite the continuous improvement of transplantation platforms, a fearful complication of transplantation from allogeneic donors. Being able to separate GvHD from GvL represents the greatest challenge in the allogeneic transplant setting. This may be possible through continuous improvement of cell therapy techniques. In this review, current cell therapies are taken into consideration which are based on the use of TCR alpha/beta depletion, CD45 RA depletion, T regulatory cells enrichment, NK cell-based immunotherapies and suicide gene therapies in order to prevent GvHD and maximally amplify the GvL effect in the setting of haploidentical transplantation.

Angiogenesis is a critical physiological response to ischemia but becomes pathological when dysregulated and driven excessively by inflammation. We recently identified a novel angiogenic role for tripartite-motif-containing protein 2 (TRIM2) whereby lentiviral shRNA-mediated TRIM2 knockdown impaired endothelial angiogenic functions in vitro. This study sought to determine whether these effects could be translated in vivo and to determine the molecular mechanisms involved. CRISPR/Cas9-generated Trim2–/– mice that underwent a periarterial collar model of inflammation-induced angiogenesis exhibited significantly less adventitial macrophage infiltration relative to wildtype (WT) littermates, concomitant with decreased mRNA expression of macrophage marker Cd68 and reduced adventitial proliferating neovessels. Mechanistically, TRIM2 knockdown in endothelial cells in vitro attenuated inflammation-driven induction of critical angiogenic mediators, including nuclear HIF-1α, and curbed the phosphorylation of downstream effector eNOS. Conversely, in a hindlimb ischemia model of hypoxia-mediated angiogenesis, there were no differences in blood flow reperfusion to the ischemic hindlimbs of Trim2–/– and WT mice despite a decrease in proliferating neovessels and arterioles. TRIM2 knockdown in vitro attenuated hypoxia-driven induction of nuclear HIF-1α but had no further downstream effects on other angiogenic proteins. Our study has implications for understanding the role of TRIM2 in the regulation of angiogenesis in both pathophysiological contexts.

A rare genetic disorder caused by col18.a1 mutations, inherited mostly in autosomal recessive and rarely in autosomal dominant pattern, giving rise to ocular abnormalities and other associated disorders, the condition is referred to as Knobloch syndrome. This paper overviews the anterior and posterior ocular symptoms in Knobloch patients, thus demonstrating the major findings in Knobloch cases including the mutational analysis which discusses the proteins involved and exon number on which mutations are detected. Animal modeling done by knocking out col18.a1 has also been discussed to determine the functions of this gene which have been identified based on anomalies found in knock-out mice.

Due to the advancement and availability of internet in present age, device tend to become wireless as well. Mobile ad-hoc network is a wireless environment that consist of advanced agility of nodes and does not contain on any central administrative authority. As it does not contain any central administrative authority so being wireless environment, the network is vulnerable to security threats and suffers in performance as well. Security of MANET is the core issue in this era, meanwhile the data is sent over untrustworthy network. Several techniques were proposed to secure data over Mobile Adhoc Network though cryptography that is one of the most reliable techniques to protect data. In our proposed methodology a Secure Cryptographic technique for Mobile Adhoc Networks (SCTMA) we proposed A Collusion attack prevention (CAP) scheme with ElGamal key generator along with DNA encryption Algorithm is used to make it more secure. The proposed scheme protects the network against collusion attacks and improves the performance as well. Performance analysis will be measured on the basis of key generation time, response time, encryption time and decryption time. The proposed scheme also protects the network against collusion attacks.

High-quality optical Fano resonances, which exist in a spherical dielectric microparticle in the spatial configurations of the "whispering-gallery modes" (WGMs) and recently are referred to as the “super-resonances”, possess extremal sensitivity not only to the micro-cavity size and shape but also to the optical properties of the particulate material. The increase in the power of light radiation coupling into a super-resonance can lead to the manifestation of strong optical nonlinearity of the resonator material due to the cubic nonlinearity (optical Kerr effect) and generation of free electron plasma in certain regions of the spherical microcavity. In fact, an optically linear medium of the resonance cavity transforms into a Drude-Kerr-type medium with a strong dependence on input laser intensity. With the help of the finite-elements numerical simulations, we theoretically analyze the transformations of the resonant contour for a number of high-quality WGMs excited in a lanthanum-glass microsphere exposed to an optical radiation of different intensity. We show that in a certain input intensity range, the competition of Kerr and plasma optical nonlinearities can stop and even reverse the Stokes shift of the super-resonance observed in a pure Kerr medium. Additionally, optical ionization and plasma generation within the mode volume significantly reduce the strength of the magnetic super-resonance and lead to its spoiling and frequency splitting.

Background: Increase of collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. We hypothesized that COL I/COL III ratio is increased in the brain arteriovenous malformations (bAVMs), which is associated with bAVM hemorrhage. Method: Surgically resected human bAVM samples and mouse bAVMs induced in three transgenic mouse lines with activin receptor-like kinase 1 or endoglin deletion in the endothelial cells or in the brain focally. Colony-stimulating factor receptor inhibitor was used to transiently deplete microglia. COL I and COL III levels, hemorrhage, and gene expression in bAVMs were analyzed. Results: The COL I and COL III levels and the COL I/COL III ratio were higher on human and mouse bAVMs than controls, which was associated with bAVM hemorrhage. Col I and Col III mRNAs were also increased in mouse bAVMs. The degree of microhemorrhage in mouse bAVMs was positively correlated with Col I/Col III ratios. Transient depletion of microglia reduced Col I/Col III ratio and microhemorrhage in mouse bAVMs. Conclusion: COL I/COL III ratio are increased in bAVM vessels, which is associated with bAVM hemorrhage. Depletion of microglia reduces Col I/Col III ratio and hemorrhage in mice bAVMs.

Data is present in the data sources like Files and Data bases, Retrieval of information from that data sources is one of the important issue nowadays. So for retrieval information from the data sources clustering is used. In the present market different types of clustering algorithms were available. But opting of the clustering is based on user requirements. This paper focuses on the study of hierarchical clustering approach on different conditions or measures or with customer choices like clustering process number of clusters generated at each level, number of levels, attributes range for performing the clustering on the given data set. In brief overview we discuss the hierarchical approach for clustering algorithm with the user opting choices.

This work is concerned with studying the change of some Optical and Electrical Properties of Ba_xFe_(1-x)TiO₄ thin films due to the change of the nano crystal size. Simple theoretical explanation based on the string theory was developed. The empirical results obtained indicated that the absorption coefficient, electrical conductivity, and the magnetic permeability increase upon decreasing the nano crystal size. However, the transmission coefficient, and the refractive index increase upon increasing the nano crystal size. All these changes are explained using a simple string model with the aid of Newton's laws. The capability of the string theory to explain this nano quantum behavior comes from the fact that the string theory recognize both the particle and the wave nature of the nano system. This is similar of course to the quantum approach which is based mainly on the dual wave particle nature of atomic systems and entities.

Natural Gas (NG) processing is a prominent industrial separation process. Among the available techniques, the innovative membrane process shows potential for efficient removal of impurities, including carbon dioxide (CO₂). This study focuses on utilizing breakthroughs in membrane separation to drive sustainable CO₂ extraction from natural gas. Through comprehensive research and analysis, we explore the effectiveness and feasibility of membrane-based systems in removing CO₂ impurities from NG, thus promoting greener and more sustainable industrial practices. Our findings underscore the transformative nature of membrane separation technology, presenting new possibilities for a more environmentally-friendly and sustainable approach to CO₂ extraction from natural gas.Natural Gas (NG) processing utilizes various techniques for impurity removal, with the membrane process emerging as a promising option for efficient carbon dioxide (CO₂) extraction. This research proposes the integration of a simple mathematical model into ASPEN HYSYS to design a membrane system for CO₂/CH₄ separation. The study also investigates parameter sensitivities by altering operating conditions, such as feed composition and pressure, as well as membrane properties, including selectivity. By analyzing these variables, we aim to optimize the performance and efficiency of the membrane system, facilitating the sustainable extraction of CO₂ from NG. The findings contribute to advancing the design and operation of membrane-based processes for CO₂ separation, paving the way for greener and more sustainable industrial practices. In addition, this study explores various configurations for optimizing the design of the membrane system, including single-stage with and without recycling as well as double-stage configurations. The investigation demonstrates that methane recovery can be enhanced through the recycling of the permeate stream and by implementing a double stage membrane system. These findings highlight the potential for improving the efficiency and performance of the membrane system, enabling higher methane recovery rates. By considering different configurations, this research contributes to the development of more effective and sustainable CO₂ extraction processes from natural gas.

Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant liver ailment attributed to factors like obesity and diabetes. While ongoing research explores treatments for NAFLD, further investigation is imperative to address this escalating health concern. NAFLD manifests as hepatic steatosis, precipitating insulin resistance and metabolic syndrome. This study aims to validate the regenerative potential of chimeric fibroblast growth factor 21 (FGF21)-Hepatocyte Growth Factor Receptor (HGFR) in NAFLD-afflicted liver cells. AML12, a murine hepatocyte cell line, was utilized to gauge the regenerative effects of chimeric FGF21/HGFR expression. Polysaccharide accumulation was affirmed through periodic acid-Schiff (PAS) staining, while LDL uptake was microscopically observed with labeled LDL. mRNA analysis via RT-PCR revealed reduced expression of key NAFLD markers, including acetyl-CoA carboxylase 1 (ACC1) and sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP), alongside elevated levels of hepatocyte growth factor (HGF), hepatocyte nuclear factor 4 alpha (HNF4A), and albumin (ALB). These findings affirm the hepatoregenerative properties of chimeric FGF21/HGFR within AML12 cells, opening novel avenues for NAFLD therapeutic exploration.

Macrophages serve as vital defenders, protecting the body by exhibiting remarkable cellular adaptability in response to invading pathogens and various stimuli. These cells express nicotinic acetylcholine receptors, with the α7-nAChR being extensively studied due to its involvement in activating the cholinergic anti-inflammatory pathway. Activation of this pathway plays a crucial role in suppressing macrophages' production of proinflammatory cytokines, thus mitigating excessive inflammation and maintaining host homeostasis. Macrophage polarization, which occurs in response to specific pathogens or insults, is a process that has received limited attention concerning the activation of the cholinergic anti-inflammatory pathway and the contributions of the α7-nAChR in this context. This review aims to present evidence highlighting how the cholinergic machinery in macrophages, led by the α7-nAChR, facilitates the polarization of macrophages towards anti-inflammatory phenotypes. Additionally, we explore the influence of viral infections on macrophage inflammatory phenotypes, taking into account cholinergic mechanisms. We also review the current understanding of macrophage polarization in response to these infections. Finally, we provide insights into the relatively unexplored partial duplication of the α7-nAChR, known as dup α7, which is emerging as a significant factor in macrophage polarization and inflammation scenarios.

Natural image matting is an essential technique for image processing that enables various applications, such as image synthesis, video editing, and target tracking. However, the existing image matting methods may fail to produce satisfactory results when computing resources are limited. Sampling-based methods can reduce the dimensionality of the decision space and therefore reduce computational resources by employing different sampling strategies. While these approaches reduce computational consumption, they may miss an optimal pixel pair when the number of available high-quality pixel pairs is limited. To address this shortcoming, we propose a novel multi-criterion sampling strategy that avoids missing high-quality pixel pairs by incorporating multi-range pixel pair sampling and high-quality samples selection method. This strategy is employed to develop a multi-criterion matting algorithm via Gaussian process, which searches for the optimal pixel pair by using the Gaussian process fitting model instead of solving the original pixel pair objective function. Experimental results demonstrate that our proposed algorithm outperforms other methods even with 1% computing resources, and achieves alpha matte results comparable to those yielded by the state-of-the-art optimization algorithms.

For the first time, this study identified seven potential ligands with high binding energies through the docking approach against the Crystal Structure of human Melanoma-associated antigen B1 (MAGEB1). The ligands—Imatinib, Bafatinib, Diosmin, Ginkgetin, Bilobetin, Amentoflavone, and Hypericin—showing strong binding energies around -10 kcal/mol, indicate a potentially robust interaction with the target protein. Moreover, the additional step of predicting toxicity properties using the pKCSM server provides valuable insights into the safety profiles of these ligands. From these results, the parameters for Diosmin: —Max. tolerated dose (human),- Oral Rat Acute Toxicity (LD50), and - Oral Rat Chronic Toxicity (LOAEL)—suggest a favorable safety profile, making it a potential candidate for further consideration against Melanoma. Moving forward, it's advisable to conduct further experimental validations, including in vitro and in vivo studies, to confirm the efficacy and safety of Diosmin and other potential ligands. Consideration of pharmacokinetics, metabolism, and specific mechanisms of action will contribute to a comprehensive understanding of these compounds' potential as therapeutic agents.

Limited scientific evidence shows that alpha lipoic acid (ALA) can induce regression rates of low-grade squamous intraepithelial lesions (LSIL) but the mechanisms of these effects have not been elucidated. To gain a broader insight into its therapeutic potential and mechanisms of action, the effects of 3-month supplementation with 600 mg of ALA on antioxidant- and lipid status param-eters in 100 patients with LSIL were investigated in randomized placebo-controlled study. Obtained results were discussed in terms of patients’ initial metabolic status and diet quality (particularly nutritional intake of antioxidants). Obtained results showed that oxidative status biomarkers were not significantly affected by ALA supplementation. However, serum superoxide dismutase (SOD) activity was positively affected in the subgroup of patients with higher dietary antioxidant intake. Surprisingly, ALA supplementation resulted with small but statistically significant increase of serum low density lipoprotein (LDL) and observed effect was significantly affected by the initial lipid status of participants. Larger studies are necessary to gain additional insights on the clinical significance of ALA as an antioxidant and hypolipemic agent and to optimize its potential application in LSIL treatment.

In this work, we introduce a new concepts for $\alpha$-type $F$-Suzuki contraction and $\alpha$-type $F$-weak-Suzuki contraction in the context of $b$-metric spaces. Compared to the $\alpha$-type $F$-contraction and $F$-Suzuki contraction mappings, these contractions are essentially weaker. For these type of contraction mappings, sufficient conditions are established for the fixed point's existence and uniqueness in $b$-metric spaces. As a result, the findings encompass several generalizations. To show the usability of our obtained results, we provide a supportive example and an application to a non-linear differential equation with fractional order.

(1) Background: Globally, about 600 million people are afflicted with diabetes, and one of its most prevalent complications is neuropathy, a debilitating condition. At present, the exploration of novel therapies for alleviating diabetic neuropathy-associated pain is genuinely captivating, considering that current therapeutic options are characterized by poor efficacy and significant risk of side effects. In the current research, we evaluated the antihyperalgesic effect of sildenafil (phosphodiesterase-5 inhibitor) – metformin (antihyperglycemic agent) combination and its impact on biochemical markers in alloxan-induced diabetic neuropathy in rats; (2) Methods: The study comprised a cohort of 70 diabetic rats and 10 non-diabetic rats which were submitted to hot, cold, and tactile stimulus tests. Morover, we investigated the influence of this combination on TNF-α, IL-6 nitrites and thiols levels in brain and liver tissues; (3) Results: The results demonstrated that all sildenafil-metformin combinations decreased the pain sensitivity in von Frey test, Hot-plate test and Cold-plate test. Furthermore, alterations in nitrites and thiols concentrations and pro-inflammatory cytokines (specifically TNF-α and IL-6) were noted following a 15-day regimen of various sildenafil-metformin combinations. (4) Conclusions: The combination of sildenafil and metformin has a synergistic effect in alleviating pain in alloxan-induced diabetic neuropathy rats. Additionally, the combination effectively decreased inflammation, inhibited the rise in NOS activity, and provided protection against glutathione depletion.

Stimulation of the alpha 7 nicotinic acetylcholine receptor (α7nAChR) has shown beneficial effects in several acute inflammatory disease models. This study aims to examine whether treatment with the selective α7nAChR agonist PHA 568487 can dampen inflammation and thereby improve cardiac function after myocardial infarction in mice. The possible anti-inflammatory properties of α7nAChR agonist PHA 568487 were tested in vivo using the air pouch model and in a permanent occlusion model of acute myocardial infarction in mice. Hematology parameters and cytokine levels were determined. Infarct size and cardiac function were assessed via echocardiography 24 h and one week after the infarction. Treatment with α7nAChR agonist PHA 568487 decreased 12 (CCL27, CXCL5, IL6, CXCL10, CXCL11, CXCL1, CCL2, MIP1a, MIP2, CXCL16, CXCL12 and CCL25) out of 33 cytokines in the air pouch model of acute inflammation. However, α7nAChR agonist PHA 568487 did not alter infarct size, ejection fraction, cardiac output or stroke volume at 24 h nor at 7 days after the myocardial infarction compared with control mice. In conclusion, despite promising immunomodulatory effects in the acute inflammatory air pouch model, α7nAChR agonist PHA 568487 did not affect infarct size or cardiac function after a permanent occlusion model of acute myocardial infarction in mice. Consequently, this study does not strengthen the hypothesis that stimulation of the α7nAChR is a future treatment strategy for acute myocardial infarction when reperfusion is lacking. However, whether other agonists of the α7nAChR can have different effects remains to be investigated.

Computed tomography (CT) is a widely employed imaging modality with diverse clinical applications in pediatric and adult populations, offering numerous advantages. Despite several alternatives to imaging modalities with ionising radiation, CT scans have demonstrated persistent global popularity, contributing to a substantial amount of effective radiation doses for patients. This exposure results in hazards, including stochastic effects that amplify the radiation-induced cancer risk proportionally to the radiation dose received. CT-related radiation comprises a substantial portion of cumulative effective doses within diagnostic radiology, specifically impacting younger patient cohorts undergoing repeated investigations for chronic diseases over time. Scientific literature over recent decades has explored various methods to mitigate radiation doses during medical imaging. One notable strategy involves implementing low-dose and ultralow-dose CT protocols, maintaining diagnostic efficacy in acute and non-acute medical and surgical conditions. Utilising innovative image reconstruction algorithms, such as iterative reconstruction and emerging deep-learning algorithms based on artificial intelligence, plays a pivotal role in achieving an approximately 80% reduction in patient radiation compared to standard doses. This review article discusses the significance of low-dose protocols across a spectrum of acute and chronic medical conditions affecting different body systems.

Background: Amyotrophic lateral sclerosis (ALS) is an incurable disease. There are no defined valid biomarkers for evaluating therapeutic outcomes of this disease. Numerous approaches have been made to meet this impact. Stem cells, one of these approaches, that might give various hopeful results that can be interpreted as a treatment for ALS This study aims to evaluate Mesenchymal Stem Cell (MSC) therapy as a promising novel treatment modality by estimating some parameters, such as immunological and biochemical factors. Methods: This study course involved 15 confirmed patients with ALS and was designed as an open-label, one-arm retrospective study to evaluate potential diagnostic biomarkers of repeated infusions of autologous bone marrow-derived mesenchymal stem cells (BM-MSC) administered at a dose of 1×106cells/kg BW with 1-month interval, in equal amounts in both intravenous (IV) and intrathecal (IT) simultaneously, by various biochemical and immunological parameters were evaluated during the three-month follow-up period. Results: Our study indicated that in the case of Immunological biomarkers ,Tumor Necrosis Factor-alpha (TNF-α) levels in the Cerebrospinal fluid (CSF) showed a significant decrease at month three after transplantation compared to levels at month zero, and the P-value was (P&lt;0.01). No statistically significant changes were observed for other immunological and biochemical parameters and P-value (P&gt;0.05). Conclusions: These results can indicate the benefit of stem cell transfusion in patients with ALS and suggest some diagnostic biomarkers. Several studies are required to approve these results.

Background: As the most invasive breast cancer (BrCa), triple-negative BrCa (TNBC) has the worst survival. The use of dexmedetomidine potentially affected BrCa surgery and dexmedetomidine was reported to have direct effects on TNBC cells. The objective of this study is to explore the mechanisms underlying the effect of dexmedetomidine on TNBC. Methods: Dexmedetomidine targets were predicted using The Cancer Genome Atlas data SwissTargetPrediction. Cell lines MDA-MB-231, MCF7, and MCF10A were used to validate the targets in TNBC with both clinical samples and cell lines. Cancer cell lines and normal breast cell lines were grouped in cancer and normal groups respectively. Both groups were exposed to dexmedetomidine treatment. Cell Counting Kit-8 was used to determine the effect of dexmedetomidine on cells with target silencing. The binding model of the candidate targets was docked and critical amino acids were mutated to validate the binding model. Results: Dexmedetomidine selectively inhibits cancer cells. Catalytic subunit of the DNA-dependent protein kinase (PRKDC), indoleamine 2,3-dioxygenase 1 (IDO1), opioid receptor kappa 1 (OPRK1), glutaminyl-peptide cyclotransferase (QPCT), macrophage migration inhibitory factor (MIF), potassium voltage-gated channel, subfamily H (Eag-related), member 2 (KCNH2), cholinergic receptor, muscarinic 3 (CHRM3), and potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4 (KCNN4) were identified as dexmedetomidine targets in TNBC. The expression levels of PRKDC, IDO1, MIF, KCNH2, CHRM3, and KCNN4 were found to be upregulated in TNBC tissues compared to non-TNBC tissues(p<0.05). Silencing of these genes was found to reduce the sensitivity of TNBC cells to dexmedetomidine(p<0.05). This effect was counteracted when the silenced genes were overexpressed, resulting in an increase in the sensitivity of cells to dexmedetomidine (p<0.05). Furthermore, a direct interaction between dexmedetomidine and IDO1 and CHRM3 was observed, which regulated the sensitivity of cells to dexmedetomidine(p<0.05).Conclusion: IDO1 and CHRM3 are direct targets of dexmedetomidine in TNBC.

The connective tissue mast cell (MC), a sentinel tissue-residing secretory immune cell, is preserved in all vertebrate classes since approximately 500 million years. No physiological role of the MCs has yet been established. Considering the power of natural selection of cells during evolution, it is likely that the MCs exert essential yet unidentified life-promoting actions. All vertebrates feature a circulatory system, and the MCs interact readily with the vasculature. It is notable that embryonic MC progenitors are generated from endothelial cells. The MC hosts many surface receptors enabling its activation by a vast variety of potentially harmful exogenous and endogenous molecules, and by reproductive hormones in the female sex organs. Activated MCs release a unique composition of pre-formed and newly synthesized bioactive molecules, like heparin, histamine, serotonin, proteolytic enzymes, cytokines, chemokines, and growth factors. MCs play important roles in immune responses, tissue remodeling, cell proliferation, angiogenesis, inflammation, wound healing, tissue homeostasis, health, and reproduction. As recently suggested, MCs enable perpetuation of the vertebrates because of key effects—spanning generations—in ovulation and pregnancy, as in life-preserving activities in inflammation and wound healing from birth till reproductive age, thus creating a permanent life-sustaining loop. Here, we present recent advances that further indicate that the MC is a specific life-supporting and progeny-safeguarding cell

Eruca sativa is a commonly used edible plant in Italian cuisine. E. sativa 70% ethanol extract (ES) was fractionated with five organic solvents. Ethyl acetate fraction(EEA) had the highest antioxidant activity, which was correlated with the total polyphenol and flavonoid content. ES and EEA acted as PPAR-α ligands by PPAR-α competitive binding assay. EEA significantly increased cornified envelope formation as a keratinocyte terminal differentiation marker in HaCaT cells. Further, it significantly reduced nitric oxide and pro-inflammatory cytokines in lipopolysaccharide-stimulated RAW 264.7 cells. The main flavonol forms detected in high amounts from EEA are mono-, and di-glycoside of each aglycone. Flavonol mono-glycosides were shown to be a potent PPAR-α ligand using molecular docking simulation and showed the inhibition of nitric oxide. These results suggest that E. sativa is suitable for use in improving skin barrier function and inflammation in skin disorders, such as atopic dermatitis.

FacioScapuloHumeral Dystrophy (FSHD) is one of the most prevalent inherited muscle disorders, and is linked to the inappropriate expression of the DUX4 transcription factor in adult muscles. The deregulated molecular network causing FSHD skeletal muscle dysfunction and pathology is still not well understood. It has been shown that the hypoxia response factor HIF1α is critically disturbed in FSHD and has a major role in DUX4 induced cell death. In this study, we further explore the relationship between DUX4 and HIF1α. We found that the DUX4 and HIF1α link differed according to the stage of myogenic differentiation and was conserved between human and mouse muscle. Furthermore, we found that HIF1α knock-down in a mouse model of DUX4 local expression exacerbated DUX4-mediated muscle fibrosis. Our data indicate that the suggested role of HIF1α in DUX4 toxicity is complex and that targeting HIF1α might be challenging in the context of FSHD therapeutic approaches.

ABSTRACTIntroduction and Purpose: Nurses are expected to be competent in practice based on the domain of standards and interpersonal soft skills (ISS). Nurses are faced with inadequate physical assessment 28%, formulating diagnoses 56%, plans 34%, implementation 31%, evaluation 37,5%, and communication skills 41%. Aims to develop an ISS learning model based on transformative learning theory and digitalization (TLTD) to improve nurses’ competencies. Method: Used Explanatory cross-sectional involved 190 practitioner nurses. Variables of individual characters (X1), facilities (X2), Social environment support/SES (X3), TLTD (X4), ISS (X5), and nursing competencies (Y) were measured. Data was collected using a checklist questionnaire, conducted on 6 June to 10 August 2022 at Dili, Baucau, and Maliana hospitals. Used descriptive and inferential analysis with SEM-PLS. Result: Five of the 11 hypotheses of statistical p-value < 0,05 and T-Test > 1,96, including X2>X4, X3>X5, X4>X5, and X5>y, to form ISS learning model. The characteristic of respondents were 81,8% young adults, 67,9% women, 57,8% undergraduates, judging the previous training 35% was unsuccessful, and 45,8% did not meet expectations. Learning facilities that are still lacking include policies 23,7%, curriculum 23,4%, guideline 22,7%, modules 27,9%, infrastructure 20,3%, social environment support 24,2% low, organizational support, 30,0% low peer support and 26,3% low family support. The average TLTD is 25,3% to 34,2%, ISS 22,1% to 30,5%, and nurse competence 25,3% to 30,5%.Suggestion: Result of the study become base to improve nurse’s competencies. Conclusion: Learning model was formed by facilities, SES, TLTD, ISS, and nurses’ competencies.

The objective of this study was to evaluate the occurrence of Clostridium perfringens in stool samples and swabs collected from wild mammals in the Amazon biome. Sixty-five faecal and swab samples were collected in situ and ex situ from 16 species and three genera of wild mammals, some of which were in good health and some of which had diarrhoea. After pre-enrichment, the samples were plated on selective agar for C. perfringens. Characteristic colonies were subjected to multiplex PCR for the detection of genes encoding the main C. perfringens toxins (alpha, beta, epsilon, and iota toxin and enterotoxin). Among the 65 samples, 40 (61.5%) were positive for the gene encoding the alpha toxin and were classified as type A. Faecal samples were more than four times more likely to be positive for C. perfringens than were swab samples. No other toxinotypes were found. The findings of this study suggest that C. perfringens type A is commonly found as a commensal in mammal species of the Amazon biome. This seems to be the first study to identify C. perfringens type A in species such as B. variegatus (common ground sloth), C. didactylus (two-toed sloth), P. flavus (Jupará), T. tetradactyla (anteater), S. collinsi (squirrel monkey), S. niger (black marmoset), and S. apella (Guyana capuchin) and in the genus Didelphis sp. (opossum).

This study addresses the central question that how can a precise measurement of the gluon Parton Distribution Function (PDF) be attained, thereby enhancing our understanding of the intricate quark-gluon composition within nucleons? Through a dual approach involving Quantum Chromodynamics (QCD) and high-energy particle collisions, the research combines computational tools and experimental techniques, focusing on protons and neutrons. Scattering experiments and advanced detectors are utilized to probe nucleon structure. Theoretical frameworks like QCD equations and the Momentum Sum Rule investigate Parton Distribution Functions at specific momentum fractions and energy scales. The primary goal is to achieve an accurate measurement of the gluon PDF, crucial for unraveling strong force complexities and internal nucleon dynamics. The study's theoretical plots and equations illustrate hypothetical behaviors of gluon distribution, quark distribution, and splitting functions, contributing to a deeper understanding of fundamental particles.

Proteins are considered to be the main carriers of antigenic properties of Mycobacterium tuberculosis and Mycobacterium bovis, the causative agents of tuberculosis, the most serious infectious disease. Neutrophils, following resident macrophages, are among the first to attack the mycobacteria in defense of the organism. Neutrophils themselves are also the target of mycobacterial products; and their effect on neutrophil functions has been less studied. We have obtained about 70 protein fractions from M. bovis lysate; among them four protein fractions (10, 22, 24, and 40 kDa) had high serological activity against the serum of a rabbit immunized with M. bovis cells. We studied the effect of the serologically active proteins isolated from M. bovis on the generation of reactive oxygen species by bone marrow granulocytes of the Balb/c mouse, evaluated by luminol-dependent chemiluminescence. For comparison, two synthetic peptides (both 3 kDa) carrying immunogenic epitopes of MPB 70 protein (M. bovis) were taken. Proteins of 10, 22, and 24 kDa at concentrations of 83, 80, and 59 ng/mL, respectively, were found to activate ROS generation by mouse granulocytes. The 10- and 40-kDa antigens inhibited the receptor-mediated respiratory responses to opsonized zymosan (OZ) and N-formyl-MLF peptide (fMLF) but significantly enhanced the response to the phorbol ester PMA, which directly activates protein kinase C. Antigens with molecular weights of 22 and 24 kDa enhanced the fMLF-induced response and had no effect on the response activated by PMA. The response to OZ was suppressed in the presence of the 22 kDa protein. Synthetic peptides over a wide range of concentrations showed no activity in any case. All M. bovis proteins examined did not affect both proliferation and cell viability of the A549 and THP-1 cells; therefore, they have no cytotoxic or proliferative effects. Thus, serologically active proteins with molecular weights of 10, 22, 24, and 40 kDa isolated from M. bovis modulated the respiratory responses of mouse granulocytes induced by the formyl peptide, while proteins of 10, 22, and 40 kDa inhibited the responses induced by OZ.

Antiphospholipid syndrome (APS) is a group of autoimmune diseases caused by antiphospholipid antibodies (aPLs) characterized by arteriovenous thrombosis and a morbid pregnancy. We deliberated a case report of seven cases to investigate whether inhibitors of tissue necrosis factor-α could reduce pregnancy dangers caused by APS. The seven patients are with increased tumor necrosis factor, poor improvement after receiving traditional inhibitory drugs. To address these situations, the tumor necrosis factor inhibitors were prescribed after getting the patient's informed consent, and the state of illness was carefully watched for. After treatment, symptoms of contractions and abdominal pain disappeared and the B ultrasound examination showed embryo survived with good obstetric outcomes. Subsequently, maternal and neonatal health is compromised. An intervention by the administration of TNF-α inhibitors was posited to be an effective way of reducing dangerous pregnancies like preterm pregnancies, premature deliveries, abortions and miscarriages. We reviewed outcomes from seven cases in an attempt to establish how TNF- α Inhibitors could save pregnancies. We focused on key pregnancy outcomes like birth weight, gestational weeks and preterm miscarriage to tell the outcomes of TNF- α Inhibitors in pregnancy. After careful evaluation of the results surrounding these aspects, we found that TNF- α Inhibitors could prolong gestational period. Other positive outcomes include the attainment of birth weights approach the threshold, zero incidence of preterm miscarriage.