Human T-lymphotropic virus type 1 (HTLV-1)–associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a slowly progressive spinal cord disorder with no effective treatment. There is much of interest in developing potential biomarkers for predicting the pathogenesis of HAM/TSP disorder. This study used Illumina massive parallel sequencing (MPS) technology to assess the cellular global noncoding RNAome expression profile in HAM/TSP patients (n = 10), asymptomatic HTLV-1 infected carriers (ASP, n = 8), and a second group of healthy controls (n = 5). Using various bioinformatics tools, the sRNA MPS reads were aligned, annotated, and profiled. There were 251 known and 50 potential novel sRNAs among the 402 detected sRNAs in the HAM and ASP groups versus the HC group. Sixty-eight known sRNAs were found to be significantly different between the ASP and HAM groups. In HAM vs ASP subjects, 88 mature miRNAs were downregulated. Three of these miRs (hsa-miR-185-5p, 32-5p, and 192-5p) have the potential to be used as biomarkers for predicting the pathogenesis of HAM/TSP. The top seven deregulated miRS target genes were linked to a variety of biological processes and molecular functions. Relevant reactome pathways to our findings provide a rich source of data and an opportunity to further understand sRNA regulation and function in HTLV-1 pathophysiology.

This study analyzes tree diversity and its ecological importance value in silvopastoral systems in the Sumaco Biosphere Reserve (SBR), Ecuador, along an altitudinal gradient of 400-2000 masl. Twenty-six plots distributed in low (400-700 masl), medium (701-1600 masl) and high (1601-2000 masl) zones were used. The Shannon index and the Importance Value Index (IVI), based on abundance, dominance and relative frequency, were estimated. The results show variations in the diameter structure of the trees, influenced by factors such as settlement history and pasture management. The lower and middle zones showed higher tree density and diversity, linked to regeneration and the presence of nearby forests. Species of high commercial value, such as Cedrela odorata and Jacaranda copaia, were common, reflecting knowledge of the local timber market. In the lower and middle zones, the 10 most important species accounted for more than 70% of the trees, and up to 96% in the upper zone, indicating the need for further research on abundance factors and promotion of diversification in pastures. A total of 51 tree species were identified, mostly native, 64.7% are classified by the IUCN as "Least Concern", 31.4% as "Not Evaluated", and 3.9% as "Vulnerable", specifically highlighting Cedrela odorata and Cedrela Montana. The study concludes with policy recommendations related to the importance of trees in silvopastoral systems for the conservation of species and the livelihoods of local communities, highlighting the need for responsible management of Amazonian pasturelands.

The objective of the current study is to evaluate the effects of nitrogen rate N on tree growth, fruit yield and quality of clementine Nules variety, budded on Flhorag and Carrizo citrange rootstocks, grown on clay soils at the Experimental station of Sidi Allal Tazi, INRA Morocco, over five seasons. The experiment has been carried out in a split-plot design with three replications, including the nitrogen doses as the main plot and rootstock the subplot. Three fertilization treatments of the rates of N (g/tree) (T0: control (native nutrient), T1: 270, T2: 540 in g/tree) and 135 P2O5, 270 K2O g/tree have been applied to citrus trees in field conditions. The study found that nitrogen rate and rootstock genotype had significant effects on vegetative growth, yield, and fruit quality of Nules clementine. As N rate increased, vegetative growth improved significantly, with the trees grafted on Carrizo citrange and fertilized with T2 (540 N g/tree) showing the best results. A strong positive correlation was also observed between canopy volume and fruit yield for both rootstock genotypes. Carrizo citrange proved to be a more efficient rootstock for Nules variety than Flhorag, with higher yield and better fruit quality. As a conclusion, the recommended NPK rate for obtaining an optimal yield and good fruit quality of Nules clementine fruits was 540 N-135 P2O5-270 K2O g/tree/year under Sidi Allal Tazi–Gharb (Morocco) conditions.

The beta-galactoside-binding mammalian lectin galectin-1 can bind, via its carbohydrate recognition domain (CRD), various cell surface glycoproteins and has been implicated in a range of cancers. As a consequence of binding to sugar residues on cell surface receptors it has been shown to have a pleiotropic effect across many cell types and mechanisms resulting in immune system modulation and cancer progression. As a result, it has started to become a therapeutic target for both small and large molecules. In previous studies, we have used fluorescence polarisation (FP) assays to determine KD values to screen and triage small molecule glycomimetics that bind to the galectin-1 CRD. In this study surface plasmon resonance (SPR) was used to compare human and mouse galectin-1 affinity measures with FP as SPR has not been applied for compound screening against this galectin. Binding affinities for a selection of mono- and di-saccharides covering a 1,000-fold range correlated well between FP and SPR assay formats for both human and mouse galectin-1. It was shown that slower dissociation drove the increased affinity at human galectin-1 whilst faster association was responsible for the effects at mouse galectin-1. This study demonstrates that SPR is a sound alternative to FP for early drug discovery screening and determining affinity estimates. Consequently, it also allows association and dissociation constants to be measured in a high throughput manner for small molecule galectin-1 inhibitors.

: AliCPT-1 is the first Cosmic Microwave Background (CMB) experiment in China, dedicated to achieve accurate measurements of B-mode polarization. Situated in Ali of Tibet, China, this telescope is currently undergoing deployment and will operate in two frequency bands centered at 90 and 150 GHz. The Far-Field Flat Mirror（FFF）is a calibration device of AliCPT-1 telescope for far-field beam mapping. The design of FFF is optimized for easy assembly and adjustment. Meteorological station data reveals that the maximum wind speed near FFF is 17.5 m/s, while the maximum wind speed on the windward side is 8 m/s. The wind pressure on FFF was analysed using a maximum wind speed of 17.5m/s as the input condition, based on the fluid-structure coupling method in ANSYS. The results demonstrate that it is safe and reliable when withstanding combined gravity and wind pressure loads. The torque on the mount is within the motor rated torque. The flatness of the FFF reflective surface can be adjusted to an RMS value of 0.05 mm when taken into account the effect of gravity and assembly accuracy. The deformation caused by the maximum wind loads is approximately 0.0587 mm under the protection of wind-proof wall. The combined deformation is 0.077 mm in RMS value combining the two influences, which is less than 1/20 of wavelength. The FFF mirror assembly is stable and precisely for telescope calibration.

Bacteria are engaged in a constant battle against preying viruses, called bacteriophages (or phag-es). These remarkable nano-machines pack and store their genomes in a capsid and inject it into the cytoplasm of their bacterial prey following specific adhesion to the host cell surface. Tailed phages possessing dsDNA genomes are the most abundant phages in the bacterial virosphere, particularly those with long, non-contractile tails. All tailed phages possess a nano-device at their tail tip that specifically recognizes and adheres to a suitable host cell surface receptor, being pro-teinaceous and/or saccharidic. Adhesion devices of tailed phages infecting Gram-positive bacte-ria are highly diverse and, for the majority, remain poorly understood. Their long, flexible and multi-domain encompassing tail limits experimental approaches to determine their complete structure. We have previously shown that the recently developed protein structure prediction program AlphaFold2 can overcome this limitation by predicting the structures of phage adhesion devices with confidence. Here, we extend this approach and employ AlphaFold2 to determine the structure of a complete phage, the lactococcal P335 phage TP901-1. Herein we report the structures of its capsid and neck, its extended tail, and the complete adhesion device, the baseplate, which was previously partially determined by X-ray crystallography.

This study aimed to identify and differentiate the factors that may affect the incidence of temporomandibular joint (TMJ) dysfunction in children with type 1 diabetes. We analyzed the TMJ symptoms, clinical and laboratory parameters of type 1 diabetes in a cohort of 101 consecutive patients. The participants were evaluated regarding the presence of pain in the masticatory muscles, TMJ sounds, mouth opening, maximum mouth opening, lateral and protrusive excursions, and Fonseca scores. The overall cohort showed a mean Fonseca score of 20 ± 13.89, referred to mild TMJ dysfunction. Of patients, 34.65% presented at least one clinical symptom and were defined as having dysfunction. The most frequently recorded symptom was TMJ sounds, presented in 16.8% of children. In subjects with dysfunction compared to those without dysfunction, a significant difference was found at height standard deviation scores, Fonseca scores and maximum mouth opening (p<0.001). HbA1c levels, diabetes duration, age and gender did not reveal any significant differences between the patients with and without dysfunction. Type 1 diabetes is often associated with limited mouth opening and mild TMJ dysfunction. This dysfunction may reflect a more chronic condition and possibly exceeds the prevalence of cheiroartropathy. This study could be a starting point towards enhancing our understanding of clinically evident TMJ involvement in type 1 diabetes.

Microglia activation causes neuroinflammation, which is a hallmark of neurodegenerative disorders, brain injury, and aging. Ladostigil, a bifunctional reagent with antioxidant and anti-inflammatory properties, reduced microglial activation and enhanced brain functioning in elderly rats. In this study, we studied SH-SY5Y, a human neuroblastoma cell line, and tested viability in the presence of hydrogen peroxide and Sin1 (3-morpholinosydnonimine), which generates reactive oxygen and nitrogen species (ROS/RNS). Both stressors caused significant apoptosis and necrotic cell death that was attenuated by ladostigil. Our results from RNA-seq experiments show that long non-coding RNAs (lncRNAs) account for 30% of all transcripts in SH-SY5Y cells treated with Sin1 for 24 hours. Altogether, we identify 94 differently expressed lncRNAs in the presence of Sin1, including MALAT1, a highly expressed lncRNA with anti-inflammatory and anti-apoptotic functions. Additional activities of Sin-1 upregulated lncRNAs include redox homeostasis (e.g., MIAT, GABPB1-AS1), energy metabolism (HAND2-AS1), and neurodegeneration (e.g., MIAT, GABPB1-AS1, NEAT1). Four lncRNAs implicated as enhancers were significantly upregulated in cells exposed to Sin1 and ladostigil. Finally, we show that H2O2 and Sin1 increased the expression of DJ-1, a redox sensor and modulator of Nrf2 (nuclear factor erythroid 2–related factor 2). Nrf2 (NFE2L2 gene) is a major transcription factor regulating antioxidant genes. In the presence of ladostigil, DJ-1 expression is restored to its baseline. The mechanisms governing SH-SY5Y cell survival and homeostasis are highlighted by the beneficial role of ladostigil in the crosstalk involving Nrf2, antioxidant transcription factor DJ-1, and lncRNAs. Stress-dependent induction of lncRNAs represents an underappreciated regulatory level that contributes to cellular homeostasis and the capacity of SH-SY5Y to cope with oxidative stress.

Background: In France, no previous studies had addressed the acquisition of multidrug resistant (MDR) bacteria and colistin resistance genes by medical students when undertaking internships abroad. Methods: Nasopharyngeal, rectal, and vaginal swabs samples were collected from 382 French medical students before and after travel to investigate the acquisition of MDR bacteria. The bacterial diversity in the samples was assessed by culture on selective media. We also genetically characterised the isolates of MDR bacteria including Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E), methicillin-resistant Staphylococcus aureus (MRSA), and Carbapenemase-producing Enterobacteriacae (CPE) using the real-time polymerase chain reaction method. The samples were collected from 293 students and were investigated for mcr colistin-resistance genes using RT-PCR directly on the samples, followed by conventional PCR and sequencing. Results: A proportion of 29.3% of the participants had acquired ESBL-E and 2.6% had acquired CPE. The most common species and ESBL-E encoding gene were Escherichia coli (98.4%) and bla_CTX-M-A (95.3%), respectively. A proportion of 6.8% of the participants had acquired mcr-1 genes, followed by mcr-3 (0.3%) and mcr-8 (0.3%). We found that taking part in humanitarian missions to orphanages, being in contact with children during travel, the primary destination of travel being Vietnam and north India, using antibiotics during travel, and studying in 2017 were associated with the acquisition of ESBL-E. When the primary destination of travel was Vietnam and the year of study was 2018, this was associated with acquisition of colistin resistance genes. Conclusion: Medical students are at a potential risk of acquiring ESBL-E, CPE and colistin resistance genes. A number of risk factors have been identified, which may be used to develop targeted preventive measures.

Individuals with autism often experience gastrointestinal issues but the cause is unknown. Many gene mutations that modify neuronal synapse function are associated with autism and therefore may impact the enteric nervous system that regulates gastrointestinal function. A missense mutation in the Nlgn3 gene encoding the cell adhesion protein, Neuroligin-3, was identified in two brothers with autism who both experienced severe gastrointestinal dysfunction. Mice expressing this mutation (Nlgn3R451C mice) are a well-studied preclinical model of autism and show autism-relevant characteristics, including impaired social interaction and communication, as well as repetitive behaviour. We previously showed colonic dysmotility in response to GABAergic inhibition and increased myenteric neuronal numbers in the small intestine in Nlgn3R451C mice bred on a mixed genetic background. Here we show that gut dysfunction is a persistent phenotype of the Nlgn3 R451C mutation in mice backcrossed onto a C57BL/6 background. We report that Nlgn3R451C mice show faster gastrointestinal transit in vivo and have longer small intestines compared to wild-types due to a reduction in smooth muscle tone. In Nlgn3R451C mice, we observed a decrease in resting jejunal diameter and neurally-regulated dysmotility as well as shorter durations of contractile complexes in the ileum. In Nlgn3R451C mouse colons, short contractions were inhibited to a greater extent by the GABAA antagonist, gabazine, compared to wild-type mice. Inhibition of nitric oxide synthesis decreased the frequency of contractile complexes in the jejunum, but not the ileum, in both wild-type and Nlgn3R451C mice. These findings demonstrate that changes in enteric nervous system function contribute to gastrointestinal dysmotility in mice expressing the autism-associated R451C missense mutation in the Neuroligin-3 protein.

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.

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.

Dietary intake of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid, EPA) exerts antiarrhythmic effects, although the mechanisms are poorly understood. Here we investigated the possible beneficial actions of EPA on saturated fatty acid-induced changes of the L-type Ca2+ channel in cardiomyocytes. Cardiomyocytes were cultured with oleic acid/palmitic acid mixture (OAPA) in the presence or absence of EPA. Beating rate reduction of cardiomyocytes caused by OAPA were reversed by EPA. EPA also retrieved a reduction of Cav1.2-L-type Ca2+ current, mRNA and protein caused by OAPA. Immunocytochemical analysis revealed a distinct downregulation of the Cav1.2 channel caused by OAPA with a concomitant decrease in the phosphorylated component of a transcription factor adenosine-3’, 5’-cyclic monophosphate (cAMP) response element binding protein (CREB) in the nucleus, which were rescued by EPA. A free fatty acid receptor 4 (FFAR4) agonist TUG-891 reversed expression of Cav1.2- and CREB-mRNA caused by OAPA, whereas an FFAR4 antagonist AH-7614 abolished the effects of EPA. Excessive reactive oxygen species (ROS) accumulation caused by OAPA decreased Cav1.2- and CREB-mRNA expressions, which were reversed by an ROS scavenger. Our data suggest that EPA rescues cellular remodeling caused by OAPA lipotoxicity and oxidative stresses via both free fatty acid receptor 4-dependent and -independent pathways.

In recent years, numerous approaches have been developed to comprehend the molecular altera-tions underlying thyroid cancer (TC) oncogenesis and explore novel therapeutic strategies for TC. It is now well established that the neurokinin-1 receptor (NK-1R) is overexpressed in cancer cells and that NK-1R is essential for viability of cancer cells. The binding of substance P (SP) to NK-1R in neoplastic cells plays a pivotal role in cancer progression by promoting neoplastic cell growth, protecting tumour cells from apoptosis, triggering invasion and metastasis through enhanced migration of cancer cells, and stimulating endothelial cell proliferation for tumour angiogenesis. Remarkably, all types of human TC (papillary, follicular, medullary, anaplastic), as well as met-astatic lesions, exhibit overexpression of SP and NK-1R compared to the normal thyroid gland. TC cells synthesize and release SP, which exerts its multiple functions through autocrine, para-crine, intracrine, and neuroendocrine processes, including the regulation of tumour burden. Con-sequently, the secretion of SP from TC results in increased SP levels in plasma, which are signifi-cantly higher in TC patients compared to controls. Additionally, NK-1R antagonists have demonstrated a dose-dependent antitumour action. They impair cancer cell proliferation on one side and induce apoptosis of tumour cells on the other side. Furthermore, it has been demonstrat-ed that NK-1R antagonists inhibit neoplastic cell migration, thereby impairing both invasiveness and metastatic abilities, as well as angiogenesis. Given the consistent overexpression of NK-1R in all types of TC, targeting this receptor represents a promising therapeutic approach for TC. Therefore, NK-1R antagonists, such as the drug aprepitant, may represent novel drugs for TC treatment.

Carnivore protoparvovirus 1 (CPPV-1) is a DNA virus causing gastrointestinal disease and immunosuppression in various terrestrial carnivores. Domestic dogs and cats are considered the primary CPPV-1 reservoirs. The habitat overlaps of wild carnivores and free-roaming dogs increases the threat of CPPV-1 transmission between them. This study explored the CPPV-1 distribution among wild carnivores through PCR screening and compared the DNA sequences of the partial capsid protein (VP2) between wild and domestic carnivores. In total, 181 samples were screened for the CPPV-1 VP2 gene, including 32 masked palm civets (Paguma larvata), 63 Chinese ferret badgers (Melogale moschata), and 86 crab-eating mongooses (Herpestes urva), from 2015 to 2019 in Taiwan. The average prevalence of CPPV-1 was 17.7% (32/181), with the highest prevalence in masked palm civets (37.5%). In addition, a masked palm civet was coinfected with two CPPV-1 strains. Among the 33 partial VP2 gene sequences, 23 were identical to sequences amplified from domestic dogs and cats in Asia and the remaining 10 were identified for the first time. This study demonstrated that CPPV-1 has circulated between domestic and wild carnivores in rural Taiwan. Therefore, further population control and health management of free-roaming domestic carnivores are recommended.

Epstein–Barr virus (EBV) has been recently shown to be co-present with high-risk human papillomaviruses (HPVs) in human cervical cancer; thus, these oncoviruses play an important role in the initiation and/or progression of this cancer. Accordingly, our group has recently viewed the presence and genotyping distribution of high-risk HPVs in cervical cancer in Syrian women; our data pointed out that HPVs are present in 95.45% of our samples. Herein, we aim to explore the co-prevalence of EBV and high-risk HPVs in 44 cervical cancer tissues from Syrian women using polymerase chain reaction (PCR), immunohistochemistry (IHC) and tissue microarray (TMA) analyses. We found that EBV and high-risk HPVs are co-present in 15/44 (34%) of the samples. Additionally, we report that the co-expression of LMP1 and E6 genes of EBV and high-risk HPVs, respectively, is associated with poorly differentiated squamous cell carcinomas phenotype; this is accompanied by a strong and diffused Id-1 overexpression, which is an important regulator of cell invasion and metastasis. These data imply that EBV and HPVs are co-present in cervical cancer in the Middle East area including Syria and their co-presence is associated with a more aggressive cancer phenotype. Future investigations are needed to elucidate the exact role of EBV and HPVs cooperation in cervical carcinogenesis.

Herpes simplex virus type 1 (HSV-1) is among the most widely spread viruses on the planet. However, the rate of binding to the receptor is not among the greatest ones. Gibbs energy of binding, which represents the driving force for antigen-receptor binding, of HSV-1 is less negative than can be expected. Furthermore, the Gibbs energy of biosynthesis of HSV-1 is among the most negative in nature. This implies high rate of multiplication of HSV-1. Obviously, HSV-1 uses specific strategy in virus-host interaction. While most other viruses increase infectivity through a high rate of antigen-receptor binding and cell entry/ highly negative Gibbs energy of binding, HSV-1 uses another strategy. It is related to a relatively slow reaction of antigen-receptor binding, which is followed by a higher rate of multiplication, which is a consequence of a highly negative Gibbs energy of biosynthesis. We can conclude empirically that both strategies are successful.

Theaflavins, the characteristic and bioactive polyphenols in black tea, possess the potential improvement effects on insulin resistance-associated metabolic abnormalities including obesity and type 2 diebetes. However, the molecular mechanisms of theaflavins improving insulin sensitivity are still not clear. In this study, we investigated the protective effects and mechanisms of theaflavins on palmitic acid-induced insulin resistance in HepG2 cells. Theaflavins could significantly increase glucose uptake of insulin-resistant cells at noncytotoxic doses. This activity was mediated by upregulating the glucose transporter 4 protein expression, increasing the phosphorylation of IRS-1 at Ser307, and reduced the phosphor-Akt (Ser473) level. Moreover, theaflavins were found to enhance mitochondrial DNA copy number through down-regulate the PGC-1β mRNA level and up-regulate PRC mRNA expression in insulin-resistant HepG2 cells. These results indicated that theaflavins could improve free fatty acid-induced hepatic insulin resistance by promoting mitochondrial biogenesis, and were promising functional food and medicines for insulin resistance-related disorders.

A finite-type immersion or smooth map is a nice tool to classify submanifolds of Euclidean space, which comes from eigenvalue problem of immersion. The notion of generalized 1-type is a natural generalization of those of 1-type in the usual sense and pointwise 1-type. We classify ruled surfaces with generalized 1-type Gauss map as part of a plane, a circular cylinder, a cylinder over a base curve of an infinite type, a helicoid, a right cone and a conical surface of $G$-type.

Background: This study aimed to evaluate the burden and impact of cardiac and cerebrovascular disease (CCD) on hospital inpatients with type 1 diabetes mellitus (T1DM). Methods: This is a retrospective nationwide cohort study of people with T1DM with or without CCD in the US National Inpatient Sample between 2016 to 2019. The in-hospital mortality rates, length of stay (LoS) and healthcare costs were determined. Results: A total of 59,860 T1DM patients had a primary diagnosis of CCD and 1,382,934 did not. The median LoS was longer for patients with CCD compared to no CCD (4.6 vs. 3 days). Patients with T1DM and CCD had greater in-hospital mortality compared to those without CCD (4.1% vs. 1.1%, p<0.001). The estimated total care cost for all patients with T1DM with CCD was approximately US $326 million. The adjusted odds of mortality compared to patients with non-CCD admission was greatest for intracranial hemorrhage (OR 17.37, 95%CI 12.68-23.79), pulmonary embolism (OR 4.39, 95%CI 2.70-7.13), endocarditis (OR 3.46, 95%CI 1.22-9.84), acute myocardial infarction (OR 2.31, 95%CI 1.92-2.77) and stroke (OR 1.47, 95%CI 1.04-2.09). Conclusions: The burden of CCD in patients with T1DM is substantial and significantly associated with increased hospital mortality and high healthcare expenditures.

Depressive disorder (DD) is a psychiatric disorder whose molecular basis is not fully understood. It is assumed that reduced consumption of fish and omega-3 fatty acids (FA) is associated with DD. Other lipids like total cholesterol (TCH), LDL- and HDL-cholesterols (LDL-CH, HDL-CH) also play a role in depression. This study aimed to investigate the relationship between depressive disorder symptoms and lipid profile, LDL- and HDL-cholesterol subfractions, Paraoxonase 1 (PON1) activities and erythrocyte membrane fluidity in 58 depressive children and adolescents, as well as the effect of omega-3 FA on the monitored parameters. Depressive symptoms were assessed by the Children's Depression Inventory (CDI), lipid profile by standard biochemical procedures, LDL- and HDL-subfractions by the Lipoprint system. Basic biochemical parameters including lipid profile were compared with levels in 20 healthy children and were in the physiological range. We are the first to report that omega-3 FAs increase after 12 weeks of supplementation large HDL subfractions (anti-atherogenic) and decrease small HDL subfractions (pro-atherogenic) in depressed children. We found a negative correlation between CDI score and HDL-CH and large HDL subfraction, but not LDL-CH subfractions. CDI score was not associated with erythrocyte membrane fluidity. Our results suggest that HDL-CH and its subfractions, but not LDL-CH may play a role in the pathophysiology of depressive disorder.

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

Rice bran arabinoxylan compound (RBAC) is derived from rice bran enzymatically treated with Lentinus Edodes mycelium. This review explores biologically active compounds and mechanisms of action that support RBAC as an immunomodulating nutraceutical in generally healthy and/or aging individuals. Thirty-seven (n=37) primary research articles fulfiled the selection criteria for review. Most research is based on Biobran MGN-3, which consists of complex heteropolysaccharides with arabinoxylan as its primary structure while also containing galactan and glucan. RBAC was found to invoke immunological activities through direct absorption via the digestive tract and interaction with immune cells at the Peyer’s patches. RBAC was shown to promote the innate defence by upregulating the macrophage phagocytosis and enhancing natural killer cell activity while lowering oxidative stress. Through induction of dendritic cell maturation, RBAC also augments adaptive immunity by promoting T and B lymphocyte proliferation. RBAC acts as an immunomodulator by inhibiting mast cell degranulation during allergic reactions, attenuating inflammation, and downregulating angiogenesis by modulating cytokines and growth factors. RBAC is shown to be a safe and effective neutraceutical for improving immune health, notably in aging individuals with reduced immune function. Human clinical trials with geriatric participants have demonstrated RBAC to have prophylactic benefits against viral infection and may improve their quality of life. Further research should explore RBAC’s bioavailability, pharmacodynamics, and pharmacokinetics of the complex heteropolysaccharides within. Translational research to assess RBAC as an nuetraceutical for the aging population is still required, particularly in human studies with larger sample sizes and cohort studies with long follow-up periods.

Bovine respiratory disease (BRD) is a major health problem within the global cattle industry. This disease has a complex aetiology, with viruses playing an integral role. In this study, metagenomics was used to sequence viral nucleic acids in the nasal swabs of BRD affected cattle. Viruses detected included those well known for their association with BRD in Australia (bovine viral diarrhea virus 1), as well as viruses known to be present but not fully characterised (bovine coronavirus) and viruses that have not been reported in BRD affect cattle in Australia (bovine rhinitis, bovine influenza D, and bovine nidovirus). Nasal swabs from a case control study were subsequently tested for 10 viruses and the presence of at least one virus was found to be significantly associated with BRD. Some of the more recently detected viruses had inconsistent association with BRD. Full genome sequences for bovine coronavirus, a virus increasingly associated with BRD, and bovine nidovirus were complete. Both viruses belong to the Coronaviridae family, which are frequently associated with disease in mammals. This study has provided greater insights into the viral pathogens associated with BRD and highlighted the need for further studies to elucidate more precisely the roles viruses play in BRD.

The high mutation rate of human immunodeficiency virus type 1 (HIV-1) plays a major role in treatment resistance from the development of vaccines to long-lasting drugs. In addressing the crux of the issue, various attempts to estimate the mutation rate of HIV-1 resulted in a large range of 10-5 - 10-3 errors/bp/cycle due to the use of different types of investigation methods. In this review, we discuss the different assay methods, their findings on the mutation rates of HIV-1 and how the location of these mutations can be further analyzed for their potential allosteric effects to reveal potentially new inhibitors with different pharmacodynamics that can be used to circumvent fast occurring HIV drug resistance. Given that HIV is one of the fastest mutating viruses, it is a good model for comprehensive study of its mutations that can give rise to much horizontal understanding towards overall viral drug resistance as well as emerging viral diseases.

The menopausal transition often accompanies distressing manifestations, including vasomotor symptoms, sleep disruptions, and depressive syndrome. Omega-3 fatty acids have emerged as a potential intervention to alleviate these symptoms. This review aimed to comprehensively assess the impact of omega-3 supplementation on vasomotor symptoms, sleep quality, and depression among postmenopausal women. We conducted a systematic search focusing on randomized control trials across the Cochrane Library, Web of Science, PubMed, CINAHL, EMBASE, and SCOPUS databases from inception to August 2023. Among the initial pool of 163 studies, 9 studies met the inclusion criteria and were incorporated into this review. Four studies suggested potential benefits of omega-3 intake for improving hot flashes and night sweats. Sleep quality outcomes displayed heterogeneity across the studies. Incorporating diverse scales such as the Hamilton Depression Rating Scale-21, the Patient Health Questionnaire depression scale, and Generalized Anxiety Disorder-7 for depression outcomes, the review found inconclusive evidence on omega-3's impact on depression. Overall, the combined analysis of these studies did not provide substantial evidence to support the efficacy of omega-3 fatty acids in improving vasomotor symptoms, sleep quality, and depression. Further well-designed RCTs with larger participant groups are crucial to validate and generalize these results.

Hepatic carboxylesterase 1(CES1) metabolizes many prodrugs into active ingredients or direct-acting drugs into inactive metabolites. We aim to develop a semi-physiologically based pharmacokinetic model(Semi-PBPK model) to simultaneously predict pharmacokinetics of CES1 substrates and their active metabolites in liver cirrhosis(LC) patients. Six prodrugs(enalapril, benazepril, cilazapril, temocapril, perindopril and oseltamivir) and three direct-acting drugs (flumazenil, pethidine and remimazolam) were selected. The parameters including organ blood flows, plasma binding protein concentrations, functional liver volume, hepatic enzymatic activity, glomerular filtration rate(GFR) and gastrointestinal transit rate were introduced into the simulation. Pharmacokinetic profiles of these drugs and their active metabolites were simulated in 100 virtual subjects. The developed semi-PBPK model, following validation in healthy subjects, was extrapolated to LC patients. Most of the observations are within the 5% and 95% quantile of simulations from 100 virtual patients. The estimated AUC and Cmax are within 0.5-2-fold of observation. The sensitivity analysis showed that the decreased plasma exposure of active metabolite due to the decreased CES1 was partly attenuated by the decreased GFR. Conclusion: The developed PBPK model has successfully predicted pharmacokinetics of CES1 substrates and their metabolites in healthy subjects and LC patients, which assists in tailoring dosages of CES1 substrates in LC patients.

Visceral leishmaniasis (VL) is a chronic systemic disease. In Brazil this infection is caused by Leishmania (Leishmania) infantum. Extracellular vesicles (EVs) released by Leishmania species have different functions like modulation of host immune system, inflammatory response, among others. This study evaluated the participation of EVs from L. (L.) infantum (Leish-EVs) in stimulation of the humoral and cellular immune responses of hosts with VL. Promastigotes were cultivated in 199 medium and, in the log phase of growth, they were centrifuged, washed, resuspended in RPMI medium and incubated for 2 to 24h, at 25ºC or 37°C to release Leish-EVs. This dynamic was evaluated by transmission (TEM) and scanning (SEM) electron microscopies, as well as nanoparticle tracking analysis (NTA). The results suggested that parasite penetration in mammal macrophages requires more Leish-EVs than those living in insect vectors, since promastigotes incubated at 37°C released more Leish-EVs than those incubated at 25ºC. In comparison to the control group, infected THP-1 cells produced a significantly higher concentration of EVs (THP-1 cells-EVs). Similar results were obtained when THP-1 cells were treated with Leish-EVs or a crude Leishmania antigen. These data suggest that the concentration of host-EVs-Can distinguish between infected and uninfected cells. THP-1 cells treated with Leish-EVs expressed more IL-12 than control THP-1 cells, but were unable to produce IFN-γ. These same cells produced IL-10, which inhibited TNF and IL-6. Equally, THP-1 cells treated with Leish-EVs up-expressed miR-21-5p and miR-146a-5p. These findings indicate that the increased levels of miR-21-5p and miR-146a-5p observed in Leish-EVs-treated-THP-1 cells lead to immunosuppression and the secretion of pro-inflammatory cytokines.

PG16 is a broadly neutralizing antibody that binds to the gp120 subunit of the HIV-1 Env protein. The major interaction site is formed by the unusually long complementarity determining region (CDR) H3. The CDRH3 residue Tyr100H is known to represent a tyrosine sulfation site; however, this modification is not present in the experimental complex structure of PG16 with full-length HIV-1 Env. To investigate the role of sulfation for this complex, we modeled the sulfation of Tyr100H and compared the dynamics and energetics of the modified and unmodified complex by atomistic molecular dynamics simulations. Our results show that sulfation does not affect the overall conformation of CDRH3, but still enhances gp120 interactions both at the site of mutation and for the neighboring residues. This stabilization affects not only protein-protein contacts, but also the interactions between PG16 and the gp120 glycan shield. Further, we also investigated whether PG16-CDRH3 is a suitable template for the development of peptide mimetics. For a peptide spanning residues 93-105 of PG16 we obtained an experimental EC50 value of 3nM for the binding of gp120 to the peptide. This affinity can be enhanced by almost one order of magnitude by artificial disulfide bonding between residues 99 and 100F. In contrast, any truncation results in significantly lower affinity, suggesting that the entire peptide segment is involved in gp120 recognition. Their high affinity makes PG16-derived peptides useful building blocks for further optimization to obtain a potent inhibitor that efficiently blocks HIV-1 infection.

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

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.

Cholest-4-en-3-one Δ1-dehydrogenase (AcmB) from Sterolibacterium denitrificans is successfully immobilized on 3-aminopropyltrimethoysilane functionalized MCF and SBA-15 silica supports using adsorption or covalently with glutaraldehyde or divinyl sulfone linkers. The best catalyst, AcmB on MCF linked covalently with glutaraldehyde, retains the specific activity of the homogenous enzyme while exhibiting a substantial increase of the operational stability. The immobilized enzyme was used continuously in the fed-batch reactor for 27 days, catalyzing 1,2-dehydrogenation of androst-4-en-3-one to androst-1,4-dien-3-one with a final yield of 29.9 mM (8.56 g/L) and 99% conversion. The possibility of reuse of the immobilized catalyst was also demonstrated and resulted with a doubling of the product amount compared to that in the reference homogenous reactor. Finally, it was shown that molecular oxygen from the air can efficiently be used as an electron acceptor either reoxidizing directly the enzyme or the reduced DCPIPH2. Keywords: 3-ketosteroid D1-dehydrogenase; KSTD; KSDH; AcmB; 1,2-dehydrogenation; cholest-4-en-3-one Δ1-dehydrogenase; enzyme immobilization, FAD-dependent enzymes; enzyme immobilization;

Let a,b,c be positive integers such that a²+b²=c², 2|b,gcd(a,b)=1. In 1956, Jesmanowicz conjectured that for any positive integer w, the only solution of (aw)^x+(bw)^y=(cw)^z in positive integers is (x, y, z) = (2, 2, 2). In this paper, based on Gaussian integer ring, we show that Je$\acute{s}$manowicz' conjecture is true for any positive integer

The following system of equations {x_1 \cdot x_1=x_2, x_2 \cdot x_2=x_3, 2^{2^{x_1}}=x_3, x_4 \cdot x_5=x_2, x_6 \cdot x_7=x_2} has exactly one solution in ({\mathbb N}\{0,1})^7, namely (2,4,16,2,2,2,2). Hypothesis 1 states that if a system of equations S \subseteq {x_i \cdot x_j=x_k: i,j,k \in {1,...,7}} \cup {2^{2^{x_j}}=x_k: j,k \in {1,...,7}} has at most five equations and at most finitely many solutions in ({\mathbb N}\{0,1})^7, then each such solution (x_1,...,x_7) satisfies x_1,...,x_7 \leq 16. Hypothesis 1 implies that there are infinitely many composite numbers of the form 2^{2^{n}}+1. Hypotheses 2 and 3 are of similar kind. Hypothesis 2 implies that if the equation x!+1=y^2 has at most finitely many solutions in positive integers x and y, then each such solution (x,y) belongs to the set {(4,5),(5,11),(7,71)}. Hypothesis 3 implies that if the equation x(x+1)=y! has at most finitely many solutions in positive integers x and y, then each such solution (x,y) belongs to the set {(1,2),(2,3)}. We describe semi-algorithms sem_j (j=1,2,3) that never terminate. For every j \in {1,2,3}, if Hypothesis j is true, then sem_j endlessly prints consecutive positive integers starting from 1. For every j \in {1,2,3}, if Hypothesis j is false, then sem_j prints a finite number (including zero) of consecutive positive integers starting from 1.

Diisocyanates, particularly toluene diisocyanate (TDI) are useful for the preparation of various polyurethanes with specific applications as leather-like materials, adhesives, insoles etc. Blocking agents can be used for the operational simplicity and reducing the hazards of TDI. In this paper we reported the use of 3-(4-bromo-phenyl)-1H-pyrazole to block toluene diisocyanate (TDI). FTIR, NMR, thermogravimetric analysis, contact angle and differential scanning calorimetry (DSC) and were used for characterization. Effectiveness of blocking was confirmed by spectroscopic techniques. DSC thermogram shows that blocked adducts deblock at 240 °C causing the regeneration of TDI and blocking agents to react with polyols of different molecular weights forming polyurethanes. The characterization of polyurethanes has been done by Infrared spectroscopy, Nuclear magnetic resonance spectroscopy, thermogravimetric analysis, differential scanning calorimetry and contact angle study.

The problem of fluid dynamics can be greatly simplified if, for every point in space, the strain-rate tensor is diagonalized. This tensor is introduced into the Navier-Stokes equations via material law and divergence of the stress tensor. This article shows that local SO(3)xU(1) gauge fields can be used to locally diagonalize the diffusion components of the strain-rate tensor. The gauge fields resulting from the connection can be interpreted as convection components of the flow, they show properties of quasiparticles and can be interpreted as elementary vortices. Thus, the proposed approach not only offers new insights for the solution and situative simplification of the Navier-Stokes equations, it also uncovers hidden symmetries within the flow convection, allowing - depending on boundary conditions - further interpretation.

C-C motif chemokine ligand 2 (CCL2), also called monocyte chemoattractant protein-1 (MCP-1) is a key β-chemokine involved in the migration of monocytes and macrophages, playing a significant role in the inflammatory responses in the airways. We aimed to assess the serum levels of MCP-1/CCL2 in a pilot cross-sectional study of Bulgarian children with bronchial asthma (BA) and cystic fibrosis (CF). Forty-two children were recruited to the study as follows: twenty with BA, twelve with CF and ten healthy children. Serum MCP-1/CCL2 levels were measured using ELISA. We found higher serum level of MCP-1/CCL2 in children with BA (191.09±64.96 pg/ml) and CF (258.51±76.45 pg/ml) compared to healthy children (70.30±64.30 pg/ml, p=0.022, and p=0.068, respectively). Younger patients with BA had higher levels of MCP-1/CCL2, as well as children with CF, with levels decreasing gradually with age. We observed also higher levels of MCP-1/CCL2 in children with moderate to severe BA compared to mild BA. We documented the significantly higher level of MCP-1/CCL2 in children with these chronic pulmonary diseases than in healthy controls, which suggesting that investigation of serum MCP-1/CCL2 levels could turn out to be beneficial for the severity of the disease.

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.

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 aim of this study was to synthetize a hydroxyapatite-capsaicin composite (HAp-CAP) and to evaluate its physicochemical data for further use in hydrogen peroxide in-office dental bleaching gel. The HAp-CAP was prepared by the precipitation method, performed in a 4:1 ratio using 3.2 g of nano-hydroxyapatite (nano-HAp) and 0.8 g of capsaicin (CAP) in 99.5% ethyl alcohol (q.s.p) and zirconia beads at SpeedMixer®. The HAp-CAP was characterized by morphological, spectroscopic, and thermal analyses. In the following, the HAp-CAP was added to an in-office dental bleaching to test its effect on reducing hydrogen peroxide diffusion into the pulp chamber, as well as the effect in the color alteration during dental bleaching. The HAp-CAP were suitably obtained by the precipitation method, and the results demonstrates that the thermal stability of the CAP is greatly improved after reaction of HAp and CAP. The HAp-CAP into a bleaching gel slightly decreased the amount of hydrogen peroxide inside the pulp chamber and didn’t interfering in the bleaching effectiveness of dental bleaching. The HAp-CAP synthesis and characterization were successfully carried out, and its use in dental materials is a challenging task that needs further study since its addition.

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.

Seasonal precipitation variance significantly alters soil water content, potentially inducing water stress and affecting plant transpiration in semiarid deserts. This study explored the effects of environmental variables and hydraulic conductance on whole-tree transpiration (ET) in Mongolian pines (Pinus sylvestris var. mongolica) across different forest stages in the semiarid deserts of northern China. We measured ET using sap flow in mature (MMP), half-mature (HMP), and young (YMP) Mongolian pine plantations. Measurements included soil-leaf water potential difference (ΔΨ), atmospheric conditions, and soil moisture contents on sunny days, both in dry and wet periods. Seasonally variable rainfall distinctly affected soil moisture, correlating ET with photosynthetically active radiation (PAR) and vapor pressure deficit (VPD). Notable nocturnal sap flow occurred during the growing season. During the dry periods, both stomatal and hydraulic conductance influenced ET, whereas during the wet periods, stomatal conductance primarily regulated it. Discrepancies between predicted and measured ET were noticed: compared to the predicted ET, measured ET was lower during dry periods while higher during wet periods. Hydraulic conductance (KT) increased with tree height (H) and ΔΨ, although tall trees exhibited lower KT rates, suggesting that hydraulic compensation had occurred. This compensation, observed between 11:00 and 13:00, aligned with increased hydraulic resistance during dry periods. Decreasing hydraulic conductance intensified leaf water stress in dry periods, especially during the time when PAR and VPD were heightened, potentially increasing stomatal sensitivity to drought, promoting water conservation and plant survival. A linear relationship between predawn and midday leaf water potentials was noticed, indicating extreme anisohydric behavior across forest stages during both dry and wet periods. Although both stomatal and hydraulic conductance influenced ET during the dry period, MMP and YMP were more susceptible to drought conditions. Understanding these dynamics could help evaluate semiarid desert ecological functions for water conservation amidst uneven seasonal precipitation in Northern China.

The longleaf pine (Pinus palustris P. Mill.) forest type occupied a much greater area in the United States prior to the arrival of Europeans, estimated to be around 37.2 million hectares. This area has been greatly reduced, and these ecosystems now occupy only about 1.2 to 1.6 million hectares. However, there has been great interest in the restoration of this forest type, and existing stands are actively managed. Thus, managers need tools to estimate site quality and ultimately productivity. Here, 16 existing equations to estimate site index and dominant height in naturally regenerated longleaf pine stands are examined for their behavior across a range of site quality and age conditions. Others can use this information as a reference to determine which equation may be best for their situation.

Through this study, we established equations for estimating the standing tree carbon stock, based on 24 tree species in multiple size classes in a case study at the Ngao Demonstration Forest (NDF) in northern Thailand. Four hundred thirty-nine wood samples from trees in mixed deciduous forest (MDF), dry dipterocarp forest (DDF), and dry evergreen forest (DEF), were collected using non-destructive methods to estimate above-ground carbon equations through statistical regression. The equations were established based on four criteria: 1) the coefficient of determination (R2), 2) Standard error of estimate (SE), 3) F-value, and 4) Significant value (p-value, α ≤ 0.05). The above-ground carbon stock (C) equations for standing trees in the MDF was C = 0.0199DBH2.1887H0.5825, for DDF was C = 0.0145DBH2.1435 H0.748, for DEF was C = 0.0167DBH2.1423H0.7070, and the general equation for all species/wood density groups was C = 0.017543DBH2.1625H0.6614, where DBH is tree diameter at breast height and H is tree total height. The above-ground carbon stock in the DDF, MDF, and DEF was 142, 53.02, and, 12 tons/ha, respectively, and the estimated above-ground carbon stock in the Mae Huad sector at the NDF was 61 tons/ha.

Imaging systems mounted to ground vehicles are used to image fruit tree canopies for estimation of fruit load, but frequently need correction for fruit occluded by branches, foliage or other fruits. This can be achieved using an orchard ‘occlusion factor’, estimated from a manual count of fruit load on a sample of trees (referred to as the reference method). It was hypothesised that canopy images could hold information related to the number of occluded fruit. Five approaches to correct for occluded fruit based on canopy images were compared using data of three mango orchards in two seasons. However, no attribute correlates to the number of hidden fruit were identified. Several image features obtained through segmentation of fruit and canopy areas, such as the proportion of fruit that were partly occluded, were used in training Random forest and multi-layered perceptron (MLP) models for estimation of a correction factor per tree. In another approach, deep learning convolutional neural networks (CNNs) were directly trained against harvest fruit count on trees. The supervised machine learning methods for direct estimation of fruit load per tree delivered an improved prediction outcome over the reference method for data of the season/orchard from which training data was acquired. For a set of 2017 season tree images (n=98 trees), a R2 of 0.98 was achieved for the correlation of the number of fruits predicted by a Random forest model and the ground truth fruit count on the trees, compared to a R2 of 0.68 for the reference method. The best prediction of whole orchard (n = 880 trees) fruit load, in the season of the training data, was achieved by the MLP model, with an error to packhouse count of 1.6% compared to the reference method error of 13.6%. However, the performance of these models on new season data (test set images) was at best equivalent and generally poorer than the reference method. This result indicates that training on one season of data was insufficient for the development of a robust model. This outcome was attributed to variability in tree architecture and foliage density between seasons and between orchards, such that the characters of the canopy visible from the interrow that relate to the proportion of hidden fruit are not consistent. Training of these models across several seasons and orchards is recommended.

Tree species composition is an important key element for biodiversity and sustainable forest management, and hyperspectral data provide detailed spectral information, which can be used for tree species classification. There are two main challenges for using hyperspectral imagery: a) Hughes phenomena, meaning by increasing the number of bands in hyperspectral imagery, the number of required classification samples would increase exponentially, and b) in a more complex environment, such as riparian mixed forest, focusing on spectral variability per pixel may not be adequate for definability of tree species. Therefore, the focus of this study is to assess spectral-spatial dimensionality reduction of airborne hyperspectral imagery by using minim noise fraction (MNF) transformation, and object-based image analysis (OBIA). An airborne prism experiment (APEX) hyperspectral imagery was used. A study area was a riparian mixed forest located along the Salzach river, and six tree species including Picea abies, Populus (canadensis and balsamifera), Fraxinus excelsior, Alnus incana, and Salix alba were selected. A machine learning algorithm random forest (RF) was used to train and apply a prediction model for classification. Using a spectral dimensionality reduced APEX, a pixel-level classification was also done. According to a confusion matrix, the object-level classification of MNF-derived components achieved the overall accuracy of 85 %, and kappa coefficient of 0.805. The performance of classes according to producer’s accuracy varied between 80% for Fraxinus excelsior, Alnus incana, and Populus canadensis to 90% for Salix alba and Picea abies. Comparison the results to a pixel-level classification, showed a better performance of object-level classification (an overall accuracy of 63% and Kappa coefficient of 0.559 were achieved for pixel-level classification). The performance of classes using pixel-based classification varied 45 % for Alnus incana to 80% for Picea abies. In general, Spectral-spatial complexity reduction using MNF transformation and object-level classification yielded a statistically satisfactory results.

We can analyze the properties of the Collatz Conjecture by using Terras’ Theorem, and computational graphical calculations. To do this, we introduce the concept of “tree" which shows the relationship between the input and output positive integers of the Collatz process. This approach offers a novel way for determining the non-existence of loops and diverge trees through computer simulations.

Irrigation is one of key agricultural management practices of crop cultivation in the world. Irrigation practice is traceable on satellite image. Most irrigated area mapping methods were developed based on time series of NDVI or back scatter coefficient within the growing season. However, it found the winter irrigation out of growing season is also dominating in north China. This kind of irrigation aims to increase the soil moisture for coping with spring drought, and also reduce the wind erosion with the wet soil in the field surface as the strong wind happens in spring. This study developed a remote sensing-based classification approach to identify irrigated fields with Radom Forest algorithm out of growing season. The results showed that the mean of the highest accuracies of 7 RF models was 94.9% and the mean of the averaged accuracies of 7 RF models was 94.1%; the overall accuracy for all 7 outputs was in the range of 86.8-92.5%, Kappa in the range of 84.0-91.0% and F-1 score in the range of 82.1-90.1%. These results showed that the classification was acceptable and not over performed as the accuracies of all classified images were lower than the models. This study also found that irrigation started to apply in early November and irrigated fields were increased and suspended in December and January due to freeze. The newly irrigated fields were found again in March and April when the temperature goes up above zero degree. The area of irrigated fields in the study area were increasing over time with sizes of 98.6, 166.9, 208.0, 292.8, 538.0, 623.1, 653.8 km2 from December to April, accounting for 6.1%, 10.4%, 12.9%, 18.2%, 33.4%, 38.7%, and 40.6% of the total irrigatable land in the study area, respectively.

Starting with a positive odd integer $n$, apply a function $f(n)$ repetitively such that $f(n) = 3n + 1$ if $n \not\equiv 0 (\text{mod}\:2)$ or $f(n) = n/2$ if $n \equiv 0 (\text{mod}\:2)$. Let the sequence of all the odd integers obtained form an orbit $n, f^1(n) , f^2(n), \ldots, f^k(n), f^{k + 1}(n)$. The $k^{th}$ odd integer is written as $f^k(n) = (3^k + \mathbf{B(k)})/2^{\mathbf{z(k)}}$ where $\mathbf{B(k)}$ is the collection of terms without the coefficient $n$. We show that when $1 - \mathbf{B(k)}/(2^{\mathbf{z(k)}} n) \approx 1$, the condition for unbounded orbit is given by OEIS A022921. Further, if there exists at least one orbit for which $f^{k + 1}(n) = n$ when $(k + 1) < 3$, we show that there exists no orbit with $k + 1 > 3$ for which $f^{k + 1}(n) = n$. The final result is that the odd integers that can violate the Collatz conjecture are smaller than 5.

(1) Background: The HIV subtype D is generally associated with a faster decline in CD4+ T cell counts, a higher viral load, and a faster progression to AIDS. However, it is still poorly characterized in Brazil. In this study, we used genomics and epidemiological data to investigate the transmission dynamics of HIV subtype D in the state of Bahia, Northeast Brazil. (2) Methods: to achieve this goal, we obtained four novel HIV-1 subtype D partial pol genome sequences using the Sanger method. To understand the emergence of this novel subtype in the state of Bahia, we used phylodynamic analysis on a dataset comprising 3,704 pol genome sequences downloaded from the Los Alamos database. (3) Results: Our analysis revealed three branching patterns, indicating multiple introductions of the HIV-1 subtype D in Brazil from the late 1980s to the late 2000s and a single introduction event in the state of Bahia. Our data further suggest that these introductions most likely originated from European, Eastern African, Western African and Southern African countries. (4) Conclusion: Understanding the distribution of HIV-1 viral strains and their temporal dynamics is crucial for monitoring the real-time evolution of circulating subtypes and recombinant forms, as well as for designing novel diagnostic and vaccination strategies. We advocate for a shift to active surveillance, to ensure adequate preparedness for future epidemics mediated by emerging viral strains.

The restriction of normal blood flow is the cause of many diseases including stroke and coronary artery diseases. To study the consequences of vessel blockade, previous models mainly focused on major arteries and have been well studied. However, the sequela from interruption of capillary vessels by microemboli was less well characterized. In this study, we exploited polystyrene microspheres as a mimicry of microemboli and found that microspheres of this size can be trapped in capillary vessels of all organs without causing apparent acute morbidities of the host. Interestingly, we accidentally found significantly increased recruitment of monocyte to the brain vasculature expressing low levels of Ly6C expression, but not to other organs. Further study revealed the spleen is the major origin of the recruited monocyte. Most importantly, VCAM-1 which is constitutively expressed on mouse brain vasculature orchestrates the recruitment of monocyte. Blockade of VCAM-1 in mice can substantially reduce monocyte recruitment. Interestingly, monocytes get activated through TNF- signaling which likely happens in the spleen instead of the brain. Collectively, we found a unique monocyte recruitment strategy in the brain comparing to other orangs, in response to capillary blockade induced by polystyrene microspheres.

Background: The prevalence of human T-lymphotropic virus type-1 (HTLV-1) infection is higher in women, and sexual intercourse has been described as an important route of male-to-female transmission. The present study aimed to quantify HTLV-1 proviral load (PVL) in vaginal fluid, and to investigate correlations with PVL in peripheral blood mononuclear cells (PBMC). Methods: HTLV-1-infected women were consecutively recruited at a multidisciplinary center for HTLV patients in Salvador-Brazil. All women underwent gynecological examinations to obtain cervicovaginal fluid and venipuncture for blood collection. PVL, as measured by real-time quantitative polymerase chain reaction (RT-qPCR), was expressed as the number of copies of HTLV-1/106 cells in blood and vaginal fluid samples. Light microscopy was used to assess cervicovaginal cytopathology and vaginal microbiota. Results: In the 56 included women (43 asymptomatic carriers and 13 diagnosed with HTLV-associated myelopathy/tropical spastic paraparesis-HAM/TSP), mean age was 35.9 (SD±7.2) years. PVL was higher in PBMCs [median: 23,264 copies/106 cells (IQR: 7,420 - 64,371)] than in vaginal fluid [451.9 copies/106 cells (IQR: 0 - 2,672)] (p<0.0001). PVL in PBMCs was observed to correlate directly with PVL in vaginal fluid (R=0.32, p=0.01). PVL was undetectable in vaginal fluid samples from 20 women (35.7%), most of whom were asymptomatic (19/20). Cytopathologic analyses revealed no differences between women with detectable or undetectable PVL. Conclusion: HTLV-1 proviral load is detectable in vaginal fluid and correlates directly with proviral load in peripheral blood. This finding suggests that sexual transmission of HTLV-1 from female to male may occur and vertical transmission, particularly in the context of vaginal delivery.

Abstract The expression patterns of microRNAs (small non-coding RNAs) are altered in many biological processes such as myogenesis. In this study, we aimed to investigate the impact of predicted miR-202, its target genes Akt2 and Rock-1 as a potential regulator of myoblast in the myocyte differentiation process using the C2C12 cell line. After confirmation of the differentiation process induced by 3% horse serum, the expression level of miRNA and its targets were evaluated. In the following, a luciferase assay was conducted to approve the effect of miRNA on its target. Our results indicated that miR-202 and Akt2 were significantly up-regulated during differentiation, while Rock-1 was downregulated. Co-transfection of miRNA with psiCHECK2-Rock-1 significantly presented that Rock-1 was directly targeted by miR-202. On the contrary, miR-202 has failed to enforce its inhibitory effect on Akt2 expression. In particular, miR-202 seems to be a regulator of muscle differentiation pathway thought targeting Rock-1.

Knowledge of the spatio-temporal occurrence of avalanche activity is critical for avalanche forecasting and hazard mapping. We present a near-real time automatic avalanche monitoring system that outputs detected avalanche polygons within roughly 10 min after Sentinel- 1 SAR data download. Our avalanche detection algorithm has an average probability of detection of 67.2 % with a false alarm rate averaging 45.9, with maximum POD's over 85 % and minimum FAR's of 24.9 % compared to manual detection of avalanches. The high variability in performance stems from the dynamic nature of snow in the Sentinel-1 data. After tuning parameters of the detection algorithm, we processed five years of Sentinel-1 images acquired over a 150 x 100 km large area in Northern Norway, with the best setup. Compared to a dataset of field-observed avalanches, 77.3 % were manually detectable. Using these manual detections as benchmark, the avalanche detection algorithm achieved an accuracy of 79 % with high POD's in cases of medium to large wet snow avalanches. For the first time, we can present a dataset of spatiotemporal avalanche activity over several winters from a large region. This unique dataset allows for research into the relationship between avalanche activity and triggering meteorological factors, mapping of avalanche prone areas and near-real time avalanche activity monitoring to assist public avalanche forecasting. Currently, the Norwegian Avalanche Warning Service is using our processing system for pre-operational use in three regions in Norway.

Aims/Hypothesis): Type 1 diabetes is an immune-mediated disease with destruction of the pancreatic β-cells, a process that is conditioned by multiple genes and other factors. HLA counts as the major susceptibility gene. Significant variations in HLA genetic susceptibility to type 1 diabetes between Caucasians, African and Asian and other ethnic groups may have led to the variation in incidence of type 1 diabetes globally. Type 1 diabetes is characterized upon HLA identification. In this chapter we discuss global variations in genetic susceptibility of HLA with regard to type 1 diabetes globally with a particular attention to Arab population. Methods): Haplotype configuration of HLA class I A, B, C and Class II –DR/DQ/DP were studied in Caucasians, African and Asian and in Arab population to see if that is responsible for the exponential rise in the rate of type 1 diabetes. Results): Although Arabs have one of the highest global incidence and prevalence rates of type 1 diabetes, unfortunately, there is a dearth amount of information regarding HLA genetic susceptibility to type 1 diabetes in the Arab world. HLA haplotype configurations contribute to its risk value. However, out of an insufficient present study there are examples of misjudgment of HLA risk according to HLA alleles rather than haplotypes. Conclusion): To date HLA outlooks for the characterization of type 1 diabetes. There is an ethnicity difference in HLA characteristics which is responsible for variation in type 1 diabetes. Although Arab population have contributed heavily in the rise of burden of type 1 diabetes, however, there is significantly a dearth amount of studies on HLA in Arab population. Obviously, any future prediction, prevention or cure of the disease will be based on the HLA genetics. There is a dire need for a systematic screening of HLA for Arab population with type 1 diabetes, identification of Arab HLA-risk values and identify those who are prone to get the disease.

Ca2+ is a crucial second messenger in plant cells, playing a vital role in various physiological and biochemical processes, including plant growth and development, photosynthesis, and enzyme regulation. Exogenous calcium concentration can have different effects on plant growth. This study aimed to investigate the optimal calcium concentration for the growth of four tree species, namely Pinus tabuliformis, Pinus sylvestris var. mongolica, Populus, and Morus alba seedlings, and whether the optimal calcium concentration varies among different tree species. The study utilized five calcium concentration gradients (0, 100, 200, 400, 800 mg·kg-1) for each species with three repeated treatments. Various growth indexes, photosynthetic parameters, chlorophyll fluorescence parameters, water use efficiency, and antioxidant enzyme activities were assessed to determine each species' calcium concentration requirements. The results showed that exogenous calcium significantly affected the growth and development of each seedling. The growth, biomass, photosynthetic parameters, photosynthetic products, photosynthetic pigments, water use efficiency, and antioxidant enzyme activity all increased initially and then decreased with increasing calcium concentration. Leaf calcium concentration also increased with the exogenous calcium content. Thus, there is an optimal calcium concentration for plant growth, and high or low calcium concentration is not conducive to plant growth. Furthermore, the study found that different tree species have varying optimal calcium concentrations. The optimal calcium concentration for Pinus tabuliformis, Pinus sylvestris var. mongolica, Populus, and Morus alba seedlings was 100, 100, 200, and 400 mg·kg-1, respectively. Finally, the study revealed that broadleaf species require higher calcium concentrations than coniferous species.

As climate change should lead to an increase in the vulnerability and the sensitivity of forests to extreme climatic events, quantifying and predicting their response to more severe droughts remains a key task for foresters. Furthermore, recent works have suggested that tree diversity may affect forest ecosystem functioning, including their response to extreme events. In this study we aimed at testing whether the growth response of forest stands to stressful climatic events varied between mixed and monospecific stands, under various environmental conditions. We focused on beech-fir forests (Fagus sylvatica [L.] and Abies alba [L.]) and beech-oak forests (Fagus sylvatica [L.] and Quercus pubescent [L.]) in the French Alps. We used a dendrochronological dataset sampled in forest plots organized by triplets (one mixture and two monospecific stands) distributed in six sites along a latitudinal gradient. We tested (1) whether stand diversity (two-species stands vs monospecific stands) modulates the stands’ response to drought events in terms of productivity, (2) whether species identity may drive the diversity effect on resistance and recovery, and (3) whether this can be explained by interspecific interactions. We found that (1) interspecific differences in response to extreme drought events (possibly due to interspecific differences in hydraulic characteristics) can induce a mixture effect on stand growth, although it appeared (2) to be strongly depending on species identity (positive effect only found for beech-fir mixed stands), while (3) there were no significant non-additive effects of diversity on stand resistance and recovery, except for some specific cases. Overall, our study shows that promoting selected mixed stands management may buffer extrem drought effect on stand productivity.

Background: Methotrexate (MTX) displayed cytotoxic properties against some cancer cells. However, there is very limited data about the possible anti-tumoral potential of them in breast cancer (BC) cells. We aimed to determine the effects of MTX, which is widely used in clinical practice, on cell viability, Hypoxia-inducible factor (HIF) -1α, HIF-2α and prolyl 4-hydroxylase-transmembrane (P4H-TM) in BC cells (MCF-7) and health breast cell (HTERT-HME1) treated with MTX. Methods: Human healthy breast cells (HTERT-HME1) and BC cells (MCF-7) treated with MTX for 24 h, 48h, and 72 h, the effects of MTX on cell viability. Results: The cell viability and with half-maximal inhibitory concentration (IC50) values of of MTX treatment in healthy breast cells were determined to be higher than in MCF-7 cells. MTX showed higher cytotoxicity against MCF-7 cells. MTX significantly reduced cell viability values in HTERT-HME1 and MCF-7 cells. HIF-1α, HIF-2α, and P4H-TM levels was significantly higher in the MCF-7 group than the other groups. Morever, there was a moderate significant correlation between HIF-1α and HIF-2α levels and between HIF-1α and P4H-TM. Conclusions: MTX will show a further decrease in cell viability in long-term treatments of 48 and 72 hours, it is predicted that short-term use may be more appropriate. P4H-TM may be a novel regulator of hypoxia in BC cells. HIF-1α, a key protein responsible for the molecular mechanism of hypoxia in cells, is a key mediator between P4H-TM and hypoxia in MTX-treated cells. HIF-1α, HIF-2α, and P4H-TM values may be markers that can be used as a panel to differentiate BC from healthy women.

Mangifera indica (mango), a member of the Anacardiaceae family, is renowned for its diverse pharmacological properties, encompassing antidiabetic, antioxidant, antiviral, cardiotonic, hypotensive, and anti-inflammatory effects. The present study delves the insulin-releasing and glucose-lowering potential of the ethanolic extract of Mangifera indica (EEMI) leaves in streptozotocin (STZ)-induced type 2 diabetic rats, concurrently investigating its phytoconstituents. EEMI's effects on insulin secretion were measured using BRIN BD11 β-cells and isolated mouse islets. It’s enzymatic inhibitory properties on carbohydrate digestion, glucose absorption, and free radicals were investigated using starch digestion, glucose diffusion and DPPH assay methods. In-vivo parameters including lipid profile and liver glycogen content were assessed on streptozotocin-induced type 2 diabetic rats. EEMI exhibited a dose-dependent increase in insulin secretion from clonal pancreatic BRIN BD11 β-cells and isolated mouse islets. EEMI inhibited starch digestion, glucose diffusion over time and DPPH activity in vitro. In acute in vivo studies, EEMI improved food intake, oral glucose tolerance. Moreover, following 28 days of treatment with EEMI, a remarkable amelioration in body weight, fasting blood glucose, plasma insulin, liver glycogen content, total cholesterol, triglyceride, LDL, VLDL and HDL levels were observed. Further phytochemical analysis with EEMI identified the presence of alkaloids, tannins, saponins, steroids, glycosides, flavonoids, and reducing sugar. The synergistic effects of EEMI, potentially attributable to naturally occurring phytoconstituents, hold promise for the development of enriched antidiabetic therapies, offering a promising avenue for the management of type 2 diabetes.

T cells follow a triphasic distinct pathway of activation, proliferation and differentiation before becoming functionally and phenotypically ‘exhausted’ in settings of chronic infection, autoimmunity and in cancer. Exhausted T cells progressively lose canonical effector functions, exhibit altered transcriptional networks and epigenetic signatures and gain constitutive expression of a broad coinhibitory receptor suite. This review outlines recent advances in our understanding of exhausted T cell biology and examines cellular and molecular mechanisms by which a state of dysfunction or exhaustion is established, and mechanisms by which exhausted T cells may still contribute to pathogen or tumour control. Further, this review describes our understanding of exhausted T cell heterogeneity and outlines the mechanisms by which checkpoint blockade differentially engages exhausted T cell subsets to overcome exhaustion and recover T cell function.

Wetlands benefits can be summarized but are not limited to their ability to store floodwaters and improve water quality, providing habitats for wildlife and supporting biodiversity, as well as aesthetic values. Over the past few decades, remote sensing and geographical information technologies has proven to be a useful and frequent applications in monitoring and mapping wetlands. Combining both optical and microwave satellite data can give significant information about the biophysical characteristics of wetlands and wetlands` vegetation. Also, fusing data from different sensors, such as radar and optical remote sensing data, can increase the wetland classification accuracy. In this paper we investigate the ability of fusion two fine spatial resolution satellite data, Sentinel-2 and the Synthetic Aperture Radar Satellite, Sentinel-1, for mapping wetlands. As a study area in this paper, Balikdami wetland located in the Anatolian part of Turkey has been selected. Both Sentinel-1 and Sentinel-2 images require pre-processing before their use. After the pre-processing, several vegetation indices calculated from the Sentinel-2 bands were included in the data set. Furthermore, an object-based classification was performed. For the accuracy assessment of the obtained results, number of random points were added over the study area. In addition, the results were compared with data from Unmanned Aerial Vehicle collected on the same data of the overpass of the Sentinel-2, and three days before the overpass of Sentinel-1 satellite. The accuracy assessment showed that the results significant and satisfying in the wetland classification using both multispectral and microwave data. The statistical results of the fusion of the optical and radar data showed high wetland mapping accuracy, with an overall classification accuracy of approximately 90% in the object-based classification. Compared with the high resolution UAV data, the classification results give promising results for mapping and monitoring not just wetlands, but also the sub-classes of the study area. For future research, multi-temporal image use and terrain data collection are recommended.

Japan Aerospace Exploration Agency (JAXA) is going to launch Advanced Land Observing Satellite 3 (ALOS-3) after 2022. ALOS-3 satellite is capable of observing global land areas with wide swath (4000 km along-track direction and 70 km cross-track direction) at high spatial resolution (panchromatic: 0.8m, multispectral: 3.2m). Maintenance and updating of land cover and vegetation information at national level is one of the major goals of the ALOS-3 mission. This paper presents the potential of simulated ALOS-3 images for the classification and mapping of land cover and vegetation types at Genus-Physiognomy-Ecosystem (GPE) level. We acquired and simulated WorldView-3 images according to the configuration of the ALOS-3 satellite sensor and the simulated ALOS-3 images were utilized for the classification and mapping of land cover and vegetation types in three sites (Hakkoda, Zao, and Shiranuka) in northern Japan. This research dealt with 17 land cover and vegetation types in Hakkoda site, 25 land cover and vegetation types in Zao site, and 12 land cover and vegetation types in Shiranuka site. Ground truth data were newly collected in three sites, and we employed eXtreme Gradient Boosting (XGBoost) classifier with the implementation of 10-fold cross-validation method for assessing the potential of ALOS-3S images. The classification accuracies obtained in Hakkoda, Zao, and Shiranuka sites in terms of f1-score were 0.810, 0.729, and 0.805 respectively. The fine scale (3.2m) land cover and vegetation maps produced in the study sites showed clear and detailed view of the distribution of plant communities. Regardless of the limited number of the temporal images, ALOS-3S images showed high potential (at least 0.729 F1-score) for the land cover and vegetation classification in all three sites. The availability of more cloud free temporal scenes is expected for improved classification and mapping in the future.

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.

This study aimed to identify new drug molecules against Leishmania parasites, leishmaniasis's causal agent, using Pistacia atlantica leaves as source. The evaluation of the anti-leishmania potential against the promastigote form of Leishmania. infantum and Leishmania. major was performed. A new in silico study was accomplished using molecular docking, with Autodock vina program, to find the binding affinity of two important phytochemical compounds from this plant (Masticadienonic acid, 3-Methoxycarpachromene) towards the trypanothione reductase as target drugs, responsible for defence mechanism against oxidative stress and virulence of this parasites. Results: Several concentrations showed a significant decrease in cell viability (P<0.0001), with IC50 values of 0.3 mg/ mL for L. infantum and 0.12 mg/ mL L. major; The molecular docking confirms the significant relationship between Leishmania survival and the inhibition of this crucial enzyme. There were promising and new positive results on binding modes of selected ligands and the trypanothione reductase for the first time. Through this work, we propose 3-Methoxycarpachromene and Masticadienonic acid as anti Trypanosomatidae species drug.

The RV144 trial represents the only vaccine trial to demonstrate any protective effect against HIV-1 infection. While the reason(s) for this protection are still being evaluated, it serves as justification for widespread efforts aimed at developing new, more effective HIV-1 vaccines. Advances in our knowledge of HIV-1 immunogens and host antibody responses to these immunogens are crucial to informing vaccine design. While the envelope (Env) protein is the only viral protein present on the surface of virions, it exists in a complex trimeric conformation and is decorated with an array of variable N-linked glycans, making it an important but difficult target for vaccine design. Thus far, efforts to elicit a protective humoral immune response using structural mimics of native Env trimers have been unsuccessful. Notably, the aforementioned N-linked glycans serve as a component of many of the epitopes crucial for the induction of potentially protective broadly neutralizing antibodies (bnAbs). Thus, a greater understanding of Env structural determinants, most critically Env glycosylation, will no doubt be of importance in generating effective immunogens. Recent studies have identified the HIV-1 Env signal peptide (SP) as an important contributor to Env glycosylation. Further investigation into the mechanisms by which the SP directs glycosylation will be important, both in the context of understanding HIV-1 biology and in order to inform HIV-1 vaccine design.

In this study, a structural profiling of equid alphaherpesvirus 1 (EHV-1) transcriptome was carried out using next-generation (Illumina) and third-generation (Oxford Nanopore Technologies) sequencing platforms. We annotated the canonical mRNA molecules and their isoforms, including transcript start and end site isoforms, and splice variants. Additionally, a number of putative 5′-truncated mRNAs containing shorter in-frame ORFs were detected. We also demonstrated that EHV-1 produces a high number of non-coding transcripts, including antisense and intergenic RNAs. One of the most remarkable features of the EHV-1 is the generation of abundant fusion transcripts some of which encoding chimeric polypeptides. We observed a higher number of splicing and transcriptional overlaps than in related viruses. Additionally, we found that many upstream genes of tandem gene clusters have their own transcript end sites (TESs) besides the co-terminal TESs, which is rare in other alphaherpesviruses. We show here that the replication origins (OriS and OriL) of the virus are co-localized with promoter sequences and overlap with specific RNA molecules. Furthermore, we discovered a novel non-coding RNA (designated as NOIR) that overlaps the 5′-ends of the longer transcript variants encoded by the two main transactivator genes ORF64 and 65 bracketing the OriL. These all suggest the existence of a central regulatory system which controls the genome-wide transcription and the replication through a mechanism based on the interference between the machineries carrying out the synthesis of DNA and RNA.

Respiratory syncytial virus (RSV) RNA synthesis takes place in cytoplasmic viral factories also called inclusion bodies (IBs), which are membrane-less organelles concentrating the viral RNA polymerase complex. IBs assembly is driven by liquid-liquid phase separation promoted by interactions between the viral nucleoprotein N and the phosphoprotein P. We recently demonstrated that cyclopamine (CPM) inhibits RSV multiplication by disorganizing and hardening IBs. Although a single mutation in the viral transcription factor M2-1 induced resistance to CPM, the mechanism of action of CPM still remains to be characterized. Here, using FRAP experiments on reconstituted pseudo-IBs both in cellula and in vitro, we first demonstrated that CPM activity depends on the presence of M2-1 together with N and P. We show that CPM impairs the competition between P and RNA binding to M2-1. As mutations on both P and M2-1 induced resistance against CPM activity, we suggest that CPM may affect the dynamics of the M2-1−P interaction, thereby affecting the relative mobility of proteins contained in RSV IBs. Overall, our results reveal that stabilizing viral protein-protein interactions is an attractive new antiviral approach. They pave the way for the rational chemical optimization of new specific anti-RSV molecules.

Background & Aims: This RCT aimed to investigate the safety and efficacy of MF4637, a medical food comprising highly concentrated, highly purified, long chain (LC) omega-3 fatty acids, (460 mg eicosapentaenoic acid (EPA) and 380 mg docosahexaenoic acid (DHA)) in correcting the omega-3 fatty acid nutritional deficiency present in non-alcoholic fatty liver disease (NAFLD). The potential for MF4637 to reduce liver fat was evaluated in a subset of patients. Methods: 176 subjects with NAFLD were randomised to receive 3 g/d of LC-omega-3 fatty acids (n=87) or placebo (olive oil; n=89) for 24 weeks, in addition to following standard-of-care dietary guidelines for these patients. Thus, interventions were given on top of the dietary advice. The omega-3 index, omega-6:omega-3 fatty acid ratio (primary outcome) and quantitative measurements of red blood cell (RBC) EPA and DHA (secondary outcome) were determined at baseline and study completion. Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) assessment of change in liver fat fraction was conducted in a subset of patients. Results: Of the 176 randomised subjects, 167 were analysed for the primary and secondary outcomes (n=81 in the MF4637 group; n=86 in the placebo group). Supplementation with MF4637 for 24 weeks significantly increased the omega-3 index and absolute values of RBC EPA and DHA, and decreased the omega-6:omega-3 fatty acid ratio in NAFLD patients compared to placebo (p<0.0001). There was a statistically significant reduction in liver fat content within both groups with no difference between them. An inverse relationship between change in absolute RBC EPA+DHA and change in liver fat, AST and ALT levels was seen suggesting that a greater increase in omega-3 content was associated with a reduction for both liver fat content and improvement in liver enzyme levels. Additionally, a significant liver fat-lowering effect of MF4637 compared to placebo was demonstrated in a subset of patients with baseline fatty liver index (FLI) score ≥ 40. There were no serious adverse events related to study interventions. Conclusions: The study results demonstrate that the medical food MF4637, was able to correct the nutritional deficiency of omega-3 in NAFLD patients above and beyond that obtained with nutritional counselling. This demonstrates that MF4637 is beneficial in raising the low omega-3 index observed in these patients. A reduction in hepatic steatosis was demonstrated with both intervention groups although no distinction between groups was seen. Further analyses demonstrate the potential to identify omega-3 sensitive patients using an easily available clinical tool for steatosis prediction.

Core chlorophytes possess glycerol-3-phosphate dehydrogenases (GPDs) with an unusual bidomain structure, consisting of a glycerol-3-phosphate phosphatase (GPP) domain fused to canonical GPD domains. These plastid-localized enzymes have been implicated in stress responses, being required for the synthesis of glycerol under high salinity and triacylglycerols under nutrient deprivation. However, their regulation under varying environmental conditions is poorly understood. C. reinhardtii transgenic strains expressing constitutively bidomain GPD2 did not accumulate glycerol or triacylglycerols in the absence of any environmental stress. Although, the glycerol contents of both wild type and transgenic strains increased significantly upon exposure to high salinity. Cycloheximide, an inhibitor of cytoplasmic protein synthesis, abolished this response in the wild type. In contrast, GPD2 transgenic strains were still capable of glycerol accumulation when cultured in medium containing cycloheximide and NaCl. Thus, pre-existing GPD2 protein appears to become activated for glycerol synthesis upon salt stress. Interestingly, staurosporine, a non-specific inhibitor of protein kinases, prevented this post-translational GPD2 protein activation. Structural modeling analyses suggested that substantial conformational rearrangements, possibly triggered by high salinity, may characterize an active GPD2 GPP domain. Understanding this mechanism(s) may provide insights into the rapid acclimation responses of microalgae to osmotic/salinity stress.

Background: We aimed to determine the splenic stiffness (SS) values in healthy individuals as measured by 3 Tesla magnetic resonance elastography (3T MRE) and to investigate the possible effects of parameters such as age, sex, spleen volume, diameter, and parenchyma thickness on SS.Methods: A total of 54 healthy volunteers were included in this cross-sectional study. Participants' age and sex information were recorded, in addition to spleen craniocaudal and anteroposterior diameter, cortical thickness, spleen volume, and SS, which were measured using 3T magnetic resonance imaging and MRE. Results: Twenty-nine male and 25 female subjects with a mean age of 54.78±15.40 years were included in the study. Mean cradiocaudal diameter was 10.46±1.16 cm, anteroposterior diameter was 9.88±1.29 cm, parenchyma thickness was 4.08±0.67 cm, SS was 3721.94±709.69 Pascal (Pa), and median spleen volume was 292.54 (239.40-311.00) cm³. A significant positive correlation was observed between age and SS (r=0.779, p<0.001). The SS values were not associated with sex, craniocaudal diameter, anteroposterior diameter, parenchymal thickness, or volume.Conclusion:Age should be considered when using SS in the diagnosis and staging of relevant diseases such as portal hypertension and esophageal varices. Our results should be confirmed by future studies using 3T MRE in larger populations.

Background: We aimed to determine the splenic stiffness (SS) values in healthy individuals as measured by 3 Tesla magnetic resonance elastography (3T MRE) and to investigate the possible effects of parameters such as age, sex, spleen volume, diameter, and parenchyma thickness on SS. Methods: A total of 54 healthy volunteers were included in this cross-sectional study. Participants' age and sex information were recorded, in addition to spleen craniocaudal and anteroposterior diameter, cortical thickness, spleen volume, and SS, which were measured using 3T magnetic resonance imaging and MRE. Results: Twenty-nine male and 25 female subjects with a mean age of 54.78±15.40 years were included in the study. Mean cradiocaudal diameter was 10.46±1.16 cm, anteroposterior diameter was 9.88±1.29 cm, parenchyma thickness was 4.08±0.67 cm, SS was 3721.94±709.69 Pascal (Pa), and median spleen volume was 292.54 (239.40-311.00) cm3. A significant positive correlation was observed between age and SS (r=0.779, p<0.001). The SS values were not associated with sex, craniocaudal diameter, anteroposterior diameter, parenchymal thickness, or volume Conclusion:Age should be considered when using SS in the diagnosis and staging of relevant diseases such as portal hypertension and esophageal varices. Our results should be confirmed by future studies using 3T MRE in larger populations.

Norovirus (NoV) is recognised as a major cause of epidemic and sporadic acute gastroenteritis (AGE) in all age groups. Information on the genetic diversity of the NoVs circulating in the 1980s and 1990s, before the development and adoption of dedicated molecular assays, is limited compared to the last decades. In the period 1986-2020, uninterrupted viral surveillance was conducted in symptomatic children hospitalized for AGE in Palermo, Italy, providing a unique time capsule for exploring the epidemiological and evolutionary dynamics of enteric viruses. In this 35-year long time span NoVs of genogroup II (GII) were detected in 15.6% of AGE requiring hospitalization, whilst GI NoVs in 1.4%. Overall, the predominant NoV capsid (Cap) genotype was GII.4 (60.8%), with temporal replacement of the GII.4 Cap variants and associated polymerase (Pol) types. The chronology of emergence and circulation of the different GII.4 variants were consistent with the data available in literature. Also, for GII.3 and GII.2 NoVs the circulation of different lineages/strains, differing in either the Cap or Pol genes or in both, was observed. This long-term study revealed the ability of NoVs to modify continuously and rapidly their genomic makeup and highlights the importance of surveillance activities for vaccine design.

Edge computing has emerged as a significant computing trend alongside the rapid expansion of the Internet of Things (IoT). Computing operations at the network’s edge offer a solution to the high latency and service overload challenges often associated with cloud computing. Additionally, the Secure Hash Algorithm-3 (SHA-3) plays a crucial role in ensuring data integrity and is implemented for numerous applications in the IoT field. Therefore, integrating the SHA-3 accelerator into edge computing is essential. Moreover, recent studies about SHA-3 have primarily focused on achieving high performance and optimizing resource utilization for SHA-3. However, these studies have overlooked the crucial aspect of data transfer between the external memory and the hash function block, as transfer time plays a significant role. This paper proposes an efficient SHA-3 architecture designed for System-on-Chip (SoC) Field Programmable Gate Array (FPGA) to address the aforementioned challenges and be suitable for real edge computing. The architecture contains three key techniques. First, the harmony of padding and Direct Memory Access (DMA) for managing the data transfer process and enhancing performance efficiency based on Serial Input to Parallel Output (SIPO) and a barrel shifter. Secondly, implementing internal pipelining within the Round Function (RF) to reduce critical path delays and optimize resource utilization. Finally, designing four modes (SHA3-224, SHA3-256, SHA3-384, and SHA3-512) to cater to various applications. Our architecture is implemented and tested on the DE10-Standard Development Kit (Cyclone V SX SoC-5CSXFC6D6F31C6N), which is integrated into the FPGA and is controlled by a Dual-Core ARM Cortex-A9 processor. The result is up to 38.34 Gbps in throughput and 5.61 Mbps/ALM in efficiency for the RF computation, 28.02 Gbps in throughput, and 3.63 Mbps/ALM for the full proposed architecture.

Cervical cancer is the most common female reproductive tract tumor and is currently the only cancer that can be prevented by vaccination. Early detection and treatment of cervical cancer can be achieved through regular screening for human papillomavirus (HPV). Therefore, in this paper, an electrochemical sensor was designed to detect HPV 16 using a dual signal amplification technique. APTES modified glassy carbon electrode to improve stability. Combining gold nanoparticles and chain amplification reactions for signal amplification purposes. The limit of detection (LOD) was 1.731×10-16 mol/L, and the detection range of this electrochemical sensor was increased in comparison to previous research, with a linear response range from 1.0×10-13 mol/L to 1.0×10-5 mol/L (R2 = 0.99232) for the target detector.In addition, the sensor showed equally good recovery in sophisticated human serum samples. It shows that it has good interference resistance and the designed biosensor can be a powerful and reliable tool for clinical disease diagnosis.

Isoamyl (E)-3-(3,4-dimethoxyphenyl)acrylate (1) was obtained 95% yield by 2-methyl-6-nitrobenzoic anhydride (MNBA)/4-dimethylaminopyridine (DMAP)-catalyzed reaction at room temperature for 190 minutes in dichloromethane. The structure of isoamyl (E)-3-(3,4-dimethoxyphenyl)acrylate (1) was established by NMR, FTIR, and the high resolution of mass spectroscopies. In vitro sun protection factor evaluation exhibited value of 37.10 ± 0.03 which indicates that isoamyl (E)-3-(3,4-dimethoxyphenyl)acrylate (1) as a sunscreen agent with high protection.

Today's major challenge for smart Microgrids is to ensure the security of communications in a large number of changing data sets that are vulnerable to attacks by denial of services in constant evolution. The Internet Protocol Traceback defines a set of methods that help identify the source of an attack with minimal requirements for memory and processing. However, the concept of Traceback is not yet being used in smart Microgrids. As a result, the main challenge of this article is to incorporate a new Traceback approach into the cybernetic system of a smart mesh Microgrid, which can be tested using a network simulator (NS-3) based on delay, debit, and packet loss rate parameters. In fact, the simulation results show the efficacy of this approach compared to others existing in the literature. Furthermore, using the proposed Traceback technique and the mesh nodes, we were able to create a smart meshed Microgrid. Moreover, using the Traceback approach given for merging Intel Galileo Gen.1 nodes with the Compex WLE200NX.11a/b/g/n to establish a secure test bench, which is deployed as a prototype at the Sfax Digital Research Center in Tunisia, we were able to create an intelligent Microgrid. In fact, by identifying all attack vectors and revealing their origins, we could boost the efficiency of our operation by 100%.

Background: Omega-3 polyunsaturated fatty acids (PUFAs) are increasingly reported to improve chronic neuroinflammatory diseases in peripheral and central nervous systems. Specifically, docosahexaenoic acid (DHA) protects nerve cells from noxious stimuli in vitro and in vivo. Recent reports link PUFA supplementation to improving painful diabetic neuropathy (pDN) symptoms. However, the molecular mechanism behind omega-3 PUFAs ameliorating pDN symptoms is lacking. Therefore, we sought to determine the distinct cellular pathways that omega-3 PUFAs dietary supplementation promotes in reducing painful neuropathy in type 2 diabetes mellitus (DM2) patients. Methods: Forty volunteers diagnosed with type 2 diabetes were enrolled in the "En Balance-PLUS" diabetes education study. The volunteers participated in weekly lifestyle/nutrition education and daily supplementation with 1,000 mg DHA and 200 mg eicosapentaenoic acid. The Short-Form McGill Pain Questionnaire validated clinical determination of baseline and post-intervention pain complaints. Laboratory and untargeted metabolomics analyses were conducted using blood plasma collected at baseline and after three months of participation in the dietary regimen. The metabolomics data was analyzed using random forest, hierarchical cluster, ingenuity pathway analysis, and metabolic pathway mapping. Results: We found that metabolites involved in oxidative stress and glutathione production shifted significantly to a more anti-inflammatory state post supplementation. Example of these metabolites include cystathionine (+90%), S-methylmethionine (+9%), glycine cysteine-glutathione disulfide (+157%) cysteinylglycine (+19%), glutamate (-11%), glycine (+11%) and arginine (+13.4%). In addition, the levels of phospholipids associated with improved membrane fluidity such as linoleoyl-docosahexaenoyl-glycerol (18:2/22:6) (+253 %) were significantly increased. Ingenuity pathway analysis suggested several key bio functions associated with omega-3 PUFA supplementation such as formation of reactive oxygen species (p = 4.38 × 10-4, z-score = -1.96), peroxidation of lipids (p = 2.24 × 10-5, z-score = -1.944), Ca2+ transport (p = 1.55 × 10-4, z-score = -1.969), excitation of neurons (p = 1.07 ×10-4, z-score = -1.091), and concentration of glutathione (p = 3.06 × 10-4, z-score = 1.974). Conclusion: The reduction of pro-inflammatory and oxidative stress pathways following omega-3 PUFAS supplementation is consistent with using omega-3 PUFAs as a complementary dietary strategy as part of the overall treatment of painful diabetic neuropathy.

Adrenergic receptor β3 (ADRβ3) is a member of the rhodopsin-like G protein-coupled receptor family. The binding of the ligand to ADRβ3 activates adenylate cyclase and increases cAMP in the cells. ADRβ3 is highly expressed in white and brown adipocytes and controls key regulatory pathways of lipid metabolism. Trp64Arg (W64R) polymorphism in the ADRβ3 has been associated with the early development of type 2 diabetes mellitus, lower resting metabolic rate, abdominal obesity, and insulin resistance. It is unclear how the substitution of W64R affects the functioning of ADRβ3. This study was initiated to functionally characterize this obesity-linked variant of ADRβ3. We evaluated in detail the expression, subcellular distribution, and post-activation behavior of the WT and W64R ADRβ3 using a single cell quantitative fluorescence microscopy. When expressed in HEK 293 cells, ADRβ3 shows a typical distribution displayed by other GPCRs with a predominant localization at the cell surface. Unlike Adrenergic receptor β2 (ADRβ2), agonist induced desensitization of ADRβ3 does not involve loss of cell surface expression. WT and W64R variant of ADRβ3 displayed comparable biochemical properties and there was no significant impact of the substitution of Tryptophan with Arginine on the expression, cellular distribution, signaling, and post-activation behavior of ADRβ3. The obesity-linked W64R variant of ADRβ3 is indistinguishable from the WT ADRβ3 in terms of expression, cellular distribution, signaling, and post-activation behavior.

GPR4, a member of proton activated GPCRs group. Previously we have reported that GPR4 is constitutively active at physiological pH and knockout of GPR4 has shown to protect dopaminergic neuronal cells from caspase-dependent mitochondrial apoptotic cell death. In this study we have investigated the role of GPR4 in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) treated mice model of Parkinson’s disease. Subchronic administration of MPTP in mice produces oxidative stress induced apoptotic cell death of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and motor deficits. Treatment with NE52-QQ57, a selective antagonist of GPR4 reduced dopaminergic neuronal loss MPTP-intoxicated C57BL6/J mice and improved motor deficit and memory impairment. Co-treatment with NE52-QQ57 significantly decreases the protein level of proapoptotic marker (Bax), and increases the antiapoptotic marker (Bcl-2) in the SNpc and striatum tissue collected from the brain of MPTP inflicted mice. Further, MPTP induced activation of caspase 3 and cleavage of poly (ADP-ribose) polymerase (PARP) was significantly decreased in the SNpc and striatum tissue of NE52-QQ57 cotreated mice. Further mice receiving both MPTP and NE52-QQ57 mice showed significantly higher TH positive cells in the SNpc and striatum than MPTP treated mice alone. Moreover, NE52-QQ57 cotreatment improved the motor activity in the rotarod test and pole test and also improved spatial memory in Y maze test. Our findings suggest GPR4 as a potential therapeutic target for PD whereas the activation GPR4 is involved in the caspase mediated apoptotic cell death in SNpc and striatum of MPTP-intoxicated mice.

We present a cost- and time-efficient method for the controlled preparation of single phase La(IO3)3 nanoparticles via a simple soft-chemical route which takes a matter of hours, thereby providing an alternative to the common hydrothermal method which takes days. Nanoparticles of pure α-La(IO3)3 and pure δ-La(IO3)3 were synthesised via the new method depending on the source of iodate ions, thereby demonstrating the versatility of the synthesis route. The crystal structure, nanoparticle size-dispersal and chemical composition were characterised via angle- and energy-dispersive powder X-ray diffraction, scanning electron microscopy and Fourier-transform infrared spectroscopy.

It was thought until the 1990s that the eukaryotic translation machinery was unable to translate a circular RNA. However internal ribosome entry sites (IRESs) and m⁶A-induced ribosome engagement sites (MIRESs) were discovered, promoting 5’end-independent translation initiation. Today a new family of so-called “non-coding” circular RNAs (circRNAs) has emerged, revealing the pivotal role of 5’end-independent translation. CircRNAs have a strong impact on translational control via their sponge function, and form a new mRNA family as they are translated into proteins with pathophysiological roles. While there is no more doubt about translation of covalently closed circRNA, the linearity of canonical mRNA is only theoretical: it has been shown for more than thirty years that polysomes exhibit a circular form and mRNA functional circularization has been demonstrated in the 1990s by the interaction of initiation factor eIF4G with poly(A) binding protein. More recently, additional mechanisms of 3’-5’ interaction have been reported, including m⁶A modification. Functional circularization enhances translation via ribosome recycling and acceleration of the translation initiation rate. This update of covalently and non-covalently circular mRNA translation landscape shows that RNA circular shape might be the rule for translation with an important impact on disease development and biotechnological applications.

Fish oil rich in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), vitamin D₃ and natural astaxanthin sustainably extracted from anchovy fillet leftovers using biobased limonene only, can be conveniently stabilized by adsorption on periodic mesoporous silicas. The simplicity of the process, the high load of entrapped fish oil, and the biocompatible nature of silica support numerous forthcoming applications of this new class of “Omeg@Silica” materials.

Extracellular vesicles (EVs) released by different cell types play significant role in many physiological and pathophysiological processes. In physiological conditions red blood cells (RBCs) derived EVs compose 4 - 8% of all circulating EVs, and oxidative stress (OS) as a consequence of different pathophysiological conditions significantly increases the amount of circulated RBC-derived EVs, however the mechanisms of EV formation are not fully defined yet. To analyze OS-induced EV formation and RBCs transformations we used flow cytometry to evaluate cell esterase activity, caspase-3 activity, and band 3 clustering. Band 3 clustering was additionally analyzed by confocal microscopy. Two original laser diffraction-based approaches were used for analysis of cell deformability and band 3 activity. Hemoglobin species were characterized spectrophotometrically. We showed that cell viability in tert-butyl hydroperoxide-induced OS directly correlated with oxidant concentration to cell count ratio, RBCs-derived EVs contained hemoglobin oxidized to hemichrome (HbChr). OS induced caspase-3 activation and band 3 clustering in cells and EVs. Importantly, we showed that OS-induced EV formation is independent from calcium. Presented data indicated that during OS RBCs eliminate HbChr by vesiculation, in order to sacrifice the cell itself thereby prolonging lifespan and delaying the untimely clearance of in all other respects healthy RBCs.

Gold clusters protected by 3-MBA ligands (MBA = mercaptobenzoic acid, -SPhCO2H) have attracted recent interest for their unusual structures and advantageous ligand-exchange and bioconjugation properties. Azubel et al. first determined the core structure of an Au68-complex, which was estimated to have 32 ligands (3-MBA groups). To explain the exceptional structure-composition and reaction properties of this complex, and its larger homologs, Tero et al. proposed a “dynamic stabilization” via carboxyl O-H--Au interactions. Herein, we report the first results of an integrated LC/MS analysis of unfractionated samples of gold / 3-MBA clusters, spanning the narrow size range 13.4 to 18.1 kDa. Using high-throughput procedures adapted from bio-macromolecule analyses, we show that integrated capillary HPLC-ESI-MS, based upon aqueous-methanol mobile phases and ion-pairing reverse-phase chromatography, can separate several major components from the nanoclusters mixture that may be difficult to resolve by standard native gel electrophoresis due to their similar size and charge. For each component, one obtains a well-resolved mass spectrum, nearly free of adducts or signs of fragmentation. A consistent set of molecular mass determinations is calculated from detected charge-states tunable from 3- (or lower), to 2+ (or higher). One thus arrives at a series of new compositions (n, p) specific to the Au/3-MBA system. The smallest major component is assigned to the previously unknown (48, 26); the largest one is evidently (67, 30), vs. the anticipated (68, 32). Various explanations for this discrepancy are considered. A prospective is given for the several members of this novel series, along with a summary of the advantages and present limitations of the micro-scale integrated LC/MS approach to characterize such metallic-core macro-molecules, and their derivatives.

Streptococcus mutans (S. mutans) is the main etiological bacteria present in the oral cavity that leads to dental caries. All of the S. mutans in the oral cavity form biofilms that adheres to the surfaces of teeth. Dental caries are infections facilitated by the development of biofilm. An esterified derivative of epigallocatechin-3-gallate (EGCG), epigallocatechin-3-gallate-sterate (EGCG-S) was used in this study to assess its ability to inhibit the growth and biofilm formation of S. mutans. The effect of EGCG-S on bacterial growth was evaluated with colony forming units (CFU) and log reduction; biofilm formation was qualitatively determined by Congo red assay, and quantitatively determined by crystal violet assay, fluorescence-based LIVE/DEAD assays to study the cell viability, and scanning electron microscopy (SEM) was used to evaluate the morphological changes. The results indicated that EGCG-S was able to completely inhibit growth and biofilm formation at concentrations of 250 µg/ml. Its effectiveness was also compared with a commonly prescribed mouthwash in the United States, chlorhexidine gluconate. EGCG-S was shown to be equally effective in reducing S. mutans growth as chlorhexidine gluconate. In conclusion, EGCG-S is potentially a natural anticariogenic agent by reducing bacterial presence in the oral cavity.

Hyperbaric oxygen (HBO) treatment has been proven to attenuate neuroinflammation in rats. This study aimed to determine the potential mechanism underlying the anti-inflammatory effects of HBO treatment on burn-induced neuroinflammation in rats. Thirty-six adult male Sprague–Dawley (SD) rats were randomly assigned to the following six groups (n = 6 per group): (1) sham burn with sham HBO treatment, (2) sham burn with HBO treatment, (3) burn with 1-week sham HBO treatment, (4) burn with 2-week sham HBO treatment, (5) burn with 1-week HBO treatment, and (6) burn with 2-week HBO treatment. SD rats that received third-degree burn injury were used as a full-thickness burn injury model. Subsequently, we analyzed the expression of proteins involved in the galectin-3 (Gal-3)-dependent Toll-like receptor-4 (TLR-4) pathway through enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC) analysis, and Western blotting, and a behavior test was also conducted. The behavior test revealed that HBO treatment significantly suppressed mechanical hypersensitivity in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). ELISA results showed that tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) levels in the dorsal horn of the spinal cord and the skin were significantly decreased in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). Western blotting results demonstrated that HBO treatment significantly reduced the expression of Gal-3 and TLR-4 in the dorsal horn of the spinal cord in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). IHC analysis results showed that the expression of Gal-3, TLR-4, CD68, and CD45 in the dorsal horn of the spinal cord was significantly lower in the burn with HBO treatment group than in the burn with sham HBO treatment group (p < 0.05), and the expression of CD68 and macrophage migration inhibitory factor (MIF) in the right hind paw skin was significantly lower. The expression of vimentin and fibroblast growth factor (FGF) in the right hind paw skin was significantly higher after HBO treatment (p < 0.05). This study proved that early HBO treatment relieves neuropathic pain, inhibits the Gal-3-dependent TLR-4 pathway, and suppresses microglia/macrophage activation in a rat model.

This dissertation presents a method for the synthesis of substituted indoles bearing heterocyclic substituents onto the 3- position. The route for the synthesis of the heterocyclic substituents indoles starts from 3-acetyl indole nucleus depend on two parts. One part: Reaction of 3-acetylindole 1 with hydrazide compounds such as phenyl hydrazine, hydrazine hydrate, and thio-semicarbazide, to yield 3-(1-(2-phenylhydrazono) ethyl)-1H-indole 2, 3-(1-hydrazonoethyl)-1H-indole 6, and thiosemicarbazone 10 respectively. 3-(1-Hydrazonoethyl)-1H-indole 6 reacted with thiophene-2-carboxaldeyde, isatin and 3-acetyl indole. In the same way, 3-(1-(2-phenylhydrazono) ethyl)-1H-indole 2 reacted with thioglycollic acid, glycine and benzaldehyde. 3-Acetylindole 1 thiosemicarbazone reacted with acetic anhydride, piperidine, concentration of hydrochloric acid and thiophene-2-carboxaldeyde. Second part. Reaction of 3-acetyl indole 1 with amines compounds such as p-nitroaniline to formed Schiff base 15 which it reacted with thioglycollic acid to give compound 16. 3-Acetyl indole 1 reacted with ethylene diamine to afford bis imine indole to afford compound 17. The reports of this docking study revealed that the new compounds exhibit good antibacterial activity. The synthesized compounds screened in vitro for their antibacterial activity revealed remarkable inhibitory effects against the selected microorganisms. And also an anti-oxidant activity studying for some synthesized compounds. Structures of the newly synthesized compounds examination by spectral data (IR, 1H- NMR and 13C -NMR).

Background: The prognostic value of erythrocyte levels of the n-6 fatty acids (FAs) for total mortality and cardiovascular disease (CVD) outcomes remains an open question. Methods: We examined CV outcomes and death in 2500 individuals in the Framingham Heart Study Offspring cohort without prevalent CVD (mean age 66 years, 57% women) as a function of baseline levels of different length n-6 FAs (18 carbon, 20 carbon and 22 carbon) in the erythrocyte membranes. Clinical outcomes were monitored for up to 9.5 years (median follow up, 7.26 years). Cox proportional hazards models were adjusted for a variety of demographic characteristics, clinical status and RBC n-6 and long chain n-3 FA content. Results: There were 245 CV events, 119 CHD events, 105 ischemic strokes, 58 CVD deaths, and 350 deaths from all causes. Few associations between either mortality or CVD outcomes were observed for the n-6 FAs, with those that were observed becoming non-significant after adjusting for n-3 FA levels. Conclusions: Higher circulating levels of the marine n-3 FA levels are associated with reduced risk for incident CVD and ischemic stroke and for death from CHD and all-causes, however in the same sample, little evidence exists for association with n-6 FAs. Further work is needed to identify a full profile of FAs associated with cardiovascular risk and mortality.

This study investigates the effects of subclinical hypothyroidism and BDNF on telomere length in T1DM mothers and their neonates. Methods: In this prospective cohort study, 70 pregnant women with T1DM were enrolled. Subclinical hypothyroidism during the first trimester was characterized by elevated thyroid-stimulating hormone (TSH) levels ranging from 2.5 to 5.0mIU/L alongside normal free thyroxine (FT4) concentrations. Participants were stratified into two groups based on TSH levels: a maternal subclinical hypothyroid group (SHG, n=35) and a maternal euthyroid group (ETG, n=35). Leukocyte telomere length (LTL) measurements were conducted using whole blood samples from the mothers and umbilical veins. Results: The maternal LTL mean was 1.7 (SD=1.1), which was significantly shorter than the neonatal telomeres, with a mean of 2.3 SD (1.2). A significant correlation was observed between maternal and neonatal LTL (r=0.750, p&lt;0.001). A positive association was found between neonatal LTL and BDNF levels in maternal circulation [β=0.421 (95% CI 0.536; 1.873; p=0.001)]. Neonatal LTL was negatively associated with gestational weight gain [β=-0.266 (95% CI-0.138; -0.009)], and with TSH in the first trimester [β=-0.237; (95% CI -0.493; - 0.010)]. Notably, neonates in the SHG exhibited shorter LTL, with a mean of 2.1 (1.0), compared to those in the ETG, who had a mean LTL of 2.7 (1.4). A positive association was found between maternal LTL and BDNF levels in maternal circulation [β=0.523 (95% CI 0.790; 1.950; P&lt;0.001)]. Maternal LTL was negatively associated with gestational weight gain [β=-0.259 (95% CI -0.122; -0.010)], and with TSH in the first trimester [β=-0.231; (95% CI -0.422; - 0.015)]. Conclusions: Genetic factors affect neonatal LTL. Maternal subclinical hypothyroidism reduces neonatal LTL. The link between maternal and neonatal LTL and BDNF reveals the complex endocrine-neurotrophic interaction in T1DM telomere dynamics.

VNREDSat-1 is the first Vietnamese satellite allowing the survey of environmental parameters such as vegetation and water coverages, or surface water quality at medium spatial resolution (from 2.5 to 10 meters depending on the considered channel). The NAOMI sensor on board VNREDSat-1 has the required spectral bands to assess the suspended particulate matter concentration, SPM. Because recent studies have shown that the remote sensing reflectance, Rrs(), at the blue (450 – 520 nm), green (530 – 600 nm), and red (620 – 690 nm) spectral bands can be assessed from NAOMI with a good accuracy, the present study is dedicated to the development and validation of an algorithm (hereafter referred to as V1SPM) to assess SPM from Rrs() over inland and coastal waters of Vietnam. For that purpose, an in situ data set of hyper-spectral Rrs() and SPM (from 0.47 to 240.14 g.m-3) measurements collected at 205 coastal and inland stations has been gathered. Among the different approaches, including 4 historical algorithms, the polynomial algorithms involving the red-to-green reflectance ratio presents the best performance on the validation data set (MAPD of 18,7%). Compared to the use of a single spectral band, the band ratio allows to reduce the scatter around the polynomial fit as well as the impact of imperfect atmospheric corrections. Due to the lack of matchup data points with VNREDSat-1, the full VNREDSat-1 processing chain (RED-NIR and V1SPM) aiming at estimate SPM from the top-of-atmosphere signal has been applied to the Landsat-8/OLI match-up data points with relatively low to moderate SPM concentration (3.33-15.25 g.m-3) showing a MAPD of 15,8%. An illustration of the use of this VNREDSat-1 processing chain during a flooding event occurring in Vietnam is provided.

PgRMC1 (progesterone receptor membrane component 1) is a progesterone-binding protein highly expressed in various cancer cells. Its expression has been associated with cancer development, chemoresistance, and poor prognosis in breast cancer through the regulation of drug and sterol metabolism, cell cycle, and apoptosis. However, the precise functions of PgRMC1 remain unclear. We examined PgRMC1 expression in breast cancer tissues and analyzed its correlation with clinicopathological characteristics and treatment response (n=112). PgRMC1 expression was detected in breast cancer tissue, while no immunoreactivity for PgRMC1 was observed in normal breast tissue. Notably, PgRMC1 expression levels were high in the HER2 subtype. Among patients treated with neoadjuvant chemotherapy, those with a poor pathological response had significantly higher PgRMC1 expression than those with a good response. PgRMC1 overexpression in breast cancer cell lines reduced chemosensitivity. Real-time qPCR analyses revealed that PgRMC1 induced the expression of differentiation markers, including CDH1 and KRT19, indicating that PgRMC1 is involved in the suppression of epithelial-mesenchymal transition and mammary luminal epithelial differentiation. Our findings suggest that PgRMC1 may contribute to chemoresistance and serve as a putative biomarker for assessing neoadjuvant chemotherapy sensitivity.

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.

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.

Soil moisture plays a crucial role in various hydrological processes and energy partitioning of the global surface. The Soil Moisture Active Passive-Sentinel (SMAP-Sentinel) remote sensing technology has demonstrated a great potential in monitoring soil moisture at a scale greater than 1 km. This capability can be applied to improve weather forecast accuracy, enhance water management for agriculture, and climate-related disasters. Despite the techniques increasing used worldwide, its accuracy still requires field validation in specific regions like Thailand. In this paper, we report on extensive in-situ monitoring of soil moisture (from surface up to 1 m depth) at 10 stations across Thailand spanning the years 2021 to 2023. The aim was to validate SMAP surface soil moisture (SSM) Level 2 product over a period of two years. Using one month averaging approach, the study revealed linear relationships between the two measurement types, with the coefficient of determination (R-squared) varying from 0.13 to 0.58. Notably, areas with more uniform land use and topography such as croplands tended to have a better coefficient of determination. We also conducted detailed soil core characterization, including soil-water retention curves, permeability, porosity, and other physics properties. These soil properties were then used for estimating the correlation constants between SMAP and in-situ soil moistures using multiple linear regression. The results demonstrated R-squared values between 0.933 and 0.847. An upscaling approach of SMAP was proposed which showed a promising results when using 3-month average of all measurements in cropland together. The finding also suggest that the SMAP-Sentinel remote sensing technology exhibits significant potential for accurate soil moisture monitoring in diverse applications. Further validation efforts and research, particularly in terms of root zone depths and area-based assessments, especially in the agricultural sector, can greatly improve the technology’s effectiveness and usefulness in the region.

Despite the numerous advances in target therapy for the treatment of colorectal cancer, aggressive colorectal cancer remains an incurable disease whose negative modulation of the immune system in the tumor microenvironment is still critical for improving the patient's prognosis. Extracellular vesicles (EVs) have received attention for their use as cell-membrane-camouflaged nanoparticles and drug delivery systems in nanomedicine derived by nearly all cell types for intercellular communication and regulation in the tumor microenvironment (TME). In this study, M1 Macrophage EVs (M1EVs) were used as nanocarriers of oxaliplatin (M1EV1) associated with retinoic acid (M1EV2) and Libidibia ferrea (M1EV3), or combined together with retinoic acid and Libidibia ferrea (M1EV4) to evaluate their antiproliferative and immunomodulatory potential on CT-26 and MC-38 colorectal cancer cell lines, as well as their capacity to prevent metastases in mouse models of colorectal cancer such as allographic and peritoneal. Tumors were evaluated by qRT-PCR and immunohistochemistry. The cell death profile and epithelial-mesenchymal transition process (EMT) were analyzed in vitro in colorectal cancer cell lines. Polarization of murine macrophages (RAW264.7 cells) was also carried out. M1EV2 and M1EV3 used alone or especially combined (M1EV4) downregulated the tumor progression by TME immunomodulation, leading to a decrease in primary tumor size and metastases in peritoneum, liver and lungs. STAT3, NF-kB and AKT were the major genes downregulated by systems of M1EVs. Tumor-associated macrophages (TAM) switched M2 phenotype (CD163) towards M1 (CD68) reducing levels of IL-10, TGF-β and CCL22. Furthermore, malignant cells showed overexpression of FADD, APAF-1, caspase-3, and E-cadherin, and decreased expression of MDR-1, survivin, vimentin, CXCR4, and PD-L1 after treatment with systems of M1EVs. The results obtained in this study provided evidence that EVs from M1 antitumor macrophages can transport drugs and increase their immunomodulatory and antitumor activity by stimulating activation or blockage of pathways involved in cell proliferation, migration, cell survival, and drug resistance processes.

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.

Docosahexaenoic acid (DHA) is an essential fatty acid (FA) with proven health effects, whom bioavailability improvement is becoming a public health issue. Unlike fish oils, the bioavailability of DHA from microalgal (A) has not been fully assessed, particularly with regard to the molecular structuring capabilities offered by A-oil. We explored the impact of 5 formulas rich in DHA, different by i) the molecular structure: ethyl ester (EE) or monoglyceride (MG) or Triglyceride (TG) and ii) the supramolecular form: emulsified TG or TG+phospholipids (blend PL), on the lymphatic kinetics of DHA absorption and the lipid characteristics of resulting lipoproteins. We demonstrated that in rat, the DHA absorption of the conventional A-DHA TG structure was more effective than the EE structure (+ 23%). More, the A-DHA MG and A-DHA Emulsion were the most favourable DHA-vectors (AUC: 89% and +42%, respectively), thanks to an improved lipolysis. The A-DHA MG and -Emulsion presented the richest DHA content in TG (+40%) and PL (+50%) of lymphatic chylomicrons, which could impact the metabolic fate of DHA. We concluded that structuring A-DHA in TG or EE would be more prone for tissue and hepatic metabolism whereas in A-DHA MG and A-DHA Emulsion could target nerve tissues.

Recently, the Third Generation Partnership Project (3GPP) introduced the New Radio (NR) technology for Vehicle-to-everything (V2X) communication to enable delay-sensitive and bandwidth-hungry applications in vehicular communication. The NR system is strategically crafted to complement the existing Long Term Evolution (LTE) Cellular-Vehicle-to-Everything (C-V2X) infrastructure, particularly to support advanced services such as the operation of automated vehicles. It is widely anticipated that the 5th generation (5G) NR system will surpass LTE C-V2X in terms of achieving superior performance in scenarios characterized by high throughput, low latency, and enhanced reliability, especially in the context of congested traffic conditions and a diverse range of vehicular applications. This article will provide a comprehensive literature review on vehicular communications from Dedicated Short Range Communication (DSRC) to NR V2X. Subsequently, it delves into a detailed examination of the challenges and opportunities inherent in NR V2X technology. Finally, we proceed to elucidate the process of creating and analyzing an open-source 5G NR V2X module in network simulation-3 (ns-3) and then demonstrate the NR V2X performance in terms of different key performance indicators implemented through diverse operational scenarios.