Despite evidence-based therapies, patients presenting with atherosclerosis involving more than one vascular bed, such as those with peripheral artery disease (PAD) and concomitant coronary artery disease (CAD), constitute a particular vulnerable group characterized by enhanced residual long-term risk for major adverse cardiac events (MACE), as well as major adverse limb events (MALE). The latter are progressively emerging as a hard outcome to be targeted, being correlated with increased mortality. Antithrombotic therapy is the mainstay of secondary prevention in both patients with PAD or CAD however, the optimal intensity of such therapy is still topic of debate, particularly in the post-acute and long-term setting. Recent well powered randomized clinical trials (RCTs) have provided data in favor of a more intense antithrombotic therapy, such as prolonged dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor or a therapy with aspirin combined with an anticoagulant drug. Both approaches increase bleeding and patients selection is a key issue. The aim of this review is therefore to discuss and summarize the most updated available evidences for different strategies of anti-thrombotic therapies in patients with chronic PAD and CAD, particularly focusing on studies enrolling patients with both type of atherosclerotic disease and comparing a higher versus a lower intensity antithrombotic strategy. The final objective is to identify the optimal tailored approach in this setting, to achieve the greatest cardiovascular benefit and improving precision medicine.

Neurodegenerative disorders are characterized by a progressive process of degeneration and neuronal death, where oxidative stress and neuroinflammation are key factors that contribute to the progression of these diseases. Therefore, two major pathways involved in these pathologies have been proposed as relevant therapeutic targets: The nuclear transcription factor erythroid 2 (Nrf2), which responds to oxidative stress with cytoprotecting activity and the nuclear factor NF-κB pathway, which is highly related to the neuroinflammatory process by promoting cytokine expression. Caffeic acid phenethyl ester (CAPE) is a phenylpropanoid naturally found in propolis that shows important biological activities, including neuroprotective activity by modulating the Nrf2 and NF-kB pathways, promoting antioxidant enzyme expression and inhibition of proinflammatory cytokine expression. Its simple chemical structure has inspired the synthesis of many derivatives, with aliphatic and/or aromatic moieties, some of which have improved the biological properties. Moreover, new drug delivery systems increase the bioavailability of these compounds in vivo, allowing its transcytosis through the blood-brain barrier, thus protecting brain cells from the increased inflammatory status associated to neurodegenerative and psychiatric disorders. This review summarizes the biosynthesis and chemical synthesis of CAPE derivatives, their miscellaneous activities, and relevant studies (from 2010 to 2023) addressing their neuroprotective activity in vitro and in vivo.

Background & aims. The fourth dose of anti-SARS-CoV-2 vaccine slightly improved the humoral response among previously seronegative liver transplant (LT) recipients. Mycophenolate (MMF) treatment worsens the vaccination response. This study aimed to evaluate whether temporary MMF interruption might improve immunogenicity of the fourth anti-SARS-CoV-2 BNT16b2 vaccine dose in nonresponsive LT recipients. Methods. LT recipients negative for anti-spike glycoprotein-specific immunoglobulin G receptor-binding domain (s-RBD) antibodies after the third vaccine dose were enrolled. Anti-SARS-CoV-2 spike-specific T cell responses were measured before and two months following the fourth vaccine dose, and anti-SARS-CoV-2-s-RBD antibodies also 6 months thereafter. MMF was suspended two weeks before and after vaccination. Results. Five LT recipients were enrolled. After a mean of 78 days after vaccination, all patients tested positive for anti-SARS-CoV-2-s-RBD antibodies. The mean antibody titer was 8944 UI/ml. The positive antibody response was maintained during a mean of 193 days of follow-up. Three patients developed a positive T cell response. Two patients (one positive for T cell response) developed a self-limited SARS-CoV-2 infection. Conclusions. Suspending MMF prior to the fourth dose of anti-SARS-CoV-2 mRNA vaccine seems feasible and safe. This procedure could restore vaccine-induced immunogenicity in a large portion of previously nonresponsive LT recipients.

The concerning rise in emergence and prevalence of resistant strains to drugs of M. tuberculosis has ,the prompted researchers to look for new and effective treatments. With this motive, biscoumarins were identified as the lead molecules on a whole-cell-based screening of several less explored low molecular weight bioactive compounds against M. tuberculosis strains. Among the screened biscoumarins, the highest dock score derivatives were synthesized (a-h) using a programmable microwave synthesizer for better yields and reaction control. The synthesized derivatives were evaluated against H37Rv, H37Ra, M. smegmatis, an MDR surrogate model, and other bacterial strains for the structure-activity response. Assessment of the synthesized library against mycobacterial strains led to the identification of compounds (f and d) as lead anti-tuberculosis agents. Compounds (f and d) exhibited less toxicity against human cell lines. At the same time, it displayed enjoyable activity wherein MIC concentrations were observed to be 16- and 32 µg/mL against the susceptible H37Rv, and H37Ra strains of M. tuberculosis and MIC value of 128 µg/mL for M. smegmatis, respectively. For mechanistic insights and identification of drug binding targets, molecular docking and dynamic simulations were employed for a panel of 16 mycobacterial enzymes essential for mycobacterial growth and survival. These in silico studies revealed the DprE1 enzyme as a druggable target for the anti-tuberculosis activity of the selected biscoumarins derivatives. Further investigation is underway in our laboratory, leading to its development as an anti-tuberculosis drug (animal model studies).

Antimicrobial resistance is on the rise, and there aren't enough new treatments to combat it. This might send the modern world back to the pre-antibiotic age. The molecular hybrids of pyrazolo[3,4-b]pyridine and triazole have been designed, synthesized, and analyzed for their drug-like molecule nature and in vitro analyses for their inhibition potentials against S. Aureus and K. Pneumoniae. The compounds CY-R2-25 and CY-R2-28 have been identified as the high potential molecules in this series based on in vitro experiments. CY-R2-25 has zone of inhibition values of 15 0.82 and 14 0.7, whilst CY-R2-28 has the zone of inhibition values of 18 0.95 and 16 0.82 against S. Aureus and K. Pneumoniae, respectively. MIC and MIB values for CY-R2-25 and CY-R2-28 against S. Aureus and K. Pneumoniae are 0.25 and 0.5, respectively.

Management of inflammatory bowel disease (IBD) often relies on biological and immunomodulatory agents for remission through immunosuppression, raising concerns regarding the SARS-CoV-2 vaccine's effectiveness. The emergent variants have hindered the vaccine neutralization capacity, and whether the third vaccine dose has the capacity to neutralize SARS-CoV-2 variants in this population remains unknown. This study aims to evaluate the humoral response of SARS-CoV-2 variants in patients with IBD 60 days after the third vaccine dose [BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)].56 su bjects with IBD and 12 healthy subjects were recruited. 90% of patients with IBD (49/56) were receiving biologics and/or immunomodulatory therapy. 24 subjects with IBD did not develop effective neutralizing capability against the Omicron variant. 70% (17/24) of those subjects were receiving anti-Tumor Necrosis Factor therapy [10= adalimumab, 7= infliximab], two of them had a history of COVID-19 infection, and one subject did not develop immune neutralization against three other variants: Gamma, Epsilon, and Kappa. All subjects in the control group developed detectable antibodies and effective neutralization against all seven SARS-CoV-2 variants. Our study shows that patients with IBD might not be protected against SARS-CoV-2 variants, and larger studies are needed to evaluate optimal immunity.

According to our previous investigation the total methanol extract from Graptopetalum paraguayense E. Walther demonstrates a significant inhibitory effect on HSV-1. To clarify what causes this inhibitory activity on HSV-1, a metabolic profile of the plant was performed. Three main fractions: non-polar substances, polar metabolites and phenolic compounds were obtained and GC-MS analysis was carried out. Since it is well known that phenolic compounds show a significant anti-herpes effect and that viral DNA polymerase (DNApol) appears to play a key role in HSV virus replication, we present a docking and quantum-chemical analysis of the binding of these compounds to viral DNApol amino acids. Fourteen different phenolic acids found by GS/MS analyses, were used in molecular docking simulations. According to the interaction energies of all fourteen ligands in the DNApol pockets based on docking results, DFT calculations were performed on the five optimally interacting with the receptor acids. It was found that hydroxybenzoic acids from phenolic fraction of Graptopetalum paraguayense E. Walther show a good binding affinity to the amino acids from the active site of the HSV DNApol, but significantly lower than that of acyclovir. The mode of action on virus replication of acyclovir (by DNApol) is different from that of the plant phenolic acids one, probably.

Flowers have always accompanied people thanks to their manifold aesthetic properties. Some species have also become a component of human diet. Recent years have seen an increased interest in edible flowers and, consequently, research has been undertaken to determine their chemical composition. Dyes abundantly contained in flowers, whose role is to attract pollinating animals, are recognized substances with health promoting properties. Anthocyanins are a group of dyes that is very common in petals and other parts of flowers. Studies carried out in the twentieth and twenty-first century have found very strong antioxidant and anti-inflammatory properties of anthocyanins. Therefore, flowers used by humans for centuries to decorate their surroundings may become an easily available source of nutrients and health-promoting substances. This paper discusses the health-promoting properties of anthocyanins and collects literature on anthocyanin content in edible flowers commonly grown on balconies, terraces and roofs.

Leaf crude extract (aqueous) of Oroxylum indicum (L.) Kurz induces genomic DNA fragmentation, comet formation, and inhibition of cell proliferation in prostate cancer cell line, PC3 as assessed by agarose gel electrophoresis, comet assay, and MTT assay respectively. The bioactive compound was purified through bioassay-guided fractionation using preparative HPLC and MTT as-say. The brown and water-soluble compound was characterized using 1H and 13C nuclear magnetic resonance (NMR), fourier transform infrared (FT-IR) and electrospray ionization (ESI) mass spectrometry, and the compound was iden-tified as a glycosylated hydroquinone derivative, 2-[p-(2-Carboxyhydrazino)phenoxy]-6-(hydroxymethyl) tetrahy-dro-2H-pyran-3,4,5-triol (molecular formula, C13H18N2O8; molecular mass = 330). The identified phytocompound has not been reported earlier elsewhere. Therefore, the common name of the novel anticancer phytocompound isolated from oroxylum indicum in this current study is named as oroxyquinone. The half-maximal inhibitory concentration (IC50) of oroxyquinone on PC3 cells was 19.44 µg/ml (95% CI = 17.97 to 21.04). Oroxyquinone induced cell cycle arrest at S phases and inhibition of cell migration on PC3 as assessed by flow cytome-try and wound healing assay respectively. On investigating the molecular mechanism of inducing apoptosis, the results indicated that the oroxyquinone induced apoptosis through the p38 pathway and cell cycle arrest, however, not through caspase-3 and PARP pathways. The present study identifies a novel an-ticancer molecule and provides scientific evidence supporting the therapeutic potency of OI for ethnomedicinal uses.

Alzheimer’s disease (AD) is a chronic neurodegenerative disease associated with the overproduction and accumulation of amyloid-β peptide and hyperphosphorylation of tau proteins in the brain. Despite extensive research on the amyloid-based mechanism of AD pathogenesis, the underlying cause of AD remains poorly understood. No disease-modifying therapies currently exist, and numerous clinical trials have failed to demonstrate any benefits. The recent discovery that the amyloid-β peptide has antimicrobial activities supports the possibility of an infectious aetiology of AD and suggests that amyloid-β plaque formation might be induced by infection. AD patients have a weakened blood-brain barrier and immune system and are thus at elevated risk of microbial infections. Such infections can cause chronic neuroinflammation, production of the antimicrobial amyloid-β peptide, and neurodegeneration. Various pathogens, including viruses, bacteria, fungi, and parasites have been associated with AD. Most research in this area has focused on individual pathogens, with herpesviruses and periodontal bacteria being most frequently implicated. The purpose of this review is to highlight the potential role of multi-pathogen infections in AD. Recognition of the potential coexistence of multiple pathogens and biofilms in AD's aetiology may stimulate the development of novel approaches to its diagnosis and treatment. Multiple diagnostic tests could be applied simultaneously to detect major pathogens, followed by anti-microbial treatment using antiviral, antibacterial, antifungal, and anti-biofilm agents.

Dehydrodiisoeugenol (DEH), a novel lignan component extracted from the Nutmeg seeds, displays noticeable anti-inflammatory and anti-allergic effects in digestive system diseases. However, the mechanism of its anti-cancer activity in gastrointestinal cancer is still to be investigated. Here, the anti-cancer effect of DEH to human colorectal cancer and its underlying mechanism were evaluated. The DEH treatment arrests the cell cycle of colorectal cancer cells at G1/S phase, which leading to a significant cell growth inhibition. Moreover, it can induce strong cellular autophagy and the autophagy would be inhibited through autophagic inhibitors with reducing EDH-induced inhibition of cell growth in colorectal cancer cells. Further studies indicated that DEH can also induce endoplasmic reticulum (ER) stress, and could subsequently stimulating autophagy through activating PERK/eIF2α and IRE1α/XBP-1s/CHOP pathways. Knockdown of PERK or IRE1α can significantly decrease the DEH-induced autophagy and retrieve cell viability in cells treated with DEH. What’s more, DEH exhibits significant anti-cancer activities through CDX- and PDX-model as well. Taken together, our studies strongly suggest that DEH might be a potential anti-cancer agent against colorectal cancer via activating ER stress-induced autophagy inhibition.

Propolis was widely used in health preservation and disease healing, it contains many ingredients. The previous study had been revealed that the propolis has a wide range of efficacy, such as antiviral, immune enhancement, anti-inflammatory and so on, but its antiviral components and underlying mechanism of action remain unknown. In this study, we investigated the chemical composition, and anti-PPV and immunological enhancement of Propolis Flavonoid(PF). Chemical composition of PF was distinguished by UPLC-Q/TOF-MS/MS analysis.The presence and characterized of 26 major components was distinguished in negative ionization modes.To evaluate the effects of PF used as adjuvant on the immune response porcine parvovirus (PPV). Thirty Landrace-Yorkshire hybrid sows were randomly assigned to 3 groups, and the sows in adjuvant groups were intramuscular injected PPV vaccine with 2.0 mL PF adjuvant (PA), oilemulsion adjuvant (OA), respectively. After that, serum hemagglutination inhibition antibody titers, IgM and IgG subclasses, eripheral lymphocyte proliferation activity, and concentrations of cytokines were measured. Results indicated an enhancing effect of PA on IgM, IL-2, IL-4, IFN-γ and the IgG subclass responses. These findings suggested that PA could significantly enhance the immune responses. Furthermore, we screened the chemical components the effective of anti-PPV, Ferulic acid have an excellently anti-PPV effective.

The increasing detection of infections of Trypanosoma cruzi, the etiological agent of Chagas disease, in non-endemic regions beyond Latin America has risen to be a major public health issue. With an impact in the millions of people, current treatments rely on antiquated drugs that produce severe side effects and are considered nearly ineffective for the chronic phase. The minimal progress in the development of new drugs highlights the need for advances in basic research on crucial biochemical pathways in T. cruzi to identify new targets. Here, we report on the T. cruzi presenilin-like transmembrane aspartyl enzyme, a protease of the aspartic class in a unique phylogenetic subgroup with T. vivax separate from protozoans. Computational analyses suggests it contains 9 transmembrane domains and an active site with the characteristic PALP motif of the A22 family. Multiple linear B-cell epitopes were identified by SPOT synthesis analysis with Chagasic patient sera. Two were chosen to generate rabbit antisera, whose signal was primarily localized to the flagellar pocket, intracellular vesicles and endoplasmic reticulum in parasites by whole cell immunofluorescence. The results suggest that the parasitic presenilin-like enzyme could have a role in the secretory pathway and serve as a biomarker for infections.

Previous research has shown that propolis has immunomodulatory activity. Extracts from two UK propolis samples were assessed for their anti-inflammatory activities by investigating their ability to alter the production of the cytokines tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6 and IL-10 from mouse bone marrow derived macrophages co-stimulated with lipopolysaccharide (LPS). The propolis extracts suppressed secretion of IL-1β and IL-6 with less effect on TNFα. In addition, propolis reduced the levels of nitric oxide formed by LPS-stimulated macrophages. Metabolomic profiling was carried out by liquid chromatography (LC) coupled with mass spectrometry (MS) on a ZIC-pHILIC column. LPS increased the levels of intermediates involved in nitric oxide biosynthesis; propolis lowered many of these. Also, LPS produced an increase in itaconate and citrate and propolis treatment increased itaconate still further while greatly reducing citrate levels. Moreover, LPS treatment increased levels of GSH and intermediates in its biosynthesis while propolis treatment boosted these still further. In addition, propolis treatment greatly increased levels of UDP-sugar conjugates. Overall, the results showed that propolis extracts exert an anti-inflammatory effect by inhibition of pro-inflammatory cytokines and by metabolic reprogramming of LPS activity in macrophages.

Neurokinin-1 receptor (NK-1R) antagonists exert an antitumor action, are safe and do not cause serious side-effects. These antagonists (via the NK-1R) exerted multiple actions against cancer: antiproliferative and anti-Warburg effects, apoptosis, anti-angiogenic and antimetastatic. These multiple effects have been shown in a broad-spectrum of cancers. The drug aprepitant (an NK-1R antagonist) is currently used in clinical practice as antiemetic. In in vivo and in vitro studies, aprepitant also showed the aforementioned multiple antitumor actions against many types of cancer. A successful combination therapy (aprepitant and radiotherapy) has recently been reported in a patient suffering from lung carcinoma: the tumor mass disappeared and side-effects were not observed. Aprepitant could be considered as an intelligent bullet against cancer. The administration of aprepitant in cancer patients to prevent recurrence and metastasis after surgical procedures, thrombosis and thromboembolism is discussed as well as the possible link, through the SP/NK-1R system, between cancer and depression. Our main aim is to review the multiple antitumor actions exerted by aprepitant and the use of this drug is suggested in cancer patients. Altogether, the data support the reprofiling of aprepitant for a new therapeutic use as an antitumor agent.

Vimentin is an intermediate filament protein that plays key roles in integration of cytoskeletal functions, and therefore in basic cellular processes such as cell division and migration. Consequently, vimentin has complex implications in pathophysiology. Vimentin is required for a proper immune response, but it can also act as an autoantigen in autoimmune diseases or as a damage signal. Although vimentin is a predominantly cytoplasmic protein, it can also appear at extracellular locations, either in a secreted form or at the surface of numerous cell types, often in relation to cell activation, inflammation, injury or senescence. Cell surface targeting of vimentin appears to associate with the occurrence of certain posttranslational modifications, such as phosphorylation and/or oxidative damage. At the cell surface, vimentin can act as a receptor for bacterial and viral pathogens. Indeed, vimentin has been shown to play important roles in virus attachment and entry of severe acute respiratory syndrome-related coronavirus (SARS-CoV), dengue and encephalitis viruses, among others. Moreover, the presence of vimentin in specific virus-targeted cells and its induction by proinflammatory cytokines and tissue damage contribute to its implication in viral infection. Here, we recapitulate some of the pathophysiological implications of vimentin, including the involvement of cell surface vimentin in interaction with pathogens, with a special focus on its role as a cellular receptor or co-receptor for viruses. In addition, we provide a perspective on approaches to target vimentin, including antibodies or chemical agents that could modulate these interactions to potentially interfere with viral pathogenesis, which could be useful when multi-target antiviral strategies are needed .

Our previous studies demonstrated that quercetin (Q) could be ingested and metabolized by macrophages and exerted prophylactic immuno-stimulatory activity and therapeutic anti-inflammatory effects on lipopolysaccharide (LPS)-treated macrophages ex vivo. To further clarify its possible anti-inflammatory mechanism, Q was selected to treat mouse peritoneal macrophages that obtained from female BALB/c mice exposed to LPS i.p. for 12 h. Relative gene expression of pro-/anti-inflammatory (TNF-α/IL-10) cytokines and components of inflammation-related intracellular signaling pathways (TLR2, TLR4, NF-κB, JAK2 and STAT3) was analyzed using two-step reverse transcription (RT) and real-time quantitative polymerase chain reaction (qPCR). STAT3 protein phosphorylation was determined using an in-cell ELISA method. As a result, Q and its metabolite quercetin-3-O-β-D-glucuronide (Q3G) decreased TNF-α gene expression amounts and ratios of pro-/anti-inflammatory (TNF-α/IL-10) cytokine gene expressions, but increased IL-10 gene expression amounts in activated inflammatory macrophages, supporting a substantial anti-inflammatory potential of Q and Q3G treatments. However, Q3G had lower effects than those of Q. Importantly, Q inhibited TLR2 gene expression and phosphorylation of STAT3 protein in the inflamed cells. Our results are the first report to suggest that Q inhibits LPS-induced inflammation ex vivo through suppressing TLR2 gene expression and STAT3 protein phosphorylation in activated inflammatory macrophages. Q has potential to further apply for treating inflammation-associated diseases.

Red djulis (Chenopodium formosanum) is a native cereal plant in Taiwan; it contains abundant polyphenols, betalian and dietary fiber. The appearance of red djulis is bright red. Therefore, it is also called the “ruby of cereals”. The antioxidative activity of red djulis extract is well-understood. However, the antiaging function still remains unclear. This study examined the potential of red djulis extract for enhancing collagen secretion and preventing cutaneous aging using red djulis extracts. The red djulis extracts are comprised of an abundant active component that can effectively enhance the ability of collagen secretion of dermal fibroblasts, prevent the glycation of collagen and resist the damage of ultraviolet light exposure. After fibroblast treatment with red djulis extracts, TGM1, KRT1, KRT10 and SOD2 genes were up-regulated significantly by 2.3, 4.3, 4.4 and 27.3 times, respectively, compared to those of the control group. Additionally, it can increase COL1A2 gene expression by 43% and decrease MMP9 gene expression 33%. Therefore, it was demonstrated that red djulis extracts affect gene expressions related to the skin barrier, antioxidation and collagen. Moreover, we found positive effects on skin barrier integrity, endogenous antioxidant activity and skin collagen-preservation. The preparation of the red djulis extracts is environmental friendly and can promote the economic value of Chenopodium formosanum; thus, the proposed extract is suitable for applications in the development of food products, especially beverages, skin care and cosmetic products.

Silybum marianum (L.) Gaertn. (aka milk thistle) constitute the almost exclusive source of silymarin, a mixture of different flavonolignans, and is thus considered as a unique model for their extraction. The present research deals with ultrasound-assisted extraction (UAE) of S. marianum flavonolignans and their quantification using LC system. The optimal conditions for UAE were: aqueous EtOH 54.5% (v/v) as solvent, applying an ultrasound frequency of 36.6 kHz during an extraction time of 60 min at 45°C with a liquid to solid ratio of 25:1 ml/g DW. Following optimization, the extraction method was validated according to international standards of the association of analytical communities (AOAC) in order to ensure its precision and accuracy for the quantitation of the individual silymarin components. The efficiency of UAE was compared with maceration protocol of the same duration. The optimized and validated conditions allowed highest extraction yields of flavonolignans in comparison to maceration. The antioxidant capacity of the extracts was confirmed by the CUPRAC assays and inhibition of advanced glycation end products. The skin anti-aging action was also confirmed toward the strong in vitro inhibition capacity of the obtained extract against collagenase and elastase enzymes. The procedure presented here allows a green efficient extraction and quantification of the main flavonolignans from the fruits of S. marianum with attractive antioxidant and anti-aging activities for future cosmetic applications.

Extensive phytochemical and chromatographic analysis of different root fractions of Jatropha pelargoniifolia Courb. (Euphorbiaceae) resulted in the isolation and identification of 22 distinct secondary metabolite compounds. Two new compounds, 6-hydroxy-8-methoxycoumarin-7-O-β-D-glycopyranoside and (3-(2-(methylamino) ethyl)-1H-indol-2-yl) methanol, were isolated and identified for the first time from a natural source. In addition, other known compounds, such as hovetricoside C and N-methyltryptamine were isolated from Euphorbiaceae, and hordenine, N-methyltyramine, their salts, cynaroside and linarin were identified in Jatropha spp. for the first time. Some isolated metabolites, such as β-sitosterol, β-sitosterol glucoside, curcusons D and C, naringenin, apigenin, cleomiscosins B and A, spruceanol, propacin, jatrophadiketone, and uracil were previously identified in various Jatropha species. The structures of the isolated compounds were determined using different spectroscopic techniques. The anti-inflammatory, antinociceptive, antipyretic, and antioxidant activities were evaluated for some adequately available isolated compounds. Compounds showed significant antinociceptive activity compared with the standard analgesic drug indomethacin. The edema size was significantly reduced (p< 0.05–0.001) in the animals treated with low doses (5 and 10 mg/kg) of the isolated compounds compared with those treated with a high dose (100 mg/kg) of standard anti-inflammatory drug (phenylbutazone). Furthermore, all tested compounds showed a significant (p< 0.05–0.001) reduction in the rectal temperature of hyper-thermic mice.

Zn–Ni plating is indispensable in various industries because of its high corrosion resistance. However, Ni has been reported to trigger allergies; thus, an alternative Ni-free plating is desired. Zn–Fe plating is considered to be a promising candidate, albeit its corrosion resistance still needs to be improved. The corrosion resistance of Zn–Fe plating is expected to increase by the addition of Mo as the third alloying element as it is more noble than Zn and Fe. In this study, Zn–Fe–Mo plating with a corrosion resistance nearly equivalent to that of the Zn–Ni plating was fabricated. Zn–Fe–Mo plating was electrically deposited from continuously agitated plating baths prepared by mixing ZnSO₄, FeSO₄, Na₂MoO₄, Na₃C₆H₅O₇, and Na₂SO₄ using Fe or Ni plates as the substrate. The surface morphology, composition, crystal phase, and electronic state of Mo of the platings were investigated by SEM-EDS, XRD, and XPS. The anti-corrosion performance was evaluated by Tafel extrapolation method. Formation of plating comprising a Mo containing alloy phase was found to be crucial for improving corrosion resistance. The Zn–Fe–Mo plating demonstrates promise for replacing anti-corrosion Zn–Ni platings.

This study aims to address the inefficiencies and time-consuming nature of traditional hot-air anti-icing system designs by introducing reduced order models (ROM) and machine learning techniques to predict anti-icing surface temperature distributions. This study compares several classic neural networks, ultimately proposing two models: POD-AlexNet and multi-CNNs with GRU (MCG). Design variables of the hot-air anti-icing cavity are used as inputs, and the corresponding surface temperature distribution data serve as outputs. The performance of these models is evaluated on the test set. The POD-AlexNet model achieves a mean prediction accuracy of over 95%, while the MCG model reaches 96.97%. Both models significantly outperform traditional numerical simulation methods, delivering faster predictions. The proposed models achieve fast prediction of anti-icing surface temperature distribution while ensuring acceptable prediction accuracy. These models greatly enhance the prediction efficiency over existing numerical simulation approaches, contributing to the design of aircraft hot-air anti-icing systems based on optimization methods such as genetic algorithms.

The skin, as the body's largest organ, is vital for protecting against environmental stressors, regulating temperature, and preventing water loss. Maintaining a healthy skin barrier is essential for overall skin health and function. We examined the potential of a mixture of five traditional Korean herbal extracts—Cimicifuga racemosa, Paeonia lactiflora, Phellodendron amurense, Rheum rhaponticum, and Scutellaria baicalensis— referred to as herbal medicine composite 5 (HRMC5) for enhancing skin health. High-performance liquid chromatography identified 14 bioactive compounds, including flavonoids, phenolic acids, anthraquinones, and alkaloids, known for their antioxidant, anti-inflammatory, and antimicrobial effects. The extract showed concentration-dependent effects on cell viability and provided UV protection at 6.25 g/L. It also significantly promoted wound healing, similar to the efficacy of epidermal growth factor. Furthermore, the mixture exhibited anti-inflammatory activity by downregulating Cox2 expression and upregulated key skin barrier proteins, including Involucrin, Claudin 1, and Collagen Type 1. These findings highlight the potential of this herbal mixture for addressing skin barrier dysfunction, inflammation, and facial redness, supporting its use in developing natural skincare products. Future studies should investigate the mechanisms behind these effects and assess its clinical applications.

Six solvent fractions isolated from flower bud and leaf ethanolic extracts of Cleistocalyx operculatus were analyzed for their phytochemical contents including phenolics, flavonoids, saponins, tannins, and alkaloids. Antioxidant activities were measured using the ABTS, DPPH, and FRAP assays. The results showed that flower bud aqueous fraction (BAF) and leaf aqueous fraction (LAF) rich in phenolic content (768.18 and 490.74 mg GAE/g dry extract, respectively) exhibited significantly higher antioxidant activities than other fractions. Flower bud hexane fraction (BHF) had remarkably high flavonoid and saponin contents (134.77 mg QE/g and 153.33 mg OA/g dry extract, respectively), followed by that of leaf hexane fraction (LHF) (76.54 mg QE/g and 88.25 mg OA/g dry extract, respectively). BHF and LHF were found to have extremely high antibacterial activity against two H. pylori strains ATCC 51932 and 43504 (MICs of 125 µg/ml). Interestingly, DMC (2’,4’-Dihydroxy-6’-methoxy-3’,5’-dimethylchalcone) isolated from BHF displayed greater antibacterial activity against the bacterial strains (MICs of 25–50 µg/ml) than those of the fractions. In addition, DMC presented potent inhibitory effects on H. pylori-urease (IC50 of 3.2 µg/ml) and α-amylase (IC50 of 83.80 µg/ml), but no inhibition against α-glucosidase. It was also demonstrated that DMC showed its pronounced inhibitory effects on urease activity and biofilm formation of H. pylori, and could increase the membrane permeability of the bacterial cells. Scanning electron micrographs depict that BHF and DMC had strong effects on the cell shape and significantly induced distortion and damage of the cell membrane. The fractions and DMC showed no significant toxicity to four tested human cell lines. Efforts to reduce antibiotic use indicate the need for further researches of the flower buds and DMC as potential products to prevent or treat gastric H. pylori infections.

Cestodes are etiological agents of neglected diseases such as echinococcosis and cysticercosis, which are major public health problems. Antiparasitic treatment relies on a small number of approved drugs, which are often only partially effective, poorly tolerated and require prolonged administration. Thus, the discovery of novel potential treatments is critical. The Stevia genus (Asteraceae) includes species that are associated with medicinal uses and are considered a source of bioactive compounds. Here, we analyzed four South American Stevia species that have previously demonstrated antiprotozoal properties. The effect of dichloromethane extracts of these species was determined by motility assays on Mesocestoides vogae, a laboratory model of cestodes. Stevia alpina showed the highest anthelmintic potential followed by S. maimarensis and S. multiaristata, while S. aristata was the least active. The sesquiterpene lactones estafietin and eupatoriopicrin were purified from S. alpina and S. maimarensis, respectively. Estafietin showed cestocidal activity, inhibiting parasite viability in a dose-dependent manner, even from the first day of incubation. Consistent with the motility effects, the extract of S. alpina and estafietin induced major alterations on the morphology of the parasite. The results of this report show that Stevia species represent a source of new molecules with potential for the treatment of neglected tropical diseases caused by cestodes.

Drp1 is considered the master regulator of mitochondrial fission and affects the proper segregation during mitosis. Here, we identified two clusters on mitochondria, including Drp1-Ser-616/Mff/Mid51 and-Drp1-Ser637/Fis1/Mid49 for midzone fission (division) and peripheral fission signatures, respectively. This study revealed that phospho-Drp1-Ser637 is involved in mitigating mitochondrial oxidative stress, resolving a long-standing localization issue. Additionally, we demonstrated that Mid49 and Mid51 exhibit distinct functions in recruiting Drp1 for mitochondrial fission. It also confirmed the essential role of the Fis1 and Mid49 adaptors contributed into mitochondrial fission within the phospho-Drp1-Ser637/Fis1/Mid49 cluster during M-phase. Moreover, it suggested that there is mutual exclusivity between two clusters of phospho-Drp1 with four adaptors on mitochondria, as well as varied responses to specific anti-cancer drugs during mitotic arrest. Remarkably, the upregulation of the spindle assembly checkpoint (SAC) was also observed, ensuring the prolongation of M-phase with the formation of multipolar spindles. Collectively, the phospho-Drp1-637/Fis1/Mid49 cluster may not only function in peripheral fission (mitophagy) but also serve as a key SAC coordinator for the regulation of spindle assembly during mitotic arrest. These findings appear to be mutually exclusive of phospho-Drp1 with four adaptors on mitochondria and vary in response to specific anti-cancer drugs.

Autism spectrum disorder (ASD) is a neurodevelopmental condition marked by re-stricted and repetitive behaviors as well as difficulties with social interaction. Nu-merous studies have revealed aberrant lipid mediators and autoimmunity as a recog-nized etiological cause of ASD that is amenable to therapeutic intervention. Methods: In this study, the relationship between the relative cyclooxygenase-2, / pros-taglandin E2 ratio (COX-2/PGE2) as lipid mediator marker and anti-nucleosome au-toantibodies as autoimmunity marker of ASD was investigated using multiple regres-sion and combined receiver operating characteristic (ROC) curve analyses. The study also sought to identify the linear combination of these variables that optimizes the partial area under the ROC curves. There were forty ASD children and forty age- and sex-matched controls included in the current study. Results: Using combined ROC curve analysis, a notable increase in the area under the curve was seen. Additionally, it was reported that the combined markers had improved specificity and sensitivity. Conclusions: This study shows that using a ROC curve analysis to measure the predictive value of specific biomarkers linked to lipid metabolism and autoimmunity in children with ASD should improve our understanding of the etiological mechanism of ASD and how it is related to metabolism. Early diagnosis and intervention may be facilitated by this knowledge.

Synthetic Aperture Radar (SAR) ship target detection has been extensively researched. However, most methods use the same dataset division for both training and validation. In practical applications, it is often necessary to quickly adapt to new loads, new modes, and new data to detect targets effectively. This presents a cross-domain detection problem that requires further study. This paper proposes a method for detecting SAR ships in complex backgrounds using fusion tensor and cross-domain adversarial learning. The method is designed to address the cross-domain detection problem of SAR ships with large differences between the training and test sets. Specifically, it can be used for the cross-domain detection task from the fully-polarised medium-resolution ship dataset (source domain) to the high-resolution single-polarised dataset (target domain). This method proposes a Channel Fusion Module (CFM) based on the YOLOV5s model. The CFM utilises the correlation between polarised channel images during training to enrich the feature information of single-polarised images extracted by the model during inference. The article proposes a module called Cross-Domain Adversarial Learning Module (CALM) to reduce overfitting and achieve adaptation between domains. Additionally, the paper introduces the Anti-Interference Head (AIH) which decouples the detection head to reduce the conflict of classification and localization problems. This improves the anti-interference and generalization ability in complex backgrounds. This paper conducts cross-domain experiments using the constructed medium-resolution SAR full polarization dataset (SFPD) as the source domain and the high-resolution single-polarised ship detection dataset (HRSID) as the target domain. Compared to the best-performing YOLOV8s model among typical mainstream models, this model improves Precision by 4.9%, Recall by 3.3%, AP by 2.4%, and F1 by 3.9%. This verifies the effectiveness of the method and provides a useful reference for improving cross-domain learning and model generalization capability in the field of target detection.

Chamazulene (CA) is an intensely blue molecule with a wealth of biological properties. In cosmetics chamazulene is exploited as a natural coloring and soothing agent. CA is unstable and tends to spontaneous degradation accelerated by light. We studied the photodegradation of CA upon controlled exposure to UVB-UVA irradiation by multi-ple techniques, including GC-MS, UHPLC-PDA-ESI-MS/MS and by direct infusion in ESI-MSn, which were matched to in silico mass spectral simulations to identify degra-dation products. Seven byproducts formed upon UVA exposure for 3 h at 70mW/cm2 (blue-to-green color change) were identified, including CA dimers and CA benzenoid which were not found on extended 6 h irradiation (green-to-yellow fading). Photosta-bility tests with reduced irradiance conducted in various solvents in the pres-ence/absence of air indicated highest degradation in acetonitrile in the presence of ox-ygen, suggesting a photo-oxidative mechanism. Testing in the presence of antioxidants (tocopherol, ascorbyl palmitate, hydroxytyrosol, bakuchiol, γ-terpinene, TEMPO and their combinations) indicated highest protection by tocopherol and TEMPO. Sun-screens ethylhexyl methoxycinnamate and particularly Tinosorb® S (but not octo-crylene) showed good CA photoprotection. Thermal stability tests indicated no degra-dation of CA in acetonitrile at 50°C in the dark for 50 days; however, accelerated deg-radation occurred in the presence of ascrorbyl palmitate.

Despite notable advancements in immunotherapy in the past decades, allogeneic hematopoietic stem cell transplantation (allo-HCT) remains a promising, potentially curative treatment modality. Only a limited number of studies has performed a direct comparison of two prevalent rabbit anti-thymocyte globulin (r-ATG) formulations — specifically, Thymoglobuline (ATG-T, formerly Genzyme) and Grafalon (ATG-G, formerly Fresenius). The primary objective of our retrospective analysis was to compare the outcomes of adult patients undergoing matched or mismatched unrelated donor (MUD/MMUD) allo-HCT, with a graft-versus-host disease (GvHD) prophylaxis based on either ATG-T or ATG-G. A total of 87 patients undergone allo-HCT between 2012 and 2022 were included. We observed no significant differences between ATG-T and ATG-G concerning the occurrence of acute graft-versus-host disease (aGvHD), regardless of its severity. Conversely, chronic graft-versus-host disease (cGvHD) occurred less frequently in the ATG-T group compared to ATG-G (7.5% vs. 38.3%, p=0.001). Patients treated with ATG-T manifested a higher incidence of cytomegalovirus (CMV) reactivations (70% vs. 31.9%, p&lt;0.001), with a shorter time between transplant and CMV (&lt;61 days, 77.8% vs. 33.3%, p=0.008) and a higher median CMV copy number (1000 vs. 0, p=0.004). Notably, despite a higher occurrence of CMV reactivations in the ATG-T cohort, most patients were asymptomatic compared to ATG-G (85.7% vs. 43.8%, p=0.005). Finally, we observed no significant differences in terms of 5-year overall survival (OS) and 3-year probability of relapse while comparing ATG-T and ATG-G (32.0% vs 40.3%, p=0.423; 63.9% vs 55.7%, p=0.438, respectively).

The review explores the therapeutic potential of mangrove plants as sources of bioactive compounds, particularly focusing on their anti-inflammatory properties. Mangroves, found in tropical and sub-tropical tidal coasts, exhibit unique ecological and biological activities. The review compiles and examines 136 research findings published between 1982 and 2018, with 41 studies specifically addressing the anti-inflammatory properties of mangroves in Indian coastal regions, including the Andaman and Nicobar Islands. It summarizes the chemical structures, molecular weights, formulas, solvents, and biological activities of these mangroves, as reported by various researchers over time. The data underscore the significant potential of tropical Indian mangroves in anti-inflammatory applications. However, a notable research gap exists regarding the extraction of bioactive compounds from mangrove species in the Andaman and Nicobar Islands compared to other regions such as Gujarat, Maharashtra, Goa, Karnataka, Kerala, Tamil Nadu, Andhra Pradesh, Odisha, West Bengal, and Puducherry. Overall, the compilation provides valuable insights into mangrove-based studies for drug discovery research, emphasizing the need for further exploration and exploitation of these natural resources.

We study Einstein's gravity coupled to nonlinear electrodynamics with two parameters in Anti-de Sitter spacetime. Magnetically charged black holes in an extended phase space is investigated. We obtain the mass and metric functions, their asymptotic and corrections to the Reissner--Nordstr\"{o}m metric function when the cosmological constant vanishes. The first law of black hole thermodynamics in extended phase space is formulated and the magnetic potential and the thermodynamic conjugate to the coupling are obtained. We proved the generalized Smarr relation. The heat capacity and the Gibbs free energy are computed and phase transitions are studied. It was shown that the electric field of charged objects at the origin and electrostatic self-energy are finite within the nonlinear electrodynamics proposed.

The role of inflammation in the pathophysiology of acute myocardial infarction (AMI) is well established. Recognizing inflammation's pivotal role in AMI, this manuscript systematically traces historical studies, spanning from early attempts to the present landscape. Several anti-inflammatory trials targeting inflammation in post-AMI have been performed. The review includes key trials, examining their designs, patient demographics, and primary outcomes. Efficacy and challenges are analyzed, shedding light on the translational implications of trial outcomes. The article also discusses emerging trends, ongoing research, and potential future directions in the field. Practical applications and implications for clinical practice are considered, providing a holistic view of the evolving landscape of anti-inflammatory interventions in the context of AMI.

Plant-based proteins, like those derived from hemp and rapeseed can significantly contribute to a balanced diet and human daily nutritional requirements by providing essential nutrients such as protein, fiber, vitamins, minerals, and antioxidants. According to numerous recent research papers the consumption of plant-based proteins has been associated with numerous health benefits, including reduced risk of chronic diseases such as heart disease, diabetes, and certain cancers. Plant-based diets are often lower in saturated fat and cholesterol and higher in fiber and phytonutrients, which can support overall health and well-being. Present research investigates the nutritional attributes, functional properties, and potential food applications of hemp and rapeseed protein for a potential use in new food product development, with a certain focus on identifying anti-nutritional factors and bioactive compounds. Through comprehensive analysis, anti-nutritional factors and bioactive compounds were elucidated, shedding light on their impact on protein quality and digestibility. The study also delves into the functional properties of hemp and rapeseed protein, unveiling their versatility in various food applications. Insights from this research contribute to a deeper understanding of the nutritional value and functional potential of hemp and rapeseed protein, paving the way for their further utilization in innovative food products with enhanced nutritional value and notable health benefits.

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, stands as a significant public health challenge in endemic regions of the Americas. Current treatment options, limited and associated with adverse effects, underscore the need for novel therapeutic approaches. This systematic review comprehensively examines existing research on natural products as potential agents against Chagas disease. Employing a systematic search strategy across diverse databases, studies meeting predefined inclusion criteria were assessed for methodological quality and relevance. The synthesis of findings reveals a spectrum of natural products showcasing promising anti-Trypanosoma cruzi properties. The review discusses the limitations of current evidence, highlights gaps in knowledge, and proposes avenues for future research. By elucidating the landscape of natural products in Chagas disease treatment, this review contributes to the ongoing pursuit of innovative and accessible therapeutic strategies.

(1) Background: Hepatitis C virus (HCV) screening mostly uses a one-assay anti-HCV testing approach, which has a higher probability of false-positive results in populations with low HCV prevalence. (2) Methods: In this investigation, 17,926 participants, were screened for HCV, and the reactives were tested using a two-assay anti-HCV approach: Elecsys ElectroChemiLuminescence (ECL) and a ChemiLuminescence ImmunoAssay (CLIA), respectively. A recombinant immunoblot assay (RIBA) was performed to confirm anti-HCV positivity. Statistical analysis was performed. (3) Results: A total of 350 specimens resulted reactive in the ECL screening, of which CLIA retesting showed that 292 (83.4%) were anti-HCV reactive (283 positive, 9 indeterminate, none negative by RIBA), but 58 (16.6%) were not anti-HCV reactive (15 positive, 12 indeterminate, 31 negative by RIBA). The two-assay strategy significantly improved the positive predictive value (PPV: 95.00%) with χ2: 7.59(p&lt;0.01) then the PPV assessed by one assay (PPV: 90.6%) with χ2: 34.51 (p&lt; 0.001). The ROC curve defined a sensibility and specificity for the dual approach of: 99.66% and 100.00%. (4) Conclusions: Compared with a one-assay testing strategy, the two-assay testing strategy may significantly reduce false positives in anti-HCV testing and identify inactive HCV infection in low seroprevalence populations.

Consumer preference not only dictates what food is consumed but how that food is produced. Ingredients in livestock feed that are not antibiotics, not genetically modified, not of animal origin, and that are nutrient-like, tend to be more acceptable to consumers, retailers, and producers. Mono- and diglycerides (MDG) fit these criteria, are commonly used in food, and are generally recognized as safe. But beyond being emulsifiers and a source of energy, MDG are also known to have antimicrobial, immune and microbiome modulation, and angiogenic activity. MDG in broiler diets have been shown to impact a variety of immune-related functions such as regulation of circulating antibodies, as well as decreased gene expression or protein concentration of pro-inflammatory cytokines like TNF-α, IL-1β, IL-6, and IFN-γ. In addition, MDG can affect metabolic function and intestinal integrity. Results of this review show that MDG can serve as antimicrobial and growth-supporting alternatives for reducing poultry production losses, improving resource utilization, and meeting consumer demand for sustainably produced and safe animal protein.

In recent years, extensive research has delved into the pathophysiology of local reactions triggered by Bothrops snake venoms. Even though antivenom works well at reducing death and systemic effects, it is still not very effective in treating local reactions because the venom works so quickly, and antivenom cannot fix injuries that have already been triggered. This might be attributed to certain molecules amplifying the venom-induced innate response. While evidence suggests endogenous mediators at the venom site play a role in this envenomation, in Brazil, concurrent use of anti-inflammatories or other drugs associated with the antivenom remains uncommon. The aim of this study was to determine how various inflammatory mediators affected the leukocyte-endothelium interaction (LEI) following a B. jararaca bite. According to our findings, nitric oxide and cyclooxygenase pathway eicosanoids significantly contribute to alteration of LEI induced by B. jararaca venom. Conversely, lipoxygenase-mediated eicosanoids, histamine, or serotonin had minimal participation. Markedly, treatment with dexamethasone alongside antivenom mitigated alterations of LEI induced by the B. jararaca snake venom. The limited efficacy of the antivenom in managing Bothrops venom-induced local reactions emphasizes the critical need for supplementary treatments to enhance therapeutic outcomes.

Lodging poses a significant challenge to rice yield, prompting the need to identify elite alleles for lodging resistance traits to improve cultivated rice varieties. In this study, a natural population of 518 rice accessions was examined to identify elite alleles associated with plant height (PH), stem diameter (SD), stem anti-thrust (AT/S), and various internode lengths: (first (FirINL), second (SecINL), third (ThirINL), fourth (ForINL), and fifth (FifINL) internode lengths). 262 SSR markers linked to these traits were uncovered through association mapping in two environmental conditions. Phenotypic evaluations revealed striking differences among cultivars, and genetic diversity assessments showed polymorphisms across the accessions. Favorable alleles were identified for PH, SD, AT/S, and 1 to 5 internode lengths, with specific alleles displaying considerable effects. Noteworthy alleles include RM6811-160 bp on chromosome 6 (which reduces PH) and RM161-145 bp on chromosome 5 (which increases SD). The study identified a total of 42 novel QTLs. Specifically, seven QTLs were identified for PH, four for SD, five for AT/S, five for FirINL, six for SecINL, five for ThirINL, six for ForINL, and four for FifINL. QTLs qAT/S-2, qPH2.1, qForINL2.1, and qFifINL exhibited the most significant phenotypic variance (PVE) of 3.99% for the stem lodging trait. AT/S, PH, ForINL and FifINL had additive effects of 5.31 kPa, 5.42 cm, 4.27cm and 4.27cm, respectively, offering insights into eight distinct cross-combinations for enhancing each trait. This research suggests the potential for cross-breeding superior parents based on stacked alleles, promising improved rice cultivars with enhanced lodging resistance to meet market demands.

Is it possible that the addition of wild-growing flowers with anti-inflammatory applications can improve the antioxidant properties of rapeseed and multifloral honey? The study objective was a comparative analysis of two honey varieties enriched by flowers of six plant species, based on the content of the antioxidant capacity as well as total flavonoids and phenolic content. Experiments demonstrated that at each level of enrichment there was an improvement in antioxidant properties compared to honey of both varieties without additives, especially in the case of dried flowers. Primula veris L. and Pulmonaria officinalis L. improved the antioxidant properties and phenolic content most effectively in honey at all levels of enrichment. Rapeseed-type honey produces a better matrix for the incorporation of natural plant metabolites into honey. The content of biologically active substances in honey enriched with flowers gives hope for new applications of health-promoting substances contained in wild plants.

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.

We compared the functional and morphologic effects in the loading dose between patients with treatment-naïve neovascular age-related macular degeneration treated with either intravitreal aflibercept (IVA) or intravitreal faricimab (IVF) injection in clinical settings. This retrospective study included 30 eyes from 28 patients who started IVA treatment between June and September 2022 and 30 eyes from 29 patients who started IVF treatment between October 2022 and March 2023. The mean best corrected visual acuity (BCVA) significantly improved from pre-treatment after loading dose in the IVA group (from 0.46 ± 0.46 to 0.36 ± 0.37, p=0.0047) and not in the IVF group (from 0.46 ± 0.41 to 0.44 ± 0.45, p=0.60). The mean central retinal thickness (CRT) significantly improved in both groups. The proportion of eyes with residual exudative change was greater in the IVF group than in the IVA group at 2 months after the first treatment. (p=0.026) We further analyzed the patients who obtained complete resolution of exudative changes after the loading dose. The IVA group had a significant improvement in BCVA, whereas the IVF group did not p=0.0047 and 0.20, respectively) Although IVA and IVF significantly improved the CRT, the BCVA improved significantly in IVA group and not in IVF group.

Background: Vaccination is one of the most effective life-saving medical interventions, and the introduction of SARS-CoV-2 vaccines was intended to prevent the serious implications of COVID-19. The objectives of the study were: i) to observe the humoral immune response to BNT162b2 vaccine and SARS-CoV-2 infection (mainly breakthrough infections), ii) to demonstrate the persistence of anti-SARS-CoV-2 antibodies over time in relation to the number of received vaccine doses and the course of infection, and iii) to determine adverse effects after primary vaccine doses. Methods: To assess the humoral response, IgG and IgA anti-S1 antibodies were quantified by ELISA assays. In total, the tests were carried out seven times in almost two years. Results: We demonstrated strong immunogenicity (compared to levels before primary vaccination, 150- and 20-fold increases in IgG and IgA, respectively) of the BNT162b2 vaccine. Over time, we observed a systematic decline in antibody levels, which may have contributed to breakthrough infections. Although they caused seroconversion similar to the booster, antibody levels in such patients fell more rapidly than after re-vaccination. On the other hand, in individuals who did not receive booster(s) and who did not present breakthrough infection, anti-SARS-CoV-2 antibodies returned to pre-vaccination levels after 20 months. The most commonly recognized adverse effects were injection site redness and swelling. Conclusion: Vaccination is highly effective in preventing the most severe outcomes of COVID-19 and should be performed regardless of prior infection. Booster doses significantly enhance anti-SARS-CoV-2 antibody levels and, in contrast to those obtained by breakthrough infection, they remain longer.

Epigenetic modifications, mainly aberrant DNA methylation, have been shown to silence the ex-pression of genes involved in epigenetic diseases, including cancer suppression genes. Almost all conventional cancer therapeutic agents, such as the DNA hypomethylation drug, 5-aza-2-deoxycytidine, have insurmountable side effects. To investigate the role of ectoine in skin cell DNA methylation and cancer cell proliferation, comprehensive methylome sequence analysis, 5-methyl cytosine (5mC) analysis, proliferation and tumorigenicity assays, and DNA methyla-tion-related gene and marker analysis were performed. The results showed that ectoine hypo-methylation in skin cells, especially in the CpG island (CGIs) element and 5mC, was significantly reduced. Moreover, ectoine mildly inhibited skin cell proliferation, but did not induce tumorigenicity in HaCaT cells injected into athymic nude mice. HaCaT cells treated with ectoine for 24 weeks modulated the mRNA expression levels of Dnmt1, Dnmt3a, Dnmt3b, Dnmt3i, Hdac1, Hdac2, Kdm3a, Mettl3, Mettl14, Igf2, Snrpn, and Mest. Overall, ectoine, an excellent DNA protectant, mildly de-methylates DNA in skin cells, modulates the expression of methylation-related genes, and reduces cell proliferation. This evidence suggests that ectoine is a potential anti-aging agent that prevents DNA hypermethylation and subsequently activates cancer-suppressing genes.

The key objective of the experiment was to show the environmental based of copper nanoparticles which counters the growth of bacterial pathogens such as Pseudomonas aeruginosa, and Staphylococcus aureus. To begin with the experiments, root extract of Asparagus racemosus was used to synthesise Copper nanoparticles. To confirm the formation of Cu-NPs, it was subjected to characterization such as Ultra Violet analysis, X-ray Diffraction method, Fourier Transform Infrared Spectroscopy and Scanning electron microscope images. Later the antibacterial activity of Cu-NPs was studied by incorporating it into two bacterial pathogens (Pseudomonas aeruginosa and Staphylococcus aureus). The outcome displayed a satisfactory antibacterial activity against the bacterial pathogens by the biosynthesized copper nanoparticles. To boost up the enzyme inhibition property of the Cu NPs, Antioxidant and Antidiabetic assay were also performed. The biosynthesised Cu NPs displayed a satisfied result in Antifouling function. The result was used assessed with green algae bloom water.

Neovascular age-related macular degeneration (nAMD) leads to visual impairment if not treated timely. Intravitreal anti-VEGF drugs have revolutionized nAMD treatment in two decades. We evaluated visual outcomes of anti-VEGF treatment in nAMD. A real-life population-based cohort study. Data included parameters for age, sex, age at the diagnosis, laterality, chronicity, symptoms, visual outcomes, lens status, and history of intravitreal injections. A total of 1088 eyes (827 patients) with nAMD were included. Visual acuity was stable or improved in 984 eyes (90%) after an average 36±25 months follow-up. Bevacitzumab was the first-line drug in 1083 (99.5%) eyes. Vision improved ≥15 ETDRS letters in 377 (35%), > 5 ETDRS letters in 309 (28%) and was stable (±5 ETDRS letters) in 298 (27%) eyes after anti-VEGF treatment. The loss of 5-<15 ETDRS letters in 44 (4%) and ≥15 ETDRS letters in 60 (6%) eyes was noted. At the diagnosis of nAMD, 110 out of 827 patients (13%) fulfilled the criteria of visual impairment, whereas 179 patients (22%) were visually impaired after the follow-up. Improvement or stabilization in vision was noted in 90% of the anti-VEGF-treated eyes with nAMD. In addition, anti-VEGF agents are crucial in diminishing nAMD-related visual impairment.

The use of anti-microbial drugs and coccidiostats in poultry farming is widespread, with a significant proportion of these drugs being excreted and released into the environment. The residues of such drugs in poultry litter (PL) can result in the development of antibiotic-resistant bacteria. The impact of different biotic treatments (aerobic, anaerobic, and stacking) on broiler litter (BL) before use as animal feed has not been studied extensively, nor have the differences between antimicrobial-dependent and independent broiler farms been investigated. This study aimed to determine the resistant bacteria in BL used as ruminant feed before and after litter treatment. The results showed that the most resistant bacteria before BL treatment were Enterococcus species. The study also found that the quantity of amoxicillin-resistant Enterococcus detected in samples from antimicrobial-dependent farms was significantly higher than in those from antimicrobial-independent farms. Additionally, 14% of bacteria were multi-resistant to tetracycline, sulfafurazole, and erythromycin in antimicrobial-independent farm litters, significantly lower than those measured in antimicrobial-dependent broiler farm litter. This study highlights the importance of better understanding, regulating, managing, and using animal waste appropriately to reduce the number of antibiotic-resistant bacteria and minimize the use of antimicrobials that carry high risks for animals, humans, and the environment

The manifold actions of the pro-inflammatory and regenerative chemokine CXCL12/SDF-1α are executed through the canonical GProteinCoupledReceptor CXCR4, and the non-canonical ACKR3/CXCR7. Platelets express CXCR4, ACKR3/CXCR7, and are a vital source of CXCL12/SDF-1α themselves. In recent years, a regulatory impact of the CXCL12-CXCR4-CXCR7 axis on platelet biogenesis i.e. megakaryopoiesis, thrombotic and thrombo-inflammatory ac-tions have been revealed through experimental and clinical studies. Platelet surface expression of ACKR3/CXCR7 is significantly enhanced following myocardial infarction (MI) in acute coro-nary syndrome (ACS) patients, also associated with improved functional recovery and progno-sis. The therapeutic implications of ACKR3/CXCR7 in myocardial regeneration and improved recovery following an ischemic episode, are well documented. Cardiomyocytes, cardi-ac-fibroblasts, endothelial lining of the blood vessels perfusing the heart, besides infiltrating platelets and monocytes, all express ACKR3/CXCR7. This review recapitulates ligand induced differential trafficking of platelet CXCR4-ACKR3/CXCR7 affecting their surface availability, and in regulating thrombo-inflammatory platelet functions and survival through CXCR4 or ACKR3/CXCR7. It emphasizes the pro-thrombotic influence of CXCL12/SDF-1α exerted through CXCR4, as opposed to the anti-thrombotic impact of ACKR3/CXCR7. Offering an innovative translational perspective, this review also discusses the advantages and challenges of utilizing ACKR3/CXCR7 as a potential anti-thrombotic strategy in platelet associated cardiovascular dis-orders, particularly in coronary artery disease (CAD) patients post-MI.

Non-genuine medical products, including diagnostic devices, have become a lucrative business for fraudsters, causing significant damage to revenues and reputation of companies, as well as posing a significant risk to the health of people and societies. Along a “digital twin” representing centrifugal microfluidic flow control on exemplary “Lab-on-a-Disc” (LoaD) systems, a novel, two-pronged strategy to safeguard miniaturized point-of-care devices by means of secret features and manufacturing challenges is outlined; such “hardware encryption” is flexibly programmed for each chip during production, and deciphered from a secure, local or online database at the time of use. This way, unlicensed copying may be efficiently deterred by an unfavourable economy-of-scale, even in absence of legal prosecution.

Utility of vaccine campaigns to control coronavirus disease 2019 (COVID-19) is not merely dependent on vaccine efficacy and safety. Vaccine acceptance among the general public and the healthcare workers, appears to have a decisive role for successful control of the pandemic. The aim of this review was to provide an up-to-date assessment of COVID-19 vaccination acceptance rates worldwide. A systematic search of the peer-reviewed English survey literature indexed in PubMed was done on December 25, 2020. Results from 30 studies, met the inclusion criteria and formed the basis for final COVID-19 vaccine acceptance estimates. Results of an additional recent survey from Jordan and Kuwait was considered in this review as well. Survey studies on COVID-19 vaccine acceptance rates were found from 33 different countries. Among adults representing the general public, the highest COVID-19 vaccine acceptance rates were found in Ecuador (97.0%), Malaysia (94.3%), Indonesia (93.3%) and China (91.3%). On the other hand, the lowest COVID-19 vaccine acceptance rates were found in Kuwait (23.6%), Jordan (28.4%), Italy (53.7), Russia (54.9%), Poland (56.3%), US (56.9%), and France (58.9%). Only eight surveys among healthcare workers (doctors, nurses) were found, with vaccine acceptance rates ranging from 27.7% in the Democratic Republic of the Congo to 78.1% in Israel. In a majority of survey studies among the general public (62%), the acceptance of COVID-19 vaccination showed a level of ≥ 70%. Low rates of COVID-19 vaccine acceptance were reported in the Middle East, Russia, Africa and several European countries. This could represent a major problem in the global efforts that aim to control the current COVID-19 pandemic. More studies are recommended to address the scope of COVID-19 vaccine hesitancy. Such studies are particularly needed in the Middle East Africa, Eastern Europe, Central Asia, Middle and Latin America.

Evolutionary medicine argues that disease can arise because modern conditions do not match those in which we evolved. For example, a decline in exposure to commensal microbes and gastrointestinal helminths in developed countries has been linked to increased prevalence of allergic and autoimmune inflammatory disorders (the hygiene hypothesis). Accordingly, microbial and helminthic probiotic therapies have been explored as Darwinian treatments for these disorders. A further possibility is that loss of old friend commensals also increases the sterile, aging-associated inflammation known as inflammaging, that contributes to a range of age-related diseases, including cardiovascular disease, dementia and cancer. Interestingly, Crowe et al. (2020) recently reported that treatment with a secreted glycoprotein from a parasitic nematode can protect against murine aging by induction of anti-inflammatory mechanisms. Here, we explore the hypothesis that restorative helminth therapy would have anti-inflammaging effects. Could worm infections provide broad-spectrum protection against age-related disease?

Repeated air pollution exposure is one of the major threats to skin health. Air pollution causes skin damage and accelerates skin ageing mainly through oxidative stress mechanisms. Since it is difficult to minimize skin exposure from air pollutants, especially in urban areas, strategies to protect the skin are needed. On the other hand, plant phenolic compounds have been found to be effective in attenuating cellular oxidative stress and inflammation induced by different air pollutants. Therefore, we conducted a 12-week randomized, placebo-controlled, double blind study to assess the efficacy of a polyphenol-enriched dietary supplement (comprised of olive leaf, lemon verbena, rosemary and Sophora japonica extracts) in reducing pollution-induced oxidative stress and in improving different skin parameters related to skin ageing of Caucasian and Asian volunteers living in a polluted urban European area (Milan). One hundred healthy women were recruited and randomized in the placebo or in the test dietary supplement treatment arms. To assess the efficacy of the dietary supplement, the total antioxidant capacity on saliva (FRAP) was determined, as well as the oxidative damage on skin (lipoperoxides content), the skin moisture (corneometry), the trans-epidermal water loss (Tewameter), the skin radiance and the skin colour, (spectrophotometry), the skin elasticity (cutometry), the skin sebum content (sebumeter), and the skin roughness (image analysis). As a result, both inter-group and intra-group analysis proved that the dietary supplement improved all clinical and biochemical monitored parameters, in both Caucasian and Asian individuals. In conclusion, the results of the study indicate a reduced oxidative stress-induced skin damage in both Asian and Caucasian women living in a polluted urban area.

Forestry and the wood-based sector, including the wood industry, which is an important element of economic systems and a source of budget revenues for many countries in the world, found itself in the first quarter of 2020 in a situation of a serious threat of a prolonged crisis as a consequence of the pandemic. In this perspective, it is necessary to review existing sector strategies and look for new solutions to ensure first survival, then functioning and finally development of entities forming the wood market. In the scientific research, which is the subject of this work, an attempt was made to multi-criteria analysis of the selection of the optimal anti-crisis strategy for actors from forestry and the wood-based sector in the face of a pandemic. Preparatory studies were conducted on the example of Poland, where both forestry and the wood industry belong to the dominant sectors of the economy, conducting them at the turn of March and April 2020. The research was referred to the primary wood raw material market in Poland, which is the main link in the value chain, created first by the dominant owner: Państwowe Gospodarstwo Leśne "Lasy Państwowe" - the “State Forests” National Forest Holding (SFNFH), and then forest service entrepreneurs, to entities representing the wood industry. The work uses a concept modified for the purposes of the author's research scenario, based on the method of multi-criteria hierarchical analysis AHP (Analytic Hierarchy Process). The best possible decision was to be searched that would allow the selection of the optimal anti-crisis strategy for enterprises - actors of the sector concerned. Based on the collected results and their expert discussion, recommendations for sectoral policy for forestry and the wood-based sector were then formulated. The proposed solutions are located against the background of a dispute between the concept of institutional intervention and a model taking into account the effects of market factors. The work is both cognitive (optimization and adaptation of the research method) and practical up-to-date. An accurate development strategy for forestry and the wood-based sector is urgently needed and necessary to implement as quickly as possible.

Angiogenesis is a term that describes the formation of new blood and lymphatic vessels from a pre-existing vasculature. This allows tumour cells to acquire sustenance in the form of nutrients and oxygen and the ability to evacuate metabolic waste. As one of the hallmarks of cancer, angiogenesis has been studied extensively in animal and human models to enable better understanding of cancer biology and the development of new anti-cancer treatments. Angiogenesis plays a crucial role in the process of tumour genesis, because solid tumour need a blood supply if they are to grow beyond a few millimeters in size. On the other hand, there is growing evidence that some solid tumour exploit existing normal blood supply and do not require a new vessel formation to grow and to undergo metastasis. This review of the literature will present the current understanding of this intricate process and the latest advances in the use of angiogenesis-targeting therapies in the fight against cancer.

As e-commerce services and Internet technology have rapidly developed in recent years, many services and applications integrating these technologies can now be completed online. These commercial activities include online auctions, online ticketing and online payments. The client shops from the store online, andthe store delivers the goods to the client. The goods can be divided into digital products without entities, as well as actual entities. If it is a physical product, the store will deliver the package to the client through itslogistics. However, there have been many cases of switched goods purchased by clients in recent years. Earlier, some scholars proposed a security mechanism with a subliminal channel for E-cash and digital content. Only the sender and the receiver would know that the secret information was hidden in the signature. So the privacy of this subliminal message couldbe ensured. We apply this concept to the logistics environment to design secure logistics architecture with subliminal messages. The client can check the subliminal message of the received package, and know whether the package has been switched by malicious people. In addition, the proposed scheme also applies sensor technology;the client can check the GPS location, the temperature and humidity at any time during the delivery process. So intelligent logisticswouldthereby be achieved. This paper proposes an intelligent and secure package sensoring logistics system based on a subliminal channel. The proposed architecture uses the related mechanisms tosolve the problems of a logistics system, including how to achieve mutual authentication, data integrity, anti-switch package, package location and status tracing, resisting replay attacks, forward and backward secrecy, and non-repudiation issues.

Specific nutrients including n-3 long chain polyunsaturated fatty acids (LCPUFAs), flavonoids, vitamin A, D and E are considered to possess protective properties on human health by impacting on immunological reactions. An ‘inflammation-suppressive’ effect appears to be the common denominator of the beneficial effects of most of these dietary components which may protect against the development of chronic immune disorders such as allergy. However, the majority of these promising data are from preclinical studies such as animal disease models, as the majority of clinical studies only indicate associations. PUFAs, especially n-3 LCPUFAs, have been shown to interact with both the sensitization as well as the effector phase in food allergy. However, it should be noted and realised that PUFAs are highly susceptible to lipid oxidation. Flavonoids and fat-soluble vitamins both contain anti-inflammatory properties and are able to act as anti-oxidants as well. Here, we explore the anti-allergic properties of PUFAs, flavonoids and fat-soluble vitamins in order to create an overview and, more importantly, suggest a strategy to target food allergies using these components and combinations thereof. Dietary n-3 LCPUFAs and the above mentioned micronutrients are promising anti‐allergy agents capable of influencing the allergic immune response through multiple and different biological pathways.

Micronutrient deficiencies are a major public health problem. Beans are an important plant-based source of iron, zinc and copper, but their absorption is reduced in the presence of anti-nutrients such as phytates, polyphenols and tannins. Soaking and discarding the soaking water before cooking is unanimously recommended, but this can result in mineral loss. Data on the consequences for mineral bioaccessibility is still limited. This study aimed to evaluate iron, zinc and copper bioaccessibility in black beans cooked (regular pan, pressure cooker) with and without the soaking water. Minerals were quantified by ICP-MS, myo-inositol phosphates (InsP₅, InsP₆) by HPLC ion-pair chromatography, total polyphenols using Folin-Denis reagent and condensed tannins using Vanillin assay. Mineral bioaccessibility was determined by in vitro digestion and dialysis. All treatments resulted in a statistically significant reduction of total polyphenols (30%) and condensed tannins (20%). Only when discarding the soaking water a loss of iron (6%) and copper (30%) was observed, and InsP₆ was slightly decreased (7%) in one treatment. Bioaccessibility of iron and zinc were low (about 0.2% iron and 35% zinc), but copper presented high bioaccessibility (about 70%). Cooking beans under pressure without discarding the soaking water resulted in the highest bioaccessibility levels among all household procedures. Discarding the soaking water before cooking did not improve the nutritional quality of the beans.

Microencapsulation of polyherbal formulation (PHF) extract was carried out by freeze drying method, by employing gum arabic (GA), gelatin (GE), and maltodextrin (MD) with their designated different combinations as encapsulating wall materials. Antioxidant components (i.e total phenolic contents (TPC),Total flavonoids contents (TFC), and total condensed contents (TCT)), antioxidant activity (i.e. DPPH, β-carotene & ABTS⁺ assays), moisture contents, water activity (aw), solubility, hygroscopicity, glass transition temperature (T_g), particle size, morphology, in vitro alpha-amylase and alpha-glucosidase inhibition and bioavailability ratios of the powders were investigated. Amongst all encapsulated products, T_B (5% GA and 5% MD) and T_C (10% GA) has proven to be the best treatments with respect to the highest preservation of antioxidant components and their antioxidant potential by DPPH and β-carotene assays and noteworthy for an ABTS⁺ assays, in addition, the aforesaid treatments also demonstrated lower moisture content, aw, particle size and higher solubility, hygroscopicity and glass transition temperature (T_g). All freeze dried samples showed irregular (asymmetrical) microcrystalline structures. Furthermore, T_B and T_C also illustrated the highest in vitro anti-diabetic potential due to great potency for inhibiting alpha-amylase and alpha-glucosidase activities. In the perspective of bioavailability, T_A, T_B and T_C demonstrated the excellent bioavailability ratios (%).Futhermore, the phytochemo-profiling of ethanolic extract of PHF was also revealed to find out the bioactive compounds.

Flavonoids, compounds present in many dietary supplements, affect growth of different bacterial species when tested as purified or synthetic substances. Here, we asked if soy isoflavone extracts, commonly used in many products sold as anti-menopausal dietary supplements, influence bacterial growth similarly to synthetic isoflavone, genistein. Four commercially available products were tested in amounts corresponding to genistein concentrations causing inhibition of growth of Vibrio harveyi (a model bacterium sensitive to this isoflavone) and Escherichia coli (a model bacterium resistant to genistein). Differential effects of various extracts on V. harveyi and E. coli growth, from stimulation, through no changes, to inhibition, were observed. Moreover, contrary to genistein, tested extracts caused a decrease (to different extends) in viability of human dermal fibroblasts. These results indicate that effects of various soy isoflavone extracts on bacterial growth and viability of human cells are different, despite similar declared composition of the commercially available products.

The therapeutic applicability of mesenchymal stem cells (MSC) for a range of conditions has garnered increasing interest. This study aimed to evaluate the mean major adverse cardiac and cerebrovascular event (MACCE)-free period in a population of 2,504 patients (age, 54.09 ± 11.65 years) receiving MSC therapy (mean dose, 1.49 ± 0.75 billion cells) for various indications (over two-thirds [n=1,700, 67.89%] received MSC therapy as an anti-ageing therapy) and evaluate for potential risk factors for MACCE development in this cohort. In multivariate Cox proportional hazards regression analysis, age, but not sex and MSC dose, was significantly associated with MACCE risk (hazard ratio=1.127; 95% confidence interval=1.0418, 1.219; p=0.0029). The adverse event rate was 0.8%, and none of the reported adverse events were severe. In conclusion, our study showed that stem cell therapy was safe in a large cohort of individuals and was associated with a low rate of MACCE.

Background: Codonopsis pilosula (CP) is one of the most popular Qi-invigorating herbal medicines and has been extensively used to promote health and vitality in China for a long time. C. pilosula polysaccharide (CPP) is the principal active components of CP, which is considered as the reason for CP widespread application. However, there are not revealed that CPP exert a Qi-invigoration effect by protecting mitochondria and/or improving mitochondrial function in the existing traditional Chinese medicine theories. Methods: Herein, we extracted CPP from C. pilosula and investigated the effects of CPP on energy metabolism and mitochondrial protection. Based on the mice chronic hypoxia model for imitating the “Qi” deficiency state of the human body in traditional Chinese medicine, which was administered with CPP by oral gavage daily for 10 days, mitochondrial permeability transition (MPT), lipid peroxidation product malondialdehyde (MDA) in brain, mitochondrial respiratory function, the levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP) in liver cells were assayed. Adenylate energy charge (AEC), total adenylate pool (TAP), ATP/ADP, and ATP/AMP ratios were calculated. Results: CPP could inhibit the formation of MDA in mice brains, decrease oxygen consuming rate and respiratory control ratio (RCR) of liver mitochondria, increase levels of ATP, TAP and AEC in liver cells under chronic hypoxia condition. Conclusion: Overall, CPP can invigorate “Qi” by improving mitochondrial energy metabolism and bioenergetic levels.

The alarming rise of antibiotic resistance has made it imperative to find novel antimicrobial medications. This study reports the design and synthesis of new molecules based on benzofu-ran-pyrazole scaffolds hybridized with various N/O heterocycles using the molecular hybridiza-tion process. The newly synthesized candidates were confirmed using micro-analytical and spectral analyses, and their antimicrobial characteristics were assessed against different bacterial and fungal isolates in comparison with novobiocin and clotrimazole as antibacterial and anti-fungal standards, respectively. In addition, the new compounds were further evaluated as in vitro antioxidants and anti-inflammatory congeners. The most promising broad spectrum antimicrobial compounds 9, 10 with values ranging from 2.50-20.60 μg/mL were further examined as E. coli DNA gyrase B enzyme suppressors using novobiocin as a reference drug. In silico computational and ADMET studies were carried out for the most active compounds.

The high thrust linear motor used for electromagnetic launch is switched with the anti-shunt thyristor as the switch. During the switching process, different current path states will appear, which will lead to changes in motor parameters and current fluctuation. Aiming at the air-core synchronous linear motor with parallel and series power supply, this paper analyzes the change of current path caused by the change of trigger signal of anti-parallel thyristor in the process of sectionalized stator switching. The motor circuit model of the switching process is derived. A new sectionalized stator switching method is proposed to realize the smooth switching of the sectionalized stator powered linear motor. Finally, the correctness of the analysis and modeling is verified by simulation, and the effectiveness of the sectionalized stator switching method is tested by using the test prototype.

Background/Objectives: The Perilla frutescens plant has historically been used to protect against inflammation and redox stress. This has been attributed in part to the high content of various polyphenols. Despite this, the complement of polyphenolic components in Perilla extract is not yet fully defined. The aim of this study was to characterise the polyphenolic composition in Perilla extract, and its effect on the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), which during inflammation and oxidative stress binds to the antioxidant response element (ARE) found on the promoter of phase II antioxidant enzymes. Methods: Following extraction using four solvents of different properties, the total phenolic, flavonoid and ortho-diphenolic content of Perilla extract were determined. Individual phenolic compounds were identified and quantified by RP-HPLC. Dual Luciferase assay using a reporter plasmid containing a human NQO1 ARE-luciferase fusion was employed to determine the potential protective effect of the Perilla fractions against redox stress. Results: HPLC analysis revealed that the highest phenolic content was present in the polar extracts. A total of 35 distinct polyphenolic compounds were identified, with rosmarinic acid being the major constituent. On cells in vitro, the methanol Perilla fraction showed protection against redox stress, with the luciferase assay displaying up to 1.5 fold increase in the induction of the human NQO1 ARE-luciferase reporter. Conclusions: While Perilla extract seems to be mainly protecting against inflammation and redox stress through the action of rosmarinic acid, further work is required on the synergystic effects between different polyphenols.

The increasing prevalence of multidrug-resistant pathogens (MDR), persistent biofilms, oxidative stress, and cancerous cell proliferation pose significant challenges in healthcare and environmental settings, highlighting the urgent need for innovative and sustainable therapeutic solutions. The exploration of nanotechnology, particularly the use of green-synthesized nanoparticles, offers a promising avenue to address these complex biological challenges due to their multifunctional properties and biocompatibility. Utilizing a green synthesis approach, Mauritia flexuosa Mf-AgONPs were synthesized and characterized exhibiting potent antibacterial effects against both non-resistant and MDR bacterial strains, with minimum inhibitory concentrations (MICs) ranging from 11.25 to 45 µg/mL. Mf-AgONPs also demonstrated significant antifungal efficacy, particularly against Candida glabrata, with a MIC of 5.63 µg/mL. Moreover, the nanoparticles showed strong biofilm inhibition capabilities and substantial antioxidant properties, underscoring their potential to combat oxidative stress. Additionally, Mf-AgONPs exhibited pronounced anti-tumor properties against various cancer cell lines, displaying low IC50 values across various cancer cell lines while maintaining minimal hemolytic activity at therapeutic concentrations. These findings suggest that Mf-AgONPs synthesized via an eco-friendly approach offer a promising alternative for biomedical applications, including antimicrobial, antifungal, antioxidant, and anticancer therapies, warranting further in vivo studies to fully exploit their therapeutic potential.

Bacterial infection poses a serious threat to human life due to its rapidly growing resistance to antibacterial drugs, which is a significant public health issue. This study was focused on the design and synthesis of a new series of 25 analogues bearing 5-cyano-6-oxo-4-substituted phenyl-1,6-dihydropyrimidine scaffold hybridized with different substituted benzene-sulfonamides through thioacetamide linker M1-25 via the treatment of the key intermediates 2-mercapto-6-oxo-4-phenyl-1,6-dihydropyrimidine-5-carbonitriles 1a-c with different 2-chloro-N-substituted benzene-sulfonamide derivatives 4a-e overnight at room temperature. The spectroscopic data of all the new compounds (IR, 1H-NMR, 13C-NMR, and Mass) was studied in detail to confirm their molecular structures. The antimicrobial activity of the new molecules was studied against various Gram-positive, Gram-negative, and fungal strains. All the tested compounds showed promising broad spectrum antimicrobial efficacy, especially against K. pneumoniae and P. aeruginosa, with ZOI values ranging from 15 to 30 mm. Furthermore, the most promising compounds M6, M19,M 20, and M25 were subjected to minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. In addition, the anti-virulence activity of the compounds was also examined using multiple biofilm assays. The new compounds revealed promising suppressing activity of microbial biofilm formation in the examined K. pneumoniae and P. aeruginosa microbial isolates. Additional in silico ADMET studies were conducted to represent their oral bioavailability, drug-likeness characteristics, and human toxicity risks. The obtained data suggest the newly prepared pyrimidine-benzene-sulfonamide derivatives may serve as model compounds amenable for further optimization and development of new antimicrobial and antisepsis candidates.

In recent decades, there has been a rising demand for anti-aging interventions aimed at postponing or potentially reversing indicators of skin aging. The use of collagen-based nutraceutical supplements has gained popularity as they have shown promise in enhancing skin health and reducing signs of aging. The aim of this randomized, placebo-controlled, blinded study was to investigate the effects of 2.5 g COLLinstant® LMW, a novel cosmeceutical containing low molecular weight (≤ 1000 Da) collagen peptides, on skin aging and health. The trial was conducted in 80 healthy women aged 30 years and older. They received a daily oral dose of either the food supplement (n = 40) or placebo (n = 40) for six weeks. Skin assessment was performed based on validated objective methods, such as Visioface 1000D (skin wrinkling), cutometry (elasticity and fatigue) and corneometry (skin hydration) at baseline (T0), and at week 6 (T6). After 6 weeks, participants that received collagen had significant improvements in biometric skin wrinkle parameters from baseline, with a reduction in volume by 46%, in area by 44%, and in depth by 9%, along with a greater increase in skin moisturization (by 34%) than those in the placebo group (p &lt; 0.001). The food supplement did not significantly modify skin firmness or fatigue and had only slight beneficial effects on skin elasticity. The investigational product was well tolerated. The observed effects aligned closely with the subjective assessments reported by study participants. The study provides substantiated evidence supporting the efficacy of low molecular weight collagen peptides in restoring altered skin biometric parameters, as objectively assessed. Thus, regular supplementation with this nutraceutical may contribute to achieving smoother and more radiant skin.

This study aims to examine the safety profile of antiepileptic drugs (AEDs) using real-world data, with a focus on neurological, skin, and sexual/reproductive disorders. Data were collected from AED-caused reports in the Korea Adverse Event Reporting System Database (KAERS-DB) from 2012 to 2022. Totally, 46,963 adverse drug reaction (ADR)-drug pairs were analyzed. At the system organ class level, the most frequently reported classes for sodium channel blockers (SCBs) were skin (37.9%), neurological (16.7%), and psychiatric disorders (9.7%). However, for non-SCBs, these were neurological (31.2%), gastrointestinal (22.0%), and psychiatric disorders (18.2%). The most common ADRs induced by SCBs were rash (17.8%), pruritus (8.2%), and dizziness (6.7%). In contrast, non-SCBs induced dizziness (23.7%), somnolence (13.0%), and nausea (6.3%). Among the most commonly reported ADRs, rash, pruritus, and urticaria occurred on average two days later with SCBs compared to non-SCBs. Sexual/reproductive disorders were reported at a frequency of 0.23%. SCBs were reported as the cause more frequently than non-SCBs (59.8% vs. 40.2%, Fisher’s exact test, p&lt;0.0001). Based on real-world data, we identified the safety profiles of AEDs. AED-induced ADRs exhibited different patterns depending on the mechanism. Therefore, it is important to establish different pharmacovigilance strategies to ensure proper monitoring.

This paper presents an approach to improve the robustness of tip-tilt controllers for fast-steering mirror (FSM)-based laser beam steering (LBS) systems in the presence of dynamic disturbances such as external shocks. To this end, we propose the addition of a disturbance observer (DOB)-based anti-shock controller in parallel to the original linear servo control loop to improve its control performance in the presence of external shocks. To increase the tip-tilt control performance against external shocks, the DOB-based control method, which is an improved control method for eliminating nonperiodic disturbances, is implemented in the original tip-tilt control system. Results indicate that the control error of the DOB-based anti-shock controller decreased, resulting in an efficient improvement in its disturbance-rejection performance.

Elastic yarns are the key component of high-performance compression garments. However, it remains a challenge to fabricate anti-fatigue yarns with high mechanical force and long elongation for generating compression garments with prolonged wear. In this paper, we report the development of anti-fatigue double-wrapped yarns with excellent mechanical properties by wrapping high-denier Spandex with nylon filaments in opposite twists. In particular, 560D high-denier Spandex as the core was untwisted which can maximumly reduce the interaction between the core and wrapping filaments, enabling high elongation of the double-wrapped yarns. In addition, we chose 70D nylon filaments with a tensile force of 387.40 ± 8.82 cN as the wrapping materials to provide sufficient force for double-wrapped yarns. Notably, opposite twists were induced for the inner and outer wrapping filaments to achieve a balanced stable yarn structure. By systematically optimizing manufacturing parameters including inner wrapping density, outer wrapping density, taking-up ratio, and drafting ratio, we obtained double-wrapped yarn with excellent tensile force (952.00 ± 24.03 cN) and elongation (357.28% ± 9.10%). Notably, the stress decay rate of optimized yarns was only 12.0% ± 2.2%. In addition, the optimized yarn was used as the weft-lining yarn for generating weft-lined fabrics, the elastic recovery rate of the obtained fabric was only 2.6% after cyclic stretching, much lower than the control fabric. Our design of anti-fatigue double-wrapped yarns could be widely used for fabricating high-performance compression garments.

Today, there are commercially available high-performance electric wheelchairs, capa-ble of responding to strong limitations. However, despite these advancements, there is a significant portion of the population with severe disabilities who cannot access this mobility solution due to safety reasons. Indeed, either due to motor issues preventing reliable control of the wheelchair's commands, or associated visual or cognitive pathologies, the use of an electric wheelchair by these individuals would put them at risk and could also constitute a danger to those around them. This is why our research team is working on the development of augmented wheelchairs that allow a greater autonomy. We are mainly developing a system compatible with all electric wheel-chairs on the market, capable of making them anti-collision and anti-fall on uneven ground (sidewalks, stairs, etc.). In this article, we present our solution regarding the anti-collision function, in particular the sensors used to do this, as well as the strategy. We will focus on the shortcomings and weaknesses of various types of sensors and demonstrate how, by combining them in a certain way, we can develop a collision avoidance device capable of managing the diversity of everyday life situations. The two types of sensors that will be combined here are an in-house developed special near infrared sensor from the laboratory and a commercially available ultrasonic sensor. We will present the internal operation of the sensors, their limitations, experimental tests involving integration with the wheelchair, and the structure of the complete device.

Despite past efforts towards therapeutical innovation, cancer remains a highly incident and lethal disease, with current treatments many times lacking efficiency and leading to severe side-effects. Hence, it is imperative to develop new, more efficient, and safer therapies. Bee venom has proven to have multiple and synergistic bioactivities, including antitumor effects. Nevertheless, some toxic effects have been associated with its administration. To tackle these issues, in this work, bee venom-loaded niosomes were developed, for cancer treatment. The vesicles had a small (150.4 ± 3.7 nm) and homogeneous (PDI of 0.162 ± 0.008) particle size, and revealed good therapeutic efficacy in in vitro gastric, colorectal, breast, lung, and cervical cancer models, with GI50 values between 12.37 ng/mL and 14.72 ng/mL. Additionally, they also revealed substantial anti-inflammatory activity, with an IC50 of 28.98 ng/mL, effects that have been reported to be complementary to direct antitumor activity. Finally, the niosomes' safety was assessed, both in vitro, on skin, liver and kidney cells, and ex vivo, in a HET-CAM assay, and results showed that compound encapsulation increased its safety. Hence, small and homogeneous bee venom-loaded niosomes were successfully developed, with substantial anticancer and anti-inflammatory effects, making them potentially promising primary or adjuvant cancer therapies.

A three-arm, randomized, placebo controlled clinical study has been performed to evaluate the effects of a lyophilized pineapple extract titrated in bromelain (Brome-Inf®), and purified bro-melain on pain, swelling, trismus and quality of life (QoL) after the surgical removal of the lower third molars. Moreover, the need for non-steroidal anti-inflammatory drugs (NSAIDs) has also been evaluated and compared with a placebo group. The study included 42 people that required the extraction of a single mandibular third molar under local anesthesia. The patients were ran-domized and distributed to receive Brome-Inf®, purified bromelain or placebo and started the treatment the day of surgery and continued it for the next 7 days. The primary outcome was the requirement of NSAIDs in the three groups. The outcome variables were pain, swelling and trismus, which were measured postoperatively at 1, 3, and 7 days. The differences in the efficacy of the freeze-dried pineapple extract and single-component bromelain were also evaluated. At the end of the study, the assumption of ibuprofen (from days 1-7) was statistically higher in the placebo group (p

Aging, a natural process occurring in both normal and degenerative conditions, is closely associated with collagen degradation, impacting various bodily systems such as the skin. The continuous aging of the skin, influenced by both intrinsic and extrinsic factors, underscores the importance of collagen in dermatological and cosmetic contexts. Notably, collagen supplements enriched with essential amino acids like proline and glycine along with marine fish collagen have become popular for their safety and effectiveness in mitigating the aging process. To compile relevant literature on the anti-aging applications of marine collagen, a systematic search and analysis of peer-reviewed papers was conducted using reputable databases including PubMed, Cochrane Library, Web of Science, and Embase, covering publications from 1956 to 2023. From in vitro to in vivo experiments, the reviewed studies elucidate the anti-aging benefits of marine collagen, emphasizing its role in combating skin aging and promoting overall skin health. Many bioactive marine peptides exhibit diverse anti-aging properties, including free radical scavenging, apoptosis inhibition, lifespan extension in various organisms, and protective effects in aging humans. Furthermore, the peptide production of hyaluronic acid is discussed as a mechanism to fortify collagen and enhance skin moisture, contributing to the anti-aging effects of collagen supplementation. The integration of bio-tissue engineering in marine collagen applications is also explored, highlighting its proven utility in addressing skin and bone damage. Insights from this review illuminate the diverse biomedical applications of marine collagen alongside keystone molecular editing tools such as CRISPR, positioning it as a versatile resource in anti-aging interventions. However, limitations to the scope of its application exist. Thus, by delving into these nuanced considerations, this review contributes to a comprehensive understanding of the potential and challenges associated with marine collagen in the realm of anti-aging applications.

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.

Amphibians are widely known as a prolific source of bioactive metabolites. In this work we isolated and characterized compounds with antiparasitic activity from the oocytes of the toad Rhinella alata collected in Panama. Bio-guided isolation and structural elucidation was carried out using chromatographic and spectroscopic techniques. The organic crude extract was subjected to solid phase extraction followed by HPLC purification of the fraction with in vitro activity against Trypanosoma cruzi trypomastigotes. Seven steroids (1-7) of the bufadienolide family were isolated and their structures determined using NMR and MS analyses; of these 19-formyl-dyscinobufotalin (3) is reported as a new natural product. Compounds 1, 3-7, resulted with a good anti-trypanosomal activity profile, among these 16β-hydroxyl-hellebrigenin (1) and bufalin (7) showed significant selectivity for T. cruzi. Furthermore, molecular docking analysis showed compounds 1, 3 and 7 interact through H-bonds with the amino acid residues GLN-19, ASP-158, HIS-159 and TRP-177 from cruzipain, at the catalytic site. Given the lack of therapeutic options to currently treat the American trypanosomiasis, this work can serve as the basis for further studies that aim the development of bufadienolides or their derivatives as drugs against Chagas disease.

High-performance properties of interpenetration polymer network (IPN) hydrogels, based on physically crosslinked chitosan (CS) and chemically crosslinked poly(N-isopropylacrylamide) (PNiPAM), have been successfully developed. The IPN of CS/PNiPAM is proposed to overcome the limited mechanical properties of the single CS network. In this study, the viscoelastic behaviors of prepared materials in both solution and gel states have been extensively examined, considering the UV exposure time and crosslinker concentration as key factors. The effect of these factors on gel formation, hydrogel structures, thermal stabilities of networks, and HeLa cell adhesion were studied sequentially. The sol-gel transition was effectively demonstrated through the scaling law, which agrees well with Winter and Chambon's theory. By subjecting the CS hydrogel to the process operation in an ethanol solution, its properties can be significantly enhanced with increased crosslinker concentration, including the shear modulus, crosslinking degree, gel strength, and thermal stability in its swollen state. The IPN samples exhibit a smooth and dense surface with irregular pores, allowing for much water absorption. The HeLa cells were adhered to and killed using the CS surface cationic derivative, then released through hydrolysis by utilizing the hydrophilic/hydrophobic switchable property or thermo-reversible gelation of the PNiPAM network. The results demonstrated that IPN is a highly attractive candidate for anti-fouling materials.

The goal of the current study was to discover a novel potential probiotic strain of Lactobacillus spp. with anti-Escherichia coli activity from locally produced yogurt in Tongi, Gazipur, Bangladesh, compare its antagonistic activity with a commercial probiotic mixture of several strains, and approve a novel method for confirming the viability and relative abundance of the microbial community in a probiotic mixer. We carried out 16S sequencing, 16S metagenomics, Transmission Electron Microscopy (TEM) analysis, and other in vitro laboratory experiments to reach this objective. The strain TY-11 was identified as Lactobacillus delbrueckii subsp. indicus (16S sequence accession number OQ652026). It was gram-positive, anaerobic, lactose fermenting, and round-ended rod that typically measured 0.7 to 1.3 µm by 2.2 to 9 µm. In addition to having seven probiotic characteristics, it also showed an antagonistic impact on six different pathogens, but what's more noteworthy is that E. coli was the pathogen it inhibited most strongly (inhibition zone diameter was 18.88±0.18 mm). The most important and ground-breaking finding of this work was determining the probiotic features of a new probiotic strain, TY-11, whose antibacterial activity was virtually as effective as that of the probiotic combination with three different strains. Furthermore, the results of 16S high throughput sequencing and the conventional plate count method demonstrated a strong correlation (0.999) at the genus level, indicating that the use of both of these approaches in combination may be a practical way to assess the relative abundance of the microbial community and their viability in commercially available probiotic blends.

Anti-DNA antibodies are hallmark autoantibodies produced in systemic lupus erythematosus (SLE), but their pathogenetic roll is not fully understood. Accumulating evidence suggests that some anti-DNA antibodies enter different types of live cells and affect the pathophysiology of SLE by stimulating or impairing these cells. Circulating neutrophils in SLE are activated by type I interferon or other stimuli and primed to release neutrophil extracellular traps (NETs) on additional stimulation. Anti-DNA antibodies are also involved in this process and may induce NET release. Thereafter, they bind and protect extracellular DNA in the NETs from digestion by nucleases, resulting in increased NET immunogenicity. This review discusses the pathogenetic role of anti-DNA antibodies in SLE, mainly focusing on recent progress in the two research fields concerning antibody penetration into live cells and NETosis.

Algal-bacterial granular sludge, a new biological technology, has been widely recognized due to its highly effective pollutant treatment and energy efficiency. This study investigated the effects of environmental concentrations of Cr(VI) (0.5-2.5 mg/L) on the performance of algal-bacterial gran-ular sludge and self-defensive responses after 90 days of cultivation. The results showed that Cr(VI) affected chemical oxygen demand (COD), ammonia-N and phosphate removal with different trends being apparent. A linear decline in COD removal was observed, whereas an initial de-creasing and then increasing ammonia-N and phosphate removal took place. Algal-bacterial granular sludge effectively removed Cr(VI) from wastewater through biological adsorption and reduction, showing the potential to treat Cr(VI)-contaminated wastewater. Cr(VI) affected the community abundance of the algal-bacterial granular sludge, in which Chlorophyceae and cya-nobacteria were vulnerable under Cr(VI)-induced stress. To reduce the toxicity of Cr(VI), over-produced EPS-PN and antioxidant enzymes (MDA, SOD and CAT) acted as self-defensive responses to resist oxidative damage. This study showed that algal-bacterial granular sludge can remove 00.5 mg/L of Cr(VI) without performance loss. It is hoped that this study can provide useful information for improved engineering feasibility of algal-bacterial granular sludge.

Objectives: Studies on the association between non-steroidal anti-inflammatory drugs (NSAIDs) and major adverse cardiovascular events (MACE) in the Arabian Gulf are scarce. The aim of this study was to evaluate the association between NSAIDs use and MACE in acute coronary syndrome (ACS) patients in the Arabian Gulf region. Methods: Data was analyzed from 3,007 consecutive patients diagnosed with ACS admitted to 29 hospitals in four Arabian Gulf countries from January 2012 to January 2013 as well as being on prior NSAIDs use during the index admission. MACE included stroke/transient ischemic attacks (TIAs), myocardial infarction (MI), all-cause mortality and readmissions for cardiac reasons. Results: The overall mean age of the cohort was 62 ± 12 years and 9.6% (n = 290) of the patients were on prior NSAID use during the index admission. At 12-months follow-up, after adjusting for confounding factors, those on NSAIDs were significantly more likely to have had MACE (adjusted OR (aOR), 1.89; 95% confidence interval (CI): 1.44-2.48; p < 0.001). Specifically, the higher event rates observed were stroke/TIA (aOR, 2.50; 95% CI: 1.51-4.14; p < 0.001) and readmissions for cardiac reasons (aOR, 2.09; 95% CI: 1.59-2.74; p < 0.001) but not MI (aOR, 1.26; 95% CI: 0.80-1.99; p = 0.320) and all-cause mortality (aOR, 0.79; 95% CI: 0.46-1.34; p = 0.383). Conclusions: NSAIDs use was associated with significant stroke/TIA events as well as readmissions for cardiac reasons. However, NSAIDs were not associated with increased MI or all-cause mortality rates in ACS patients in the Arabian Gulf.

: (1) Background: Hepatitis B core antibodies (anti-HBc) are a marker of hepatitis B virus (HBV) exposure; hence a normal HBV serology profile is characterized by HBV surface antigen (HBsAg) and anti-HBc positivity. However atypical HBV serologies occur and we aimed to determine the prevalence of an atypical profile (HBsAg+/anti-HBc-) in a cohort of people with HIV-1 (PWH) in Botswana. (2) Methods: Plasma samples from an HIV-1 cohort in Botswana (2013-2018) were used. Samples were screened for HBsAg and anti-HBc. Next generation sequencing was done using the GridION platform. Wilcoxon rank-sum test and Chi-squared tests were used for comparison of continuous and categorical variables respectively. (3) Results: HBsAg+/anti-HBc- prevalence was 13.7% (95% CI 10.1 – 18.4) (36/263). HBsAg+/anti-HBc- participants were significantly younger (p&lt;0.001), female (p=0.02), ART naïve (p=0.04) and had detectable HIV viral load (p=0.02). There were no mutational differences in sequences isolated from participants with HBsAg+/anti-HBc- versus those with HBsAg+/anti-HBc+ serology. (4) Conclusions: We report a high HBsAg+/anti-HBc– atypical serology profile prevalence among PWH in Botswana. We caution against HBV testing algorithms that consider only anti-HBc+ samples for HBsAg testing as they are likely to underestimate HBV prevalence. Studies to elucidate the mechanisms and implications of this profile are warranted.

Lipoxygenases are non-heme iron-containing enzymes that catalyze the oxidation of polyunsaturated fatty acids, resulting in the production of lipid hydroperoxides, which are precursors of inflammatory lipid mediators. The enzymes are widely distributed in humans, other eukaryotes, and cyanobacteria. Lipoxygenases hold promise as therapeutic targets for several human diseases, including cancer and inflammation-related disorders. Inhibitors of lipoxygenase have potential applications in pharmaceuticals, cosmetics, and food. Bioactive peptides are short amino acid sequences embedded within parent proteins, which can be released by enzymatic hydrolysis, microbial fermentation, and gastrointestinal digestion. A wide variety of bioactivities have been documented for protein hydrolysates and peptides derived from different biological sources. Recent findings indicate that protein hydrolysates and peptides derived from both edible and non-edible bioresources can act as lipoxygenase inhibitors. In this review, we explore current knowledge on the production of anti-lipoxygenase protein hydrolysates and peptides from millet grains, chia seeds, insects, milk proteins, fish feed, velvet antler blood, fish scales, and feather keratins. We delve into the anti-lipoxygenase activities and modes of action of these protein hydrolysates and peptides, while also highlighting the strengths and shortcomings of previous research. Additionally, we propose potential research directions and areas of improvement that can propel the discovery of anti-lipoxygenase peptides in the near future.

This paper presents designing an attitude motion control strategy for a half-car model using an anti-jerk predictive controller. Anti-jerk predictive controller based on active aerodynamics surfaces is employed to deal with the anticipated future road maneuvers and improve vehicle ride performance by canceling out external jerks acting on the vehicle body. The body jerks are produced during vehicle traversing on a double lane-change maneuver, acceleration, or braking. The control strategy helps the vehicle to achieve a realistic operation of the active aerodynamic surface to improve the vehicle’s ride performance, i.e., ride comfort and road holding during cornering, acceleration, or braking. The anti-jerk predictive controller is developed based on the predictive control strategy, which predicts future road inputs and uses them to compensate for the vehicle’s attitude motion. The simulation results show that the proposed control strategy effectively reduces the effects of vehicle body jerks transmitted to the passengers, improving ride comfort without degrading vehicle handling. The anti-jerk predictive controller successfully tracks the desired attitude position by canceling the external body jerks.

Metformin (MeT) is an FDA-approved drug with a myriad of health benefits. Besides being used as an anti-diabetic drug, MeT is also effective against various cancers, liver-, cardiovascular-, and renal diseases. It has also been proven to demonstrate anti-ageing and neuroprotective effects. This study was undertaken to examine its unique potential as an anti-virulence drug against an opportunistic bacterial pathogen, Pseudomonas aeruginosa. Due to the menace of multidrug resistance in pathogenic microorganisms, many novel or repurposed drugs with anti-virulence prospects are emerging as next-generation therapies with the aim to overshadow the application of existing antimicrobial regimens. The quorum sensing (QS) mechanisms of P. aeruginosa are an attractive drug target for attenuating bacterial virulence. In this context, the anti-QS potential of MeT was scrutinized using biosensor assays. MeT was comprehensively evaluated for its effects on different motility phenotypes, virulence factor production (phenotypic and genotypic expression) along with biofilm development in P. aeruginosa in vitro. At sub-lethal concentrations, MeT displayed prolific quorum quenching (QQ) ability and remarkably inhibited AHL biosynthesis in P. aeruginosa. Moreover, MeT (1/8 MIC) effectively downregulated the expression levels of various QS- and virulence genes in P. aeruginosa, which coincided with a notable reduction in the levels of alginate, hemolysin, pyocyanin, pyochelin, elastase, and protease production. In silico analysis through molecular docking also predicted strong associations between the QS receptors of P. aeruginosa and MeT. MeT also compromised the motility phenotypes and successfully abrogated biofilm formation by inhibiting EPS production in P. aeruginosa. Hence, the QQ, anti-virulence, and anti-fouling potential of MeT was elucidated for the first time against P. aeruginosa.

According to the eminent scholar, philosopher, and physician Avicenna, "the doctor has three tools: the word, the plant, the knife." The plant kingdom is recognized as humanity's earliest and most ancient healing source, employed for the management and prevention of illnesses. Tracing back through history, the most ancient documented proof of plants' utilization in medicine dates back to a Sumerian clay slab discovered in Nagpur roughly 5000 years ago. This artifact included a compilation of twelve medicinal recipes that involved over 250 diverse plant species. Sumerian healers extracted powders and infusions from plant roots and stems, while also crediting healing properties to pears and figs. Additionally, they utilized dried and ground young shoots of willow and plum trees, pine and fir needles as a component in compresses and poultices. Often, powders from animal and mineral sources were blended with those extracted from dried and crushed plants. Notably, in addition to water, wine and beer served as solvents. Thus, at least 80 centuries ago, people utilized the most uncomplicated medicinal plant-based preparations for treatment [1]. The "Pen T'Sao," an ancient Chinese text on roots and herbs, authored by Emperor Shen Nung approximately 2500 BC, contains descriptions of 900 medicaments (comprising dried components of medicinal plants). Several of these substances are still in use today, including Rhei rhisoma, camphor, Theae folium, Podophyllum, great yellow gentian, ginseng, datura, cinnamon bark, and ephedra [2]. Regarding Kazakh folk medicine, an area that has yet to be fully explicated and substantiated, it can be stated that the traditional medicinal knowledge of the Kazakh people transcends the mere treatment of ailments and rests on robust theoretical underpinnings. Oteiboydak Tleukabyluly (1388-1478), an astute healer and prominent figure in Kazakh folk medicine during the 15th century, comprehensively explicated the secrets of the healing art in his medical and ethnographic work "Medical Narrative," which he composed between 1466 and 1473 at the behest of az-Zhanibek Khan, who held him in high esteem as a great healer. This medical encyclopedia delineates the functions of various organs of the human body and provides a catalogue of the primary diseases associated with them. Furthermore, it includes a meticulous description of the methods used in traditional medicine at present, such as setting bones, listening to the pulse, and incantations. Through practical experimentation and experimentation conducted in the steppe laboratory, the healer formulated a total of 1,108 different medicinal compounds, of which 858 were derived from medicinal plants, 318 were extracted from animal organs, and roughly 60 were sourced from metals. The moniker "Teacher without a teacher" was bestowed on Oteiboydak Tleukabylov, who discovered methods for treating 1,050 different diseases [3]. At present, the employment of phytotherapy has gained widespread acceptance on a global scale. According to the World Health Organization's (WHO) global review of national policies concerning traditional, complementary, and alternative medicine, as well as the regulation of herbal medicines, there is an evident growth in the European and Asian market for herbal medicines [4]. Kazakhstan boasts a natural flora of over 6,000 plant species [5]. The exact number of medicinal plant species present in Kazakhstan remains uncertain, as the list continues to expand annually. More than 150 plant species have been employed in both official and folk medicine for various ailments. This review focuses on a selection of medicinal plants growing within the territory of the Republic of Kazakhstan that have traditionally been used to alleviate skin diseases. In conducting this study (2010-2023), emphasis was placed on the plants' phytochemical composition, with a particular focus on the principal components responsible for their therapeutic effects against inflammatory skin conditions such as dermatitis, atopic dermatitis, and eczema.

We report the isolation of two novel degrading bacterial strains active against the potential environmental pollutant acetamino-phen/paracetamol. Streptomyces Chrestomyceticus (RS2) and Streptomyces Flavofuscus (M33) collected from El-Natrun Valley, Egypt, water, sediment, and sand samples were taxonomically characterized via conidiophores morphologic characterization under Trans-mission Electron Microscope (TEM). Genotypic identification, done based on their 16S rRNA gene sequence analysis followed by BLAST alignment and deposited on the NCBI as 2 novel strains. The phylogenetic tree was constructed using an appropriate software. Acetaminophen degradation-products chemical structure was identified by GC/LC MS. The biological antimicrobial activity of some selected acetaminophen degradation-products extracts and derived compounds was examined against panel of test micro-organisms and found to be have high anti-microbial effect. In addition, in silico cheminformatics Swiss ADMET evaluation of these selected deg-radation extract for gastric absorption, distribution, hepatic metabolism, renal excretion as well as distribution to CNS and finally not mutagenic/teratogenic or genotoxic virtually. In vitro cytotoxic activity of these selected bio-degradation products was performed against HepG2 and MCF7 cancer cell lines, revealing that M33 and RS2 extract effect on acetaminophen/paracetamol bio-degradation products are potentially safe with higher IC50 on HepG2 and MCF7, in comparison to acetaminophen/paracetamol with IC50 of 108.5 μg/ml. Moreover, the in vivo acute oral single dose toxicity experiment was conducted, being compared with acetamino-phen/paracetamol to confirm that the bio-degradation products have lower toxicity than acetaminophen in vivo and in silico.

In cystic fibrosis (CF), pulmonary infection with Pseudomonas aeruginosa is a cause of increased morbidity and mortality, especially in patients for whom infection becomes chronic and there is reliance on long-term suppressive therapies. Current antimicrobials, though varied mechanistically and by mode of delivery, are inadequate not only due to eradication failure in many cases, but also because they do not halt the progression of lung function decline over time. One of the reasons for this failure is thought to be the biofilm mode of growth of P. aeruginosa, wherein self-secreted exopolysaccharides (EPSs) provide physical protection against antibiotics and an array of niches with resulting metabolic and phenotypic heterogeneity. Targeting the three EPSs secreted by P. aeruginosa (alginate, Psl and Pel) is currently under investigation as a way of disrupting the biofilm extracellular matrix to potentiate the action of antibiotics. In this review, we look at each EPS as a potential therapeutic target for combatting pulmonary infection with P. aeruginosa in CF, with a particular focus on the current evidence for these emerging therapies and barriers to bringing these therapies into clinic.

A new treatment option for cluster headache (CH) prevention is needed. Monoclonal antibodies (mABs) against calcitonin gene-related peptide (CGRP) ligands are used as a preventative treatment for migraine. Considering the CGRP’s role in the CH attack’s ignition and upkeep, fremanezumab and galcanezumab have been evaluated for CH preventative treatment. However, only high-dose (300 mg) galcanezumab was proven for episodic CH prevention. We herein report 3 cases of migraine and comorbid CH with previous failures of preventive treatments. The 2 cases were treated with fremanezumab and the one with non-high-dose galcanezumab. All 3 cases showed good results not only on migraine but also on CH attacks. Our report suggested the efficacy of CGRP-mABs for CH prevention. Our cases differed from the cases in the phase 3 trials of CGRP-mABs for CH prevention in the following 2 points. First, the patients had both migraine and comorbid CH. Second, the combined use of CGRP-mABs with preventative drugs for CH, such as verapamil and/or prednisolone, was performed. Future accumulation of real-world data may prove the efficacy of CGRP-mABs for CH prevention.

Age-related macular degeneration is a progressive retinal disease that is associated with factors such as oxidative stress, decreased phagocytic activity, and inflammation. In this study, we evaluated the protective effects of SIG-1451, a non-steroidal anti-inflammatory drug developed for treating atopic dermatitis and known to inhibit toll-like receptor 4, on light-induced photoreceptor degeneration. SIG-1451 was intraperitoneally injected into rats once a day before exposure to 1000 lx light for 24 h; one day later, optical coherence tomography showed a decrease in retinal thickness, and electroretinogram (ERG) amplitude was also found to have decreased 3 d after light exposure. Moreover, SIG-1451 protected against this decrease in retinal thickness and increase in ERG am-plitude. One day after light exposure, upregulation of inflammatory response-related genes was observed, and SIG-1451 was found to inhibit this upregulation. Iba-1, a microglial marker, was suppressed in SIG-1451-injected rats. To investigate the molecular mechanism underlying these effects, we used lipopolysaccharide (LPS)-stimulated rat immortalised Müller cells. The upregu-lation of C-C motif chemokine 2　by LPS stimulation was significantly inhibited by SIG-1451 treatment, and western blot analysis revealed a decrease in phosphorylated I-κB levels. These results indicate that SIG-1451 protects photoreceptor cells by attenuating light damage progression through inhibiting inflammatory responses.

Torenia Concolor Lindley var. formosama Yamazaki ethanolic extract (TCEE) is reported to have anti-inflammatory and anti-obesity properties. However, the effects of TCEE and its underlying mechanisms in the activation of endothelial nitric oxide synthase (eNOS) have not yet been investigated. Increasing the endothelium-derived nitric oxide (NO) production has been known to be beneficial against the development of cardiovascular diseases. In this study, we investigated the effect of TCEE on eNOS activation and NO-related endothelial function and inflammation by using in vitro system. In endothelial cells (ECs), TCEE increased NO production in a concentration-dependent a manner without affecting the expression of eNOS. In addition, TCEE increased the phosphorylation of eNOS at serine 635 residue (Ser635) and Ser1179, Akt at Ser473, calmodulin kinase II (CaMKII) at threonine residue 286 (Thr286) and AMP-activated protein kinase (AMPK) at Thr172. Moreover, TCEE-induced NO production, and EC proliferation, migration and tube formation were diminished by pretreatment with LY294002 (an Akt inhibitor), KN62 (a CaMKII inhibitor) and compound C (an AMPK inhibitor). Additionally, TCEE attenuated the tumor necrosis factor-α-induced inflammatory response as evidenced by the expression of adhesion molecules in ECs and monocyte adhesion onto ECs. These inflammatory effects of TCEE were abolished by L-NG-nitroarginine methyl ester (a NOS inhibitor). Collectively, our findings suggest that TCEE confers protection from endothelial dysfunction by activating the Akt/CaMKII/AMPK/eNOS/NO signaling pathway.

The proposed research methodology aims to design a generally implementable framework for providing a house owner/member with the immediate notification of an on-going theft (unauthorized access to their premises). For this purpose, a rigorous analysis of existing systems was undertaken to identify research gaps. The problems found with existing systems were that they can only identify the intruder after the theft, or cannot distinguish between human and non-human objects. Wireless Sensors Networks (WSNs) combined with the use of Internet of Things (IoT), Cognitive Internet of Things, Internet of Medical Things, and Cloud Computing are expanding smart home concepts and solutions, and their applications. The primary objective of the present research work was to design and develop IoT and cloud computing based smart home solutions. In addition, we also propose a novel smart home anti-theft system that can detect an intruder, even if they have partially/fully hidden their face using clothing, leather, fiber, or plastic materials. The proposed system can also detect an intruder in the dark using a CCTV camera without night vision facility. The fundamental idea was to design a cost-effective and efficient system for an individual to be able to detect any kind of theft in real-time and provide instant notification of the theft to the house owner. The system also promises to implement home security with large video data handling in real-time.

Lung cancer is one of the deadliest cancers, leading to about 125,070 deaths in the U.S. each year. Survival rates depend on the type and spread of cancer, with localized non-small cell lung cancer (NSCLC) having a 5-year survival rate of 64%. High mortality is primarily due to late detection and the older age of patients, making surgery too risky. As a result, preventative measures like vaccines are crucial. This paper reviews the literature on CIMAvax-EGF, an EGF-based vaccine for lung cancer, evaluating its preventive potential, impact on survival in advanced NSCLC, and effect on lung cancer mortality in combination with other therapies. CIMAvax-EGF is a promising vaccine targeting the Epidermal Growth Factor (EGF), which promotes cancer cell growth. The vaccine prevents EGF from binding to its receptor by inducing anti-EGF antibodies, potentially halting cancer progression. It shows significant potential for treating advanced NSCLC, with vaccinated patients having a median overall survival of 12.43 months compared to 9.43 months in unvaccinated individuals. A Phase III trial showed that 78.8% of patients had a good antibody response (GAR), leading to longer survival. CIMAvax-EGF is well-tolerated, with mild to moderate side effects, and its efficacy is enhanced when combined with other therapies, such as immune checkpoint inhibitors. Given its ability to target cancer's underlying mechanisms and boost other treatments, CIMAvax-EGF represents a significant advancement in the fight against lung cancer. Administering this vaccine preventively and during treatment could be a major step in reducing lung cancer mortality.

Flavonoids are secondary plant metabolites involved in biological activity that are present in plentiful proportions in many plant origin foods and beverages. Owing to their chemical difference and qualities that make them beneficial for human health, they have received a lot of focus in research. This review therefore presents an account on the chemical structure of flavonoids, food sources and their metabolism with emphasis on bioavailability. And they also examine their antioxidant, anti-inflammatory, anticancer, cardiovascular protective, neuroprotective, and antimicrobial properties and reveal related molecular processes. In addition, it overviews the clinical data concerning their possible use in the prevention and treatment of chronic diseases. Some of the problems that attend current flavonoid research are also dealt with; such issues as variation in the bioactivity of flavonoids and scarcity of clinical studies. This review is designed to present current state of knowledge and to provoke further research concerning the further potential of flavonoids in enhancing human health.

Plant-Derived Extracellular Vesicles (PDEVs) contain high levels of antioxidants, especially when deriving from organic. PDEVs from different vegetal sources has shown an increased antioxidant power, compared to PDEVs from single plants, suggesting a synergistic effect of the bioactives constitutively expressed in the PDEVs from single fruits. With this study we wanted to investigate the beneficial effects of a mix of PDEVs on human skin cells. We found detectable levels of Citric Acid, Ascorbic Acid, Glutathione, Catalase and SOD in a mix of PDEVs deriving from 5 different fruits (Grape, Red Orange, Papaya, Pomegranate and Tangerine). We then treated H2O2-conditioned fibroblasts with the mix of PDEVs. The results showed that the PDEVs ‘mix reverted the H2O2-induced redox imbalance, restoring the mitochondrial homeostasis, with a strong reduction of mitochondrial anion superoxide and increase of sirtuin levels. The antioxidant action was consistent with a wound repair on a lesion produced in a Fibroblasts’ monolayer. This result was consistent with an increased level of Vimentin and Matrix Metalloproteinase-9, whose expression is directly related to the efficiency of the reparative processes. These data support a beneficial role of PDEVs in both preventing and treating skin injuries, through their potent antioxidant and reparative activities.

Rising obesity and associated multi-systemic complications amplify the health burden. Euphorbia kansui (EK) extract is clinically recognized for managing obesity. In human study, 240 obese individuals were categorized into two cohorts: those receiving solely herbal medicine (HM group), and those administered EK concomitantly with herbal medicine (EK group). An in vivo examination using C57BL/6-Lepob/Lepob mice elucidated mechanisms involving macrophages and gut microbiota, with associated metabolic advantages. The clinical study revealed a significant 7.22% body weight reduction during 91.55 average treatment days, and examined 16.71% weight loss at 300 days after treatment. In the whole subjects, 60.4%, 21.3% and 6.3% achieved weight reductions exceeding 5%, 10% and 15%, respectively. Impressively, the EK group exhibited superior weight loss compared to the HM group (EK: -7.73% vs. HM: -6.27%, p=0.012). The anti-obesity effect was positively associated with EK therapy frequency and herbal medicine duration. In vivo, EK significantly improved insulin sensitivity and mitigated infiltration of adipose tissue macrophages (ATMs) by modulating the CD11c+ and CD206+ subtypes. EK also correlated with increased Bacteroidetes and Firmicutes populations and reduced Proteobacteria and Verrucomicrobia. Consequently, EK is an effective adjunctive anti-obesity therapy offering metabolic benefits by modulating ATMs and gut microbiota profiles.

Background. Coronary artery disease (CAD) with extensive stenosis presents significant clinical challenges. This case report details the management and outcomes of a 61-year-old male with a notable history of CAD, initially treated with coronary artery bypass grafting (CABG), followed by an innovative intravenous hydrogen and oxygen nanobubble therapy due to recurrent symptoms.Case Presentation. Mr. BH was diagnosed with significant stenosis in the left anterior descending (LAD) artery and left circumflex (LCx) artery, initially managed by CABG. Recurring symptoms led to the adoption of a novel treatment involving hydrogen and oxygen nanobubbles. Following treatment initiation, Mr. BH experienced substantial improvements in physical capacity and symptomatic relief, with an ability to climb 22 flights of stairs and resolution of previous symptoms such as dyspnea and cough. Despite these improvements, subsequent imaging revealed in-stent restenosis and progression of graft disease.Discussion. The application of hydrogen and oxygen nanobubbles as a therapy in CAD is explored, highlighting potential mechanisms such as reduction of oxidative stress and improvement in endothelial function. This case contrasts the effects of conventional surgical and pharmaceutical interventions with the novel nanobubble therapy, illustrating both the benefits and complexities of managing advanced CAD with innovative treatments.Conclusion. While Mr. BH showed clinical improvement with nanobubble therapy, the development of new severe stenosis and restenosis underscores the need for further research to understand the long-term efficacy and mechanisms of nanobubble therapy in complex CAD cases. This case suggests that while innovative therapies may provide symptomatic relief and functional improvement, they do not obviate the need for ongoing surveillance and possibly further intervention.

The aim of this article is to present the course of the COVID-19 pandemic in Poland in 2020-2022, the formation of ad hoc health and anti-crisis policies, an assessment of crisis management and the perceived impact of the pandemic and anti-crisis measures.The paper draws on literature, official reports on the pandemic, data from Eurostat and other information from state institutions and public organisations.Particular attention was paid to the analysis and evaluation of the objectives, instruments and effects of the policies pursued by the state in a coordinated manner, i.e. the anti-pandemic policy and the anti-crisis policy. The anti-pandemic policy in Poland has failed to protect the country from significant personal losses and negative impacts on the health of the population and demographic processes.The anti-crisis policy of the state carried out with the mobilisation of businesses and disciplined society, in the form of anti-crisis shields supplemented and adjusted on an ongoing basis, allowed Poland to avoid a deep crisis and economic recession. Attention was drawn to the need to coordinate the management of health and economic crises nationally and internationally, and to the need to have a medium-term anti-crisis state strategy and a system for the early detection of crisis symptoms.

Both soybean variety and processing affect product characteristics. This study’s objective was to characterize the effect of four extraction methods (variations of soaking and grinding) combined with cooking on the content and composition of phenolic substances, antioxidant and anti-DU145 prostate cancer cell proliferative properties of soymilk prepared from a yellow soybean of the ProSoy variety, which is a high protein variety. Results showed soymilk processing yield was the greatest by Method 4, but Method 2 gave the highest solids and protein yields by about 14 and 12%, respectively. Method 4, a two-step grinding also increased yields (8 and 7%, for solids and protein, respectively), and in all but one instance produced higher total phenolic content (TPC), total flavonoid content (TFC), condensed tannin content (CTC) and total isoflavone content in both raw and cooked soymilk as compared to Method 1. Cooking soymilk reduced 14-17% of total phenolic substances. Cooking reduced anticancer capacity of Method-4-prepared soymilk phenolic extract by increasing IC50 value from about 4.9 mg/mL to 6.8 mg/mL. The increases in phenolic compounds and antioxidants produced in Prosoy soymilk by Methods 2 and 4 with simultaneous increases in product solids yield are significant to benefit the soymilk industry and consumer health. Keywords: ProSoy yellow soybean, soymilk processing, phenolics, isoflavones, antioxidant capacity, anti-DU145 prostate cancer proliferation

Litsea martabanica root's antioxidant and AChE activity showed promise as a pesticide detoxification agent in our previous study. In addition to roots, its leaves can help mitigate pesticide exposure, although there is limited scientific evidence supporting their efficacy. However, the use of roots in many countries, such as Thailand, could contribute to environmental degradation, as highland communities traditionally cut down whole trees to obtain them. This study aims to evaluate the antioxidant activity and anti-pesticide potential of water extracts from L. martabanica leaves instead of its roots through in vitro and in vivo investigations. The findings showed that L. martabanica water extracts and fractions demonstrated varied antioxidant activity. The water extract, obtained using traditional extraction methods, was chosen for in vivo experiments. Rats received the extract followed by chlorpyrifos exposure for 16 days. Results indicated reduced acetylcholinesterase activity in chlorpyrifos-exposed rats, while treatment with leaf extract led to increased activity, suggesting its potential as a detoxifying agent. Histopathological examination revealed no liver cell necrosis and showed liver cell regeneration, indicating potential protection against free radical-induced liver damage without affecting rat liver weight or biochemical profiles. Utilizing L. martabanica leaves for healthcare purposes holds promise without negative environmental impact.