Leishmanial skin lesions are characterized by inflammatory hypoxia alongside the activation of hypoxia inducible factors, HIF-1a and HIF-2a, and subsequent expression of the HIF-a target VEGF-A during Leishmania major infection. However, the factors responsible for HIF-a activation are not known. We hypothesize hypoxia and pro-inflammatory stimuli contribute to HIF-a activation during infection. RNASeq on leishmanial lesions found transcripts associated with HIF-1a signaling are induced. To determine whether hypoxia contributes to HIF-a activation, we followed the fate of myeloid cells infiltrating from the blood and into hypoxic lesions. Recruited myeloid cells experience hypoxia when they enter inflamed lesions, and the length of time in lesions increases their hypoxic signature. To determine whether pro-inflammatory stimuli in the inflamed tissue can also influence HIF-a activation, we subjected macrophages to various pro-inflammatory stimuli and measured VEGF-A. While parasites alone did not induce VEGF-A, and pro-inflammatory stimuli only modestly induce VEGF-A, HIF- stabilization increases VEGF-A during infection. HIF-a stabilization does not impact parasite entry, growth or killing. Alternatively, the absence of ARNT/HIF- signaling enhances parasite internalization. Altogether, these findings suggest HIF-a is active during infection, and while macrophage HIF-a activation promotes lymphatic remodeling through VEGF-A production, HIF-a activation does not impact parasite internalization or control.

Background and objectives: Contrast-induced nephropathy (CIN), is an acute renal damage due to contrast agents. This study is conducted to determine the potential diagnostic value of hypoxia-inducible factor 2-alpha (HIF2-α) and to evaluate the renal protective effects of N-acetyl cysteine (NAC) and sildenafil in a rat CIN model. Material/Methods: This randomized, controlled, interventional animal study was conducted on Wistar rats. Totally, rats (n = 36) were randomly assigned to four groups: control (n = 9), CIN group (n = 9), CIN+NAC group (n = 9), and sildenafil (n = 9). The rat model was used to form iohexol-originated CIN. During the modelling, prophylactic treatment was performed at 24th and 48th hours. After 48 hours of the modelling; blood, urine, tissue samples were obtained for biochemical analyses. HIF-2-α levels were measured in renal tissue, serum and urine samples. Renal sections were performed in order for histopathologic and immunohistochemical evaluations. Results: In the CIN model, HIF-2α levels and other biochemical parameters were significantly increased (p < 0.01). Both sildenafil and NAC, efficiently decreased the renal damage due to contrast agents (p < 0.05). Similarly, after treatment with sildenafil and NAC, HIF-2α levels were significantly decreased (p < 0.05). Conclusions: The current study constructs an experimental base for the use of HIF-2α for clinical prevention and treatment of CIN. Several mechanisms may be postulated for the changes in HIF-2α levels. Besides, the increased HIF-2α levels with CIN and decreased HIF-2α levels after treatment may be used for the treatment and follow-up of patients with CIN.

Intracellular aggregates of the alpha-synuclein protein result in cell loss and dysfunction in Parkinson’s disease and atypical parkinsonism, such as multiple system atrophy and dementia with Lewy bodies. Each of these neurodegenerative conditions, known collectively as alpha-synucleinopathies, may be characterized by a different suite of molecular triggers that initiate pathogenesis. The mechanisms whereby alpha-synuclein aggregates in turn mediate cytotoxicity also remain to be fully elucidated. However, recent studies have implicated the cell-to-cell spread of alpha-synuclein as the major mode of disease propagation between brain regions during disease progression. Here, we review the current evidence for different modes of alpha-synuclein cellular release, movement and uptake, including exocytosis, exosomes, tunnelling nanotubes, glymphatic flow and endocytosis. A more detailed understanding of the major modes by which alpha-synuclein pathology spreads throughout the brain may provide new targets for therapies that halt the progression of disease.

Mathematical literacy is a very hot issue in the development of mathematics learning, apart from mathematical literacy, another interesting thing is the entrepreneurial spirit that must be given from an early age, especially for vocational students. This research was conducted at SMK Rosma Karawang in the Department of Computer and Network Engineering, West Java Province with the XI grade students. The teaching materials developed by applying the principles of the development model developed with the ADDIE model consist of analysis, design, development, implementation and evaluation. This research and development model is considered suitable for developing teaching tools and materials which is used for the purposes of the learning process. Based on the results of data analysis and processing that have been carried out in this study, the development of teaching materials using the ADDIE model has met the appropriate and valid criteria by media, language and media expert valuators. Another result of developing this teaching material besides meeting the eligibility criteria is that the teaching materials developed are able to increase mathematical literacy and instill entrepreneurial spirit for students.

The inhibition of alpha-glucosidase and alpha-amylase is one of clinic strategies for remedy the type II diabetes. Herbal medicines are reported to alleviate hyperglycemia. However, the constituents from those sources whether are targeted to the alpha-glucosidase and alpha-amylase still unexplored. This study attempted to select the compounds for efficacy of hypoglycemia via cellular and mouse levels. The results illustrated that the cytotoxicity in all tested compounds at various concentrations except the concentration of 16-hydroxy-cleroda-3,13-dine-16,15-olide (HCD) at 30 µM were not significant difference (p > 0.05) when compared with the untreated control. Acarbose (reference drug), Antroquinonol, Catechin, Quercetin, Actinodaphnine, Curcumin, HCD, Docosanol, Tetracosanol, Berberine, and Rutin could effectively inhibit the alpha-glucosidase activity of Caco-2 cells when compared with the control (maltose). The compounds (Curcumin, HCD, Tetracosanol, Antroquinonol, Berberine, Catechin, Actinodaphnine, and Rutin) could reduce blood sugar level at 30 min in tested mice. The effects of tested compounds on area under curve (AUC) were significant (p < 0.05) among Acarbose, Tetracosanol, Antroquinonol, Catechin, Actinodaphnine, and Rutin along with Berberine and Quercetin. In in vitro (alpha-glucosidase) with in vivo (alpha-amylase) experiments suggest that bioactive compounds can be a potential inhibitor candidate of alpha-glucosidase and alpha-amylase for the alleviation of type II diabetes.

Hypoxia is one of the most common pathological conditions which results from ischemic injury, trauma, inflammatory conditions, tumors, The adaptation of the body to hypoxia is a phenomenon that is of great importance both in normal conditions and in Most of the cellular response’ reactions to hypoxia is associated with a family of transcription factors called hypoxia-inducible factors (HIF). They induce the expression of a wide range of genes that help cells adapt to a hypoxic HIF functions are currently being extensively studied. In 2019, William G. Kaelin and Gregg Semenza from the USA and Sir Peter J. Ratcliffe from the UK received the Nobel Prize in Physiology or Medicine for the discovery of the basic mechanisms of adaptation to hypoxia and investigation of the role of HIF factor in the regulation of the hormone erythropoietin Based on its pivotal physiological importance, the HIF factor attracts more and more attention as a new potential target for treating a large number of diseases associated with Most of the experimental work dealing with the HIF factor is focused on its role in liver and However, increasing amount of experimental results clearly demonstrates that the HIF factor-based response represents an universal adaptation mechanism for all kinds of tissues, including the nervous system where HIF is critical for regulating neurogenesis, nerve cell differentiation, and neuronal This review provides actual overview about the complex role of HIF-1 in the adaptation of nerve cells to hypoxia with the focus on its potential role by various neuronal

Cancer is often characterised by the presence of hypoxia and inflammation. Paramount to the mechanisms controlling cellular responses under such stress stimuli, are the transcription factor families of Hypoxia Inducible Factor (HIF) and Nuclear Factor of kappa-light-chain-enhancer of activated B cells (NF-кB). Although, a detailed understating of how these transcription factors respond to their cognate stimulus is well established, it is now appreciated that HIF and NF-кB undergo extensive crosstalk, in particular in pathological situations such as cancer. Here, we focus on the current knowledge on how HIF is activated by inflammation and how NF-кB is modulated by hypoxia. We summarise the evidence for the possible mechanism behind this activation and how HIF and NF-кB function impacts cancer, focusing on colorectal, breast and lung cancer. We discuss possible new points of therapeutic intervention aiming to harness the current understanding of the HIF-NF-кB crosstalk.

Diabetes mellitus (DM) is one of the most dangerous metabolic diseases with high rate of mortality worldwide. It is well known that insulin resistance and deficiency in insulin production from pancreatic β-cells are the main characteristic of DM. Due to the detrimental side effects of the current treatment, there is a considerable need to develop new effective antidiabetic drugs, especially alpha-glucosidase and alpha-amylase inhibitors with lesser adverse effects. These inhibitors are known to be directly involved in the delay of carbohydrate digestion, resulting in a reduction of glucose absorption rate and consequently reduce the post-prandial raise of plasma glucose, which can reduce the risk of long-term diabetes complications. Hence, natural products are well-known sources for the discovery of new scaffold for drugs discovery, including new antidiabetic drugs. The phytochemical investigation of Salvia aurita collected from Hogobach pass, Eastern Cape, South Africa (SA), yielded four known abietane diterpenes namely carnosol (1), rosmanol (2), 7-methoxyrosmanol (3), 12-methoxycarnosic acid (4) and one flavonoid named 4,7-dimethylapigenin (5). Structural characterization of these isolated compounds was conducted using 1 and 2D NMR, in comparison with reported spectroscopic data. These compounds are reported for the first time from S. aurita. The biological evaluation of the isolated compound against alpha-glucosidase exhibited strong inhibitory activities for 3 and 2 with IC50 values of 4.2 ± 0.7 and 16.4 ± 1.1 µg/mL respectively, while 4 and 1 demonstrated strong alpha-amylase inhibitory activity amongst the isolated compounds with IC50 of 16.2 ± 0.3 and 19.8 ± 1.4 µg/mL. Molecular docking analysis confirms strong inhibitory activity of 3 against alpha-glucosidase. Additionally, excellent antioxidant capacities were displayed by 2, 1 and 3 respectively as ORAC (25789.9 ± 10.5; 23961.8 ± 14.1; 23939.3 ± 2.4) µM TE/g; 1 and 2 as FRAP (3917.8 ± 2.1; 1522.3 ± 0.9) µM AAE/g; 5 and 2 as TEAC (3190.4 ± 2.8; 2055.0 ± 2.6) µM TE/g. The methanolic extract of S. aurita is a rich source of abietane diterpenes with excellent antioxidant and anti-diabetic activities that can be useful to modulate oxidative stress, and might possibly be excellent candidates for the management of diabetes. This is the first scientific report on the phytochemical isolation and biological evaluation of alpha-glucosidase and alpha-amylase inhibitory activities of Salvia aurita.

The asymmetric skew divergence smooths one of the distributions by mixing it, to a degree determined by the parameter $\lambda$, with the other distribution. Such divergence is an approximation of the KL divergence that does not require the target distribution to be absolutely continuous with respect to the source distribution. In this paper, an information geometric generalization of the skew divergence called the $\alpha$-geodesical skew divergence is proposed, and its properties are studied.

PBRM1, a component of the chromatin remodeller SWI/SNF, is often deleted or mutated in human cancers, most prominently in renal cancers. Core components of the SWI/SNF complex have been shown to be important for the cellular response to hypoxia. Here we investigated how PBRM1 controls HIF-1alpha activity. We find that PBRM1 is required for HIF-1alpha transcriptional activity and protein levels. Mechanistically, PBRM1 is important for HIF-1alpha mRNA translation, as absence of PBRM1 results in reduced activly transalting HIF-1alpha mRNA. Interestingly, we find that PBRM1, but not BRG1, interacts with the m6A reader protein YTHDF2. HIF-1alpha mRNA is m6A modified, bound by PBRM1 and YTHDF2. PBRM1 is necessary for YTHDF2 binding to HIF-1alpha mRNA and reduction of YTHDF2 results in reduced HIF-1alpha protein expression in cells. Our results identify a SWI/SNF independent function for PBRM1, interacting with HIF-1alpha mRNA and the epitranscriptome machinery. Furthermore, our results suggests that the epitranscriptome associated proteins play a role in the control of hypoxia signalling pathways

The ongoing global pandemic caused by coronavirus disease 2019 (COVID-19) has once again demonstrated the significance of the Coronaviridae family in causing human disease outbreaks. As SARS-CoV-2 was first detected in December 2019, information on its tropism, host range, and clinical presentation in animals is limited. Given the limited information, data from other coronaviruses may be useful to inform scientific inquiry, risk assessment and decision-making. We review the endemic and emerging alpha- and betacoronavirus infections of wildlife, livestock, and companion animals, and provide information on the receptor usage, known hosts, and clinical signs associated with each host for 15 coronaviruses discovered in people and animals. This information can be used to guide implementation of a One Health approach that involves human health, animal health, environmental, and other relevant partners in developing strategies for preparedness, response, and control to current and future coronavirus disease threats.

Cytochrome-c-oxidase (COX) subunit 4 (COX4) plays important roles in the function, assembly and regulation of COX (mitochondrial respiratory complex 4), the terminal electron acceptor of the oxidative phosphorylation (OXPHOS) system. The principal COX4 isoform, COX4-1, is expressed in all tissues, whereas COX4-2 is mainly expressed in the lungs, or under hypoxia and other stress conditions. We have previously described a patient with a COX4-1 defect with a relatively mild presentation compared to other primary COX deficiencies, and hypothesized that this could be the result of compensatory upregulation of COX4-2. To this end, COX4-1 was downregulated by shRNAs in human foreskin fibroblasts (HFF), and compared to patient's cells. COX4-1, COX4-2 and HIF-1α were detected by immunocytochemistry. The mRNA transcripts of both COX4 isoforms and HIF-1 target genes were carried out by RT-qPCR. COX activity and OXPHOS function were measured by enzymatic and oxygen consumption assays, respectively. Pathways were analyzed by CEL-Seq2 and by RT-qPCR. We demonstrate elevated COX4-2 levels in the COX4-1-deficient cells with a concomitant HIF-1α stabilization, nuclear localization and upregulated hypoxia and glycolysis pathways. We suggest that COX4-2 and HIF-1α has the are upregulated, also in normoxia as a compensatory mechanism in COX4-1 deficiency.

Hypoxia — reduction in oxygen availability—plays key roles in both physiological and pathological processes. Given the importance of oxygen for cell and organism viability, mechanisms to sense and respond to hypoxia are in place. A variety of enzymes utilise molecular oxygen, but of particular importance to oxygen sensing are the 2-oxoglutarate (2-OG) dependent dioxygenases (2-OGDs). Of these, Prolyl-hydroxylases have long been recognised to control the levels and function of Hypoxia Inducible Factor (HIF), a master transcriptional regulator in hypoxia, via their hydroxylase activity. However, recent studies are revealing that dioxygenases are involved in almost all aspects of gene regulation, including chromatin organisation, transcription and translation. We highlight the relevance of HIF and 2-OG dioxyenases in the control of gene expression in response to hypoxia and their relevance to human cancers.

Chemotherapy treatment based on Cisplatin (CDDP) is established as the drug of choice for head and neck squamous cell carcinoma (HNSCC). Malignant tumors respond to microenvironment alteration through a dynamic balance of mitochondrial fission and fusion. HNSCC is known to have hypoxic conditions, yet the effects and underlying mechanisms of hypoxia on chemosensitivity and mitochondrial dynamics remain unclear. We found that hypoxia promoted mitochondrial fission and CDDP sensitivity in HNSCC cells. Importantly, Mff was shown to be correlated with chemosensitivity in clinical samples of HNSCC that underwent a hypoxic condition. Hypoxia-inducible factor 1 α-subunit (HIF-1α) dramatically increased Mff transcriptional expression and directly bound to Mff. Hypoxia enhanced the release of reactive oxygen species (ROS) and upregulated the expression of Mff via HIF-1α in HNSCC cells. ROS depletion in HNSCC cells attenuated HIF-1α, Mff expression, and mitochondrial fission. Moreover, a knockdown of Mff suppressed hypoxia-induced mitochondrial fission and decreased CDDP chemosensitivity in vivo and in vitro. Our findings revealed that the hypoxia-induced release of ROS promoted mitochondrial fission and CDDP chemosensitivity via the regulation of HIF-1α/Mff in HNSCC cells, indicating that Mff may serve as a new biomarker to predict neoadjuvant chemosensitivity in HNSCC patients

Ataxin-2 (human gene symbol ATXN2, protein ATXN2) is the disease protein of Spinocerebellar Ataxia type 2 (SCA2). The large expansions of a polyglutamine (polyQ) stretch above a threshold of ~33 glutamines cause the multi-system nervous atrophy SCA2, while intermediate expansions of 29-32 glutamines contribute to the risk of the motor neuron diseases Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal Lobar Dementia (FTLD). To elucidate the cellular function of ATXN2, we further characterized its direct interaction with alpha-Actinin-1 (symbol ACTN1), which had been observed in high-throughput yeast-two-hybrid surveys. An endogenous complex of ATXN2 and ACTN1 proteins was detected by co-immunoprecipitation. In vitro GST-tag pull-down experiments showed that the Calponin-Homology-domain at the N-terminus of ACTN1 binds to the N-terminus of ATXN2. Although an impact of the polyQ expansion on the interaction was not evident in pull-down experiments, a recent characterization of aged Atxn2-CAG100-KnockIn mice provides evidence. Both proteins associated in the cytosol and at the plasma membrane, as determined by sedimentation experiments in mouse brain, and by immunofluorescence microscopy of a transfected monkey cell line and of rat primary hippocampal neurons. In view of the roles of ACTN1 for spine plasticity and postsynaptic receptor control via reassembly of cortical actin, our data help to explain the impaired dendrite maintenance in SCA2.

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

HIF-1α is a master regulator of oxygen homeostasis involved in different stages of cancer development. Thus, HIF-1α inhibition represents an interesting target for anti-cancer therapy. It was recently shown that HIF-1α interaction with NQO1 inhibits its proteasomal degradation, thus suggesting that targeting the stability of NQO1 could led to destabilization of HIF-1α as a therapeutic approach. Since the molecular interactions of NQO1 with HIF-1α are beginning to be unraveled, we review here our current knowledge on the intracellular functions and stability of NQO1, its pharmacological modulation by small ligands, and the molecular determinants of its roles as a chaperone of many different proteins including cancer-associated factors such as p53 and p73α. This knowledge is then discussed in the context of potentially targeting the intracellular stability of HIF-1α by acting on its chaperone, NQO1. This could result in novel anti-cancer therapies.

NF-B signalling is crucial for cellular responses to inflammation but has also been associated with the hypoxia response. NF-B and HIF transcription factors possess an intense molecular crosstalk. Although it is known that HIF-1beta modulates NF-kappaB transcriptional response, very little is understood regarding how HIF-1beta contributes to NF-kappaB signalling. Here, we demonstrate that HIF-1beta is required for full NF-kappaB activation in cells following canonical and non-canonical stimuli. We found that HIF-1beta specifically controls TRAF6 expression in human cells but also in Drosophila melanogaster. HIF-1beta binds to the TRAF6 gene and controls its expression independently of HIF-1alpha. Furthermore, exogenous TRAF6 expression is able to rescue all of the cellular phenotypes observed in the absence of HIF-1beta. These results indicate that HIF-1beta is an important regulator of NF-kappaB with consequences for homeostasis and human disease.

Non-canonical NF-kB signalling plays important roles in development and function of the immune system but also is deregulated in a number of inflammatory diseases. Although, NF-kB and HIF crosstalk has been documented, this has only been described following canonical NF-kB stimulation, involving RelA/p50 and the HIF-1 dimer. Here we report that the non-canonical inducer TNFSF14/LIGHT leads to HIF induction and activation in cancer cells. We demonstrate that only HIF-2a is induced at the transcriptional level following non-canonical NF-kB activation, via a mechanism dependent on the p52 subunit. Furthermore, we demonstrate that p52 can bind to the HIF-2a gene in cells. These results indicate that non-canonical NF-kB can lead to HIF signalling implicating HIF-2a as one of the downstream effectors of this pathway in cells.

In the last two decades, the discovery of various pathways involved in renal cell carcinoma (RCC) have led to the development of biologically-driven targeted therapies. Hypoxia inducible factors (HIFs), angiogenic growth factors, von Hippel-Lindau (VHL) gene mutations and oncogenic miRNAs play essential roles in the pathogenesis and drug resistance of clear cell renal cell carcinoma. These insights have led to the development of VEGF inhibitors, mTOR inhibitors and immunotherapeutic agents which have significantly improved outcomes of patients with advanced RCC. HIF inhibitors will be a valuable asset in the growing therapeutic armamentarium of RCC. Various histone deacetylase (HDAC)inhibitors, including selenium and agents such as PT2385 and PT2977, are being explored in various clinical trials as potential HIF inhibitors to ameliorate the outcomes of RCC patients. In this article, we will review the current treatment options and highlight the potential role of selenium in the modulation of drug resistance biomarkers expressed in ccRCC tumors.

By combining general relativity and CPT symmetry, the theory of CPT gravity predicts gravitational repulsion between matter and CPT-transformed matter, i.e. antimatter inhabiting an inverted space-time. Such repulsive gravity turned out to be an excellent candidate for explaining the accelerated expansion of the Universe, without the need for dark energy. The recent results of the ALPHA-g experiment, which show gravitational attraction between antihydrogen atoms and the Earth, seem to undermine this success in the cosmological field. Analyzing the above theory, we find two solutions that can be consistent with the experimental results, while preserving the large-scale gravitational repulsion. The first highlights how repulsive gravity can be the result of the interaction with an inverted space-time, but occupied by matter and not antimatter, and therefore the antimatter present in our space-time has no reason to exhibit gravitational repulsion. The second retains the original CPT transformation, resulting in repulsive gravity between matter and antimatter, but with the caveat that antimatter immersed in our space-time cannot exhibit the PT transformation which is the cause of the repulsion. Finally, it is shown that, in a Newtonian approximation of the geodesic equation, time reversal is not a necessary operation for repulsive gravity, therefore opening the possibility of an expanding cosmos with a single time direction.

Rapid assessment of maize yields in smallholder farming system is important to understand its spatial and temporal variability and for timely agronomic decision-support. Imageries acquired with unmanned air vehicles (UAV) offer opportunity to assess agronomic variables at field scale, however, it is not clear if this can be translated into reliable yield assessment on smallholder farms where field conditions, maize genotypes, and management practices vary within short distances. In this study, we assessed the predictability of maize grain yield using UAV-derived vegetation indices (VI), with(out) biophysical variables, in smallholder farms. High-resolution images were acquired with UAV-borne multispectral sensor at 4 and 8 weeks after sowing (WAS) on 31 farmers’ managed fields (FMFs) and 12 nearby Nutrient Omission Trials (NOT), all distributed across 5 locations within the core maize region of Nigeria. The NOTs included non-fertilized and fertilized plots (with and without micronutrients), sown with open-pollinated or hybrid maize genotypes. Acquired multispectral images were post-processed into several three (s) vegetation indices (VIs), normalized difference vegetation index (NDVI), normalized difference red-edge (NDRE), green-normalized difference vegetation index (GNDVI). Biophysical variables, plant height (Ht) and percent canopy cover (CC), were measured with the georeferenced plot locations recorded. In the NOTs, the nutrient status, not genotype, influenced the grain yield variability and outcome. The maximum grain yield observed in NOTs was 9.3 tha^-1, compared to 5.4 tha^-1 in FMF. Without accounting for between- and within-field variations, there was no relationship between UAV-derived VIs and grain yield at 4WAS (r<0.02, P>0.1), but significant correlations were observed at 8WAS (r≤0.3; p<0.001). Ht was positively correlated with grain yield at 4WAS (r=0.5, R²=0.25, p<0.001), and more strongly at 8WAS (r=0.7, R²=0.55, p<0.001), while relationship between CC and yield was only significant at 8WAS. By accounting for within- and between-field variations in NOTs and FMF (separately) through linear mixed-effects modeling, predictability of grain yield from UAV-derived VIs was generally (R²≤0.24), however, the inclusion of ground-measured biophysical variable (mainly Ht) improved the explained yield variability (R² ≥0.62, RMSEP≤0.35) in NOTs but not in FMF. We conclude that yield prediction with UAV-acquired imageries (before harvest) is more reliable under controlled experimental conditions (NOTs), than in actual farmer-managed fields where various confounding agronomic factors can amplify noise-signal within the vegetation canopy.

Three-dimensional (3D) bioprinting promises to be essential in tissue engineering for solving the rising demand for organs and tissues. Some bioprinters are commercially available, but their impact on the field of TE is still limited due to their cost or difficulty to tune. Herein, we present a low-cost easy-to-build printhead for microextrusion-based bioprinting (MEBB) that can be installed in many desktop 3D printers to transform them into 3D bioprinters. We can extrude bioinks with precise control of print temperature between 2 - 60 ºC. We validated the versatility of the printhead, by assembling it in three low-cost open-source desktop 3D printers. Multiple units of the printhead can also be easily put together in a single printer carriage for building a multi-material 3D bioprinter. Print resolution was evaluated by creating representative calibration models at different temperatures using natural hydrogels such as gelatin and alginate, and synthetic ones like poloxamer. Using one of the three modified low-cost 3D printers, we successfully printed cell-laden lattice constructs with cell viabilities higher than 90% after 24h post printing. Controlling temperature and pressure according to the rheological properties of the bioinks was essential in achieving optimal printability and great cell viability. The cost per unit of our device, which can be used with syringes of different volume, is less expensive than any other commercially available product. These data demonstrate an affordable open-source printhead with the potential to become a reliable alternative to commercial bioprinters for any laboratory.

Most of α-thalassemia cases are caused by deletions of the structural α-globin genes. The degree of microcytosis and hypochromia has been correlated with the number of affected α-globin genes, suggesting a promising role of hematologic parameters as predictive diagnostic tools. However, specific cut-off points for these parameters to discriminate between the different subtypes of α-thalassemia remain to be clearly defined. Six hematologic parameters (total number of erythrocytes, hemoglobin concentration, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration and red cell distribution width) were evaluated in 174 cases of deletional α-thalassemia (92 heterozygous α+ thalassemia, 39 homozygous α+ thalassemia, 34 heterozygous α0 thalassemia and 9 cases of Hb H disease). A good correlation between the number of deleted alpha genes and MCV (r = -0.672, p<0.001), MCH (r = -0.788, p<0.001) and RDW (r = 0.633, p<0.001) was observed. The deletion of at least two alpha genes in adult individuals with microcytosis without iron deficiency and normal values of Hb A2 and Hb F should be discarded when MCH levels are lower than 23.15 pg. Furthermore, MCH <21.90 pg and/or MCV <70.80 fL are strongly suggestive of the presence of one α0 allele. Finally, an accurate presumptive diagnosis of Hb H disease can be made if both RDW ≥20% and MCH <18.45 pg are seen.

To close the nutrient-related yield gaps in maize, balanced nutrition using primary and secondary macronutrients as well as micronutrients is recommended. Multi-nutrient diagnostic field trials were conducted in Guinea Savanna of Nigeria to assess the interactive effects of macronutrients and micronutrients on maize grain yields, nutrient uptake as well as N, P and K use efficiencies. The treatments consisted of a control (zero fertilizer applied), an NPK treatment and 10 other treatments in which macronutrient (Mg, S) and/or micronutrients (B, and Zn) were added to the NPK. The experiment was laid out in Randomized Complete Block Design with 3 replications. Data collected were subjected to mixed model with nutrient management strategy as fixed effects while replication nested in location and interaction between location and nutrient management strategy as random effects. The results revealed significant effects (P < 0.05) of nutrient management strategy on maize yield, nutrient uptake and nutrient use efficiencies of N, P and K. The study revealed that yield advantage over the recommended NPK fertilizer as a result of application macronutrients and micronutrients were highest with Mg in Lere (2.4 t ha⁻¹), S + B + Zn in Faskari (2.8 t ha⁻¹), S + B in Doguwa (1.5 t ha⁻¹) and S + Zn in Toro (2.4 t ha⁻¹). Addition of Mg, S and B significantly increases macronutrient uptakes over the recommended NPK only. Agronomic use efficiency, internal utilization efficiency, apparent recovery efficiency and partial factor productivity were significantly increased with the addition of S, Mg, and B but were not improved with Zn application. It was concluded that nutrient limitations to maize in the Guinea Savanna go beyond N, P and K. This study recommends that S, Mg, and B are needed to improve maize productivity and engender improve the use efficiency of NPK fertilizers.

Solid tumors are typically associated with unbridled proliferation of malignant cells, accompanied by an immature and dysfunctional tumor-associated vascular network. Consequent impairment in transport of nutrients and oxygen eventually leads to a hypoxic environment wherein cells must adapt to survive and overcome these stresses. Hypoxia inducible factors (HIFs) are central transcription factors in the hypoxia response and drive the expression of a vast number of survival genes in cancer cells and in cells in the tumor microenvironment. HIFs are tightly controlled by a class of oxygen sensors, the HIF-prolyl hydroxylase domain proteins (PHDs), which hydroxylate HIFs, thereby marking them for proteasomal degradation. Remarkable and intense research during the past decade has revealed that, contrary to expectations, PHDs are often overexpressed in many tumor types and that inhibition of PHDs can lead to decreased tumor growth, impaired metastasis and diminished tumor-associated immune-tolerance. Therefore, PHDs represent an attractive therapeutic target in cancer research. Multiple PHD inhibitors have been developed that have either been recently accepted in China as erythropoiesis stimulating agents (ESA) or are currently in phase III trials. We review here the function of HIFs and PHDs in cancer and related therapeutic opportunities.

It has been long recognized that under hypoxia conditions cancer cells reprogram their metabolism through shift from oxidative phosphorylation (OXPHOS) to glycolysis to meet elevated requirements in energy and nutrients for proliferation, migration and survival. However, data accumulated over the last years increasingly evidence that cancer cells can revert from glycolysis to OXPHOS and maintain both reprogrammed and oxidative metabolism even in the same tumor. The phenomenon denoted as cancer cell metabolic plasticity or hybrid metabolism depends on a tumor micro-environment, which is highly heterogeneous and influenced by intensity of vasculature and blood flow, oxygen concentration, nutrient and energy supply, and requires regulatory interplay between multiple oncogenes, transcription factors, growth factors, reactive oxygen species (ROS), etc. Hypoxia-inducible factor-1 (HIF-1) and AMP-activated protein kinase (AMPK) represent key modulators of switch between reprogrammed and oxidative metabolism. The present review focuses on cross-talks between HIF-1, GLUTs, and AMPK and other regulatory proteins including oncogenes such as c-Myc, p53 and KRAS, growth factor-initiated PKB/Akt, PI3K and mTOR signaling pathways and tumor suppressors such as LKB1 and TSC1 in controlling cancer cell metabolism. The multiple switches between metabolic pathways can underlie chemo-resistance to conventional anti-cancer therapy and should be taken into account in choosing molecular targets to discovery novel anti-cancer drugs.

Tumor necrosis factor-α (TNFα), one of the major pro-inflammatory cytokines, plays a key role in an effective immune response. However, the chronic presence of TNFα can lead to several inflammatory disorders like rheumatoid arthritis, psoriasis, Crohn’s disease etc. Inhibition of TNFα by pharmacological inhibitors or antibodies has proven to be effective in palliative treatment to some extent. The aim of this study was to develop an anti-TNFα antibody which may be used as a therapeutic option to inhibit TNFα-mediated cytotoxicity. We characterized several hybridoma clones secreting monoclonal antibodies (mAbs) to human-TNFα. Four mAbs rescued L929 fibroblast cells from TNFα-triggered cell death and one of these, namely C8 was found to have the highest affinity. To gain insights into the mechanism by which mAb C8 inhibits human TNFα-mediated toxicity, the epitope corresponding to the mAb was delineated. The antigenic determinant was found to comprise of the stretch of amino acids 99-120, of which, 102-104 (QRE) form the core epitope. The observation was supported by bioinformatics analyses of an antigen-antibody complex model. In addition, the binding affinity of mAb C8 to TNFα was found to be comparable with that of Infliximab which is a commercially available anti TNFα mAb.

In this study, the fuzzy c- means classifier has been studied with nine other similarity and dissimilarity measures: Manhattan distance, chessboard distance, Bray-Curtis distance, Canberra, Cosine distance, correlation distance, mean absolute difference, median absolute difference and normalised squared Euclidean distance. Both single and composite modes were used with a varying weight constant (m) and also at different α-cuts. The two best single norms obtained were combined to study the effect of composite norms on the datasets used. An image to image accuracy check was conducted to assess the accuracy of the classified images. Fuzzy Error Matrix (FERM) was applied to measure the accuracy assessment outcomes for a Landsat-8 dataset with respect to the Formosat-2 dataset. To conclude FCM classifier with Cosine norm performed better than the conventional Euclidean norm. But, due to the incapability of the FCM classifier to handle noise properly, the classification accuracy was around 75%.

I wish to suggest a physiological function for alpha-synuclein (a-syn) that has the potential to explain its role in pathology. Intraneuronal proteinaceous Lewy Bodies (LBs), the pathological hallmark of Parkinson’s disease and other synucleinopathies, consist majorly of a-syn. Ample evidence suggests that LBs are not the result of simple amyloidosis of cytosolic a-syn. Benign soluble unstructured a-syn gets converted into toxic species which preferentially accumulates in LBs. But how these aberrant a-syn molecules are produced in the cytosol, is still not clear. The present hypothesis is an effort to relate a metabolic reaction specific to neuronal function, that is, phase transition, with the pathobiology of a-syn. During high frequency stimulation, which entails rapid phase transition reactions at the presynaptic compartment, aberrant interaction of a-syn with the membrane occasionally generates toxic a-syn molecules. My conjecture is that the physiological function of a-syn is to modulate membrane fluidity by a process wherein it goes through a conformation cycle driven by a flux of energy from mitochondria. It is the range of toxic a-syn produced during aberrant phase transition reaction that is responsible for pathology, not the normal a-syn that reenters the conformation cycle, thereby, resolving the paradox of the Janus-face of a-syn.

The main regulatory factors during the adaptation of cancer cells to hypoxic stress are the hypoxia-inducible factors (HIFs), which are being increasingly recognized as an interesting and challenging target for the design of new chemotherapeutic molecules. HIF2A was found to have an large internal hydrophilic cavity within its PAS-B domain, unique to this sub-unit and is suggested to be a possible ligand-binding site. Regulation of HIF2A by cellular molecules is still greatly unknown. In This paper we have employed in-silico techniques, such as molecular docking and dynamic simulation, to design new direct inhibitors against HIF-2A subunit via targeting one of its critical domains and the final top screened molecules have been tested on hypoxic cancer cells for further validation of their inhibitory potential. we targeted the hydrophilic cavity inside the PAS-B domain of the HIF2A to identify novel molecules with a high binding capacity. Virtual Screening methodology was used for molecular docking of NSC library against the target domain inside the HIF2A PAS-B domain with the top 5% compounds with significant MolDock and Re-rank scores were selected for further analysis. The NSC 106416, NSC 217021, NSC 217026, and NSC 215639 compounds were selected based on their docking scores. NSC 215639 had the minimum polar solvation energy and also had a relative strong binding energy. NSC 217026 had the strongest binding energy among other compounds.

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

Low soil nitrogen status of savanna soils in Nigeria contributes to the persistent Striga hermonthica (Del.) Benth. infestation that limits maize production. The application of nitrogen fertilizer to Striga-resistant hybrids may reduce Striga infection and increase grain yields. This study assessed the performance of maize hybrids at low (30 kg ha-1) and high (120 kg ha-1) nitrogen application under natural infestation with Striga at Kafin Madaki and Tudun Wada in 2014 and 2015. Results showed that the application of nitrogen at 120 kg ha-1 reduced number of Striga plants by 59% compared to application at 30 kg N ha-1 in Kafin Madaki and by 21% in Tudun Wada. Compared to 30 kg N ha-1, the 120 kg N ha-1 rate also reduced Striga damage rating by 22% in Kafin Madaki and by 33% in Tudun Wada across the hybrids. Hybrids 8338-1 (5.3) and OBASUPER 1 (4.3) were the only entries with Striga damage rating greater than 4.5 (SDR > 4.5) when averaged across the nitrogen levels at both locations. Grain yield was 86 and 98% higher in Kafin Madaki and Tudun Wada, respectively when N was applied at 120 kg N ha-1 than at 30 kg N ha-1. The hybrids M1124-3 and M1227-14 produced grain yields that were significantly higher than those of the other hybrids in all locations. The hybrid 8338-1 produced the lowest grain yield across locations. Our results showed that, the application of 120 kg N ha-1 to Striga resistant maize hybrids will reduce Striga infection and increase grain yield.

Neurodegenerative diseases, including Alzheimer's, Huntington's, Parkinson’s, and Amyotrophic Lateral Sclerosis, involve neuron degeneration linked to the misfolding of amyloidogenic proteins, resulting in β-sheet-enriched aggregates. This phenomenon disrupts the normal folding of proteins critical for cellular function. Genetic mutations, proteolytic cleavage, oxidative stress, and aging contribute to misfolding. Parkinson's disease (PD) is closely tied to alpha-synuclein (αS) misfolding, with A53T mutation and Lewy bodies (LB) in PD brains pivotal to understanding the disease mechanism. Other synuclein homologues (βS, γS) further contribute to synucleinopathies. Mutants (A30P, A53T, E46K, H50Q, and G51D) underscore αS&#39;s role in PD development. This concise review focuses on molecular and pathological aspects of neurodegenerative diseases, emphasizing αS in PD. The integration of genetic, structural, and mechanistic insights highlights the disorders. complexity, paving the way for future therapeutic strategies targeting protein misfolding and aggregation.

A full potential all-electron density functional method within generalized gradient approximation is used to investigate the electronic, elastic and transport properties of cubic copper sulphide and copper selenide. The electronic structure suggests metallic behavior with a zero energy band gap for both materials. Elastic property calculations suggest a stiff material with the bulk to shear modulus ratio of 0.35 and 0.44 for Cu2S and Cu2Se respectively. The transport properties were estimated using the Boltzmann transport approach. Seebeck coefficient, electrical conductivity, thermal conductivity, and power factor all suggest a potential p-type conductivity for Cu2S and n-type conductivity for Cu2Se.

Neurodevelopmental and late-onset neurodegenerative disorders present as separate entities that are clinically and neuropathologically quite distinct. However, recent evidence has highlighted surprising commonalities and converging features at the clinical, genomic, and molecular level between these two disease spectra. This is particularly striking in the context of autism spectrum disorder (ASD) and Parkinson’s disease (PD). Genetic causes and risk factors play a central role in disease pathophysiology and enable the identification of overlapping mechanisms and pathways. Here, we focus on clinico-genetic studies of causal variants and overlapping clinical and cellular features of ASD and PD. Several genes and genomic regions were selected for our review, including SNCA (alpha-synuclein), PARK2 (parkin RBR E3 ubiquitin protein ligase), chromosome 22q11 deletion/DiGeorge region, and FMR1 (fragile X mental retardation 1) repeat expansion, which influence development of both ASD and PD with converging features related to synaptic function and neurogenesis. Both PD and ASD display alterations and impairments at the synaptic level, representing early and key disease phenotypes which support the hypothesis of converging mechanisms between the two types of diseases. Therefore, understanding the underlying molecular mechanisms might inform on common targets and therapeutic approaches. We propose to re-conceptualize how we understand these disorders and provide a new angle into disease targets and mechanisms linking neurodevelopmental disorders and neurodegeneration.

Inflammation is a vital aspect of the body's immune response, appearing either as an acute reaction that swiftly develops (e.g., after injury or during an infection) or as a chronic condition that persists over a prolonged period, often linked with autoimmune disorders or cancer. This study introduces potential TNF-alpha inhibitors investigated by Molecular Docking investigation. They are Dactolisib with a binding energy of -10.1 kcal/mol, Nilotinib with -9.6 kcal/mol, Eltrombopag with -9.7 kcal/mol, Radotinib with -9.6 kcal/mol, and Nilotinib again with -9.7 kcal/mol. Additionally, Hypericin exhibited a notable binding energy of -9.9 kcal/mol, suggesting its potential as a natural TNF-alpha inhibitor. While these computational results are preliminary, they provide a foundation for further biological studies to confirm their efficacy. The significance of these findings extends to the scientific community, offering potential applications in the field of inflammatory diseases.

The genetic diversity of coronavirus (CoV) is high, and its infection in animals has not yet been fully revealed. By RT-PCR detection of partial RNA dependent RNA polymerase (RdRp) gene of CoV, we screened a total of 502 small mammals belonging to 18 species in 12 genera and 4 orders collected in Dali and Nujiang Prefecture of Western Yunnan Province, China. The prevalence of β-CoV in Chevrieri's field mouse (Apodemus chevrieri) and Lancangjiang field mouse (A. ilex) were 3.54% (4/113) and 6.67% (6/90), respectively; the prevalence of α-CoV in White-footed Indochinese rat (Rattus nitidus) and long-tailed red-toothed shrew (Episoriculus leucops) was 75% (3/4) and 5.88% (1/17), respectively. The co-infection rates of β-CoV and α-CoV in Kachin red-backed vole (Eothenomys cachinus), Norway rat (R. norvegicus) were 2.22% (2/90), 3.85% (1/26) respectively. The identity of the partial RdRp genes obtained of 13 strains of β-CoV was 83.42%-99.23% at nucleotide level, and it is worth noting that the two strains from Kachin red-backed vole showed highly homology to BOV-36/IND/2015 from Indian bovine and DcCoV-HKU23 from one-humped camel (Camelus dromedarius) in Morocco, the nucleotide similarity between 97.86%-98.33%. Similarly, the identity of the 7 strains of α-CoV among the partial RdRp sequences was 94.00%-99.18% at nucleotide levels. The viral load in different tissues was measured by quantitative RT-PCR (qRT-PCR). The average CoV viral load in small mammalian intestinal tissue was 1.25×106copies/g, differently, the mean CoV viral load in liver, heart, lung, spleen and kidney tissue was from 1.29×103 to 4.02×103copies/g, which revealed that CoV has extensive tropism of intestinal tissue in small mammals (P &lt; 0.0001). This result revealed the genetic diversity, epidemiology, and infective tropism of α-CoV and β-CoV in small mammals from Dali and Nujiang, which deepens the comprehending of the retention and infection of coronavirus in natural hosts.

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

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

Background: Body dysmorphic disorder (BDD) is a psychiatric disorder characterized by excessive preoccupation with imagined defects in appearance. Optical illusions induce illusory effects that distort the presented stimulus thus leading to ambiguous percepts. Using electroencephalography (EEG), we investigated whether BDD is related to differentiated perception during illusory percepts. Methods: 18 BDD patients and 18 controls were presented with 39 optical illusions together with a statement testing whether or not they perceived the illusion. After a delay period, they were prompted to answer whether the statement is right/wrong and their degree of confidence for their answer. We investigated differences of BDD on task performance and self-reported confidence and analysed the brain oscillations during decision-making using nonparametric cluster statistics. Results: Behaviorally, the BDD group exhibited reduced confidence when responding incorrectly, potentially attributed to higher levels of doubt. Electrophysiologically, the BDD group showed significantly reduced alpha power at mid-central scalp areas, suggesting impaired allocation of attention. Interestingly, the lower the alpha power of the identified cluster, the higher the BDD severity, as assessed by BDD psychometrics. Conclusions: Results evidenced that alpha power during illusory processing might serve as a quantitative EEG biomarker of BDD, potentially associated with reduced inhibition of task-irrelevant areas.

In the present work we study the properties of geodesic sub-$ (\alpha,b,s) $-preinvex functions on Hadamard manifolds and establish some basic properties in both general and differential cases. Further, we study sufficient conditions of optimality and proved some new inequalities under geodesic sub-($ \alpha,b,s $)-preinvexity.

Adding zinc (II) and formate anions improves the thermal phase-stability of alpha-FAPbI3 materials and the spin-coated thin films of such doped FAPbI¬3 show an increased emission lifetime of up to 3.7 microsecond on quartz. This work investigates the effects of zinc and formate on the stability and time resolved photoluminescence of FAPbI3 perovskites for solar cell applications. Perovskite samples with varying concentrations of zinc and formate were made by incorporating different amounts of zinc formate and zinc iodide and characterized with XRD. Doping levels of 1.7% Zn(II) and 1.0% formate (relative to Pb) seem optimal. The thermal stability of the perovskite powders and thin films were assessed. XRD was virtually unchanged after 6 months. The time-resolved photo-luminescence spectroscopy of the doped spin-coated perovskite samples is reported. The results show that synergy between an anionic and a cationic dopant can take place, making the perovskite thermally more stable with a longer charge carrier lifetime.

Onion is one of the most economically and nutritionally important vegetable crops in West Africa. However, high-yielding varieties that are accessible to farmers remain scarce. Onion lines from the World Vegetable Center’s Allium program were evaluated during the cool and dry season from September to March for three years to identify adapted onion lines suitable for sustainable intensi-fication of production systems in Northern Ghana and Southern Mali. Trials were implemented in the Upper East and Northern Regions of Ghana and in two districts in the Sudan savanna zones of Mali (Bougouni and Koutiala). Nine onion lines, including a check variety were assessed for yield stability using a randomized complete block design. The trials were carried out in “technology parks” under the joint management of farmers and researchers. Onion bulb weight was recorded for each plot after harvest. Separate analyses of variances were performed for each location and season. Analysis of variance of combined locations, seasons and lines was made to determine the most stable varieties using the line-superiority measure and ecovalence stability coefficients. Results indicated that lines AVON1310 and AVON1325 were most stable for yield performance over lo-cations and seasons. From the genotype main effects and genotype-by-environment interaction (GGE) biplot, the best performing lines were AVON1310 (33.32 t.h-1), AVON1308 (28.81 t.h-1) and AVON1325 (31.68 t.h-1). These lines are potential candidates for sustainable intensification of onion production in Ghana and Mali.

Hypertension (HT) is a very common risk factor and a frequent cause of morbidity and mortality worldwide mainly due to much increase in overweight (OW) and obesity that manifests in various forms of cardiovascular disease (CVD). There are a number of factors that may cause overweight hypertension (OHT). However, we planned to conduct the present work to study the HT and OHT men for finding the variation, interrelationship and association of important cytokines mainly serum leptin (Lep) and tumor necrosis factor-alpha (TNF-α), serum testosterone (ST), total cholesterol (TC) and inflammatory status by measuring interleukin-6 (IL-6). Three groups of subjects, the normal controls (NC; n:98; age range: 51-60 years), HT (n: 97; age range: 51-60 years) subjects, and OHT (n: 97; age range: 51-60 years) subjects were studied. Comparisons for Lep, ST, TNF-α, IL-6 and TC levels for the subject groups showed significant variations. The ST indicated significant difference only for NC vs. OHT. The IL-6 gave significant difference for NC vs. OHT and HT vs. OHT. The one-way ANOVA showed significant difference among groups for BMI, TC, IL-6, TNF-α, ST and Lep levels. Significant positive linear correlation for all groups among Lep, TNF-α, IL-6 and TC were found. The ST against TC for HT and OHT groups presented non-significant negative linear correlations. The ST showed significant negative linear correlation with other variables. Conclusively, the present study uncovers the interactive impact of serum leptin, TNF-α, testosterone, total cholesterol and IL-6 in hypertensive and overweight-related hypertensive men.

We construct a novel family of summation-integral type hybrid operators in terms of shape parameter $\alpha\in \lbrack 0,1]$ in this paper. Basic estimates, rate of convergence, and order of approximation are also studied using the Korovkin theorem and the modulus of smoothness. We investigate the local approximation findings for these sequences of positive linear operators utilising Peetre's K-functional, Lipschitz class, and second-order modulus of smoothness.

Twelve overnight fasted, healthy, male volunteers received on separate days a test breakfast consisting of (A) 100 g fresh white bread (providing 50 g starch) and 250 mL drinking water, (B) the same bread with a supplement of 10 g alpha-cyclodextrin dissolved in the drinking water (250 mL), and (C) 250 mL drinking water containing 25 g alpha-cyclodextrin. Capillary and venous blood samples were collected before breakfast and at regular intervals for a period of 3 hours thereafter. Plasma glucose was determined in capillary blood and plasma insulin in venous blood samples. Breakfast (A) let to the expected rise in blood glucose and insulin concentrations. Breakfast (C) did not produce a significant glycemic and insulinemic response, demonstrating that alpha-cyclodextrin is not hydrolyzed to glucose in the human digestive tract. Mild intestinal symptoms after the ingestion of alpha-cyclodextrin were reported by 4 subjects. The postprandial rises of plasma glucose and insulin were significantly smaller after breakfast (B) than (A). Under the conditions of this study, alpha-cyclodextrin reduced the glycemic and insulinemic index of white bread by 57 and 55 %, respectively. The postprandial time profile of plasma glucose and insulin suggests that, in an initial phase, the digestion of starch is inhibited by alpha-cyclodextrin almost completely. Yet, despite the delayed and reduced digestion of starch, the intake of breakfast (B) was not associated with flatulence or any other gastrointestinal symptoms.

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

Rotational microwave jet spectroscopy studies of the monoterpenol α-fenchol have so far failed to identify its second expected torsional conformer, despite computational predictions that it is only very slightly higher in energy than the most stable conformer. Vibrational FTIR and Raman jet spectroscopy investigations reveal unusually complex OH and OD stretching spectra compared to other alcohols. Via modelling of the torsional states, observed spectral splittings are explained by delocalization of the hydroxy hydrogen atom through quantum tunneling between the two non-equivalent but accidentally near-degenerate conformers separated by a low and narrow barrier. The energy differences between the torsional states are determined to be only 16(1) and 7(1) cm$^{−1}hc$ for the protiated and deuterated alcohol, respectively, which further shrink to 9(1) and 3(1) cm$^{−1}hc$ upon OH or OD stretch excitation. Comparisons are made with the more strongly asymmetric monoterpenols borneol and isopinocampheol as well as with the symmetric, rapidly tunneling propargyl alcohol. Assigned are also for α-fenchol the third – in contrast localized – torsional conformer and the most stable dimer, as well as for propargyl alcohol the two most stable dimers.

We investigate new graph characteristics namely total (vertex, edge) face irregularity strength of gen- eralized plane grid graphs Gmn under k-labeling Phi of type (Alpha, Beta, Gamma). The minimum integer k for which a vertex-edge labelled graph has distinct face weights is called the total face irregularity strength of the graph and is denoted by tfs(Gmn). In this article, the graphs G = (V;E; F) under consideration are simple, fi nite, undirected and planar. We will estimate the exact tight lower bounds for the total face irregularity strength of some families of generalized plane grid graphs.

In this article, the geometry of pseudoparallel, Ricci-generalized pseudoparallel and 2-Ricci-generalized pseudoparallel invariant submanifolds of an almost $\alpha$-cosymplectic $(\kappa,\mu,\nu)$ space has been searched under the some conditions. We also give some characterizations for such submanifolds. I think that obtained new results contribute to differential geometry.

Apoptosis under severe hypoxia is induced through p53 phosphorylation and HIF-1α-dependent p53 accumulation via ATR activation by DNA damage response (DDR) activation through replication stress. We previously demonstrated that the topoisomerase I catalytic inhibitor, 3EZ, 20Ac-ingenol, specifically induced apoptosis in Jeko-1 and Panc-1 cells, both of which are cell lines that show cyclin D1 overexpression. After progression to the S phase facilitated by nuclear cyclin D1, in the presence of 3EZ, 20Ac-ingenol, an intra S phase checkpoint was induced in ATR activation as part of replication stress-induced DDR. In this study, we examined whether 3EE, 20Ac-ingenol induces a higher degree of p53 phosphorylation and additional HIF-1α and p53 accumulation in response to replication stress-induced DDR activation under the hypoxic condition than under the normoxic condition by controlling ATR activation. 3EE, 20Ac-ingenol induced p53 activation and HIF-1α-dependent p53 accumulation through cooperative ATR activation via induced DDR with the hypoxia in Panc-1 cells. The Jeko-1 cells showed slight HIF-1α accumulation under hypoxia, but this was not decreased by 3EE, 20Ac-ingenol, so that the cells remained resistant to hypoxia. 3EE, 20Ac-ingenol induces an intricate interplay between p53 and HIF-1α accumulation via ATR activations that results in high p53 accumulation, which advanced transient expression and early disappearance of HIF-1?. The strong p53 accumulation and consequent PTEN activation also decreased HIF-1α accumulation and PD-L1 expression, which resulted in intense apoptosis.

In this study we introduce the new classes $\mathcal{M}_{\alpha}(\sin)$ and $\mathcal{M}_{\alpha}(\cos)$ of $\alpha$-convex functions associated with sine and cosine functions. Also, we obtain the initial coefficient bounds for the first five coefficients of the functions that belong to these classes. Further, we determine the upper bound of Zalcman functional for the class $\mathcal{M}_{\alpha}(\cos)$ for the case $n=3$, showing that the Zalcman conjecture holds for this value. Moreover, the problem of the Fekete-Szeg\H{o} functional estimate for these classes is studied.

Oral cancer ranks sixth among Taiwan's top 10 cancers, and most patients with poor prognosis acquire metastases. The essential fatty acid alpha-linolenic acid (ALA) has been found to diminish many cancer properties. However, the anti-cancer activity of ALA in oral cancer has yet to be determined. Migration and invasion assays confirmed OSCC cells' EMT capabilities, whereas flow cytometry and Western blotting identified the molecular pathways. ALA dramatically reduced cell growth in a concentration dependent manner, according to the findings. Low concentrations of ALA (100 or 200 μM) inhibit colony formation, expression of Twist and EMT-related proteins, expression of MMP2/-9 proteins and enzyme activity, as well as cell migration and invasion. Treatment with high concentrations of ALA (200 or 400 μM) greatly increases JNK phosphorylation and c-jun nuclear accumulation, then upregulates the FasL/caspase8/caspase3 and Bid/cytochrome c/caspase9/caspase3 pathways, leading to cell death. Low concentrations of ALA inhibit SAS and GNM cell migration and invasion by suppressing Twist and downregulating EMT-related proteins, or by decreasing the protein expression and enzyme activity of MMP-2/-9, whereas high concentrations of ALA promote apoptosis by activating the JNK/FasL/caspase 8/caspase 3-extrinsic pathway and the Bid/cytochrome c/caspase 9 pathway. ALA demonstrates potential as a treatment for OSCC patients.

Although domestic cats are susceptible to infection with SARS-CoV-2, the role of the virus in causing feline disease is less well defined. We conducted a large-scale study to identify SARS-CoV-2 infections in UK pet cats, using active and passive surveillance. Remnant feline respiratory swab samples, submitted for other pathogen testing between May 2021 and February 2023, were screened using RT-qPCR. In addition, we appealed to veterinarians for swab samples from cats suspected of having clinical SARS-CoV-2 infections. Bespoke testing for SARS-CoV-2 neutralising antibodies was also performed, on request, in suspected cases. One RT-qPCR-positive cat was identified from the active surveillance (1/549, 0.18 %), during the Delta wave (1/175, 0.57 %). Passive surveillance detected one cat infected with the Alpha variant, and two of ten cats tested RT-qPCR-positive during the Delta wave. No cats tested RT-qPCR-positive after the emergence of Omicron BA.1 and its descendants although 374 were tested by active and eleven by passive surveillance. We describe four cases of SARS-CoV-2 infection in pet cats, identified by RT-qPCR and/or serology, that presented with a range of clinical signs, as well as their SARS-CoV-2 genome sequences. Our results demonstrate that, although uncommon, clinical infections in cats can and do occur.

Pseudopterosin, produced by the sea whip of the genus Antillogorgia, possesses a variety of promising biological activities including potent anti-inflammatory effects. However, few studies examined pseudopterosin in the treatment of cancer cells and, to our knowledge, the ability to inhibit triple negative breast cancer (TNBC) proliferation or invasion has not been explored. Thus, we evaluated the as yet unknown mechanism of action of pseudopterosin: Pseudopterosin was able to inhibit proliferation of TNBC. Interestingly, analyzing breast cancer cell proliferation after knocking down glucocorticoid receptor α (GRα) revealed that anti-proliferative effects of pseudopterosin were significantly inhibited when GRα expression was reduced. Furthermore, pseudopterosin inhibited invasion of MDA-MB-231 3D tumor spheroids embedded in an extracellular-like matrix. Remarkably, the knockdown of GRα in 3D tumor spheroids revealed increased ability of cells to invade the surrounding matrix. In a co-culture, encompassing peripheral blood mononuclear cells (PBMC) and MDA-MB-231 cells, production of interleukin 6 (IL-6) and interleukin 8 (IL-8) significantly increased compared to monoculture. Notably, pseudopterosin proved to block cytokine elevation, representing key players in tumor progression, in the co-culture. Thus, our results reveal pseudopterosin treatment as a potential novel approach in TNBC therapy.

Hypoxia-inducible factor (HIF)-1α represents the oxygen-sensitive subunit of HIF transcriptional factor, usually degraded in normoxia and stabilized in hypoxia to regulate several target gene expression. Nevertheless, in the skeletal muscle satellite stem cells (SCs), an oxygen level-independent regulation of HIF-1α has been observed. Although HIF-1α has been highlighted as SC function regulator, its spatio-temporal expression and role during myogenic progression remain controversial. We herein analyzed HIF-1α expression and localization in differentiating murine C2C12 myoblasts and SCs under normoxia and evaluated matrix metalloproteinase (MMP)-9 as a HIF-1α target, by biomolecular, biochemical, morphological and electrophysiological analyses. HIF-1α expression increased after 24/48 h of differentiating culture and tended to decline after 72 h/5 days. Committed and proliferating mononuclear myoblasts exhibited nuclear HIF-1α expression, differently from the more elongated and parallel-aligned cells, likely ready to fuse with each other, which show mainly a cytoplasmic localization of the factor. Multinucleated myotubes displayed both a nuclear and cytoplasmic HIF-1α expression. The MMP-9 and MyoD (myogenic activation marker) expression synchronized with that of HIF-1α, increasing after 24 h of differentiation. Short-interfering RNA silencing of HIF-1α and MMP-9 and MMP-9 pharmacological inhibition unraveled MMP-9 as HIF-1α downstream effector and HIF-1α/MMP-9 axis essential for the morpho-functional cell myogenic commitment.

Central adiposity is one of the significant determinants of obesity-related hypertension risk, which may arise due to the abdominal fat depot's pathogenic inflammatory nature. Pro-inflammatory cytokines and adipokines up-regulation through nuclear factor-kappa B (NF-κB) activation in adipose tissue has been considered an essential function in the pathogenesis of obesity-related hypertension. This study aimed to ascertain the NF-κB inhibitor (SN50) effect on TNF-α and angiotensinogen (AGT) secretion and expression in mediating the anti-inflammatory effect through its impact on NF-κB activity in humans adipose tissue. Primary human adipocytes were isolated from 20 subjects among 10 overweight and 10 obese with and without hypertension and treated with 10ng/ml LPS in the presence and absence of NF-κB inhibitor, SN50 (50μg/ml). TNF-α secretion and NF-κB p65 activity were detected in supernatants extracted from cultured cells treated and untreated with LPS (10ng/ml) and SN50 (50μg/ml) using enzyme-linked immunosorbent assay (ELISA). The western blot technique detected the protein of NF-κB p65 and AGT. Gene expression of TNF-α and AGT was detected in cells and performed using quantitative real-time polymerase chain reaction (RT-PCR). Treatment of AbdSc adipocytes with LPS (10ng/ml) caused a significant increase in NF-κB p65 among overweight and obese subjects with and without hypertension (P= 0.001) at 24 hours incubation. In contrast, SN50-NF-κB inhibitor causes a reduction of NF-κB p65 in overweight (P= <0.001) and obese subjects with and without hypertension (P= 0.001) at 24 hours incubation. Treatment of AbdSc adipocytes with 10ng/ml LPS caused a significant increase in TNF-α secretion in overweight and obese subjects at all-time points (P= <0.001), whereas SN50 leads to a decrease in TNF-α secretion at 3 and 12 hours incubation. Treatment of AbdSc adipocytes with LPS (10ng/ml) caused increased TNF-α and AGT gene expression twofold compared with untreated cells, whereas, in the presence of SN50, it reduces mRNA AGT levels in both groups. Taken together, these adipokines with NF-κB activation may represent essential biomarkers to evaluate hypertension risk and to provide insight into the pathogenesis of obesity-related hypertension.

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

In this paper, experiences of the last 20 years with the PERALS-technique are described. PERALS stands for Photo Electron Rejecting Alpha Liquid Scintillation. This LSC-technique was developed by Jack McDowell in the 70ies and is a powerful technique for the analyses of many natural alpha nuclides. The principle is based on a selective extraction of the radionuclide from the water phase by means of a complexing or ion pair reagent. The extractant contains also a suitable cocktail for the scintillation counting. Therefore, the extract can be analysed directly after the extraction step. After removing quenchers, such as oxygen, and the proper setting of a pulse shape discriminator, alpha pulses can be counted with a photomultiplier. The paper describes the development of robust analysis schemes for the determination of traces of polonium, radon, radium, strontium, thorium, uranium and other actinides in water samples (groundwater, rain water, river water, drinking water, mineral water, sea water).

Interferon alpha (IFNα) is a protein drug used to treat viral infections and cancer diseases. Due to its poor stability in the gastrointestinal tract, only parenteral administration ensures bioavailability, which is associated with severe side effects. We hypothesized that the nanoencapsulation of IFNα within nanoparticles of the mucoadhesive polysaccharide chitosan would improve the oral bioavailability of this drug. In this work, we produced IFNα-loaded chitosan nanoparticles by the ionotropic gelation method. Their size, size distribution and concentration were characterized by dynamic light scattering and nanoparticle tracking analysis. After confirming their good cell compatibility in Caco-2 and WISH cells, the permeability of unmodified and PEGylated nanoparticles was measured in monoculture (Caco-2) and co-culture (Caco-2/HT29-MTX) cell monolayers. Results indicated that the nanoparticles cross the intestinal epithelium mainly by the paracellular route. Finally, the oral pharmacokinetics in BalbC mice of nanoencapsulated IFNα revealed that it was absorbed reaching an area-under-the-curve of 56.9 pg.h/mL.

Obesity and metabolic syndrome involve chronic low-grade inflammation called metabolic inflammation as well as metabolic derangements from increased endotoxin and free fatty acids. It is debated whether the endoplasmic reticulum (ER) stress in monocytic cells can contribute to amplify metabolic inflammation; if so, by which mechanism(s). To test this, metabolic stress was induced in THP-1 monocytic cells by treatments with lipopolysaccharide (LPS), palmitic acid (PA), or oleic acid (OA), in the presence or absence of ER stressor thapsigargin (TG). Gene expression of tumor necrosis factor (TNF)-α and markers of ER/oxidative stress was determined by qRT-PCR, TNF-α protein by ELISA, ROS by DCFH-DA assay, HIF-1α/p38/ERK-1,2/NF-κB phosphorylation by immunoblotting, and insulin sensitivity by glucose-uptake assay. Regarding clinical analyses, adipose TNF-α was assessed by qRT-PCR/IHC and plasma TNF-α/hs-CRP/MDA/OX-LDL by ELISA. We found that the cooperative interaction between metabolic and ER stresses promoted TNF-α, ROS, CHOP, ATF6, SOD2, and NRF2 expression (P≤0.0183),. However, glucose uptake was not impaired. TNF-α amplification was dependent on HIF-1α/p38/NF-κB phosphorylation, while MAPK/NF-κB inhibitors and antioxidants/ROS scavengers attenuated TNF-α production (P≤0.05). Individuals with obesity displayed increased adipose TNF-α gene/protein expression as well as elevated plasma levels of TNF-α, CRP, MDA, and OX-LDL (P≤0.05). Our findings support a cooperative interaction between metabolic and ER stresses, favoring inflammation by triggering TNF-α production via the ROS/CHOP/HIF-1α and MAPK/NF-κB dependent mechanisms. This study also shows the therapeutic potential of ROS scavengers/anti-oxidants in inflammatory conditions involving metabolic/ER stresses.

COVID-19 pandemic outbreak challenged the global public health in last couple of years. Throughout the pandemic period, numbers of mutant strains of SARS- CoV-2 created challenges for the infected patients with diverse pathophysiology and immune response. Variant of Concern (VOC) alpha (B.1.1.7), delta (B.1.617.2) and omicron (B.1.1.529) grew most notable for causing the epidemiological manifestations, which eventually caused elevated infectivity resulting in significant mortality. This review indicates the comparative analysis of the immune-pathophysiological mechanisms in respect to the aforementioned strains of SARS-CoV-2.

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

Study of gross alpha (GA) and gross beta (GB) activity in road and surface deposited sediments were performed in various geographical areas in three Russian cities. To perform radiation measurements, new methods were applied which allow dealing with low mass and low volume dust size (2-100μm) samples obtained after the size fractionation procedure. The 2-10 μm fraction size has the highest gross beta activity concentration (GB)– 1.32Bq/g in Nizhny Novgorod (NN) and Rostov-On-Don (RND) while the 50-100 μm fraction size in Ekaterinburg. This is maybe associated with the subsistence of radionuclides that conveyed through natural processes and anthropogenic applications. The highest gross alpha activity concentration (GA) in fraction sizes was found in Rostov-on-Don city within the 50-100 μm– 0.22Bq/g. The fraction size 50-100 μmhas a higher gross alpha activity concentration than 2-10 and 10-50 μmfraction sizes due to natural partitioning of the main minerals constituting the urban surface deposited sediment (USDS). The geochemical processes that occur during the formation and transportation of USDS are reflected in the observed dependencies.Developed experimental methods of radiation measurements allowed to the extent the methodological base of urban geochemical studies.

Alpha-fetoprotein (AFP) is a major embryo- and tumor-associated protein capable of binding and transporting variety of hydrophobic ligands including estrogens. AFP has been shown to inhibit estrogen receptor (ER)-positive tumor growth and this can be attributed to its estrogen-binding ability. Despite AFP has long been investigated, its three-dimensional (3D) structure has not been experimentally resolved and molecular mechanisms underlying AFP-ligand interaction remain obscure. In our study we constructed homology-based 3D model of human AFP (HAFP) with the purpose to perform docking of ERα ligands, three agonists (17β-estradiol, estrone and diethylstilbestrol) and three antagonists (tamoxifen, afimoxifene and endoxifen) into the obtained structure. Based on ligand docked scoring function, we identified three putative estrogen- and antiestrogen-binding sites with different ligand binding affinities. Two high-affinity sites were located in (i) a tunnel formed within HAFP subdomains IB and IIA and (ii) opposite side of the molecule in a groove originating from cavity formed between domains I and III, while (iii) the third low-affinity site was found at the bottom of the cavity. 100 ns MD simulation allowed studying their geometries and showed that HAFP-estrogen interactions occur due to van der Waals forces, while both hydrophobic and electrostatic interactions were almost equally involved in HAFP-antiestrogen binding. MM/GBSA rescoring method estimated binding free energies (ΔG_bind) and showed that antiestrogens have higher affinities to HAFP as compared to estrogens. We performed in silico point substitutions of amino acid residues to confirm their roles in HAFP-ligand interactions and showed that Thr132, Leu138, His170, Phe172, Ser217, Gln221, His266, His316, Lys453, and Asp478 residues along two disulfide bonds, Cys224-Cys270 and Cys269-Cys277 have key roles in both HAFP-estrogen and HAFP-antiestrogen binding. Data obtained in our study contribute to understanding mechanisms underlying protein-ligand interactions and anti-cancer therapy strategies based on ER-binding ligands.

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

Aggregated alpha-synuclein (-synuclein) is the main component of Lewy bodies (LBs), Lewy neurites (LNs), and glial cytoplasmic inclusions (GCIs), which are pathological hallmarks of idiopathic Parkinson’s disease (IPD) and multiple system atrophy (MSA), respectively. Initiating factors that culminate in forming LBs/LNs/GCIs remain elusive. Several species of -synuclein exist, including phosphorylated and nitrated forms. It is unclear which -synuclein post-translational modifications (PTMs) appear within aggregates throughout disease pathology. Herein we aimed to establish the predominant synuclein PTMs in post-mortem IPD and MSA pathology using immunohistochemistry. We examined the patterns of three -synuclein PTMs (pS87, pS129, nY39) simultaneously in pathology-affected regions of 15 PD, 5 MSA, 6 neurologically normal controls. All antibodies recognized LBs, LNs, and GCIs, albeit to a variable extent. pS129 -synuclein antibody was particularly immunopositive for LNs and synaptic dot-like structures followed by nY39 -synuclein antibody. GCIs, neuronal inclusions, and small threads were positive for nY39 -synuclein in MSA. Quantification of the LB scores revealed that pS129 -synuclein was the dominant and earliest -synuclein PTM followed by nY39 -synuclein, while lower amounts of pSer87 -synuclein appeared later in disease progression in PD. These results may have implications for novel biomarker and therapeutic developments.

The abnormal assembly of α-synuclein (α-Syn) is an initial step in the formation of Lewy bodies in the brain, which finally causes the neuronal death, being considered as a pathological hallmark in Parkinson’s disease (PD). Certain food bioactives or their metabolites at very low concentrations can trespass the blood brain barrier (BBB) that might, thereafter, act simultaneously. The aim of this work was to evaluate the inhibitory and destabilising capacities on α-Syn kinetics and the neuroprotective effects of three well-known bioactive compounds able to cross the BBB and present in foods; melatonin (MEL), protocatechuic acid (PCA) and hydroxytyrosol (HT), and their combinations. For this purpose, different in vitro techniques (Thioflavin T (ThT), Transmission Electronic Microscopy (TEM), electrophoresis and MTT assay) were used. All tested compounds and their combinations were able to abolish the toxicity induced by α-Syn. In addition, the combination of PCA (100 µM) +HT (100 µM) showed the highest inhibitory effect against α-Syn fibril formation and destabilises α-Syn fibrils (88 and 62%, respectively). This is the first time that MEL, PCA and HT prove a joint effect against α-Syn aggregation and toxicity when they are tested together.

The study compared antibacterial potential of hydrolysates of casein and alpha-lactalbumin from cow and goat milk on diarrhea-causing Escherichia coli and Staphylococcus aureus. Milk samples were aseptically obtained from lactating cows and goats. The samples were skimmed; casein was isolated using acetic acid and alpha-lactalbumin by filtrate thermoprecipitation at 75 °C. 50% of each isolate was reconstituted in a buffer and hydrolyzed with papain at 55 °C for 2 hours. The hydrolysates were heated to 75 °C to inactivate papain, cooled and their antibacterial activity determined by disc diffusion method. Results showed alpha-lactalbumins had higher degrees of hydrolysis and antibacterial activity than caseins; goat alpha-lactalbumin had the highest antibacterial activity with mean inhibition zones of 19.60 mm and 19.50 mm on E. coli and S. aureus. Cow alpha-lactalbumin inhibited E. coli more than S. aureus with inhibition zones of 16.80 mm and 12.50 mm. Cow and goat milk casein hydrolysates inhibited E. coli with mean inhibition zones of 8.00 mm and 10.90 mm and inhibited S. aureus with inhibition zones of 4.13 mm and 1.90 mm respectively. The research showed that the milk hydrolysates can be a source of antibiotics for diarrhea treatment. Research should be done to establish the peptide fractions associated with the observed bioactivity.

Emerging evidence demonstrated that using a new manufacturing technology to produce γ-aminobutyric acid (GABA)-fortified oolong (GO) tea could relieve human stress and exert versatile physiological benefits. The purpose of this human research aims to investigate therapeutic effects of daily GO tea consumption on the improvement of blood pressure, relaxation-related brain waves and quality of life (QOL) during a period of 28 consecutive days. Total polyphenols, major catechins and free amino acids were analyzed via HPLC assay. Changes of heart rate, blood pressure, α-brain wave (index of relaxation) and eight-item QOL score were investigated on day 0, 7, 14, 21 and 28, respectively. The chemical analysis results showed that GO tea contained the most abundant amino acids and GABA, contributing to the relaxation activity. Among all study participants, daily drinking GO tea could reduce systolic blood pressure on day 21 and diastolic blood pressure on day 28 (p &lt; 0.05, respectively). For participants with pre-hypertension, GO tea could effectively reduce heart rate, systolic and diastolic blood pressure on day 28 (p &lt; 0.05). At the end of the study, incremental changes in alpha-brain wave and QOL scores were also demonstrated (p &lt; 0.05, respectively). This study recommended that GO tea might potentially serve as a natural source of alternative therapy to benefit blood pressure, stress-relief and QOL.

SARS-CoV-2 is severe acute respiratory syndrome coronavirus 2 which induces severe pneumonia that has considerable death rate. In this article, we summarised the evolution of SARS CoV-2 from alpha to omicron variant. The origin, transmission capability, and innate immunity potential of the Omicron variety remain unknown in the aftermath of its appearance. It's also unclear whether further varieties based on Omicron may emerge in the future. However, there is no question that the Omicron version of SARS-CoV-2 would not be the last. The COVID-19 pandemic has become more difficult to control due to the constant appearance of new SARS-CoV-2 mutations. We have discussed about the epidemiology, treatment plans for SARS CoV-2 and preventive strategies for future pandemic.

The present study explored whether exposure to complex childhood trauma (CCT) is reflected in the resting-state electroencephalography (EEG) temporal alpha power of complex trauma-exposed adolescents, given the association of temporal alpha with fear circuitry (learning and conditioning) in a sample of 25 adolescents and similar controls, ages 12-17 years. Both trauma and psychopathology were screened or assessed, and resting-state EEG was recorded, following a preregistered protocol for data collection. Temporal alpha power, corresponding to T5 and T6 electrode location (10-20 international system), was extracted from resting-state EEG in both eyes-open and eyes-closed conditions. We found that in the eyes-open condition, right, but not left, temporal alpha was significantly higher in adolescents exposed to CCT, relative to healthy controls, suggesting that childhood trauma exposure may have a measurable impact on alpha oscillatory patterns, specifically in the right temporal region. Our study highlights the importance of considering neural markers, such as temporal alpha power, in understanding the long-term consequences of CCT exposure in developmental samples, with possible important clinical implications in guiding neuroregulation interventions.

In this paper, we consider the temporal development of the optical density of the H$_\alpha$ spectral line in a hydrogen laser induced plasma. This is achieved by using the so-called duplication method in which the spectral line is re-imaged onto itself and the ratio of the spectral line with it duplication is taken to its measurement without the duplication. We asses the temporal development of the self-absorption of the H$_\alpha$ line by tracking the decay of duplication ratio from its ideal value of 2. We show that when 20% loss is considered along the duplication optical path length, the ratio is 1.8 and decays to a value of 1.25 indicating an optically thin plasma grows in optical density to an optical depth of 1.16 by 400 ns in the plasma decay for plasma initiation conditions using Nd:YAG laser radiation at 120 mJ per pulse in a 1.11$\times10^{5}$ Pa hydrogen/nitrogen gas mixture environment. We also go on to correct the H$_\alpha$ line profiles for the self-absorption impact using two methods. We show that a method in which the optical depth is directly calculated from the duplication ratio is equivalent to standard methods of self-absorption correction when only relative corrections to spectral emissions are needed.

To assess the genetic diversity of circulating dengue virus 2 in Senegal in 2018 we performed molecular characterization by complete genome sequencing and performing phylogenetic analysis. Sequenced strains belong to Cosmopolitan genotype of DENV-2 we observed intra-genotype variability leading to a divergence in two clades with differential geographic distribution. We report two variants namely; the “Northern variant” harbouring three nonsynonymous mutations (V1183M, R1405K, P2266T) located respectively on NS2A, NS2B and NS4A and the “Western variant” with two nonsynonymous mutations (V1185E, V3214E) located respectively in the NS2A gene and the NS5 gene. Findings calls for in depth in vitro and functional study to elucidate the impact of observed mutations on viral fitness, spread, epidemiology and disease outcome.

Aggregation of the protein α-Synuclein (αSyn) is a hallmark of Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple systems atrophy, and alleviating the extent of αSyn pathology is an attractive strategy against neurodegeneration. The engineered binding protein β-wrapin AS69 binds monomeric αSyn. AS69 reduces primary and secondary nucleation as well as fibril elongation in vitro. It also mitigates aSyn pathology in a mouse model based on intrastriatal injection of aSyn pre-formed fibrils (PFF). Since the PFF-based model does not represent all aspects of PD, we tested here whether AS69 can reduce neurodegeneration resulting from αSyn overexpression. Human A53T-αSyn was overexpressed in the mouse Substantia nigra (SN) by using recombinant adeno-associated viral vector (rAAV). AS69 was also expressed by rAAV transduction. Behavioral tests and immunofluorescence stainings were used as outcomes.Transduction with rAAV-αSyn resulted in αSyn pathology as reported by phospho-αSyn staining and caused degeneration of dopaminergic neurons in the SN. The co-expression of rAAV-AS69 did not reduce αSyn pathology or degeneration of dopaminergic neurons. We conclude that αSyn monomer binding by rAAV-AS69 was insufficient to protect from aSyn pathology resulting from αSyn overexpression.

Background: Deficiency of alpha-1 antitrypsin (AAT1) is a rare disorder that represents a significant health threat and early diagnostic a priority issue. We investigate the usefulness of the serum protein electrophoresis (SPE) as an opportunistic screening tool for AAT1 deficiency. Methods: For 6 months, all SPE carried out for any reasons were evaluated in our center. In those with less than 3% of Alpha-1 globulins, AAT1 concentrations were studied. The SERPINA1 gene was subsequently sequenced in those subjects displaying concentrations below 100 mg/dL. Results: Out of the total, 14 patients (0.3%) were identified with low AAT1 concentrations, 11 of them agreeing to enter the study. Of those, mutations in the SERPINA1 gene were discovered in 10 subjects (91%). Heterozygous mutations were detected in 7 patients; 3 had the c.1096G>A mutation (p.Glu366Lys; Pi*Z), 2 the c.863A>T mutation (p.Glu288Val; Pi*S), one the c.221_223delTCT mutation (p.Phe76del; Pi*Malton) having the last one the c.1066G>A (p.Ala356Thr) mutation not previously described. Finally one patient had the c.863A>T mutation in homozygosis whereas two double heterozygous patients c.863A> T/ c.1096G>A were detected. Conclusions: an altered result in the concentration of AAT1 anticipates a mutation in the SERPINA1 gene in a manner close to 91%. The relationship between a decrease in the Alpha-1 globulin band of the SPE and an alteration in the AAT1 concentration is direct in basal states of health. The SPE is presented as a highly sensitive test for opportunistic screening of AAT1 deficiency.

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

Erlotinib inhibits epithelial growth factor receptor (EGFR) kinase activity and is used to treat non-small cell lung cancer (NSCLC). Despite its high efficacy, recurrence can occur in patients who become resistant to the drug. To address the underlying mechanism of Erlotinib resistance, we investigated additional mechanisms related to mode-of-drug-action, by multiple protein-binding interactions, besides EGFR by using drug affinity responsive target stability (DARTS) and liquid chromatography-mass spectrometry (LC-MS/MS) methods with non-labeled Erlotinib. DNA polymerase alpha subunit B (POLA2) was identified as a new Erlotinib binding protein that was validated by the DARTS platform, complemented with cellular thermal shift assays. Genetic knock-down of POLA2 promoted the anti-proliferative effect of the drug in the Erlotinib-resistant cell line H1299 with high POLA2 expression, whereas overexpression of POLA2 restored anti-proliferative effects in the Erlotinib-sensitive cell line HCC827 with low POLA2 expression. Importantly, POLA2 expression levels in four NSCLC cell lines were positively correlated with anti-proliferative Erlotinib efficacy, verified by bio-statistical analysis (Pearson correlation coefficient, R=0.9886). These results suggest that POLA2 is a novel complementary target protein of Erlotinib, and could clinically provide validity as a surrogate marker for drug resistance in patients with NSCLC.

Rapid proliferation of traditional gold mining sites in Kédougou a Southeast region in Senegal, led to mass population migration from the neighboring West African countries and rapid expansion of small mining villages with poor hygiene and sanitation conditions. An outbreak of hepatitis E was reported in 2014 with several cases of febrile jaundice among traditional mine workers. In this study, we analyzed both HEV IgM and IgG seroprevalence and the associated risk factors of infection by testing any suspected case and contacts collected from February 2012 to November 2014. RNA-negative sera from suspected cases and contacts were tested for anti-HEV IgM and anti-HEV IgG. A total of 799 sera were collected from 290 suspected cases, 470 contacts and 39 individuals with missing information. The median age of the cohort study was 19 years (1-88 years) with a male/female sex-ratio of 1.9. We found an overall prevalence of 43.68% (332/760) of anti-HEV IgM and 38.15% (290/760) of anti-HEV IgG sera. Our data provide new insights into the HEV epidemiology and point to the crucial need to estimate the disease’s burden in Kédougou and assess the viral mechanisms driving the disease’s severity in pregnant women.

Fisheries and bottom seawater data were collected in July in 2022 and 2023 from 15 sampling stations in the Huanghe River Estuary and adjacent seas in China. The patterns of functional alpha- and beta-diversity of fish communities in this area and their relationship with environmental factors were studied using trait-based analysis. Five functional classifications, which included 16 functional traits, four functional alpha-diversity indices (functional richness, functional evenness, functional divergence, and community-weighted mean), three functional beta-diversity indices (functional beta-diversity and its turnover and nestedness components), and 14 bottom environmental factors were considered. The dominant traits of fish communities were: benthivorous feeding habits, small and front-facing mouths, high trophic level, demersal, anguilliform, low growth coefficient, medium resilience, low vulnerability, and adapted to warm temperate conditions. The dominant migration traits and types of fish eggs varied by year, and fish abundance was the main factor affecting the dominant traits of the communities. The results of multiple regression on distance matrices and variance partitioning analysis indicated that ammonia nitrogen content, total phosphorus content, and pH were the main environmental factors that affected fish functional diversity. The N/P ratio had an upward control effect on fish functional diversity. Our findings also revealed that high pH gradients and distant geographical distances can inhibit trait turnover in fish communities.

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

This work aimed to study the effect of repeated exposure to low doses of ozone on alpha-synuclein and the inflammatory response in the substantia nigra, jejunum, and colon. Seventy-two male Wistar rats were divided into six groups. Each group received one of the following treatments: The control group was exposed to air. Ozone groups were exposed for 7, 15, 30, 60, and 90 days for 0.25 ppm. for four hours daily. Afterward, they were anesthetized, and their tissues were extracted and processed using western blotting, immunohistochemistry, and qPCR. The results indicate a significant increase in alpha-synuclein in the substantia nigra and jejunum from 7 to 60 days of exposure, an increase in NFκB from 7 to 90 days in the substantia nigra, while in the jejunum, a significant increase is observed at 7 and 15 days and a decrease at 60 and 90 days for the colon. Interleukin IL-17 shows an increase at 90 days in the substantia nigra in the jejunum and increases at 30 days and in the colon at 15 and 90 days. Exposure to ozone increases the presence of al-pha-synuclein and the loss of regulation of the inflammatory response, which contributes significantly to degenerative processes.

Photothrombotic stroke (PTS) stimulates the level of N- and C-terminal fragments of Amyloid precursor protein (APP) growth in the cytoplasm of ischemic penumbra cells not earlier but at 24 hours. Here we have shown that APP fragments are visualized in thin unmyelinated fibers of neurons, in containing mitochondria large fibers and in synapses but absent in the nuclei. At 24 hours after PTS, some elements of the destroyed tissue accumulated a significant amount of APP protein. The level of ADAM10 α-secretase decreased on the first day after PTS in the rat brain cortex and ADAM-10 co-localized with the lipid raft marker caveolin-1. PTS caused no changes in the level of β-secretase BACE1 either on the first day after PTS or in the early recovery period. The expression of proteins of the γ-secretase complex: presenilin-1 and nicastrin increased in astrocytes, but not in penumbra neurons after PTS. The β-secretase inhibitor LY2886721 did not affect the infarct size of the mouse cerebral cortex and the level of apoptosis of cells in the perifocal region after PTS. Whereas the inhibitor of γ-secretase DAPT reduced the expression of glial fibrillary acidic protein (GFAP) in astrocytes, prevented the growth of apoptosis of mouse cerebral cortex cells reducing the infarct volume on the 7th and 14th days after PTS. DAPT may be considered as a drug for stroke therapy.

The aim of this study was to examine oxidative stress and low level of alpha-1-antitrypsin (A1AT) in primary Sjögren's syndrome (pSS), and evaluate the associated autoreactivity against unmodified and their 4-hydroxy-2-nonenal (HNE)-modified peptides with pSS. Two differentially expressed proteins, alpha-1-acid glycoprotein 1 (A1AG1) and A1AT, exhibited 2-fold differences, and their HNE modifications were identified by depleted-albumin and immunoglobulin G (IgG) serum protein, in-solution digestion, in-gel digestion, and nano-LC-MS/MS from pSS patients and age-matched healthy controls (HCs). Furthermore, levels of proteins, confirmation of HNE modifications, HNE-protein adducts and autoreactivity against unmodified and their HNE-modified peptides were further validated. Levels of the HNE-protein adduct and A1AG1 were significantly higher in pSS patients than HCs, but levels of A1AT were significantly lower in pSS patients compared to HCs. Only the HNE modification of A1AT was confirmed. Further, concentrations of anti-A1AT^50-63 IgG and anti-A1AT^50-63 HNE IgA were significantly lower in pSS patients than HCs. Our study suggests that elevated HNE-protein adduct, oxidative stress, level [odds ratio (OR) 4.877, p = 0.003], lowered A1AT level (OR 3.910, p = 0.010) and a decreased level of anti-A1AT^50-63 IgG (OR 3.360, p = 0.010) showed an increased risk in pSS patients compared to HCs, respectively.

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

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

The potato tuber moth PTM, Phthorimaea operculella, is one of the most economically important potato pests worldwide. In the present study, the potential of Steinernema feltiae and Steinernema carpocapsae for controlling PTM in potato tubers was evaluated compared to alpha-cypermethrin. Steinernema carpocapsae in both concentrations (12.6×10⁶IJs and 6.2×10⁶IJs) showed a lower number of emerged insects than alpha-cypermethrin (10 mg ai l^-1). Alpha-cypermethrin (20 mg ai l^-1) showed the highest efficacy against PTM (81.17%), S.carpocapsae (12.6×10⁶IJs), and alpha-cypermethrin (10 mg ai l^-1) showed similar efficacy (72.53%) while S. feltiae (6.2×10⁶IJs) showed the lowest efficacy (39.04%). The results showed that S.carpocapsae in both concentrations and S. feltiae (12.6×10⁶IJs) were efficient the same as alpha-cypermethrin (10 mg ai l^-1) having no environmental and health adverse impacts issued in the chemical insecticides usage. Both concentrations of alpha-cypermethrin and S. carpocapsae showed the least tuber damage with no significant differences, while it was as high as the control (59.26%) in both concentrations of S. feltiae. This promising finding introduces EPNs as a part of the potato tuber protection program in storage. Accordingly, EPNs can be considered as an appropriate alternative to synthetic chemicals for PTM control without any residue and health problems.

Hepatitis B virus (HBV) infection is a major factor in development of various liver diseases such as hepatocellular carcinoma (HCC). Among HBV encoded proteins, HBV X protein (HBx) is known to play key role in development of HCC. Hepatocyte nuclear factor 4α (HNF4α) is a nuclear transcription factor which is critical for hepatocyte differentiation. However, the expression level as well as its regulatory mechanism in HBV infection have yet to be clarified. Here, we observed the suppression of HNF4α in cells which stably express HBV whole genome or HBx protein alone, while transient transfection of HBV replicon or HBx plasmid had no effect on the HNF4α level. Importantly, in the stable HBV- or HBx-expressing hepatocytes, the downregulated level of HNF4α was restored by inhibiting ERK signaling pathway. Our data showed that HNF4α was suppressed during long-term HBV infection in cultured HepG2-NTCP cells as well as in mouse model following hydrodynamic injection of pAAV-HBV or in mice intravenously infected with rAAV-HBV. Importantly, HNF4α downregulation increased cell proliferation which contributed to the formation and development of tumor in xenograft nude mice. The data presented here provided several proofs for the effect of HBV infection in manipulating HNF4α regulatory pathway in HCC development.

The gut microbiota plays a crucial role in maintaining host health and has a significant impact on human health and disease. In this study, we investigated the alpha diversity of gut microbiota in COVID-19 patients and analyzed the impact of COVID-19 variants, antibiotic treatment, type 2 diabetes (T2D), and metformin therapy on gut microbiota composition and diversity. We used a culture-based method to analyze the gut microbiota and calculated alpha-diversity using the Shannon H' and Simpson 1/D indices. We collected clinical data, such as length of hospital stay (LoS), C-reactive protein (CRP) levels, and neutrophil-to-lymphocyte ratio (NLR). We found that patients with T2D had significantly lower alpha-diversity than those without T2D. Antibiotic use was associated with a reduction in alpha-diversity, while metformin therapy was associated with an increase. We did not find significant differences in alpha-diversity between the Delta and Omicron groups. Length of hospital stay, CRP levels, and NLR showed weak to moderate correlations with alpha diversity. Our findings suggest that maintaining a diverse gut microbiota may benefit COVID-19 patients with T2D. Interventions aimed at preserving or restoring gut microbiota diversity, such as avoiding unnecessary antibiotic use and promoting metformin therapy, may improve patient outcomes.

Patients with transfusion-dependent thalassemia (TDT) show disorders in calcium metabolism. The α-klotho protein is predominantly expressed in tissues that are involved in calcium homeostasis, and lowered levels are associated with bone disease. Aim of the study. To study the associations between low α-klotho status and calcium metabolism in relation to iron status in children with TDT. Methods. α-klotho, calcium, parathyroid hormone (PTH), calcyphosin, vitamin D3, phosphorous, fibroblast growth factor receptor 2 (FGFR2), as well as iron and erythron biomarkers were measured in 60 children with TDT and 30 healthy control children. Results. A meaningful part of TDT patients showed lowered α-klotho levels, and those children also showed low serum total and ionized calcium concentrations. TDT patients showed increased PTH, FGFR2, and calcyphosin and lowered vitamin D3 as compared with healthy children. The α-klotho levels were significantly correlated with total and ionized calcium (positively) and with iron overload biomarkers and the number of blood transfusions (inversely). Partial Least Squares path analysis showed that 40.1% of the variance in serum total calcium could be explained by the regression on α-klotho, vitamin D3 (both positively), and calcyphosin (inversely) and that the effects of the latter are mediated by iron overload and the number of blood transfusions. Conclusion. In TDT, iron overload and its consequences may induce lowered levels of α-klotho which in turn may lead to lower calcium thereby explaining at least in part the effects of TDT on bone metabolism including spontaneous pathological fractures, osteoporosis, osteopenia, and skeletal deformities.

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

Cartilage development is a tightly regulated process that involves multiple molecules and signaling pathways. The loss of expression of a single gene can alter cell behavior and disrupt the development of the cartilage. Col11a1 encodes the alpha one chain of the minor fibrillar collagen type XI that is essential in skeletal development. We used an RNAi mediated knockdown approach to investigate the role of Col11a1 expression during chondrogenesis in ATDC5 cells. Col11a1 expression promotes the transition of mesenchymal cells to the chondrogenic phenotype, and reduction of Col11a1 expression interferes with cellular differentiation. Our results indicate that collagen α1(XI) protein is required for chondrocyte cell shape, matrix production, mineralization and gene expression through a mechanism that involves AKT/GSK3β/β-catenin and TCF/LEF activity in ATDC5 cells.

Globally 390 millions of people are at risk of dengue infection; over the past 50 years the virus incidence increased thirty-fold. In Senegal, an unprecedented occurrence of outbreaks and sporadic cases was noticed since 2017. In October 2018 an outbreak of DENV-2 was reported in Rosso area in the north of Senegal at the border with Mauritania. Out of the 187 blood specimen samples collected, 27 were positives by qRT-PCR and 8 were serologically positive for DENV IgM. Serotyping using qRT-PCR reveals that isolates were positive for DENV-2. A subset of DENV-2 positives samples was selected and subjected to full genome sequencing followed by phylogenetic analysis. Analysis of 06 nearly completed genome sequences (n= 6) revealed that isolates belong to the cosmopolitan genotype and are closely related to the Mauritanian strains detected between 2017 and 2018 and those detected in many West African countries such as Burkina Faso or Cote d’Ivoire. Our results suggest a transboundary circulation of the DENV-2 cosmopolitan genotype between Senegal and Mauritania and call for a need of coordinated surveillance of arboviruses between these two countries. Interestingly, high level of homology between West African isolates highlights endemicity and call for a set-up of sub-regional viral genomic surveillance which will lead to a better understanding of viral dynamic, transmission and spread across Africa.

The X-ray induced spin crossover transition of an Fe(II) molecular thin film in the presence and absence of a magnetic field has been investigated. The thermal activation energy barrier in the soft X-ray activation of the spin crossover transition for [Fe{H2B(pz)2}2(bipy)] molecular thin films is reduced in the presence of an applied magnetic field, as measured through X-ray absorption spectroscopy at various temperatures. The influence of a 1.8 T magnetic field is sufficient to cause deviations from the expected exponential spin state transition behavior that is measured in the field free case. We find that orbital moment diminishes with increasing temperature, relative to the spin moment in the vicinity of room temperature.

Dengue virus is becoming a major public health threat worldwide principally in Africa. From 2016 to 2020, 23 outbreaks were reported in Africa principally in West Africa. In Senegal outbreak are reported yearly since 2017 ; data about the circulating serotypes and their spatial and temporal distribution are limited to 2017 – 2018 period. Herein we describes up to date molecular surveillance of circulating DENV serotypes in Senegal between 2019 to 2023 and their temporal and spatial distribution around the country. For this purpose collected suspected DENV infections samples were subjected to dengue detection and serotyping using RT-qPCR methods. Positive samples subjected to temporal and spatial mapping. Subset of DENV+ samples were then sequenced and subjected to phylogenetic analysis. Results show a co-circulation of three DENV serotypes with a overall predominance of DENV-3 followed by DENV-1 with scarce cases of DENV-2 from 02_2019 to 02_2022. Interestingly data shows extinct of both serotype 1 and serotype 2 and the only circulation of DENV-3 from March 2022 to July 2023. At the genotype level analysis shows that sequenced strains belong to same genotype as previously described DENV-1 belong to genotype V, DENV-2 to cosmopolitan genotype and DENV-3 to Genotype III. Interestingly newly obtained DENV 1-3 sequences cluster in different clades within genotypes. This co-circulation of strains belonging to different clades could have effect on virus epidemiology and transmission dynamic. Overall our results highlight DENV serotypes replacement by DENV-3 accompanied by wider geographic distribution in Senegalese regions. All unmentioned results highlight the importance of virus genomic surveillance and call for further fitness studies using both in vitro and in vivo model as well as in depth phylogeographic study to uncover the virus dispersal patterns across the country.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

Bottlenose dolphin (Tursiops truncatus) belongs to the Cetartiodactyla and similarly to the other cetaceans represent the most successful mammalian colonization of the aquatic environment. Here we report a genomic, evolutionary and expression study of Tursiops truncatus T cell receptor beta (TRB) genes. Although the organization of the dolphin TRB locus is similar to that of the other artiodactyl species, with three in tandem D-J-C clusters located at its 3’ end, its uniqueness is given by the reduction of the total length due essentially to the absence of duplications and to the deletions that have drastically reduced the number of the germline TRBV genes. We have analyzed the relevant mature transcripts from two subjects. The simultaneous availability of rearranged TRA and TRB cDNA from the peripheral blood of one of the two specimens, and the human/dolphin amino acids multi sequence alignments, allowed us to calculate the most likely interactions at the protein interface between the alpha/beta heterodimer in complex with major histocompatibility class I (MH1) protein. Interacting amino acids located in the CDR-IMGT of the dolphin variable V alpha and beta domains were identified. According to comparative modelisation, the atome pair contact sites analysis between the human MH1 grove (G) domains and the TR V domains confirms conservation of the structure of the dolphin TR/pMH.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.