Valsartan (Val) is an important antihypertensive medication with side effects such as dizziness and angioedema. These constraints are due to the low oral bioavailability and relatively short half-life. The goal here is to incorporate Val into a mixed micelles system that can enhance transdermal delivery. Thin-film hydration and micro-phase separation were used to produce Val-loaded mixed micelle systems. A variety of factors, including surfactant type and drug-to-surfactant ratio, were optimized to produce micelles with low size and high Val entrapment efficiency (EE). The size, polydispersity index (PDI), zeta-potential, and drug entrapment efficiency of the prepared micelles were all measured. The drug release profiles in vitro were assessed using dialysis bags, and the permeation through abdominal rat skin was assessed using a Franz diffusion cell. All formulations had high EE levels exceeding 90% and low particle charges. The micellar sizes ranged from 107.6 to 191.7nm, with average PDI values of 0.3. The in vitro release demonstrated a uniform slow rate that lasted one week with varying extents. F7 demonstrated a significant (P < 0.01) transdermal efflux of 68.84 ± 3.96 µg/cm2/h through rat skin when compared to the control. As a result, the enhancement factor was 16.57. Val-loaded mixed micelles were successfully prepared using two simple methods with high reproducibility, and extensive transdermal delivery was demonstrated in the absence of any aggressive skin modifying enhancers.

The experiment was carried out during October 2022 to January 2023 at Mae Hea Agricultural Research, Demonstration and Training Center, Faculty of Agriculture, Chiang Mai University, Chiang Mai Province, Thailand; latitude: 18° 44′ 36″ North, Longitude: 98° 57′ 50″ East, and an al-titude 304 msl. Evaporative greenhouse, 9.6 x 40 square meters, with 8 planting troughs was prepared, Sensors and Internet of Things (IoT) system were installed to monitor continuously vital parameters, collect data, and send timely alerts to facilitate problem resolution. The data were displayed via IoT platform dashboard. An average air temperature, light intensity, media moisture and CO2 concentration in the greenhouse during 4 months was 21.1 ◦C, 12,948 Lux, 2 kPa and 495 ppm, respectively. The average maximum temperature in the evaporative greenhouse was 29.6 ◦C, which 4.2 ◦C lower than outside; 33.8 ◦C. Root-zone cooling of the strawberry planting was de-signed as factorial 3x4 in completely randomized design (CRD). Factor A was the short-day strawberry cultivars: 1) “Pharachatan 88” 2) “Pharachatan 80” and 3) “Akihime”. Factor B was the root-zone cooling treatments: 1) normal water dripping (NWD) 2) cold water dripping (CWD) 3) cold water dripping + cold water piping (CWD+CWP) and 4) normal water dripping + cold water piping (NWD+CWP). The results revealed that there was an interaction between the two factors on canopy width, leave width, crown diameter, number of flowers, fruit qualities and fruit color, whereas plant height, leaves length, SPAD and number of inflorescences were not affected by the interaction between the two factors. Four months after the experiment, the root-zone cooling treatments had no effect on chlorophyll contents, whereas “Pharachatan 80” had lower chlorophyll content than others. The CWD+CWP treatment could reduce 2 °C of root-zone temperature and leading to promote vegetative and reproductive growth in strawberry plants. Anyhow, without the root-zone cooling treatment, “Akihime”and “Pharachatan 88” still could produce flowers and yield, but “Pharachatan 80” could not. Furthermore, “Akihime” seemed appreciable in flowering, TSS and yield as compared to others.

In this work, anchoring of cinchona derivatives to trifunctional cores (hub approach) was demonstrated to obtain size-enlarged organocatalysts. By modifying the cinchona skeleton in different positions, we prepared four C3-symmetric size-enlarged cinchona derivatives (hub-cinchonas), which were tested as organocatalysts and their catalytic activities were compared with the parent cinchona (hydroquinine) catalyst. We showed that in the hydroxyalkylation reaction of indole, hydroquinine provides good enantioselectivities (up to 73% ee), while the four new size-enlarged derivatives gave significantly lower values (up to 29% ee) in this reaction. Anchoring cinchonas to trifunctional cores was found to facilitate nanofiltration-supported catalyst recovery using PolarClean alternative solvent. The C3-symmetric size-enlarged organocatalysts were completely rejected by all the applied membranes, whereas the separation of hydroquinine was found to be insufficient using organic solvent nanofiltration. Furthermore, the asymmetric catalysis was successfully demonstrated in the case of Michael reaction of 1,3-diketones and trans-β-nitrostyrene using Hub3-cinchona (up to 96% ee) as a result of the positive effect of the C3-symmetric structure using a bulkier substrate. This means an increased selectivity of the catalyst in comparison to hydroquinine in the latter Michael reaction.

The incidence of human papillomavirus-related head and neck squamous cell carcinoma (HPV+HNSCC) has reached epidemic levels in the last decade. While prophylactic vaccines will prevent future HPV infections, there are currently no HPV-specific antiviral drugs to treat current HPV infections or HPV+HNSCC. HPV replication and transcription are promising targets for anti-HPV therapeutics, as modulation of these processes can alter expression levels of HPV E6 and E7, which are required for maintenance of the transformed phenotype. This is a particularly attractive target in in HPV+HNSCC where the majority of tumors have episomal genomes replicating in an E1-E2 dependent manner. Here, we describe a model system to study HPV16 E1-E2 mediated DNA replication and HPV16 E2-mediated transcriptional activation and repression in multiple HNSCC cell lines. Our results demonstrate that low levels of IFIT1 are required for HPV16 replication in HNSCC cell lines and HPV16 E1 interacts with IFIT1. Restoration of IFIT1 expression in HNSCC cell lines partially inhibits HPV16 E1-E2 mediated replication. This system can be used to study replication and transcription by HPV16 E1 and E2 in HNSCC as well as be utilized to screen potential anti-HPV therapeutics that target HPV16 replication and transcription.

Cyclin E2, a member of the cyclin family, is a key cell cycle-related protein. This protein plays essential roles in cancer progression, and as such, an inhibitor of cyclin E2 has been approved to treat several types of cancers. Even so, mechanisms underlying how to regulate cyclin E2 expression in cancer remain largely unknown. The current study found that miR-3687 is up-regulated in clinical bladder cancer (BC) tumor tissues, TCGA database and human BC cell lines. Inhibition of miR-3687 expression significantly reduces human BC cell proliferation in vitro and tumor growth in vivo, which are concurrently with the induction of G0/G1 cell cycle arrest and downregulation of cyclin E2 protein expression. Interestingly, overexpression of cyclin E2 reversed the inhibition of BC proliferation induced by miR-3687. Mechanistic studies suggest that miR-3687 could bind to the 3'-UTR of foxp1 mRNA, downregulates FOXP1 protein expression, and in turn promotes the transcription of cyclin E2, thereby promoting the growth of BC cells. Collectively, the current study not only establishes a novel regulatory axis of miR-3687/FOXP1 in regard to regulation of cyclin E2 expression in BC cells, but also provides strong suggestive evidence that miR-3687 and FOXP1 may be potentially promising targets in therapeutic strategies of human BC.

Background. COVID-19 patients suffer from hypercoagulation and activated immune-inflammatory pathways. This study was performed to assay serum complement C3 and C4, and thromboxane A2 (TxA2) and prostacyclin (PGI2) in association with chest CT scan anomalies (CCTAs) and peripheral oxygen saturation (SpO2) Methods. Serum levels of C3, C4, TxA2, and PGI2 were measured by ELISA and albumin, calcium, and magnesium by spectrophotometric method in 60 COVID-19 patients and 30 controls. Results. C3 and C4 are significantly decreased and TxA2 and PGI2 significantly increased in COVID-19 patients as compared with controls. Neural networks showed that a combination of C3, albumin, and TxA2 yielded a predictive accuracy of 100% in detecting COVID-19 patients. SpO2 was significantly decreased in COVID-19 patients and was inversely associated with TxA2 and PGI2, and positively with C3, C4, albumin, and calcium. CCTAs were accompanied by lower SpO2 and albumin, and increased PGI2 levels. Patients with positive IgG results show significantly higher SpO2, TxA2, PGI2, and C4 levels than IgG negative patients. Conclusion. Hypoalbuminemia, which is strongly associated with lung lesions and lowered peripheral oxygen saturation, is characterized by increased TxA2, suggesting that interactions between immune-inflammatory pathways and platelet hyperactivity participate in the pathophysiology of COVID-19 and consequently may play a role in enhanced risk of hypercoagulability and venous thromboembolism. These mechanisms are aggravated by lowered calcium and magnesium levels.

Hepatitis C Virus (HCV) is the main causative factor for liver cirrhosis and the development of liver cancer, with a confirmed ~ 180 million infections worldwide. E2 is an HCV structural protein responsible for virus entry to the host cell. Heat Shock Protein A5 (HSPA5), also termed BiP and GRP78, is the master regulator of the unfolded protein response mechanism, where it mainly localizes in the lumen of the Endoplasmic Reticulum (ER) in normal conditions. Under the stress of HCV infection or carcinogenesis, HSPA5 is upregulated. Consequently, HSPA5 escapes the ER retention localization and translocates to the cytoplasm and plasma membrane. Pep42, a cyclic peptide that was reported to target explicitly cell-surface HSPA5 in vivo. Owing to the high sequence and structural conservation between the C554-C566 region of HCV E2 and the Pep42, then we propose that the HCV E2 C554-C566 region could be the recognition site. The motivation of this work is to predict the possible binding mode between HCV E2 and HSPA5 by implementing molecular docking to test such proposed binding. Docking results reveal the high potent binding of the HCV E2 C554-C566 region to HSPA5 substrate-binding domain β (SBDβ). Moreover, the full-length HCV E2 also exhibits high binding potency to HSPA5 SBDβ. Defining the binding mode between HCV E2 and HSPA5 is of significance, so one can interfere with such binding and reducing the viral infection.

Citron watermelon (Citrullus lanatus var. citroides) is an underexploited and under-researched crop species with potential to contribute to crop diversification in sub-Saharan Africa and beyond. The species is commonly cultivated in the drier parts of Southern Africa, mainly by smallholder farmers who maintain a wide range of landraces. Understanding the molecular and morpho-physiological basis for drought adaptation of Citron watermelon in these dry environments can aid in screening local germplasm, identification of suitable traits for crop improvement and improving food system resilience among smallholder farmers by adding to crop diversification. This paper reviews literature on drought adaptation of C. lanatus spp. (C3 xerophytes), using the systematic review approach. The review discusses; (i) the potential role of citron watermelon in adding to crop diversification, (ii) alternative food uses and potential by-products that can be processed from citron watermelon and (iii) the role of Sub-Saharan farmers as key actors in conserving citron watermelon germplasm and biodiversity. Finally, the review provides a summary of significant findings and identifies critical knowledge gaps for further research.

The processing of alkanes (the main components of natural gas) for obtaining of industrially important chemical products is one of the most urgent environmental problems, because the major share of raw materials are burned in torches. Therefore, the main goal of the work is the development of catalysts and conditions for obtaining of important petrochemical products from light alkanes. For the preparation of catalysts, Mo, Cr and Ga oxide catalysts as well as catalysts based on heteropoly compounds, supported on natural materials were used. The catalysts were prepared by the capillary impregnation method and used in oxidative conversion in a flowing unit while varying the process conditions. It has been determined that 5 and 10% MoCrGa catalysts are optimal for obtaining of liquid and gaseous products, and 1% catalyst is more favorable for the synthesis of gaseous products. Supported catalysts from heteropoly acid Н₃PW₁₂O₄₀ are highly active in oxidative dehydrogenation and cracking processes, which are concurrent. High activity is caused by dispersity of catalysts, formation of crystal hydrates and amorphous phase of heteropoly acid in a condition of interaction with carrier. Maximum yield of C₂H₄ - 35.2% at 973 K, C₃H₆ – 20.0% and C₄H₈ – 14.3% at 773 К were observed.

Oxidative stress and inflammation are basic pathogenic factors involved in tissue injury, pain, as well as acute and chronic diseases. Since long-term uses of steroids and non-steroidal anti-inflammatory drugs (NSAIDs) cause severe adverse effects, novel effective materials with minimal side effects are required. In this study, polyphenol content and antioxidative activity of rosebud extracts from 24 newly-crossbred Korean roses were analyzed. Among them, Pretty Velvet rosebud extract (PVRE) were found to contain high polyphenols and to show in vitro antioxidative and anti-inflammatory activities. In RAW 264.7 cells stimulated with lipopolysaccharide (LPS), PVRE down-regulated mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and thereby decreased nitric oxide (NO) and prostaglandin E2 (PGE2) production. In an air-pouch inflammation model, treatment with PVRE decreased λ-carrageenan-induced tissue exudation, infiltration of inflammatory cells including neutrophils, monocytes and lymphocytes, and tumor necrosis factor-α and interleukin-1β concentrations, as achieved with dexamethasone (a steroid). Notably, PVRE also inhibited PGE2, similar to dexamethasone and indomethacin (an NSAID). The anti-inflammatory effects of PVRE were confirmed by microscopic findings, attenuating tissue erythema, edema, and inflammatory cell infiltration. These results indicate that PVRE exhibits dual (steroid- and NSAID-like) anti-inflammatory activities by blocking both the iNOS ― NO and COX-2 ― PG pathways, and that PVRE could be a promising anti-inflammatory material for diverse issue injuries.

Breast cancer is the most widespread malignancy in women from corner to corner of the world. Nanostructured lipid carrier (NLC) proved its efficacy in the treatment of cancer. NLC loaded with Imatinib (IMA) (NANIMA) was prepared and evaluated for in vitro efficacy in MCF-7 breast cancer cells. Hot homogenization method was used for the preparation of NANIMAs. Aqueous solution of surfactants (hot) was mixed with molten mixture of stearic acid and sesame oil (hot) under homogenization. The prepared NANIMAs were characterized and evaluated for size, polydispersity index, zeta potential, encapsulation efficiency, release studies, stability studies and MTT assay (cytotoxicity studies). The optimized NANIMA revealed particle size of 104.63 ± 9.55 d.nm, PdI of 0.227 ± 0.06 and EE of 99.79 ± 0.03. All NANIMAs revealed slow and sustained release behaviour. The surfactants used in the preparation of NANIMAs exhibited their effects on particle size, zeta potential, encapsulation efficiency, stability studies and release studies. The cytotoxicity studies unveiled 8.75 times increase in cytotoxicity for optimized NANIMA (IC50 = 6 µM) when compared with IMA alone (IC50 = 52.5 µM) on MCF-7 breast cancer cells. After this, NLC containing IMA possibly will be employed for the cure of breast cancer. A lesser amount of IMA loaded NLC will be sufficient than IMA alone for the treatment of breast cancer. Moreover, the patient will exhibit not as much of adverse effects as in case of IMA alone. Consequently, NANIMA could prove to be useful for effective therapeutic outcome in breast cancer treatment.

PHA synthases (PhaC) are grouped into four classes based on the kinetics and mechanisms of reaction. The grouping of PhaC enzymes into four classes is dependent on substrate specificity, according to the preference in forming short chain length (scl) or medium chain length (mcl) polymers: class I, class III, and class IV produce scl-PHAs depending on propionate, butyrate, valerate and hexanoate precursors, while class II phaC synthesize mcl-PHAs based on the alkane (C6 to C14) precursors. PHA synthases of class I, in particular PhaC_Cs from Chromobacterium USM2 and PhaC_Cn/RePhaC1 from Cupriavidus necator/R. eutropha, have been analysed and the crystal structures of the C-domains have been determined. PhaC_Cn/RePhaC1 was also studied by small angle X-ray scattering (SAXS) analysis. Models have been proposed for dimerization, catalysis mechanism, substrate recognition and affinity, product formation and product egress route. The assays based on amino acid substitution by mutagenesis have been useful to validate the hypothesis on the role of amino acids in catalysis and in accommodation of bulky substrates, for the synthesis of PHB co-polymers and medium chain length-PHA polymers with optimized chemical properties.

Far-red fluorescent reporter genes can be used for tracking cells non-invasively in vivo using fluorescence imaging. Here, we investigate the effectiveness of the far-red fluorescent protein, E2-Crimson (E2C), for tracking mouse embryonic cells (mESCs) in vivo following subcutaneous administration into mice. Using a knock-in strategy, we introduced E2C into the Rosa26 locus of an E14-Bra-GFP mESC line, and after confirming that the E2C had no obvious effect on the phenotype of the mESCs, we injected them into mice and imaged them over 9 days. The results showed that fluorescence intensity was weak, and cells could only be detected when injected at high densities. Furthermore, intensity peaked on day 4 and then started to decrease, despite the fact that tumour volume continued to increase beyond day 4. Histopathological analysis showed that although E2C fluorescence could barely be detected in vivo at day 9, analysis of frozen sections indicated that all mESCs within the tumours continued to express E2C. We hypothesise that the decrease in fluorescence intensity in vivo was probably due to the fact that the mESC tumours became more vascular with time, thus leading to increased absorbance of E2C fluorescence by haemoglobin. We conclude that the E2C reporter has limited use for tracking cells in vivo, at least when introduced as a single copy into the Rosa26 locus.

Background: The oldest old people (≥ 85 years) represent the fastest growing age group in Western populations. Knowledge on early outcomes of acute ischemic stroke (AIS) in very old female patients remains limited. Methods: We assessed gender differences and female-specific clinical data and in-hospital mortality in very old patients with AIS. Acute cerebral infarction was diagnosed in 506 very old female patients from a total of 4,600 acute cerebrovascular infarctions available in an ongoing 24-year hospital stroke data bank. A comparative analysis of vital status at discharge (alive versus dead) was performed in terms of cardiovascular risk factors, clinical data, and early outcomes. Results: The overall in-hospital mortality rate was 20.4%. In multivariate analysis, sudden onset, altered level of consciousness, and neurological, respiratory, cardiological or hemorrhagic complications, and lacunar infarcts appeared to be independent predictors of in-hospital mortality. Conclusions: Female patients ≥85 years with AIS are an unfavorable subgroup of stroke patients with a high risk of early mortality, which may be due to comorbidity, stroke subtype distribution, and higher frequency of medical complications. However, the presence of lacunar infarcts showed a significant protective effect.

Lactobacilli are considered an inexhaustible source of potentially bioactive substances; indeed, several products from their metabolism are known to have immunomodulatory and anti-inflammatory activity. Recently, we demonstrated that cell-free supernatants (CFS) obtained from Lactobacillus (L.) acidophilus, L. plantarum, L. rhamnosus and L. reuteri can impair Candida pathogenic potential in an in vitro model of epithelial vaginal infection. This effect could be ascribed to a direct effect of living lactobacilli on Candida virulence and to the production of metabolites which are able to impair fungal virulence. In the present work, stemming from those data, we deepened our knowledge on the CFS from these 4 lactobacilli by performing a metabolomic analysis to better characterize their composition. By using an untargeted metabolomic approach, we detected consistent differences in the metabolites produced by these four different lactobacilli. Interestingly, L. rhamnosus showed the most peculiar metabolic profile. Specifically, after a hierarchical clustering analysis in positive and negative ionization mode, L. rhamnosus showed a specific area of significant overexpressed metabolites that strongly differed from the same area in other lactobacilli. In this area, inosine was identified among the overexpressed metabolites of L. rhamnosus. This molecule has been described to have antioxidant, anti-inflammatory, anti-infective and neuroprotective properties. The biological significance of its overproduction by L. rhamnosus might be important in its probiotic and/or postbiotic activity.

Previous studies found high but very variable levels of tetranor-PGEM and PGD-M (urine metabolites of prostaglandin (PG) E2 and PGD2, respectively) in persons with cystic fibrosis (pwCF), which correlated with the severity of the CF transmembrane receptor (CFTR) genetic alteration. This study aims to assess the potential role of cyclooxygenase (COX)-1 and COX-2 genetic polymorphisms in the variability of PG production, and determine the potential role of PG metabolites as markers of symptoms severity and imaging findings. Thirty healthy subjects and 103 pwCF were included in the study. Clinical and radiological CF severity was evaluated using clinical scoring methods and the extent of bronchiectasis and air trapping were assessed by chest computed tomography (CT). Urine metabolites were measured using liquid chromatography/tandem mass spectrometry. The presence of variants in the COX-1 gen (PTGS1 639 C>A, PTGS1 762+14delA, and COX-2 gen: PTGS2-899G>C (-765G>C) and PTGS2 (8473T>C) were analysed. PGE-M and PGD-M urine concentrations were significantly higher in pwCF than in healthy controls. There were also statistically significant differences between clinically mild and moderate disease and severe disease. Patients with bronchiectasis and/or air trapping had higher PGE-M levels than patients without these complications. The four polymorphisms did not associate with clinical severity, air trapping, bronchiectasis, or urinary PG levels. Taken together, the present study suggests that urinary PG level testing can be used as a biomarker of CF severity. We found no relationship between COX-1 and COX-2 genetic polymorphisms in the variability of PG production.

Chemo-resistance is a substantial challenge in the realm of cancer treatment that requires exploring new therapeutic approaches for effective mitigation. Achieving this goal requires examination of the molecular mechanisms involved in both tumor growth and therapeutic interventions. The potential of NRF2 (Nuclear factor E2-related factor 2) in addressing resistance to chemotherapy across diverse cancer types highlights its value as a promising therapeutic approach based on cancer characteristics. Manipulating the NRF2 signaling pathway has a dual impact, offering promise for both preventing and treating cancer, as well as inhibiting carcinogenesis. The influence of the NRF2/KEAP1 pathway on the progression of tumor formation and resistance to drugs has been well-documented. The interplay between the NRF2 signaling pathway and processes such as endoplasmic reticulum (ER) stress, unfolded protein response (UPR), and autophagy plays a crucial protective role. A deeper understanding of NRF2's role in the modulating these pathways is necessary to develop novel approaches for improving chemotherapeutic efficacy. This article discusses the significance of the NRF2-KEAP1 pathway in preventing/promoting cancer and resistance mechanisms to various chemotherapeutic agents, with a focus on the complementary effects of antioxidants via NRF2-mediated signaling pathways. This study aims to provide a molecular basis for targeting NRF2 via inhibitors/activators as promising therapeutic strategies to overcome chemo-resistance.

Agriculture uses a lot of fuel, fertilizers, pesticides and other substances, while emitting large amounts of GHGs. It is important to optimize these inputs and outputs. One such way is increas-ing crop biodiversity. For this reason, single crops and mixtures of maize, hemp and faba bean as binary and ternary crops were investigated at the Experimental Station of Vytautas Magnus Uni-versity, Lithuania. Results showed that consumption of diesel fuel was by the 31-46% higher than in single and 22-35% higher than in binary cultivations was found in a ternary crop. This influenced on the highest energy input or near twice higher than in maize and hemp single crops and maize+hemp binary crop, but similar with binary crops with faba bean. Despite this, the productivity of the trinary crop and, at the same time, the energy output were 2-5 times higher than in other treat-ments. This compensated for higher energy inputs and the energy efficiency ratio. In ternary crop, energy productivity was from 1.1 to 2.8 times higher and net energy was by 1.9-5.3 times higher than in other tested cultivations. The highest total GHG emissions were obtained in binary maize+hemp and maize+faba bean cultivations (1729.84 and 2067.33 CO2eq ha-1). Ternary cultiva-tion with the highest energy inputs initiated average GHG emission - 1541.90 kg ha-1 CO2eq. For higher efficiency, ternary crop could be sown and harvested in one machine pass. Faba beans should be included in the ter-nary crops, as their biomass takes a significant part of the total biomass produced. We recommend to review the inter-cropped faba bean seeding rates as faba bean seeds have a high energy input equivalent.

Background: Frail elderly patients are exposed to suffering the consequences of heart diseases that are not managed timely such as receiving anticoagulation to prevent stroke associated to atrial fibrillation (AF). Referral to the cardiological outpatient department can be cumbersome as it often requires repeated visits. The aim of this project was to use AF as a showcase to develop and implement CardioShare, a shared-care model where primary care leads patient management, using an easy-to-use compact Holter monitor device with asynchronous remote support from cardiologists. Methods: This complex intervention has been developed during a feasibility phase, tested in a pragmatic cluster-randomization trial (primary care clinic as clusters) and its implementation potential evaluated with an escalation test. Mixed methods were used to evaluate the impact of the intervention, comprising quantitative observations, semi-structured interviews, and workshops. Results: Between February 2020 and December 2021, 314 patients (30% frail) were included of whom 75% had AF diagnosed/not found within 13 days. More than 80% in both groups avoided referral to cardiologists. Patients felt safe and primary care clinicians satisfied. In the escalation test, 58 primary-care doctors used CardioShare to manage 93 patients over three months with remote support from four hospitals in the Capital Region of Denmark. Conclusions: CardioShare was successfully implemented for AF evaluation in primary care.

Cellular oxidation is responsive to external and internal stimulation and is generated via signal molecules in defense mechanisms through networks of cell proliferation, differentiation, intracellular detoxification, bacterial infection, and immune reactions. Oxidative stress is not necessarily harmful per se; it depends on the balance between oxidation and antioxidation cascades, which are induced according to stimuli and can maintain oxygen homeostasis. The reactive oxygen species (ROS) that are generated during influenza virus (IV) infection have critical effects on both the virus and host cells. In this review, we outline the link between viral infection and ROS production, using IV as an example. We introduce the current state of knowledge on the molecular relationship between cellular oxidation mediated by ROS production and various effects of IV infection. We also summarize the potential anti-IV agents that act by targeting oxidative stress.

Background and aims: Only one cohort study exists on the incidence of the risk of malnutrition (RM) in older adults, though numerous cross-sectional –and that cohort research– have reported several risk factors associated with the prevalence and incidence of this condition. However, alterations of body composition and impaired physical performance as exposition variables of RM have not been explored. This study assessed the incidence of RM and determined its association with excess fat mass, low total lean tissue, gait speed, and handgrip strength as exposition variables for RM in community-dwelling older adults. Methods: This is a secondary analysis in older adults (≥60 years old) derived from the study “Frailty, dynapenia, and sarcopenia in Mexican adults (FraDySMex)” a prospective cohort project conducted from 2014 to 2019 in Mexico City. At baseline, volunteers underwent body composition analysis and physical performance tests. Several covariates were identified through comprehensive geriatric assessment. At baseline and follow-up, RM was assessed using the long form of the mini nutritional assessment (MNA-LF) scale. Associations between the exposition variables and RM were assessed by multiple logistic regression. Results: The cohort included 241 subjects. Average age was 75.6±7.8 years; 83.4% were women. The mean follow-up period was 4.1 years, during which 28.6% of subjects developed RM. This condition was less likely to occur in subjects with excess fat mass index, even after adjusting for several covariates. RM was also more likely to occur in subjects with low total lean tissue index, according to both an unadjusted model and after adjusting for the corresponding variables. Regarding the association between RM and gait speed, RM was also more likely to occur in subjects with low gait speed according to both the unadjusted and adjusted models. Similar results were found for RM in relation to low handgrip strength; however, after adjusting for the associated covariates, models 1 and 2 no longer reached the level of significance. Conclusion: The risk of malnutrition diagnosed by MNA-LF was significantly less likely to occur among subjects with excess fat mass, but possibility was significantly higher in those with low total lean tissue and low gait speed after 4.1 years of follow-up in community-dwelling older adults. These results highlight that excess fat mass, low total lean tissue, and low gait speed are first than risk of malnutrition and not vice versa.

Lettuce is a salt-sensitive crop and has a threshold electrical conductivity of 1.3–2.0 mS cm-1 and above that is considered detrimental. As there has been very little information on the physio-logical response of different critical stages of lettuce under different salt stress (SS), the current study is focused on investigating the effects of SS on the critical physiological traits influencing the carbon assimilation in different growth stages of lettuce. The experiment was conducted in deep-water culture hydroponic system in a greenhouse condition. Four levels of sodium chloride salt treatments (EC: 20, 16, 8, and 1.8 mS cm-1) were applied. During both growth stages (day 11 (GS1) and day 19 (GS2) after salt treatment), the leaf transpiration rate, stomatal conductance, and intercellular CO2 were severely decreased. However, the carbon assimilation rate remained unchanged under SS. Similarly, the water use efficiency increased under the SS. It is concluded that the increasing SS increased stomatal and non-stomatal limiting factors during GS1 suggesting the enhanced limitation in photosynthetic activity while no such trend was observed during GS2. The decreased gm with increased SS at GS1 and GS2 suggested that SS induced the irreversible decrease of gm, which in turn can be responsible for the transient reduction in the Vcmax and Jmax during GS2. Taken together, the evidence from this research recommends that varying the SS levels can significantly affect the physiological performance of lettuce at both growth stages.

Since its 2013 emergence in the Americas, chikungunya virus (CHIKV) has posed a serious threat to public health. Early and accurate diagnosis of the disease, though currently lacking in clinics, is integral to enable timely care and epidemiological response. We developed a dual detection system: a CHIKV antigen E1/E2-based enzyme-linked immunosorbent assay (ELISA) and a lateral flow test using high-affinity anti-CHIKV antibodies. The ELISA was validated with 100 PCR-tested acute Chikungunya fever samples from Honduras. The assay had an overall sensitivity and specificity of 51% and 96.67%, respectively, with accuracy reaching 95.45% sensitivity and 92.03% specificity at a Ct cutoff of 22. As the Ct value increased from 22, ELISA sensitivity decreased. We then developed and validated two lateral flow tests using independent antibody pairs. The sensitivity and specificity reached 100% for both lateral flow tests using 39 samples from Colombia and Honduras at Ct cutoffs of 20 and 27, respectively. For both lateral flow tests, sensitivity decreased as the Ct increased after 27. Because CHIKV E1/E2 are exposed in the virion surfaces in serum during the acute infection phase, these sensitive and specific assays demonstrate opportunities for early detection of this emerging human pathogen.

High Brassicaceae consumption reduces the risk of developing several cancer types, probably due to their glucosinolate amount. Extracts from Sinapis nigra L. and Sinapis alba L. have been obtained from leaves and seeds under different conditions using ethanol/water mixtures because well accepted by food industry. The EtOH/H2O 8:2 mixture gives better yields in glucosinolate amounts from grinded seeds, mainly sinalbin in S. alba and sinigrin in S. nigra. The highest antiproliferative activity in both non-tumour and tumour cell lines was induced by S. alba seeds extract. To evaluate whether Sinapis spp effect was only due to glucosinolate content or it was influenced by the extracts’ complexity, cells were treated with extracts or glucosinolates, in the presence of myrosinase. Pure sinigrin did not modify cell proliferation, while pure sinalbin was less effective than the extract. The addition of myrosinase increased the antiproliferative effects of the S. nigra extract and sinigrin. Antiproliferative activity was correlated to MAPKs modulation, which was cell and extract-dependent. Cell-cycle analysis evidenced a proapoptotic effect of S. alba on both tumour cell lines and of S. nigra only on HCT 116. Both extracts showed good antimicrobial activity in disc diffusion tests and on ready-to-eat fresh salad. These results underline the potential effects of Sinapis spp in chemoprevention and food preservation.

Delay in data transmission is one of key performance indicators (KPIs) of a network. The planning and project value of delay in network management is of crucial importance for the optimal allocation of network resources and their performance focuses. To create optimal solutions, predictive models, which are currently most often based on machine learning (ML), are used. This paper aims to investigate the training, testing and selection of the best predictive delay model for a VoIP service in an Long Term Evolution (LTE) network using three ML techniques - Neural Networks (NN), Support Vector Machines (SVM) and k-Nearest Neighbors (k-NN). The space of model input variables is optimized by dimensionality reduction techniques: RReliefF algorithm, Backward selection via the recursive feature elimination algorithm and the Pareto 80/20 rule. A three-segment road in the geo-space between the cities of Banja Luka (BL) and Doboj (Db) in the Republic of Srpska (RS), Bosnia and Herzegovina (BiH), covered by the cellular network (LTE) of the M:tel BL operator was chosen for the case study. The results show that, in all three optimization approaches, the k-NN model is selected as the best solution. For the RReliefF optimization algorithm, the best model has 6 inputs and minimum relative error (RE), RE=0.109; for the Backward selection via the recursive feature elimination algorithm, the best model has 4 inputs and RE=0.041; and for the Pareto 80/20 rule, the best model has 11 inputs and RE= 0.049. The comparative analysis of the results concludes that according to observed criteria for the selection of the final model, the best solution is an approach to optimizing the number of predictors based on the Backward selection via the recursive feature elimination algorithm.

The article aims to find potential biomarker for the detection of tubular damage in pediatric neurogenic bladder (NB) by investigating urinary levels of liver-type fatty acid-binding protein (uL-FABP). This prospective analysis was conducted on two groups: 42 children with NB and 18 healthy children. The uL-FABP concentrations were measured using ELISA methods. The children’s medical charts were analyzed to determine age, sex, anthropometric measurements, activity assessment using Hoffer’s scale and renal function parameters. The results revealed that the uL-FABP/creatinine ratio was higher in the studied group compared with the reference group. A significant positive correlation between uL-FABP and proteinuria was found. Children with a history of vesicoureteral reflux (VUR) tended to have elevated uL-FABP. In conclusion, uL-FABP may be considered a potential tubular damage biomarker in children with NB. Proteinuria and history of VUR may be the factors influencing uL-FABP.

Background: The management of erectile dysfunction (ED) shows several grey zones and new treatments for reduce the percentage of patients who discontinued the treatment are required. Here, we aim to evaluate the role of a natural mixture of named Icarifil (L-Citrulline, L-Carnitine, Eruca vesicaria, Panax ginseng, Tribulus terrestris, Turnera diffusa, Taurine, Vitamin E, Zinc) in the management of patients with ED. Methods: From September 2022 to March 2023, all patients attending 3 urological institutions due to ED were randomized to receive: Icarifil 1 sachet every 24 h (Group 1) or Icarifil 1 sachet + tadalafil 5 mg 1 tablet every 24 h (Group 2) or tadalafil 5 mg 1 tablet daily (Group 3), for 3 months. All patients underwent urologic visit and dedicated questionnaires (IIEF-5, SEP-2, SEP-3) at the enrollment and at the follow-up evaluation (3 months). Patient Reported Outcomes (PROs) at the follow-up evaluation were used. Primary endpoint was the difference in the questionnaires at the follow-up visit when compared with enrollment among the study groups. Results: In the per-protocol analysis, 52 patients in the Group 1, 55 in the Group 2 and 57 in Group 3 have been analyzed. At the follow-up evaluation, IIEF-5 have been improved in all the 3 Groups between enrollment and follow-up evaluation, but a statistically significant difference has been reported between Group 2 (+7.4) versus Group 1 (+4.1) or 3 (+5.1), (p&lt;0.001; p&lt;0.001). Moreover, 47 patients (94.0%) in the Group 2 showed an improvement in the SEP questionnaires, when compared with the baseline, while 29 in the Group 1 (56.9%) and 42 in the Group 3 (82.3%) with a statistically significant difference (p=0.004; p=0.003) among the Groups. The PROs analysis reported a better efficacy and patients’ satisfaction in Group 2 when compared with Group 1 or 3. Conclusions: In conclusion, Icarifil is able to improve penile erectile function in mild–moderate ED and it is able to significantly improve the clinical efficacy of tadalafil 5 mg daily use. Icarifil could be represent an interesting alternative treatment in patients experiencing adverse effects or with contraindications for chronic treatment with PDE5-is.

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

Thirteen benzylethylenearyl ureas and one carbamate have been designed, synthesized and biologically evaluated as regards their antiproliferative activity on tumor cell lines HEK-293 and A-549 and on the immune and endothelial Jurkat T cells and HMEC-1, respectively. A relationship between the structure of the synthetic compounds and their antiproliferative activity has been established. Compounds C.1, C.3, C.12 and C.14 were chosen for further biological studies in order to determine their potential as oncoimmunomodulating agents. Some compounds exhibited significant inhibitory effects on both total PD-L1 and VEGFR-2 in HT-29 cell line, showing urea C.12 active against both targets. Some compounds could reduce more than 50% of cancer living cells, compared to non-treated ones, when assessed in co-cultures using HT-29 and THP-1 cells. In addition, these compounds showed no effect on the immune cell viability and significantly reduce CD11b expression, which is a promising target for immune modulation in anti-cancer therapies.

Water stress is one of the main factors affecting the development of agricultural crops. An inno-vative alternative to improve tolerance to water stress is the application of biostimulants. In the present study, the efficacy and physiological and biochemical responses of different biostimulants were evaluated in beans under moderate and severe stress. The treatments consisted of three types of irrigation: FC100, without water stress, FC75, irrigation reduced by 25% (moderate water stress) and FC50, irrigation reduced by 50% (severe water stress). In the treatments with water deficit, foliar biostimulants were applied: zinc oxide nanoparticles plus chitosan, Codasil®, Osmoplant®, Stimplex® and salicylic acid. Foliar application of ZnO + chitosan nanoparticles benefited biomass accumulation and yield under moderate water stress (FC75) and Codasil® and Osmoplant® under severe water stress (FC50). Proline, free sugars and gas exchange were higher under the application of ZnO + chitosan nanoparticles under moderate water stress and under Codasil® and Osmoplant® under severe water stress. Depending on the severity of water stress, ZnO + chitosan nanoparticles, Codasil® and Osmoplant® are viable products to increase tolerance in green bean cv. Strike plants.

There are many medicinal plants that have various medicinal properties in their different parts. The medicinal plants are major backbone of pharmaceutical industries. In this article we compare the antioxidants properties from various plants parts (root, stem, leaf, flower and bark) of the most important medicinal plant, Justicia adhatoda L. Various plant parts showed the good amount of antioxidant properties. These results enhance the medicinal properties of this plant due to the presence of good amount of antioxidants; among all the plant parts leaves and flowers showed maximum natural antioxidants, hence the study could be saying that this plant has good efficacy of antioxidants.

The precise mathematical description of gaze patterns is still an unsettled matter of debate. This can, consequently, affect the analysis of this type of data in its practical applications. In this scope, we show evidence that a Lévy-flight description of eye-gaze trajectories is not only appropriate but its scale invariant properties are remarkably useful to assist in diagnosing children with Attention Deficit and Hyperactivity Disorder (ADHD), alongside with the usual cognitive tests. Using this picture, we find that the distribution of the characteristic exponent of Lévy-flights statistically is different in children with ADHD. Furthermore, we observe that these children deviate from a strategy that is considered optimal for searching processes, in contrast to non-ADHD children. We focus on the case where both eye-tracking data and data from a cognitive test are present and show that the study of gaze patterns in children with ADHD can help in identifying this condition. Since eye-tracking data can be gathered during cognitive tests without needing extra time-consuming specific tasks, we argue that it is in prime position to provide assistance in the arduous task of ADHD diagnosing.

Many cancers utilize L-glutamine as a major energy source. This “L-glutamine addiction” involves a well-characterized pathway whereby L-glutamine is hydrolyzed by a glutaminase (GLS) to L-glutamate, which is then converted to α-ketoglutarate, the carbons of which enter the tricarboxylic acid (TCA) cycle. However, mammalian tissues/cancers possess a rarely mentioned alternative pathway (the glutaminase II pathway): L-Glutamine is transaminated to α-ketoglutaramate (KGM), followed by ω-amidase (ωA)-catalyzed hydrolysis of KGM to α-ketoglutarate. Uncertainty may prevail over the name glutaminase II which may be confused with the enzyme named glutaminase 2 (GLS2). Thus, we recently suggested a new name for the glutaminase II pathway, namely the glutamine transaminase-ω-amidase (GTωA) pathway. Herein, we 1) evaluate three recent articles that mention L-glutamine addiction, but not the GTωA pathway, 2) summarize the metabolic importance of the GTωA pathway, including its role in closing the methionine salvage pathway, and 3) as a source of anaplerotic α-ketoglutarate. An advantage of the GTωA pathway [i.e., L-glutamine + α-keto acid + H2O α-ketoglutarate + L-amino acid + +NH4] is that it is irreversible and that there is no net change in redox status, permitting α-ketoglutarate production during hypoxia. Finally, we discuss possible clinical benefits of GTωA pathway inhibitors.

Heteromorphic sex chromosomes are rarely found in plants. They were observed only in 47 species from phylogenetically distant families, suggesting that the evolution of sex chromosomes was independent in these species. It was shown that DNA repeat sequences are one of the major factors driving sex chromosomes evolution, and an accumulation or elimination of the repetitive DNA elements are closely linked with the formation of differences in the sex chromosomes. The goal of this study was to characterize the transposon composition in male and female plants of Cannabis sativa L., Humulus lupulus L. and Humulus japonicus Siebold &amp; Zucc. For the first time, the male and female genomes of H. japonicus as well as male genomes of H. lupulus and C. sativa have been sequenced (there were no open data about them). The analysis of genome-wide sequencing data with using Repeatexplorer2 and author’s scripts was carried out. It was shown that accumulation of Ty3-gypsy may be associated with speciation in Cannabaceae family which is the opposite of the theory of speciation throw whole-genome duplication. Moreover, the sex-specific DNA repeat clusters in C. sativa and H. japonicus were found. The analysis also revealed that the concentration of Tekay, Retand and Ikeros repeats in the Y chromosome of C. sativa is lower than in the X chromosome and the Angela concentration is higher in the Y chromosome.

Gut colonization by multidrug resistant organisms(MDROs) is a risk factor for bloodstream infections(BSI) in the early phase of Hematopoietic Stem Cell Transplantation(HSCT). We evaluated, in an exploratory study, the impact of Lactobacillus plantarum on modulation of the gut microbiome in HSCT patients colonized by MDROs. Participants were allocated to an intervention group(IG=22) who received capsules of L. plantarum(5x109 CFU) twice a day until the onset of neutropenia and a control group(CG=20). The V4 region of the 16S bacterial rRNA gene in 93 stool samples from a subset of 33 patients was sequenced(IG=20 and CG=13). Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) (PICRUSt2) program was used for prediction of metagenome functions. L. plantarum had an average 86%(±11%) drug-target engagement at 43(±29) days of consumption and it was safe, tolerable and associated with an increase in the abundance of the Lactobacillales(p=0.004). A significant increase of Lactococcus and reduction of Turicibacter(p<0.05) were identified on the second-week of L. plantarum use. Although Enterococcus abundance had a greater rise in the CG (p=0,07), there were no significant differences concerning the gram-negative MDROs. No serious adverse effects was reported in the IG. . We observed greater non-significant pyruvate fermentation to propanoate I (p=0.193) relative abundance in the IG comparing with CG. L. plantarum use was safe and tolerable by HSCT patients. Although it may have impact on Enterococcus abundance and reduction of Turicibacter, it has not showed impact on Gram-Negative MDRO abundance in MDRO gram-negative colonized HSCT patients.

Utilization of medicine derived from plants has been documented in various traditional systems of medicines throughout the world for different diseases. Therefore, the current research work was carried out to evaluate the phytochemical and biological potential of Ficus carica L ethanolic leaf extract. For this purpose, physicochemical and phytochemical analysis, total phenolic and flavonoids contents was performed. Antioxidant potential was determined by FRAP, DPPH and H2O2 assay. Proteinase inhibition, heat induced hemolysis and BSA denaturation assay was carried out for inflammation. Antiglycation potential was assessed by fructosamine assay, Congo-red assay and estimation of free carbonyl groups. In-vivo antidiabetic, anti-obesity, effect on liver and kidney were investigated by high fat high sugar diet model. FTIR, HPLC and LCMS/MS analysis was performed to find out the compounds. Tablet based formulation was developed using wet granulation method and tested for physicochemical parameters. Results shows that total phenolic and flavonoids content was (333 mg GAE/g) and (123 mg RE/g) respectively, H2O2 assay shows 35.6% free radical inhibition potential, DPPH assay shows (IC50) inhibitory concentration at 0.58 mg/mL, and 88.769 µg/g Fe2SO4 solution FRAP values. Proteinase inhibition assay, Heat induced hemolysis and BSA-denaturation assay shows percentage inhibition of 28 ± 0.01, 55 ± 0.03 and 51.2 ± 0.05 respectively. In Antiglycation activity β-amyloid formation assay shows absorption of 0.017, Fructosamine assay shows inhibition of 19.4±0.06 and free carbonyl group estimation shows inhibition of 17.0±0.03. In in-vivo study FLE at (500 mg/kg) significantly decreased total bilirubin (p ≤ 0.001), decreased (p ≤ 0.05) alanine transferase, aspartate aminotransferase, alkaline phosphatase, decreased blood glucose, triglycerides and total cholesterol (p ≤ 0.01) while HDL (p ≤ 0.01) was significantly increased in comparison to obesity and diabetic-obesity groups. Different functional groups presence was confirmed by FTIR spectrum. HPLC analysis revealed the existence of ferulic acid, rutin, chlorogenic acid, coumarin and thymoquinone and these results are corelated by LC-MS/MS. Pre-compression characterization showed angle of repose (33.04°), bulk density (0.54 g/cm3), tapped density (0.73 g/cm3), compressibility index (35.179 %) and Hausner’s ratio (1.35), while the post-compression characterization showed weight variation 826±4.17 mg, thickness 10.50±0.25 kg/cm2, friability 0.57 %, and disintegration time 8.19 min. From the above results it is concluded that F. carica L. leaves extract has strong antioxidant, antidiabetic and hypolipidemic potential and can be used for an obesity and diabetes treatment.

Modern research achievements support health-promoting effects of natural products and diets rich in polyphenols. Pomegranate (PG) (Punica granatum L.) contain a considerable number of bioactive compounds that exert a broad spectrum of beneficial biological activities, including antimicrobial, antidiabetic, antiobesity, and atheroprotective properties. In this view, the reviewed literature shows that PG intake might reduce insulin resistance, cytokine levels, redox gene expression, blood pressure elevation, vascular injuries and lipoprotein oxidative modifications. Lipid parameters corrective capabilities of PG-ellagitannins are also sufficiently reported to be significantly effective in reducing hyperlipidemia (TC, LDL-C, VLDL-C, and TAGs), plasma HDL-C concentrations, TC/HDL-C and LDL-C/HDL-C ratio. The health benevolent effects of pomegranate consumption appear to be produced through the amelioration of adipose tissue endocrine function, fatty acid utilization, GLUT receptor expression, paraoxonase activity enhancement, PPAR and NFκB modulation. Although the results from animal experiments are encouraging, human findings published in this field are inconsistent and still limited in many points of view. The present review discusses and provides a critical analysis of PG's bioeffects on metabolic syndrome components, type-2 diabetes, obesity, and dyslipidemia, as well as on some cardiovascular-related diseases. A brief overview of the pharmacokinetic properties, safety, and bioavailability of PG-ellagitannins is also included.

Mycelial cultures of Lentinula edodes, an edible and medicinal mushroom, have been used in our previous research to obtain selenium-containing immunomodulatory preparations. Our current attempts to obtain a new preparation containing both selenium and zinc, two micronutrients necessary for the functioning of the immune system, extended our interest in the simultaneous accumulation of these elements by mycelia growing in media enriched with selenite and zinc(II) ions. Subsequently, we have studied the effects of new L. edodes mycelium water extracts with different proportions of selenium and zinc concentrations on activation of T cell fraction of human peripheral blood mononuclear cells (PBMCs). Flow cytometry analysis was used to measure the expression of activation markers on human CD4+ and CD8+ T cells stimulated by anti-CD3 and anti-CD3/CD28 antibodies (Abs). It was demonstrated that all extracts with different proportions of polysaccharides, selenium and zinc tended to upregulate the expression of all activation markers on both types of T cell populations stimulated in parallel with anti-CD3/anti-CD28 beads, however, statistically significant changes were observed for PD-1 and CD25 antigens on CD8+ T cells. The selenium and zinc content in the examined preparations modified the immunomodulatory activity of mycelial polysaccharides, however, the mechanisms of action of various active ingredients of the mycelial extracts seem to be different.

Vibrio splendidus is the main pathogen infect a wide range of hosts, especially sea cucumber Apostichopus japonicus. Our previous studies had shown that the level of L-glutamic acid (L-Glu) was significantly increased under heat stress and it was one of the best carbon sources that could be used by V. splendidus AJ01. In this study, the effects of exogenous L-Glu on the coelomocyte viability, tissue status and individual mortality of sea cucumbers were analyzed. The results showed that 10 mM L-Glu decreased coelomocyte viability and increased mortality, with tissue rupture and pyknosis, while 0.1 mM L-Glu slightly affected the survival of sea cucumbers without obvious damages at both cellular and tissue levels. Transcriptomic analysis showed that there were 343 upregulated and 206 downregulated genes regulated by exogenous L-Glu. GO analysis showed that differentially expressed genes (DEGs) were mainly enriched in signaling and membrane formation, while KEGG analysis showed that DEGs were significantly enriched in the upregulated endocytosis and downregulated lysosomal pathways. The coelomocyte viability further decreased 20% in the simultaneous presence of exogenous L-Glu and V. splendidus AJ01, compared to that of V. splendidus AJ01 infection alone. Consequently, a higher mortality of sea cucumber was also observed in the presence of exogenous L-Glu challenged by V. splendidus AJ01. Real time reverse transcriptase PCR showed that L-Glu specifically upregulated the expression of the fliC gene, conding the subunit protein of flagellar filament, with promoted swimming motility activity of V. splendidus. Our result indicated that L-Glu should be kept in a state of equilibrium, and the excess L-Glu in the host-pathogen interface would prompt the virulence of V. splendidus via increasing bacterial motility.

Many factors affect the quality of red meat. The aim of the study, carried out on 44 Polish Merino lambs, was analysis of physicochemical traits (pH, meat color, expressed juice, content of moisture, protein, fat, total collagen and fatty acid ) and content of carnosine, taurine, L-carnitine on fresh and meat aged for 7 and 14 d in the longissimus lumborum (LL) and gluteus medius (GM) muscles., Higher (p&lt;0.05) redness value (a*), lower yellowness (b*) were recorded in meat after of aging in gluteus medius muscle. A lower value (p&lt;0.05) of expressed juice was found in both LL and GM after 7 days of aging. The increase (p&lt;0.05) in protein and fat content in both muscle and collagen content in LL was observed in aged meat. There was no difference in fatty acid groups and C18:2 c9, t11 content between GM and LL muscle and fresh and aging meat. A higher TBARS content (p&lt;0.05) was recorded in meat after aging in both GM and LL. The meat aging process increased (p&lt;0.05) the content of carnitine and taurine, while the content of carnosine decreased. In summary the processes that turn muscles into meat in different types of muscles affect the physicochemical characteristics and the content of bioactive ingredients.

After the discovery of Corynebacterium glutamicum from the avian feces contaminated soil, its enigmatic L-glutamate secretion by corynebacterial MscCG-type mechanosensitive channels has been utilized for the industrial monosodium glutamate production. Bacterial mechanosensitive channels are activated directly by increased membrane tension upon hypoosmotic downshock, thus the physiological significance of the corynebacterial L-glutamate secretion has been considered as adjusting turgor pressure by releasing cytoplasmic solutes. In this review, we present information that corynebacterial mechanosensitive channels have been evolutionally specialized as carriers to secrete L-glutamate into the surrounding environment in their habitats rather than osmotic safety valves. The lipid modulation activation of MscCG channels in L-glutamate production can be explained by the “Force-From-Lipids” and “Force-From-Tethers” mechanosensing paradigms and differs significantly from the mechanical activation upon hypoosmotic shock. The review also provides information on the search for possibilities that Corynebacterium glutamicum was originally a gut bacterium in the avian host in the aim of understanding physiological roles of corynebacterial mechanosensing. Corynebacterium glutamicum is able to secrete L-glutamate by mechanosensitive channels in the gut microbiota and help the host brain function via the microbiota-gut-brain axis.

In this study, fig leaves, zeolite and alginate were used to prepare a biocomposite for the adsorption of Pb(II) ions from aqueous solutions. Effects of various parameters on the biosorption process such as pH, temperature, initial lead concentration and contact time have been investigated. Maximum uptake of Pb(II) ions (85%) has been achieved at pH 6, with 25 mg/L of initial concentration and at a temperature of 288.15 K. Among the applied models, the data correlated well with Freundlich and D-R models and it was established that the biosorption was physical in nature. The amount of adsorbed lead per gram of sorbent was found to be 150.3 mg/g. Thermodynamic parameters showed the exothermic heat of biosorption and the feasibility of the process. Results have suggested that the prepared biosorbent possesses promising biosorption potential.

The aim of the study was to analyze the in ovo injection of chemically and biologically synthesized silver nano-particles (Ag NPs) using Brassica oleracea L. var capitate f. Rubra, (BOL) conjugation with L-Arginine (L-Arg) on the immune, muscle growth, survivability and hatchability of the broiler chickens. L-Arg (100 μg) conjugated with 1000 µg of Ag NPs synthesized by (BOL)-extract and L-Arg (100 μg) conjugated with 100 µg of Ag NPs chemically synthesized were injected into fertile eggs at 8d, 14d and 18d of incubation. Living embryo and hatched chicks were calculated. Survivability and hatchability were not affected by the injected dose of L-Arg (100 μg) with 1000 µg (BOL-Ag NPs) and L-Arg (100 μg) with 100 µg (C-Ag NPs) but it significantly improved when the eggs were injected on day 14 of incubation compared with those injected on days 8 or 18. Moreover, the protein expression of muscle development markers such as myogenin and myoD were significantly up-related in 14 d of incubation whereas the heat shock proteins (HSPs) such as HSP-60 and HSP-70 were significantly up-regulated in 18 d incubation. In addition, the in ovo injection on 18 d significantly increased the serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) as well the immunoglobulin (IgM) levels were increased in 14d incubation period in serum at the same concentration.

The aim of the study was to analyze the in ovo injection of chemically and biologically synthesized silver nano-particles (Ag NPs) using Brassica oleracea L. var capitate f. Rubra, (BOL) conjugation with L-Arginine (L-Arg) on the immune, muscle growth, survivability and hatchability of the broiler chickens. L-Arg (100 μg) with 1000 µg (BOL-Ag NPs) and L-Arg (100 μg) with 100 µg (C-Ag NPs) were injected into fertile eggs at 8, 14 and 18 of incubation. Survival and hatched chicks were calculated. Survivability and hatchability were unaffected by the injected dose of L-Arg (100 μg) with 1000 µg (BOL-Ag NPs) and L-Arg (100 μg) with 100 µg (C-Ag NPs) but it significantly improved when the eggs were injected on day 14 of incubation compared with those injected on days 8 or 18. Moreover, the protein expression of muscle development markers such as myogenin and myoD were significantly up-related in 14 d incubation whereas the heat shock proteins (HSPs) such as HSP-60 and HSP-70 were significantly up-regulated in 18 d incubation. In addition, the in ovo injection on 18 d significantly increased the serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) as well the immunoglobulin (IgM) levels were increased in 14-day incubation period in serum at the same concentration. Collectively, these results indicate that injecting L-Arg (100 μg) with 1000 µg of BOL-Ag NPs or L-Arg (100 μg) with 100 µg of C-Ag NPs to eggs at day 14 after incubation could improve their hatchability, survival rate, and muscle growth marker.

The study was done to determine the effect of supplementing different forms of L-methionine (L-Met) and acetate on protein synthesis in immortalized bovine mammary epithelial cell line (MAC-T Cell): Control, L-Met, conjugated L-Met and acetate (CMA), and non-conjugated L-Met and Acetate (NMA). Protein synthesis mechanism was determined by omics method. NMA group had the highest protein content in the media and β-casein mRNA expression levels (P < 0.05). The number of upregulated and downregulated proteins observed were 77 and 62 in CMA group and 50 and 81 in NMA group from 448 proteins, respectively (P < 0.05). NMA and CMA treatments stimulated pathways related to protein and energy metabolism (P < 0.05). Metabolomic analysis also revealed CMA and NMA treatments resulted in increases of several metabolites (P < 0.05). In conclusion, NMA treatment increased protein concentration and expression level of β-casein mRNA in MAC-T cells compared to CMA.

In the international scenario of agriculture, Brazil stands out as the main producer and consumer of common bean (Phaseolus vulgaris L.) The increase in the productive potential of the crop is mainly due to breeding programs. The objective of this study was to estimate genetic parameters, predict genotypic values with REML/BLUP (Restricted Maximum Likelihood/Best Linear Unbiased Prediction) and, based on these values, study the variability in common bean cultivars with carioca and black grain. Twenty three agromorphological descriptors were evaluated, among them grain yield. Deviance analysis detected significant differences between the cultivars in both groups. Selective accuracy (Ac) was considered high for most of the traits. Broad-sense heritability (h_g² ) ranged from 0.05 to 0.72, but it was low for the trait yield (YLD). In the carioca grain group, the h_g² values for the traits related to plant morphology were higher than in the black group. Nevertheless, the h_g² values in the black group were higher in relation to the pod and seed traits. The correlations for YLD were moderate but different in the two commercial groups studied. In the black group, variables related to the seed morphology were correlated with grain yield, and in the carioca group, traits related to seed quantity. Based on the groupings, variability among the cultivars was observed. Three distinct clusters were formed for the carioca group and four for the black group. Based on the predicted genetic values, genetic variability and the most adapted and stable cultivars were detected among the cultivars in the studied environments.

Nitrogen fertilization can provide greater nutritional support and mitigate salt stress in the millet crop. The aim of this study was to evaluate the physiological responses and agronomic performance of millet crops subjected to nitrogen fertilization and irrigation water salinity. The study was carried out in a greenhouse, using a completely randomized design in a 5 x 2 factorial scheme, with 4 rep-lications, with five doses of nitrogen (40; 60; 80; 100 and 120 kg ha-1 of N) and two levels of elec-trical conductivity of the irrigation water: 0.3 and 4.0 dS m-1. We concluded that salt stress in-creased leaf sodium levels and had a negative impact on stalk dry mass and panicle dry, leaf gas exchange, mineral element concentrations (K, P and Ca), and water use efficiency. The use of lower salinity water associated with increased nitrogen fertilization provides greater stalk dry mass and panicle dry, photosynthesis, water use efficiency, chlorophyll index, leaf potassium concentration, and biomass production. Salt stress negatively affected transpiration, stomatal conductance, leaf P and Ca levels, and increased leaf sodium levels as nitrogen fertilization increased in millet plants grown under pot conditions. These results can be used to create a strategy to reduce the negative impact of salt stress associated with the nutrition of millet plants, using nitrogen fertilization.

Malaria remains an important and challenging infectious disease, and novel antimalarials are required. Benzyl isothiocyanate (BITC), the main breakdown product of benzyl glucosinolate, is present in all parts of Tropaeolum majus L. (T. majus) and has antibacterial and antiparasitic activities. To our knowledge, there is no information on the effects of BITC against malaria. The present study evaluates the antimalarial activity of BITC and T. majus seeds, leaves, and stems aqueous extracts. We used flow cytometry to calculate the growth inhibition (GI) percentage of the extracts and BITC against unsynchronized cultures of chloroquine-susceptible Plasmodium falciparum (P. falciparum) 3D7-GFP strain. Extracts and/or compounds with at least 70% GI were validated by IC50 estimation against P. falciparum 3D7-GFP and Dd2 (chloroquine-resistant strain) unsynchronized cultures by flow cytometry, and the resistance index (RI) was determined. T. majus aqueous extracts showed some antimalarial activity higher in seeds than in leaves or stems. BITC’s GI was comparable to chloroquine’s. BITC’s IC50 was similar in both strains, thus a cross-resistance absence with aminoquinolines was found (RI < 1). BITC presented features that could open new avenues for malaria drug discovery.

Keywords: apoptosis; arbutus unedo L; formaldehyde; hippocampus; oxidative stress

In descriptive statistics, U -statistics arise naturally in producing minimum-variance unbiased estimators. In 1984, Serfling considered the distribution formed by evaluating the kernel of the U -statistics and proposed generalized L-statistics which includes Hodges-Lehamnn estimator and Bickel-Lehmann spread as special cases. However, the structures of the kernel distributions remain unclear. In 1954, Hodges and Lehmann demonstrated that if X and Y are independently sampled from the same unimodal distribution, X − Y will exhibit symmetrical unimodality with its peak centered at zero. Building upon this foundational work, the current study delves into the structure of the kernel distribution. It is shown that the kth central moment kernel distributions (k > 2) derived from a unimodal distribution exhibit location invariance and is also nearly unimodal with the mode and median close to zero. This article provides an approach to study the general structure of kernel distributions.

Bacillus subtilis NCD-2 showed a promising biocontrol effect against plant soil-borne diseases, and was developed as a commercial microbial fungicide against cotton verticillium wilt in China. Spores were main ingredient of the fungicide and played the crucial role in biological control of plant diseases. Therefore, the key to reducing the cost of fungicide was to find ways to increase the number of spores of strain NCD-2 during fermentation. In this study, 755 substances were evaluated by Phenotype Microarray technology, and 5 kinds of carbon sources and 1 kind of nitrogen source were found to promote the metabolism of strain NCD-2. Among carbon sources L-arabinose showed strongest ability to promote the bacteria growth and sporulation of strain NCD-2. When L-arabinose was used as a single carbon source, it could increase the bacteria concentration and the sporulation efficiency of strain NCD-2 by 2.04 times and 1.99 times, respectively, compared with D-glucose. Moreover, L-arabinose could significantly decrease the autolysis of strain NCD-2 revealed by microscopy observation. The mechanism for promoting the sporulation by L-arabinose was analysed by RNA-seq sequencing. Results showed that total of 790, 923 and 1270 genes were up-regulated and 639, 850 and 1001 genes were down-regulated under L-arabinose supplies when cultured at 8 h, 12 h and 16 h, respectively. Fourteen differentially expressed genes associated with arabinose transportation and sporulation were selected for qRT-PCR analysis, and the result showed basically consistent expression trend with transcriptome. Notably, genes associated with arabinose metabolism, sporulation, spore resistance to heat and spore coat formation were significantly up-regulated, and genes associated with sporulation-delaying protein were significantly down-regulated under L-arabinose supplies. msmX gene which was involved in arabinose transport in Bacillus genus was deleted, and the mutant decreased the growth and sporulation by 53.71% and 86.46%, respectively, when compared to strain NCD-2 wild type. Complementary of the mutant by importing intact msmX gene could restore the growth and sporulation of the mutant strain. In conclusion, arabinose played an important role in regulating the growth and sporulation of strain NCD-2.

The use of nitrogen fertilizers can be a source of environmental pollution; the use of or-ganomineral fertilizers can become a nutritional source for crops, ensuring sustainability in the production system. Another alternative approach is through the inoculation and co-inoculation of microorganisms. The objective was to evaluate the development, nutrition, and agronomic yield of common bean through fertilization with organomineral formula "FMO" derived from sewage sludge biosolids, combined with Rhizobium tropici inoculation and co-inoculation with Azospirillum brasilense techniques. Three bean cultivars from different commercial groups, Pérola, BRS Esteio, and BRS Pitanga, were tested. They were subjected to organomineral fertilizer application, orga-nomineral fertilizer application combined with seed inoculation with R. tropici and re-inoculation; seed co-inoculation with R. tropici + A. brasilense prior to sowing, and foliar re-inoculation with R. tropici + A. brasilense. Seed inoculation, combined with foliar re-inoculation at the V4 stage, resulted in higher productivity of common bean. The combination of R. tropici with co-inoculation with A. brasilense generally led to increased productivity compared to mineral nitrogen fertilization. The use of organomineral fertilizer alone enabled gains in development, as well as productivity. The Pérola bean cultivar showed better adaptation to the applied treatments.

Bioinformatics analysis of the sequences of orthologous zinc-containing peptidases of the M15_C subfamily revealed the presence of a conserved tryptophan residue near the active site, which is not involved in the formation of the protein core. Site-directed mutagenesis of this Trp114/109 residue using two representatives of the family, L-alanoyl-D-glutamate peptidases of bacteriophages T5 (Calcium-activated EndoT5) and RB49 (EndoRB49, without ion regulation) as an example, and further analysis of the 1H NMR spectra of the mutants showed that a decrease in the volume of the W → F → A residue leads to changes in the hydrophobic core and active center of the protein, and also decreased affinity for regulatory Ca2+ in the EndoT5 mutants. The inactive T5W114A mutant lacks the ability to bind the substrate. In general, the conserved Trp114/109 residue, due to the spatial restrictions of its side chain, significantly affects the formation of the catalytically active form of the enzyme and is critical for catalysis.

Febuxostat (FBX), a selective xanthine oxidase inhibitor, belongs to BCS class II showing low solubility and high permeability with a moderate F value (&lt; 49%). Recently, FBX/L-pyroglutamic acid cocrystal (FBX-PG) was developed with improving 4-fold increase of the FBX solubility. Nevertheless, in vivo pharmacokinetic property of FBX-PG has not been evaluated yet. Therefore, the pharmacokinetic feasibility of FBX in FBX and FBX-PG-treated rats and mice was compared in this study. The results showed that the F values of FBX were 210% and 159% in FBX-PG rats and mice, respectively. The 2.10-fold greater AUC of FBX was due to the increased absorption (i.e., 2.60-fold higher Cmax,1 at 15 min) and entero-hepatic circulation of FBX (i.e., 1.68-fold higher Cmax,2 at 600 min) in FBX-PG rats compared to the FBX rats. The 1.59-fold greater AUC of FBX was due to a 1.65-fold higher Cmax,1 at 5 min, and 1.15-fold higher Cmax,2 at 720 min of FBX in FBX-PG mice than those in FBX mice. FBX was highly distributed in the liver, stomach, small intestine, and lungs in both groups of mice, and the FBX distributions to the liver and lungs were increased in FBX-PG mice compared to FBX mice. The results suggest the FBX-PG has a suitable pharmacokinetic profile of FBX for improving its oral F value.

This study proposed a spatially and temporally improving methodology adopting the Regional Frequency Analysis with L-moments approach to estimate rainfall quantiles from 22787 grids of radar rainfall in Taiwan for a 24-hour duration. Due to limited radar coverage in the eastern region, significant discordant grids were found in the coastal area of the eastern region. A K-means cluster analysis using scaled at-site characteristics was used to group the QPESUMS grids in Taiwan into 22 clusters/sub-regions based on their characteristics. Spatially, homogeneous subregions with QPESUMS data produce more detailed homogeneous subregions with clear and continuous boundaries, especially in the mountain range area where the number of rain stations is still very limited. According to the results of z-values and L-moment ratio diagrams, the Wakeby (WAK), Generalized Extreme Value (GEV), and Generalized Pareto (GPA) distributions of rainfall extremes fitted well for the majority of subregions. The Wakeby distribution was the dominant best-fitted distribution, especially in the central and eastern regions. The east of the northern part and southern part of Taiwan had the highest extreme rainfall for each return period. Both areas were frequently struck by typhoons. By using grid-based (at-site) as the basis for assessing regional frequency analysis, the results show that the regional approach in determining extreme rainfall is very suitable for large-scale applications and even better for smaller scales such as watershed areas. The spatial investigation was performed by establishing regions of interest in small subregions across the northern part. It showed that regionalization was correct and consistent.

Cells actively sense differences in topology, matrix elasticity and protein composition of the extracellular microenvironment and adapt their function and morphology. In this study, we focus on the cross-talk between matrix stiffness and protein coating density that regulate morphology and proliferation dynamics of single myocytes. For this, C2C12 myocytes were monitored on L-DOPA functionalized hydrogels of 22 different elasticity and fibronectin density compositions. Static images were recorded and statistically analyzed to determine morphological differences and to identify the optimized extracellular matrix (ECM). Using that information, selected ECMs were used to study the dynamics before and after cell proliferation by statistical comparison of distinct cell states. We observed a fibronectin density independent increase of the projected cell area until 12 kPa. Additionally, changes in the fibronectin density led to an area optimum at about 2.6 μg/cm, which was confirmed by an independent F-actin analysis, revealing a maximum actin filament to cell area ratio of 7.5 %. The proliferation evaluation showed an opposite correlation between cell spreading duration and speed to the matrix elasticity and protein density, which did not affect the cell cycle duration. In summary, we identified an optimized ECM composition, while independent matrix properties regulate distinct cell characteristics.

The aim of the study was to assess the chemical and biochemical composition of heat-treated dates palm fruits (Phoenix dactylifera L.) cultivated in Algeria and stored under Modified Atmosphere Packaging (MAP). In this research, fresh dates palm fruits at harvest (Phoenix dactylifera L.) have been subjected at heat treatment at 55 ± 2°C for 20 min in a ventilated oven. The samples were packed in specific Polyethylene Terephthalate packaging (PET) bags with a thickness of 2.5 μm under MAP condition. The effect of this heat treatment on date fruits quality was investigated during 5 months of storage at room temperature storage (22 ± 1°C of temperature with 75 to 80% of relative humidity (RH), and 10 ± 1°C with 85 to 90% of RH). Chemical and biochemical composition of the samples were studied. Results indicated that during storage the Brix degree, protein, and vitamin C content changed significantly (p&lt;0.05). The major change was observed for lipid values varied from about 0.02 to 0.06% at 10°C, and 0.04 to 0.07% at 22°C for samples not heat-treated unpacked after 5 months of storage, these results represent a highly significant difference (p&lt;0.01). Harvesting at Tamr stage followed by treating the fruits with heat disinfestation packed in MAP, and storing at 10 ± 1°C showed to be a promising method for maintaining dates fruits storage quality.

For screening excellent lactic acid bacteria (LAB) strains to inhibit Escherichia (E.) coli (ETEC) K88, inhibitory activities of more than 1100 LAB strains isolated from different materials and kept in the lab were evaluated in this study. Nine strains with inhibition zone at least 22.00 mm (including that of hole puncher 10.00 mm) and good physiological and biochemical characteristics identified by 16S DNA gene sequencing and recA gene multiple detection, were assigned to Lactobacillus (L.) plantarum subsp. plantarum (5), L. fermentum (1), L. reuteri (1), W. cibaria (1) and E. faecalis (1), respectively. As investigated for their tolerance abilities and safety, only strain ZA3 possessed high hydrophobicity and auto-aggregation abilities, had high survival rate in low pH, bile salt environment and GI fluids, sensitive to ampicillin, resistant to norfloxacin and amikacin, without hemolytic activity and didn’t carry antibiotic resistance genes, exhibited broad spectrum activity against a wide range of microorganisms, and antibacterial substance may attribute to organic acids, especially lactic acid and acetic acid. The results indicated that the selected strain L. plantarum subsp. plantarum ZA3 could be considered a potential probiotic to inhibit ETEC K88 for further research.

Flower color and color patterns are important traits for ornamental species; for this reason, a comprehensive understanding of the genetic mechanisms underlying these characters is extremely significant for plant breeders. The tulip tree (Liriodendron tulipifera Linn.) is well known for its flowers, odd leaves and tree form. However, the genetic mechanism underlying its flower color remains unknown. In this study, a putative LtuPTOX gene was identified based on multiple databases of differential transcript expression at various developmental stages and the complete genome sequence of Liriodendron. Then, the full-length cDNA of LtuPTOX was derived from tepals and leaves using RACE approaches. Furthermore, the gene structure and a phylogenetic analysis of PTOX as well as AOXs, highly similar homologs in the AOX family, were used to distinguish between the two subfamilies of genes. In addition, transient transformation and qPCR methods were used to determine the subcellular localization and tissue expression pattern of the LtuPTOX gene. Moreover, the expression of LtuPTOX as well as pigment contents was investigated to illustrate the function of this gene during the formation of orange bands on petals. The results showed that the LtuPTOX gene encodes a 358-aa protein that contains a complete AOX domain (PF01768.17). Accordingly, Liriodendron PTOX and AOX genes were identified as only paralogs since they were rather similar in the sequence. LtuPTOX showed chloroplast localization, and expressed in the colored organs such as petals and leaves. In addition, increasing pattern of LtuPTOX transcripts lead to carotenoids accumulation on the orange-band in the development period of flower bud. Taken together, our results provide that LtuPTOX is involved in petal carotenoid metabolism and orange band formation in L. tulipifera. Meanwhile, the identification of this potentially involved gene will lay a foundation for further uncovering the mechanism of flower color formation in L. tulipifera.

In this review, the relevance of plants belonging to the Pedicularis L. genus was explored from different points of view. Particular emphasys was given especially to the phytochemistry and the ethnopharmacology of the genus since several classes of natural compounds have been evidenced within it and several Pedicularis species are well known to be employed in the traditional medicine of many Asian countries. Nevertheless, some important conclusions on the chemotaxonomic and chemosystematic aspects of the genus were also provided for the first time. This work represents the first total comprehensive review on the genus Pedicularis.

Globally, the gastroenteritis or diarrhoea has become a more significant problem today due to infection caused by foodborne/ waterborne pathogen Vibrio cholera. In this concern, an investigation was carried out to evaluate the vibriocidal potential of the different solvent extracts of leaf and rhizome of Maranta arundinacea under in vitro condition. For this, aqueous, methanolic, ethanolic and hexane extracts of both leaf and rhizome of M. arundinacea were tested against the pre-isolated strains of Vibrio cholerae such as SPAB1, SPAB4 and SPAB5 by agar well diffusion and minimum inhibitory concentration (MIC) method. All the solvent extracts of both leaf and rhizome were found to be active against the tried strains of V. cholera however, ethanolic extract showed maximum inhibitory effect against SPAB1 strain with an inhibition zone of 26.23 ± 0.53 mm (MIC of 80.00 ± 10.06 µg/ ml) and 24.27 ± 0.12 mm (MIC of 100.00 ± 12.82 µg/ ml) in rhizome and leaf samples, respectively. Then, the effectiveness was followed in SPAB4 and SPAB5 however, it was not much more significant to that of SPAB1. Therefore, it was suggested that the rhizome and leaf extracts which proved to be potentially effective can be used as the natural alternative for the treatment of diarrhoea caused by Vibrio infection.

Hesperidin is a major flavonoid isolated from citrus fruits that exhibits several biological activities. This study aims to evaluate the effect of hesperidin on cardiovascular remodeling induced by N-nitro L-arginine methyl ester (L-NAME) in rats. Male Sprague-Dawley rats were treated with L-NAME (40 mg/kg); L-NAME plus hesperidin (15 mg/kg), or hesperidin (30 mg/kg), or captopril (2.5 mg/kg) for five weeks (n = 8/group). Hesperidin or captopril significantly prevented the development of hypertension in L-NAME rats. Moreover, hesperidin or captopril alleviated L-NAME-induced cardiac remodeling; increases in wall thickness, cross sectional area (CSA) and fibrosis of left ventricular (LV), and vascular remodeling; increases in wall thickness, CSA, vascular smooth muscle cells and collagen deposition in the aorta. These were associated with reduced oxidative stress markers, tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta 1 (TGF-β1) and enhancing plasma nitric oxide metabolite (NOx) in L-NAME treated groups. Furthermore, up-regulation of tumor necrosis factor receptor type 1 (TNF-R1) and TGF-β1 protein expression and the over-expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) were suppressed in L-NAME rats treated with hesperidin or captopril. These data suggested that hesperidin had cardioprotective effects in L-NAME hypertensive rats. The possible mechanism may involve its antioxidant and anti-inflammatory effects.

The dioecious property of sea buckthorn (Hippophae rhamnoides L.) prevents sex recognition via traditional observation at the juvenile stage, thus impeding breeding and economic cropping; RAPD and SCAR markers were used to identify the sexes. A total of 45 random decamer primers were used to screen genomic DNA pools of staminate and pistillate genotypes for genetic polymorphisms. One female sex-linked marker was identified. D15 (5′-CATCCGTGCT-3′) amplified a particular band of 885 bp, which showed polymorphism among staminate and pistillate genotype plants. The SCAR marker Hrcx-15 was obtained by sequencing the fragment. The alleles of 140 pistillate genotypes were examined but not of the 140 staminate genotypes discerned via taxonomy. Staminate and pistillate genotypes of sea buckthorn plants can be distinguished, using Hrcx-15 as a genetic marker for sex identification and for expediting cultivation for commercial applications.

Historically, Mangifera indica L. cultivations have been widely rooted in tropical areas of India, Africa, Asia and Central America. However, at least 20 years ago its spreading allowed the development of some cultivars, also in Sicily, the South of Italy, where the favorable subtropical climate and adapted soils represent the perfect field to create new sources of production for Sicilian agricultural supply chain. Currently, cultivations of Kensington Pride, Keitt, Klenn, Maya and Tommy Atkins varieties are active in Sicilian island and their products meet the requirements of local and European markets. Mango plants produce fleshy stone fruits rich in phytochemicals with an undisputed nutritional value for its high content of flavonoids, vitamins, micro- and macro-elements, vital for maintaining health. This review provides an overview of the antioxidant, anti-inflammatory and anticancer properties of Mango, a fruit that should be included in everyone’s diet for its multifaceted biochemical actions and nutraceutical potential.

We used atomistic molecular dynamics (MD) simulations to study polyelectrolyte brushes based on anionic α-L-glutamic acid and α-L-aspartic acid grafted on cellulose in the presence of divalent CaCl2 salt at different concentrations. The motivation is the search of the ways to control properties such as sorption capacity and the structural response of the brush to multivalent salts. For this detailed understanding of the role of side chain length, chemical structure and their interplay is required. It was found that in the case of glutamic acid oligomers, the longer side chains facilitate attractive interactions with the cellulose surface, which forces the grafted chains to lie down on the surface. The additional methylene group in the side chain enables side chain rotation enhancing this effect. On the other hand, the shorter and more restricted side chains of aspartic acid oligomers prevent attractive interactions to a large degree and push the grafted chains away from the surface. The difference in side chain length also leads to differences in other properties of the brush in divalent salt solutions. At a low grafting density, the longer side chains of glutamic acid allow the adsorbed cations to be spatially distributed inside the brush resulting in a charge inversion. With an increase in grafting density, the difference in the total charge of the aspartic and glutamine brushes disappears, but new structural features appear. The longer sides allow for ion bridging between the grafted chains and the cellulose surface without a significant change in main chain conformation. This leads to the brush structure being less sensitive to changes in salt concentration.

Let b∈Cn∖{0} be a fixed direction. We consider slice holomorphic functions of several complex variables in the unit ball, i.e. we study functions which are analytic in intersection of every slice {z0+tb:t∈C} with the unit ball Bn={z∈C:|z|:=|z|12+…+|zn|2&lt;1} for any z0∈Bn. For this class of functions there is introduced a concept of boundedness of L-index in the direction b where L:Bn→R+ is a positive continuous function such that L(z)&gt;β|b|1−|z|, where β&gt;1 is some constant. For functions from this class we describe local behavior of modulus of directional derivatives on every ’circle’ {z+tb:|t|=r/L(z)} with r∈(0;β],t∈C,z∈Cn. It is estimated by value of the function at center of the circle. Other propositions concern a connection between boundedness of L-index in the direction b of the slice holomorphic function F and boundedness of lz-index of the slice function gz(t)=F(z+tb) with lz(t)=L(z+tb). Also we show that every slice holomorphic and joint continuous function in the unit ball has bounded L-index in direction in any domain compactly embedded in the unit ball and for any continuous function L:Bn→R+.

L-Theanine, a unique non-protein amino acid, is an important bioactive component of green tea. Previous studies have shown that L-theanine has many potent health benefits, such as anti-anxiety effect, regulation of immune response, relaxing neural tension, reducing oxidative damage. However, little is known concerning whether L-theanine can improve the clearance of mitochondrial DNA (mtDNA) damage in organisms. Here, we reported that L-theanine treatment increased ATP production and improved mitochondrial morphology to extend the lifespan of UVC-exposed nematodes. Mechanistic investigations showed that L-theanine treatment enhanced the removal of mtDNA damage and extended lifespan by activating autophagy, mitophagy, mitochondrial dynamics, and mitochondrial unfolded protein response (UPRmt) in UVC-exposed nematodes. In addition, L-theanine treatment also up-regulated the expression of genes related to mitochondrial energy metabolism in UVC-exposed nematodes. Our study provided a theoretical basis for the possibility that tea drinking may prevent mitochondrial related diseases.

Natural products from medicinal plants, either as pure compounds or as standardized extracts, provide unlimited opportunities for new drug leads because of the unmatched availability of chemical diversity. The objects of the study are medicinal plant raw materials Saussurea sordida Kar&Kir and Saussurea alpina DC. collected from South Kazakhstan during the flowering period in the spring-summer months of 2021. The present study was aimed to investigate the toxic effects acute administration of ethanol extracts from plants S. sordida and S. alpina in male Wistar rats. The ethanol extract by subjected to Phytochemical Screening, Fourier transform infrared spec-troscopy (FTIR) analysis. Phytochemical screening of the extract revealed the presence of phenolic compounds. FT-IR spectroscopic analysis revealed various characteristic band values with various functional groups in the formulation extract such as amines, alcohol, phenol, alkane, alkene, and conjugated acid groups. FT-IR analysis of peak values with various functional compounds such as alcohols, phenols, carboxylic acids, aldehydes, amides, amino acids, anhydrides, esters, ketones, unsaturated aliphatic, aromatics, unsaturated heterocycles, amines, nitro compound, alkanes, al-kenes and sugars. Histological examination of organ samples after studying the chronic toxicity of ex-tracts of two plant species (S. sordida . and S. alpina) revealed no pathological changes. The acute toxicity study revealed no lethal effects and behavioral signs of toxicity at the tested doses indicating that LD50 is greater than 2000 mg/kg. These results show low toxicity of on short-term use and liver toxicity on long-term use. This study helps to predict the formula and structure of active molecules which can be used as medicinal drugs. This result also enhances the traditional usage of S. sordida and S. alpina , which possesses a number of bioactive compounds.

The present study focuses on the yield, chemical composition, and antioxidant activity of essential oils from the leaves and fruit of wild-grown bay laurel (Laurus nobilis L.) in Montenegro. The chemical composition of isolated essential oils was determined by GC/MS and GC/FID. Antioxidant activity was determined using the DPPH assay. The laurel bay essential oil (LEO) yield was 0.88% in fruits and 2.65% in the leaves. The results obtained from this study indicate that the LEOs obtained from the different plant parts (leaves, fruit) display different compositions. Fifty components were identified in LEO leaves, with 1,8-cineole (39.4%), linalool (13.9%), α-terpinyl acetate (11.2%), sabinene (6.7%), methyl eugenol (5.7%), β-pinene (3.2%), and α-pinene (3.1%) being the most abundant ones. Fifty-five components were isolated in LEO fruits with 1,8-cineole (34.2%), α-pinene (6.6%), sabinene (6.1%), β-bisabolene (5.8%), β-pinene (4.8), α-terpinyl acetate (4.5%), and α-terpineol (4.3%) as the main components. However, this study is the first to present the chemical composition of the LEO fruits from Montenegro. The results indicate that the composition of LEO is similar to recent studies from Balkan and Mediterranean areas. The degree of DPPH radical neutralization increased with the incubation time. The LEO isolated from leaves showed better antioxidant activity (EC50 value of 1.43 mg/mL) in comparison to the LEO isolated from fruits (EC50 value of 3.74 mg/mL) during the incubation time of 120 min. Taken together, this study indicates that the LEO from leaves and fruits possesses significant antioxidant activities (possibly due to the high level of 1,8-cineole) and is an important component in the food and pharmaceutical industries. All plant parts of L. nobilis can be successfully used in LEO extraction and isolation.

Inositol is a natural carbocyclic sugar that plays an essential role in regulating the vital cellular functions of plants and animals. Current research has explored methyl derivatives of inositol, reporting on their various biological activities, including antitumor, anti-inflammatory, and anti-osteoporosis activities. Our previous study demonstrated that L-quebrachitol, a methyl derivative of inositol, enhances osteoblastogenesis and bone formation; however, its effect on osteoclastogenesis remains unclear. Consequently, we aimed to investigate the effect of L-quebrachitol on the receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis in pre-osteoclastic RAW 264.7 cells. The results revealed that L-quebrachitol suppressed RANK-mediated signalling, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Fos proto-oncogene (cFOS) pathways, at both gene and protein levels. Moreover, the critical transcription factor for osteoclastogenesis, nuclear factor of activated T cells c1 (NFATc1), was downregulated. Inhibition of osteoclast-associated marker genes encoding proteolytic enzymes, such as tartrate-resistant acid phosphatase (TRAP), matrix metallopeptidase 9 (MMP-9), and cathepsin K, led to reduced formation of TRAP-positive multinucleated cells and resorption pits. These findings demonstrate the dose-dependent inhibitory effect of L-quebrachitol on osteoclastogenesis through the modulation of receptor activator of nuclear factor κB (RANK)-mediated signalling pathways. However, further exploration of L-quebrachitol's potential as a therapeutic approach for osteoporosis is warranted.

Radish (Raphanus sativus L.), a root vegetable belonging to the Brassicaceae family, is considered as one of the representative crops displaying sporophytic self-incompatibility (SSI). The utilization of a self-incompatibility system in F1 breeding can improve the efficiency of cross combinations, leading to a reduction in breeding time and aiding in the development of novel F1 varieties. The successful implementation of this system necessitates the rapid and accurate identification of S haplotypes in parental lines. In this study, we identified a total of 9 S haplotypes among 22 elite radish lines through Sanger sequencing. Subsequently, we obtained sequences for showing 95% similarity to 9 S haplotypes, along with sequences identified by other researchers using BLAST. Following this, multiple sequence alignment (MSA) was conducted to identify SRK and SLG sequence similarities, as well as polymorphisms within the class I, II groups. Subsequently, S haplotype-specific marker sets were developed, targeting polymorphic regions of SRK and SLG alleles. These markers successfully amplified each of 9 S haplotypes. these markers will play a crucial role in the rapid and precise identification of parental S haplotypes in the radish F1 breeding process, proving instrumental in the radish F1 purity test.

Low efficiency and excessive application of nitrogen (N) fertilizers is a frequent problem in agriculture that impacts the environment. Omeprazole (OMP) has been reported to promote N uptake and assimilation in tomato, basil, and corn. However, information about the effect of omeprazole on N assimilation, recovery and N use efficiency parameters for bean plants is limited. Therefore, the objective of the present study was to determine the effect of foliar application of OMP at 0, 1, 10 and 100 µM on nitrogen assimilation, growth, yield, nitrogen use efficiency parameters and recovery percentage in green bean plants. Green bean plants cv. Strike grown in pots were used. Biomass, yield, nitrate reductase activity, photosynthetic pigments concentration, soluble amino acids and protein concentration, total nitrogen concentration, nitrogen use efficiency parameters and nitrogen recovery were analyzed. The results obtained indicate that the application of OMP at 1 µM increased yield, biomass and promoted N assimilation through higher NR enzyme activity, higher amino acid concentration, higher N use efficiency coefficient and allowed a more efficient nitrogen recovery percentage.

Polysaccharide from Ficus carica L. (FCP) exert multiple biological activities, as a biological macromolecule, the available knowledge about the specific structures and mechanisms of biological activity of purified 'Brunswick' fig polysaccharide is currently limited. In the present study, by chemical purification and characteristics identified via specific instruments, and then the impact of FCP on the immunomodulation activity in vitro and in vivo was examined. Structural char-acteristics showed that the molecular weight of the FCP was determined to be 127.5 kDa, the primary monosaccharides present in the FCP were galacturonic acid (GalA), arabinose (Ara), galactose (Gal), rhamnose (Rha), glucose (Glc), and xylose (Xyl) at a ratio of 0.321:0.287:0.269:0.091:0.013:0.011. Based on the investigation of in vitro immunomodulatory ac-tivity, FCP was found to stimulate the production of NO, TNF-α, and IL-6 and increased the pi-nocytic activity of macrophages. Further analysis revealed that FCP activated macrophages by interacting with toll-like receptor 4 (TLR4). Moreover, the in vivo test results indicate that FCP showed significant increase serum pro-inflammatory factors in immunosuppressed mice. Overall, this study suggests that FCP has the potential to be utilized as a novel immunomodulator in the pharmaceutical and functional food industries.

The principal goal of this current study was to isolate a new potential probiotic strain to prepare contamination-free probiotic dahi in a dosage form with desired shelf life. To achieve our target, firstly, probiotic dahi was prepared by a probiotic strain, Lactobacillus acidophilus JB2CON (OM909067) (identified by 16S sequencing) isolated from natural dahi in Dhaka, Bangladesh. The isolate showed five probiotic features by in vitro test and had an antagonistic effect against five different pathogens. More interestingly, it inhibited Escherichia coli (diameter of zone of inhibition = 15.75±0.35) the most. In the time-kill analysis method, E. coli was killed totally within 5.50 hours of fermentation. Finally, the time duration of 14 days was an ideal shelf life, because the probiotic count increased but a slight change in pH did not affect the taste (sourness/acidity) of dahi. The most significant impact of this research is that the probiotic dahi of our experiment might be used as a cheap option for preventing pathogenic Escherichia coli-related foodborne diseases worldwide, especially in underdeveloped countries like Bangladesh.

Nemaline myopathy (NM) is one of the most common forms of congenital myopathy and it is identified by the presence of "nemaline bodies" (rods) in muscle fibers by histopathological exam-ination. The most common forms of NM are caused by mutations in the ACTA1 (Actin Alpha 1) and NEB (Nebulin) genes. Clinical features include hypotonia and muscle weakness. Unfortunate-ly, there is no curative treatment and the pathogenetic mechanisms remains unclear. In this man-uscript, we examined the pathophysiological alterations in NM using dermal fibroblasts derived from patients with mutations in ACTA1 and NEB genes. Patients’ fibroblasts were stained with rhodamine phalloidin to analyze the polymerization of actin filaments by fluorescence microsco-py. We found that patients' fibroblasts showed incorrect actin filament polymerization compared to control fibroblasts. Actin filament polymerization defects was associated with mitochondrial dysfunction. Furthermore, we identified two mitochondrial boosting compounds, linoleic acid (LA) and L-carnitine (LCAR), that improved the formation of actin filaments in mutant fibro-blasts and corrected mitochondrial bioenergetics. Our results indicate that cellular models can be useful to study the pathophysiological mechanisms involved in NM and to find new potential therapies. Furthermore, targeting mitochondrial dysfunction with LA and LCAR can revert the pathological alterations in NM cellular models.

L-asparaginase from bacterial sources have been used in antineoplastic treatments and the food industry. A novel type II L-a sparaginase encoded by the N-truncated gene ansZP21 of halotolerant Bacillus subtilis CH11 isolated from Chilca salterns in Peru was expressed using a heterologous system in Escherichia coli BL21 (DE3)pLysS. The recombinant protein was purified using one-step nickel affinity chromatography and exhibited activity of 234.38 U mg-1 and a maximum catalytic activity at pH 9.0 and 60 °C. The enzyme shows a homotetrameric form with an estimated molecular weight of 155 kDa by gel filtration chromatography. The enzyme half-life at 60 °C was 3 h 48 min, and L-asparaginase retained 50% of initial activity for 24 h at 37 °C. The activity was considerably enhanced by KCl, CaCl2, MgCl2, mercaptoethanol, and DL-dithiothreitol (p-value &lt; 0.01). Moreover, the Vmax and Km were 145.2 µmol mL-1 min-1 and 4.752 mM, respectively. These findings evidence a promising novel type II L-asparaginase for future industrial applications.

Current environmental conditions have prompted agri-food systems to explore new strategies for improving the production of crops in a sustainable manner. The use of omeprazole (OMP) and melatonin (MEL) have been proposed as innovative strategy for crop improvement when applied as biostimulants. However, although their role in the growth of several species has been studied, the results in photosynthetic efficiency parameters are still scarce. Therefore, the objec-tive of the present study was to evaluate the effect of foliar application of OMP and MEL on bi-omass, yield, SPAD values, leaf chlorophyll fluorescence (Fv/Fm), photochemical quenching (qP), Non-photochemical quenching (NPQ), quantum yield of photosystem II (PhiPSII) and elec-tron transport rate (ETR) in bean plants. Treatments were applied separately at doses of 1, 10, and 100 µM, plus a control without application. The results obtained indicate that OMP and MEL were able to increase biomass, yield, SPAD values, as well as photochemical quenching, fluores-cence, and PhiPSII coefficients. Finally, it is concluded that foliar application of OMP and MEL at a dose of 1 and 10 µM can increase photosynthetic efficiency and decrease photoinhibition, which is reflected in higher biomass accumulation and yield in green bean plants cv. Strike.

The rye (Secale cereale L.) crop shows a high potential to collaborate in the sustainability of high Andean livestock because it supports the agroclimatic conditions and acid soils in the Peruvian Andes. The production of green forage, hay, and grain of the rye crop in acid soils was studied with the use of different levels of phosphorus and potassium fertilization in four local rye ecotypes (CBI-001, CSM-001, CJS-001, and CCE-001). The green forage yield (FV) ranged from 32.35 to 53.62 t ha-1, dry matter from 6.05 to 8.56 t ha-1, and hay from 7.0 to 10.36 t ha-1; nutritional levels ranged from 9.02 % to 13.56 % protein and 6.50 to 7.75 % ash levels, mainly with differences between ecotypes (p&lt;0.05). No differences existed between fertilization levels for the number of stems per plant, and flowering stems per plant, and grains per ear (p&gt;0.05). Also, CBI-001 and CCE-001 were superior with 1868.4 and 1797.8 kg ha-1 of grain, respectively (p=0.0072); the use of 60 kg ha of Nitrogen, 120 kg ha-1 of P2O5 and 80 kg ha-1 of K2O gave higher grain and residue yields. The high nutritional value and yield of the rye ecotypes studied in acid soil conditions and without irrigation can be an alternative for livestock feeding and grain production in the rainy season in the Andes as a dual-purpose crop.

The olive wide genetic variability can be used to overcome some of the challenges faced by olive growing, including climate warming. One effect of climate warming in olive is the difficulty to fulfill the chilling requirements for flowering due to high winter temperatures. In the present work, we evaluate seven olive cultivars for their adaptation to high winter temperatures by comparing their flowering phenology in the standard Mediterranean climate of Cordoba, Southern Iberian Peninsula, with the Subtropical climate of Tenerife, Canary Islands. Flowering phenology in Tenerife was significantly earlier and longer than in Cordoba. However, genotype seems to have little influence on the effects of lack of winter chilling temperatures as in Tenerife. This even though the cultivars studied have a high genetic distance between them. In fact, all the cultivars tested in Tenerife flowered the three years under study but showing asynchronous flowering bud burst. Only ‘Arbequina’ showed an earlier day of full flowering than the rest of cultivars. The results observed here could be of interest to refine the phenological simulation models and including of the length of the flowering period. More genetic variability should be evaluated in warm winter conditions to look for adaptation to climate warming.

In the present study the effects of Origanum onites L. extract and essential oil of O. onites L. on the antioxidant status of the liver and brain of mice were investigated. Due to certain disadvantages of essential oils, such as poor solubility, high volatility, sensitivity to UV light and heat, formulation of liposomes with Oregano essentials (OE) was optimized and used in this study. The results demonstrated that the best composition of the lipid carriers and Oregano essentials were conducted in terms of the PDI, mean particle size and EE. The LE4 formulation contained Lipoid S100 of 45 mg, Lipoid S75 of 45 mg and 90 mg of EO. The administration of O. onites L. extract to mice for 21 days significantly decreased glutathione (GSH) level in the liver and brain of mouse as well as malondialdehyde (MDA) concentration in the liver. In the brain of mice MDA level significantly increased after this extract consumption. Whereas liposomes with OE significantly decreased GSH concentration in mouse brain and MDA concentration in mouse liver but increased (p&gt;0.05) GSH level in liver and MDA concentration in brain of mice compared with the control group. It was investigated that both, O. onites L. extract as well as liposomes with OE of this plant material make changes in the antioxidant status in the liver and brain of mice.

Sperm morphology can predict the reproductive male fertilizing potential. This study aimed to determine the morphological and morphometric spermatozoa characteristics from guinea pigs subjected to different photoperiodic stimulation. Thirty F1 guinea pigs were randomly assigned to three photoperiodic treatments: FT1 (photoperiod with 10L/14D LED light), FT2 (photoperiod with 10L/14D sunlight), and FT0 (room without direct light source). At 107 ± 9.8 days of age, sperm concentration and motility were higher in FT0 and FT1 (p<0.05); furthermore, there were no differences in nucleus length and ellipticity between FT0 and FT1, but FT1 was higher in perimeter and nuclear area, while FT0 was higher in roughness, regularity, midpiece length and tail (p<0.01). Expanding acrosome (Type 2) was more frequent in FT2, but there was variation in head measurements between all morphological categories. Pregnancy rate, calving age and mating age were higher in FT0, meanwhile FT1 initiated successful matings earlier (p<0.01). FT0 had a higher fertility rate, and FT1 age of mating and first calving were earlier than FT0 but no pregnancies were reported for FT2. The photoperiodic stimulation can increase the morphometric dimensions of guinea pig spermatozoa, favoring the reproductive characteristics, but sunlight could reduce their size due to heat stress.

Acute lymphoblastic leukemia (ALL) is the most common cancer among children worldwide, characterized by an overproduction of undifferentiated lymphoblasts in the bone marrow. The treatment of choice for this disease is the enzyme L-asparaginase (ASNase) from bacterial sources. ASNase hydrolyzes circulating L-asparagine in plasma, leading to starvation of leukemic cells. The ASNase formulations of E. coli and E. chrysanthemi present notorious adverse effects, especially the immunogenicity they generate, which undermines both their effectiveness as drugs and patient safety. In this study, we developed a humanized chimeric enzyme from E. coli L-asparaginase, which would reduce the immunological problems associated with current L-asparaginase therapy. For these, the immunogenic epitopes of E. coli L-asparaginase (PDB: 3ECA) were determined and replaced with those of the less immunogenic Homo sapiens asparaginase (PDB:4O0H). The structures were modeled using the Pymol software and the chimeric enzyme was modeled using the SWISS MODEL service. A humanized chimeric enzyme with four subunits similar to the template structure was obtained, and the presence of asparaginase enzymatic activity was predicted by protein-ligand docking.

Methylmercury is a neurotoxin present in fish tissues that permeates the blood-brain barrier after consumption. Previous research has shown that methylmercury is harmful to neurons, causing pH alterations, oxidative stress, excitotoxicity, and parenchymal damage. Methylmercury is a known factor of neurological disorders including Alzheimer's and Parkinson's. The method by which methylmercury passes through the blood-brain barrier is largely unknown. According to preliminary studies, one way methylmercury crosses the blood-brain barrier is by creating a complex with L-Cysteine, which facilitates its passage by the LATs system through mimicking another amino acid existing in the body. The human blood-brain barrier was studied using C. elegans as a model organism. It was hypothesized that if methylmercury passes through the blood-brain barrier of C. elegans faster with L-Cysteine present than without L-Cysteine present, the methylmercury's adverse effects (death and locomotive difficulty) will occur sooner. Each of the four experimental groups contained one C. elegans: the control, the L-Cysteine group, the methylmercury group, and the methylmercury and L-Cysteine combination group. The effects of L-Cysteine and methylmercury on C. elegans were studied using three metrics: viability, locomotive disability, and time for locomotive effects to occur. The group that received both methylmercury and L-Cysteine had reduced viability rates and a decreased time for locomotive difficulty to develop, supporting the hypothesis. These findings suggest that L-Cysteine aids methylmercury permeation through the blood-brain barrier. Because the experiment indicates how methylmercury penetrates the blood-brain barrier, these results aid in finding a therapeutic solution to reverse methylmercury neurotoxicity in the brain. Additionally, this study further opens channels into potential therapeutic and preventative measures for dementia, improving morbidity and mortality in neurodegenerative diseases.

Increasing genetic diversity in crop plants has been used for chemical mutagenesis. Through the application of various mutagenic agents, over 430 new varieties have been derived as rice mutants (Oryza sativa L.) Chemical mutagens such as ethyl methane sulphonate (EMS), diepoxybutane derivative (DEB), sodium azide, and gamma ray, x-ray, and quick neutron irradiation have been commonly used to induce a large number of functional variations in rice and others crops. Among chemical mutagens, ethyl methane sulfonate (EMS) is the alkylating agent most widely used in plants because it induces nucleotide substitutions to be extremely frequent, as detected in various genomes. In this study, seeds of potential genotype of the popular variety, (Oryza sativa L. Super Basmati variety) were treated with EMS at concentrations of 0.25%, 0.50%, 0.75%, 1% and 1.5%. Various measurements on the M1 generation determined EMS sensitivity. As concentration of applied EMS increased, will decrease in germination, shoot length, root length, plant height, productive tillers, Panicle Length, Total Spikelet, sterile spikelet and fertility under field conditions were observed in M1 generation as compared to the non-treatment control. Emergence, shoot length, root length, plant height, productive tillers, Panicle Length, Total Spikelet, sterile spikelet and fertility also decreased with increases in EMS mutagenesis in an approximately linear fashion. The LD₅₀ values were observed based on growth reduction of seedlings after EMS treatment with 0.25% and 0.50% on the rice variety (Oryza sativa L. spp.).

This study aimed at the investigation of the effect of substrate preheating on residual stress in laser powder bed fusion using a physics-based analytical model. In this study, an analytical model is proposed to predict the residual stress through the calculation of preheating affected temperature profile and thermal stress. The effect of preheating is super-positioned with initial temperature in the modeling of temperature profile using a moving heat source approach; the resultant temperature gradient is then employed to predict the thermal stress from a point body load approach. If the thermal stress exceeds the yield strength of the material, then the residual stress under cyclic heating and cooling will be calculated based on the incremental plasticity and kinematic hardening behavior of metal. IN718 is used as a material example to pursue this investigation. To validate the predicted residual stress, experimental measurements are conducted using X-ray diffraction on IN718 samples manufactured via laser powder bed fusion under different process conditions. Results showed that preheating of the substrate could reduce the residual stress in an additively manufactured part due to the reduction in temperature gradient and resultant shrinkage stresses. However, the excessive preheating could have an opposite impact on residual stress accumulation. Moreover, the results confirm that the proposed model is a valuable tool for the prediction of residual stress- eliminating the costly experiments and time-consuming finite element simulations.

The widely adopted temperature for solid solution heat treatment (ST) for the conventionally fabricated Inconel 718 is 1100 °C for a hold time of 1 h or less. This ST scheme is however not enough to dissolve Laves and annihilate dislocations completely in samples fabricated with Laser metal powder bed fusion (L-PBF) additive manufacturing (AM)-Inconel 718. In spite this, the highest hardness obtained after aging for ST temperatures (970 - 1250 °C) is at 1100 °C/1h [1]. The unreleased residual stresses in the retained lattice defects are potentially affecting other properties of the material. Hence, this work aims to investigate if a longer hold time of ST at 1100 °C will lead to complete recrystallization while maintaining the strength after aging or not. For this study, L-PBF-Inconel 718 samples were ST at 1100 °C at various hold times (1, 3, 6, 9, 16 or 24 h) and aged to study the effects on microstructure and hardness. In addition, a sample was directly aged to study the effects of bypassing ST. The samples (ST and aged) gain hardness by 43 – 49 %, depending on hold time. A high density of annealing twins evolved during 3 h of ST and the quantity only slightly varies for longer ST.

The infections caused by Chikungunya virus (CHIKV), genus Alphavirus, have become a health problem around the world, due to this virus’s widespread occurrence and high morbidity rate and the absence of vaccines or antiviral drugs. In this study, we analyzed a competitive inhibitor of ornithine decarboxylase—an enzyme that is key in the biosynthesis of polyamines (PAs), N-ω-chloroacetyl-L-ornithine (NCAO), which is a possible inhibitor of CHIKV replication because intracellular polyamines participate in the in vitro transcription and translation of CHIKV. NCAO does not have any cytotoxic effect on C6/36 cells even at 1000 μM at 72 h post-exposure. However, in Vero cells, a cytotoxic effect was present above 380 μM at 48 h post-exposure, which was considered when determining the inhibitory effect on viral replication. In this work, we demonstrate that NCAO inhibits the replication of CHIKV in Vero and C6/36 cells in a dose-dependent manner, causing a decrease in the PFU/mL of at least 4 logarithms (p <0.01) in both cell lines. Viral yields were restored by the addition of exogenous polyamines, mainly putrescine. The HPLC analyses showed that NCAO decreases the content of intracellular PAs, even though mainly spermidines and spermines are present in infected cells. NCAO inhibits CHIKV replication by depleting the intracellular polyamines in Vero and C6/36 cells, suggesting that this compound is a possible antiviral for CHIKV infections.

Cucumber green mottle mosaic virus (CGMMV) is a re-emerging threat to greenhouse cucumber and other Cucurbitaceae crop productions worldwide. This seed-borne virus can easily spread from a contaminated seed to seedlings and to adjacent plants through mechanical contact of the foliage of diseased and healthy plants causing extensive yield losses. Additionally, infection may not be limited to the current crop but may also affect subsequent crops due to the long-term persistence of the virus on contaminated crop residues, greenhouse hard surfaces and soil or soil-less greenhouse substrates. In the present work, three greenhouse trials were conducted to develop an integrated pest management strategy towards controlling CGMMV in commercial cucumber greenhouses, by implementing an effective sanitization program and using resistant and grafted cucumber varieties. Results of sanitization trial highlighted that pressure washing and cleansing with an alkaline foam cleanser has eliminated CGMMV on some of the most heavily infested areas. However, three successive applications of cleanser and disinfectants were essential to completely eliminate CGMMV on porous and uneven surfaces, such as cement alleyway, tray gutter and floor mats. The varietal trial revealed that out of 15 cucumber varieties evaluated, two Mini (‘Katrina’ and ‘Khassib’) and three Long English (‘Sepire’, ‘Bomber’ and ‘LC13900’) had reduced or delayed CGMMV infection spread in the greenhouse but were intermediate in yield. The varieties ‘Sunniwell’ and ‘Bonbon’ were the most tolerant to CGMMV. They showed a high CGMMV infection level without compromising yield. These results proved the need for new productive cucumber varieties with CGMMV resistance. Grafting experiment showed only yield increase in case of grafted ‘Picowell’ over ‘Bonbon’ and not marked CGMMV resistance, which is a much desirable result when the grafting experiments are evaluated for their economic potential. In all, the current experimental trials unfold unique methodologies on CGMMV management in commercial greenhouses that are recommended to the growers to be followed for reducing crop losses and get benefitted on revenue compromise.

Background and objectives: This study were designed to determine uric acid concentration and renal histopathology of M. calabura L. stem bark extract in diabetic rats and to compare the natural product of M. calabura L. stem bark extract with allopurinol. Materials and Methods: A completely randomized design was used for the experiment which consisted of 6 treatment groups, each consisting of 4 rats, as follows: 1) NR, normal rat; 2) KN, diabetic rat (negative control); 3) KP, diabetic rats given allopurinol 10 mg/kg body weight; 4) EM150, diabetic rats given the test extract 150 mg/kg body weight/day; 5) EM300, diabetic rats given the test extract 300 mg/kg body weight/day; and 6) EM450, diabetic rats given the test extract 450 mg/kg body weight/ day. Results: The results showed that M. calabura L. stem bark extract decrease (p<0.05) uric acid levels in diabetic rats and no specific damage to renal proximal tubular cells was seen. Conclusions: It was concluded that M. calabura L. stem bark extract has a potential as an antihyperuricemic in diabetic rats. The recommended does was 300 mg/kg body weight to provide a significant effect on reducing the uric acid level in diabetic rats. Our findings support the use of this plant as a treatment for gout and other inflammatory diseases.

Photosynthetic function, photoprotection, and the response of related proteomics of mulberry (Morus alba L.) seedling leaves under NaCl and NaHCO3 stress with the same Na+ concentration (100 mmol•L-1) were studied by using photosynthetic gas exchange and chlorophyll fluorescence techniques combined with TMT proteomics. The results showed that NaCl stress had no significant effect on photosystem II (PSII) activity in mulberry seedling leaves, and the expressions of the related proteins, OEE3-1 and PPD4, of the PSII oxygen-evolving complex (OEC) and the antenna proteins, CP24 10A, CP26, and CP29, of LHCII in the leaves also increased to varying degrees. The photosystem I (PSI) activity in the leaves of mulberry seedling also increased, and the expressions of some proteins, PsaF, PsaG, PsaH, PsaL, PsaN, and Ycf4, in PSI increased significantly under NaCl stress. Under NaHCO3 stress, the activity of PSII and PSI and the expression of their protein complexes and the electron transfer-related proteins significantly decreased. NaCl stress had little effect on RuBP regeneration during dark reaction in the leaves and the expressions of glucose synthesis related proteins and net photosynthetic rate (Pn) did not decrease significantly. The leaves could adapt to NaCl stress by reducing stomatal conductance (Gs) to increase water use efficiency (WUE). Under NaHCO3 stress, the expression of dark reaction-related proteins was mostly down-regulated, and Gs was significantly reduced, which indicated that non-stomatal factors were important reasons for the significant inhibition of carbon assimilation. In the photoprotective mechanism under NaCl stress, the expression of cyclic electron flow (CEF) related proteins, ndhH, ndhI, ndhK, and ndhM, involved in NAD(P)H dehydrogenase (NDH) and the key enzyme of the xanthophyll cycle, violaxanthin de-epoxidase (VDE) were up-regulated. In addition, the ratio of xanthophyll cycle components (A+Z)/(V+A+Z) was increased. The expressions of proteins FTR and Fd-NiR, which are related to Fd-dependent ROS metabolism and nitrogen metabolism, were also significant up-regulated under NaCl stress, which can effectively reduce the electronic pressure on Fd. Under NaHCO3 stress, the expressions of CEF-related proteins, VDE, ZE, FTR, Fd-NiR, Fd-GOGAT, SGAT, and GGAT, were significant down-regulated, and the photoprotective mechanism, like the xanthophyll cycle, CEF, and photorespiration, might be damaged, resulting in the inhibition of PSII activity and carbon assimilation in leaves of mulberry seedling under NaHCO3 stress.

L-glutamate is one the most important excitatory neurotransmitter at central nervous system level and it is implicated in several pathologies. So, it is very important to monitor its variations, in real time in animal models’ brain. Amperometric biosensors have been used because of their very high temporal and spatial resolution, and because suitable for a short to mid-term implantation. The present study aimed to develop and characterize a new glutamate biosensor design that exploits the selectivity of Glutamate Oxidase (GluOx) for l-glutamate, and the capability of a small molecule as propylene glycol (PG) to influence and extend the stability and the activity of enzyme. Different designs were evaluated by modifying the main components in their concentrations to find the most suitable design. Moreover, enzyme concentrations from 100 U/ml up to 200 U/ml were verified and different PG concentrations (1%, 0.1% and 0.05%) were tested. The most suitable selected design was Pt_c/PPD/PEI(1%)₂/GlutOx₅/PG(0.1%) and it was compared to the same already described design loading PEDGE, instead of PG, in terms of over-time performances. PG has proved to be capable of determining an over-time stability of the glutamate biosensor in particular in terms of linear region slope (LRS) up to 21 days.

Extracts obtained from leaves of Moringa tree (Moringa oleifera) are a rich source of many bioactive compounds: flavonoids, phenolic acids or carotenoids. It also contains such components as, vitamins (A, C, niacin, pantothenic acid), alkaloids, tannins or saponins. Extracts and plant substances derived from the leaves of Moringa oleifera L. have a strong antioxidant, toning and anti-inflammatory effect. The work attempts to obtain a multifunctional plant extract derived from Moringa tree leaves. Obtained extracts was analyzed for their biochemical and physicochemical properties. The obtained results indicate on a strong antioxidative potential of the tested extracts. The further step was an attempt to apply the extracts in the model body wash cosmetic. The biological activity of extracts and model cosmetic formulation were assayed by in vitro analysis on two human cell lines: keratinocytes (HaCat,) and fibroblasts (BJ). The results showed that the tested extracts may affect on increasing of cell proliferation and reduce oxidative stress in cells. The addition of the tested extracts to the model cosmetic formulation, were contributed to the reduction of their ability to irritate the skin and improve the safety of use of the product.

The objective of this study was to evaluate the evolution of the Syrah red and sparkling Moscatel wines stored for 12 months in green, amber and clear bottles. The phenolic compounds profile and antioxidant activity in vitro were determined. Commercial wines were bottled in an automatic filling machine, stored and analyzed every three months for one year. Several phenolic compound families were quantified through reversed-phase high performance liquid chromatography (RP-HPLC) coupled to diode-array detection (DAD) and fluorescence detection (FD). The different bottle colors studied did not influence the evolution of the sparkling Moscatel and Syrah red wines, since the main variations obtained were related to storage time. The main changes were observed in the Syrah wine, where storage time was associated with an increase in hue (h*), decrease in catechins, increase in procyanidins and, most notably, a decrease in the anthocyanin malvidin 3-glucoside. In general, the wines showed good stability in relation to the antioxidant activity in vitro.

This study evaluated the influence of the addition of increasing quantities of Hippophae rhamnoides L. leaves (HRL) on the radical scavenging activity, main oenological parameters and organoleptic characteristics of three white wines made from moschofilero and one white wine made from riesling grapes respectively. Radical Scavenging activity, reducing power, total phenol content (TPC) and color intensity increased in a linear manner in relation to HRL treatments. Indicatively the addition of 0.8 g/L of HRL increased the radical scavenging activity as determined via the inhibition of the DPPH radical from 23.2 to 58.4% in comparison to the initial values. Equally the reducing power as determined by the FRAP assay increased from 34.5 to 82.3%, TPC increased from 12.3 to 26.8% and the color intensity increased from 39-50% . The main oenological attributes examined, remained unchanged after the HRL addition. The addition of up to 0.4 g/L of HRL did not have a major impact on the organoleptic characteristics of the wines tasted whereas concentrations higher than 0.8 g/L were not considered beneficial. Results denote that the addition of Hippophae rhamnoides L. leaves to white wines contributes positively to the overall antioxidant capacity and could be used as an antioxidant agent in wines vinified in the absence of sulphur dioxide.

To substitute of conventional manure and peat with alternatives sourcing from environmental conservation concerns, several promising alternatives has been attracting scientific parties’ interest, recently. However, among them compost perform the best, mostly and support carbon sequestration and mitigation against climate change. The article describes the made locally produced 70% in volume olive pruning branches compost (COMP) performance in two trials as an organic amendment in pepper production and an olive sapling substrate during 2019-2021 organic management in Turkey. The application of COMP to pepper trial conducted using factorial randomised block design with 4 replications and 6 treatments increased total organic matter and soil organic carbon, significantly (p<0.05) as compared to non-used plots in two locations. The olive sapling trial was conducted using a randomised plot design with 4 replications and 4 treatments. After the 12 months of growth, compost had the largest architecture rooted plants significantly different (p<0.05). Fresh volume (cm³) of COMP used saplings were obtained 35% less than 40% peat treatment, significantly (p<0.05) while 6^th month measurement was found as 40%. It is concluded that to enhance circular economy recycling and composting olive pruning branches is lucrative for the country to reduce external input usage in organic horticultural production.

Cervical cancer is caused by a persistent and high-grade infection, caused by the Human Papilloma Virus (HPV), which, when entering cervical cells, alters their physiology and generates serious lesions. HPV 18 - is among those most involved in carcinogenesis in this region, but there are still no drug treatments that cause cure or total remission of lesions caused by HPV. Knowing that L-Asparaginase is an amidohydrolase, which plays a significant role in the pharmaceutical industry, particularly in the treatment of specific cancers, due to its antitumor properties, some studies have demonstrated its cytotoxic effect against cervical cancer cells. However, the commercial version of this enzyme has side effects, such as hypersensitivity, allergic reactions and silent inactivation due to the formation of antibodies. To mitigate these adverse effects, several alternatives have been explored, including the use of L-asparaginase from other microbiological sources, which is the case with the use of the fungus Aspergillus niger, a high producer of L-asparaginase. The study investigated the influence of the type of fermentation, precipitant, purification, characterization and in vitro cytotoxicity of L-asparaginase. The results revealed that semisolid fermentation produced higher enzymatic activity and protein concentration of A. niger. The characterized enzyme showed excellent stability at pH 9.0, temperature of 50ºC, resistance to surfactants and metallic ions, and an increase in enzymatic activity was also noted with the organic solvent ethanol. Furthermore, it exhibited low cytotoxicity in GM and RAW cells, and significant cytotoxicity in HeLa cells. These findings indicate that L-asparaginase derived from Aspergillus niger may be a promising alternative for pharmaceutical production. Its attributes, including stability, activity and low toxicity in healthy cells, suggest that this modified enzyme could overcome challenges associated with antitumor therapy.

The present work was aimed at the chemical characterization and antimicrobial activity of some extracts of aerial parts (essential oils from leaves and inflorescences, and resins from inflorescences) of two legal hemp (Cannabis sativa) varieties, Tisza and Kompolti, grown in Sardinia. Chemical characterization was carried out by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) techniques. The antimicrobial activity of these extracts against a panel of microorganisms was also determined via minimum inhibitory concentration (M.I.C.) determination. While the results showed a minor or negligible antimicrobial activity of the extracts against Gram+ and Candida strains, a good antibacterial activity (especially of resins) was recorded against S. aureus; no substantial differences were detected between of the chemical compositions of the two Cannabis varieties.

The aim of this study was to determine the changes in chemical composition of the fresh red raspberry ‘Willamette’ fruits, caused by the presence of raspberry leaf blotch emaravirus (RLBV). In three experimental orchards of ‘Willamette’ raspberry, fruits were harvested from RLBV‒free and RLBV-infected plants in 2019 and 2020. Fruits were collected at appropriate maturity stages and further analyzed on total phenolics, total anthocyanins, and selected individual phenolics. In all three experimental orchards, the phenolic profiles of infected and uninfected fruit samples were considerably different during both studied years. Nonetheless, the intensity of the modifications varied greatly depending on location and harvest year. Statistical analysis revealed that the influence of RLBV infection on the studied features is undeniable, although the influences of weather conditions and soil composition outweigh the influence of RLBV. Taking into consideration all experimental and statistical data, it can be concluded that raspberry 'Willamette' fruits may be RLBV-tolerant, while sensitivity to environmental conditions and soil composition is emphasized.

Fifteen transgenic shoot clones (TS A-TS O) regenerated from Hypericum perforatum hairy roots were evaluated for growth characteristics, phenylpropanoid, and naphthodianthrone production, as well as non-enzymatic and enzymatic antioxidant status. Transgenic shoots displayed higher biomass production and non-altered phenotype compared to control shoots. Phenylpropanoid production in TS was not related to phenylalanine ammonia lyase activity indicating that alternative enzymes could be involved in the regulation of phenylpropanoid/flavonoid biosynthesis. The positive correlation between phenylpropanoids (phenolic acids, flavonoids, flavan-3-ols, tannins) and non-enzymatic antioxidant assays suggested that these compounds are the main contributors to the redox state and radical scavenging properties of TS clones. More importantly, enhanced naphthodianthrone production (hypericin, pseudohypericin and protopseudohypericin) in TS was associated with the number of leaf dark glands. Concerning the enzymatic antioxidant status of TS, guaiacol peroxidase was shown as the main enzyme that turn down H2O2 levels, while the up-regulation of superoxide dismutase coincided with decreased O2•− production. The efficiency of antioxidant enzymes for O2•− and H2O2 neutralization declined the MDA level and consequently delayed lipid peroxidation in TS clones. Altogether, H. perforatum transgenic shoots could be proposed as a prospective biotechnological system for scale-up production of naphthodianthrones and phenylpropanoids with antioxidant properties.

Ipomoea batatas L. (IBL) has gained significant popularity as a complementary therapy or herbal medicine in the treatment of anti-diabetes. The objective of this review is to examine the mechanism of action of flavonoid compounds found in IBL that can activate GLP-1 as an anti-diabetic agent. The review article refers to PRISMA guidelines. The literature search was conducted using electronic databases such as Crossref, Pubmed, Scopus, and Science Direct. The search query was based on specific keywords, including Ipomoea batatas OR sweet potato AND anti-diabetic OR hypoglycemic. A total of 1055 articles were found, but only 32 articles were selected for further review based on inclusion and exclusion criteria. IBL contains various compounds, including phenolic acid, flavonols, flavanols, flavones, and anthocyanins, which exhibit activity against anti-diabetes. Flavonols, flavonols, and flavones belong to a group of flavonoids that possess the ability to form complexes with AlCl3 and Ca2+. Retention of Ca2+ within intracellular L cells, resulting in the release of GLP-1. Flavonols, flavones, and flavone groups have been found to strongly interact with DPP-IV, which inhibits the degradation of GLP-1. This mechanism effectively prolongs the half-life of GLP-1 in the systemic system, thereby contributing to the anti-diabetic activity of IBL