Mothers of children with a specific clinical condition such as type 1 diabetes mellitus (T1DM) may experience higher levels of stress predisposing them to a poorer perception of quality of life and alterations in nutritional status. The aim of this research was to evaluate the relationship between nutritional status and quality of life perception of mothers caring for children with Type 1 Diabetes Mellitus. This research was conducted from July to September 2022, with mothers of children aged 5 to 10 years with diabetes. Data were collected through an online questionnaire including soci-oeconomic information, anthropometric data, clinical data of the children, and the WHO-QOL-abbreviated quality of life questionnaire. For statistical analysis, Statistical Package for Social Science 24 was used. Fifty-five mothers of children with diabetes were evaluated. Over 33% of the mothers were overweight and reported a regular perception of quality of life. Higher BMI was associated with poorer perception of quality of life in the psychological and self-assessment domains, and longer diagnosis time was associated with better perception of quality of life in the physical, psychological, and environmental domains. Therefore, it is understood that actions aimed at improving the quality of life of these mothers are necessary.

The purpose of this study was to determine the maximum tolerated dose (MTD) for stereotactic body radiation therapy (SBRT) in the treatment of non-metastatic prostate cancer. This study was a phase 1 dose escalation trial conducted in Japan. Patients with histologically proven prostate cancer without lymph node or distant metastasis were enrolled. The prescribed doses were 42.5, 45, or 47.5 Gy in five fractions. Dose-limiting toxicity (DLT) was defined as grade (G) 3+ gastrointestinal or genitourinary toxicity within 180 days after SBRT completion and a 6 plus 6 design was used as the method of dose escalation. A total of 16 patients were enrolled, with 6 in the 42.5 Gy group and 10 in the 45 Gy group. No DLT was observed in the 42.5 Gy group. In the 45 Gy group, one patient experienced G3 rectal hemorrhage, and another had G4 rectal perforation, leading to the determination of 42.5 Gy as the MTD. None of the patients experienced biochemical recurrence or death during the follow-up period. We concluded that SBRT for non-metastatic prostate cancer at 42.5 Gy in 5 fractions could be safely performed, but a total dose of 45 Gy increased severe toxicity.

The main purpose of this article is to consider the smoothness control of a weak solution after some moment if there is known solution regularity until this moment. The necessary tools can be varied. It is possible to control kinetic energy dissipation to fix moment or changing of velocity square or summability of acceleration square to fix at point time.

Mutations of PKD1 coding for polycystin-1 (PC1) account for most of the autosomal dominant polycystic kidney disease (ADPKD). The extracellular region of PC1 contains many evolutionarily conserved domains for ligand interactions. Among these is the leucine-rich repeats (LRR) in the far N-terminus of PC1. Using zebrafish (Danio rerio) as an in vivo model system, we explored the role of LRR in the function of PC1. Zebrafish expresses two human PKD1 paralogs, pkd1a and pkd1b. Knockdown of both genes in zebrafish by morpholino antisense oligonucleotides produced phenotypes of dorsal axis curvature and pronephric cyst formation. We found that overexpression of LRR suppressed both phenotypes in pkd1-morphant zebrafish. Purified recombinant LRR domain inhibited proliferation of HEK cells in culture and interacted with the heterotrimeric basement membrane protein laminin-511 (α5β1γ1) in vitro. Mutations of amino acid residues in LRR structurally predicted to bind laminin-511 disrupted LRR-laminin interaction in vitro and neutralized the ability of LRR to inhibit cell proliferation and cystogenesis. Our data support the hypothesis that the extracellular region of PC1 plays a role in modulating PC1 interaction with the extracellular matrix and contributes to cystogenesis of PC1-deficiency.

In 2019, due to the global pandemic of the new coronavirus (SARS-CoV-2), lockdown was imposed in Greece. Children with Type 1 Diabetes (T1D) during that period had to maintain a good level of glycemic control despite the subversive changes in their lives. The aim of this study was to assess the impact of lockdown on glycemic control and lifestyle changes of children with type 1 diabetes. The present cross-sectional study included 59 children with T1D who measured their glucose levels through glucose monitoring systems (Continuous Glucose Monitoring, CGM) and Flash Glucose Monitoring (FGM)). Their glycemic profile and demographic data were recorded in three different periods (before, during and after the lockdown). The changes in their daily routine were farther investigated through a short questionnaire which assesses changes in lifestyle-related behavior during COVID 19 pandemic. A significant improvement was noted in the glycemic control of children with T1D during the restrictive measures. Boys scored higher on scale of lifestyle behavior changes during the pandemic (-0.1 vs. -0.3, p=0.015). The results of this study highlight the need for continuous education and insistence on children's adherence with the treatment plan and the beneficial effects of using the new technology for easier monitoring.

Polydatin, a polyphenolic compound sourced from various natural origins, has garnered attention due to its potential anti-tumor properties and low toxicity. This research utilized Molecular Docking methods to investigate the molecular interactions between Polydatin and the Crystal Structure of Human UDP-glucuronic acid decarboxylase (UXS1), aiming to uncover the mechanisms contributing to its anti-tumor effects. The study revealed a substantial binding energy value of approximately -10 kcal/mol for the Polydatin-UXS1 interaction, indicating a robust and favorable binding. This suggests that Polydatin holds significant promise in cancer research, offering insights into its ability to interact with and potentially modulate the activity of UXS1. Moreover, the additional step of predicting toxicity properties using the pKCSM server provides valuable insights into the safety profiles of polydatin ( or piceid). From these results, the parameters for polydatin: —Max. tolerated dose (human),- Oral Rat Acute Toxicity (LD50), and - Oral Rat Chronic Toxicity (LOAEL)—suggest a favorable safety profile.These findings position Polydatin as a compelling candidate for further exploration in cancer research, highlighting both its efficacy and safety considerations.

Human sepsis is one of the leading cause of death worldwide and is known to be a harmful damaging host inflammatory condition, primarily caused by endotoxin released by gram-negative bacteria. Despite antibiotics administration being widely used to treat disease, effective targeted therapeutic strategies for the sepsis are still lacking. Here, we demonstrate that CM1, a derivative of natural polyphenol chrysin, exerts anti-inflammatory activity by inducing the ubiquitin-editing protein TNFAIP3 and NAD-dependent deacetylase sirtuin 1 (SIRT1). We found that CM1 attenuated Toll-like receptor 4 (TLR4)-induced the generation of inflammatory cytokines by inhibiting the extracellular-signal-regulated kinase (ERK)/MAPK and nuclear factor kappa B (NF-κB) signaling pathway. In addition, the treatment of macrophages with CM1 induced the expression of TNFAIP3 and SIRT1 in TLR4-stimulated primary macrophages, however the anti-inflammatory properties of CM1 was disappeared by siRNA silencing of TNFAPI3 or by the genetic and pharmacologic inhibition of SIRT1. Importantly, intravenously administration of CM1 resulted in the decreased susceptibility to endotoxin-induced sepsis, leading to inhibition of the generation of proinflammatory cytokines and neutrophils infiltration into lung than control mice. Collectively, these findings suggest that CM1 has the potential to be a treatment candidate for diverse inflammatory diseases including sepsis.

The 2-Acetyl-1-pyrroline (2-AP) is the most important volatile in determining the aroma of fragrant rice, however, the transcriptional regulation mechanism of 2-AP biosynthesis in fragrant rice is still unclear. In this study, the Osp5cs1 knockout mutant lines and OsP5CS1 over-expression lines were constructed by genetic transformation of indica rice cultivar i.e., ‘Zhonghua11’, which was knocked out OsBADH2 to produce fragrance in aromatic rice. The OsP5CS1 gene was also identified as a key gene in the 2-AP biosynthesis pathway of aromatic rice. The OsP5CS1 promoter was used as bait, and the transcription factor OsbZIP60-like was screened by yeast one-hybrid assays. The transcription factor OsbZIP60-like specifically bound to the OsP5CS1 gene. The dual luciferase reporting system found that OsbZIP60-like transcription factor promoted the transcriptional activation of OsP5CS1. Compared with the wild type, the OsP5CS1 gene expression was significantly down-regulated in Osbzip60-like mutant, and resulted in substantial reduction in 2-AP biosynthesis. Moreover, the OsP5CS1 gene expression was significantly up-regulated in OsbZIP60-like over-expressed plants, and the 2-AP concentrations were also increased whereas the Osbzip60-like mutants were found to be sensitive to Zn deficiency. Overall, the OsbZIP60-like transcription factor promoted the 2-AP accumulation. This study provides a theoretical basis for the transcriptional regulation mechanism of 2-AP biosynthesis and explores the function of OsbZIP transcription factor in fragrant rice.

Introduction. This retrospective study aimed to compare the risk factors for vascular calcification (VC) between pre-hemodialysis (HD) and prevalent HD adult patients while investigating associations with calcification biomarkers. Methods. Baseline data from 30 pre-HD and 85 HD patients were analyzed, including iPTH, vitamin D, FGF23, fetuinA, sclerostin, and VC scores (Adragao method). Multivariable linear regression identified VC predictors. Results: The prevalence of VC was similar in both groups, but HD patients had more pronounced VC scores ≥6. Pre-HD patients were older, with higher prevalence of Balkan endemic nephropathy, hypertension, and less frequent use of calcium phosphate binders. Both groups exhibited similar patterns of hyperphosphatemia, low vitamin D, and iPTH levels. In HD group normal phosphate was significantly common in patients with VC, whereas hyperphosphatemia was significantly common in patients without VC. Fetuin-A levels were higher in pre-HD patients, while FGF23 was elevated in HD patients. In pre-HD patients, male gender was associated with reduced VC risk, while in HD patients, malignancies and serum phosphate levels were negative VC predictors. Conclusion: Effective monitoring and tailored treatment of VC in CKD are still focused on phosphate regulation. Besides, mineral disturbances, hormones and biomarkers regulation, and patient-specific variables need to be considered.

This review summarizes the currently known biochemical neuroadaptive mechanisms of remote ischemic conditioning. In particular, it focuses on the significance of the pro-adaptive effects of remote ischemic conditioning, which allow prevention of neurological and cognitive impairments associated with hippocampal dysregulation after brain damage. The neuro-immuno-humoral pathway of transmitting a conditioning stimulus, as well as the molecular basis of the early and delayed phases of neuroprotection, including anti-apoptotic, antioxidant and anti-inflammatory components, are also outlined. Based on the close interplay between the effects of ischemia, especially mediated by interaction of HIF factors and steroid hormones, the involvement of the hypothalamic-pituitary-adrenocortical system in remote ischemic conditioning is also discussed.

Cisplatin (CDDP), an important chemotherapeutic agent, could result in potential hepatotoxicity, but the precious molecular mechanisms remain unclear. In this study, the protective effect of ellagic acid (EA) on CDDP exposure-induced hepatotoxicity and underlying molecular mechanisms were investigated using a mouse model. Mice were randomly divided into control, CDDP model, EA100 (i.e., EA 100 mg/kg/day), and CDDP plus EA 25, 50, and 100 mg/kg/day. Mice in all CDDP-treated groups were intraperitoneally injected with CDDP 20 mg/kg/day for 2 days. In all EA co-treatments, mice were orally administrated with EA for 7 days. Our results found that, compared to the control group, CDDP treatment resulted in liver dysfunction, oxidative stress, and hepatocyte necrosis, which are effectively revised by EA supplementation in a dose-dependent manner. Meanwhile, EA supplementation inhibited CDDP-induced the elevation of caspases-9 and -3 activities in the liver tissues of mice. Furthermore, EA supplementation significantly downregulated CDDP exposure-induced the increases of NF-κB, IL-1β, TNF-α, and IL-6 proteins and mRNAs, while further upregulated the expression of Nrf2, and HO-1 proteins and mRNAs. Taken together, our results reveal that EA supplementation could ameliorate CCDP-induced liver injury in mice via the opposite regulation of Nrf2/HO-1 and NF-kB pathways.

Microbial-mediated biogeochemical cycling of iron is widespread in anaerobic environments such as sediments and deep Earth aquifers, and is one of the major pathways for metabolising iron in nature. Organic matter containing quinone groups can act as electron shuttles to transfer electrons between microorganisms and Fe(III) oxides, facilitating the biotransformation of iron; this process also influences the transport transformation of pollutants. In this paper, the reduction of Fe(III) oxides by aniline in the heterogeneous iron-reducing bacterium Shewanella oneidensis MR-1 mediated by the electron shuttle AQS was investigated. The results showed that aniline significantly promoted the reduction of Fe(III) by MR-1 in the AQS-mediated reaction, and the best Fe(III) reduction was achieved in the reaction group of "GT+MR-1+0.5mM AQS+3μM aniline", in which the Fe(II) production was significantly higher than that in the reaction groups of only microorganisms and no aniline reaction. The amount of Fe(II) produced was significantly higher than that of the microorganism-only and aniline-free reaction groups, and the addition of aniline also significantly increased the consumption of sodium lactate by MR-1 in the reaction system. The solid mineral Fe(II)-O content increased to 41.32% after the reaction. However, the structure of needle ferrite is relatively stable, and the surface morphology did not change significantly by SEM, and the generation of other secondary minerals was not observed in the XRD results. The results of this experimental study can help to understand the biogeochemical cycle of iron in multicomponent reactions and are of great significance for environmental management.

The natural flavonoid epigallocatechin gallate (EGCG) has a wide range of biological activities including binding to nucleic acids; however, mechanisms of interaction of EGCG with DNA organized in chromatin have not been systematically studied. In this work, interaction of EGCG with chromatin in cells, and with nucleosomes and chromatosomes in vitro was studied using fluorescent microscopy and single particle Förster resonance energy transfer approaches, respectively. EGCG effectively penetrates into the nuclei of living cells and binds to DNA there. Interaction of EGCG with nucleosomes in vitro induces large-scale, reversible uncoiling of nucleosomal DNA that occurs without dissociation of DNA or core histones at sub- and low-micromolar concentrations of EGCG. EGCG does not reduce the catalytic activity of poly(ADP-ribose) polymerase 1 (PARP1), but causes modulation of the structure of the PARP1-nucleosome complex. EGCG significantly changes the structure of chromatosomes, but does not cause dissociation of the linker histone. Reorganization of nucleosomes and chromatosomes by EGCG might facilitate access of protein factors involved in DNA repair, replication and transcription to DNA and thus might contribute to the modulation of gene expression by EGCG that was reported earlier.

The human T-cell leukemia virus type 1 (HTLV-1) is the only known human oncogenic retrovirus. HTLV-1 can cause a cancer called adult T-cell leukemia/lymphoma (ATL). The virus is transmitted through body fluids of infected individuals, primarily breast milk, blood, and semen. At least 5–10 million people in the world are infected with HTLV-1. In addition to ATL, HTLV-1 infection can also cause HTLV-I-associated myelopathy (HAM /TSP). ATL is characterized by low viral ex-pression and poor prognosis. The oncogenesis triggered by HTLV-1 is extremely complex and the molecular mechanisms are not fully understood. However, viral regulatory proteins Tax and HTLV-1 bZIP factor (HBZ) have been shown to play key roles in the transformation of HTLV-1-infected T cells. Moreover, several studies have shown that the final fate of HTLV-1-infected transformed T cell clones is the result of a complex interplay of HTLV-1 oncogenic protein expression with cellular transcription factors that subvert the cell cycle and disrupt reg-ulated cell death, thereby exerting their transforming effects. This review provides updated in-formation on the mechanisms underlying the transforming action of HTLV-1 and the potential therapeutic targets to combat ATL.

Soluble cell adhesion molecules (sCAMs) are secreted ectodomain fragments of surface adhesion molecules, ICAM1 and VCAM1. sCAMs have diverse immune functions beyond their primary function, impacting immune cell recruitment and activation. Elevated sVCAM1 levels have been associated with poor cardiovascular disease (CVD) outcomes, supporting its role as a potential diagnostic marker and therapeutic target. Inhibiting sVCAM1 release or interaction with immune cells could offer cardioprotection in conditions such as diabetes. Membrane bound surface adhesion molecules are widely expressed in a wide variety of cell types with higher expression in endothelial cells (ECs), but the source of sCAMs in the circulation is not clear. Hypothesizing that endothelial cells (ECs) could be a potential source of sCAMs, this study investigated whether dysfunctional EC signaling mechanisms during diabetes cause VCAM1 ectodomain shedding. Our results from samples from a inducible diabetic mouse model revealed increased sVCAM1 plasma levels in diabetes. Protein analysis indicated upregulated VCAM1 expression and metalloproteases ADAM10 and ADAM17 in diabetic ECs. ADAMs are known for proteolytic cleavage of adhesion molecules, contributing to inflammation. GSK3β, implicated in EC VCAM1 expression, was found to be activated in diabetic ECs. GSK3β overexpression in control ECs increased ADAM10/17 and VCAM1. A GSK3β inhibitor reduced active GSK3β and VCAM1 ectodomain shedding. These findings suggest that diabetic ECs with elevated GSK3β activity led to VCAM1 upregulation and ADAM10/17-mediated sVCAM1 shedding. This mechanism underscores the potential therapeutic role of GSK3β inhibition in reducing the levels of circulating sVCAM1. The complex roles of sCAMs extend well beyond CVD. Thus, unraveling the intricate involvement of sCAMs in the initiation and progression of vascular disease particularly in diabetes, holds significant therapeutic potential.

Glycated hemoglobin (HbA1c) is used to assess glycemic control in Type 1 diabetes (DM1) patients. Apolipoproteins play an essential role in DM1 pathophysiology and may be associated with complications, as well as HbA1c. This cross-sectional observational study consisting of 81 children and adolescents of both sexes diagnosed with DM1 investigated the relationship between body fat distribution and lean mass with HbA1C and apolipoprotein values analyzing biochemical and body composition measurements. Shapiro-Wilk test with Lilliefors correction, non-parametric Mann-Whitney test, and others were used with a significance level of 5%. The sample had a diagnosis time of 4.32 years and high blood glucose levels (mean 178.19 mg/dL) and HbA1c (mean 8.57%). Subjects also had a moderate level of adiposity, as indicated by arm and thigh fat areas. The study also found significant differences in the distribution of patients concerning levels of apolipoproteins A and B, with a smaller proportion of patients having undesirable levels. Finally, the study found a significant difference in the distribution of patients with estimated cardiovascular risk based on the ApoB/ApoA-1 ratio. Conclusively, visceral fat in children and adolescents with DM1 may increase the risk of DM1 long-term complications owing to its association with elevated HbA1C and apolipoprotein values.

Type 1 diabetes (T1D) is associated with hyperglycaemia-induced hypoxia and inflammation. The study assessed the effects of a single high-intensity interval exercise (HIIE) on glycaemia (BG) and serum level of pro-inflammatory cytokines and an essential mediator of adaptive response to hypoxia in T1D patients. The macronutrients intake was also evaluated. Nine patients suffering from T1D for about 12 years and nine healthy individuals (CG) were enrolled and completed one session of HIIE at the intensity of 120% lactate threshold and duration of 4 x 5 min intermittent with 5 min rest after each bout of exercise. Capillary and venous blood was withdrawn at rest, immediately after and at the 24 h post-HIIE for analysis of BG, hypoxia-inducible factor alpha (HIF-1α), tumour necrosis factor alpha (TNF-α) and vascular-endothelial growth factor (VEGF). Pre-exercise BG was significantly higher in the T1D compared to the CG (p = 0.043). HIIE led to a significant decline in T1D patients’ BG (p = 0.027) and to a tendency for a lower BG at 24-h post-HIIE vs pre-HIIE. HIF-1α was significantly elevated in the T1D compared to CG and there was a trend for HIF-1α to decline, and VEGF, TNF-α to increase in response to HIIE in the T1D group. Both groups consumed higher and lower than recommended amounts of protein and fat, respectively. In T1D group, a tendency for a higher digestible carbohydrate intake and more frequent hyperglycaemic episodes on the day after HIIE were observed. HIIE was effective in reducing T1D patients’ glycaemia and improving the short-term glycaemic control. HIIE has the potential to improve adaptive response to hypoxia by elevating the serum level of VEGF. Patients’ diet and level of physical activity should be screened on a regular basis, and they should be educated on the glycaemic effects of digestible carbohydrates.

The altimeter-derived ocean currents have been sparsely evaluated against in situ measurements in the Arctic, particularly for extended time periods. This study uses the extensive mooring array situated in the Fram Strait, representing one of the longest ocean current records, to investigate the relationship between in situ and satellite-derived currents in the region. The primary objective of this research is to analyze the vertical structure of the West Spitsbergen Current (WSC), its spatio-temporal coherence, and its association with surface geostrophic currents during the period of 1997-2012. To assess the vertical structure of the WSC, we utilized the Empirical Orthogonal Functions (EOF) and cross-correlation analysis between neighboring moorings. Remarkably, both velocity components exhibited robust vertical coherence, particularly within the waters of the North Atlantic Inflow, at depths exceeding 800 m. These findings underscore the potential for surface measurements to effectively complement data gaps and facilitate the reconstruction of deeper currents with a monthly temporal resolution. Notably, the surface measurements explain approximately 67% of the variance in the top 800 m of the water column.This comprehensive investigation advances our understanding of the West Spitsbergen Current and its vertical characteristics in the Arctic. Moreover, our findings highlight the valuable synergy between in situ and satellite-derived data, providing critical insights for future ocean current studies in this ecologically sensitive region.

Background: With the increasing global incidence of diabetes mellitus (DM), diabetic retinopathy (DR) has become one of the leading causes of blindness in developed countries. DR leads to changes in retinal neurons and microcirculation. Rtx1TM (Imagine Eyes, France) is a microscope that allows histological visualisations of cones and retinal microcirculation throughout the DM duration. Objective: This study aimed to analyse the cones and retinal microvascular changes in 50 diabetic individuals and 18 healthy volunteers. The patients participated in the initial visit and two fol-low-up appointments: one and two years after the study, beginning with rtx1 image acquisition, visual acuity assessment, macular OCT scans and blood measurements. Results: The study revealed significant differences in the cone density, mosaic arrangement and vascular morphology between healthy and diabetic patients. The final measurements have shown decreased photoreceptor and microvascular parameters in the DR group compared to the control group. Furthermore, in the 2-year follow-up, both groups' rtx1-acquired morphological changes were statistically significant. Conclusions: Rtx-1 technology was successfully used as a non-invasive method of photoreceptors and retinal vasculature assessment over time in patients with diabetic retinopathy. The study has revealed a trend toward more vascular morphological changes occurring over time in diabetic patients.

Diabetes may cause an increase blood levels of cytokines inducing a rising of C reactive protein (PCR) and fibrinogen stimulating a subclinical inflammation which lead to adhesive molecules expression and to endothelial disfunction. A comprehensive panel of type 1 diabetes mellitus (T1DM) interleukins polymorphisms is not provided yet. As chronic periodontitis (CP) is considered the sixth complication of DM, a clarification is needed about the inflammatory role managed by single nucleotides polymorphisms (SNPs). The goal of this review is to focus on the significant diversity of SNPs in T1DM patients with and without CP. After a digital search on PubMed and Scopus with reference to the last 5 years, 21 items were enrolled. Several ILs were analyzed. T1DM still needs to be thoroughly explored regarding the ILs polymorphisms panel, however the last 5 years have led to the increased independence of this condition, causing autonomous inflammatory effects which requires further investigations. CP and T1DM association in children and adolescents represents a severe gap in literature that should be filled, the scarce presence of studies also about adults serves as a motivation for ulterior clinical researches

Background and Objectives: Mechanical and biological complications can lead to system fracture or screw loss on dental implants. Narrow and regular platforms have been used without a consensus about the effect of distance the abutment from the prosthetic platform margin. The aim of this study is to evaluate different insertion torques in the deformation of tri-channel platform connections through two- and three-dimensional measurements with micro-CT. Materials and Methods: 164 implants were divided into groups (platform diameter and type): 3.5, 3.75, and 4.3 mm NP (Narrow Platform), and 4.3 mm RP (Regular Platform). Each implant-platform group was then divided into four subgroups (n = 10) with different torques: T45 (45 Ncm), T80 (80 Ncm), T120 (120 Ncm) and T150 (150 Ncm). The implant-abutment-screw assemblies were scanned and the images obtained were analyzed. Results: A significant difference was observed for the linear and volume measures between the different platforms (p <0.01) and the different implant insertion torques (p <0.01). Qualitative analysis suggested higher deformation resistance for the 3.75 NP compared to the 3.5 NP, and RP was more resistant compared to the NP. Conclusions: The 0.25-mm increment in the implant platform did not increase the resistance to the applied insertion torques; the 4.3-mm implant was significantly stronger compared to the 3.5-mm implant and the proposed micro-CT analysis was considered valid for both 2D and 3D analyses of micro gaps, qualitatively and quantitatively.

Porcine parvovirus (PPV) 1 is a major causative pathogen of reproductive failure, and porcine circovirus (PCV) 2 is an etiological pathogen causing PCV-associated and PCV diseases worldwide. PPV2–6 and PCV3 were recently identified as newly emerging viruses with unknown pathogeneses. However, little is known of PPV1–6 and PCV3 effects or their co-infections with PCV2. In this study, we examined 926 samples (272 aborted pig fetuses and 654 pig lung tissues) from domestic pig farms for the presence of PPV1–6 or PCV3 and for PCV2 co-infection with these seven viruses. The prevalence of PPV and PCV was significantly greater in lung tissue samples than aborted pig fetus samples. PPV3–6 were detected for the first time in Korean domestic pigs. Co-infection rates with PCV2 and other viruses were significantly higher in abattoir samples than that in aborted pig fetus samples. Concurrent infections are more common than single infection in pig population and nu-merous infectious pathogens such as PPV and PCV2 can impact the respiratory diseases. Fur-thermore, Korean PPV1 strain (PPV1-82) was identical to the virulent PPV-27a strain in this respect. Our results describe, for the first time the prevalence of PPV1–6 and PCV3 infections and their co-infection rates with PCV2 in Korean domestic pigs.

Crataegus Oxyacantha is used in the treatment of cardiovascular diseases. In related to your biosafety, only in vitro and in vivo genotoxicity of the fruit and the leaf is described, however, the teratogenic potential is unknown. The aim this study was evaluating the transplacental genotoxicity effect of aqueous and hydroalcoholic extract of leaves C. oxyacantha in a rat model and the quantification of malondialdehyde (MDA) in liver. Three different doses of the aqueous and hydroalcoholic extracts of the C. oxyacantha leaf were administered orally (500, 1000 and 2000 mg/kg) to Wistar rats during 5 days through the pregnancy term (16-21 days), sampling in rats were every 24 h during the last 6 days of gestation and only one sample was taken in neonates at birth. A sample of the mother's and neonate's liver was taken for the determination of MDA. The results show that, at the hepatic level, the evaluated doses of extracts C. oxyacantha in pregnant rats and their pups did not show cytotoxicity. However, the aqueous and hydroalcoholic extract generated cytotoxic and genotoxic damage in the short term. On the other hand, only the aqueous extract showed a teratogenic effect. Based on these results, the aqueous and hydroalcoholic extracts of the C. oxyacantha leaf should not be administered during pregnancy.

A large body of evidence indicates that environmental agents can induce alterations in DNA methylation (DNAm) profiles. Radiofrequency electromagnetic fields (RF-EMFs) are radiations emitted by everyday devices which have been classified as “possibly carcinogenic”, however their biological effects are unclear. As aberrant DNAm of genomic repetitive elements (RE) may promote genomic instability, here we sought to determine whether exposure to RF-EMFs could affect DNAm of different classes of RE, such as long interspersed nuclear element1s (LINE-1), Alu short interspersed nuclear element and ribosomal repeats. To this purpose, we analysed DNAm profiles of cervical cancer and neuroblastoma cell lines (HeLa, BE(2)C and SH-SY5Y) exposed to 900 MHz GSM-modulated RF-EMF through an Illumina-based targeted deep bisulfite sequencing approach. Our findings showed that radiofrequency exposure did not affect DNAm of Alu elements in any of the cell lines analysed. Conversely, it influenced DNAm of LINE1 and ribosomal repeats in terms of both average profiles and organization of methylated and un-methylated CpG sites, in different ways in each of the three cell lines studied.

HAX1 is a multifunctional protein involved in the antagonism of apoptosis in cellular response to oxidative stress. In the present study we identified HAX1 as novel binding partner for Che-1/AATF, a pro-survival factor which plays a crucial role in fundamental processes, including response to multiple stresses and apoptosis. HAX1 and Che-1 proteins show extensive colocalization in mitochondria and we demonstrated that their association is strengthened after oxidative stress stimuli. Interestingly, in MCF-7 cells, resembling luminal estrogen receptor (ER) positive breast cancer, we found that Che-1 depletion correlates with decreased HAX1 mRNA and protein levels, and this event is not significantly affected by oxidative stress induction. Furthermore, we observed an enhancement of the previously reported interaction between HAX1 and estrogen receptor alpha (ERα) upon H2O2 treatment. These results indicate the two anti-apoptotic proteins HAX1 and Che-1 as coordinated players in cellular response to oxidative stress with a potential role in estrogen sensitive breast cancer cells.

Background: Visceral leishmaniasis affects approximately 12 million people worldwide. Current existing drugs cause several side effects and resistance, the identification of new therapeutic targets for the development of new drugs is necessary. The vesicular trafficking in the parasite flagellar pocket is essential for parasite survival and proliferation, but little is known about the proteins involved in the endocytic/secretory pathways. In this work, we are describing the characterization of a transporter cargo protein SFT-2/Got-1 like in Leishmania infantum. Material and Methods: Using bioinformatics tools, the putative Got-1 protein A4HSK3 was characterized structurally and phylogenetically. Molecular biology was used to clone and express the protein and confocal fluorescence to determine its subcellular localization. Results: The Got-1 like protein presents four alpha helix TM conserved domains (aa38-aa147) characteristics of the Got-1/SFT-2 family proteins and an important Pen-2 conserved motif LGDYXXF located in the extracellular loop. Confocal microscopy suggests that Got-1/SFT-2 like is localized in the flagellar pocket, and is partially co-localized with the L. infantum presenilin-like protein. Phylogenetically, the Leishmania sp Got-1 like is contained in a subgroup of proteins clearly detached from the other Trypanosomatidae, such as T. cruzi and T. brucei. Conclusions: Our data show the presence of an important transported proteins, and its colocalization with the presenilin aspartyl protease in the flagellar pocket of the L. infantum open new perspectives to identify novel targets, which can be an alternative therapeutic strategy against leishmaniasis.

Using the nematode C. elegans germline as a model system, we previously reported that PUF-8 (a PUF RNA-binding protein) and LIP-1 (a dual-specificity phosphatase) repress sperm fate at 20°C and the dedifferentiation of spermatocytes into mitotic cells (termed "spermatocyte dedifferentiation") at 25°C. Thus, double mutants lacking both PUF-8 and LIP-1 produce excess sperm at 20°C, and their spermatocytes return to mitotically dividing cells via dedifferentiation at 25°C, resulting in germline tumors. To gain insight into the molecular competence for spermatocyte dedifferentiation, we compared the germline phenotypes of three mutant strains – fem-3(q20gf), puf-8(q725; fem-3(q20gf), and puf-8(q725); lip-1(zh15). Both fem-3(q20gf) and puf-8(q725); fem-3(q20gf) mutants produced excess sperm like puf-8(q725); lip-1(zh15) double mutants. Our results show that spermatocyte dedifferentiation was not observed in fem-3(q20gf) mutants, but it was more aggressive in puf-8(q725); lip-1(zh15) than in puf-8(q725); fem-3(q20gf) mutants. These results suggest that MPK-1 (the C. elegans ERK1/2 MAPK ortholog) activation by removing the function of LIP-1 in the absence of PUF-8 promotes spermatocyte dedifferentiation. This idea was confirmed using Resveratrol (RSV), a potential activator of MPK-1 and ERK1/2 in C. elegans and human cells. Notably, spermatocyte dedifferentiation was significantly enhanced by RSV treatment, and its effect was blocked by mpk-1 RNAi. We, therefore, conclude that PUF-8 and MPK-1 are normally required to inhibit spermatocyte dedifferentiation and tumorigenesis. Since these regulators are broadly conserved, we suggest that similar regulatory circuitry may control cellular dedifferentiation and tumorigenesis in other organisms, including humans.

A new variant of the SARS-CoV-2 Omicron BA.5 virus has displaced all previous variants of the virus around the world. Preliminary assessment of the effectiveness of drugs for the prevention and treatment of COVID-19 requires the availability of infection models in animals. In this study, we characterize the infection model SARS-CoV-2 Omicron BA.5 and its progeny sublineage BE.1 in hACE2-transgenic mice and in Syrian hamsters. Both sublineages turned out to be pathogenic for animals – the challenged animals showed weight loss, a high level of viral load and acute inflammation in the lungs. Part of BA.5-infected mice died after virus challenge, indicating that this virus variant is more pathogenic than the previous BA.1 variant but less pathogenic than Wuhan variant.

Currently SARS-CoV-2 is spreading around the world as an Omicron strain. Recently, the Omicron variants (BQ.1 and BQ.1.1) were identified as novel Variants of Concern. UpToDate, there is little information about the Omicron Variants BQ.1 and BQ.1.1. The widely altered Omicron variants are spread globally, providing a high risk of infection surges with devastating consequences in some areas. The Omicron type of SARS-CoV-2 has a harm risk of reinfection, according to early reported findings. COVID-19 Variants particularly, BQ.1 and BQ.1.1 have gained global attention and caused a worldwide sensation since their discovery. Therefore, this communication discusses the present status of COVID-19 Variants BQ.1 and BQ.1.1, and their consequences.

The detection of waste plastics in the marine and terrestrial environment using satellite Earth Observation data offers the possibility of large-scale mapping, and reducing on-the-ground manual investigation. In addition, costs are kept to a minimum by utilizing free-to-access Copernicus data. A Machine Learning based classifier was developed to run on Sentinel-1 and -2 data. In support of the training and validation, a dataset was created with terrestrial and aquatic cases by manually digitizing varying landcover classes alongside plastics under the sub-categories of greenhouses, plastic, tyres and waste sites. The trained classifier, including an Artificial Neural Network and post-processing decision tree, was verified using five locations encompassing these different forms of plastic. Although exact matchups are challenging to digitize, the performance has generated high accuracy statistics, and the resulting land cover classifications have been used to map the occurrence of plastic waste in aquatic and terrestrial environments.

G‐quadruplexes (G4) are structures formed at the ends of the telomere, these are rich in guanines and were stabilized by molecules that bind to specific sites. TMPyP4 and Thymoquinone (TQ) are small molecules that bind to the G4, they have drawn attention because of their role as telomerase inhibitors. The aim of this study was to evaluate the effects of telomerase inhibitors on cellular proliferation, senescence, and death. Two cell lines LC‐HK2 (NSCLC) and RPE‐1 were treated with TMPyP4 (5μM) and TQ (10μM). Both inhibitors were effective in decreasing telomerase activity. TMPyP4 increased the percentage of cells with membrane damage associated with cell death and decreased the frequency of cells in the S‐phase. TMPyP4 changed the cell adhesion ability and modified the pattern of focal adhesion. TQ acted in a dose‐dependent manner, increasing the frequency of senescent cells, and inducing cell cycle arrest in the G1. In conclusion, the effects of both drugs on LC-HK2 and RPE-1 cell lines were different although both are telomerase inhibitors, because TMPyP4 decreased proteins of cell adhesion and TQ induces a decrease in cell viability.

The KRAS mutant population has been undruggable for 40 years. G12C inhibitors and immunotherapy are the beginning of success. It is necessary to summarize the successful experience of the existing treatment model and explore the direction of the next treatment. In this review, we discuss the latest developments in targeted therapy and immunotherapy for KRAS-mutation NSCLC, aiming to provide direction or enlightenment for future treatment strategies.

Bone marrow derived adult human mesenchymal stem cells (hMSCs) possess therapeutic qualities that enable them to enhance wound repair. However, the mechanisms by which this occurs remains poorly understood. Basic mechanisms may include the directed migration of delivered cells to target sites and/or the production and release of soluble factors that act at a distance. Allogeneic and even xenogeneic cells may effectively participate in wound repair. Labeled hMSCs were delivered to full-thickness skin wounds that were created in immunologically competent mice. The delivery occurred on day 3 post-wounding using two different carriers; one which released cells and one which retained cells. The fates of the delivered cells were tracked for up to 25 days. During this period, released cells migrated as a tight cohort deep into the wound to reach the subdermal vascular plexus. Simultaneously, enhanced formation of granulation tissue was evident. This migration of hMSCs was not essential in that enhanced granulation tissue formation and wound contraction occurred when cells were retained in the carrier matrix. This provided further evidence for the release of therapeutic factors by hMSCs to sites of injury.

The functioning of the parents’ emotional sphere is very important to a child’s mental and physical health. This study focused on investigating the association between mothers’ emotional intelligence (EI) and paediatric type I diabetes (T1DM) disease management in their children. We hypothesized that mothers’ EI is associated with T1DM outcomes. Mothers of children with T1DM aged 6-12 years were surveyed. One hundred and thirty-four mothers, the main caregivers of their diabetic children, provided measures of EI and completed a demographic questionnaire. The primary indicator of diabetes management was haemoglobin A1c (HbA1c; the main form of glycosylated haemoglobin). EI scales and subscales were associated with glycaemic management indices. Logistic regression analysis was applied for the assessment of the association between parents’ EI and their paediatric with T1DM disease management. The analysis demonstrated a statistically significant correlation between T1DM management and mothers’ ability to understand and control own emotions, to transform their own negative emotions into positive and to control own negative emotions. Mothers’ EI scales and subscales of understanding and regulating their own emotions, subscales of transforming their own negative emotions into positive ones and controlling their own negative emotions were statistically reliable predictors of glycaemic control in children with T1DM.

Characterised by the growth of benign tumours, fibropapillomatosis (FP) is a debilitating disease that predominantly afflicts the endangered green turtle (Chelonia mydas). A growing body of histological and molecular evidence has consistently associated FP tumours with Chelonid alphaherpesvirus 5 (ChHV5), leading this virus to be considered the most likely aetiological agent of FP. However, a recent study which detected both ChHV5 and Chelonia mydas papillomavirus 1 (CmPV1) DNA in FP tumour tissues has challenged this hypothesis. The present study aimed to establish the wider prevalence of CmPV1 and co-occurrence with ChHV5 in marine turtles in waters adjacent to the east coast of Queensland, Australia. This comprehensive molecular survey screened a total of 353 samples from 275 foraging turtles using probe-based qPCR. Three sample categories were used in this study: Group A (FP tumours), Group B (non-tumoured skin from turtles with FP tumours) and Group C (non-tumoured skin from turtles without FP tumours). Concurrent detection of ChHV5 and CmPV1 DNA is reported for all three categories, with the highest rate of concurrent detection reported for Group A samples (43.5%). Collectively, these results pivot the way we think about FP; as an infectious disease where two separate viruses may be at play.

Objective: We previously provided evidence to confirm that soluble Fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and their ratio, are useful tools to direct the management of preeclampsia (PE), fetal growth restriction (FGR), and PE+FGR near delivery. In this study we examine the potential additive value of Inhibin-A, a hormone marker of the transforming growth factor family. Methods: We used a cohort of 125 pregnant women enrolled near delivery at clinics of the University Medical Center of Ljubljana, Slovenia. There were 31 cases of PE, 16 of FGR, 42 of PE+FGR, 15 iatrogenic preterm delivery (PTD), and 21 unaffected controls with delivery of a healthy baby at term. Cases delivered before 34 weeks’ gestation included 13 of PE, 12 of FGR, 22 of PE+FGR, and 6 of PTD. We recorded demographic characteristics and medical history and the levels of PlGF, sFlt-1 and Inhibin-A. The predictive accuracy of each biomarker, their ratios, and combinations was estimated from areas under the curve (AUC) of Receiver Operating Characteristics (ROC) curves. We estimated accuracy by the continuous marker model and a cut-off model. Results: Combining Inhibin-A with PlGF or with the sFlt-1 / PlGF ratio showed a 10-20% increase in AUCs and 5-15% increase in the detection rate, at 10% false positive rate, of PE, and a lower, but significant, increase for PE+FGR but not for FGR alone. The use of a cut-off model was adequate, although a bit higher accuracy was obtained from the continuous model. Highest correlation was found for PlGF with all three complications. Conclusion: Inhibin-A improves the accuracy of predicting PE and PE+FGR provided by the angiogenic markers alone, bringing the results to a diagnostic level, thus assisting in directing clinical management. Inhibin-A had no added value for the accuracy of predicting FGR alone.

The theories of quantum mechanics and relativity dramatically altered our understanding of the universe ushering in the era of modern physics. Quantum theory deals with objects probabilistically at small scales, whereas relativity deals classically with motion in space and time. We show here that the mathematical structures of quantum theory and of relativity follow together from pure thought, defined and uniquely constrained by the same elementary ``combining and sequencing'' symmetries that underlie standard arithmetic and probability. The key is uncertainty, which inevitably accompanies observation of quantity and imposes the use of pairs of numbers. The symmetries then lead directly to the use of complex \sqrt{-1} arithmetic, the standard calculus of quantum mechanics, and the Lorentz transformations of relativistic spacetime. One dimension of time and three dimensions of space are thus derived as the profound and inevitable framework of physics.

Hepatic encephalopathy (HE) is a form of brain dysfunction that is specifically caused by liver insufficiency and/or portal-systemic shunt. The exact nature of HE is debated, so that conflicting uses of the term HE may cause inconsistencies in its detection and, in turn, issues with its management. This review highlights the meaning of the term HE on the basis of both its historical origins and current consensus. It also provides criteria for the diagnosis of the condition, on the basis of its phenotypes and the risk factors for its occurrence. The procedure for differential diagnosis from other conditions which result in similar phenotypes is considered, together with precipitants and confounders. Finally, the current multidimensional approach for the correct clinical recording of HE episodes is discussed.

The main objective of this study is to develop a Hapke photometric model that is suited for Chang’E-1 (CE-1) Interference Imaging Spectrometer (IIM) data. We first divided the moon into three areas including ‘maria’, ‘new highland’ and old ‘highland’ with similar photometry characteristic based on the Hapke parameters of the moon derived from Lunar Reconnaissance Orbiter Camera (LROC) Wide Angle Camera (WAC) multispectral data. Then, we selected the sample data in the ‘maria’ area and obtained a new set of Hapke model’s parameters that can best fit these data. Result shows that photometric correction using Hapke model with these new derived parameters can eliminate the effect of variations in viewing and luminating geometry, especially ‘opposition surge’, more efficiently than the empirical model. The corrected mosaic shows no significant artifacts along the tile boundaries, and more detailed information of the image can be exhibited due to a better correction of ‘opposition surge’ at small phase angle (g <15°).

Background: Oenothera biennis (evening primrose) produces bioactive substances with a diverse range of pharmacological functions. However, it is currently unknown whether extract prepared from the aerial parts of O. biennis (APOB) can protect the skin against oxidative stress. To investigate the protective effects of APOB against oxidative stress-induced damage in human skin keratinocytes (HaCaT) and elucidate the underlying mechanisms. Methods: We pretreated HaCaT cells with various concentrations of APOB or the antioxidant N-acetyl-L-cysteine before applying H2O2. We then compared the cell viability, intracellular reactive oxygen species (ROS) production, and DNA and mitochondrial damage between pretreated and untreated control cells using a range of assays, flow cytometry, and Western blot analysis and also examined the reducing power and DPPH free radical-scavenging activity of APOB. Results: APOB pretreatment significantly increased cell viability, effectively attenuated H2O2-induced comet tail formation, and inhibited H2O2-induced phosphorylation of the histone γH2AX, as well as the number of apoptotic bodies and Annexin V-positive cells. APOB was found to have a high reducing power and DPPH radical-scavenging activity and also exhibited scavenging activity against intracellular ROS accumulation and restored the loss of mitochondrial membrane potential caused by H2O2. APOB pretreatment almost totally reversed the enhanced cleavage of caspase-3, the degradation of poly (ADP-ribose)-polymerase (PARP), DNA fragmentation that usually occurs in the presence of H2O2 and increased the levels of heme oxygenase-1 (HO-1), a potent antioxidant enzyme that is associated with the induction of nuclear factor-erythroid 2-related factor 2 (Nrf2). Conclusions: APOB can protect HaCaT cells from H2O2-induced DNA damage and cell death by blocking cellular damage related to oxidative stress via a mechanism that affects ROS elimination and by activating the Nrf2/HO-1 signaling pathway.

It is proposed that both human creativity and human consciousness are (unintended) consequences of the human brain’s extraordinary energy efficiency. The topics of creativity and consciousness are treated separately, though have a common sub-structure. It is argued that creativity arises from a synergy between two cognitive modes of the human brain (which broadly coincide with Kahneman’s Systems 1 and 2). In the first, available energy is spread across a relatively large network of neurons. As such, the amount of energy per active neuron is so small that the operation of such neurons is susceptible to thermal (ultimately quantum decoherent) noise. In the second, available energy is focussed on a small enough subset of neurons to guarantee a deterministic operation. An illustration of how this synergy can lead to creativity with implications for computing in silicon are discussed. Starting with a discussion of the concept of free will, the notion of consciousness is defined in terms of an awareness of what are perceived to be nearby counterfactual worlds in state space. It is argued that such awareness arises from an interplay between our memories on the one hand, and quantum physical mechanisms (where, unlike in classical physics, nearby counterfactual worlds play an indispensable dynamical role) in the ion channels of neural networks. As with the brain’s susceptibility to noise, it is argued that in situations where quantum physics plays a role in the brain, it does so for reasons of energy efficiency. As an illustration of this definition of consciousness, a novel proposal is outlined as to why quantum entanglement appears so counter-intuitive.

The process of viral integration into the host genome is an essential step of the HIV-1 life cycle. The viral Integrase (IN) enzyme catalyses integration. IN is an ideal therapeutic enzyme targeted by several drugs; raltegravir (RAL), elvitegravir (EVG), dolutegravir (DTG) and bictegravir (BIC) having been approved by the USA Food and Drug Administration (FDA). Due to high HIV-1 diversity, it is not well understood how specific naturally occurring polymorphisms (NOPs) in IN may affect the structure/function and binding affinity of Integrase Strand Transfer Inhibitors (INSTIs). In this study, we applied computational methods of molecular modelling and docking to analyse the effect of NOPs on the full-length IN structure and INSTI binding. We identified 16 NOPs within the Cameroonian derived CRF02_AG IN sequences and further identified 17 NOPs within HIV-1C South African sequences. The NOPs in the IN structures did not show any effect on INSTI binding. INSTIs displayed similar binding affinities to each IN structure. All INSTIs are clinically effective against diverse HIV-1 strains from INSTI treatment naïve populations. This study supports the use of second-generation INSTI DTG as part of first-line combination antiretroviral therapy (cART) regimens, due to DTG possessing a stronger genetic barrier to the emergence of drug resistance.

The maintenance of high quality standards for prolonging shelf life of fruit and maintaining sensory and nutritional quality is a priority the horticultural products. The aim of this work was to test the effectiveness of a single treatment of edible coating based on Aloe arborescens and a combined treatment of 1-Methylcycyclopropene and edible coating to prolong the shelf-life of "Settembrina" white flesh peach fruit. White flesh peach fruit were harvested at the commercial ripening stage and treated with edible coating (EC) or 1-MCP +EC and stored for 28 days at 1°C. After 7, 14, 21 and 28 days fruits were removed from cold storage, transferred at 20°C and then analyzed immediately (cold out) and after 6 days (shelf life) to evaluate the combined effect of cold storage and room temperature. Weight loss, physical, chemical and sensory parameters were measured. Fruit treated with EC and 1-MCP +EC kept their marketing values better than CTR after 14 days of storage and 6 days of simulated shelf life, in terms of flesh firmness, total soluble solids and titratable acidity as well as sensory parameters. After 21 days of storage, all treatments showed a deterioration of the quality parameters. The single and combined application of Aloe-based coating (with 1-MCP) slowed down the maturation processes of the fruit, limited the weight loss and preserved its organoleptic characteristics.

Background: Lung cancer (LC) is a major leading cause of death worldwide. Immunomodulators that target several immune mechanisms have proven to reduce tumor burden in experimental models through induction of the immune microenvironment. We hypothesized that other biological mechanisms may also favor tumor burden reduction in lung cancer-bearing mice treated with immunomodulators. Methods: Tumor weight, area, and immune cells (T, B, macrophages, and TNF-alpha levels, immunohistochemistry) and tumor growth, oxidative stress, apoptosis, autophagy, and sirtuin-1 markers were analyzed (immunoblotting) in subcutaneous tumor of BALB/c mice injected with LP07 adenocarcinoma cells treated with monoclonal antibodies (CD-137, CTLA-4, PD-1, and CD-19, N=9/group) and non-treated control animals. Results: Compared to non-treated cancer mice, in tumors of monoclonal-treated animals, tumor area and weight and ki-67 significantly reduced, while T cell counts, oxidative stress, apoptosis, autophagy, and sirtuin-1 marker increased. Conclusion: Immunomodulators elicited a reduction in tumor burden (reduced tumor size and weight) through decreased tumor proliferation and increased oxidative stress, apoptosis, autophagy, and sirtuin-1 levels, which may have interfered with the immune profile of the tumor microenvironment. Future research should be devoted to the elucidation of the specific contribution of each biological mechanism to the reduced tumor burden.

The co-circulation of duck hepatitis A virus subtypes 1 (DHAV-1) and 3 (DHAV-3) in ducklings has resulted in significant economic losses. Because ducklings infected with DHAV-1 or DHAV-3 show similar clinical signs and gross lesions, it is important to discriminate these subtypes as early as possible for better clinical management. On the basis of multiple alignments of the 5′-noncoding region sequences of strains DHAV-1 and DHAV-3, universal and type-specific primers were designed and synthesized. Using the primers in a one-tube reverse transcription-PCR (RT-PCR) assay, reference strains of DHAV-1 and DHAV-3 (isolated over a span of 60 years and covering many different countries) were successfully amplified, indicating that the primer sequences were completely conserved. The amplicon sequences results and the sizes of amplicons from reference DHAV-1 and DHAV-3 isolates correlated completely with their genotypes. Moreover, with this one-tube RT-PCR system, the amplicon sizes of liver samples of reference DHAV-1- or DHAV-3-infected birds matched perfectly with their respective genotypes, as determined by virus isolation and neutralization tests. No other RNA viruses of duck origin were detected with the synthesized primers. The sensitivity of viral RNA detection was 10 pg. With this system, 20% genotype 1, 45% genotype 3, and 9% co-infection of the two genotypes were detected in 55 clinical samples. This novel approach could be used for the rapid genotyping DHAV-1 and/or DHAV-3 infection in routine clinical surveillance or epidemiologic screening.

The peripheral lymphatic system plays a crucial role in the recovery mechanisms after many pathological changes, such as infection, trauma, vascular, or metabolic diseases. The lymphatic clearance of different tissues from waste products, viruses, bacteria and toxic proteins significantly contributes to the correspondent recovery processes. However, understanding of the meningeal lymphatics functions is a challenging problem. The exploration of mechanisms of lymphatic communication with brain fluids as well as the role of the lymphatic system in the brain drainage, clearance and recovery are still in its infancy. Here we review novel concepts on the anatomy and physiology of the lymphatics in the brain, which warrant a substantial revision of our knowledge about the role of lymphatics in the rehabilitation of the brain functions after neural pathologies. We discuss a new vision on how to recruit the meningeal lymphatics by the opening of blood-brain barrier as a trigger mechanism of activation of the meningeal lymphatic drainage. This leads to innovative strategies in neurorehabilitation therapy.

Herpes simplex virus (HSV) infections can be treated with direct acting antivirals like acyclovir and foscarnet, but long-term use can lead to drug resistance, which motivates research into broadly-acting antivirals that can provide a greater genetic barrier to resistance. Photodynamic inactivation (PDI) employs a photosensitizer, light, and oxygen to create a local burst of reactive oxygen species that inactivate microorganisms. The botanical plant extract Orthoquin^TM is a powerful photosensitizer with antimicrobial properties. Here we report that Orthoquin also has antiviral properties. Photoactivated Orthoquin inhibited herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) infection of target cells in a dose-dependent manner, across a broad range of sub-cytotoxic concentrations. HSV inactivation required direct contact between Orthoquin and the inoculum, whereas pre-treatment of target cells had no effect. Orthoquin did not cause appreciable damage to viral capsids or pre-mature release of viral genomes as measured by qPCR for the HSV-1 genome. By contrast, immunoblotting for HSV-1 antigens in purified virion preparations suggested that higher doses of Orthoquin had a physical impact on certain HSV-1 proteins that altered protein mobility or antigen detection. Orthoquin PDI also inhibited the non-enveloped adenovirus (AdV) in a dose-dependent manner, whereas Orthoquin-mediated inhibition of the enveloped vesicular stomatitis virus (VSV) was light-independent. Together, these findings suggest that broad antiviral effects of Orthoquin-mediated PDI may stem from damage to viral attachment proteins.

Though melatonin is known to improve ultraviolet B (UVB)-induced oxidative damage and inflammatory conditions via blockade of nuclear factor (NF)-κB, interleukin (IL)-6, there is no report on anti-wrinkle effect of melatonin to date. Hence in the present study, anti-wrinkle mechanism of melatonin was elucidated in UVB treated HaCaT keratinocytes and hairless mice. Herein melatonin protected against a radical initiator tert-Butyl hydroperoxide (t-BOOH) induced reactive oxygen species (ROS) production, matrix metalloprotease 1 (MMP-1) and cytotoxicity in HaCaT keratinocytes. Also, melatonin suppressed the expression of sonic hedgehog (SHH) and GLI for hedgehog signaling, p-NF-kB, cyclooxygenase (COX-2), p-ERK for inflammatory responses in UVB treated HaCaT keratinocytes. Furthermore, melatonin protected skin from wrinkle formation, transdermal water loss in hairless mice irradiated by UVB for 8 weeks. Notably, melatonin prevented against epidermal thickness and dermal collagen degradation in UVB irradiated hairless mice by Hematoxylin & Eosin and Masson’s trichrome staining. Taken together, these findings suggest that melatonin reduces wrinkle formation via inhibition of ROS/SHH and inflammatory proteins such as NF-kB/COX-2/ERK/MMP1.

Acid proteins capable of nucleating Ca2+ and displaying aggregation capacity play key roles in the formation of calcium carbonate biominerals. EF-hands are among the largest Ca2+-binding motif in proteins. Gad m 1, an Atlantic cod β-parvalbumin isoform, is a monomeric EF-hand protein that acts as a Ca2+ buffer in fish muscle and is able to form amyloids under acidic conditions. Since nucleating Ca2+ protein have a propensity to form extended β-strand structures, we wondered whether amyloid assemblies of a protein containing refolded EF-hand motifs were able to influence the in vitro calcium carbonate crystallization. Here we have used the Gad m 1 chain as model to generate monomeric and amyloid assemblies and analyze their effect on in vitro calcite formation. We found that only amyloid assemblies alter calcite morphology.

We recently reported that in the spinal cord of PPMS or SPMS patients, large areas of periplaque demyelinating lesions extend distance away from plaque borders. Such lesions are characterized by a progliotic TGF-beta 1 signature accompanied by: i) a low-grade inflammatory reaction, ii) an extensive astrocytosis and iii) a process of incomplete demyelination. It was proposed that, while efficiently dampening inflammation in MS spinal cords, TGF-beta 1 could promote astrocytosis, prevent remyelination and possibly trigger alterations of myelin synthesis. In light of these findings, a re-interpretation of two large neuropathological studies performed on MS brains and spinal cords is provided here. While results from these studies clearly showed that active plaques do not display any region-specific distribution, an important point was apparently overlooked and not discussed by the authors: a significantly higher percentage of inactive plaques was found in MS spinal cords as compared to brains and, conversely, the percentage of slowly-expanding (or smoldering) lesions was significantly lower in the spinal cord as compared to the brain. These data indicate that the spinal cord environment may be more favorable to the resolution of inflammation. Downstream of the autoimmune process leading to plaque formation, region-specific mechanisms may thus drive the outcome of active plaques. While inflammation triggers tissue destruction, inflammation may also be needed for effective tissue repair and an inappropriate dampening of inflammatory events may possibly translate into a poor level of remyelination in MS spinal cords. It is proposed here that TGF-beta 1 is involved in such a brain-spinal cord dissociation of active plaques outcome.

Distribution systems can form islands when faults occur. Each island represents a subsection with variable boundaries subject to the location of a fault(s) in the system. A subsection with variable boundaries is referred to as island in this paper. For operation in autonomous mode, it is imperative to detect the island configurations and stabilize these subsections. This paper presents a novel scheme for the detection of islanding boundaries and stabilizing the system during autonomous operation. In the first stage, a boundary detection method is proposed to detect the configuration of the island. In the second stage a dynamic voltage sensitivity factor (DVSF) is proposed to assess the dynamic performance of the system. In the third stage, a wide area load shedding program is adopted based on DVSF to shed the load in weak busbars and stabilize the system. The proposed scheme is validated and tested on a generic 18-bus system using a combination of EMTDC/PSCAD and MATLAB softwares.

The nature of the interaction between Th17 cells and the blood-brain barrier (BBB) is critical for the development of autoimmune inflammation in the central nervous system (CNS). TNF-a or IL-17 stimulation is known to enhance the adherence of Th17 cells to the brain endothelium. The brain endothelial cells (bEnd.3) express VCAM-1, the receptor responsible for inflammatory cell adhesion, which binds VLA-4 on migrating effector lymphocytes at the early stage of brain inflammation. The present study examines the effect of the pro-inflammatory cytokines TNF-a and IL-17 on the adherence of Th17 cells to bEnd.3 The bEnd.3 cells were found to increase production of CCL2 and CXCL1 after stimulation by pro-inflammatory cytokines, while CCL2, CCL5, CCL20 and IL17 induced Th17 cell migration through a bEnd.3 monolayer. This interaction between Th17 cells and the brain endothelium appears to be mediated by VCAM-1 and some chemotactic cytokines. This observation may suggest potential therapeutic targets for the prevention of autoimmune neuroinflammation development in the CNS.

Caveolin-1 (Cav-1) is 22 kDa caveolae protein, acts as a scaffold within caveolar membranes. It interacts with alpha subunits of G-protein and thereby regulates their activity. Earlier studies reported elevated or up-regulated levels of caveolin-1 in the serum of prostate cancer patients. Secreted Cav-1 promotes angiogenesis, cell proliferation and anti-apoptotic activities in prostate cancer patients. Cav-1 upregulation is mainly related to prostate cancer metastasis. Keeping above facts in view, the present study was designed to explore Cav-1 as a target for prostate cancer therapy using computational approach. Molecular docking, structural base molecular modelling and molecular dynamics simulations were performed to investigate Cav-1 inhibitors. A predictive model was generated and validated to establish a stable structure. ZINC database of biogenic compounds was used for induced fit docking (IFD) and high throughput virtual screening. The H-bond interactions of the compounds with active site residues of Cav-1 were estimated by IFD and 100 ns long molecular dynamic simulations. The reported compounds showed significant binding and thus can be considered as potent therapeutic inhibitors of Cav-1. This study provides a valuable insight into biochemical interactions of Cav-1 for therapeutic applications and warrants for experimental validation of the predicted ‘active(s)’.

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.

Background: Fullerenes and metallofullerenes can be considered promising nanopharmaceuticals themselves and as a basis for chemical modification. As reactive oxygen species homeostasis plays a vital role in cells, the study of their effect on genes involved in oxidative stress and anti-inflammatory response is of particular importance. Methods: Human fetal lung fibroblasts were incubated with aqueous dispersions of C60, C70, and Gd@C82 in concentrations of 5 nM and 1.5 µM for 1, 3, 24, and 72 hours. Cell viability, intracellular ROS, NOX4, NFκB, PRAR-γ, NRF2, heme oxygenase 1, and NAD(P)H quinone dehydrogenase 1 expression have been studied. Results &amp; conclusion: The aqueous dispersions of C60, C70, and Gd@C82 fullerenes are active participants in ROS homeostasis. Low and high concentrations of AFDs have similar effects. C70 was the most inert substance, C60 was the most active substance. All AFDs have both a “prooxidant” and “antioxidant” effect, but with a different balance. Gd@C82 was a substance with more pronounced antioxidant and anti-inflammatory properties, while C70 had more pronounced “prooxidant” properties.

This study evaluated the neuroprotective potential of peptain-1 conjugated to a cell-penetrating peptide (CPP-P1) in an ocular hypertension model of glaucoma. Brown Norway (BN) rats were subjected to intraocular pressure (IOP) elevation via intracameral injection of silicone oil (SO), with concurrent intravitreal injections of either CPP-P1 or a vehicle. Retinal cross-sections were analyzed for markers of neuroprotection, including cAMP Response Element-Binding Protein (CREB), phosphorylated CREB (p-CREB), growth-associated protein-43 (GAP43), synapsin-1 (SYN1), and superoxide dismutase 2 (SOD2). Hematoxylin and eosin staining was used to assess retinal layer thickness. SO-treated rats exhibited significant reductions in the thickness of the inner nuclear layer (INL, 41%, p=0.016), inner plexiform layer (IPL, 52%, p=0.0002), and ganglion cell layer (GCL, 57%, p=0.001). CPP-P1 treatment mitigated these reductions, preserving INL thickness by 32% (p=0.059), IPL by 19% (p=0.119), and GCL by 31% (p=0.057). Increased levels of CREB and p-CREB were observed in IOP-elevated, CPP-P1-treated retinas compared to IOP-elevated vehicle-treated retinas. Although overall GAP43 levels were low, there was a modest increase in expression within the IPL and GCL in SO- and CPP-P1-treated retinas (p=0.15 and p=0.09, respectively) compared to SO- and vehicle-treated retinas. SO injection reduced SYN1 expression in both IPL and GCL (p=0.01), whereas CPP-P1 treatment significantly increased SYN1 levels in the IPL (p=0.03) and GCL (p=0.002). While SOD2 expression in the GCL was minimal across all groups, a trend toward increased expression was observed in CPP-P1-treated animals (p=0.16). The SO model was replicated with SO removal after 7 days and monitored for 21 days followed by retinal flat-mount preparation to assess retinal ganglion cell (RGC) survival. A 42% loss in RGCs (p=0.009) was observed in SO-injected eyes, which was reduced by approximately 37% (p=0.03) with CPP-P1 treatment. These findings suggest that CPP-P1 is a promising neuroprotective agent that promotes retinal ganglion cell survival and the preservation of other retinal neurons, potentially through enhanced CREB signaling in a rat model of SO-induced ocular hypertension.

Objective: To analyze the relationship and predictive value of Netrin-1 expression and ultrasonic blood flow parameters with the severity of cervical intraepithelial neoplasia (CIN). Methods: The receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of Netrin-1 expression and ultrasonic blood flow parameters for the severity of cervical intraepithelial neoplasia. Results: FI, VI, and VFI levels increased sequentially, and the differences in levels between grade II, III patients, and the control group were statistically significant (P < 0.05). Netrin-1 was negatively correlated with ultrasonic blood flow parameters FI, VI, and VFI (r = -0.287, -0.309, -0.298, P < 0.05). The results of multifactorial logistic regression analysis showed that Netrin-1 positivity was a protective factor for CIN III lesions, while FI, VI, and VFI were risk factors for CIN III lesions. The AUC area of Netrin-1 was 0.712, with a sensitivity and specificity of 76.4% and 79.5%, respectively, which were higher than those of other indicators (P < 0.05). Conclusion: Netrin-1 is under-expressed in CIN patients, while ultrasonic blood flow parameters FI, VI, and VFI are over-expressed, and both are closely related to the severity of the patient's lesions. Netrin-1 is negatively correlated with ultrasonic blood flow parameters FI, VI, and VFI. Netrin-1 positivity is a protective factor for CIN III lesions, while FI, VI, and VFI are risk factors for CIN III lesions. The expression levels of both have a certain predictive guiding role in the early screening, diagnosis, and prevention of cervical cancer.

The detection of complex formations, initially suspected to be oil spills, is investigated using atmospherically corrected multi-spectral satellite images and deep learning techniques. Several formations have been detected in an inland lake in Northern Greece. Four atmospheric corrections (ACOLITE, iCOR, Polymer, and C2RCC) that are specifically designed for water applications are examined and implemented on Sentinel-2 multispectral satellite images to eliminate the influence of the atmosphere. Out of the four algorithms, iCOR and ACOLITE are able to depict the formations sufficiently; however, the latter is chosen for further processing due to fewer uncertainties in the depiction of these formations as anomalies across the multi-spectral range. Furthermore, a number of formations are annotated at a pixel level for the 10 m bands (Red, Green, Blue, and NIR), and a deep neural network (DNN) is trained and validated. Our results show that the 4-band configuration provides the best model for the detection of these complex formations. Despite not being necessarily related to oil spills, studying these formations is crucial for environmental monitoring, pollution detection, and the advancement of remote sensing techniques.

Reiner Gamma is a potential target for low-orbiting spacecraft or even surface-landed missions in the near future. Unfortunately, thus far no comprehensive low altitude (below 20 km) or surface measurements of the magnetic field, magnetic source and plasma environment have been made post-Apollo to complement and complete our understanding of the solar wind interaction with lunar magnetic anomalies and swirl formation. Acquiring the detailed geological knowledge of the Reiner Gamma region is significant for the above scientific targets. In this study, the following research work in the lunar Reiner Gamma magnetic anomaly region was carried out for the regional geological investigation: (1) the topographic and geomorphologic analysis; (2) elements, minerals and sequence analysis; (3) 1:10,000 regional geological map analysis. Our work helps define measurement requirements for possible future low-orbiting or surface-landed missions to the Reiner Gamma area or similarly magnetized regions of the lunar surface.

Fusarium solani KMZW-1, is recognized for its potential as a biocontrol agent against agricultural and forestry pests, particularly due to its compatibility with integrated pest management (IPM) strategies. This study aimed to investigate the complete genome of F. solani KMZW-1 and assess its pathogenicity against Bactrocera dorsalis. Whole genome sequencing revealed a genome size of 47,239,278 bp, comprising 27 contigs, with a GC content of 51.16% and fungus identified as F. solani KMZW-1. The genome completeness was assessed as 97.93% using BUSCO analysis, DFVF sequence identifier was Fusarium 0G092560.1, AntiSMASH analysis identified 29 gene clusters associated with secondary metabolite biosynthesis providing insights into the genetic basis of its pathogenic mechanisms and biocontrol potential. Comparative genomic analysis found 269 unique genes of F. solani KMZW-1 and the collinearity analysis exhibited a high degree of synteny with Fusarium solani-melongenae. The pathogenicity of F. solani KMZW-1 was assessed using concentrations ranging from 1×10^4 to 1×10^11 conidia/mL. Higher concentrations (1×10^10 to 1×10^11 conidia/mL), resulted in significantly increased cumulative mortality rates of B. dorsalis adults compared to the control group. Notably, the pathogenicity was higher in male adults than in females. Probit regression analysis yielded LogLC50 values as 5.662 for fe-male and 4.486 for male B. dorsalis adults. In summary, F. solani KMZW-1 exhibits strong insecti-cidal activity against B. dorsalis and shows potential as a biocontrol agent with IPM strategies. These findings provide robust genomic evidence supporting the use of F. solani KMZW-1 in managing against B. dorsalis populations.

Diuretic resistance is a servomechanism involving superoxide that results from the use of escalating doses of diuretics in the treatment of heart failure. Without intervention this may lead to increased heart failure mortality. Recent heart failure studies involving the use of SGLT2 inhibitors and GLP-1 agonists have shown reductions in the need for loop diuretics along with reductions in hospitalizations for heart failure and cardiovascular mortality. Multiple mechanisms have been proposed to explain the benefits of both these drug classes but this paper is the first to explain and propose superoxide induced diuretic resistance as a therapeutic target for the treatment of heart failure.

Exposure to cadmium sulfate (CdSO4) can lead to neurotoxicity. Nevertheless, the precise molec-ular mechanisms underlying this phenomenon remain unclear, and effective treatment strategies are scarce. This study explored the protective effects of ellagic acid (EA), a natural polyphenolic compound, against CdSO4 exposure-induced neurotoxicity in HT22 cells. Additionally, the inves-tigation sought to elucidate the molecular mechanisms underlying this phenomenon. Our findings demonstrated that exposure of HT22 cells to CdSO4 resulted in apoptosis, which was effectively reversed by EA supplementation. EA supplementation also decreased reactive oxygen species (ROS) and mitochondrial ROS productions, reduced malondialdehyde (MDA) levels, and restored the activities of superoxide dismutase (SOD) and catalase (CAT). Additionally, EA supplementation at 5–20 μM significantly counteracted Cd-induced mitochondrial membrane potential and ATP losses and reduced the ratio of Bax/Bcl-2 and cleaved-caspase-3 protein expression. Furthermore, EA supplementation upregulated Nrf2 and HO-1 protein expression while downregulating the phosphorylation of JNK and p38 proteins. Pharmacological inhibition of JNK partially inhibited CdSO4-induced Nrf2/HO-1 activation and exacerbated its cytotoxicity. In conclusion, our results indicate that EA supplementation provides protection against CdSO4-induced cell apoptosis in HT22 cells by inhibiting oxidative stress and activating the Nrf2 pathway. Activation of the JNK pathway plays a protective role in CdSO4-induced cell apoptosis in HT22 cells.

Blueberries are rich in a variety of functional substances and have high nutritional and health values, but they are not resistant to decline during fresh storage. Here, the effects of six Bacillus species on storage quality of, and antioxidant levels in, the southern highbush blueberry ‘O'Neal’ fruit were investigated. Bacillus treatments reduced the fruit decay rate, slowed fruit quality decline, inhibited malondialdehyde accumulation, and increased superoxide dismutase and peroxidase activity levels. Bacillus altitudinis Y-14 had the best effect overall. Further, the effects of 1-methylcyclopropene (1-MCP), B. altitudinis Y-14, and 1-MCP+B. altitudinis Y-14 treatments on the storage quality and antioxidant of rabbiteye blueberry ‘Brightwell’ fruit were investigated, and each treatment effectively reduced the decay rate and weight loss of fruit. When stored for 25 days, the decay rate of the 1-MCP+B. altitudinis Y-14 group was only 8.33%, significantly lower than that of the control. The three treatments delayed the fruit quality decline, inhibited malondialdehyde accumulation, and increased superoxide dismutase and peroxidase activity levels. The 1-MCP+B. altitudinis Y-14 treatment had the best effect. Thus, the combined 1-MCP and B. altitudinis Y-14 treatment may be an effective way to improve the storage quality and extend the storage period of blueberries.

Increased activity of transforming growth factor-beta (TGF-β) is a key factor mediating kidney impairment in diabetes. Glomerular podocytes, the crucial component of the renal filter, are a direct target of TGF-β action, resulting in irreversible cell loss and progression of chronic kidney disease (CKD). Urolithin A (UA) is a member of the family of polyphenol metabolites produced by gut microbiota from ellagitannins and ellagic acid-rich foods. The broad spectrum of biological ac-tivities of UA makes it a promising candidate for the treatment of podocyte disorders. In this in vitro study, we investigated whether UA influences the changes exerted in podocytes by TGF-β and high glucose. Following a 7-day incubation in normal (NG, 5.5 mM) or high (HG, 25 mM) glucose the cells were treated with UA and/or TGF-β1 for 24 hours. HG and TGF-β1, each independent and in concert reduced expression of nephrin, increased podocyte motility and up-regulated expression of b3 integrin and fibronectin. These typical for epithelial-to-mesenchymal transition (EMT) effects were inhibited by UA in both HG and NG conditions. UA also reduced the typically elevated in HG expression of TGF-β receptors and activation of TGF-β signal transducer Smad2. Our results indicate that in podocytes cultured in conditions mimicking diabetic milieu, UA inhibits and reverses changes underlying podocytopenia in diabetic kidneys. Hence, UA should be considered as a po-tential therapeutic agent in podocytopathies.