Atherosclerosis (AS) is a chronic progressive disease caused by various factors, and causes various cerebrovascular and cardiovascular diseases (CVDs). Reducing the plasma levels of low-density lipoprotein-cholesterol (LDL-C) is the primary goal in preventing and treating AS. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) plays a crucial role in regulating LDL-C metabolism. Panax notoginseng has potent lipid-reducing effects and protects against CVDs, and its saponins induce vascular dilatation, inhibit thrombus formation, and are used in treating CVDs. However, the anti-AS effect of the secondary metabolite, 20(S) -protopanaxatriol (20(S)-PPT), remains unclear. In this study, the anti-AS effect and molecular mechanism of 20(S)-PPT were investigated in vivo and in vitro by western blotting, real time-polymerase chain reaction (RT-PCR), Enzyme-linked Immunosorbent Assay (ELISA), immunofluorescence staining, and other assays. The in vitro experiments revealed that 20(S)-PPT reduced the levels of PCSK9 in the supernatant of HepG2 cells, upregulated low density lipoprotein receptor (LDLR) protein levels, promoted LDL uptake by HepG2 cells, and reduced PCSK9 mRNA transcription by upregulating the levels of FoxO3 protein and mRNA and decreasing the levels of HNF1α protein and mRNA. The in vivo experiments revealed that 20(S)-PPT upregulated aortic αSMA expression, increased the stability of atherosclerotic plaques, and reduced aortic plaque formation induced by a high-cholesterol fed in ApoE-/- mice (HCF group). Additionally, 20(S)-PPT reduced the aortic expression of CD68, reduced inflammation in the aortic root, and alleviated the hepatic lesions in the HCF group. The study revealed that 20(S)-PPT inhibited LDLR degradation via PCSK9 to alleviate AS.

During the last trimester of gestation and for the first 18 months after birth, both docosahexaenoic acid,22:6n-3 (DHA) and arachidonic acid,20:4n-6 (ARA) are preferentially deposited within the cerebral cortex at a rapid rate. Although, the structural and functional roles of DHA in brain development are well investigated, similar roles of ARA are not well documented. The mode of action of these two fatty acids and their derivatives at different structural-functional roles and their levels in the gene expression and signaling pathways of the brain have been continuously emanating. In addition to DHA, importance of ARA has been much discussed in recent years for fetal and postnatal brain development and the maternal supply of ARA and DHA. These fatty acids are also involved in various brain developmental processes; however, their mechanistic cross talks are not clearly known yet. This review describes the importance of ARA, in addition to DHA to support the optimal brain development and growth and functional roles in the brain.

To date, radiation adaptation response has been reported as a low-dose related phenomenon and has been associated with radiation hormesis. Well-known cancers are caused by non-radiation active reactants, in addition to radiation. A model of suppression for radiation-specific cancers was previously reported, but the model did not target radiation-nonspecific cancers. In this paper, we describe kinetic models of radiation-induced suppressors for general radiation non-specific cancers, estimating the dose that induces the maximum hormesis effect while satisfying the condition that the risk is approximately proportional to dose above 100 mSv. It was found that the radiation hormesis effect is maximal at about 20 mSv when the rate constant for generation is the same as the rate constant for decomposition. When the two rate constants are different, the dose at which the radiation hormesis effect is maximized depends on both rate constants, but the dose increases as the two rate constants approach each other, reaching a maximum of about 20 mSv. This conclusion may lead to the discovery of unknown cancer suppressors at low doses and the development of cancer suppression methods in the future.

The strategy of any organization is based on the growth of its customer base, and one of 5 its principles is that selling a product to an existing customer is much more profitable than acquiring 6 a new customer. However, this approach has several opportunities for improvement, since it usu- 7 ally has a totally reactive approach, which does not give opportunity to the areas specialized in 8 customer experience and recovery, to give an effective response for that moment, since the customer 9 is gone at the time of the intervention. This happens because usually a diagnostic analysis of cus- 10 tomers who have stopped buying products or services in a defined period, commonly three (3) pe- 11 riods or months, is performed. This thesis work challenges the way to face this problem, and pro- 12 poses the development of a complete solution, which does not focus exclusively on the prediction 13 of churn, as is usually done in the state of the art research, but to intervene in different interactions 14 that can be carried out with customers. The above focused not only to prevent customer churn, but 15 to generate an added value of continuous improvement in sales processes, increase customer pene- 16 tration, leading to an improvement in customer experience and consequently, an increase in cus- 17 tomer loyalty.

The strategy of any organization is based on the growth of its customer base, and one of 5 its principles is that selling a product to an existing customer is much more profitable than acquiring 6 a new customer. However, this approach has several opportunities for improvement, since it usu- 7 ally has a totally reactive approach, which does not give opportunity to the areas specialized in 8 customer experience and recovery, to give an effective response for that moment, since the customer 9 is gone at the time of the intervention. This happens because usually a diagnostic analysis of cus- 10 tomers who have stopped buying products or services in a defined period, commonly three (3) pe- 11 riods or months, is performed. This paper challenges the way to face this problem, and proposes 12 the development of a complete solution, which does not focus exclusively on the prediction of 13 churn, as is usually done in the state of the art research, but to intervene in different interactions 14 that can be carried out with customers. The above focused not only to prevent customer churn, but 15 to generate an added value of continuous improvement in sales processes, increase customer pene- 16 tration, leading to an improvement in customer experience and consequently, an increase in cus- 17 tomer loyalty.

Запропонована методика спрямована на визначення та прогнозування технічного стану елементів мосту, що може слугувати прогресивним інженерним інструментом для оцінки надійності та довговічності. Розроблено на основі фундаментальних досліджень, які узагальнюють досвід вивчення фізико-механічних і фізико-хімічних властивостей матеріалів мостових конструкцій, що експлуатуються в реальних умовах. Теоретичною основою методики є модель надійності та прогнозування залишкового ресурсу елементів мосту на основі теорії Маркова. Розроблена методика призначена для оцінки технічного стану окремих елементів мосту з подальшою комплексною оцінкою всієї конструкції. За показник технічного стану прийнята надійність при експлуатації. Цей кількісний показник надійності в моделі є критерієм для: оцінки рівня безпеки елементів мосту; ранжування елементів мосту за необхідністю для конкретних видів ремонту, реконструкції або заміни; стратегічне планування витрат на ремонт або реконструкцію в умовах обмеженого фінансування; прогнозування залишкового ресурсу елементів. Для застосування розробленої методики запропоновано алгоритм оцінки та прогнозування технічного стану мостів. Було проведено математичний експеримент розробленої методики, який підтвердив адекватність висунутої гіпотези, тобто використання моделі надійності та прогнозування залишкового ресурсу елементів мосту. По-перше, запропоновано триступеневий механізм уточнення технічного стану мосту, суттєво підвищення точності розрахунків. Тому розроблена методика має практичне значення і може слугувати основою для інформаційно-аналітичних систем управління станом мостів.

The timely diagnosis of defects at their incipient stage of formation is crucial to extend the life-cycle of technical appliances. This is the case of mechanical-related stress, either due to long aging degradation processes (e.g., corrosion) or in-operation forces (e.g., impact events), which might provoke detrimental damages, such as cracks, disbonding or delaminations, most commonly followed by the release of acoustic energy. The localization of these sources can be successfully fulfilled via adoption of Acoustic Emission (AE)-based inspection techniques through the computation of the Time of Arrival (ToA), namely the time at which the induced mechanical wave released at the occurrence of the acoustic event arrives to the acquisition unit. However, the accurate estimation of the ToA may be hampered by poor Signal-to-Noise ratios (SNRs). In these conditions, standard statistical methods typically fail. In this work, two alternative Deep Learning methods are proposed for ToA retrieval, namely a Dilated Convolutional Neural Network (DilCNN) and a Capsule Neural Network for ToA (CapsToA). These methods have the additional benefit of being portable on resource-constrained microprocessors. Their performance has been extensively studied on both synthetic and experimental data, focusing on the problem of ToA identification for the case of a metallic plate. Results show that the two novel methods can achieve localization errors which are up to 70% more precise than those yielded by conventional strategies, even when the SNR is severely compromised (i.e., down to 2 dB). Moreover, DilCNN and CapsNet have been implemented in a tiny machine learning environment and then deployed on microcontroller units, showing a negligible loss of performance with respect to offline realizations.

Degradation of intracellular components through autophagy is a fundamental process to maintain cellular integrity and homeostasis. Recently a glycogen-selective autophagy pathway has been described, termed ‘glycophagy’. Glycogen is a primary storage depot and regulator of glucose availability, and glycophagy is emerging as a critical physiological process involved in energy metabolism. Glycophagy-mediated degradation of glycogen appears to operate in parallel with the well-described canonical pathway of glycogenolysis involving glycogen phosphorylase. Evidence suggests that starch-binding domain protein-1 (Stbd1) is a key glycogen-binding protein involved in tagging glycogen for glycophagy, and that Gabarapl1 is primarily involved as the Atg8 family protein recruiting the Stbd1-glycogen complex into the forming glycophagosome. The nuances of glycophagy protein machinery, regulation and lysosomal glucose release are yet to be fully elucidated. In this mini-review, we critically analyze the current evidence base for glycophagy as a selective-autophagy process of physiological importance and highlight areas where further investigation is warranted.

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.

Disturbed metabolism of vitamins B1 or B6, which are essential for neurotransmitters homeostasis, may cause epilepsy. Our study aims at revealing therapeutic potential of vitamins B1 and B6 in epilepsy by estimating effects of their combined administration on a seizure and its consequences in rats subjected to pentylenetetrazole (PTZ). The PTZ dose dependence of a seizure and its parameters according to Racine’s scale along with delayed physiological and biochemical consequences next day after the seizure are assessed regarding sexual dimorphism in epilepsy. PTZ sensitivity is stronger in the female than male rats. Next day after a seizure, gender differences in behavior and brain biochemistry arise. The induced gender differences in anxiety, exploratory and locomotor activity correspond to disappearance of gender differences in the brain GABA, aspartate, alanine and serine, with appearance of those in glutamate, glutamine and tyrosine. PTZ decreases the brain malate dehydrogenase activity, glutamine and urea in the males, and phenylalanine in the females. Administration of vitamins B1 and B6 24 h before PTZ delays a seizure in female rats only. This desensitization is not observed at short intervals (0.5-2 h) between the vitamins and PTZ administration. With the increasing interval, the pyridoxal kinase (PLK) activity in the female brain decreases, suggesting that the PLK downregulation by vitamins contributes to the desensitization. Delayed effects of vitamins and/or PTZ are mostly gender-specific and interacting. Our findings on the gender differences in sensitivity to epileptogenic factors, action of vitamins B1/B6 and associated biochemical events have medical implications.

This contribution is an attempt to reconstruct the favorable atmosphere that prevailed in Lau-sanne in 1986-87 and provided the backdrop of our invention of two-dimensional ion cyclotron resonance mass spectroscopy (2D ICR-MS). To avoid a self-centered histoire d’ancien combattant, we shall try to emphasize the context, the contributions of key players within our nascent research group at UNIL and the established group of Tino Gäumann at EPFL, the role of external speakers, and the open atmosphere that was not yet polluted by bibliometrics, obsessive concern with im-pact factors, and top-down management of research. We shall also explain why the idea of 2D ICR-MS has been ignored for many years and still has a limited impact: different scientific cul-tures in the ICR and NMR communities, different concerns with fundamental vs. applied research, different status of theory and numerical simulations, different levels of commitment of instrument manufacturers, not to mention many theoretical problems that appear to be at least as challenging in ICR as in NMR.

This paper presents work done as part of a transformation effort towards a greener and more sustainable Aluminium manufacturing plant. The effort includes reducing the carbon footprint by minimising waste and increasing operational efficiency. The contribution of this work includes the reduction of waste through the implementation of autonomous, real-time quality measurement and classification at an Aluminium casthouse. Data is collected from the MV20/20 which uses ultrasound pulses to detect molten Aluminium inclusions, which degrade the quality of the metal and cause subsequent metal waste. The sensor measures cleanliness, inclusion counts and distributions from 20 - 160 microns. The contribution of this work is in the development of business analytics to implement condition-based monitoring through anomaly detection, and to classify inclusion types for samples that failed. For anomaly detection, multivariate K-Means and DBSCAN algorithms are compared as they have been proven to work in a wide range of datasets. For classification, a two-stage classifier is implemented. The first stage classifies the success or failure of the sample, while the second stage classifies the inclusion responsible for the failed sample. The algorithms considered include logistic regression, support vector machine, multi-layer perceptron and radial basis function network. The multi-layer perceptron offers the best performance using k-fold cross-validation, and is further tuned using grid search to explore the possibility of an even better performance. The results reveal that the model has achieved a global maximum in performance. Recommendations include the integration of additional sensor systems and the improvements in quality assurance practices.

This study investigates the spatio-temporal variability of the onset, offset, and Length of the rainy season in Senegal over the 1981-2018 period. The onset, offset dates, and length of the rainy season are crucial parameters for agricultural planning in West Africa, which exhibits high interannual and spatial variability in rainfall. The objective is to detect and spatially classify these phenological parameters across Senegal using different approaches. Daily precipitation data from the Climate Hazards group InfraRed Precipitation with Stations (CHIRPS) dataset over the study period and ERA5 reanalysis were used. The method of was applied to detect the onset, offset dates, and length of the rainy season. The Kohonen algorithm was then used to spatially classify these parameters on topological maps. A hierarchical ascendant classification was also performed to reduce the number of classes obtained. Finally, a composite analysis of moisture transport before the onset and end of the 1984 and 2007 seasons was conducted with ERA5 data. The results show a meridional gradient of the start of the season, progressively later from southeast to northwest, while the end follows a north-south gradient. The duration of the rainy season ranges from 45 days in northern Senegal to 150 days in the south. The maximum number of dry days also decreases from north to south. The Kohonen self-organizing maps allow spatial prediction of the onset, end date, and duration of the rainy season across Senegal. The dynamics analysis reveals that early onset years are associated with stronger and earlier northward moisture transport over West Africa, underscoring the role of this parameter in triggering the rainy season. These promising results can provide an early warning to policymakers and farmers on the start and end dates of the season in each area of Senegal.

Over the last decades, the increased incidence of metabolic disorders such as type 2 diabetes and obesity has motivated researchers to investigate new enzyme inhibitors. In this study, the inhibitory effects of synthetic amino acid derivatives (PPC80, PPC82, PPC84, PPC89, and PPC101) on the activity of digestive enzymes was assessed by in vitro assays. The inhibitory effect was determined by the inhibition percentage and the 50% inhibitory concentration (IC50), and the mechanism of action was investigated by Lineweaver–Burk plots. PPC80, PPC82, and PPC84 inhibited pancreatic lipase (IC50 of 1.67–10.23 x 10-1 mmol/L). The activity of pancreatic α-amylase was suppressed by PPC80, PPC82, PPC84, PPC89, and PPC101 (IC50 of 1.62–5.19 x 10-1 mmol/L). Finally, PPC84, PPC89, and PPC101 also showed a potent inhibitory effect on α-glucosidase (IC50 of 0.51–3.53 x 10-1 mmol/L). PPC80 and PPC82 followed a non-competitive inhibition mechanism against pancreatic lipase, while PPC84 acted through competitive inhibition. The inhibition of pancreatic α-amylase by the derivatives was non-competitive, as well as for PPC84, PPC89 and PPC101 against α-glucosidase. The results suggest that these synthetic amino acid derivatives have inhibitory potential against digestive enzymes and may be used as therapeutic agents to control metabolic disorders.

An Environmental Decision Support System (EDSS) can be used as an important tool for rehabilitation and preservation of ecosystems. Nonetheless, high assimilation costs (both money and time) are one of the main reasons that these tools are not widely adapted in practice. This work presents a low-cost paradigm of "EDSS as a Service", this paradigm is demonstrated for developing Water Quality EDSS as a Service that utilizes the well-known CE-QUAL-W2 model as a kernel for deriving optimized decisions. The paradigm is leveraging new open-source technologies in software development (e.g. Docker, Kubernetes, and Helm) with cloud computing in order to significantly reduce assimilation costs of the EDSS for organizations and researchers working on rehabilitation and preservation of water bodies.

Research has shown that the consumption of herbal teas is linked with positive effects on the regulation of postprandial blood glucose level. In this study, a comparative analysis of aqueous and ethanol extractions is performed on four herbal teas (Mallotus, Cyclocarya, Rubus, Vine) to evaluate their phytochemical profiles and functional activities. Investigations of phytochemical contents, antioxidant activities, α-glucosidase inhibitory activities and chemical compositions are carried out through colorimetric analyses and UPLC-Q-Orbitrap HRMS/MS, respectively. Results showed that among the studied herbal teas, Vine exhibited the highest glucose re-gulating abilities under both aqueous and ethanol extractions. Overall, ethanol extracted samples yielded higher phytochemicals content, but the compositions of the phytochemicals varied. Meanwhile, aqueous extracts showed surprisingly strong antioxidant activities and comparable α-glucosidase inhibitory activities with ethanol extracts. Phytochemicals contents presented a positive correlation with antioxidant activities and α-glucosidase inhibitory activities. Nevertheless, antioxidant activities displayed a weak positive correlation with α-glucosidase inhibitory activities. Results from this study provided evidence that aqueous extracts from herbal teas possessed valuable phytochemicals composition for antioxidants and the hyperglycemic populations, and are promising candidates for potential applications as functional ingredients with health promoting effects and as natural additives to boost the nutritional value of herbal food products.

The α-glucosidase inhibitor is of interest to researchers due to its association with type-II diabetes treatment by suppressing postprandial hyperglycemia. Hesperidin is a major flavonoid in orange fruit with diverse biological properties. This paper evaluates the effects of hesperidin on α-glucosidase through inhibitory kinetics, fluorescence quenching, and molecular docking methods for the first time. The inhibition kinetic analysis showed that hesperidin reversibly inhibited the α-glucosidase activity with an IC50 value of 18.52 M and the inhibition was performed in an uncompetitive type. Fluorescence quenching studies indicated that the intrinsic fluorescence of α-glucosidase was quenched via a static quenching process and only one binding site was present between hesperidin and α-glucosidase. The interaction between them was spontaneous and mainly driven by hydrogen bonds as well as hydrophobic forces. Furthermore, molecular docking results suggested that hesperidin might bond to the entrance or outlet part of the active site of α-glucosidase through a network of five hydrogen bonds formed between hesperidin and the four amino acid residues (Trp709, Arg422, Asn424, and Arg467) of ?-glucosidase and hydrophobic effects. These results provide new insights into the inhibitory mechanisms of hesperidin on α-glucosidase, supporting the potential application of hesperidin-rich orange product as a hypoglycemic functional food.

β-glucosidases (BGLs) play a crucial role in the degradation of lignocellulosic biomass as well as in industrial applications such as pharmaceuticals, foods, and flavors. However, the application of BGLs has been largely hindered by issues such as low enzyme activity, product inhibition, low stability, etc. Many approaches have been developed to engineer BGLs to improve these enzymatic characteristics to facilitate industrial production. In this article, we review the recent advances in BGL engineering in the field, including the efforts from our laboratory. We summarize and discuss the BGL engineering studies according to the targeted functions as well as the specific strategies used for BGL engineering.

Acetic acid bacteria (AAB) form a bacterial film on the surface of alcoholic solutions and ferment ethanol to acetic acid while also producing bioactive compounds. To discover functional AAB for industrial use, we isolated and selected strains from farm-produced vinegars using a CaCO3-containing medium. The seven strains belonged to Acetobacter cerevisiae and A. pasteurianus. Physiological properties were determined, including ethanol tolerance at up to 12% (v/v). Acidification at a growth temperature of 40 ℃ was seen for GHA 7, GYA 23, JGB 21-17, and GHA 20 strains, which may be useful in vinegar production where thermotolerant AAB are required. The seven AAB isolates had strong antibacterial activity against Staphylococcus aureus. Antioxidant activity was 2- and 4-fold higher, respectively, for A cerevisiae and A. pasteurianus than for the control, 1% acetic acid. We also observed 91.3% inhibition of angiotensin-converting enzyme activity for the KSO 5 strain, higher than that for the positive control, 0.1% captopril (76.9%). All strains showed complete inhibition of α-glucosidase, except JGB 21-17 and GHA 7 with 98.3% inhibition. Our work suggests usefulness of the strains selected as seed strains for highly efficient production of functional vinegar and illustrates identification of useful functional characteristics on a scientific basis.

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

Wendan (a type of pomelo), as a popular fruit in China, is less known in other countries. Its peel is widely used in food and traditional medicine. Four different origins of Wendan pomelo were selected, and crude extracts were obtained by the Soxhlet extraction method. The composition of Wendan peel was analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS) in positive ion mode. The compounds were identified by searching the Metabolite Link (METLIN), Spectral Database for Organic Compounds (SDBS) and referring to literature reports. A total of 20 compounds were identified among the samples from the four origins, of which 8 compounds were common. The majority of the compounds belonged to the flavonoid and coumarin classes, Meranzin hydrate was identified for the first time in pomelo peel. In vitro antioxidant activity experiments showed that samples from Taizhou, Zhejiang exhibited the highest antioxidant activity in the DPPH, ABTS, and FRAP assays, with values of 0.59 mg/mL, 97.06 μmol TE/g, and 60.62 μmol Fe2+/g, respectively. Samples from Zhangzhou, Fujian showed antioxidant activity second only to the samples from Taizhou, Zhejiang. The sample from Zhangzhou, Fujian Province, showed excellent inhibitory activity in the α-glucosidase inhibition assay (IC50=7.99 mg/mL).

Alginate extraction is from seaweed, and lignin separation is from by-product corn (stalks and leaves). Alginate/lignin is a synthetic polymer rich in biological activity of great interest. Antioxidant activities of alginate/lignin were evaluated, such as total antioxidant activity, reducing power activity, DPPH free radical scavenging activity, and α – glucosidase inhibition activity. The test of anticancer activity was on four cell lines (Hep G2, fibroblast, MCF-7, and NCI H460). Determination of physical-chemistry characteristics of alginate/lignin was through FTIR, DSC, SEM_EDS, SEM_EDS mapping, XRD, XRF, and 1H-NMR. A study of acute toxicity of alginate/lignin was on Swiss albino mice. The results showed alginate/lignin possessed antioxidant activity such as total antioxidant activity, reducing power activity, especially, α – glucosidase inhibition activity, and no free radical scavenging activity. Alginate/lignin did not be typical in cancer cell lines. Alginate/lignin existed in a thermally stable regular spherical shape in the investigated thermal region. Some specific functional groups of alginate and lignin did not exist in alginate/lignin crystal. Elements such as C, O, Na, and S were popular in the alginate/lignin structure. LD0 and LD100 of alginate/lignin in mice were 3.91 g/kg and 9.77 g/kg, respectively. Alginate/lignin is the potential for application as pharmaceutical materials, functional foods, and supporting diabetes treatment.

This study investigates the long-term stability of the Suomi National Polar-orbiting Partnership (S-NPP) Visible Infrared Imaging Radiometer Suite (VIIRS) moderate-resolution Thermal Emissive Bands (M TEBs; M12 – M16) covering a period from February 2012 to August 2020. It also assesses inter-sensor consistency of the VIIRS M TEBs among three satellites-S-NPP, NOAA-20, and NOAA-21 over eight months spanning from March 18 to November 30, 2023. The field of interesting is limited to the ocean surface between 60°S and 60°N, specifically under clear-sky conditions. Taking radiative transfer modeling (RTM) as the transfer reference, we employed the Community Radiative Transfer Model (CRTM) to simulate VIIRS TEB brightness temperature (BTs), incorporating European Centre for Medium-range Weather Forecasts (ECMWF) reanalysis data as inputs. Our results reveal two key findings. Firstly, the reprocessed S-NPP VIIRS TEBs exhibit a robust long-term stability, as demonstrated through analyses of the observation minus background BT differences (O-B ∆BTs) between VIIRS measurements (O) and CRTM simulations (B). The drifts of the O-B BT differences are consistently less than 0.105 K/Decade across all S-NPP VIIRS M TEB bands. Notably, observations from VIIRS M14 and M16 stand out with drifts well within 0.04 K/Decade, reinforcing their exceptional reliability for climate change studies. Secondly, excellent inter-sensor consistency among these three VIIRS instruments is confirmed through the double-difference analysis method (O-O). This method relies on the O-B BT differences obtained from daily data. The mean inter-VIIRS O-O BT differences remain within 0.08 K for all M TEBs, except for M13. Even in the case of M13, the O-O BT differences between NOAA-21 and NOAA-20/S-NPP have values of 0.312 K and 0.234 K, respectively, which are comparable to the 0.2 K difference between some TEBs among VIIRS and MODIS. These disparities are primarily attributed to the significant differences in the Spectral Response Function (SRF) of NOAA-21 compared to NOAA-20 and S-NPP. Our study confirms the RTM-based TEB quality evaluation method’s versatility and effectiveness in assessing long-term sensor stability and inter-sensor consistency. The double-difference approach effectively mitigates uncertainties and biases inherent to CRTM simulations, establishing itself a robust mechanism for assessing inter-sensor consistency. In addition, we’ve observed that, except for M13, M12 always exhibits larger spatial variations of O-O BT differences with greater uncertainties compared to the other M TEBs. The influence of solar contribution through sea surface reflection on the Top of Atmosphere (TOA) radiance measurements during daytime in M12 should not be underestimated.

The class I carcinogen aflatoxin B1 (AFB1) poses a significant risk to human health. The contamination of food sources contributes to the spread of AFB1, mainly through grains and nuts, from Aspergillus flavus. The high percentage of aflatoxin contamination in various imported nuts in the Republic of Kazakhstan has encouraged researchers to develop a local method of AFB1 detoxification. This research was focused on studying the ability of Ziziphora serpyllace leaf extract growing in the Akmola region of the Republic of Kazakhstan to inactivate aflatoxin B1 in various nuts. For the first time, an extract of Ziziphora serpyllace leaves growing in the territory of the Republic of Kazakhstan was used to detoxify AFB1 in nuts, and this demonstrated low cytotoxic activity, high antimicrobial and high antifungal activity, while preserving the qualitative characteristics of the nuts.

Mycotoxins are produced by more than one hundred fungi and produce secondary metabolites that contaminate various agricultural commodities, especially rice and corn. Their presence in the food chain is considered a serious problem worldwide. In recent years, a link between exposure to mycotoxins and impaired fertility has been suggested. Consequently, it has become vital to investigate the interactive effects of these mycotoxins on ovarian function. In this study, we investigated the intergenerational effects of mycotoxin fumonisin B1 (FB1) on ovarian structure and function. Virgin Wistar albino female rats were separated into control and FB1 treatment groups and examined from day 6 of pregnancy until delivery (20 and 50 mg/kg/day). The obtained females of the first (F1) and second generations (F2) were euthanized at 4 weeks of age, and ovary samples were collected. We found that the ovary weight index increased with the high dose of treatment (50 mg/kg/day) among both F1 and F2, similar to that observed in polycystic ovary syndrome. As expected, FB1 at a high dose (50 mg/kg) reduced the number of primordial follicles in F1 and F2, leading to an accelerated age-related decline in reproductive capacity. Moreover, it reduced the fertility rate among F1 females by affecting follicle growth and development, as the number of secondary and tertiary follicles was decreased. Histopathological changes were evidenced by the altered structures of most of the growing follicle oocytes, as revealed by a thinning irregular zona pellucida and pyknosis in granulosa cells. These findings are concomitant with steroidogenesis- and folliculogenesis-related gene expression, as evidenced by the decrease in CYP19 activity and estrogen receptor beta (ESR2) gene expression. Additionally, GDF-9 mRNA levels significantly decreased, and IGF-1 mRNA levels significantly increased. However, the results from the ovaries of the F2 treatment groups were different and unexpected. While there was no significant variation in CYP19 compared to the control, ESR2 significantly increased, leading to stereological and histopathological changes similar to those of the control, except for some altered follicles. The hallmark histological feature was the appearance of vacuolar structures within the oocyte and between granulosa cell layers. Interestingly, the autophagic marker LC3 significantly increased in F2 offspring, whereas this protein significantly decreased in F1 offspring. Therefore, we suggest that the promotion of autophagy among the ovaries of F2 offspring may be considered a recovery mechanism from the effect of prenatal FB1 exposure. Thus, autophagy corrected the effect of FB1 during the early life of F1 females, leading to F2 offspring with ovarian structure and function similar to those of the control. However, the offspring treated females may have early ovarian aging because their ovarian pool was affected.

Subchondral bone loss is an important pathological feature of early-stage temporomandibular joint (TMJ) osteoarthritis (OA). Previous studies focused mainly on the bone resorption by osteoclasts in early-stage OA, but the bone formation feature has not drawn enough attention. Sema4D/Plexin-B1 is a pair of molecules expressed by osteoclast/osteoblast, which is capable of inhibiting bone formation by osteoblasts. The present study found that subchondral bone loss in early-stage TMJ OA was accompanied by up-regulated expression of Sema4D in cartilage and subchondral bone and Plexin-B1 in subchondral bone. Reducing Sema4D level could inhibit the subchondral bone loss and cartilage degeneration of early-stage TMJ OA. In vitro, results revealed that Sema4D could reduce the expression of osteocalcin (OCN) and alkaline phosphatase (ALP), and increase the migrating capability of Plexin-B1-positive osteoblasts. Our results revealed that elevated Sema4D expression in early-stage TMJ OA might decrease the bone formation activity of osteoblasts in the subchondral bone by binding to Plexin-B1 expressed by osteoblasts. Inhibiting Sema4D/Plexin-B1 signaling in the early-stage OA holds promise as a strategy for new therapeutic approaches to osteoarthritis.

Naturally fermented dairy products are an important component of the human diet. They are a valuable source of nutrients as well as vitamins and minerals. Their importance as a source of probiotic bacterial strains should not be overlooked. A number of studies highlights the positive effects of species of the Lactobacillacea on the intestinal microbiota, the overall homeostasis of the body, as well as a complementary treatment for some diseases. However, data on the effects on intestinal epithelial cells of postmetabolites released by bacteria are incomplete. This is likely due to the fact that these effects are species and strain specific. In the present study, we investigated the effects of postmetabolites produced by a pre-selected candidate probiotic strain Limosilactobacillus fermentum on HT-29 intestinal epithelial cells. Our data showed a pronounced proliferative effect, evaluated by flow cytometry, quantification of cell population, and determination of mitotic index. This was accompanied by stabilization of the cell monolayer, measured by increase of TEER (trans epithelial electric resistance) and reorganization of actin filaments. The data obtained are a clear indication of the positive effects, that the products secreted by L. fermentum strain 53 have on the intestinal epithelial cells.

Seeds from several Ribes taxa were surveyed for phenolic compounds and in vitro antiproliferative activity against HT-29 colorectal cancer cells. Total phenolic compounds were analysed through the Folin-Ciocalteu procedure, while phenolic profiles were analysed by LC coupled to a single mass spectrometer Orbitrap using an electrospray interface (ESI). Antitumor effects were established using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Total phenolics ranged from 11.4 in R. alpinum to 94.8 mg of caffeic acid equivalents (CAE)/g in R. nigrum 'Koksa'. Concerning phenolic compounds, four were hydroxylated benzoic acids, four cinnamic acid derivatives, eight flavonoids, and nine flavonoid glycosides. The growth inhibition against HT-29 cancer cells was exercised much better by R. nigrum 'Koksa' and Ribes 'Erkeeni' (GI50 37 and 42 µg/ml). All Ribes extracts, except R. nigrum 'Hara katarlik', showed higher activity than that of R. rubrum (GI50 at 72 h: 99 µg/ml). Interestingly, the highly bioactive extract from Ribes 'Erkeeni' contains all detected phenolics, while R. nigrum 'Koksa' lacks only populnin. Therefore, the high bioactivity found for such extracts could be due to a synergy due to all detected compounds. This work constitutes a comprehensive action for expanding knowledge on the phenolic profiles and antitumor activity of GLA-rich Ribes seeds.

This study focuses on the potential medicinal properties of Campsis radicans L. extracts and its aim is to investigate the antioxidant and antiproliferative effects of these extracts on the human colon adenocarcinoma cell line (HT-29). Cytotoxic activity in the HT-29 cell line was evaluated, and the 3-dimensional structures of phenolic compounds were obtained using the GC-MS method. Docking simulations were performed with AutoDock Vina, targeting proteins that are crucial in the apoptotic pathway (Bax, Bcl-2, and Caspase-3). Drug similarities and ADMET estimates of the phenolic compounds were obtained from databases. The highest antioxidant activity of Campsis radicans L. plant was observed in ethanol and water extracts, with notable inhibition capacities. While the total phenolic content was highest in ethanol, water, and ether extracts respectively the total flavonoid content was highest in ethanol, then ether, and water extracts. Certain elements were undetectable in mineral determination, and others exceeded the toxic doses for plants. The water extract exhibited dose-dependent cytotoxic activity in the HT-29 cell line, with an IC50 value of 4.47 mg/mL. Molecular docking results revealed the binding of phenolic molecules to the active sites of apoptotic pathway proteins. The findings suggest that Campsis radicans L. plant possesses cytotoxic properties, significant phenolic and flavonoid content, and a high antioxidant capacity. These properties make it a potential candidate for treatment use, emphasizing its potential therapeutic value in the HT-29 cell line. Further research and exploration on the identified phenolic compounds could contribute to the development of novel therapeutic agents.

Using the Super-SBM method, this study calculates the carbon emission efficiency (CEE) of 30 provinces in mainland China from 2011 to 2019. Then, using the systematic GMM model, spatial Durbin model, and mediating effect model, it examines the direct effect, spatial effect, and influence mechanism of the digital economy (DE) on CEE. It was found that (1) the DE significantly promoted regional CEE, but had a negative effect on CEE in provinces with high economic correlation; (2) mechanism studies showed that the DE improved CEE by reducing energy intensity, promoting industrial upgrading and green technology innovation; (3) regional heterogeneity analysis found that the DE significantly improved CEE in eastern provinces, but not in central and western provinces. DE improves CEE in provinces with high level of economic development, but decreases CEE in provinces with low level of economic development.This paper provides some empirical and theoretical references for the development of DE to improve CEE.

The synergistic effect of silicon and cerium addition on the oxidation resistance of pack cementation aluminide coating applied on Ni-based superalloy substrate was investigated. The effect of cerium and silicon on the scale morphology, oxidation behavior, and scale spallation tendency are discussed based on the experimental results, using X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray analyses (EDX). In addition, the oxidation resistance was evaluated by measuring the weight of samples after each 16-hour cycle at 1100˚C for 50 cycles. The experiments indicated that silicon addition to aluminide coating improves the oxidation resistance through the formation of β-NiAl1-nSin and δ-Ni2Al3-nSin and δ-Ni2Si phases. Furthermore, the addition of 1% cerium to modified aluminide enhances the formation of the fine-grained microstructure of the β-NiAl and δ-Ni2Al3 and reduces the outward/inward diffusion of elements (so-called blocking effect) which significantly modifies the hot oxidation resistance. The addition of 2% cerium, owing to the distortion of the β-NiAl and δ-Ni2Al3 phases, strictly decreases the hot oxidation resistance and the coating is exfoliated after 450 h at 1100 °C. The cyclic oxidation tests showed that the samples containing 1% cerium and 6% silicon possess the highest hot oxidation resistance in which 2 mg/cm2 weight loss of Ce-Si-aluminide was reported after 800 h. This is attributed to the simultaneous effect of cerium and silicon during the deposition process which reduces the oxygen diffusion and reduces the growth rate of α-Al2O3 during oxidation tests. The α-Al2O3 oxidation layer morphology showed that finer grains are formed in samples containing optimum ratios of cerium and silicon which indicates that these elements improve the coating adhesion and oxidation resistance simultaneously.

Soy isoflavones are considered important sources of bioactive compounds, but they are poorly absorbable, due to their large hydrophilic structures. Some biotransformation strategies have been used to convert the glycosidic form into aglycones, making them available for absorption. This study evaluated the potential of enzymatic and/or microbial fermentation bioprocesses in soymilk extract before and after gastrointestinal in vitro digestion. Commercial β-glucosidase and mix of commercial probiotics containing Lactobacillus acidophilus, L. casei, Lactococcus lactis, Bifidobacterium bifidum e B. lactis were used to biotransform soymilk extract. Isoflavone profile was quantified by HPLC-DAD, total phenolic content by Folin–Ciocalteu test, and antioxidant capacity by ORAC and FRAP. Soymilk enzymatically treated (ET) followed by microbial fermentation (ET+F) resulted in the conversion of glycosylated isoflavones (6-fold lower than control for daidzin and 2-fold for genistin) to aglycones (18-fold greater than control for dadzein and genistein), besides to increase the total phenolic content (3.48 for control and 4.48 mg/ml ET+F) and to improve antioxidant capacity represented by the ORAC (120 for control and 151 mg/ml ET+F) and by the FRAP (285 for control and 317 µl/ml for ET+F) before in vitro digestion. Further, the digested ET+F samples resulted a higher content of genistein (2-fold higher than control) also an increase in the total phenolic content (2.81 for control and 4.03 mg/ml for ET+F) and antioxidant capacity by ORAC were greater compared to undigested samples. In addition, the microbial fermentation process isolated also resulted in the positive effects, but de combination of ET followed by F presented a synergistic effect, suggesting the greater potential for both bioprocesses to contribute to functional and nutritional properties on fermented soy-based products.

New class of triazinoindole bearing thiosemicarbazide (1-25) was synthesized and evaluated for α-glucosidase inhibitory potential. All synthesized analogues exhibited excellent inhibitory potential having IC50 values ranging from 1.30 ± 0.01 to 35.80 ± 0.80 µM when compared with the standard acarbose having IC50 value 38.60 ± 0.20 µM. Among series the analogues 1 and 23 was found the most potent having IC50 values 1.30 ± 0.05 and 1.30 ± 0.01 µM respectively. Structure activity relationship (SAR) was mainly based upon by bring about difference of substituents on phenyl rings. To confirm the binding interactions, molecular docking study was performed. Synthesized analogues were characterized through HREI-MS, 1H and 13C-NMR analysis.

(1) Background: There is a risk of Aflatoxin B1(AFB1) pollution in yellow rice wine[1],threatening human life and health, the risk is a major focus of government attention and social concern.The current detection technology cannot meet the needs of large-scale testing due to the disadvantages of high false positive, cumbersome operating procedures or high cost.Therefore, it is urgent to study and establish a high-sensitivity and high-fast detection method for AFB1 to provide technical support for yellow rice wine quality supervision and risk assessment.; (2) Methods: In this study, three-factor and three-level orthogonal experiments were carried out for oscillation time, reaction temperature and tomography time to determine the best reaction conditions for pretreatment.AFB1 detection was carried out by aflatoxin time-resolved fluorescence immunochromatography technology，Through the ratio of the T signal value of the detection line to the C signal value of the quality control line and the natural logarithmic value of the standard solution concentration[2], a rapid detection technology of time-resolution fluorescence immunochromatography is established.The technology was methodically assessed, the actual yellow rice wine samples were tested, and the results were compared with the HPLC method; (3) Results: The results show that the optimal reaction conditions for pretreatment are: the sample oscillation time is 20min, the sample reaction temperature is 37°C, and the sample chromatography time is 6min. In the actual sample detection of yellow rice wine, The time-resolved fluorescence immunochromatography detection technology established in this study detects AFB1. The detection limit is 0.3 μg·kg-1,The linear range is 0.8-12.0μg·kg-1,The linear equation of the corresponding standard curve y=-0.1913x+0.5206 (R2=0.9948),The standard deviation is 0.029.The results of the in-batch accuracy and precision of this method show that the addition and recovery rate is 77.9% - 105.7%,The coefficient of variation is in 4.5% - 10.3%; Inter-batch accuracy and precision test results show that the addition recovery rate is75.9% - 85.8%,the coefficient of variation is in 8.1% - 13.9%,explain that the detection technology has good accuracy and precision.Compared with HPLC, the relative error is less than 10%,It shows that aflatoxin time-resolution fluorescence immunochromatography technology is in good agreement with the test results of national standard methods; (4) Conclusions:he rapid detection technology of time-resolution fluorescence immunochromatography of AFB1 in yellow rice wine is easy to operate with fast detection speed, high sensitivity, good repeatability and stability, and has broad application prospects.

Nuts are a staple food consumed throughout the world, and their purity is essential to maintaining human health. However, fungal mycotoxins pose one of the real challenges in keeping nuts clean for human consumption. The high cost of equipment, reagents used, standard samples, as well as increased requirements for personnel qualifications limit the use of chromatographic methods in testing laboratories, both manufacturing enterprises and organizations monitoring food safety. The present study aimed to test a new method for extracting aflatoxin B1 using sodium chloride and citric acid instead of methanol present in imported nuts obtained from local markets in Astana (Kazakhstan). The proposed method for extracting aflatoxin B1 from nuts is chemically safe, since the substances used belong to hazard class 3 of the international classification and do not require separate premises in food safety laboratories of the Astana markets and special training of specialists. The technical objective of the method is to replace the reagent (methanol) during the sample preparation process when conducting cocuret enzyme-linked immunosorbent assay. Aflatoxin B1 levels varied depending on the type of nut. Aflatoxin contamination was observed in 35.8% of samples analyzed. These levels of mycotoxin contamination are alarming and raise serious questions about the purity of imported nuts to ensure food safety.

Background: Exposure to chronic low levels of aflatoxin B1 (AFB1) contamination can lead to immune suppression and nutritional consequences that might greatly contributed in the increase of hepatocellular carcinoma (HCC). The toxicity of AFB1 is greatly vary between different population, affected by age, gender, and environmental factors. Material and subjects: Aflatoxin B1 (AFB1) was measured in 50 blood samples collected from non B, C hepatitis viruses and non CMV-Ab liver disease patients from different general hospitals and polyclinic in KSA during period 01-2013 to 06-2014. All Patients demonstrate elevation of ALT and AST with unknown etiology. Serum samples were obtained and kept at −20 °C for AFB1detection. Results: Out of the 50 blood samples, 38 demonstrate a detectable serum level of AFB1 while the remaining 12 patients were AFB1 negative and used as control participants. While AST was non-significantly different in AFB1 exposed patients, ALT was significantly higher in AFB1 positive samples compared to control AFB1-negative. AFB1 was positively correlated with AST and ALT as liver function enzymes and with age as a risk factor of long duration of AFB1 chronic exposure. Multiple linear regression analysis ascertained the association between AFB1 chronic exposure and ALT increase in liver dysfunction Saudi patients. Conclusion: Measurement of elevated ALT as marker of liver injury in AFB1 chronically exposed Saudi patients can help to avoid the future development of HCC. Moreover, early detection of AFB1 exposure, together with early vaccination against HBV and HCV can remove the synergistic effects of these two etiological factors and thus decrease the risk of developing liver cancer.

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

Cordia dichotoma Forst. (F. Boraginaceae) has been traditionally used for the management of a variety of human ailments. In our earlier work, the antidiabetic activity of methanolic bark extract of C. dichotoma (MECD) has been reported. In this paper, two flavonoid molecules were isolated (by column chromatography) and identified (by IR, NMR and Mass spectroscopy/spectrometry) from the MECD with an aim to investigate their antidiabetic effectiveness. Molecular docking and ADMET studies were carried out using AutoDock Vina software and Swiss ADME online tool, respectively. The isolated flavonoids were identified as 3,5,7,3’,4’-tetrahydroxy-4-methoxyflavanone-3-O-L-rhamnopyranoside and 5,7,3’-trihydroxy-4-methoxyflavanone-7-O-L-rhamnopyranoside (quercitrin). Docking and ADMET studies revealed the promising binding affinity of flavonoid molecules for human lysosomal alpha-glucosidase and human pancreatic alpha-amylase with acceptable ADMET properties. Based on computational studies, our study reports the antidiabetic potential of the isolated flavonoids with predictive pharmacokinetics profile.

Background: The intrauterine and early extrauterine development represents a “window of opportunity” in the immunological development. The underlying mechanisms are still poorly understood. The aim of this study was to provide reference values B cell subpopulations in cord blood of term newborns, juveniles and in adults to find the spectrum of their physiological age-related variation. Methods: In this study, we used flow cytometry to evaluate human B lymphocytes and subpopulations in cord blood (n = 10), in peripheral blood from healthy juveniles aged 1 to 17 years (n=20) and from donors aged 24 to 62 years (n = 10). Results: Our findings showed increasing frequencies of IgM memory B cells, class-switched memory B cells, marginal zone B cells and plasmablasts, from cord blood to peripheral blood of juveniles and adults. In con-trast, the percentage of naïve B cells was higher in newborns than in juveniles and adults. The frequencies of were similar in cord blood and peripheral blood of adults. Interestingly, transitional B cells frequencies were similar in cord blood and adults but significantly lower in juveniles. Conclusions: The frequencies of circulating B cell subpopulation are subject to considerable changes during on-togeny, reflecting overlying effects of maturation and of the acquisition of an adaptive immune memory.

In this work a series of experiments on the retention of B1 (riboflavin), B2 (thiamine) and B3 (nicotinic acid) vitamins in the HILIC and RPLC conditions have been performed involving the effects of organic modifier type and content, pH of the eluent, and buffering salt (ammonium acetate) concentration in the mobile phase, as well as temperature of the system. For the needs of this studies three columns of different features have been chosen: Acclaim™ Mixed-Mode HILIC-1 (Dionex), Eurospher II 100-5 HILIC (Knauer) and the RPLC column Nucleodur® C18 Gravity – SB (Macherey –Nagel). The influence of acetonitrile and methanol content in the eluent and process temperature have been tested and basing on that the most promising systems have been selected regarding the possible separation of the vitamins mixture. Both pH and buffering salt concentrations in the eluent have been adjusted in order to indicate the most effective system which turned out to be the one involving the Nucleodur column and the eluent with 90% methanol, at pH 6 and Cbuff = 20 mmol/dm3 that enables separation of the mixture within the time as short as 2.5 minutes at 1.0 mL/s flowrate in isocratic conditions.

Ce-promoted NiMgAl mixed-oxide (NiCex-C, x = 0, 1,5,10) catalysts were prepared from the quaternary hydrotalcite precursors for CO2 hydrogenation to methane. By engineering the Ce contents, NiCe5-C showed its prior catalytic performance in low-temperature CO2 hydrogenation, being about 3 times higher than that of Ce-free NiCe0-C catalyst (TOF of NiCe5-C and NiCe0-C: 1.19 h-1 vs 0.39 h-1 @ 250 oC). With extensive characterization, it was found that Ce dopants promoted the reduction of NiO by adjusting the interaction between Ni and Mg(Ce)AlOx support. The higest ratio of surface Ni0/(Ni2+Ni0) was obtained over NiCe5-C. Meanwhile, the surface basicity was tailored with Ce dopants. The strongest medium-strength basicity and highest capacity of CO2 adsorption was achieved on NiCe5-C with 5wt% Ce content. The TOF tests indicated a good correlation with medium-strength basicity over the NiCex-C samples. The results showed that the high medium-strength and Ce-promoted surface Ni0 species endows the enhanced low-temperature catalytic performance in CO2 hydrogenation to methane.

A series of LaF₃:Ce³⁺ phosphors for the application in photodynamic therapy is synthesized using a one-stage solvothermal synthesis. The conditions providing the maximum intensity of UV- and X-ray-excited luminescence, lowest size and highest colloidal stability of the phosphor nanoparticles are found to respectively include cerium content 5% mol., use of ethanol as the reaction medium for the solvothermal synthesis and addition of polyvinylpyrrolidone as a stabilizer in an optimized amount.

To elucidate the chemical compositions of the sugar fall maple leaves, the methanol extracts were firstly fractionated by ethyl acetate and n-butanol respectively. The phenolic acids-rich fractions (ethyl acetate extracts) were further purified by various chromatographic columns including XAD macroporous resin, Sephadex LH-20, ODS and semi-preparative HPLC to yield the compounds. The isolated compounds were characterized by ¹H-Nuclear Magnetic Resonance (¹H-NMR), ¹³C-NMR, and high resolution electrospray ionisation mass spectral (HR-ESI-MS) spectroscopy. Twenty eight phenolics including fourteen flavonoids (1-14), five quinic acid derivatives (15-19), five galloyl tannins (20-24) and four other phenolic acids (25-28) were isolated and their structures were identified. The isolated compounds were evaluated for their antioxidant and α-glucosidase inhibitory activities. All of the phenolics constituents showed DPPH scavenging antioxidant activities. While, glycosides of quercetin and myricetin, galloyl tannins were showed promising α-glucosidase inhibitory activity. All of the compounds except 4, 11, 12 and 28 were isolated from sugar maple for the first time. Moreover, Compounds 9, 10, 14, 20, 21, 23, 25 and 26 were isolated from the Acer species for the first time.

To determine the mode of action of the effects of phytoalexins in soybeans, we analyzed enzyme inhibition kinetics using Michaelis–Menten plots and the Lineweaver–Burk plots. The results showed that glyceollin showed competitive inhibition, genistein showed noncompetitive, daidzein was uncompetitive, and luteolin showed a mixed mode of action. The Ki values were determined using a Dixon plot as: glyceollin, 18.99; genistein, 15.42; luteolin, 16.81; and daidzein, 9.99 μM, respectively. Furthermore, potential synergistic effects between glyceollin and the three designated polyphenols were investigated. A combination of glyceollin and luteolin (the ratio of 3:7 of glyceollin and luteolin) had synergistic effects on α-glucosidase inhibition according to combination index (CI)-isobologram equation. Collectively, these results showed that a combination of glyceollin and luteolin has the potential to inhibit α-glucosidase activity via a synergistic mode of action.

Abstract: The kallikrein-kinin system consists of the two kininogen substrates, present in blood plasma, and of two serine proteases, the plasma and tissue kallikreins. The action of the latter on kininogens produce small peptides, the kinins, short lived but endowed by powerful pharmacologic actions on blood vessels and other tissues. Many recent and exciting therapeutic developments in the field are briefly summarized. Notably, various novel strategies are being clinically developed to inhibit the formation of bradykinin or block its receptors in the management of hereditary angioedema. The interventions include orally bioavailable drugs, biotechnological proteins, and gene therapy. These approaches are currently explored in a variety of other inflammatory and thrombotic disorders. Harnessing controlled kinin formation is also of potential therapeutic interest as shown by the clinical development of recombinant tissue kallikrein for ischemic stroke and renal disease. Biomarkers of a kinin-mediated disorders, frequently implicating edemas, include the consumption of kininogen(s), plasma kallikrein activity, and the detection of circulating kinin metabolites such as fragments BK_1-5 and BK_2-9. Novel opportunities to clinically apply the underexploited drugs of the kallikrein-kinin system are briefly reviewed. This personal perspective is offered by an observer of, and a participant in drug characterization during the last 4 decades.

High temperature titanium alloys are widely used in aerospace hot parts, however, the thermal barrier temperature of 600 oC limits its service temperature. In this paper, a two-step hot-dip plating method is proposed to prepare the composite coating containing Ce on the surface of titanium alloy, which can make the oxidation resistance temperature of titanium alloy reach 800 oC The microstructure, phase composition and element distribution of Ce-containing Ti-Al-Si hot-dip coating, Ce-containing Ti-Al-Si pre-oxidation coating and Ce-containing Ti-Al-Si high-temperature oxidation coating were studied by X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS), respectively. The results show that the Ti-Al-Si hot-dip coating containing Ce is mainly composed of (Ti,Ce)(Al,Si)3 alloy phase layer, and the Ti-Al-Si pre-oxidation coating containing Ce is mainly composed of Ti-Al binary system phase layer and dense Al2O3 layer rich in CeO2. Ce in the high temperature oxidation coating of Ti-Al-Si containing Ce is mainly distributed in Ti3Al, TiAl, TiAl3+Ti5Si3 mixed phase layer and Al2O3. The addition of Ce can promote the formation of continuous Al2O3 layer, improve the uniformity of composite coating, prevent the spread of cracks, and improve the high temperature oxidation resistance of Ti-Al-Si coating.

The two-dimensional, laterally-averaged mechanistic eutrophication model CE-QUAL-W2 version 3.72 was used to predict chlorophyll-a concentrations across two different time periods in the Neuse River Estuary, North Carolina. Chlorophyll calibration was performed for two time periods simultaneously by performing by a full-factorial experiment that tested seven algal kinetic growth parameters over three levels for a single algal group. A cluster of up to six computers each running between two and ten instances of the program was used to complete and manage the data for 2187 runs for each time period. A set of six criteria were used to determine which runs performed acceptably, yielding a group of 27 cases that met all of the criteria. Calibration performance of the set of cases outperformed a previously calibrated model using three algal groups that met only four of the six selection criteria. Calibration performed this way allowed for a more rational specification of model calibration performance and provided uncertainty estimates of model predictions, albeit at the cost of a considerable increase in computational requirements that necessitated the use of a computer cluster.

Curcuma longa is only a rich source of curcumin (1) and its major analogues demethoxycurcumin (2) and bisdemethoxycurcumin (3) among the Curcuma species. The content ratio of these three curcumins in turmeric is depended on the varieties and growing environment. Recently, curcumin (1) has been reported as potential inhibitor of hepatic and enzymatic protein tyrosine phosphatase 1B (PTP1B) and its related disorders such as hypertriglyceridemia, hyperlipidemia and liver steatosis. Thus, we further purified curcumins (1–3) from C. longa and investigated their inhibitory effects against PTP1B and α-glucosidase enzymes. As the result, curcumins (1–3) exhibited potential PTP1B inhibition with IC50 values of 37.8 ± 1.4, 45.3 ± 0.7, and 72.6 ± 1.1 μM, respectively, and α-glucosidase inhibition with similar manner (IC50 values of 78.2 ± 0.2, 82.4 ± 0.6, and 90.6 ± 1.0 μM, respectively). These results reveal a key role of methoxylation in the variation of PTP1B and α-glucosidase inhibitory activity for these curcumins. In addition, density functional theory (DFT) was used accompanying with molecular docking (MD) to analyze the ligand stability and the interaction of curcumins (1–3) with PTP1B and glucoside hydrolase proteins. Assay-based results and the MD data obtained are highly correlation suggesting that the deterioration of the enzyme activity caused by the distortion of structural conformation of PTP1B and glucoside hydrolase may be related to the arrangement of amino acids in protein structure. This reported for the first time that inhibitory effects of curcumins (1–3) against PTP1B and glucoside hydrolase have been examined in vitro and in silico as well.

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

Endotoxins are toxic substances that widely exist in the environment and can enter the intestine with food and other substances. Intestinal epithelial cells are protected by a mucus layer that contains MUC2 as its main structural component. However, a detailed understanding of the mechanisms involved in the function of the mucus barrier in endotoxin penetration is lacking. Here, we established the most suitable proportion of Caco-2/HT-29 co-culture cells as a powerful tool to evaluate the intestinal mucus layer. Our findings significantly advance current knowledge as focal adhesion and ECM-receptor interaction were identified as the two most significantly implicated pathways in MUC2 small interfering RNA (siRNA)-transfected Caco-2/HT-29 co-culture cells after 24 h of LPS stimulation. When the mucus layer was not intact, LPS was found to damage the tight junctions of Caco-2/HT29 co-cultured cells. Furthermore, LPS was demonstrated to inhibit the integrin-mediated focal adhesion structure and damage the matrix network structure of the extracellular and actin microfilament skeletons. Ultimately, LPS inhibited the interactive communication between the extracellular matrix and the cytoskeleton for 24 h in the siMUC2 group compared with the LPS(+) and LPS(-) groups. Overall, we recognized the potential of MUC2 as a tool for barrier function in several intestinal bacterial diseases.

Aflatoxin B1 (AFB1) is a mycotoxin considered as a potent carcinogenic for humans that contaminates a wide range of crops. Various strategies have been established to reduce or block the synthesis of AFB1 in food and feeds. The use of aqueous extracts derived from plants with high antioxidant activity has been a subject of study in recent years due to their efficacy in inhibiting AFB1. In this study, we assessed the effect of Aloysia citrodora aqueous extract on Aspergillus flavus growth and on AFB1 production. A bio-guided fractionation followed by High Performance Liquid Chromatography (HPLC) and Mass spectrometry analysis of active fraction were applied to identify the candidate molecules responsible for the dose-effect inhibition of AFB1 synthesis. Our results revealed that polyphenols are the molecules implicated in AFB1 inhibition, achieving almost a total inhibition of the toxin production (99%). We identified luteoline 7- diglucuronide as one of the main constituents in A. citrodora extract, and demonstrated that it is able to inhibit, by itself, AFB1 production by 57%. This is the first study demonstrating the anti-Aflatoxin B1 effect of this molecule, while other polyphenols surely intervene in A. citrodora anti-AFB1 activity.

Several therapeutic monoclonal antibodies are approved by FDA against the PD-1/PD-L1 (programmed death-1/programmed death ligand-1) immune checkpoint, which has been a great success in cancer treatment. However, existing therapeutics, including small molecules inhibitors against PD-L1 checkpoint have certain drawbacks such as high cost and drug resistance that challenge the current available anti-PD-L1 therapy. Thereof, this study presents the screening of 32552 compounds from Natural Product Atlas database against PD-L1, including three steps of structure-based virtual screening and binding free energy refinement for the selection of potent PD-L1 inhibitors. Subsequently, five natural compounds, i.e., Neoenactin B1, Actinofuranone I, Cosmosporin, Ganocapenoid A, and 3-[3-hydroxy-4-(3-methylbut-2-enyl)phenyl]-5-(4-hydroxybenzyl)-4-methyldihydrofuran-2(3H)-one, were collected based on the ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiling and binding free energy (>-70 kcal/mol) for further computational investigation by comparison to co-crystallised ligand, i.e. JQT inhibitor. Based on interaction mapping, explicit 100 ns molecular dynamics simulation, and post binding free energy calculations, all the compounds exhibited intermolecular interactions (hydrogen and hydrophobic) with essential residues and substantial complex stability by comparison to the JQT inhibitor. Collectively, the calculated results advocate the selected natural compounds as the putative potent inhibitors of PD-L1 and, therefore, can be considered for further development of PD-L1 immune checkpoint inhibitor in cancer immunotherapy.

Increased gut permeability (leaky gut) with increased translocation of Gram-negative bacteria plays a role in the gut-brain axis through effects on systemic immune-inflammatory processes. Deficit schizophrenia is characterized by an immune-inflammatory response combined with a deficit in natural IgM antibodies to oxidative specific epitopes (OSEs), which are a first line defense against bacterial infections. This study measured plasma IgA/IgM responses to 5 Gram-negative bacteria in association with IgM responses to malondialdehyde (MDA) and azelaic acid in 80 schizophrenia patients (40 with the deficit syndrome and 40 without) and in 38 healthy controls.Deficit schizophrenia was characterized by significantly increased IgA responses to Hafnei alvei, Pseudomonas aeruginosa, Morganella morganii and Klebsiella pneumoniae as compared with non-deficit schizophrenia. The presence of deficit schizophrenia was highly predicted by increased IgA responses to Pseudomonas putida and IgM responses to all 5 Gram-negative bacteria and lowered natural IgM to MDA and azelaic acid with a bootstrap area under the ROC curve of 0.960 (2000 random curves). A large proportion of the variance (41.5%) in the PANSS negative score was explained by the regression on IgA responses to K. pneumoniae and IgM responses to the 5 enterobacteria coupled with lowered IgM antibodies to azelaic acid. There were significant associations between IgA levels to Gram-negative bacteria and Mini Mental State Examination, Boston naming test, Verbal Fluency and Word List Memory test scores.These findings provide further evidence that deficit schizophrenia is a distinct phenotype of schizophrenia, which is characterized by an increased impact of Gram-negative commensal bacteria coupled with a deficit in natural IgM, pointing to aberrations in B1 cells. It is concluded that increased bacterial translocation and deficits in the compensatory immune-regulatory system (CIRS) may drive negative symptoms and neurocognitive impairments, which are hallmarks of deficit schizophrenia.

Data-driven models (DDMs) are extensively used in environmental modeling but face challenges due to limited training data and potential results not adhering to physical laws. To address this challenge, this study developed a process-guided deep learning (PGDL) model, integrating a long short-term memory (LSTM) neural network and a process-based model (PBM), CE-QUAL-W2 (W2), to predict water temperature in a stratified reservoir. The PGDL included an energy constraint term from W2's thermal energy equilibrium into the cost function of the LSTM, besides the mean square error term. In PGDL, parameters were optimized by penalizing deviations from the energy law, ensuring adherence to physical constraints. Compared to LSTM, PGDL demonstrated enhanced satisfaction with the energy balance and superior performance in water temperature prediction. Even with less field data for training, PGDL outperformed both LSTM and calibrated W2 after pre-training with data generated using the uncalibrated W2. Therefore, integration of DDM with a PBM ensured physical consistency in water temperature prediction for complex stratified reservoirs with limited data. Moreover, pre-training the PGDL with PBM proved highly effective in mitigating bias and variance due to insufficient field measurement data.

Keywords: Wall-like RC columns; Strengthening; FRP; NSM rebars; Steel plates; Testing; FE modeling; Preloading.

The incidence of chronic enteropathies (CE), in particular food-responsive enteropathies (FRE) in dogs, is on the rise in veterinary practice. The symptoms of these digestive disorders cannot be alleviated with the use of commercial hypoallergenic feeds. The applicability of novel substrates in hypoallergenic dog feeds is limited, and edible insects could pose a viable alternative. Insects have a high nutritional value, and their potential can be harnessed to design personalized nutrition strategies. However, the use of insects in animal feeds should be rigorously tested. The aim of this study was to analyze the applicability of edible insects as a source of dietary protein for companion animals, including the current and future prospects. Canine food formulas should be evaluated in a clinical setting. The role edible insects in pet diets and the efficacy of this substrate in animal nutrition should be examined in advanced clinical trials in gastroenterology, histology, immunology, and microbiology. These efforts are required to guarantee the safety and efficacy of innovative insect-based feeds and to increase their popularity among veterinary practitioners, pet food producers, and animal owners.

The textile and clothing (T&C) industry is not usually viewed as an exemplar of sustainable de-velopment and the circular economy, as the industry has hitherto made its products in linear fashion, with relatively little recycling of the finished goods. This article examines the industry’s approach to the core sustainability concept and the circular economy in particular, through a re-view of the available academic literature, evidence from corporate sustainability reports and websites, and feedback from an online survey of industry professionals. The role of digital technology deployment in engendering sustainability and the circular economy in the industry is also explored. The study finds that whilst sustainability is now firmly embedded at the strategic level in the vast majority of companies studied, attitudes towards the circular economy remain fickle. The use of digital technologies in support of sustainability objectives is also limited at present, but the article concludes that the need to meet compliance requirements and new cus-tomer perceptions of sustainability will speed the transition to circular economy activities, facili-tated by greater exploitation of digital technologies. Building upon the research findings, existing models and an initial conceptual framework, a simple operational model for initiating such a transition for small-to-medium sized enterprises in the T&C industry is put forward.

Concern over potential antimony mediated toxicity from mining and smelting activities has instigated novel concepts toward removing aqueous antimony ions. The iron based adsorbent Fe3O4/HCO was found to be efficient for treating antimony-containing wastewater However, ineffective methodology for preparation limited its effective adsorption capacity and thus wider application. In this study, a new type of HCO-doped-(Fe3O4)x adsorbent was prepared by co-precipitation method for doping Fe3O4 into HCO sludge (HCO), thereby improving adsorption performance for Sb(III) and Sb(V) ions, with the maximum adsorbing capacity being 44.46 mg/g and 47.91 mg/g, respectively. According to the results of BET, SEM-EDS, XRD and XPS, it were confirmed that the FeOOH and X≡Fe-OH were formed during the preparation process, bring about the increased the surface area, thus resulting in further increase of surface area, hydroxyl groups and the net negative ionic charge. Moreover, the adsorption kinetics followed the pseudo-second-order kinetic model which indicated that adsorption process of Sb(III)/Sb(V) by HCO-doped-(Fe3O4)x adsorbent was controlled by chemical reaction. The main adsorption mechanism is that antimony ion and amorphous iron oxide X≡Fe-OH undergo coordination exchange reaction and complexation reaction with CeO2 or Ce2O3. Furthermore, HCO-doped-(Fe3O4)x could adapt to wide pH and had stable adsorption ability after regeneration. The good adsorption performance of HCO-doped-(Fe3O4)x makes it a potential applications of adsorbent for removal of antimony.

Separase is a key cysteine protease to separate sister chromatids through digestion of cohesion ring that inhibits chromosome segregation as trigger of metaphase–anaphase transition in eukaryotes and highly regulated its activity by binding with securin and cyclinB-CDK1 complex. Those bindings prevent proteolytic activity of separase until the onset of anaphase. Chromosome missegregation and aneuploidy are frequently observed in malignancies. However, there are some difficulties for biochemical examinations due to instability of separase in vitro and a few spatiotemporal resolution approaches monitoring live separase activity throughout mitotic processes. Here we have developed FRET-based molecular sensors including GFP variants with separase cleavable sequences as donor and covalently attached fluorescent dye as acceptor molecules applicable to conventional live cell imaging and flow cytometric analysis because of efficient live cell uptake. We investigated performance of equivalent molecular sensors localized or not localized inside nucleus under cell cycle control using flow cytometry. Synchronized cell cycle progression rendered significant separase activity detections in both molecular sensors. We obtained consistent outcomes with localized molecular sensor introduction and cell cycle control by fluorescent microscopic observations. We thus established live cell separase activity monitoring systems specifically or statistically that could lead to elucidate separase properties in detail.

Hypertrophic Cardiomyopathy (HCM) is a common inherited disorder characterized by unexplained left ventricular hypertrophy, with or without left ventricular outflow tract (LVOT) obstruction. Single nuclei RNA-sequencing (snRNA-seq) of both obstructive and nonobstructive HCM patient samples have revealed alterations in communication between various cell types but a direct and integrated comparison between the two HCM phenotypes has not been reported. We performed a bioinformatic analysis of HCM snRNA-seq datasets from obstructive and nonobstructive patient samples to identify differentially expressed genes and distinctive patterns of intercellular communication. Differential gene expression analysis revealed 37 differentially expressed genes, predominantly in cardiomyocytes but also in other cell types, relevant to aging, muscle contraction, cell motility and the extracellular matrix. Intercellular communication was generally reduced in HCM, affecting the extracellular matrix, growth factor binding, integrin binding, PDGF binding and SMAD binding, but with increases in adenylate cyclase binding, calcium channel inhibitor activity, and serine-threonine kinase activity in nonobstructive HCM. Increases in neuron to leukocyte and dendritic cell communication, in fibroblast to leukocyte and dendritic cell communication and in endothelial cell communication to other cell types, largely through changes in expression of integrin-b1 and its cognate ligands, were also noted. These findings indicate both common and distinct physiological mechanisms affecting the pathogenesis of obstructive and nonobstructive HCM and provide opportunities for personalized management of different HCM phenotypes.

Obesity results in hepatic fat accumulation, i.e., steatosis. Besides the fat overload, impaired fatty acid β-oxidation also promotes steatosis. Fatty acid β-oxidation takes place in mitochondria and peroxisomes. Usually very long chain and branched-chain fatty acids are first oxidized in peroxisomes, and the resultant short chain fatty acids are further oxidized in mitochondria. Peroxisome biogenesis is regulated by peroxin 16 (PEX16). In liver-specific PEX16 knockout (Pex16Alb-Cre) mice, hepatocyte peroxisomes were absent, but hepatocytes proliferated, and liver mass was enlarged. These results suggest that normal liver peroxisomes restrain hepatocyte proliferation and liver sizes. After high fat diet (HFD) feeding, body weights were increased in PEX16 floxed (Pex16fl/fl) mice and adipose-specific PEX16 knockout (Pex16AdipoQ-Cre) mice but not in the Pex16Alb-Cre mice, suggesting that the development of obesity is regulated by liver PEX16 but not by adipose PEX16. However, it was previously reported that HFD-induced obesity in the Pex16AdipoQ-Cre mice was more severe than in the wild type mice, which was not observed until 27 weeks of HFD feeding. Thus, liver initiates the development of obesity, which is enhanced by abnormal adipocytes. HFD increased liver mass in the Pex16fl/fl mice but somehow reduced the already enlarged liver mass in the Pex16Alb-Cre mice. Basal levels of serum triglyceride, free fatty acids and cholesterol were decreased whereas serum bile acids were increased in the Pex16Alb-Cre mice, and HFD-induced steatosis was not observed in the Pex16Alb-Cre mice. These results suggest that normal liver peroxisomes contribute to the development of liver steatosis and obesity.

The solute carrier family 25 (SLC25) participates in the transport of metabolites and cofactors across the membranes of mitochondria, plastids, peroxisomes, and endoplasmic reticulum. By calling for genomic blocks involved in adjacent metabolic reactions, this report introduces gene clusters of the Slc25 subfamily 44, stilbene and chalcone synthases, and subunits of the mitochondrial electron transfer complexes. The Slc25A44 gene was found ubiquitously expressed and transcriptionally co-regulated with energy metabolism genes in human, mouse, and Arabidopsis thaliana. The Slc25A44s also had no homozygous missense mutation and were highly conserved at intra-species level with the majority of polymorphism present in the non-coding regions. When expressed in oocytes, AdSlc25A44 from Arachis duranensis showed transport activity for the common precursors of flavonoids, stilbenoids, and ubiquinone. Accordingly, AdSLC25A44 and its human orthologue HsSLC25A44 elevated the production of para-coumaric, 4-aminobenzoic, and 4-hydroxybenzoic acids in Saccharomyces cerevisiae strains designed to produce para-coumaric acid via different pathways. Moreover, the engineered SLC25 subfamily specific signature, i.e., AdSLC25A44^LWW206IQF, had a stronger effect on para-coumaric acid secretion than the native variant. Importantly, the aerobic growth-rate of S. cerevisiae was significantly higher when expressing the AdSLC25A44, HsSLC25A44, or AdSLC25A44^LWW206IQF. These results suggest that SLC25A44 is an essential mitochondrion-ER-nucleus zone transporter associated with metabolism of secondary metabolites and energy.

Statistical denoising techniques have been well studied, however many challenges still remain. This 9 article focuses on determining the least necessary number of significant samples in a statistical pop-10 ulation sampling, while minimizing the impact on the statistical detection of the fiber Bragg grating 11 (FBG) power spectra. This is achieved by using Bayesian decision making, small population statis-12 tics while excluding false detection. First, we investigate the impact of two-sided sliding window 13 technique applied near the cell under the test. The window size varies from 8 to 60 samples. The 14 considered maximum size of population sampling is connected with the number of wavelength 15 samples within the bandwidth of the symmetrical FBG power spectra peaks. Regarding the sym-16 metry of FBG power spectra peaks and the possible reduction of computational demands, we inves-17 tigate the impact of a one-sided sliding window. This enables to achieve less processing latency for 18 real time applications thus brings benefits to FBG-based fiber optical sensing. Both, two- and one-19 sided small population sampling techniques are then experimentally verified. Detection results are 20 analyzed in depth via calculating detection thresholds by using the small size window sliding along-21 side the waveband. From results achieved, it was found that the normality three-sigma rule does 22 not need to be followed while using the small population sampling. Experimental demonstrations 23 and analyses showed that the proposed concept of denoising and statistical threshold detection 24 based on the sliding window does not depend on the prior knowledge of probability distribution 25 functions of the FBG power spectra peaks level and background noise. We have also found that the 26 thresholds’ adaptability mainly depends on the statistical numerical characteristics of the above ad-27 ditive mixture of the FBG power spectra peaks signals and background noise.

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.

The first detection of gypsum (CaSO4.2H2O) by the Mars Science Laboratory (MSL) rover Curiosity in the Gale Crater, Mars created a profound impact on planetary science and exploration. The unique capability of plasma spectroscopy involving in situ elemental analysis in extraterrestrial environments, suggesting the presence of water in the red planet based on phase characterization and providing a clue to Martian paleoclimate. The key to gypsum as an ideal paleoclimate proxy lies in its textural variants, and in this study terrestrial gypsum samples from varied locations and textural types have been analyzed by Laser Induced Breakdown Spectroscopy (LIBS) technique. Petrographic, sub-microscopic and powder X-ray diffraction characterizations confirm the presence of gypsum (hydrated calcium sulphate; CaSO4.2H2O), bassanite (semi-hydrated calcium sulphate; CaSO4.1/2H2O) and anhydrite (anhydrous calcium sulphate; CaSO4) along with accessory phases (quartz and jarosite). The principal component analysis of LIBS spectra from texturally varied gypsums can be differentiated from one another because of the chemical variability in their elemental concentrations. The concentration of gypsum is determined from the partial least-square regressions model. Rapid characterization of gypsum samples with LIBS is expected to work well in extraterrestrial environments.

The human chromosome 11q13 (HSA 11q13) genomic locus is a major cancer hotspot and has been established as the most frequently altered by amplification in a variety of human cancers. The fatty acid desaturase genes (FADS1, FADS2 and FADS3) localize to the 11q12- 13.1 region. FADS2 activity is promiscuous, catalyzing biosynthesis of polyunsaturated and monounsaturated fatty acids, including unsaturated branched chain fatty acids (BCFA) by Δ6, Δ8, and Δ4 desaturation toward at least 16 substrates. Our main aim here is to review known and putative consequences of FADS2 dysregulation due to effects on the 11q13 locus in various cancer types. We searched PubMed and Google Scholar databases for articles that showed 11q13 amplification and studies reporting FADS2 function in various cancer types. FADS2 silencing causes synthesis of sciadonic acid (ScA, 5Z,11Z,14Z-20:3) in MCF7 cells and breast cancer in vivo. 5Z,11Z,14Z-20:3 is structurally identical to the eicosanoid precursor arachidonic acid (5Z,8Z,11Z,14Z–20:4) except it lacks the internal Δ8 double bond required for prostaglandin and leukotriene synthesis, among other eicosanoids. Melanoma, prostate, liver and lung cancer cells insensitive to SCD inhibition show increased FADS2 activity leading to sapienic acid (16:1n10) biosynthesis from 16:0. Elevated serum mead acid (20:3n-9) levels were found in more than a third of hepatocellular carcinoma patients, indicative of an unsatisfied demand for arachidonic acid, likely as a substrate for eicosanoids. A highly expressed circular RNA (hsa_circ_022382) within an exonic region of FADS2 is associated with shorter overall survival in colorectal cancer patients. Similarly, in lung cancer tissues circFADS2 RNA is highly expressed. Palmitic acid (16:0) is a common substrate for SCD and FADS2. FADS2 circular RNAs are at high levels in colorectal and lung cancer tissues. The evidence thusfar supports an effort for future research on the role of FADS2 as a tumor suppressor in a range of neoplastic disorders.

Background: Cord blood represents a link between intrauterine and early extrauterine development. Cord blood cells map an important time frame in human immune imprinting processes. It is unknown whether sex of the newborn affects the lymphocyte subpopulations in cord blood. Methods: 9 B and 21 T cell subpopulations were characterized by flow cytometry in human cord blood from 16 male and 21 female newborns, respectively. Results: Except for marginal zone B cells and transitional B cells, B cell count in all subsets was higher in cord blood of male newborns than in female newborns. Frequency of naive thymus negative Th cells was significantly higher in male cord blood whereas the remaining T cell subpopulations showed a higher count in cord blood of female newborns. Conclusion: Our study is the first revealing sex differences in B and T cell subpopulations of human cord blood. These results indicate that sex might have a higher impact for the developing immune system urging the need to expand research in this area.

Choline is metabolized by the gut microbiota into trimethylamine (TMA), the precursor of pro-atherosclerotic molecule trimethylamine N-oxide (TMAO). Reduction of TMA formation has been shown to provide to cardioprotective effects, and some phytochemicals may produce such reduction. This study aimed to develop an optimized, high-throughput anaerobic fermentation methodology to study inhibition of choline microbial metabolism into TMA by phenolic compounds with healthy human fecal starter. Optimal fermentation conditions were: 20 % fecal slurry (1:10 in PBS), 100 M choline, and 12 h fermentation. Also, 10 mM of 3,3-dimethyl-1-butanol (DMB) was defined as a positive TMA production inhibitor, achieving a ~50 % reduction in TMA production. Gallic acid and chlorogenic acid reported higher TMA inhibitory potential (maximum of 80 -90 % in. TMA production inhibition), with IC50 around 5 mM. Nor DMB neither gallic acid and chlorogenic acid reduced TMA production through cytotoxic effects, indicating mechanisms such as altered TMA lyase activity or expression.

In recent years there has been increasing interest in the discovery of new natural herbal remedies for the treatment of common conditions such as diabetes and inflammatory diseases. In this context, this paper analyzed the antidiabetic and anti-inflammatory potential of two plants of the genus Artemisia: Artemisia absinthium (wormwood) and Artemisia vulgaris (mugwort) and Trigonella foenum-graecum (fenugreek) plants less studied from this point of view. Thus, hydroal-coholic extracts (50% EtOH v/v, 10% mass) were made, which were processed by membrane technologies, micro- and ultrafiltration, in order to concentrate the biologically active principles. The extracts were then analyzed in terms of content in active principles of interest (polyphenols, flavones). The antidiabetic activity of the extracts was analyzed by testing their ability to inhibit α-amylase and α-glucosidase and the anti-inflammatory activity by testing the ability to inhibit hyaluronidase (HYA) and lipoxygenase (LOX). Thus, the T. foenum-graecum extracts showed a high inhibitory activity on α-amylase 3.22 ± 0.3 g / mL (compared to the standard used - IC50 acarbose = 3.5 g / mL) and a high inhibitory activity on LOX: 19.69 ± 0.52 g/mL (compared to all standards used). The concentrated extract of Artemisia vulgaris showed increased activity of inhibition of α-amylase - IC50 = 8.57 ± 2.31g/mL and moderate activity of inhibition of HYA - IC50 = 17.18 g/mL compared to ibuprofen, the standard used - IC50 = 5.73 g/mL. The concentrated extract of Artemisia absinthium showed a pronounced activity of inhibition of LOX - IC50 = 19.71 g / mL, compared to the standard - rutin - IC50 = 22.34 g/mL).

Telomeres in epithelial tumours are usually maintained by telomerase, however, in the breast cancer MDA-MB-231 cell line, polyploid cells, induced by doxorubicin (DOX) were found, after mitotic slippage, transiently shifting to recombinatory alternative telomere lengthening (ALT) in PML bodies (APBs). The involvement of the meiotic recombination proteins was evidenced here by juxta-co-localisation of SPO11, DMC1 and RAD51/γH2AX with APBs in these and melanoma SkMel28-DOX-treated cells. Using sublethal doses of DOX we also observed the formation of the PML dimeric rod tandems linking γH2AX/TRF2 foci into ribbons discontinuously inserted into lamin B1 and circumventing cell nuclei. Next, we link these PML-lamin B1 insertions and peripheral rotation of the tandemly linked telomere repeats with the mobility of the nuclear envelope limited chromatin sheets (ELCS). ELCSs comprise two layers of the criss-crossed ~30 nm granules derived from surface heterochromatin (epichromatin) which contains telomere repeats enriched in GpC, PML, and ALU. ELCS protrude, circumvent, loop, split, fuse, and rejoin polyploid cell nuclei. We propose this gear-wheel-like turnover of telomere repeats to be used for the homology search. Interstitial and end-telomere repeats flanked by fragile ALU-Z flipons become recognised by SPO11 nuclease, attract TRF2, PML, and meiotic recombinases. Subsequently, they perform ALT recombining subtelomeres and telomeres or undergo non-homologous end-joining and chromosome rearrangements with ELCS. This mechanism increases the chance of cell survival and may be involved in chromothripsis.

Fosmidomycin (FOS) is a naturally occurring compound active against the enzyme DXR in the MEP pathway, and using it as a template for lead structure design is an effective strategy in developing new active compounds. In this work, by replacing the hydroxamate unit of FOS with pyrazole, isoxazole and the related heterocycles that also have the metal ion binding affinity, while retaining the monophosphonic acid in FOS or replacing it with a bisphosphonic acid group, heterocycle-containing mono- and bisphosphonic acid compounds as FOS analogs were designed. The key steps involved in the facile synthesis of these FOS analogs include the Michael addition of diethyl vinylphosphonate or tetraethyl vinylidenebisphosphonate to β-dicarbonyl compounds and the subsequent cyclic condensation with hydrazine or hydroxylamine. Two additional isoxazolinone-bearing FOS analogs were synthesized by the Michaelis-Becker reaction with diethyl phosphite as a key step. The bioactivity evaluation on model plants demonstrated that several compounds have better herbicidal activities compared to FOS, with the most active compound showing a 3.7-fold inhibitory activity on Arabidopsis thaliana, while on the root and stalk of Brassica napus L. and Echinochloa crus-galli in pre-emergence inhibitory activity test, the activities of this compound were found to be 3.2- and 14.3-, 5.4- and 9.4-fold, respectively, and in post-emergency activity test on Amaranthus retroflexus and Echinochloa crus-galli, 2.2- and 2.0-fold inhibition activities were displayed. Despite the significant herbicidal activity, this compound exhibited a DXR inhibitory activity lower than that of FOS but comparable to that of other non-hydroxamate DXR inhibitors, and the dimethylallyl pyrophosphate rescue assay gave no statistical significance, suggesting a different target might be involved in the inhibiting process. This work demonstrates that using bioisosteric replacement can be considered a valuable strategy for discovering new FOS analogs that may have high herbicidal activity.

This work reports of the use of a bench scale chemostat (CSTR) in continuous mode and of a pilot scale membrane bioreactor (MBR) in fed-batch mode to intensively produce acetic and butyric acids using Cl. butyricum grown on synthetic media. These studies were then used to perform a cost estimation study of the MBR system to assess the potential economic impact of this proposed methodology. The MBR system was found highly productive reaching 37.88 g L-1 h-1 of acetic and 14.44 g L-1 h-1 of volumetric cell productivity, favoring acetic acid production to butyric at a ratio 3:1. The cost of preparation and production of carboxylic acids using this system was found as 0.0062 £PS/kg respectively and an up to 99% carbon recovery.

Lignocellulosic biomass fractionation is typically performed using methods that are somehow harsh to the environment, such as in the case of the kraft pulping. In recent years, the development of new sustainable and environmentally friendly alternatives has grown significantly. Among the developed systems, bio-based solvents emerge as promising alternatives for biomass processing. Therefore, in the present work, the bio-based and renewable chemicals, levulinic acid (LA) and formic acid (FA), were combined to fractionate lignocellulosic waste (i.e., Maritime pine sawdust) and isolate lignin. Different parameters, such as LA/FA ratio, temperature, and extraction time, were optimized to boost the yield and purity of extracted lignin. The LA/FA ratio was found to be crucial regarding the superior lignin extraction from the waste biomass. Moreover, the increase in temperature and extraction time enhances the amount of extracted residue but compromises the lignin purity and reduces its molecular weight. The electron microscopy images revealed that biomass samples suffer significant structural and morphological changes, which further suggests the suitability of the new developed bio-fractionation process. Same was concluded by the FTIR analysis, in which no remaining lignin was detected in the cellulose-rich fraction. Overall, the novel combination of bio-sourced FA and LA has shown to be a very promising system for lignin extraction of high purity from biomass waste, thus contributing to extend the opportunities of lignin manipulation and valorisation into novel added-value biomaterials.

The food additive sorbic acid is considered as an effective preservative for certain cereal products, and propionic acid is commonly added in bakery wares, e.g. bread and fine bakery wares. The aim of this study is to develop and validate a new nuclear magnetic resonance spectroscopy (¹H NMR) method for routine screening and quantification of sorbic and propionic acids in bread and several bakery products for quality control purposes. Results showed that none of the screened samples contained higher concentrations than regulatory maximum limits. However, for some samples, labelling of preservatives was lacking or they were used in food categories, for which the use is not approved. It can be concluded that the developed NMR method can be used for routine screening of bakery products.

Sulfonated carbon was used as an efficient and reusable heterogeneous solid acid catalyst for the synthesis of biodiesel via esterification of oleic acid with methanol under high voltage conditions. Using an inexpensive and reusable catalyst, environmental benignity, excellent yields in short times, synthesis in atmospheric pressure and low temperature conditions are some of the important features of this protocol. In the final results were confirmed by GC.

Ageing is associated with a decline in both Nrf2 activity and DNA repair efficiency, leading to the accumulation of DNA damage and an increased risk of cancer. Understanding the mechanisms behind the increased level of damaged DNA during ageing is crucial for developing interventions to mitigate age-related cancer risk and improve overall health in older individuals. (Poly)phenols are plant-derived bioactive compounds that undergo metabolism into simpler phenolic catabolites following ingestion. While these compounds have been associated with various health benefits, further analysis of their bioavailable catabolites is necessary. To this end, four phenolic catabolites derived from colonic microbiota were investigated for their ability to reduce DNA damage in response to oxidative challenge and modulate the Nrf2-Antixoidant Response Element pathway. Normal and adenocarcinoma colonocyte cell lines (CCD 841 CoN, & HT29 respectively) were exposed to sub cytotoxic concentrations (>10 µM,) of hydroxylated (4-hydroxybenzoic acid, 3-(3’-hydroxyphenyl) propionic acid) and non-hydroxylated (benzoic acid or 3-phenylpropionic acid) phenolic acids. Using the COMET assay, each catabolite demonstrated significant (p<0.001) geno-protective activity, albeit with varying potency. They also significantly modulated expression of key genes in the Nrf2-ARE pathway, including Nrf2, Heme oxygenase-1 (HO-1), and NAD(P)H dehydrogenase quinone 1 (NQO1). Hydroxylation of the phenolic acids appeared to have a limited effect with respect to bioactivity. Overall, the colon derived phenolic metabolites, when assessed at physiologically relevant concentrations, reduced DNA damage in both normal and adenocarcinoma colonic cells in response to oxidative challenge, mediated – at least in part via upregulation of the Nrf2-ARE pathway.

Oxalate is a divalent organic anion that has implications across many biological and commercial processes. It is derived from plant sources, such as spinach, rhubarb, tea, cacao, nuts, and beans, and therefore is commonly found in raw or processed food products. Oxalate can also be made endogenously by humans and other mammals as a byproduct of hepatic enzymatic reactions. It is theorized that oxalate is useful for plants to store calcium and protect against herbivory. Clinically, oxalate is best known to be a major component of kidney stones, which commonly contain calcium oxalate crystals. Oxalate can induce an inflammatory response that decreases the immune system’s ability to remove renal crystals. When formulated with platinum as oxaliplatin (an anticancer drug), oxalate has been proposed to cause neurotoxicity and nerve pain. There are many sectors of industry that are hampered by oxalate, and some that depend on it. For example, calcium oxalate is troublesome in the pulp industry and the alumina industry as it deposits on machinery. On the other hand, oxalate is a common active component of rust removal and cleaning products. Due to its ubiquity, there is interest in developing efficient methods to quantify oxalate. Over the past four decades several diverse methods have been reported. These approaches include electrode-based detection, liquid chromatography or gas chromatography coupled with mass spectrometry, enzymatic degradation of oxalate with oxalate oxidase and detection of hydrogen peroxide as a product, and indicator displacement-based methods employing fluorescent or UV light-absorbing compounds. It has become clear that no single method will work best for every purpose. This review describes the strengths and limitations of each method, and may serve as a reference for investigators to decide which approach is most suitable for their work.

Hyaluronic acid, known also as hyaluronan, is the most abundant glycosaminoglycan in the extracellular matrix. It is produced by most of the cells in the human body, possibly contributing to various fundamental biological processes. This prompts interest in its therapeutic value. Hyaluronic acid (HA) has been used for various treatments owing to its broad range of properties in medical and dental field specially in periodontology. The review gives an overview on the effects of HA on fibroblasts, bone, wound healing, periodontal regeneration, aphthous ulcer/stomatitis and stem cells. Outcomes of including Hyaluronic acid in non-surgical periodontal therapy, drug delivery system and surgical procedures such as root coverage, papilla regeneration, root conditioning, intrabony defects, guided tissue regeneration are rather optimistic. HA has shown astounding potential in treating periimplantitis. Newer frontiers have to be explored to comprehend the other promising properties of HA. Keyword – Hyaluronic Acid, Periodontology.

p-Toluenesulfonic acid is commercially available, non-toxic, cheap organic compound with robust stability. p-Toluenesulfonic acid is solid, non-corrosive and a strong organic acid that can be handled easily. Due to this p-toluenesulfonic acid could be the better replacement of other conventional acids like nitric acid, sulfuric acid, perchloric acid and AlCl3 in organic transformations. Moreover, p-toluenesulfonic acid could be used synergistically with other mode of catalysis like transition metal catalysis and photocatalysis. In recent years, the use of this solid organic acid in organic and polymer synthesis has grown tremendously. In this review, we present an overview of p-toluenesulfonic acid promoted various organic reactions with particular emphasis to the more recently reported methods. In some cases, we also detailed the understanding of the reactions by providing the reaction mechanism. Despite these advances, there are still many opportunities for the development of new reactions using PTSA. Industry and academia have become more conscious to adopt sustainable chemical processes using safer reagents and solvents and the use of PTSA in this context is highly significant. This review will inspire researchers for further reaction development employing p-toluenesulfonic acid.

Legumes are a diverse and important group of plants that play a vital role in agriculture, food security, and environmental sustainability. Rhizobia are symbiotic bacteria that form nitrogen-fixing nodules on legume roots, providing the plant with a valuable source of nitrogen. Phenolic acids are a group of secondary metabolites produced by plants that have a wide range of biological functions, including defense against pests and diseases, tolerance to abiotic stresses, and nutrient uptake. In the context of climate change and the imperative for sustainable agriculture, this study delves into the dynamic responses of legume species to varying light intensities and their intricate interactions with soil microorganisms. We investigated the impact of light intensity and rhizobial inoculation on the biomass, nitrate reductase, acid phosphatase, and production of phenolic acids in the roots of four legume species, Trifolium repens, Vicia sativa, Ornithopus compressus, and Coronilla juncea. Plants were grown under three light intensity regimes (low, medium, and high) and inoculated with either rhizobia or a non-inoculated control. The results highlights that shaded-light-adapted species, T. repens and V. sativa, increased root exudate production when exposed to high light intensity. This response aligns with their mining strategy, effectively allocating resources to optimize nutrient acquisition under varying conditions. In contrast, species hailing from well- illuminated environments, O. compressus and C. juncea, displayed distinct strategies by significantly increasing biomass under high irradiance, capitalizing on the available light and nutrients. The mining strategy of legumes emerged as a central theme, influencing biomass production, nitrogen dynamics, and enzymatic activities. The strong correlations between biomass and total nitrogen accumulation underscore the role of the mining strategy in efficient nutrient acquisition. Inoculated plants, which rely more on biological nitrogen fixation (BNF), exhibited lower δ15N values, indicative of a successful mining strategy to acquire and utilize atmospheric nitrogen. Enzymatic activities and phenolic acids exhibited significant interspecies variations, reflecting the adaptability of legumes to different light conditions. The findings of this study could be used to develop new strategies for improving legume stress tolerance, nutrient uptake capacity, and rhizosphere health.

We present synthetic experiments of lactic acid (LA) polycondensation to produce poly(lactic acid) (PLA), as well as kinetic modeling calculations that capture the polymer molecular weight increase with time, given the initial concentrations. Tin-octoate-catalyzed polycondensation of (D,L)- or L-lactic acid, was carried out in pre-dried toluene after azeotropic dehydration for 48-120 hours at 130-137 °C. The polymerization was optimized by varying lactic acid and catalyst concentrations as well as the temperature. Gel Permeation Chromatography was used to experimentally follow the evolution of molecular weights and the products were characterized by NMR, TGA, DSC and IR. Under optimal conditions, PLLA with weight-average molecular weight (Mw) of 161 kDa could be obtained. The rate equations that describe polycondensation kinetics were recast in a condensed form that allowed very fast numerical solution and calculation of the number-average molecular weight with time. Deviations with respect to the experiment were minimized in a least-squares fashion, to determine rate constants. The optimized kinetics parameters are shown to reproduce the experimental data accurately

Coffee is one of the most popular beverages in the world. Annual coffee consumption continues to increase, but at the same time, it generates a large amount of spent coffee grounds from the brewing process, that arises environmental problems. An appropriate solution to manage these spent coffee grounds becomes crucial. Our project aims to discuss the feasibility of utilizing the spent coffee ground to synthesize polylactic acid as a recycling application for spent coffee ground. This paper will discuss the properties and potential recycling applications of spent coffee grounds, the brief production process of polylactic acid, and the potential process for converting spent coffee ground to lactic acid. From our review, it is feasible to utilize spend coffee ground as the primary sources for lactic acid production by bacteria fermentation, and further produce bioplastics, polylactic acids by ring-opening polymerization. Possible ways to improve the yield and corresponding cost analysis are also discussed.

Plants are constantly exposed to a variety of different environmental stresses, including drought, salinity, and elevated temperatures. These stress cues are assumed to aggravate in the future driven by the global climate change scenario which we are currently experiencing. These stressors have largely detrimental effects on plant growth and development and, therefore, put global food security in jeopardy. For this reason, it is necessary to expand our understanding of the underlying mechanisms by which plants respond to abiotic stresses. Especially boosting our insight into the ways by which plants balance their growth and their defense programs appears to be of paramount importance, as this may lead to novel perspectives that can pave the way to increase agricultural productivity in a sustainable manner. In this review, our aim was to present a detailed overview of different factettes of the crosstalk between the antagonistic plant hormones abscisic acid (ABA) and auxin, two phytohormones that are the main drivers of plant stress responses, on the one hand, and plant growth, on the other.

Acid fracturing simulation is used widely to optimize carbonate reservoirs and improve acid fracturing treatment performance. In this study, a method was used to minimize the risk of the acid fracturing treatment. First, optimal fracture geometry parameters with UFD methods are calculated. After that, design components change as long as fracture geometry parameters reach their optimal values. The results showed a high flow rate needed to achieve optimal fracture geometry parameters with increasing acid volume. Sensitivity analysis was performed on controllable and reservoir parameters. It observed that a high flow rate should be applied for a low fluid viscosity to achieve the optimization goals. Straight acid reaches optimal conditions at a high flow rate and low volume. These conditions for retarded acids appear only at a low flow rate and high volume. The study of the acid concentration for gelled acid showed that as it increased, the flow rate and volume increased. Besides, for low permeability formation, a large fracture half-length and small fracture width are desirable. In this case, a higher flow rate will be required. The sensitivity analysis showed that the optimum flow rate and acid volume increase and decrease for the high Young's modulus. The effect of closure stress was also investigated and observed for a sample with high closure stress, low flow rate, and high acid volume are required.

Tea and coffee are the most commonly used beverages throughout the world. Both decoctions are rich in small organic molecules such as phenolics/polyphenolics, purine alkaloids, many methylxanthines, substituted benzoic and cinnamic acids. Many of these molecules are physiologically chemopreventive and chemoprotective agents against many severe conditions such as cancer, Alzheimer, Parkinsonism, inflammation, sleep apnea, cardiovascular disorders, bradycardia, fatigue, muscular relaxation, and oxidative stress. Caffeine, a purine alkaloid, is a common metabolite of both tea and coffee aqueous decoctions and its concentration in tea/coffee depends on the fermentation process, preparation of the water extract and quality of tea leaves/coffee beans. A 250 ml of a coffee cup contains 100-150 mg caffeine while the same volume of strong tea contains 25-40 mg caffeine. The present paper presents the potential of caffeine as a potent chemopreventive agent that can be used for numerous physiological disorders.

In the last decades, cultivation of chia (Salvia hispanica L.) has expanded around the world and the seeds have become well known due to their rich composition in nutrients and bioactive compounds. The aim of this work was to evaluate the physical, chemical and nutritional profile of eight chia seeds grown in different Latin-American countries (Argentina, Bolivia, Chile, Ecuador, Mexico, Paraguay and Peru). The results showed that several nutritional parameters such as the protein content and amino acid profile, dietary fiber content, lipid content, mineral composition and phytate present in the seeds depend on the location they were grown in. Other parameters such as ash content, fatty acid profile or physical parameters were uniform across locations (except for color parameters). The results support the notion that nutritional characteristics of seeds are determined by the seed's origin, further analysis is needed to define the exact mechanisms that control the changes in the seeds nutritional properties.

Ecuador is the world's fifth largest cocoa producer, generating hundreds of annual tons of residues from this fruit. This research aims to value this residual (cocoa pod husk) by using it as raw material to obtain pectin, which is widely used in the food and pharmaceutical industries. For them, the extraction of three different organic acids with GRAS status (and therefore safe for their use), citric, malic and fumaric acids, were studied. In addition, two other factors, temperature (70-90°C) and extraction time (60-90 min), were explored in a central composite design of experiments. Under the conditions of the experiment, it was obtained that the best yields were reached for citric acid, malic acid and fumaric acid and for ~86 min of extraction time. The temperature did not show a significant influence on the yield. The pectins obtained under optimal conditions were characterised, showing their similarity with commercial pectin. However, the equivalent weight and the esterification degree of the pectin obtained with fumaric acid classify it as having a high equivalent weight and a low degree of esterification. It differs significantly from the other two acids, perhaps due to the limited solubility of fumaric acid.

The rise in prevalence of obesity in women of reproductive age in both developed and developing countries might propagate intergenerational cycles of detrimental effects on metabolic health, contributing to substantial economic burden on society. Placental lipid metabolism might be disrupted by maternal obesity, which possibly affects the life-long health of the offspring. Here, we investigated placental lipid metabolism and handling from women with pre-gestational obesity as a sole pregnancy complication and compared to placental responses of lean women. Open profile and targeted lipidomics were used to assess placental lipids and oxidized products of docosahexahenoic acid (DHA), neuroprostanes, and arachidonic acid (AA), isoprostanes. Placental fatty acid transporters FABP1, FABP3 and endothelial lipase protein were measured. Despite no signs of overall alterations in lipid content, increased contents of DHA, AA, DHA-derived neuroprostanes and AA-derived isoprostanes and decreased content of FABP1 protein were found in placentas from obese women. Multivariate analyses suggested that these oxidised fatty acids are associated with maternal and placental inflammation and also with birth weight. These results might shed light on the molecular mechanisms associated with altered fatty acid metabolism and lipid handling in maternal pre-gestational obesity, placing these oxidized fatty acids as novel mediators of placental function.

Thai basil is a renowned medicinal plant and a rich source of bioactive antioxidant compounds having several health benefits, with actions to prevent of cancer, diabetes and cardiovascular disease. Plant cell and tissue culture technologies can be routinely established as an important, sustainable and low-cost biomass source for the production of high-value phytochemicals. The current study aimed at developing an effective protocol for the production of Thai basil leaf derived callus cultures with sustainable and high production of biomass and antioxidants as an alternative of leaves production. MS basal medium with various concentrations of plant growth regulators (PGRs) compatible with nutraceutical applications (i.e., gibberellic acid (GA3) and 6-benzylaminopurine (BAP) either alone or in combination with naphthalene acetic acid (NAA)) were evaluated. Among all tested PGRs, the combination BAP:NAA (5 mg/L:1 mg/L) yield maximum biomass accumulation (fresh weight (FW): 190 g/L and dry weight (DW): 13.05 g/L) as well as enhanced phenolic (346.08 mg/L) production. HPLC quantification analysis indicated high productions of chicoric acid (35.77 mg/g DW) and rosmarinic acid (7.35 mg/g DW) under optimized callus culture conditions. Antioxidant potential was assessed using both in vitro cell free and in vivo cellular antioxidant assays. Maximum in vitro antioxidant activity DPPH (93.2 % of radical scavenging activity) and ABTS (1322 µM Trolox equivalent antioxidant capacity) was also observed for the extracts from callus cultures grown on optimal conditions. In vivo cellular antioxidant activity assay confirmed the effective protection against oxidative stress of the corresponding extract by the maximum inhibition of ROS and RNS production. Compared to commercial leaves, callus extracts showed higher production of chicoric acid and rosmarinic acid associated with higher antioxidant capacity. In addition, this biological system also has a large capacity for continuous biomass production, thus demonstrating its high potential for possible nutraceutical applications.

Lysophosphatidic acid (LPA) type 3 (LPA3) receptor mutants were generated in which the sites detected phosphorylated were substituted by non-phosphorylatable amino acids. Substitutions were made in the intracellular loop 3 (IL3 mutant), the carboxyl terminus (Ctail), and both domains (IL3/Ctail). The wild-type (WT) receptor and the mutants were expressed in T-REx HEK293 cells, and the consequences of the substitutions were analyzed employing different functional parameters. Agonist- and LPA-mediated receptor phosphorylation was diminished in the IL3 and Ctail mutants and essentially abolished in the IL3/Ctail mutant, indicating that the main sites were substituted and distributed in both domains. The WT and mutant receptors increased intracellular calcium and ERK 1/2 phosphorylation in response to LPA and PMA. An increase in baseline ERK phosphorylation was detected in the IL3/Ctail mutant. LPA and PMA-induced receptor interaction with β-arrestin 2 and LPA3 internalization were severely diminished in the mutants. Mutant-expressing cells also exhibit increased baseline proliferation and response to different stimuli, which were inhibited by the antagonist Ki16425, suggesting a role of LPA receptors in this process. Migration in response to different attractants was markedly increased in the Ctail mutant, which the Ki16425 antagonist also attenuated.

The host glycosylation mechanism synthesizes the carbohydrates of glycoproteins of viral envelopes. Due to the loss of the Cytidine Monophospho-N-Acetylneuraminic Acid Hydroxylase gene by some mammalian species, including humans (negative-CMAH), Neu5Gc is no longer synthesized. Uptake of Neu5Gc by negative-CMAH species, through the intake of food products derived from positive-CMAH mammals, leads to incorporating Neu5Gc-glycans in the glycocalyx (xenosialylation). Neu5Gc, being a Mammalian-associated Carbohydrate Antigen (MCA), acts as a non-self-antigen, inducing an inflammatory reaction (Xenosialitis), and triggering the production of circulating antiNeu5Gc antibodies to attack/remove all incorporated Neu5Gc. In the state of Xenosialitis, the virus-neutralizing antibodies produced by a heavily xenosialylated patient following exposure to viral infection (including SarsCoV2) or anti SarsCoV2 vaccination cross-react against all incorporated non-self Neu5Gc-MCA glycans due to their resemblance with viral envelope antigens synthesized by the host glycosylation mechanism. In addition, the circulating anti-XeSias antibodies determine the massive removal of the circulating neutralizing FC-xeno-contaminated antibodies by the serum, living only the hyper-inflammatory agalattosylated antiviral IgG antibodies. Therefore, we hypothesize that the combination of antibody cross-reaction against non-self Neu5Gc-MCA glycans and the massive removal of the xeno-contaminated newly formed neutralizing antibodies in favor of hyper reactive antibodies, could be the cause of the massive inflammatory reaction (cytokine storm, coagulopathies, neuropathies) observed in Covid 19 patients or after anti-SarsCoV2 vaccination. This analysis is an invitation to investigate the post-infectious and/or post-vaccination adverse phenomena in the light of xenosialization as a key to understanding the severe post viral and post vaccine complications, including SARS-CoV2 infection or related vaccination.

To study the fermentation process of biocatalyzing decanoic acid to synthesize trans-2-decenoic acid, this study was based on the engineering E.coli constructed in the laboratory in the early stage and studied the effect of seed liquid culture time, culture temperature, inoculum amount, induction temperature, dissolution effects of substrate solvent, metal ions, and substrate loading on the yield of trans-2-decenoic acid. Based on single-factor experimental optimization, the Box–Behnken design was used to conduct response surface testing using the substrate feeding concentration, inducer concentration, and MnCl2 concentration as response variables and trans-2-decenoic acid production as the response value. The optimal fermentation process was determined through experiments: seed culture time 20 h, culture temperature 37°C, inoculation amount 1%, induction temperature 30°C, substrate flow amount 0.15 g/L, inducer concentration 5.60 g/L, MnCl2 concentration was 0.10 mM. Under these conditions, the average production of trans-2-decenoic acid was 1.982 ± 0.110 g/L. Compared with the basic LB medium, the production of trans-2-decenoic acid increased by 1.042 g/L; compared with the previous period, the yield of trans-2-decenoic acid studied increased by 1.501 ± 0.110 g/L, which provides a reliable basis for further research on the fermentation process of biocatalytic decanoic acid synthesis of trans-2-decenoic acid.

Pentadecanoic acid (C15:0) is an essential odd-chain saturated fatty acid with broad activities relevant to protecting cardiometabolic, immune, and liver health. C15:0 activates AMPK and inhibits mTOR, both of which are core components of the human longevity pathway. To assess the potential for C15:0 to enhance processes associated with longevity and healthspan, we used human cell-based molecular phenotyping assays to compare C15:0 with three longevity-enhancing candidates: acarbose, metformin, and rapamycin. C15:0 (n=36 activities in 10 of 12 cell systems) and rapamycin (n=32 activities in 12 of 12 systems) had the most clinically relevant, dose-dependent activities. At their optimal doses, C15:0 (17 µM) and rapamycin (9 µM) shared 24 activities across 10 cell systems, including anti-inflammatory (e.g., lowered MCP-1, TNFɑ, IL-10, IL-17A/F), antifibrotic, and anticancer activities, which are further supported by previously published in vitro and in vivo studies. Paired with prior demonstrated abilities for C15:0 to target longevity pathways, hallmarks of aging, aging rate biomarkers, and core components of type 2 diabetes, heart disease, cancer, and nonalcoholic fatty liver disease, our results support C15:0 as an essential nutrient with activities equivalent to, or surpassing, leading longevity-enhancing candidate compounds.

This study examines the behavior of stearic acid (SA) and 12-hydroxystearic acid (12-HSA) aqueous mixtures as a function of temperature and 12-HSA/SA molar ratio (R). Whatever R, the system exhibits a morphological transition at a given threshold temperature, from multilamellar self-assemblies at low temperature towards small micelles at high temperature, as shown by a combination of transmittance measurements, Wide Angle X-ray diffraction (WAXS), small angle neutron scattering (SANS) and differential scanning calorimetry (DSC) experiments. Such transition originates from the melting of the crystallized fatty acids within the lamellar phase. The precise determination of the threshold temperature, which ranges between 20°C and 50°C depending on R, allows for the construction of the whole phase diagram of the system as a function of R. At high temperature the micelles that are formed are oblate for pure SA solutions (R = 0) and prolate for pure 12-HSA solution (R = 1). In the case of mixtures, there is a progressive continuous transition from oblate to prolate shape when increasing R, with micelles that are almost purely spherical for R = 0.33.

Ludwigia octovalvis (Jacq.) P.H. Raven is widely used in traditional medicine for different illnesses included diabetes and hypertension. However, its impact on lipotoxicity and metabolic syndrome in vivo has not been addressed. Therefore, the aim of this study was to evaluate the effects of this plant on the metabolic syndrome parameters in a C57BL6J mouse hypercaloric diet model. L. octovalvis hydroalcoholic extract and its ethyl acetate fraction (25 mg/kg/day) were used for sub-chronic assessment (10 weeks). Also four subfractions (25 mg/kg) were evaluated in the postprandial triglyceridemia test in healthy C57BL6J mice. The hydroalcoholic extract and ethyl acetate fraction significantly decreased body weight gain (-6.9 g and -1.5 g), fasting glycemia (-46.1 and -31.2 mg/dL), systolic (-26.0 and -22.5mmHg) and diastolic (-8.1 and 16.2 mmHg) blood pressure, free fatty acid concentration (-13.8 and -8.0 μg/mL) and insulin-resistance (measured by TyG index, -0.207 and -0.18) compared to the negative control. Postprandial triglyceridemia test showed that the effects in the sub-chronic model are due, at least in part, to improvement in this parameter. L. octovalvis treatments, particularly the hydroalcoholic extract, improve MS alterations and decrease free fatty acid concentration. These effects are possibly due to high contents of corilagin and ellagic acid.

We describe the behavior of mixtures of stearic acid (SA) and its hydroxylated counterpart 12-hydroxystearic acid (12-HSA) in aqueous mixtures at room temperature, as function of the 12-HSA/(fatty acid) mole ratio R. The morphologies of the self-assembled aggregates are obtained by a multi-structural approach that combines confocal and cryo-TEM microscopies with Small-Angle Neutron Scattering (SANS) and Wide-Angle X-Rays Scattering (WAXS) measurements, coupled with rheology measurements. Fatty acids are solubilized by an excess of ethanolamine counterions, so that their heads are negatively charged. The behavior is driven by the competition between mixing entropy and enthalpic effects. A clear trend towards partitioning between the two types of fatty acids is observed, presumably driven by the favorable formation of a H-bond network between hydroxyl OH function on the 12th carbon. For all R, the self-assembled structures are locally lamellar, with bilayers composed of crystallized and strongly interdigitated fatty acids. At high R, multi-lamellar tubes are formed, similarly as for pure aqueous solutions of 12-HSA. The doping by a low amount of SA molecules only slightly modify the dimensions of the tubes (radius and length), and slightly decreases the bilayers rigidity. The solutions have a gel-like behavior originating from entanglements between tubes and show a yield stress. At intermediate R, a partial local partitioning occurs between the two types of fatty acids. The tubes coexist in solution with helical ribbons. The two structures possibly merge to form very long snaky objects with straight and curved parts. The rigidity of the bilayers and the rheological behavior of the solutions are very similar to those of the high R case. At low R, local partitioning also occurs, and the architecture of the self-assemblies associates the two morphologies of the pure fatty acids systems, respectively 2-D planar bilayers for SA and the tubes describe above for the 12-HSA molecules: they are facetted objects with planar domains enriched in SA molecules, capped with curved domains enriched in 12-HSA molecules. The rigidity of the bilayers is strongly increased, as well their storage modulus, compared to systems with larger R. The solutions remain however viscous fluids in this regime of low R.

Cholestasis is a condition defined as an abnormal decrease of bile flow due to progressive pathological states or cholestatic liver diseases that affect the biliary tree at intrahepatic and extrahepatic level. It induces complications such as cirrhosis, liver failure, malignancies, pruritus, fatigue, bone disease and nutritional deficiencies that merit close follow-up and specific interventions to improve quality of life. Furthermore, cholestasis can progress to end-stage liver disease and represents an entity with high morbidity and mortality; and economic burden, Therefore, it is important that clinicians understand the treatment options for cholestatic liver diseases. This review addresses the pathophysiology of cholangiopathies, a general view of current treatments and their molecular targets, and a specific review of those groups of drugs. The objective is to provide clinicians with an overview of the current treatment of cholangiopathies based on evidence on its efficacy and safety.

A new pathway leading to the n-10 fatty acid series has been recently evidenced, starting from sapienic acid - a monounsaturated fatty acid (MUFA) resulting from the transformation of palmitic acid by delta-6 desaturase. Sapienic acid attracts attention as novel marker of cancer cell plasticity. Here, we analyzed fatty acids including the n-10 fatty acid contents, and compared for the first time cell membranes and the corresponding extracellular vesicles (EV) of two human prostatic adenocarcinoma cell lines of different aggressiveness (PC3 and LNCaP). The n-10 components were 9-13% of the total fatty acids in both cancer cell lines and EVs, with total MUFA levels significantly higher in EVs of the most aggressive cell type (PC3). High sapienic/palmitoleic ratios indicated the preference for delta-6 vs. delta-9 desaturase enzymatic activity in these cell lines. The expressions analysis of enzymes involved in desaturation and elongation by qRT-PCR showed a higher desaturase activity in PC3 and a higher elongase activity toward polyunsaturated fatty acids than toward saturated fatty acids, compared to LNCaP cells. Our results improve the present knowledge in cancer fatty acid metabolism and lipid phenotypes, highlighting EV lipidomics to monitor positional fatty acid isomer profiles and MUFA levels in cancer.

Uric acid being a diagnostic biomarker of gout and therapeutic agent in homeopathic medicines necessitates to develop simple and specific method for its determination. Therefore, present study describes the development and validation of simple and specific colorimetric method for determination of uric acid in homeopathic tablets. Uric acid upon reaction with acid and reagent mixture produced coloured derivative which was detected at 411 nm. The method was found linear over the whole range investigated with the correlation coefficient (R²) = 0.9975. Beer’s law was obeyed over the concentration ranges from 5.0 µg/mL to 240 µg/mL. The method was found to be reliable (95.7 to 108.2% recovery), repeatable intra-day accuracy (97.01 to 107.4%) and reproducible-inter day accuracy (99.45 to 107.8%) with relative standard deviation less than 5%. The results of the present study indicate the method is easy to perform, specific and suitable to be used for the determination of uric acid in homeopathic Acid Uric Tablet using less expensive derivitization.

The direct Cr (VI) reduction process by oxalic acid was conducted and the results showed that the Cr (VI) was efficiently reduced by oxalic acid at high reaction temperature and high dosage of oxalic acid. The reduced product, Cr (III), was easily generated stable complex compounds (Cr(HC2O4)3) with oxalate, which displayed a negative effect on the reduction process. The high reaction temperature and high acidic medium could destroy the stable structure of a complex compound to release oxalate, and facilitate the reduction of Cr (VI). Generally, the present study provided a versatile strategy for Cr (VI) reduction, exhibiting a bright application future for real wastewater treatment.