Metal organic frameworks (MOFs) are used in catalysis due to their high specific surface area and porous structure. The dispersed active sites and limited reaction space render MOFs have the potential for highly selective electrocatalytic CO2 reduction reaction (ECO2RR). Meanwhile, formic acid (HCOOH) is attracting attention as a liquid product with high economic benefits. This review summarizes the MOFs and their derivatives applied for ECO2RR into HCOOH products. The preparation methods of MOFs as electrocatalysts and their unique advantages are discussed. A series of MOFs, and MOFs derivatives obtained by electrochemical reduction or carbonization processes are highlighted, including metal nanomaterials, carbon-based nanocomposites, single-atom catalysts, and bimetallic nanocomposites. Depending on the MOFs building units (metal ions and organic linkers) and the reaction conditions of derivatization, MOFs-based catalysts exhibit rich diversity and controllable modulation of catalytic performance. Finally, the challenges encountered at this stage and the future research directions of MOFs-based catalysts are proposed.

High-performance electromagnetic interference (EMI) shielding materials with ultralow density and environment friendly properties are greatly demanded to address electromagnetic radiation pollution. Herein, carbon nanotubes/polylactic acid (CNTs/PLA) materials with different CNTs contents, which exhibit characteristics of light weight, environmental protection and good chemical stability, are fabricated by 3D printing technology, where CNTs are evenly distributed and bind well with PLA. The performances of 3D printed CNTs/PLA composite are improved compared to pure 3D printed PLA composite, which include mechanical properties, conductive behaviors and electromagnetic interference (EMI) shielding. The EMI shielding effectiveness (SE) of CNTs/PLA composite could be improved when the contents of CNTs increase. When it reaches 15 wt%, the EMI SE of 3D printed CNTs/PLA composite could get up to 47.1 dB, which shields 99.998% of electromagnetic energy. Meanwhile, the EMI shielding mechanism of 3D printed CNTs/PLA composite is mainly of absorption loss, and it generally accounted for more than 80% of the total shielding loss. These excellent comprehensive performances endow the 3D printed CNTs/PLA composite with great potential for use in industrial and aerospace area.

As part of valorisation of agricultural waste into bioactive compounds, a series of structurally novel oleanolic acid ((3β-hydroxyolean-12-en-28-oic acid, OA-1)-phtalimidines (isoindolinones) conjugates 18a-v bearing 1,2,3-triazole moieties were designed and synthesized by treating a previously azide 4 prepared from OA-1 isolated from olive pomace (Olea europaea L.) with a wide range of propargylated phtalimidines using the Cu(I)-catalyzed click chemistry approach. OA-1 and its newly prepared analogues 18a-v were screened in vitro for their antibacterial activity against two Gram-positive bacteria, Staphylococcus aureus and Listeria monocytogenes; and two Gram-negative bacteria, Salmonella thyphimurium and Pseudomonas aeruginosa. Attractive results were obtained notably against L. monocytogenes. Compounds 18d, 18g and 18h exhibited the highest antibacterial activity when compared with OA-1 and other compounds in the series against tested pathogenic bacterial strains. Molecular docking study was performed to explore the binding mode of the most active derivatives against the target protein from L. monocytogenes. Results showed the importance of both hydrogen bonding and hydrophobic interactions with the target protein and are in favor to the experimental data.

Regulatory macrophages (Mregs) are unique in that they have anti-inflammatory and immunosuppressive properties. Thus, treating inflammatory diseases using Mregs is an area of active research. Human Mregs are usually generated by culturing peripheral blood monocytes stimulated by macrophage colony-stimulating factor with interferon (IFN)-. Here, we generated Mregs with an elongated cell morphology from THP-1 cells stimulated with phorbol 12-myristate 13-acetate and cultured with arginylglycylaspartic acid and vitamin D3. These Mregs regulated macrophage function, and respectively downregulated and upregulated the expression of pro-inflammatory and immunosuppressive mediators. They also expressed Mregs-specific marker, such as dehydrogenase/reductase 9, even when exposed to inflammatory stimulants such as IFN-, lipopolysaccharide, purified xenogeneic antigen, and xenogeneic cells. The Mregs also exerted anti- inflammatory and anticoagulatory actions in response to xenogeneic cells and immunosuppressive effects on mitogen-induced Jurkat T-cell proliferation. Our method of generating functional Mregs in vitro without cytokines is simple and cost-effective.

Coffee berry borer (CBB), Hypothenemus hampei (Ferrari) (Coleoptera: Curculionidae: Scolytinae), is the pest that causes the most economic damage to coffee crops. Chemical control of this insect is based on the use of insecticides that can affect the environment and nontarget organisms. Despite the fact that caffeine has shown potential as an insecticide, a caffeine-based product for field use is currently not available on the market. As a new alternative to control CBB and other coffee pests, such as Monalonion velezangeli, a caffeine-oleate was developed. The caffeine oleate formulation showed laboratory efficacy by causing mortality of more than 90% of CBB adults in preventive tests in which the insecticide was sprayed prior to insect attack on the coffee fruits. In the curative tests, in which spraying occurred after CBB infested the fruits, the formulation caused 77% mortality of the insects. Under controlled field conditions, the product kept CBB infestation below 20%, reducing the number of fruits attacked by the insect by up to 70%. In addition, no phytotoxic effects were observed in coffee plants. The insecticide was also effective against M. velezangeli causing 100% mortality. A caffeine oleate formulation that could be part of a strategy for integrated CBB management as well as other pests of coffee was developed. The components of the insecticide are food grade; the product would provide greater security to the coffee ecosystem and coffee growers.

Porphyrias are human metabolic diseases characterized by different modes of inheritance and clinical manifestations and caused by deficiency of enzymes of the heme biosynthetic pathway. The forms of porphyria are characterized by elevated levels of δ-aminolevulinic acid and porphobilinogen. Acute hepatic porphyrias are a subgroup of porphyrias characterized by the appearance of neurovisceral attacks with or without cutaneous signs. Acute hepatic porphyrias include four diseases: acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and hereditary δ-aminolevulinic acid dehydratase deficiency. These enzymatic deficiencies cause a harmful accumulation of porphyrins in the liver and bone marrow that trigger a wide range of signs and symptoms. Patients suffering from different forms of acute hepatic porphyria present a high risk of liver cancer, precisely hepatocellular carcinoma and cholangiocarcinoma, determined by the activity of the disease even though an exact mechanism of carcinogenesis has not been recognized yet. Here, we present the clinical case of a 72 year old woman who, approximately 29 years after the diagnosis of acute intermittent porphyria, presented with intrahepatic cholangiocarcinoma with histological diagnosis of adenocarcinoma starting from the biliary-pancreatic ducts, which was diagnosed during the clinical and anatomopathological evaluation of a pathological fracture of the femur.

Introduction: Individuals with gout are at higher risk of developing chronic conditions, such as diabetes, chronic kidney disease (CKD), and cardiovascular diseases. In this study, the association between urate-lowering therapy (ULT) use and the prevalence of these conditions was evaluated. Methods: This observational, cross-sectional pharmacoepidemiologic study used the 2013-2018 biannual cycles of the National Health and Nutrition Examination Survey. The inclusion criteria were adults 30 years of age and older with a diagnosis of gout. The association between ULT treatment status and dyslipidemia, coronary heart disease, heart failure, hypertension, and chronic kidney disease was evaluated, as well as associations with select clinical laboratory biomarkers. Results: Use of ULT was 28.9% (95%CI 24.3%-33.9%). There was no significant association between ULT use and the prevalence of heart failure, coronary heart disease, hypertension, or dyslipidemia (p>0.05). Those on ULT had a lower mean eGFR compared to those not on treatment (68.03 versus 74.74 mL/min/1.73m², p=0.014). LDL- and HDL- and total cholesterol were significantly lower among those receiving ULT treatment (p<0.05). Conclusion: ULT use continues to be low among those with gout. Those on ULT were more likely to be diagnosed with CKD, college graduates and above, older males, and obese. Clinical guidelines conditionally recommend ULTs in co-morbid kidney disease; while our results may reflect guidelines recommendation for ULT use in CKD patients, worsening kidney function while taking ULT is unlikely. Further research is necessary to determine the long-term impact of ULTs on kidney function and cardiovascular biomarkers.

46 patients with a newly diagnosed, histologically verified glioma that was visually classified as [18F]FET-negative were included. Tumor volumes were defined using routine T2/FLAIR MRI data and applied to extract information from dynamic [18F]FET PET data, i.e. early and late tu-mor-to-background (TBR5-15, TBR20-40) images and time-to-peak (TTP) images. Radiomic features of healthy background were calculated from the tumor volume-of-interest mirrored to the con-tralateral hemisphere. Differences between tumor and healthy tissue features were compared us-ing Wilcoxon test. Additionally, the ability to distinguish tumor from healthy tissue was assessed using logistic regression. 5 % of features derived from TBR20-40 images were significantly differ-ent; 16 % of features derived from TBR5-15 images and 69 % of features derived from TTP images. The high number of significantly different features derived from TTP images was even found in isometabolic gliomas (after exclusion of photopenic gliomas) with visually normal [18F]FET up-take in static images. However, the differences did not reach satisfactory predictability for ma-chine learning based identification of tumor tissue. In conclusion, radiomic features derived from dynamic [18F]FET PET data may extract additional information even in [18F]FET-negative glio-mas, which should be investigated in larger cohorts and correlated with histological and out-come features in future studies.

Normal function of placental extravillous trophoblasts (EVTs), which are responsible for uteroplacental vascular remodeling, is critical for adequate delivery of oxygen and nutrients to the developing fetus and normal fetal programming. Proliferation and invasion of spiral arteries by EVTs depends upon adequate levels of folate. Multidrug resistance-associated protein 1 (MRP1), which is an efflux transporter, is known to remove folate from these cells. We hypothesized that palmitic acid increases MRP1-mediated folate removal from EVTs, thereby interfering with EVTs’ role in early placental vascular remodeling. HTR-8/SVneo and Swan-71 cells, first trimester human EVTs, were grown in the absence or presence of 0.5 mM and 0.7 mM palmitic acid, respectively, for 72 h. Palmitic acid increased ABCC1 gene expression and MRP1 protein expression in both cell lines. The rate of folate efflux from the cells into the media increased with a decrease in migration and invasion functions in the cultured cells. Treatment with N-acetyl cysteine (NAC) prevented the palmitic acid mediated upregulation of MRP1 and restored invasion and migration in the EVTs. Finally, in an ABCC1 knockout subline of Swan-71 cells, there was a significant increase in invasion and migration functions. The novel finding in this study that palmitic acid increases MRP1-mediated folate efflux provides a missing link that helps to explain how maternal consumption of saturated fatty acids compromises the in-utero environment.

In this work, polyacrylic acid-functionalized MCM-41 was synthesized, which was further interacted with calcium ions, to realize enhanced pH-responsive nanocarrier for sustained drug release. First, mesoporous silica nanoparticles (MSNs) were prepared by the sol-gel method. Afterward, (3-trimethoxysilyl)propyl methacrylate (TMSPM) modified surface was prepared by using the post-grafting method, then polymerization of acrylic acid was proceeded. After adding calcium chloride solution, polyacrylic acid-functionalized MSNs with calcium-carboxyl ionic bonds in the polymeric layer, which can prevent the cargo from leaking out of the mesopore, were prepared. The structure and morphology of the modified nanoparticles (PAA-MSNs) were characterized by X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, transmission electron microscopy (TEM), and N2 adsorption-desorption analysis, etc. The controlled release of guest molecules was studied by using 5-fluorouracil (5-FU). The drug molecules-incorporated nanoparticles showed different releasing rates under different pH conditions. It is considered that our current materials have the potential as pH-responsive targeted nanocarriers in the field of medical treatment.

Four naturally occurring zeolites AZLB-Ca and AZLB-Na (Bowie, Arizona), NM-Ca (Winston, New Mexico), and NV-Na (Ash Meadows, Nevada) were studied to evaluate structural modifications after treatment with HCl acid. AZLB-Ca and AZLB-Na are chabazite-like species and become amorphous when boiled in concentrated HCl acid as confirmed by powder X-ray diffraction. In contrast, NM-Ca and NV-Na which are clinoptilolite-like species withstood boiling in concentrated HCl acid. This treatment removes calcium, magnesium, sodium, potassium, aluminum, and iron atoms or ions from the framework while leaving the silicon framework intact as confirmed via X-ray fluorescence and diffraction. SEM images on calcined and HCl treated NV-Na were obtained. BET surface area analysis confirmed an increase in surface area for the two zeolites after treatment, NM-Ca (20.0(1) to 111(4) m2/g) and NV-Na (19.0(4) to 158(7) m2/g). 29Si and 27Al MAS NMR were performed on the natural and treated NV-Na zeolite and the data for the natural NV-Na zeolite suggested a Si:Al ratio of 4.33 similar to that determined by X-Ray fluorescence of 4.55. Removal of lead ions from solution decreased from the native (NM-Ca, 0.27(14), NV-Na, 1.50(17) meq/g) compared to the modified zeolites (30 min HCl treated NM-Ca 0.06(9) and NV-Na, 0.41(23) meq/g) and also decreased upon K+ ion pretreatment in the HCl modified zeolites.

The present study assessed the effect of abscisic acid (ABA; 25 µM) and/or nitrogen (N; 10 mM) in minimization of salinity (NaCl; 100mM)-impact on growth, photosynthetic efficiency, Rubisco activity, nitrogen and sulfur assimilation, oxidative stress (H2O2), lipid peroxidation measured as thiobarbituric acid reactive substances, (TBARS), osmolyte (Proline) content, and the activity of antioxidant enzymes (superoxide dismutase, SOD glutathione reductase, GR; ascorbate peroxidase, APX) in cultivar RH0-749 of Brassica juncea L. NaCl stress caused significant elevations in H2O2 and TBARS, and differentially modulated proline content, the activity of antioxidant enzymes, and impaired growth and photosynthetic functions. Exogenously applied 25 µM ABA negatively affected plant growth and photosynthesis in B. juncea without NaCl. In contrast, exogenously applied 25 µM ABA and 10 mM N, alone or in combination minimized oxidative stress, and maintained a fine-tuning between proline content and the activity of antioxidant enzymes, and thereby improved plant growth and photosynthetic functions in NaCl exposed B. juncea.

The present study assessed the effect of abscisic acid (ABA; 25 µM) and/or nitrogen (N; 10 mM) in minimization of salinity (NaCl; 100mM)-impact on growth, photosynthetic efficiency, Rubisco activity, nitrogen and sulfur assimilation, oxidative stress (H₂O₂), lipid peroxidation measured as thiobarbituric acid reactive substances, (TBARS), osmolyte (Proline) content, and the activity of antioxidant enzymes (superoxide dismutase, SOD glutathione reductase, GR; ascorbate peroxidase, APX) in cultivar RH0-749 of Brassica juncea L. NaCl stress caused significant elevations in H₂O₂ and TBARS, and differentially modulated proline content, the activity of antioxidant enzymes, and impaired growth and photosynthetic functions. Exogenously applied 25 µM ABA negatively affected plant growth and photosynthesis in B. juncea without NaCl. In contrast, exogenously applied 25 µM ABA and 10 mM N, alone or in combination minimized oxidative stress, and maintained a fine-tuning between proline content and the activity of antioxidant enzymes, and thereby improved plant growth and photosynthetic functions in NaCl exposed B. juncea.

Introduction: Increased oxidative stress, including elevated homocysteine (Hcy) plasma levels, and lowered levels of antioxidants participate in the pathophysiology and progression of chronic kidney disease (CKD). Paraoxonase (PON)1 activity and folic acid are antioxidants which play a role in Hcy metabolism. However, there are no data whether, in CKD, treatment with folic acid improves glomerular filtration rate (GFR) through effects on PON1 activity and Hcy concentrations. Methods: In the current study, we determined PON1 genotypes and activity, Hcy and estimated GFR (eGFR) both before and after treatment with folic acid (5 mg/d) versus no treatment during three consecutive months in 113 outpatients with CKD classified into stages 4, 3b and 3a. Results: PON1 CMPAase and AREase activities were significantly lower in patients allocated to CKD stage 4 as compared with stages 3b and 3a. Treatment with folic acid significantly improved eGFR and increased levels of CMPAase and AREase in patients allocated to classes 4 and 3b, but not 3a. The improvement of eGFR was associated with increased CMPAase and AREase activities, while the latter were associated with increased levels of folic acid. Treatment with folic acid significantly reduced plasma Hcy levels and the Hcy/PON1 activity ratio. The effects of folic acid increasing PON1 activities were not mediated by changes in Hcy. Discussion: Treatment of CKD patients in early/intermediate stages of CKD patients improves oxidative stress by rebalancing the prooxidant (Hcy) / antioxidant (PON1 activities) ratio. Treatment with folic acid significantly improves eGFR and these effects are mediated via increased PON1 activities. Treatment with folic acid in phase G3b and G4 may reduce renal disease progression by enhancing antioxidant defenses.

The myocardial extracellular matrix is not a passive entity, but rather a complex and dynamic microenvironment which represents an important structural and signaling system within the myocardium. Understanding the fundamental role of hypoxia and peroxidation in the genesis of many cardiovascular diseases has stimulated the development of strategies that can enhance the energy-producing functions of cells. Revealing the alterations in cardiac metabolism and function associated with sustained exposure to high altitude advances our understanding of hypoxia-related disease. The study was conducted on 26 adult males of Wistar rats weighing 220–310 g, divided into 3 groups. The first control group consisted of 6 intact animals, the second group included 10 rats which were exposed to hypobaric hypoxia without medication for 30 days. Third group was composed of 10 rats, which were medicated by succinic acid solution which was injected intraperitoneally once a day at the rate of 0.5 mL/100 g of animal body weight 15 minutes before hypoxic exposure for 30 days. Fibrosis in the myocardium inevitably leads to increased myocardial stiffness, resulting in systolic and diastolic dysfunction, neurohormonal activation and, ultimately, heart failure Changes in cardiac highenergy phosphate metabolism may underlie the myocardial dysfunction caused by hypobaric hypoxia. Reduced oxygen delivery by microvascular damage, increased perivascular fibrosis associated with reduced cellular oxygen availability may contribute to contractile failure. Succinic acid combined with inosine acts as a high-energy phosphate reserve, to maintain adenosine triphosphate at levels sufficient to support contractile function.

Lead Acid Batteries (LABs) are used for starting, lighting, and igniting, as well as in air conditioning systems and to supply power to electric engines in transport vehicles (TVs). However, the application of LABs for TVs has faced a number of market challenges, mounted by the upcoming high energy density and long lifespan batteries, such as lithium ion. LABs, on the other hand, are inexpensive. The key research question is, how can the lifespan of LABs used in automotive industries be increased, while still ensuring a low cost solution? Thus, integrating LABs with the supercapacitor (known as an electric double layer capacitor—EDLC) is likely to outperform the competing alternative batteries for TVs. This paper proposes a multiple stage approach to hybrid lead acid batteries and a supercapacitor system for TVs that is capable of maintaining the battery state-of-charge (SOC) at statistically high limits, ranging between 90% and 95%. This SOC target will likely ensure that the lifespan of the hybrid battery system can be elongated (extended) more than its competitors. In this study, the multiple stage approach of concatenated converters has been designed in order to satisfy all energy storage requirements for different characteristics of LABs and the supercapacitor. The designed hybrid system has been simulated using Matrix Laboratory (MATLAB/Simulink (version R2016a, MathWorks, Natick, MA, USA)). The simulated results show that high transient currents from the direct current (DC) bus of LABs, caused by the regenerative braking or deceleration of the TVs, reduce the battery lifespan and induce mechanical stress. The supercapacitor reduces the stress on the LAB by absorbing high transient currents. This, in turn, keeps the LABs’ SOC between 90% and 96% and the voltage at 12 V. As indicated by the simulated results, the hybrid battery SOC is maintained at 90–96% and the terminal voltage is approximately 12 V.

The aim of this study was synthesize and evaluate the effects of Poly (D, L-Lactide-co-glycolide) (PLGA) Nanoparticles (NPs) of metformin (PLGA+ Met) on inflammation, and bone loss in a ligature-induced periodontitis rat model. The prepared NPs were characterized by mean diameter, size particle, polydispensity index and encapsulation efficiency by Atomic force microscopy (AFM). Male albino Wistar rats were randomly divided into four groups of 20 rats in each group, and given the following treatments for 10 days to evaluate in vivo activity: (1) Sham: no ligature + water; (2) Positive control: ligature + water (with Periodontal disease and Diabetes); (3) ligature + PLGA+ 10 mg/kg Met (With Periodontal disease and Diabetes); and (4) ligature + PLGA+ 100 mg/kg Met (with Periodontal disease and Diabetes). Water or PLGA + Met was administered orally by gavage. Maxillae were fixed and scanned using Micro-computed Tomography (μCT) to quantify linear of bone loss. Histopathological characteristics were assessed through immunohistochemical staining for Osteocalcin, Cathepsyn K, RANKL/RANK/OPG pathway. IL-1β and TNF-α from gingival tissues were analysed by Elisa immunoassay. Quantitative RT-PCR reaction was used to evaluate gene expression of AMPK, NF-κB p-65, Hmgb1 and TAK-1 from gingival tissues. Statistical analysis was performed using one-way ANOVA at 5% significance. The mean diameter of MET-loaded PLGA nanoparticles was in a range of 457.1 ± 48.9 nm with a polydispersity index of 0.285, zeta potential: 8.16 ± 1.1 mV and entrapment efficiency (EE) was 70%. The results suggest that the addition of MET in the core slightly affected the particle sizes. Treatment with PLGA+ 10 mg/kg Met showed low inflammatory cells, decreased bone loss and integrity cement and levels of IL-1β, and TNF-α (p < 0.05) were significantly reduced. Additionally, weak staining was shown by RANKL, Cathepsyn K, OPG, and osteocalcin. Radiographically, linear measurements showed a statistically significant reduction in bone loss after treatment with PLGA+ 10 mg/kg Met compared to the positive control (p < 0.05). RT-PCR showed increased AMPK expression (p < 0.05) and decreased expression of NF-κB P65, HMGB1 and TAK-1 after PLGA+ 10 mg/kg Met (p < 0.05). The PLGA nanoparticle + 10 mg/kg Met decreased glucose levels and also decreased the inflammatory response, and bone loss in ligature-induced periodontitis in rats.

We evaluated oleanolic acid (OA)-induced anti-cancer activity, apoptotic mechanism, cell cycle status, and MAPK kinase signaling in DU145 (prostate cancer), MCF-7 (breast cancer), and U87 (human glioblastoma) cells. The IC50 values for OA-induced cytotoxicity were 112.57 in DU145, 132.29 in MCF-7, and 163.60 in U87 cells, respectively. OA (at 100 µg/mL) increased the number of apoptotic cells to 27.0% in DU145, 27.0% in MCF-7, and 15.7% in U87 cells, when compared to control cells. This enhanced apoptosis was due to increases in p53, cytochrome c, and Bax expression. OA-treated DU145 cells were arrested in G2 because of the activation of p-ERK and p21, and the decrease in cyclin B1 and cyclin E expression. Furthermore, OA-treated MCF-7 cells were arrested in G1 owing to the activation of p-JNK, p-ERK, p21, and p27, and the decrease in p-AKT, cyclin E, and CDK2. U87 cells also exhibited G1 phase arrest caused by the increase in p-ERK, p-JNK, p21, and p27, and the decrease in CDK2. Thus, OA arrests the cell cycle in different phases, and increases apoptosis in cancer cells. These results suggest that OA may alter the expression of cell cycle regulatory proteins in a cancer type-dependent manner.

Dermal injections of hyaluronic acid gel for aesthetic skin rejuvenation are increasingly popular nowadays. Although these products are classified as medical devices, the regulations on their administration by licensed practitioners are still weak, whereas their manufacturers increasingly highlight and advertise the cellular effects that underpin the efficacy of these injections. In this re-view, we discuss all current knowledge on the mode of action of dermally injected hyaluronic acid and the potential toxicological implications especially from crosslinked gels in conjunction with the current global regulations. We conclude that dermal injections of hyaluronic acid have several therapeutic implications that warrant further research, and that strict regulations must be applied on their manufacture/quality control and the required qualifications of licensed aesthetic injectors.

Starvation of photoreceptors induced by reduced dysregulated ocular blood flow is proposed as a common pathway for the pathogenesis of retinitis pigmentosa (RP). The current study evaluated the safety and efficacy of ophthalmic nerve stimulation (ONS) as an ocular blood flow neuromodulator, combined with ascorbic acid (AA) as a potent anti-oxidant in the treatment of RP. Additionally, the initial characteristics of rod responders were identified. Forty participants with simple, non-syndromic RP presented with a characteristic triad of RP (the bone spicule pigmentation, attenuation of retinal blood vessels, and waxy optic disc pallor), were en-rolled in a prospective open-label single-armed interventional study. The severity of the disease was clinically graded into six stages. Patients with an established diagnosis of RP; aged ≥ 4 years, with best corrected visual acuity (BCVA) ≥ 20/400 were included. All participants were daily treated with bilateral ONS sessions combined with intravenous administration of AA for two weeks. The primary efficiency endpoint was 6 months’ changes in scotopic vision as measured by a 10-item, 100-point, Low Luminance Questionnaire-10 (LLQ-10). The secondary efficiency points included best corrected visual acuity (BCVA) and contrast sensitivity. Rod responders were defined by ≥ 25 points increment of LLQ-10 score at 6 months after treatment. The results showed that ONS combined with AA treatment significantly improved low luminance vision, BCVA, and contrast sensitivity in patients with RP (p≤ 0.05). At 6-month visit, twenty-four (60%) patients were identified as rod responders and 16 (40%) patients were rod-non-responders. The mean change in LLQ-10 score was (46.35 ±16.81) in rod responders versus (4.9 ± 7.6) in non-responders (p < 0.0001). A clinically significant improvement of BCVA (≥0.2 logMAR) and contrast sensitivity (≥0.3 log unit) were demonstrated in 50% of the right eyes of rod responders. No serious adverse effects were reported and headache in 5 patients (12.5%) was the only en-countered side effect in this study. In conclusion, ocular neuromodulation is a safe therapeutic strategy for RP. It significantly improved night vision, BCVA, and contrast sensitivity. Determinants of rod responders include a shorter duration of night blindness, an earlier stage of the disease, and a relatively thicker ganglion cell layer at baseline. Additionally, two therapeutic scenarios were recognized; an early disease-modifying intervention that restores night vision and reverses the disease process and a late cone rescue intervention that improves/maintains central vision.

Neurodegenerative disorders are characterized by a progressive process of degeneration and neuronal death, where oxidative stress and neuroinflammation are key factors that contribute to the progression of these diseases. Therefore, two major pathways involved in these pathologies have been proposed as relevant therapeutic targets: The nuclear transcription factor erythroid 2 (Nrf2), which responds to oxidative stress with cytoprotecting activity and the nuclear factor NF-κB pathway, which is highly related to the neuroinflammatory process by promoting cytokine expression. Caffeic acid phenethyl ester (CAPE) is a phenylpropanoid naturally found in propolis that shows important biological activities, including neuroprotective activity by modulating the Nrf2 and NF-kB pathways, promoting antioxidant enzyme expression and inhibition of proinflammatory cytokine expression. Its simple chemical structure has inspired the synthesis of many derivatives, with aliphatic and/or aromatic moieties, some of which have improved the biological properties. Moreover, new drug delivery systems increase the bioavailability of these compounds in vivo, allowing its transcytosis through the blood-brain barrier, thus protecting brain cells from the increased inflammatory status associated to neurodegenerative and psychiatric disorders. This review summarizes the biosynthesis and chemical synthesis of CAPE derivatives, their miscellaneous activities, and relevant studies (from 2010 to 2023) addressing their neuroprotective activity in vitro and in vivo.

Diamidophosphate has been identified as a possible prebiotic compound used in the precursor membranes of the first ‘life’. Compounds such as these will be helpful in developing novel biomimetic approaches in synthetic chemistry. Thermochemical data for this type of compounds are not available. Hess’ law and estimates from calorimetric measurements used by Wakefield in the 1970s for other amido phosphates have been used to estimate the thermochemical values for the diamido and monoamido-phosphoric acid. Enthalpy of formation at 298.15 ^oC is calculated as – 821.9 kJ/mol and the free energy of formation calculated as -813.5 kJ/mol for the diamidophosphoric acid. The calculated enthalpy of formation of monoamidic phosphoric acid is -1117.1 kJ/mol and its free energy of formation is - -1105 kJ/mol.

The factors that determine the relative rates of amino acid substitution during protein evolution are complex and they are known to vary among taxa. We estimated relative exchangeabilities for pairs of amino acids from clades spread across the tree of life and assessed the historical signal in the distances among these clade-specific models. We trained these models separately on collections of arbitrarily selected protein alignments and on ribosomal protein alignments. In both cases we found a clear separation between the models trained using multiple sequence alignments from bacterial clades and the models trained on archaeal and eukaryotic data. We assessed the predictive power of our novel clade-specific models of sequence evolution by asking whether fit to the models could be used to identify the source of multiple sequence alignments. Model fit was generally able to classify protein alignments correctly at the level of domain (bacterial versus archaeal), but the accuracy of classification at finer scales was much lower. The only exceptions to this were the relatively high classification accuracy for two archaeal lineages: Halobacteriaceae and Thermoprotei. Genomic GC content had a modest impact on relative exchangeabilities despite having a large impact on amino acid frequencies. Relative exchangeabilities involving aromatic residues exhibited the largest differences among models. There were a small number of exchangeabilities that exhibited large differences in comparisons among major clades and between generalized models and ribosomal protein models. Taken as a whole, these results reveal that a small number of relative exchangeabilities are responsible for much of the structure of the “model space” for protein sequence evolution. If we look beyond the information that these clade-specific models reveal about protein evolution the models themselves are likely to be useful tools for phylogenomic inference across the tree of life.

Pathogens that adapt to environmental stress can develop an increased tolerance to some physical or chemical antimicrobial treatments. The main objective of this study was to determine if acid adaptation increased the tolerance of Escherichia coli O157:H7 to high voltage atmospheric cold plasma (HVACP) in raw pineapple juice. Samples (10 ml) of juice were inoculated with non-acid-adapted (NAA) or acid adapted (AA) E. coli to obtain a viable count of ~ 7.00 log10 CFU/ml. The samples were exposed to HVACP (70 kV) for 1 to 7 min with inoculated non-HVACP-treated juice serving as control. Juice samples were analyzed for survivors at 0.1 h, and after 24 h of refrigeration (4 °C). Samples analyzed after 24 h exhibited significant decreases in viable NAA cells with sub-lethal injury detected in both NAA and AA survivors (P&lt;0.05). No NAA survivor in juice exposed to HVACP for 5 or 7 min was detected after 24h. However, numbers of AA survivors were 3.33 and 3.09 log10 CFU/ml in juice treated for 5 and 7 min, respectively (P&lt;0.05). These results indicate that acid adaptation increases the tolerance of E. coli to HVACP in pineapple juice. The potentially higher tolerance of AA E. coli O157:H7 to HVACP should be considered in developing safe juice processing parameters for this novel non-thermal technology.

(1) Background: The typical transporter protein, P-glycoprotein (P-gp), has been proven to be associated with multidrug resistance (MDR). Pyxinol and 24S-Pyxinol amino acid ester derivatives had been demonstrated to be promising P-gp inhibitors for reversal of tumor MDR in KBV cells, however, their roles in MDR reversal in other tumor-resistant cells are still unclear. (2) Methods: In the present study, we synthesized 40 amino acid ester derivatives of Pyxinol and 24S-Pyxinol. The MDR reversal effects of these derivatives were evaluated in A549/Tax, MCF-7/ADR, and HCT-8/VCR cells using the CCK-8 assay. Subsequently, western blot assay, intracellular Rhodamine123 (Rh123) accumulation assay and P-gp ATPase activity assay were utilized to investigate the effects of active compound on P-gp. Molecular docking was used to predict the possible binding patterns of active compound to P-gp. Moreover, based on UPLC-Q/TOF-MS cellular metabolomics technology to identify endogenous differential metabolites and metabolic pathways associated with tumor MDR effects of the active compound. (3) Results: The results of the CCK-8 assay showed that compounds 8, 14, 16, 17, 18, 23, 25, 34, 36, 37 exhibited strong MDR reversal effect in A549/Tax, MCF-7/ADR and HCT-8/VCR cells, which were screened by reversal fold (RF) greater than 5. Among them, 10 μM of derivative 37 (new compound) showed the outstanding activity (RF: 15.31) in reversing MDR in A549/Tax cells. Compound 37 could act as a substrate for P-gp and inhibit the efflux function of P-gp by competitively binding to the binding site of antitumor drugs. Meanwhile, the molecular docking results confirmed that compound 37 was identified to under-go high-affinity binding to the drug binding site of P-gp. In addition, 14 endogenous differential metabolites and 6 metabolic pathways involved closely associated with the reversal of tumor MDR effects of compound 37 were identified. (4) Conclusions: Overall, a new candidate compound 37 (24S-3-L-threonyl-Pyxinol) could be provided for reversing tumor MDR by this study.

Retinal lipofuscin accumulates with age in the retinal pigment epithelium (RPE) where its fluorescence properties are used to assess the retinal health. It was observed that there is a decrease in lipofuscin fluorescence above the age of 75 years and in early stages of age-related macular degeneration (AMD). The purpose of this study was to investigate the response of lipofuscin isolated from human RPE, and lipofuscin-laden-cells to visible light, and determine whether an abundant component of lipofuscin, docosahexaenoate (DHA) can contribute to lipofuscin fluorescence upon oxidation. Exposure of lipofuscin to visible leads to a decrease of its long-wavelength fluorescence at about 610 nm with concomitant growth of the short-wavelength fluorescence. The emission spectrum of photodegraded lipofuscin exhibits similarity with that of oxidized DHA. Exposure to light of lipofuscin-laden cells leads to loss of lipofuscin granules from cells, while retaining cell viability. The spectral changes of fluorescence in lipofuscin-laden cells resemble those seen during photodegradation of isolated lipofuscin. Our results demonstrate that fluorescence emission spectra together with quantitation of intensity of long-wavelength fluorescence can serve as a marker useful for lipofuscin quantification and for monitoring its oxidation, thereby useful for screening the retina for increased oxidative damage and early AMD-related changes.

Gamma-aminobutyric acid (GABA) and glycine act as inhibitory neurotransmitters. Three types of inhibitory neurons and terminals, GABAergic, GABA/glycine co-releasing, and glycinergic, are orchestrated in the spinal cord neural circuits and play key roles in the regulation of pain, locomotive movement, and respiratory rhythms. Herein, we first describe GABAergic and glycinergic transmission and inhibitory networks, which consist of three types of terminals, in the mature mouse spinal cord. Second, we describe the developmental formation of GABAergic and glycinergic networks, with specific focus on the differentiation of neurons, formation of synapses, maturation of removal systems, and changes in their action. GABAergic and glycinergic neurons are derived from the same domains of the ventricular zone. Initially, GABAergic neurons are differentiated and their axons form synapses. Some of these neurons remain GABAergic in lamina I and II. Many of GABAergic neurons convert to co-releasing state. The co-releasing neurons and terminals remain in the dorsal horn, whereas many of co-releasing ones ultimately become glycinergic in the ventral horn. During the development of terminals and the transformation from radial glia to astrocytes, GABA and glycine receptor subunit compositions markedly change, removal systems mature, and GABAergic and glycinergic action shifts from excitatory to inhibitory.

This research evaluated the role and feasibility of the granular nanocellulose particles (GNC) from sugarcane bagasse obtained from enzymatic hydrolysis in reducing lipid digestibility and permeability in the in vitro simulated gastrointestinal (GI) system. GNC concentration (0.02%, w/v) had significantly affected the released free fatty acid (FFA) reduction of approximately 20%. The Pick-ring emulsion of the GNC and olive oil simulation mixture revealed higher oil droplet size distribution and stability in the initial stage than the vortexed mixture formation. The difference in particle size distribution and zeta potential of the ingested GNC suspension and GNC-olive oil emulsion were displayed during the in vitro gastrointestinal simulation. GNC particles interacted and distributed surrounding the oil droplet leading to the interfacial emulsion. The GNC concentration (0.01-0.10%, w/v) showed low toxicity on the HIEC-6 cell, ranging from 80.0 to 99% of cell viability. The release of FFA containing the ingested GNC suspension and GNC-olive oil emulsion was about 30% reduction compared to without GNC digest solution. The FFA and triglyceride permeability through the HIEC-6 intestinal epithelium monolayer were deceased in the digesta containing the ingested GNC and emulsion. This work indicated that GNC represented a significantly critical role and properties in the GI tract and reduced lipid digestion and absorption. This GNC could be utilized as an alternative food additive or supplement in fatty food for weight control due to their inhibiting lipid digestibility and assimilation.

Mycobacteria can be one of the main contaminants of biological products, and their presence can have serious consequences on patients’ health. Thus, specific testing is necessitated by regulations such as the European Pharmacopoeia. The current pharmacopeial reference i.e., microbial culture method cannot ensure an exhaustive detection of mycobacteria due to their growth characteristics. Additionally, the method is time-consuming and requires a continuous supply of culture media, which could be further challenging. Thus, to overcome these challenges, pharmaceutical industries need to consider alternative non-microbiological techniques to detect these fastidious, slow-growing contaminating agents. This review provides an overview of alternative methods, which could be applied within a quality control environment of biological products, and underlines advantages and limitations of these methods. Nucleic acid amplification techniques or direct measurement of mycobacteria stands out as the most suitable alternatives for mycobacterial testing in biological products.

One of the earliest hallmarks of plant immune response is production of reactive oxygen spe-cies (ROS) in different subcellular compartments, which regulate plant immunity. A suitable equilibrium, which is crucial to prevent ROS over-accumulation leading to oxidative stress, is maintained by salicylic acid (SA), a chief regulator of ROS. However, ROS are not only acting downstream of SA signaling, but were also proposed to be a central component of a self-amplifying loop that regulates SA signaling as well as the interaction balance between dif-ferent phytohormones. The exact role of this crosstalk, the position where SA interferes with ROS signaling and ROS interferes with SA signaling and the outcome of this regulation depend on the origin of ROS but also on the pathosystem. The precise spatiotemporal regulation of or-ganelle specific ROS and SA levels determine the effectiveness of pathogen arrest and is there-fore crucial for a successful immune response. However, the regulatory interplay behind still remain poorly understood, as up till now, the role of organelle specific ROS and SA in HR-conferred resistance has mostly been studied by altering the level of a single component. In order to address these aspects, a sophisticated combination of research methods for monitoring the spatiotemporal dynamics of key players and transcriptional activity in plants is needed, and will most probably consist of biosensors and precision transcriptomics.

The behaviour of the pseudo-protic ionic liquids TOAH+Cl- and TODAH+Cl- in the facilitated transport of indium(III) from HCl solutions is described. Metal transport is investigated as a function of different variables: hydrodynamic conditions, HCl concentration in the feed phase and indium and carrier concentrations. The experimental data are used to model both transport systems and to estimate diffusional parameters associated to them.

The endo- and exo-N-heterocyclic carbene precursors based on camphor were prepared diastereoselectively in five synthetic steps starting from (1S)-(+)-ketopinic acid. The obtained N-heterocyclic carbene precursors were investigated in an asymmetric benzoin reaction. All new compounds were fully characterized and the absolute configurations were determined by X-ray diffraction and NOESY measurements.

The dye effluent is usually difficult to be degraded by conventional wastewater treatment in leather industry. In order to develop efficient and cost-effective treatment methods, we evaluate the effect of white-rot fungus immobilization for dye decolorisation in this paper. The Phanerochaete chrysosporium BKM-F-1767 was used for immobilization. This research found that the white-rot fungus immobilization had an obviously decolorisation effect in dye wastewater treatment, and plant carriers such as sorghum stalk and corn cob were helpful to the growth of Phanerochaete chrysosporium in white-rot fungus immobilization. Due to the stability and recyclability, the white-rot fungus co-immobilization was considered as the most suitable treatment for decolorisation of dye effluent which enjoyed the advantages of both adsorption immobilization and entrapment immobilization. Furthermore, the dye decolorisation evaluation was carried out to find the most suitable carrier for co-immobilization, and it found that sorghum stalk - calcium-alginate gel spherical particle (SS-CGPB) has better decolorisation effect than corn cobs - calcium-alginate gel spherical particle (CC-CGPB), and the dye decolorisation rate was 86.77%. After 5 cycles, the dye decolorisation rate was 85.87% which indicated the SS-CGPB preserved functional integrity successfully. By further analyzing the biodegradation process with white-rot fungus immobilization, the intermediate products were observed and the degradation pathway of acid golden yellow dye molecular was proposed. The results showed that the C-N single bonds attached to the central benzene in the dye molecule were attacked and destroyed in white-rot fungus co-immobilization treatment, thus the structure of dye molecule could be successfully degraded into small molecules which would be more easily treated by conventional treatment methods. Therefore, the white rot fungus co-immobilization might be appropriate for pre-treatment as an important biotechnology for the advanced treatment of dye effluent.

Hydrogels have gained significant attention as vehicles for transdermal delivery systems. These polymeric-structured substances have been implemented in pharmaceutical and cosmetic applications. Many factors are employed in their preparation. Light, pH, temperature and specific molecules ligands are commonly used in the production of hydrogels. The Transdermal delivery system (TDD) is a widely used route, used to deliver actives/drugs via the skin. Hydrogels as a TDD have been shown to be efficient in enhancing the efficacy in delivering the actives and drugs. The aim of this review is to discuss the hydrogels application in both dermatological therapeutic and cosmetic applications, covering the types, and properties of hydrogel polymer networks. Furthermore, this review presents one of the most extensively used polymers (Hyaluronic acid HA) in this field and discusses the properties, preparation methods and applications of HA hydrogel patches as a delivery system, including methods of loading the actives and the releasing of these actives from them.

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

Active vitamin D derivatives (VDDs) – 1α,25-dihydroxyvitamin D3/D2 and their synthetic analogs – are well-known inducers of cell maturation with the potential for differentiation therapy of acute myeloid leukemia (AML). However, their dose-limiting calcemic activity is a significant obstacle to using VDDs as an anticancer treatment. We have shown that different activators of the NF-E2-related factor-2/Antioxidant Response Element (Nrf2/ARE) signaling pathway, such as the phenolic antioxidant carnosic acid (CA) or the multiple sclerosis drug monomethyl fumarate (MMF), synergistically enhance the antileukemic effects of various VDDs applied at low concentrations in vitro and in vivo. This study aimed to investigate whether glutathione, the major cellular antioxidant and the product of the Nrf2/ARE pathway, can mediate the Nrf2-dependent differentiation-enhancing activity of CA and MMF in HL60 human AML cells. We report that glutathione depletion using L-buthionine sulfoximine attenuated the enhancing effects of both Nrf2 activators concomitant with downregulating vitamin D receptor (VDR) target genes and the activator protein-1 (AP-1) family protein c-Jun levels and phosphorylation. On the other hand, adding reduced glutathione ethyl ester to dominant negative Nrf2-expressing cells re-stored both the suppressed differentiation responses and the downregulated expression of VDR protein, VDR target genes, as well as c-Jun and P-c-Jun levels. Finally, using the transcription factor decoy strategy, we demonstrated that AP-1 is necessary for the enhancement by CA and MMF of 1α,25-dihydroxyvitamin D3-induced VDR and RXRα protein expression, transactivation of the vitamin D response element, and cell differentiation. Collectively, our findings suggest that glutathione mediates, at least in part, the potentiating effect of Nrf2 activators on VDDs-induced differentiation of AML cells, likely through the positive regulation of AP-1.

The growth of two pairs of co-cultures (Escherichia coli/Geotrichum candidum, and Staphylococcus aureus/Geotrichum candidum) with a starter culture of lactic acid bacteria was studied in milk at temperatures related to artisanal cheesemaking ripening. For an inoculum of approximately 106 CFU/mL, LAB not only induced an early stationary phase of E. coli (two strains BR and PS2) and S. aureus (strains 2064 and 14733) but affected their death phase. G. candidum was found to be the subject of interactions with LAB within a given temperature range only partially. To develop a tertiary model for the growth curves of the populations, a one-step approach was used, combining two types of primary models (Huang and Gimenez and Dalgaard) with secondary square root models for growth rate and lag time. Furthermore, the reparametrized Gompertz-inspired function with the Bigelow secondary model was used to describe the death phase of the E. coli and S. aureus strains. The prediction ability of the growth of the H-GD tertiary model for co-cultures was cross-validated within the strains and data sets in milk and milk medium with 1 % NaCl.

Nanosized drug delivery systems (DDS) have been studied as a novel strategy against cancer due to their potential to simultaneously decrease drug inactivation and systemic toxicity and increase passive and/or active drug accumulation within the tumor(s). Triterpenes are plant-derived compounds with interesting therapeutic properties. Betulinic acid (BeA) is a pentacyclic triterpene which has great cytotoxic activity against different cancer types. Herein, we developed a nanosized protein-based DDS of bovine serum albumin (BSA) as the drug carrier combining two compounds: doxorubicin (Dox) and the triterpene BeA using an oil-water-like micro-emulsion method. Spectrophotometric assays were performed to determine protein and drug concentrations in the DDS. The biophysical properties of these DDS were characterized using dynamic light scattering (DLS) and circular dichroism (CD) spectroscopy confirming nanoparticle (NP) formation and drug loading into the protein structure, respectively. The encapsulation efficiency was 77% for Dox and 18% for BeA. More than 50% of both drugs were released within 24 h, at pH 6.8, while less drug was released at pH 7.4 in this time period. Co-incubation viability assays of Dox and BeA alone for 24 h demonstrated synergistic cytotoxic activity in the low μM range against the non-small cell lung carcinoma (NSCLC) A549 cells. Viability assays of the BSA(Dox+BeA) DDS demonstrated a higher synergistic cytotoxic activity than the two drugs with no carrier. Moreover, confocal microscopy analysis confirmed cellular internalization of the DDS and nucleus accumulation of the Dox. We determined the mechanism of action of the BSA(Dox+BeA) DDS, confirming S-phase cell cycle arrest, DNA damage, caspase cascade activation, and downregulation of the epidermal growth factor receptor (EGFR) expression. This DDS has the potential to synergistically maximize the therapeutic effect of Dox and diminish chemoresistance induced by EGFR expression using a natural triterpene against NSCLC.

This work aims to investigate systematically the influence of process temperature and biomass-to-water ration on the chemical composition of aqueous and gaseous phases and mass production of chemical by hydrothermal processing of Açaí (Euterpe Oleraceae, Mart.) seeds. The hydrothermal carbonization carried out at 175, 200, 225, and 250 °C, 2 °C/min, biomass-to-water ratio of 1:10, and at 250 °C, 2 °C/min, and biomass-to-water ratios of 1:10, 1:15, and 1:20, in technical scale. The chemical composition of aqueous phase determined by GC and HPLC and the volumetric composition of gaseous phase by using an infrared gas analyzer. For constant biomass-to-water ratio of 1:10, the yields of solid, liquid, and gaseous phases varied between 53.39 and 37.01% (wt.), 46.61 and 59.19% (wt.), and 0.00 and 3.80% (wt.), respectively. The yield of solids shows a smooth exponential decay with temperature, while that of liquid and gaseous phases a smooth growth. By variation of biomass-to-water ratios, the yields of solid, liquid, and gaseous reaction products varied between 53.39 and 32.09% (wt.), 46.61 and 67.28% (wt.), and 0.00 and 0.634% (wt.), respectively. The yield of solids decreases exponentially with increasing water-to-biomass ratio and that of liquid phase increases in a sigmoid fashion. For constant biomass-to-water ratio, the concentrations of Furfural and HMF decrease drastically with temperature, reaching a minimum at 250 °C, while that of phenols increases. In addition, the concentrations of CH3COOH and total carboxylic acids increase, reaching a maximum at 250 °C. For constant process temperature, the concentrations of aromatics vary smoothly with the temperature. The concentrations of furfural, HMF, and cathecol decrease with temperature, while that of phenols increases. The concentrations of CH3COOH and total carboxylic acids decrease exponentially with temperature. Finally, for the experiments with varying water-to-biomass ratios, the productions of chemicals (furfural, HMF, phenols, cathecol, and acetic acid) in the aqueous phase is highly dependent on the biomass-to-water ratio.

In the last decades, studies on the inflammatory signaling pathways in multiple pathological contexts revealed new targets for novel therapies. Among the family of G-protein-coupled Proteases Activated Receptors, PAR2 was identified as a driver of the inflammatory cascade in many pathologies, ranging from autoimmune disease to cancer metastasis. For this reason, many efforts have been focused on the development of potential antagonists of PAR2 activity. This work focuses on a small molecule, 1-Piperidine Propionic Acid (1-PPA), previously described to be active against inflammatory processes, but whose target is still unknown. Stabilization effects observed by cellular thermal shift assay coupled to in-silico investigations, including molecular docking and Molecular Dynamics simulations, suggested that 1-PPA binds PAR2 in an allosteric pocket of the receptor inactive conformation. In addition, this compound was found able to inhibit platelet aggregation, a process mediated by PAR family members, including PAR2. Since the allosteric pocket binding 1-PPA is highly conserved in all the members of the PAR family, the evidence reported here suggests that 1-PPA could represent a promising new small molecule targeting PARs with antagonistic activity.

Recent lines of evidence suggest the intriguing hypothesis that consuming common culinary herbs of the mint family might help prevent or treat Covid. Individual citizens could easily explore the hypothesis using ordinary kitchen materials. I offer a philosophical framework to account for the puzzling lack of public health messaging about this interesting idea.

The combined effects of the thermal processing (i.e., sterilisation treatment) and the prior frozen storage time (3 or 6 months at –18 ºC) on the quality loss in canned Atlantic horse mackerel (Trachurus trachurus) were determined. Thus, the sterilisation step led to a remarkable (p&lt;0.05) formation in canned fish muscle of fluorescent compounds, free fatty acids (FFAs) and trimethylamine and to an increase of the L* and b* colour parameters; meantime, a decrease (p&lt;0.05) of the total ω3 FA/total ω6 FA ratio and the a* colour value were detected. The prior frozen storage period led to an increased (p&lt;0.05) lipid oxidation (peroxide, thiobarbituric acid reactive substance and fluorescent compound formation) and hydrolysis (FFA formation) development and to increased L* and b* colour values in the corresponding canned samples; additionally, a lower (p&lt;0.05) polyene index and phospholipid content were observed in canned fish previously subjected to frozen storage. In most indices, physico-chemical changes related to quality loss were found higher if the previous storage period was increased. According to the marked effects of the sterilisation step and the prior frozen storage period, optimisation of such processing conditions is recommended to maximise the quality of canned horse mackerel.

Biphasic bone substitutes (BBS) are nowadays established biomaterials. Through their constant development even natural components like hyaluronic acid (HY) are added to improve both their handling and also their regenerative properties. However, low knowledge exists regarding the consequences of the HY addition for their biocompatibility and the inflammatory tissue reactions. Thus, the present study was conducted aiming to analyze the influence of two different amounts of high molecular weight HY (HMWHY) combined with a BBS on the in vitro biocompatibility and the in vivo tissue reaction. Established in vitro procedures using L929 cells were used for cytocompatibility analyses under the test conditions of DIN EN:ISO 10993-5. For the in vivo study part, calvarial defects were created in 20 Wistar rats and subsequently filled with the BBS and the BBS combined with two different HMWHY amounts, i.e., BBS+HY(L) and BBS+HY(H). As controls empty defects were used. Established histological, immunohistochemical and histomorphometrical methods were applied to analyze the tissue reactions to the three different materials, including the induction of pro- and anti-inflammatory macrophages and multinucleated giant cells (BMGCs). The in vitro results showed that none of the materials or compositions caused biological damages to the L929 cells and can considered to be non-toxic. The in vivo results showed that only the addition of high doses of HY to a biphasic bone substitute significantly decreases the occurrence of proinflammatory macrophages (* p < 0.05) comparable to the numbers found in the control group, while no significant differences within the three study groups for M2-macrophages nor BMGCs were detected. In conclusion, the addition of different amounts of HMWHY does not seem to affect the inflammation response to the BBS while improving the material handling properties.

This work aims to investigate systematically the influence of process temperature, bio-mass-to-water ratio, and production scales (laboratory and pilot) on the chemical composition of aqueous and gaseous phases and mass production of chemical by hydrothermal processing of Açaí (Euterpe Oleraceae, Mart.) seeds. The hydrothermal carbonization carried out at 175, 200, 225, and 250 °C, 2 °C/min, biomass-to-water ratio of 1:10, and at 250 °C, 2 °C/min, and biomass-to-water ratios of 1:10, 1:15, and 1:20, in technical scale, as well as at 200, 225, and 250 °C, 2 °C/min, bio-mass-to-water ratio of 1:10, in laboratory scale. The elemental composition (C, H, N, S) of solid phase determined to compute the HHV. The chemical composition of aqueous phase determined by GC and HPLC and the volumetric composition of gaseous phase by using an infrared gas an-alyzer. For the experiments in pilot scale with constant biomass-to-water ratio of 1:10, the yields of solid, liquid, and gaseous phases varied between 53.39 and 37.01% (wt.), 46.61 and 59.19% (wt.), and 0.00 and 3.80% (wt.), respectively. The yield of solids shows a smooth exponential de-cay with temperature, while that of liquid and gaseous phases a smooth growth. By varying the biomass-to-water ratios, the yields of solid, liquid, and gaseous reaction products varied be-tween 53.39 and 32.09% (wt.), 46.61 and 67.28% (wt.), and 0.00 and 0.634% (wt.), respectively. The yield of solids decreases exponentially with increasing water-to-biomass ratio and that of liquid phase increases in a sigmoid fashion. For constant biomass-to-water ratio, the concentrations of Furfural and HMF decrease drastically with increasing temperature, reaching a minimum at 250 °C, while that of phenols increases. In addition, the concentrations of CH3COOH and total car-boxylic acids increase, reaching a maximum at 250 °C. For constant process temperature, the concentrations of aromatics vary smoothly with the temperature. The concentrations of furfural, HMF, and cathecol decrease with temperature, while that of phenols increases. The concentra-tions of CH3COOH and total carboxylic acids decrease exponentially with temperature. Finally, for the experiments with varying water-to-biomass ratios, the productions of chemicals (furfu-ral, HMF, phenols, cathecol, and acetic acid) in the aqueous phase is highly dependent on the biomass-to-water ratio. For the experiments in laboratory scale with constant biomass-to-water ratio of 1:10, the yields of solid ranged between 55.9 and 51.1% (wt.), showing not only a linear decay with tem-perature, but also a lower degradation grade. The chemical composition of main organic compounds (furfu-ral, HMF, phenols, cathecol, and acetic acid) dissolved in the aqueous phase in laboratory scale shows the same behavior of those in obtained in pilot scale.

Solid-state fermentation (SSF) is the bioprocess where microorganisms are cultivated in the absence of free water under control conditions. Lactic acid can be produced by fermenting grape stalks with Rhizopus oryzae in SSF. During the microorganism growth, the temperature and water content of the solid bed fluctuate, leading to areas of either dry or excessive moisture in the solid substrate. Therefore, it's crucial to control the supply of water to the matrix. In this work, we obtain lactic acid through SSF of grape stalks using Rhizopus oryzae NCIM 1299. The SSF was conducted at a fixed temperature of 35 °C, with three constant relative humidity levels: 50, 65, and 80 %RH. Mathematical models, including the Logistic and First Order Plus Dead Time models for fungal biomass growth and the Luedeking and Piret with Delay Time model for lactic acid production, were adjusted to kinetic curves. Growth kinetic parameters (Xmax, μmax, Tp, T0, Yp/x and td) were determined for all conditions. These kinetic parameters were then correlated with relative humidity using a second-degree polynomial relationship. We observed a decrease in Xmax with increasing %RH, while the value of Yp/x increased at higher %RH. Finally, the optimal variable relative humidity profile was obtained by applying the Dynamic Optimization Technique, resulting in a 15.30% increase in lactic acid production.

The parts obtained by FFF technology are anisotropic in any direction; while the whole part constitutes out of layers, each of the layers include one or more perimeters of shell and the infill with density from 0 to 100%. Mechanical performance of FFF parts depends on its shape, orientation, constitution and 3D printing parameters. A classification for shapes of parts obtained by FFF and stressed during its operation is provided. For the most questionable class (parts with interrupted shell critically stressed on interlayer boundaries) a representative sample and testing apparatus is developed. Different approaches to the sample shape modification were applied and tested. The part shape optimization resulted in increment of the force, required to fracture the part from 483 to 1096 N.

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

Based on the electron-deficient property of picric acid (PA), two neutral Ir(III) complexes 1 and 2 modified with the electron-rich carbazolyl groups were synthesized and characterized. Both 1 and 2 exhibit aggregation-induced phosphorescence emission (AIPE) properties in THF/H2O. Among them, 2 is extremely sensitive for detecting PA with a limit of detection of 0.15 μM in THF/H2O. Furthermore, the selectivity for PA is significantly higher compared to other analytes, enabling efficient detection of PA in four common water samples. The density functional theory calculations and the spectroscopic results confirm that the sensing mechanism is photo-induced electron transfer.

Knee Osteoarthritis (KOA), the most common knee degenerative disease, involve a slow destructive process, leading to disability and ultimately total knee replacement. The progression of KOA is related to the loss of rheological properties of the synovial fluid (SF), due to slow immunological, inflammatory and enzymatic processes that cleave the hyaluronic acid (HA) and decrease the concentration of specific proteins. Since no effective treatments have been found to halt the progression of KOA, injection of HA-based viscoelastic gels combined with physiotherapy (PT) is an alternative to symptomatic therapies. In order to evaluate the effect of viscosupplementation and PT on the SF characteristics, the SF aspirated from the KOA was spectrophotometrically and rheological analyzed, comparing the receiving groups of HA Kombihylan® and groups that received Kombihylan® and complex PT. In patients treated with PT, SF extracted 6 weeks after viscosupplementation had a superior elastic moduli (G') and viscous moduli (G") profile behavior, having a homogeneous distribution of proteins and polysaccharides in the SF, stimulating stronger interactions. In the absence of PT the G' and G" profiles are non-uniform, suggesting an unorganized supplemented SF with some clustering phenomena, proteins aggregation and a low level of entanglement between HA and macromolecular components in the SF.

Background: In the present study, cisplatin, artemisinin and oleanolic acid were evaluated alone and in combination, on human ovarian A2780, A2780ZD0473R and A2780cisR cancer cell lines with aim of overcoming cisplatin resistance and side effects. Methods: Cytotoxicity was assessed by MTT reduction assay. CI values were used as a measure of combined drug effect. MALDI TOF/TOF MS/MS and 2-DE gel electrophoresis were used to identify protein biomarkers in ovarian cancer and to evaluate combination effects. Results: Synergism from combinations was dependent on concentration and sequence of administration. Generally, bolus was most synergistic. 49 proteins differently expressed by 2 ≥ fold were: CYPA, EIF5A1, Op18, p18, LDHB, P4HB, HSP7C, GRP94, ERp57, mortalin, IMMT, CLIC1, NM23, PSA3,1433Z, and HSP90B were down-regulated, whereas hnRNPA1, hnRNPA2/B1, EF2, GOT1, EF1A1, VIME, BIP, ATP5H, APG2, VINC, KPYM, RAN, PSA7, TPI, PGK1, ACTG and VDAC1 were up-regulated, while TCPA, TCPH, TCPB, PRDX6, EF1G, ATPA, ENOA, PRDX1, MCM7, GBLP, PSAT, Hop, EFTU, PGAM1, SERA and CAH2 were not-expressed in A2780cisR cells. The proteins were found to play critical roles in cell cycle regulation, metabolism and biosynthetic processes and drug resistance and detoxification. Conclusion: Results indicate that appropriately sequenced combinations of cisplatin with ART and OA may provide a means to reduce side effects and circumvent platinum resistance.

Titanium micro-scale topography results in excellent osteoconductivity and bone-implant integration. However, the biological effects of sub-micron topography are unknown. We compared osteoblastic phenotypes and in vivo bone and implant integration abilities between titanium surfaces with micro- (1–5 µm) and sub-micro-scale (0.1–0.5 µm) topographies and machined titanium. Average roughness was 12.5 ± 0.65 nm, 123 ± 6.15 nm, and 24 ± 1.2 nm for machined, micro-rough, and sub-micro-rough surfaces, respectively. The micro-rough surface showed the fewest cells attaching during the initial stage and the lowest proliferation. Calcium deposition and expression of osteoblastic genes were highest on the sub-micro-rough surface and lowest on the machined surface. Bone-to-implant integration was strongest for the micro-rough surface, consistent with it having the greatest ability to retain cells in vitro. Thus, the biological effects of titanium surfaces are not necessarily proportional to the degree of roughness in osteoblastic cultures or in vivo. Sub-micro-rough titanium ameliorates the disadvantage of micro-rough titanium by restoring cell attachment and proliferation and enhances the rate of osteoblastic differentiation over that of micro-rough titanium; however, bone integration and the ability to retain cells are compromised due to its lower interfacial mechanical locking compared to that of micro-rough titanium.

Aquaculture is an important source of food for the growing global population. To meet the increasing demand for fish, intensive aquaculture methods are commonly used. However, these methods can lead to stress and disease in fish, which can result in significant economic losses. Gamma-aminobutyric acid (GABA) is a non-protein amino acid that is found in the brain and central nervous system of animals as inhibitory neurotransmitter. It has been shown to have a variety of physiological functions, including stress reduction and immune enhancement. This study investigated the effects of dietary supplementation of GABA on growth, serum biochemistry, innate immunity and disease resistance in juvenile olive flounder (Paralichthys olivaceus) challenged with Edwardsiella tarda under high stocking density. A control diet and three experimental diets were prepared, with 150 mg/kg (GABA150), 200 mg/kg (GABA200), and 250 mg/kg (GABA250) of GABA added to each diet, respectively. The actual GABA content of the experimental diets was analyzed and found to be 63.9 mg/kg (CON), 231.3 mg/kg (GABA150), 291.6 mg/kg (GABA200), and 323.9 mg/kg (GABA250). Each experimental diet was fed to olive flounder with an initial weight of 12.75 g ± 0.3 g in 40 L tanks at two stocking densities: normal density (20 fish/tank) and high density (40 fish/tank). The experiment was conducted in triplicate for each diet and stocking density. The water temperature was maintained at 17.5 ± 1℃ and the salinity at 33 ± 1 ppt. After 8 weeks of feeding trial, growth, feed utilization, whole-body proximate composition, blood analysis, non-specific immune response, and challenge test were performed. There were no significant difference in weight gain and specific growth rate among the GABA concentrations and density × GABA concentration interaction groups. However, the low-density groups showed significantly higher values than the high-density groups (P &lt; 0.05). There was no significant difference in feed efficiency and protein efficiency ratio among all groups. Moreover, there was no significant difference in the whole-body general composition analysis (P &gt; 0.05). In the hematological analysis, there was no significant difference in cortisol in terms of diet and density × GABA concentration interaction, but the high-density experimental group showed a significantly higher value. Blood GABA significantly increased in proportion to the addition amount regardless of the density group (P&lt;0.05). Superoxide dismutase activity in the non-specific immune response showed that the GABA-added experimental group had a significantly higher value than the control group, but there was no significant effect of the density densities or density × GABA concentration interaction (P&lt;0.05). Myeloperoxidase activities in fish fed the GABA200 and GABA250 diets showed significantly higher values, and a density × GABA concentration interaction effect was observed (P&lt;0.05). Lysozyme activity was significantly higher in the GABA150 group than in the CON, GABA200, and GABA250 groups (P &lt; 0.05). After 15 days of challenge test by intraperitoneal injection of Edwardsiella tarda, the cumulative survival rates of the GABA150, GABA200, and GABA250 groups were significantly higher than that of the CON group (P &lt; 0.05). The results suggested that the optimal dietary GABA level for juvenile olive flounder culture is 150 mg/kg, regardless of rearing density, to enhance growth, immune function and disease resistance.

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.

The efficient extraction of phthalate acid esters (PAEs) is challenging due to their extremely low concentration, complicated matrices and hydrophilicity. Herein, hol-low microspheres, as an ideal coating, possesses significant potential for solid-phase microextraction (SPME) due to their fascinating properties. In this study, multi-walled carbon nanotubes hollow microspheres (MWCNTs-HMs) were utilized as a fiber coating for the SPME of PAEs from tea beverages. MWCNTs-HMs were ob-tained by dissolving the polystyrene (PS) cores with organic solvents. Interestingly, MWCNTs-HMs well maintain the morphology of the precursors MWCNTs@PS. The layer-by-layer (LBL) assembly of MWCNTs on PS microsphere templates was ac-quired through electrostatic interactions. Six PAEs, di-ethyl phthalate (DEP), di-iso-butyl phthalate (DIBP), di-n-butyl phthalate (DBP), benzyl butyl phthalate (BBP), di-2-ethylhexyl phthalate (DEHP) and di-n-octyl phthalate (DOP), were se-lected as target analytes for assessing the efficiency of the coating for SPME. The stirring rate, sample solution pH and extraction time were optimized by using the Box-Behnken design. Under optimal working conditions, the proposed MWCNTs-HMs/SPME was coupled with gas chromatography-tandem mass spec-trometry (GC-MS/MS) to achieve high enrichment factors (118–2137), wide linearity (0.0004-10 μg L-1), low limits of detection (0.00011-0.0026 μg L-1) and acceptable recovery (80.2%-108.5%) for the detection of PAEs. Therefore, the MWCNTs-HMs coated fibers are promising alternatives in the SPME method for the sensitive detec-tion of PAEs at trace levels in tea beverages.

The emergence of the COVID-19 pandemics prompted a fast development of novel diagnostic methods of the etiologic virus SARS-CoV-2. Methods based on CRISPR-Cas systems have been particularly promising because they can achieve a similar sensitivity and specificity to the golden standard RT-qPCR, especially when coupled to an isothermal pre-amplification step. Furthermore, they have also solved inherent limitations of RT-qPCR that impede its decentralized use and deployment in the field, such as the need for expensive equipment, high cost per reaction, and delivery of results in hours, among others. In this review, we evaluate publicly available methods to detect SARS-CoV-2 that are based on CRISPR-Cas and isothermal amplification. We critically analyze the steps required to obtain a successful result from clinical samples and pinpoint key experimental conditions and parameters that could be optimized or modified to improve clinical and analytical outputs. The COVID outbreak has propelled intensive research in a short time, which is paving the way to develop effective and very promising CRISPR-Cas systems for the precise detection of SARS-CoV-2. This review could also serve as an introductory guide to new labs delving into this technology.

In this study, ozone oxidation experiment was carried out for the removal of fluorescent whitening agent which is widely used in textile dyeing and paper industry. The stilbene fluorescent whitening agent has been industrialized since the earliest, and the amount of current production is the highest. Due to the characteristics of the fluorescent whitening agent that cannot be removed by conventional wastewater treatment methods, the fluorescent whitening agent in wastewater treatment has difficulty in using as recycled water in the process. Pre-treatment ozone oxidation experiment was conducted prior to the introduction of Membrane Bio Reactor (MBR) treatment process by converting biodegradable materials into biodegradable materials. The removal efficiencies of fluorescent whitening agents, a diaminostilbene disulfonic acid derivative by ozone oxidation were evaluated by UV254 Scan, COD, T-N and color using a synthetic wastewater sample (COD=433.0 mg/ℓ) and paper and paper mill wastewater (COD=157.2 mg/ℓ).

Modification the biodegradable matrix was carried by graft-copolymerization polylactide with methacrylic acid of various concentrations. Ultraviolet irradiation with different exposure times to the samples was chosen as the initiator of copolymerization. In the experiment the effect of ultraviolet light on polylactide and graft copolymerization was investigated: the resulting samples were studied by viscosimetry, gravimetry, FTIR, static cation- exchange capacity analysis . The conditions for obtaining grafted copolymers and the dependence of the characteristics on the reaction conditions are established.

Activated platelets are involved in blood coagulation by exposing phosphatidylserine (PS), which serves as a substrate for assembling coagulation complexes. Platelets accelerate fibrin formation and thrombin generation, two final reactions of the coagulation cascade. We investigated the effects of antiplatelet drugs on platelet impact in these reactions and platelet ability to expose PS. Washed human platelets were incubated with acetylsalicylic acid (ASA), ticagrelor, ASA in combination with ticagrelor, ruciromab (glycoprotein IIb-IIIa antagonist) or prostaglandin E1 (PGE1). Platelets were not activated or activated by collagen, sedimented in multiwell plates and plasma was added after supernatant removal. Fibrin formation (clotting) was monitored in a recalcification assay by light absorbance and thrombin generation in a fluorogenic test. PS exposure was assessed by annexin V staining using flow cytometry. Ticagrelor (alone and in combination with ASA), ruciromab and PGE1, but not ASA prolonged the lag phase and decreased the maximum rate of plasma clotting, and decreased the peak and maximum rate of thrombin generation. Inhibition was observed when platelets were not treated with exogenous agonists (activation by endogenous thrombin) and pretreated with collagen. Ticagrelor (alone and in combination with ASA), ruciromab and PGE1, but not ASA decreased PS exposure on washed platelets activated by thrombin and by thrombin + collagen. PS exposure on activated platelets in whole blood was lower in patients with acute coronary syndrome receiving ticagrelor + ASA in comparison with donors free of medications. These results indicate that antiplatelet drugs are able to suppress platelet coagulation activity not only in vitro but also after administration to patients.

Microplastics and radionuclides pose significant challenges to the sustainable management of water systems. The interaction of uranium-232 and americium-241 with polyurethane (PU) and polylactic acid (PLA) microplastics has been investigated in aqueous laboratory and environ-mental solutions (e.g., seawater and wastewater) as a function of temperature in various pH (4, 7, 9). The temperature increase affects positively the binding of uranium-232 and americium-241. The highest adsorption efficiency for uranium and americium is observed at the neutral and al-kaline pH region, respectively. In environmental water samples (pH ~8) the adsorption efficiency decreases significantly due to the competitive adsorption of other metals present in natural wa-ters (e.g., Ca2+) as well as the stabilization of the actinides (particularly uranium) in solution (e.g., UO2(CO3)34-). The solution composition which governs both the actinide speciation, and the type of surface-active sites is strongly associated with the surface adsorption thermodynamics and de-termines the values of the associated parameters (ΔΗo and ΔSo). Generally, the values of ΔΗo and ΔSo are positive indicating an entropy-driven reaction. However, in the case of the U(VI) adsorp-tion by PLA in seawater samples both ΔΗo and ΔSo values become negative suggesting an enthal-py-driven binding mechanism associated with a decline in randomness at the surface upon ad-sorption.

In the present study, the problem of the sulfuric acid recycling from spent copper plating solution was solved using a hybrid membrane technology, including diffusion dialysis and electrodialysis. A real solution from the production of copper-coated steel wire, containing 1.45 mol/L of sulfuric acid, 0.67 mol/L of ferrous sulfate and 0.176 mol/L of copper sulfate was processed. Diffusion dialysis with anion-exchange membranes was used to separate sulfuric acid and salts of heavy metals. Then purified dilute sulfuric acid was concentrated by electrodialysis. Energy consumption for sulfuric acid electrodialysis concentration at a current density of 400 A/m2 was 162 W·h/mol with current efficiency 16 %. After processing according to the hybrid membrane scheme, the solution contained 1.13 mol/L sulfuric acid, 0.077 mol/L ferrous sulfate and 0.022 mol/L copper sulfate. The resulting acid solution with a small amount of ferrous sulfate and copper sulfate met the established requirements for a copper plating bath solution and can be reused in production.

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

Chitosan treatment results in significantly lower serum LDL cholesterol concentrations. To assess the working mechanism of chitosan, we measured serum surrogate markers of cholesterol absorption (campesterol, sitosterol, cholestanol), synthesis (lathosterol, lanosterol, desmosterol), and degradation to bile acids (7α-hydroxy-cholesterol, 27-hydroxy-cholesterol) corrected for cholesterol concentration (R_sterols). Over 12 weeks, 116 obese subjects (BMI 31.7, range 28.1 – 38.9 kg/m²) were studied under chitosan (n=61) and placebo treatment (n=55). The participants were briefly educated regarding improvement of nutrition quality and energy expenditure. Daily chitosan intake was 3200 mg. Serum LDL cholesterol concentration decreased significantly more (P=0.0252) under chitosan (-8.67 ± 18.18 mg/dl, 5.6%) than under placebo treatment (-1.00 ± 24.22 mg/dl, 0.9%). This reduction was not associated with the expected greater decreases in markers of cholesterol absorption under chitosan treatment. Also, increase in markers of cholesterol synthesis and bile acid synthesis under chitosan treatment was not any greater than under placebo treatment. In conclusion, a significant selective reduction of serum LDL cholesterol under chitosan treatment is neither associated with a reduction of serum surrogate markers of cholesterol absorption nor with an increases of markers for cholesterol and bile acid synthesis.

The increased consumption of high fat-containing foods has been linked to the prevalence of obesity and abnormal metabolic syndromes. Rhizopus oligosporus, a fungus in the family Mucoraceae, is widely used as a starter for homemade tempeh. Although R. oligosporus can prevent the growth of other microorganisms, it grows well with lactic acid bacteria (LAB). Lactobacillus plantarum can produce β-glucosidase, which catalyzes the hydrolysis of glucoside isoflavones into aglycones (with greater bioavailability). Therefore, the development of a soybean-based functional food by the co-inoculation of R. oligosporus and L. plantarum is a promising approach to increase the bioactivity of tempeh. In this study, the ameliorative effect of L. plantarum in soy tempeh on abnormal carbohydrate metabolism in high-fat diet (HFD)-induced hyperglycemic rats was evaluated. The co-incubation of L. plantarum with R. oligosporus during soy tempeh fermentation reduced the homeostatic model assessment of insulin resistance, HbA1c, serum glucose, total cholesterol, triglyceride, free fatty acid, insulin, and low-density lipoprotein contents and significantly increased the high-density lipoprotein content in HFD rats. It also increased the LAB counts as well as the bile acid, cholesterol, triglyceride, and short-chain fatty acid contents in the feces of HFD rats. Our results suggested that the modulation of serum glucose and lipid levels by LAB occurs via alterations in the internal microbiota, leading to the inhibition of cholesterol synthesis and promotion of lipolysis. Tempeh, produced with both L. plantarum and R. oligosporus, may be a beneficial dietary supplement for individuals with abnormal carbohydrate metabolism.

In our previous papers, we demonstrated that inflammation and aging are the common roots of cancer and Alzheimer’s disease (AD). In both diseases, there is an inhibition of the mitochondria. In cancer, the alkaline intracellular pH (pHi) is associated with cell proliferation; acidic pHi causes apoptosis in AD. This difference is because cancer feeds on chemically neutral glucose, while neurons feed on acidic lactic acid. Increased uptake of lactic acid is responsible for acidic pH and cell death. Similarly, to AD, inflammation is responsible for metabolic shifts in age-related macular degeneration (AMD). In AD, there is hyperosmolarity responsible for increased lactic secretion by glial cells. Increased lactic secretion will cause neo-angiogenesis and neural cell death. Drugs increasing hyperosmolarity (Polyethylene Glycol) cause neo-angiogenesis and drusen-like structures in rodents. The link between AMD and inflammation is reinforced by the fact that treatments aiming at restoring mitochondrial activity, such as lipoic acid and/or methylene blue, have been experimentally shown to be effective in each set of diseases. The role of osmolarity has been demonstrated in the pathologies of the anterior segment of the eye, such as dry eye, corneal ulceration, cataracts, and glaucoma. The role of increased osmolarity in age-related macular degeneration (AMD) has been largely overlooked. We herein suggest that metabolic shift, inflammation, and hyperosmolarity are key players in the pathogenesis of AMD.

: Digital communication is becoming an integral component of contemporary society and the use of mobile devices is increasing faster than ever. The function of message communication is becoming more popular as for mobile phone users, a short messaging service (SMS) requires an extremely high level of security. Any SMS that enters a person's smartphone must be considered a private affair, with privacy and security safeguarded. This research study found a novel Deoxyribonucleic acid (DNA) Cryptography method that uses a dynamic DNA sequence table to increase security. Cryptography is a popular approach for ensuring the confidentiality of a message. This paper proposed an Efficient Cryptographic Scheme for SMS (ECSS) algorithm to protect texts received from an Android smartphone. ECSS-based encryption has been identified as a novel method of securing information in the form of DNA molecules that employ DNA strands to conceal the information. This Paper provides the DNA cryptography approach for encrypting and decrypting plain texts in this work. The primary goal of ECSS cryptography is to guarantee secrecy when people transfer data across a network. This paper examines DNA Crypto, the distinction between classical cryptography and DNA Data encryption. An Android-based app is created to perform the proposed technique and the results show that the algorithms produce a consistent encryption result in which the length of the message before encryption is always the same as the length of the message after decryption. The suggested security solution has the potential to greatly improve the security of mobile communication. This Paper also provides experimental results for our chat application performance, such as received text message correctness, cipher text, average encryption time and average decryption time. According to the findings/results of this study, the speed of average encryption and decryption of the description is roughly 0.011 and 0.037 sec and prevents plaintext and dictionary attacks.

Investigations are currently in progress to assess the potential of elevated FABP3 levels as biomarkers for assessing cardiac and cerebral injury post-stroke. Ongoing research endeavors are concentrated on elucidating the specific mechanisms by which FABPs, particularly FABP3, contribute to the complex processes involved in ischemic stroke. This study employs molecular docking techniques within a Virtual Screening framework to examine the interaction between various natural substances and the active site of human heart fatty acid-binding protein (PDB Code 4TKH). Utilizing Pyrx and Autodock Vina, the research aims to pinpoint compounds demonstrating robust binding interactions, characterized by high binding energy scores (kcal/mol) and the formation of multiple chemical bonds. The anticipated outcomes have the potential to yield valuable insights into the molecular interactions influencing human heart fatty acid-binding protein, suggesting possible implications for therapeutic interventions using these natural substances.From the docking and predicted toxicity results, Resistomycin has demonstrated superior characteristics compared to Morusin.

Melittin, a natural antimicrobial peptide, displays a broad-spectrum antimicrobial activity, which has caused increasing attention as a potential antibiotic alternative. However, melittin has not been used widely at present due to its high hemolysis and low proteolytic stability. In this study, N-terminal fatty acid was conjugated to melittin to develop new melittin-derived lipopep-tides (MDLs) for improving the limitation of melittin. Our results showed that, the antimicrobial activity of MDLs was increased by 2 to 16 times compared with native melittin, and the stability of these MDLs against trypsin and pepsin degradation was increased by 50 to 80%. Besides, the hemolytic of the MDLs decreased when the length of the carbon chain of fatty acids exceeded 10. Among them, the newly designed analog Mel-C8 showed optimal antimicrobial activity and protease stability. The antimicrobial mechanism studied revealed that the MDLs showed a rapid bactericidal effect by interacting with LPS or LTA and penetrating the bacterial cell membrane. In conclusion, we designed and synthesized a new class of MDLs with potent antimicrobial activity, high proteolytic stability, and low hemolysis through N-terminal fatty acid conjugation.

Cut flowers of Gerbera jamesonii, renowned globally for their vibrant colors and extended shelf life, play a pivotal role in the flourishing floriculture industry. However, repeated fertigation in nethouses/polyhouses poses a significant challenge leading to production losses. In response to this challenge, we hypothesized that the application of Ascorbic acid (AsA), an antioxidant, in optimal concentrations could alleviate the detrimental effects of salt toxicity and enhance Gerbera production. Our objective was to investigate the impact of exogenous AsA (1.0 mM, 2.0 mM, and 4.0 mM) as a foliar spray, followed by NaCl (200 mM) treatment, across two cultivars of Gerbera: white-flowered (salt sensitive) and yellow flowered (salt tolerant) cultivars. The research employed a comprehensive approach, applying AsA and NaCl treatment to evaluate their effects on chlorophyll, proline, and total soluble protein content, MDA, H2O2, and antioxidant enzyme activities (SOD, CAT, APX, GR, and POD). Following exposure to 2.0 mM AsA, treated plants displayed a notable increase in chlorophyll, Proline, and soluble protein content. Concurrently, MDA and H2O2 levels, indicator of intracellular damage, exhibited a decrement, suggesting AsA's protective role against salt stress. Moreover, enhanced antioxidant Enzyme activities were observed. The application of AsA (2.0 mM) not only induced salt tolerance in Gerbera but also showed potential benefits for its overall growth and development. This study underscores the promising role of AsA in mitigating salt-induced challenges in Gerbera cultivation.

Recent developments in artificial nucleic acid and drug delivery systems (DDS) present possibilities for the symbiotic engineering of oligonucleotide therapeutics, such as antisense oligonucleotides (ASOs), and small interfering RNA (siRNA). These technologies can also be applied for triplex-forming oligonucleotides (TFOs) to develop symbiotic genome-targeting tools and a new class of oligonucleotide drugs. Many reports have described the functionalization of TFOs and the enhancement of TFO activities. In particular, the tethering of crosslinking groups to TFOs enables irreversible triplex formation and is frequently exploited for antigene and genome-editing experiments. These crosslinkable TFOs have shown considerable potential for therapeutic application. In this review, we revisit these crosslinking techniques and explore the combination of these techniques with recent artificial oligonucleotide and DDS technologies.

Modification of Scots pine sapwood (Pinus sylvestris L.) with heterocyclic compounds, imidazole and succinimide, was investigated. Pressure-impregnation with aqueous solutions containing imidazole, imidazole + citric acid, succinimide, succinimide + citric acid, and citric acid + sorbitol (CIOL®) at 5%, 10%, and 15% solid content was followed by oven-curing at 220 °C for 1 hour. Mass changes during treatment steps, bending properties, and anti-swelling efficiency (ASE) were examined. Results indicate that solid concentrations within the range of 5% to 10% were optimal. Results seem to show there are two differing mechanisms in the modification of imidazole and succinimide, respectively. Mass loss due to the heat treatment was highest in imidazole-treated specimens, whereas it remained low and concentration-independent in succinimide-treated specimens. ASE after three cycles reached 31% for imidazole-treated specimens and improved to 38% with the addition of citric acid. For succinimide, ASE increased from 17% to 41%. Bending properties generally showed improvement, except for succinimide + citric acid and CIOL®, which displayed a reduced modulus of rupture. Chemical analyses are warranted to fully understand the reaction mechanisms of the treatments. Imidazole treatment's positive effects are suggested to stem from a thermal reaction between the chemical and wood, indicated by substantial mass loss during leaching and specimen darkening. Succinimide and citric acid might exhibit polymerization with each other and wood components, akin to the CIOL® process. Further research should delve into reaction mechanisms and the impact of imidazole and succinimide on biological durability.

This study describes the AMD impacted environments and critically discusses the effects of AMD, current prediction and prevention methods and treatment technologies. The study further, crit-ically analyses the case studies, gaps in AMD research and the challenges and opportunities of-fered by AMD. The study outlined future technological intervention aiming at a paradigm shift towards reducing the volume of sludge generated as well as the operating cost and improving AMD treatment efficiency. The integrated AMD treatment technologies that result in a holistic approach toward sustainable AMD treatment are a current need. As a result, a sustainable AMD treatment strategy has been made possible due to water reuse and rich resource recoveries such sulphuric acid, rare earth elements, and metals. The cost of AMD treatment can be decreased with the use of recovered water and resources, which is essential for developing a sustainable AMD treatment process.

Background: The presence of single nucleotide polymorphisms in the gene encoding key en-zyme in the folate pathway methyltetrahydrofolate reductase (MTHFR), causes methylation disorders associated with CAD development. Methods: Study group: 42 patients with CAD con-firmed by coronary angiography. Controls: 16 patients without CAD symptoms or significant coronary artery stenosis, based on invasive coronary angiography or multislice computed to-mography with coronary artery calcification scoring. Real-time PCR genotyping was assessed using TaqMan™ probes. Folic acid and 5-MTHF concentrations in blood serum were determined by LC-MS. Results: c.[1286A>C];[1286A>C] MTHFR polymorphism occurred significantly more often in (CAD+) patients compared to (CAD-) cohort and to the European population. The con-centration of 5-MTHF and folic acid in the subgroups of patients with methylation disorders di-vided by genotypes and (CAD+) was lower compared to (CAD-). Conclusions: The homozygous c.1286 A>C MTHFR variant can be considered as CAD genetic marker. In the subjects with the c.1286 A>C heterozygous and homozygous genotypes, lower concentrations of methyltetrahy-drofolate (5-MTHF) were observed. 5-MTHF can be considered as a biomarker of CAD. Identifi-cation of people at high risk of CAD using genetic tests can contribute to personalized therapy using active (methylated) form of folic acid (5-MTHF) in CAD patients with MTHFR polymor-phisms.

Single-Molecule Magnets (SMMs) have attracted much interest because of their spin properties and potential technological applications. Besides, a great effort has been devoted to their functionalization, which is made with functional groups convenient to connect suitable SMMs to junction devices or to perform their grafting on surfaces of different substrates. We have synthesized and characterized two lipoic acid-functionalized and oxime-based MnIII compounds, of formula [Mn6(μ3-O)2(H2N-sao)6(lip)2(MeOH)6][Mn6(μ3-O)2(H2N-sao)6(cnph)2(MeOH)6]}·10MeOH (1) and [Mn6(μ3-O)2(H2N-sao)6(lip)2(EtOH)6]·EtOH·2H2O (2) [H2N-saoH2 = salicylamidoxime, lip = lipoate anion, cnph = 2-cyanophenolate anion]. 1 crystallizes in the triclinic system with space group Pī and 2 crystallizes in the monoclinic system with space group C2/c. In their crystal packing, adjacent Mn6 complexes are connected through non-coordinating solvent molecules, which are H-bonded to N atoms of –NH2 groups of salicylamidoxime ligand. In addition, Hirshfeld surfaces of 1 and 2 were calculated to study the variety of intermolecular interactions and different level of importance that take place in their crystal lattice, this type of computed study being the first time performed on Mn6 molecules. The study of the magnetic properties of 1 and 2 through dc magnetic susceptibility measurements reveals the coexistence of ferro- and antiferromagnetic exchange couplings between the Mn(III) metal ions in both compounds, the latter being the predominant magnetic interaction. A ground state spin value of S = 4 was obtained through isotropic simulations of the experimental magnetic susceptibility data for both 1 and 2. Ac magnetic susceptibility measurements show the occurrence of slow relaxation of the magnetization in 1 and 2, which indicate that SMM behavior take place in both compounds.

A non-steady state mathematical model of amino acid (phenylalanine (Phe)) and mineral salt (NaCl) solution separation by neutralization dialysis (ND) carried out in a batch mode is proposed. The model takes into account the characteristics of membranes (thickness, ion-exchange capacity and conductivity) and solutions (concentration, composition), as well as the flow rate of the solution in the dialyzer compartments. As compared to previously developed models, the new one considers the local equilibrium of Phe protolysis reactions in solutions and membranes and, also, the transport of all the phenylalanine forms (zwitterionic, positively and negatively charged) through membranes. A series of experiments on ND demineralization of NaCl and Phe mixed solution was carried out. In order to minimize Phe losses, the solution pH in the desalination compartment was controlled by changing the concentrations of the solutions in the acid and alkali compartments of the ND cell. The validity of the model was verified by comparison of simulated and experimental time dependencies of solution electric conductivity and pH, as well as the concentration of Na+, Cl– ions and Phe species in the desalination compartment. Based on the simulation results, the role of Phe transport mechanisms in the losses of this amino acid during ND was discussed.

Molecular therapies exploiting mRNA vectors embody enormous potential, as evidenced by the utility of this technology for the context of the COVID-19 pandemic. None-the-less, broad implementation of these promising strategies has been restricted by the limited repertoires of delivery vehicles capable of mRNA transport. On this basis, we explored a strategy based on exploiting the well characterized entry biology of adenovirus. To this end, we studied an adenovirus-polylysine (AdpL) that embodied “piggyback” transport of the mRNA on the capsid exterior of adenovirus. We hypothesized that the efficient steps of Ad binding, receptor-mediated entry, and capsid-mediated endosome escape could provide an effective pathway for transport of mRNA to the cellular cytosol for transgene expression. Our studies confirmed that AdpL could mediate effective gene transfer of mRNA vectors in vitro and in vivo. Facets of this method may offer key utilities to feasibilize the promise of mRNA-based therapeutics.

Salinity is a serious environmental hazard which limits world agricultural production by adversely affects plant physiology and biochemistry. Hence increase tolerance against salt stress is very important. In this study, we explored the function of β-aminobutyric acid (BABA) in enhancing salt stress tolerance in rapeseed (Brassica napus L.). After pretreatment with BABA, seedlings were exposed to NaCl (100 mM and 150 mM) for 2 days. Salt stress increased Na content and decreased K content in shoot and root. It disrupted the antioxidant defense system by producing reactive oxygen species (ROS; H2O2 and O2•−), methylglyoxal (MG) content and causing oxidative stress. It also reduced the growth and photosynthetic pigments of seedlings but increased proline (Pro) content. However, BABA pretreatment in salt-stressed seedlings increased ascorbate (AsA) and glutathione (GSH) contents; GSH/GSSG ratio; and the activities of ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), glutathione reductase (GR), glutathione peroxidase (GPX), superoxide dismutase (SOD), catalase (CAT), glyoxalase I (Gly I), and glyoxalase II (Gly II) as well as growth and photosynthetic pigments of plants. In addition, compared to salt stress alone BABA increased Pro content, reduced the H2O2, MDA and MG contents and decreased Na content in root and increased K content in shoot and root of rapeseed seedlings.

A method for sequencing a protein from a codon sequence is proposed. An unfolded protein molecule is threaded through a nano-sized pore in an electrolytic cell carboxyl end first and held with a voltage such that only the first residue is exposed in the trans chamber of the cell. A tRNA molecule in trans with matching anticodon for the residue binds itself to the latter in the presence of suitable catalysts. It is then cleaved and transferred to an extended electrolytic cell with N pores, 40 ≤ N ≤ 61, in N individual cis chambers and a single trans chamber. Each pore holds an RNA molecule ending in a unique codon that is held exposed in the trans chamber. In the presence of suitable catalysts the anticodon in the transferred tRNA binds with the codon of a matching RNA molecule. By reversing the voltages in the extended cell every RNA molecule except the one to which the transferred tRNA is bound retracts into its cis chamber, this identifies the residue unambiguously. The detected residue in the first cell is cleaved and the process repeated. Unlike in other nanopore-based methods, it suffices to detect the occurrence of a current blockade without having to measure the pore current precisely. A simplified but more time-consuming version that uses only the first cell is also described. In either case no a priori information about the protein is needed so de novo sequencing is possible. A feasibility analysis of the proposed scheme is presented.

For the diagnosis of disease, the ability to quantitatively detect trace amounts of the causal proteins from bacteria/viruses as biomarkers in patient specimens is highly desirable. Here we introduce a simple, rapid, and colorimetric assay as a de novo, ultrasensitive detection method. This ultrasensitive assay consists of sandwich enzyme-linked immunosorbent assay (ELISA) and thionicotinamide-adenine dinucleotide (thio-NAD) cycling, forming an ultrasensitive ELISA, in which the signal substrate (i.e., thio-NADH) accumulates in a triangular manner, and the accumulated thio-NADH is measured at its maximum absorption wavelength of 400 nm. We have successfully achieved a limit of detection of ca. 10–18 moles/assay for a target protein. As an example of infectious disease detection, HIV-1 p24 could be measured at 0.0065 IU/assay (i.e., 10⁻¹⁸ moles/assay), and as a marker for a lifestyle-related disease, adiponectin could be detected at 2.3 × 10⁻¹⁹ moles/assay. In particular, despite the long-held belief that the trace amounts of adiponectin in urine can only be detected using a radioisotope, our ultrasensitive ELISA was able to detect urinary adiponectin. This method is highly versatile, because simply changing the antibody enables the detection of various proteins. This assay system requires only the measurement of absorbance, thus it requires equipment that is easily obtained by medical facilities, which facilitates diagnosis in hospitals and clinics. Moreover, we describe an expansion of our ultrasensitive ELISA to a non-amplification nucleic acid detection method for nucleic acids using hybridization. These de novo methods will enable simple, rapid, and accurate diagnosis.

Lichen secondary metabolites are generally considered as repellent compounds for lichen feeders. Nevertheless, if the only food available consists in lichens rich in secondary metabolites, lichenophages such as Notodiscus hookeri, a gastropod native from the Possession Island, seem able to implement strategies to overcome the toxicity of these metabolites. Thus, the balance between phagostimulant nutrients and deterrent metabolites appears to play a key role in their feeding preferences. To further understand lichen-gastropod interactions, we studied the feeding behavior of Notodiscus hookeri fed exclusively with Usnea taylori, a lichen rich in usnic acid and arabitol. Snail feeding choice experiments with intact lichens vs acetone-rinsed lichens were carried out to study the influence of secondary metabolites. Simultaneously, usnic acid and arabitol were quantified and localized within the lichen thallus using HPLC-DAD-MS and in situ imaging by mass spectrometry to assess whether their spatial distribution induce preferential snail grazing. Then, no-choice feeding experiments were devised using usnic acid and arabitol embedded in artificial diet, separately or together. This case study demonstrated that the nutritional activity of N. hookerii was governed by the chemical quality of the food and primarily by nutrient availability (arabitol), despite the presence of deterrent metabolites (usnic acid).

The prevalence and incidence of obesity and the comorbidities linked to it are increasing in the world population. Current therapies for obesity and associated pathologies have proven to cause a broad number of adverse effects and often, they are overpriced or not affordable for all patients. Among the alternatives currently available, natural bioactive compounds stand out. These are frequently contained in pharmaceutical presentations, nutraceutical products, supplements, or functional foods. The clinical evidence for these molecules is increasingly solid, among which epigallocatechin-3-gallate, ellagic acid, resveratrol, berberine, anthocyanins, probiotics, carotenoids, curcumin, silymarin, hydroxy citric acid, and α-lipoic acid stand out. The molecular mechanisms and signaling pathways of these molecules have been shown to interact with the endocrine, nervous, and gastroenteric systems, as well as regulate the expression of multiple genes and, therefore, proteins involved in starvation-satiety processes, activation of brown adipose tissue, increased lipolysis, decreased lipogenesis, and inflammation, beneficial changes in metabolism and improved insulin sensitivity. This review provides a comprehensive view of nature-based therapeutic options to address the increasing prevalence of obesity. It offers a valuable perspective for future research and subsequent clinical practice, addressing everything from the molecular, genetic, and physiological bases to the clinical study of the bioactive compound.

Foliage-feeding fall armyworm (Spodoptera frugiperda) and root-feeding western corn rootworm (Diabrotica virgifera virgifera) are maize (Zea mays L.) pests that cause significant yield losses. Jasmonic acid (JA) play pivotal defense role against insects. 12-oxo-phytodienoic acid (12-OPDA) is converted into JA by peroxisome-localized OPDA reductases (OPR). However, little is known about the physiological functions of cytoplasmic OPRs. Here, we show that disruption of ZmOPR2 reduced wound-induced JA production and defense against FAW while accumulating more JA catabolites. Overexpression of ZmOPR2 in Arabidopsis enhanced JA production and defense against beet armyworm (Spodoptera exigua). In addition, lox10opr2 double mutants were more susceptible than either single mutant, suggesting that ZmOPR2 and ZmLOX10 uniquely and additively contributed to defense. In contrast to the defensive role of ZmOPR2 and ZmLOX10 in leaves, single mutants did not display any alteration in root herbivory defense against WCR. Feeding on lox10opr2 double mutants resulted in increased WCR mortality associated with greater herbivory-induced production of insecticidal death acids and ketols. Thus, ZmOPR2 and ZmLOX10 cooperatively inhibit synthesis of these metabolites during herbivory by WCR. We conclude that ZmOPR2 and ZmLOX10 regulate JA-mediated resistance in leaves against FAW while suppressing insecticidal oxylipin synthesis in roots during WCR infestation.

Punica granatum L., commonly known as pomegranate, is a typical fruit of Asia, Mediterranean countries, Middle East and USA areas. While in the ancient time pomegranate was considered an ornamental plant, nowadays numerous scientific studies have highlighted its antioxidant and anti-radical activities, up to consider pomegranate as a “superfood”. Pomegranate presents a high content of natural bioactive compounds (NBCs) and its consumption appears to exert numerous healthy beneficial effects, in particular, in several pathological conditions, namely in patients affected by metabolic syndrome, cancer, nephrolithiasis, urinary tract infections and neurodegenerative diseases. Moreover, recent studies pointed out the possible beneficial action of pomegranate on oral health. For these reasons, the utility of pomegranate in internal medicine and in dentistry represents a promising field, as it could permit the development of innovative natural adjuvant therapies, able to empower the standard pharmaceutical therapies.

In this study, the corrosion performances of ammonium copper quat (ACQ) and boric acid (BA) wood preservatives were investigated, with micronized copper quat (MCQ) and nano boron (NB) used as reference materials. In the study, Scots pine (Pinus sylvestris L.) wood samples were impregnated according to the full-cell process method with ACQ at 2.4% concentration, BA at 4% and MCQ and NB at 1%. The ACQ- and BA-impregnated samples were then impregnated for a second time using five different water-repellent materials: tall oil, linseed oil, sodium silicate, methyl hydrogen silicone and N'-N- (1, 8-Naphthalyl) hydroxylamine. Polyethylene glycol (PEG) 600 and aluminum sulfate were introduced as single impregnations in the form of homogeneous mixtures with the ACQ and BA. The corrosion properties of the impregnated and control samples, including metal weight loss (MWL) and corrosion depth, were examined. As a result, the MWL values of the ACQ-impregnated samples showed an increase compared to the control group. The MWL values of the MCQ-impregnated samples were lower than those of the samples impregnated with ACQ, whilst the MWL values of the BA-impregnated samples were higher than those of the samples impregnated with NB.

: Cardiac surgery (CS) with extracorporeal circulation (ECC), induces oxidative stress and systemic inflammatory response, which may seriously affect postoperative lung function. We aimed to test if high parenteral (200mg/kg/24h) perioperative (48h) doses of Vitamin C (VitC) may reduce the incidence and severity of postoperative pulmonary complications (PPC) in selected CS patients. Single centered, prospective, randomized, single-blinded, interventional study included 150 patients, assigned to control group A (n=75) and interventional group B (n=75). Group B intraoperatively received 1/4 of the planned daily Vit C dose (200mg/kg/24h), diluted in 10 ml of normal saline, divided into three parts, while Group A received an equal volume of normal saline at the same time frames. After 6 h from the first intraoperative dose, the following regimen was applied: Group B: 200 mg/kg/24h - 30 min i.v. infusion of VitC in 50 ml of normal saline, every 6h, for the next 48h, and Group A: 30 min i.v. infusion of an equal volume of normal saline every 6 hours, for the next 48h. Modified Kroenke’s score was used to determine the incidence and severity of PPC. The overall incidence of PPC was 36.7% and was significantly lower in Group B (13.3% v.s. 60.0%, p&lt;0.001). The severity of PPC was also significantly lower in Group B [1(1) v.s. 3(2), p&lt;0.001]. Besides, patients from Group B had significantly less damaged lungs and better postoperative renal function, shorter ICU stay, fewer ICU re-admissions, and lower hospital mortality. High parenteral daily VitC doses (200mg/kg/24h) given to selected CS patients for 48h after CS are safe and effective in reducing the incidence and severity of PPC. Further multicenter RCT is needed to confirm these results.

The influence of diet and nutritional status of milk donors on the nutritional composition of donor human milk (DHM) is unknown. The present study aimed to determine the nutritional profile of DHM and the associations of donors’ dietary intake and nutritional status with micronutrient and lipid composition in DHM. For this purpose, 113 donors completed a food frequency questionnaire, provided a 5-day weighed dietary record, and collected milk for 5 consecutive days. Nutrient determinations in donors’ erythrocytes, plasma, urine, and milk were performed. Multiple linear regressions were conducted for the evaluation of the associations. We highlight the following results: DHM docosahexaenoic acid (DHA) was positively associated with donors’ plasma DHA content and donors’ DHA intake (R2 0.45, p < 0.001). For every 1 g/day of DHA intake, the percentage of DHA in DHM increased by 0.38% (% of total fat) and the percentage of total omega-3 in DHM increased by 0.78% (R2 0.29, p < 0.001). DHM saturated fatty acids were positively associated with erythrocyte dimethyl acetals, plasma stearic acid, trans fatty acids intake, and breastfeeding duration, and negatively associated with erythrocyte margaroleic acid (R2 0.34, p < 0.01). DHM cholecalciferol was associated with plasma cholecalciferol levels and dairy intake (R2 0.57, p < 0.01). Other weaker associations were found for free thiamine, free riboflavin, pyridoxal, dehydroascorbic acid, and lipid profile in DHM. In conclusion, the diet and nutritional status of donors influences the fatty acid profile and micronutrient content of DHM.

This study aimed to elucidate the antibacterial efficacy and unique chemical compositions generated from plasma-activated water (PAW) when utilized a novel vaginal cleansing device. We conducted an analysis of antibacterial activity against probiotics and several chemical compositions including ions under various operational parameters of PAW, including electrical power (12 and 24 V), treatment duration (1, 10, and 20 min), and stay duration (immediate, 30 and 60 min). Our findings revealed that as treatment duration increased, hypochlorous acid (HOCl), Ca2+, and Mg2+ concentrations increased and Cl−concentrations decreased. Higher electrical power and longer treatment duration resulted in increased HOCl levels, which acts to prevent the growth of general microorganisms. Notably, PAW exhibited no antibacterial effects against a type of probiotic, Lactobacillus reuteri that produces lactic acid for vaginal health. This result demonstrated the ability of the vaginal cleaning device to generate ions, primarily HOCl and some cations (Ca2+ and Mg2+), thereby providing vaginal mucosa protecting and cleansing effects with the vaginal environment.

Tomato pomace (TP), an agricultural industrial waste product from the tomato processing industry, was valorized by being used as a rearing substrates for Tenebrio molitor (L.). This study evaluated bran-based diets with increasing tomato pomace (0%, 27%, 41% and 100%). Protein sources, as brewer’s spent grain and yeast, are used in TP27 and TP41 diets, respectively, to ensure equal protein content to control diet (TP0). Results showed larval survival, larval and pupal weight no different between diets; however, growth time significantly increases in TP100 compared at all diets. The feed conversion rate progressively increases from 2.7 to 4.3, respectively from TP0 to TP100. Conversely, Lycopene and β-Carotene increases in the larvae. Fatty acid composition improves by increasing polyunsaturated fatty acids (mainly -Linoleic acid). Although the best nutritional quality was obtained in T100, the TP41 is the optimal diet for balance between larval performance and qualitative improvement of larvae. Therefore, tomato pomace is suitable for the formulation of mealworm diets, even in high dosages when supplemented with sustainable protein sources.

The aim of this study was to identify the differentially expressed genes (DEG) from the skeletal muscle and liver samples of animal model for metabolic diseases in human. To perform the study, the fatty acid (FA) profile and RNA sequencing (RNA-Seq) data of 35 samples of liver tissue (SOY1.5, n=17 and SOY3.0, n=18) and 36 samples of skeletal muscle (SOY1.5, n=18 and SOY3.0, n=18) of Large White pigs were analyzed. The FA profile of the tissues was modified by the diet, mainly those related to monounsaturated (MUFA) and polyunsaturated (PUFA) FA. The skeletal muscle transcriptome analysis revealed 45 DEG (FDR 10%), and the functional enrichment analysis identified network maps related to inflammation, immune process, and pathways associated with the oxidative stress, type 2 diabetes and metabolic dysfunction. For the liver tissue, the transcriptome profile analysis revealed 281 DEG, which participate in network maps related to neurodegenerative diseases. With this nutrigenomics study, we verified that different levels of soybean oil in the pig diet, an animal model for metabolic diseases in humans, affected the transcriptome profile of skeletal muscle and liver tissue. These findings may help to better understand the biological mechanisms that can be modulated by the diet.

Triglycerides of waste cooking oil reacted with methanol in refluxing toluene to yield mixtures of diglycerides, monoglycerides and fatty acid methyl esters (FAMEs) in the presence of 20% (w/w) catalyst/oil using the hydrophilic sulfonated silica (SiO₂-SO₃H) catalyst alone or with the addition of 10% (w/w) co-catalyst/oil [(Bun4N)](BF₄) or Aliquat 336]. The addition of the ammonium salts to the catalyst lead to a decrease in the amounts of diglycerides in the products, but the concentrations of monoglycerides increased. Mixtures of [(Bun4N)](BF4)/catalyst were superior to catalyst alone or Aliquat 336/catalyst for promoting the production of mixtures with high concentrations of FAMEs. The same experiments were repeated using DMSO as the solvent. The use of the more polar solvent resulted in excellent conversion of the triglycerides to FAME esters with all three-catalyst media. A simplified mechanism is presented to account for the experimental results.

: The primary objective of this study was to investigate the association of certain genetic alterations and intraoperative fluorescent activity of 5-aminolevulinic acid (ALA) in brain metastasis (BM) of lung adenocarcinoma. A retrospective cohort study was conducted among 72 patients who underwent surgical resection of BM from lung adenocarcinoma at our institute for 5 years. Cancer cell infiltration was estimated by the intraoperative fluorescent activity of 5-ALA, and genetic alterations were analyzed by next-generation sequencing (NGS). The sensitivity and specificity for detecting cancer cell infiltration using 5-ALA were 87.5% and 96.4%, respectively. Genes associated with cell cycle regulation (p = 0.003) and cell proliferation (p = 0.044) were significantly associated with positive fluorescence activity of 5-ALA in the adjacent brain tissue. Genetic alterations in cell cycle regulation and cell proliferation were also associated with shorter recurrence-free survival (p = 0.013 and p = 0.042, respectively) and overall survival (p = 0.026 and p = 0.042, respectively) in the multivariate analysis. The results suggest that genetic alterations in cell cycle regulation and cell proliferation are associated with positive fluorescence activity of 5-ALA in the adjacent infiltrative brain tissue and influence the clinical outcome of BM of lung adenocarcinoma.

Chlorotoxin (CTX) is a 36–amino acid peptide with 8 Cys residues that forms four Cys-Cys bonds. It has high affinity for the glioma-specific chloride channel and matrix metalloprotease-2. Structural and binding properties of CTX analogs with various Cys residue substitutions with L-a-aminobutyric acid (Abu) have been previously reported. Using 4.2 ìs molecular dynamics, we compared the conformational and essential space sampling of CTX and analogs [Abu/Ser^2,19]CTX, [Abu/Ser^5,28]CTX, [Abu/Ser^16,33]CTX, [Abu/Ser^20,35]CTX, and [Abu/Ser^{2,5,16,19,20,28,33,35}]CTX. The native and substituted peptides maintained a high degree of a-helix propensity from residues 8 through 21, with the exception of [Ser^5,28]CTX and [Abu^16,33]CTX. In agreement with previous circular dichroism spectropolarimetry results, the C-terminal b-sheet content varied less from residues 25 through 29 and 32 through 36 and was well conserved in all analogs, except: [Abu^16,33]CTX, [Ser^20,35]CTX, [Abu^{2,5,16,19,20,28,33,35}]CTX, and [Ser^{2,5,16,19,20,28,33,35}]CTX. The Cys¹⁶-Cys³³ and Cys²⁰-Cys³⁵ Cys-Cys bonds appear to be required to maintain the ab-motif of CTX. Their selective substitution with Ser^16,33 however, may mitigate the destabilizing effect of Cys¹⁶-Cys³³ substitution by the formation of an inter residue H-bond from OgH of Ser¹⁶ to OgH of Ser³³ bridged by a water molecule. All peptides shared considerable sampled conformational space, which explains the retained receptor binding of the nonnative analogs.

This study was aimed to investigate the effect of xylan depolymerizing enzyme namely endo-xylanase (Xyn) combined with debranching enzymes namely arabinofuranosidase (Afd) and feruloyl esterase (FE) on digestion, growth performance and intestinal volatile fatty acid profile of piglets. The in vitro experiments were firstly conducted to examine the enzymological properties of Xyn, Afd and FE, the synergy among these enzymes, together with the effect of combination of these enzymes on digestion of piglet diet. The in vivo experiment was then implemented by allocating 270 35-d-old postweaning piglets into 3 treatment groups: control group, Xyn group and (Xyn+Afd+FE) group. Each group had 6 replicates (15 piglets/replicate). The results revealed a satisfying thermostability and pH stability of Xyn, Afd and FE. Combination of Xyn, Afd and FE had a superiority (P < 0.05) over Xyn alone and its combination with Afd or FE in promoting degradation of different bran fibers rich in arabinoxylan (Abx). Treatment with combination of Xyn, Afd and FE had advantages over Xyn alone to induce increasing trends (P < 0.10) of in vitro digestibility of dietary nutrients (dry matter, crude protein, crude ash and gross energy) and piglet growth performance (average daily gain, final body weight and feed efficiency), concurrent with a reduction (P < 0.05) of diarrhea rate and increases (P < 0.05) in cecal acetic acid, butyric acid and total volatile fatty acids concentrations as well as pH value of piglets. Collectively, combination of Xyn, Afd and FE was efficient in benefiting degradation of Abx in brans, as well as improving digestion, growth performance and intestinal volatile fatty acid profile of piglets.

The viability, productivity and survival of higher plants under the adverse factors influence are largely determined by the functional activity of the antioxidant system. The aim of our work was to investigate changes in formation of high-molecular (superoxide dismutase and peroxidase) and low-molecular (phenolics, including flavanols and proanthocyanidins) antioxidants in callus culture of Camellia sinensis under influence of phenolic precursors (L-phenylalanine – 3 mM, trans-cinnamic acid – 1 mM, naringenin – 0.5 mM). According to the data obtained, precursors effect on tea callus cultures did not lead to significant increasing of superoxide dismutase and peroxidase activity in most cases. However, it led to the increased accumulation of the total phenolics content, as well as flavanols and proanthocyanidins contents. For C. sinensis callus cultures, the most promising regulator of phenolic compounds was L-phenylalanine, in the presence of which its content increased almost twice. Thus, the exogenous effect of various precursors is possible to use for the targeted regulation of the certain phenolics classes accumulation in plant cells.

Three kinds of hydrophobic groups grafted starches of maleic anhydride grafted starch (MAH-g-starch), lactic acid grafted starch (LA-g-starch), and methyl acrylate grafted starch (MA-g-starch) were prepared by in-situ solid phase polymerization. The results of Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS) were confirmed successful grafting. The grafting ratios of MAH-g-starch, LA-g-starch and MA-g-starch were 6.50%, 12.45%, and 0.57%, respectively. Influenced by the grafting ratio, LA-g-starch had the best hydrophobic properties and the largest molecular weight, and those for MA-g-starch was the worst. The surfaces of grafted starches were covered with graft polymer, with obvious surface roughness and bond degree of MAH-g-starch and LA-g-starch. The crystalline structure of grafted starches showed some damage, with LA-g-starch exhibiting the greatest decrease in crystallinity, and less of a change for MA-g-starch. Overall, the grafting reaction improved thermoplasticity, with LA-g-starch the most improved, followed by MAH-g-starch, and then MA-g-starch.

Almond (Prunus dulcis (Mill.) D.A.Webb) is one of the most important nut crops both in terms of area and production. Over the last decades, an important part of the beneficial actions for health associated with their consumption was attributed to the phenolic compounds, mainly accumulated in almond skin. Interestingly, after cold-pressed oil extraction, most of these antioxidant phenolic compounds are retained in a skin-enriched by-product, so-called almond cold-pressed oil residue. In Morocco, ranked fifth producer in the world, this production generates an important part of this valuable byproduct. In the present study, using a multivariate Box-Behnken design, an ultrasound-assisted extraction (USAE) method of phenolic compounds from Moroccan almond cold-pressed oil residue was developed and validated. Response surface methodology resulted in the optimal extraction conditions: the use of aqueous EtOH 53.0% (v/v) as green solvent, applying an US frequency of 27.0 kHz for an extraction duration of 29.4 min. The present USAE allowed substantial gains in terms of extraction efficiency compared to conventional heat reflux extraction. Applied to 3 different local Beldi genotypes growing at 3 different experimental sites, the optimal USAE conditions led to a total phenolic content of 13.86 mg/g dry weight (DW). HPLC analysis revealed that the main phenolic compounds from this valuable byproduct were: chlorogenic acid followed by protocatechuic acid, p-hydrobenzoic acid and p-coumaric acid. The accumulation of these phenolic compounds appeared to be more dependent on the genetic background than on the environmental impact here represented by the 3 experimental culture sites. Both in vitro cell free and cellular antioxidant assays were performed, and revealed the great potential of these extracts. In particular, correlation analysis evidenced the prominent roles of chlorogenic acid, protocatechuic acid and p-hydrobenzoic acid. To summarize, the USAE method presented here is a quick, green, simple and efficient validated USAE for the possible valorization of antioxidant phenolic compounds from Moroccan almond cold-Pressed oil residues, making it possible to generate extracts with attractive antioxidant activities for future nutraceutical and/or cosmetic applications.

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

The application of diffusion dialysis using various types of ion-exchange membranes for the separation of sulfuric acid and nickel sulfate has been evaluated. The process of dialysis separation of a real waste solution from an electroplating facility containing 252.3 g/L of sulfuric acid, 20.9 g/L of nickel ions and small amounts of zinc, iron, copper ions, etc. has been studied. Heterogeneous cation-exchange membrane containing sulfo groups and heterogeneous anion-exchange membranes with different thicknesses (from 145 μm to 550 μm) and types of fixed groups (4 samples with quaternary amino groups and 1 sample with secondary and tertiary amino groups) are used. The diffusion fluxes of sulfuric acid, nickel sulfate, and the total and osmotic fluxes of the solvent are determined. The use of a cation-exchange membrane does not allow separation of the components, since the fluxes of both components are low and comparable in magnitude. The use of anion-exchange membranes makes it possible to efficiently separate sulfuric acid and nickel sulfate. At the same time, the thin dialysis membrane turns out to be the most effective, as well as the membranes with quaternary amino groups, and the membrane with secondary and tertiary amino groups proved to be the least effective.

Geminiviruses possess single-stranded, circular DNA genomes, and control the transcription of their late genes, including BV1 of many bipartite begomoviruses, through transcriptional activation by the early expressing AC2 protein. DNA binding by AC2 is not sequence-specific, hence the specificity of AC2 activation is thought to be conferred by plant transcription factors (TFs) recruited by AC2 in infected cells. However, the exact TFs AC2 recruits are not known for most viruses. Here we report a systematic examination of the BV1 promoter (PBV1) of mungbean yellow mosaic virus (MYMV) for conserved promoter motifs. We found that MYMV PBV1 contains three abscisic acid (ABA)-responsive elements (ABREs) within its first 70 nucleotides. Deleting these ABREs, or mutating them all via site-directed mutagenesis, abolished the capacity of PBV1 to respond to AC2-mediated transcriptional activation. Furthermore, ABRE and other related ABA-responsive elements were prevalent in more than a dozen Old World begomoviruses we inspected. Together these findings suggest that ABA-responsive TFs may be recruited by AC2 to BV1 promoters of these viruses to confer specificity to AC2 activation. These observations are expected to guide the search for the actual TF(s), furthering our understanding of the mechanism of AC2 action.

The study aimed to isolate and characterize bacteriocin-producing Enterococcus species from Ethiopian traditional fermented foods and beverages. The bacteriocin bioassay was tested against food-borne pathogens at various temperatures, pH, solvents, additives, and enzymes. A solvent extraction method was established to concentrate bacteriocins from Enterococcus species. The study found that crude extracts with proteinase K, pepsin, and trypsin deactivated antimicrobial activity, confirming their proteinaceous nature. Organic solvents were more effective at extracting bacteriocins from CFS, with chloroform alone and in combination providing rapid and efficient recovery. The optimal bacteriocin production and strong inhibition activity were achieved at 37°C with a pH range of 5.5 to 6.5 incubated for 16-18 hours. The six Enterococcus faecium species were the best bacteriocin-producing isolates. Optimizing bacteriocin production and changing environmental growing circumstances can enhance the application of bacteriocins as food preservation agents. Traditional fermented products are potential sources of bacteriocin-producing LAB.

To evaluate the behaviour of the relevant microbial populations during stretched cheese production, the quantitative microbiological analysis was performed during the critical steps of the preparation. The obtained data distributions proved statistically significant increases in all indicators, on average by 4.55 ± 0.64 log CFU/g of presumptive lactococci counts, 4.06 ±0.61 of lactobacilli, 1.53 ± 0.57 log CFU/g of coliforms, 2.42 ± 0.67 log CFU/g of Escherichia coli, 1.53 ± 0.75 log CFU/g of yeasts and moulds, and 0.99 ± 0.27 log CFU/g of presumptive Staphylococcus aureus, from the early stage of milk coagulation until curd ripening (0–24 h). The following steaming/stretching process caused reductions in viable counts with the most significant inactivation effect on coliform bacteria, including E. coli (-4.0 ± 1.0 log CFU/g). Total viable counts and yeasts and moulds showed 2 and almost 3 log reduction (-2.2 ± 1.1 log CFU/g and -2.6 ± 0.9 log CFU/g), respectively. The lowest decreases in presumptive S. aureus counts were estimated at the level of -1.50 ± 0.64 log CFU/g. The counts of yeasts and moulds showed the best indicatory function during the entire storage period of vacuum-packaged cheeses at 6 °C.