High Effect Research Articles

Evaluation of nematicidal potential of leaves extract of Afrohybanthus enneaspermus for management of Meliodogyne incognita in Tomato

The resistance of nematode pests to synthetic nematicides and its attendant hazards both to the crops and the ecosystem have caused growing interest. This study is aimed at investigating the nematicidal potential of the leaves extract of Afrohybanthus enneaspermus. Afrohybanthus enneaspermus is an evegreen shrub found in the tropical regions. The herbs have been used in ethonomedicine in the treatment of various ailments such as fever, diabetes, cough, skin infections and so on. According to standard methods in this study, in-vivo and In-vitro nematicidal screening of leaves extract was carried out against juvenile nematode pest (Meliodogyne incognita) while the pot experiment was carried out on tomato plants infected with root knot nematode. At the growth rate of the Tomato (Tropimech +), plant height was significantly lowered at 4 WAP (four weeks after planting) in tomato plants inoculated with 2,000 root-knot nematodes (RKN) applied with 20 g powered of Afrohybanthus enneaspermus compared with the rest of the treatments. With the application of 15% aqueous plant extracts and the inoculation of 2,000 RKN, plant height was significantly higher (32.8), followed by Plant alone and 20% aqueous plant extract. However, plant height was significantly lowered in plants applied with 20g powered of Afrohybanthus enneaspermus and nematode compared to the other treatments. At 6 weeks plant height is significantly higher in tomato plants inoculated with 5% aqueous plant extract with 2000RKN followed by others that are at the same range except 20g powered extract with 2000RKN that is significantly lowered . At 7 weeks plant height is significantly higher in tomato plants inoculated with 5% aqueous plant extract with 2000 RKN followed by others that are at the same range except 20g powdered extract with 2000 RKN that is significantly lowered. The research concluded that leaves extract of Afrohybanthus enneaspermus is effective in management of root Knot nematodes, however, in- vitro experiments, it is established that the powder form of the leave has higher effectiveness in management of nematode than its organic extract.

Co-delivery of Interferon Regulatory Factor 5 (IRF5) siRNA and dasatinib by a disulfide bond bearing polymeric carrier for enhanced anti-inflammatory effects

Co-delivery of chemical drugs and nucleic acids has attracted a great interest recently for treatment of inflammatory diseases. Dasatinib (DB), a tyrosine kinase inhibitor with anti-cancer effects, and Interferon Regulatory Factor 5 (IRF5) siRNA have shown anti-inflammatory effects. In the present study, a novel redox-responsive polymeric micelle was designed for co-delivery of DB and IRF5 siRNA-expressing plasmid (psiRF5) to enhance anti-inflammatory effects on macrophages. psiRF5 was condensed efficiently to redox-responsive micelles of DB-conjugated chitosan (CN) composed of disulfide bond, from different molecular weights of CN to form CN-SS-DB/psiRF5 micelles. The micelles with optimum N/P ratios had particle sizes of 287.8 and 245.4 nm and positive zeta potentials. The disulfide bond bearing micelles showed a redox-responsive drug release, protected the plasmid from being dissociated or degraded in exposure with heparin, serum and DNase I, and significantly enhanced the transfection efficiency and IRF5-gene silencing compared to naked psiRF5. The optimum micelles exhibited a dramatic reduction in IRF5 expression and revealed a notably higher anti-inflammatory effect than either DB or psiRF5, as indicated by more IL-10 and less IL-6 and TNF-α production by LPS-stimulated RAW264.7 macrophages incubated with the co-delivery system. The resultant nanocarriers might be promising for more effective treatment of inflammatory diseases.

Estro-Androgenic Disrupting Effects of Halogenated Disinfection Byproducts: A Comprehensive Evaluation and Comparison.

Drinking water halogenated disinfection byproducts (DBPs) have become an increasing health concern. However, the endocrine-disrupting effects of DBPs have not been well evaluated, and the limited available data have inhibited a comprehensive understanding of their health risks. In this study, a total of 43 DBPs were evaluated for their estro-androgenic effects using two types of human breast cancer cells. Among the tested DBPs, 16 exhibited estrogenic/antiestrogenic/androgenic/antiandrogenic effects, and the effects could be observed even at concentrations typically detected in drinking water. Iodinated and polyhalogenated DBPs generally showed higher effects than other species. For a broader comparison, DBP endocrine-disrupting effect data from this study and previous studies were summarized. It was found that the endocrine disruption efficacy of DBPs followed the rank order of iodinated > brominated > chlorinated species, and halophenolic DBPs were potential endocrine-disrupting compounds. Moreover, molecular docking results demonstrated that the binding of DBPs to estro-androgenic receptors was dominated by hydrophobic bonding, hydrogen bonding, halogen bonding, and van der Waals forces. The force strength and molecular volume were related to the magnitude of the estro-androgenic effects. Iodinated DBPs and polyhalogenated DBPs tended to have larger binding forces than other analogues and thus exhibited stronger effects.

Comparison Between Brain and Cerebellar Autoradiography Using [18F]Flortaucipir, [18F]MK6240, and [18F]PI2620 in Postmortem Human Brain Tissue.

Our objective was to evaluate the invitro binding properties of [18F]flortaucipir, 6-(fluoro-18F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([18F]MK6240), and 2-(2-([18F]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5c']dipyridine ([18F]PI2620) head-to-head in postmortem human brain tissue. Methods: Autoradiography was used to assess uptake of [18F]flortaucipir, [18F]MK6240, and [18F]PI2620 in control and Alzheimer disease (AD) autopsy-confirmed brain tissues. The study focused on the analysis of the prefrontal cortex, hippocampus, and cerebellum sections in 12 controls and 12 AD cases, as well as whole-brain hemisphere in 1 control and 1 AD sample, for each radiotracer. The binding values of [18F]flortaucipir, [18F]MK6240, and [18F]PI2620 were calculated from regions of interest manually drawn in the prefrontal, hippocampal, and cerebellar cortices. Results: For all 3 radioligands investigated, we observed significant tracer binding differences between control and AD tissues in the whole-brain hemisphere, prefrontal cortex, and hippocampus but not in the cerebellar cortex. [18F]MK6240 and [18F]PI2620 had higher effect sizes to differentiate control and AD cases than did [18F]flortaucipir. Bland-Altman analyses revealed strong correlations between [18F]MK6240, [18F]PI2620, and [18F]flortaucipir, with the highest agreement found for [18F]MK6240 versus [18F]PI2620. Conclusion: The 3 radioligands showed comparable diagnostic properties to assess tau aggregates invitro. Binding to AD brain tissues was higher for [18F]MK6240 and [18F]PI2620 than for [18F]flortaucipir. Additionally, [18F]MK6240 and [18F]PI2620 had greater selectivity, displaying decreased uptake in control brain tissue compared with [18F]flortaucipir. These results might provide insights on ongoing initiatives to create a universal scale for tau imaging studies.

Biological effectiveness of uniform and nonuniform dose distributions in radiotherapy for tumors with intermediate oxygen levels

Objective. We propose a criterion of biological effectiveness of nonuniform hypoxia-targeted dose distributions in heterogeneous hypoxic tumors based on equivalent uniform aerobic dose (EUAD). We demonstrate the utility of this criterion by applying it to the model problems in radiotherapy for tumors with different levels of oxygen enhancement ratio (OER) and different degrees of dose nonuniformity.Approach. The EUAD is defined as the uniform dose that, under well-oxygenated conditions, produces equal integrated survival of clonogenic cells in radiotherapy for heterogeneous hypoxic tumors with a non-uniform dose distribution. We define the dose nonuniformity effectiveness (DNE) in heterogeneous tumors as the ratio of the EUAD(DN) for a non-uniform distributionDNand the reference EUAD(DU) for the uniform dose distributionDUwith equal integral tumor dose. The DNE concept is illustrated in a radiotherapy model problem for non-small cell lung cancer treated with hypoxia targeted dose escalation. A two-level cell population tumor model was used to consider the hypoxic and oxygenated tumor cells.Results. Theoretical analysis of the DNE shows that the entire region of the OER can be separated in two regions by a threshold OERth: (1) OER > OERthwhere DNE > 1 indicating higher effectiveness of nonuniform dose distributions and (2) OER < OERthwhere DNE < 1 indicating higher effectiveness of uniform dose distributions. Our simulations show that the value of the threshold OERthin radiotherapy with conventional fractionation is significant in the range of about 1.2-1.6 depending on selected radiotherapy parameters. In general, the OERthincreases with reoxygenation rate, relative hypoxic volume and dose escalation factor. The threshold value of OERthis smaller of about 1.1 for hypofractionated radiotherapy.Significance. The analysis of dose distributions using the DNE shows that the uniform dose distributions may improve biological cell killing effect in heterogeneous tumors with intermediate oxygen levels compared to targeted nonuniform dose distribution.

Wave–Tide–Surge Interaction Modulates Storm Waves in the Bohai Sea

Typhoons, extratropical cyclones, and cold fronts cause strong winds leading to storm surges and waves in the Bohai Sea. A wave–flow coupled numerical model is established for storm events observed in 2022 caused by three weather systems, to investigate how storm waves are modulated by wave–tide–surge interaction (WTSI). Wave response is basically controlled by water level change in coastal areas, where bottom friction or breaking dominates the energy dissipation, and determined by the current field in deep water by altering whitecapping. Wave height increases/decreases are induced by positive/negative water level or obtuse/acute wave–current interaction angle, leading to six types of field patterns for significant wave height (Hs) responses. For the three storm events, Hs basically changed within ±5% in central deep water, while the maximum increase/decrease reached 160%/−60% in the coastal area of Laizhou Bay/Liaodong Bay. Based on maximum Hs and its occurrence time, WTSI modulation is manifested as the superposition effect of wave–tide and wave–surge interactions in both space and time scales, and occurrence time depends more on tide than surge for all three storms. The enhancement/abatement of WTSI modulation happens for consistent/opposite changing trends of wave–tide and wave–surge interaction, with the ultimate result showing the side with a higher effect.

Investor horizon, experience, and the disposition effect

The disposition effect, characterized by the tendency to sell winning assets too soon and hold onto losing assets for too long, is a widely documented phenomenon among investors. Using granular trade-level data, we examine the disposition effect among different categories of foreign institutional investors (FIIs) in the context of an emerging market. Using survival analyses over several years, we find that short-term investors are most prone to disposition effects, while long-term investors are least prone. We also find that experience, as indicated by cumulative years in the market and the volume of stocks traded, mitigates the disposition effects, but only among long-term FIIs. While FIIs exhibit higher disposition effects during crisis periods, this effect is mitigated by experience, particularly among long-term FIIs. Our findings suggest that accounting for heterogeneity in institutional investors, rather than treating them as a whole, is important for a better understanding of financial markets.

Preferences for genetic interventions for SCA and Huntington’s disease: results of a discrete choice experiment among patients

BackgroundAlthough genetic interventions are on the horizon for some polyglutamine expansion diseases, such as subtypes of spinocerebellar ataxia (SCA) and Huntington’s disease (HD), the patients’ preferences regarding these new therapies are unclear. This study aims to get insight into what extent different characteristics of genetic interventions affect the preferences of patients with SCA and HD with regard to these interventions.MethodsManifest and premanifest patients with SCA or HD were recruited online by platforms of patient associations. The respondents conducted a questionnaire that included a discrete choice experiment (DCE). The experimental design included 24 choice sets, but these were divided into three blocks of eight to reduce the number of tasks per respondent. Each choice set included two alternative treatments and consisted of four attributes (mode and frequency of administration, chance of a beneficial effect, risks, and follow-up), each with three or four different levels. The forced choice-elicitation format was used. Data were analyzed by using a multinominal logistic regression model.ResultsResponses of 216 participants were collected. The mode and frequency of administration of a genetic intervention, as well as the chance of a beneficial effect both influence the choice for a genetic intervention. Respondents less prefer repeated lumbar punctures compared to a single operation. As expected, a higher beneficial effect of treatment was preferred. Risks and follow-up did not influence the choice for a genetic intervention.ConclusionsThe results can be used for the design and implementation of future genetic interventional trials as well as of patient-centered care pathways for rare movement disorders such as SCA and HD.

Exploring the spatiotemporal trends and influencing factors of human settlement suitability in Hunan province traditional villages

The conservation and sustainable development of traditional villages have raised global attention in the context of rapid urbanization and modernization. Taking 703 traditional villages in Hunan Province as an example, this study first constructed a Traditional Village Human Settlement Suitability (TVHSS) evaluation system based on the Pressure-State-Response (PSR) model. Then, the entropy weighting method was used to assess the spatiotemporal evolution of TVHSS from 2005 to 2020, while the Geographically Weighted Regression (GWR) model was employed to analyze the influencing factors. The results indicate that the overall TVHSS score increased from 0.521 to 0.776 from 2005 to 2020, with a spatial distribution characterized by lower suitability in the northwest and higher suitability in the southeast. During this period, the pressure subsystem experienced an increase, peaking at 0.058 in 2015 before declining to 0.055 in 2020. Meanwhile, the state subsystem remained relatively stable, with scores slightly decreasing from 0.040 in 2005 to 0.033 in 2020. In contrast, the response subsystem showed a continuous upward trend, rising from 0.430 in 2005 to 0.688 in 2020. The distance to educational institutions, degree of relief, distance to water, and distance on intangible cultural heritage sites have the highest effects on TVHSS. These findings provide a scientific basis for the conservation and sustainable development of traditional villages and offer a replicable analytical framework for similar contexts globally. By addressing the complex interactions between environmental, social, and economic factors, this study contributes to the global discourse on rural sustainability, offering insights that can inform policy-making and guide the preservation of cultural heritage in the face of modernization pressures.

Advance Screening of Bis- Azetidinone Derivatives: Synthesis, Spectroscopy, Antioxidant and Antimicrobial Analysis with Molecular Docking Assessment

Introduction: This study includes synthesis, characterizations, antimicrobial, antiox-idant, and docking molecular study of novel Bis-Azetidinone compounds that combined two units of β-lactam rings .In the present investigation, the aromatic aldehydes with primary amine were condensed to create Schiff's base, which was then reacted with chloroacetylchloride to pro-duce bis-Azetidinone compounds. Methods: Melting points, FTIR, and NMR spectrum analyses were used to examine the mor-phological and topological characteristics of the Bis-Azetidinone compounds. The results indi-cate that the prepared Compounds synthesis has excellent antimicrobial activity against both Gram-negative (Escherichia coli,), Gram-positive bacteria (Staphylococcus aureus) and fungal (Candida albicans) and also indicated that the Compounds synthesis (A2) gave a higher antimi-crobial effect than the B2, C2. The synergistic activity was examined against the pathogenic microbial strains. It was observed that employing compound synthesis combined with antibiot-ics enhanced the synergistic efficacy compared to using compound synthesis alone or antibiotic alone on Gram-positive bacteria and fungi. Results: The antioxidant efficiency was assessed by DPPH, the results show that the compound synthesis has antioxidant activity, and also indicated that the synthesized compound (A2) gave a higher antioxidant effect than the B2, C2. Docking study confirmed via redocking of crystal-ized substrate or inhibitor within target binding pocket. The docking results reveal that the syn-thesized compounds, with a total binding affinity of less than -48 kcal/mol, could be clinically used for future therapeutic purposes. Conclusion: The present research demonstrates the advantageous effectiveness of a simpler pro-duction procedure, novel Bis-Azetidinone compounds, for producing high-purity with low haz-ard that may be utilized as future possible medical therapies.

Nanomaterials in asphalt cement: Exploring their single and combined effects on the physical and rheological properties

Pavement deterioration due to rutting, fatigue, and thermal cracking poses significant challenges to road infrastructure. Traditional asphalt modifiers often fall short in addressing these issues, leading to growing interest in advanced materials such as nanomaterials. This study investigates the individual and combined effects of three nanomaterials: nano-titanium dioxide (NT), nano-alumina (NA), and nano-silica (NS), on the physical and rheological properties of asphalt binders when used in dosages of 0%, 1%, and 2% by the weight of asphalt. This study aims to enhance asphalt performance and contribute to international research efforts focused on pavement durability. The experimental program evaluated the penetration, softening point, mass loss after aging, and viscosity properties, in addition to rutting and fatigue resistance through dynamic shear rheometer (DSR) tests. Scanning electron microscopy (SEM) was also employed to observe morphological changes. Results showed that 2% NA reduced penetration by 3.19%, while 2% NS increased the softening point by 2.41%. The combination of NA and NS had the highest effect on the softening point (F = 6.21, p = 0.008). NA and NT reduced mass loss, with 2% NA lowering it from 0.432% to 0.201%. Viscosity increased by 17.4% with 2% NA, while the NA and NS combination had the most significant overall impact (F = 44.78, p = 0.000). At higher temperatures, 2% NA was the most effective in reducing aging. Optimizing the use of NA and NS, either individually or combined, offers the best improvements in binder stiffness, thermal stability, and aging resistance.

Is compensation a myth? Modelling the use of public and private urban green spaces in relation to the geographical context

The compensation hypothesis postulates that the absence of green spaces in residential areas leads to a greater use of public green spaces and nature in general. This paper tests this hypothesis by focusing on the use of public and private urban green spaces. A holistic approach is adopted that considers the complexity of residential context and the use of urban, peripheral and private green spaces. A survey was conducted in two medium-sized French cities (Dijon and Besançon) to identify how their green spaces were used and perceived. The residential context was described through multiple spatial and environmental metrics (physical and visual access to nature, noise level, private green space area) that were GIS-referenced to postal addresses. On the basis of that data, the compensation hypothesis was explored using a PLS path model. The results show the absence of compensatory behaviour when considering just the overall relationships between the use of different types of green spaces. However, conditional compensatory behaviours can be detected when allowance is made for other variables (physical and visual accessibility to nature, type of housing, dwelling floor area, noise level). These results remain dependent on the geographical context of the city, with a higher compensation effect where natural areas are less accessible.

Onion Peel Extract Prevents Intestinal Inflammation via AMK-Activated Protein Kinase Activation in Caco-2/HT-29 Cells.

Obesogenic diets cause intestinal inflammation and dysfunction. Polyphenols have shown a positive impact on reducing inflammation in in vitro studies. However, their bioactivity may not be the same in the in vivo system due to structural alteration by the gastrointestinal digestive process. The purpose of this study was to investigate the anti-inflammatory effect of onion peel and its major bioactive compound, quercetin, in the intestine and further examine the impact of intestinal digestion on this effect. Onion peel extract (OPE) and quercetin (Q) were digested using gastrointestinal digestive enzymes in vitro and then treated into lipopolysaccharide (LPS)-stimulated Caco-2/HT-29 cells. Genes and proteins related to tight junction, inflammation, and epithelial integrity were measured. OPE and digested OPE (DOPE) had a higher protective effect on LPS-induced tight junction and inflammatory genes and paracellular permeability than Q and digested Q (DQ). DOPE was more effective than OPE, while digestion did not change the activity of Q. The anti-inflammatory effect of OPE and Q with or without digestion was achieved by inhibiting nuclear factor kappa B through AMP-activated protein kinase-activated silent mating-type information regulation 2 homolog 1. It was the first to find that a crude extract, after undergoing gastrointestinal digestion, demonstrated a notably superior anti-inflammatory effect in the cell study, suggesting the consumption of onion peels could potentially yield similar benefits in the human intestine. This discovery underscores the potential of onion peel polyphenols in combating intestinal inflammation, making them a compelling area of research for future therapeutic applications using food byproducts.

Artificial intelligence assisted prediction of optimum operating conditions of shell and tube heat exchangers: A grey‐box approach

AbstractIn this study, a Grey‐box (GB) model was developed to predict the optimum mass flow rates of inlet streams of a Shell and Tube Heat Exchanger (STHE) under varying process conditions. Aspen Exchanger Design and Rating (Aspen‐EDR) was initially used to construct a first principle model (FP) of the STHE using industrial data. The Genetic Algorithm (GA) was incorporated into the FP model to attain the minimum exit temperature for the hot kerosene process stream under varying process conditions. A dataset comprised of optimum process conditions was generated through FP‐GA integration and was utilised to develop an Artificial Neural Networks (ANN) model. Subsequently, the ANN model was merged with the FP model by substituting the GA, to form a GB model. The developed GB model, that is, ANN and FP integration, achieved higher effectiveness and lower outlet temperature than those derived through the standalone FP model. Performance of the GB framework was also comparable to the FP‐GA approach but it significantly reduced the computation time required for estimating the optimum process conditions. The proposed GB‐based method improved the STHE's ability to extract energy from the process stream and strengthened its resilience to cope with diverse process conditions.

Counteraction of unconjugated bilirubin against heme-induced toxicity in platelets

Platelets are essential for normal hemostasis and thrombosis but become hyperactive in hemolytic disorders. Cell-free heme is known to be toxic to platelets and endothelial cells, playing a significant role in the progression of pathological complications in various hemolytic conditions. The abnormal activation of circulatory platelets results in micro/macrovascular thrombosis and clot formation in the lungs, worsening the disease. This work aimed to establish the potent bioactive molecule that can regulate the heme-induced toxicity in platelets. We found that unconjugated bilirubin (UCB), an endogenous antioxidant and a byproduct of heme degradation, exhibited a higher protective effect against hemin-induced platelet aggregation and activation. This protective effect could mainly be due to reducing ROS and lipid peroxidation-mediated ferroptosis in hemin-treated platelets. Further experiments suggested that by blocking the interaction between hemin and the CLEC-2 receptor, UCB regulates the downstream Syk phosphorylation, a key event in hemin-induced platelet toxicity. Thus, UCB is emerging as a natural regulatory molecule that mitigates hemin-induced platelet toxicity and holds promise as an adjunctive therapy for managing platelet-associated complications, particularly in hemolytic disorders.

A select thiosemicarbazone copper(II) complex induces apoptosis in gastric cancer and targets cancer stem cells reducing pluripotency markers

Copper(II)-based complexes are promising candidates as anti-cancer agents due to their ability to target cancer cells. Here we describe the synthesis and characterization of two copper(II) thiosemicarbazone complexes with the ligands 4-(dimethylamino)benzaldehyde N4-methylthiosemicarbazone (HL1) and 4-(dimethylamino)benzaldehyde N4-(4-(dimethylamino)phenylthiosemicarbazone (HL2) and general formula [Cu(L)2]. The complexes show stability in aqueous solution with 1 % of DMSO that allows to stablish its solution profile in biological buffers. Compound [Cu(L1)₂] lipophilicity was lower than [Cu(L2)₂], however, its solubility in biological buffer was not only better but also its DLS and ζ-potential data. In vitro studies demonstrate a higher cytotoxic effect of [Cu(L1)₂] on gastric cancer cells. The proposed mechanism of action consists in the generation of free radicals that induce DNA lesions, oxidative stress and ultimately autophagy deregulation and apoptosis. Additionally, [Cu(L1)₂] is equally active on gastric cancer stem cells and tumor cells resistant to cisplatin. More importantly, stem cells treated with [Cu(L1)₂] show a downregulation of pluripotency markers such as TWIST, NANOG and OCT4. Overall, our results with [Cu(L1)₂] prompt a significant advancement in the development of rational-designed pharmaceuticals for combating cancer.

Intraoperative contrast-enhanced cone beam CT allows visualization of the ‘dark side’ of the clot and improves mechanical thrombectomy performance

BackgroundVisualization of the clot is key to the endovascular treatment of ischemic stroke, but identification of the distal part of the clot and distal arteries during mechanical thrombectomy (MT) remains...

Coordination mechanisms applied to logistical systems for local disaster preparedness: a Latin American case

Purpose The study aims to present an agent-based simulation model (ABM) for exploring interorganizational coordination scenarios in local disaster preparedness. This approach includes local actors and logistical processes as agents to compare various strategic coordination mechanisms. Design/methodology/approach The ABM model, developed in the Latin American context, specifically focuses on a case study of Colombia. Three coordination mechanisms (centralized, decentralized and cluster-type) have been evaluated using three performance indicators: effectiveness, efficiency and flexibility. Findings Simulation results show that the decentralized scenario outperforms in terms of efficiency and flexibility. On the contrary, the centralized and cluster-type scenarios demonstrate higher effectiveness, achieving a greater percentage of requirements coverage during the disaster preparedness stage. The ABM approach effectively evaluates strategical coordination mechanisms based on the analyzed performance indicators. Research limitations/implications This study has limitations due to the application of results to a single real case. In addition, the focus of the study is primarily on a specific type of disaster, specifically hydrometeorological events such as flash floods, torrential rains and landslides. Moreover, the scope of decision-making is restricted to key actors involved in local-level disaster management within a municipality. Originality/value The proposed ABM model has the potential as a decision-making tool for policies and local coordination schemes for future disasters. The simulation tool could also explore diverse geographical scenarios and disaster types, demonstrating its versatility and broader applicability for further insights and recommendations.

Mechanistic in vitro study of the effect of Cucurbita moschata (Cucurbitaceae) on carbohydrate digestive enzymes.

Diabetes is marked by postprandial hyperglycemia (PHG), an abnormal rise in blood glucose after meals. A key therapeutic goal to reduce PHG is the inhibition of α-amylase (αAM) and α-glucosidase (αGL), enzymes that break down carbohydrates into sugars. Cucurbita moschata has been shown to inhibit both enzymes. However, its inhibition mechanism has not been explored. This study investigated the in vitro inhibition mechanisms of αAM and αGL and conducted a metabolomic analysis of C. moschata (edible part) water-extract (CME), aiming to preliminarily identify its bioactive compounds (BCs). The inhibitory mechanisms were determined using Lineweaver-Burk plots. The BCs were identified and quantified using HPLC-QTOF-MS, employing both targeted and untargeted metabolomic approaches. CME had a significant higher effect (p<0.05) on αAM activity than against αGL with IC50 of 28.99 and 698.42mg/mL, respectively. The extract showed mixed and uncompetitive type inhibitions on αAM and αGL, respectively. The lowest inhibition constant (Ki) was 47.68mg/mL on αAM activity at 20mg/mL. Untargeted metabolic profiling by UPLC-MS-ESI-QTOF putatively identified 30 compounds in CME, such as amino acids, vitamins, phytohormones, fatty acids, cucurbitacins and phenolic acids, and flavonoids. Functional analysis of CME identified significant pathways, including pantothenate and CoA biosynthesis and phenylpropanoids, among others. The targeted analysis by UPLC-MS-ESI-QqQ allowed us to identify 12 compounds, with l-phenylalanine, p-hydroxybenzoic, and p-coumaric acid as majors. This study demonstrated the inhibitory potential of CME on αAM and αGL activities, which may be attributed to its metabolites. Thus, this plant represents a valuable source of BC against PHG. Practical Application: The research highlights that Cucurbita moschata has significant potential in managing postprandial hyperglycemia in diabetic patients by inhibiting enzymes like α-amylase and α-glucosidase. In addition, the identification of its compounds emphasizes its importance as a source of bioactive compounds. Therefore, C. moschata could be effectively utilized in the development of nutraceuticals or as an ingredient in functional foods specifically designed for postprandial hyperglycemia management. Thus, integrating C. moschata as part of the daily diet could offer patients with diabetes a natural alternative to control their blood glucose levels after eating.

The effect of myo-inositol antioxidant activity on human sperm parameters and DNA damage in ultra-rapid and conventional freezing methods

Male fertility preservation is still challenged by cell damage induced during sperm cryopreservation and impaired sperm structure and function. Sperm ultra-rapid freezing, despite a higher protective effect compared to conventional freezing method, is still associated with suboptimal sperm cryosurvival and needs to be modified to increase its efficiency in sperm protection. Sperm freezing media supplemented with antioxidants can improve sperm parameters following freezing-warming process. In this study, we aimed to investigate the effect of employing ultra-rapid freezing and myo-inositol on sperm cryosurvival. Thirty semen samples with normal sperm parameters were collected and each one was divided into four portions to cryopreserve by conventional freezing, ultra-rapid freezing, conventional freezing + myo-inositol 2 mg/ml, and ultra-rapid freezing + myo-inositol 2 mg/ml. Sperm samples warmed after at least 24 h of freezing and sperm cryosurvival were analyzed by evaluation of sperm motility, viability, morphology and DNA fragmentation index (DFI). Freezing method had a significant influence on post-thaw sperm DFI and morphology (p < 0.05) and the interaction between freezing method and antioxidant supplementation significantly affected sperm morphology (p < 0.05). The highest percentage of sperm normal morphology and minimal DFI was achieved using ultra-rapid freezing supplemented by myo-inositol antioxidant compared to other groups (P < 0.05). The highest sperm DNA damage after freezing-warming was observed following the conventional freezing method. In conclusion, sperm freezing method was identified as factor strongly influencing sperm DFI and morphology after thawing/warming. Sperm samples can be rapidly frozen using the modified freezing media supplemented by myo-inositol without impacting sperm DNA and morphology.