Objective: To observe the effects of exosomes derived from human umbilical cord mesenchymal stem cells on the proliferation and invasion of pancreatic cancer cells, and to analyze the contents of exosomes and explore the mechanisms affecting pancreatic cancer cells. Methods: Exosomes extracted from human umbilical cord mesenchymal stem cells were added to pancreatic cancer cells BxPC3, Panc-1 and mouse models of pancreatic cancer, respectively. The proliferative activity and invasion abilities of BxPC3 and Panc-1 cells were measured by cell counting kit-8 (CCK-8) and Transwell assays. The expressions of miRNAs in exosomes were detected by high-throughput sequencing. GO and KEGG were used to analyze the related functions and the main metabolic pathways of target genes with high expressions of miRNAs. Results: The results of CCK-8 cell proliferation assay showed that the absorbance of BxPC3 and Panc-1 cells in the hucMSCs-exo group was significantly higher than that in the control group [(4.68±0.09) vs. (3.68±0.01), P<0.05; (5.20±0.20) vs. (3.45±0.17), P<0.05]. Transwell test results showed that the number of invasion cells of BxPC3 and Panc-1 in hucMSCs-exo group was significantly higher than that in the control group (129.40±6.02) vs. (89.40±4.39), P<0.05; (134.40±7.02) vs. (97.00±6.08), P<0.05. In vivo experimental results showed that the tumor volume and weight in the exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs-exo) group were significantly greater than that in the control group [(884.57±59.70) mm(3) vs. (695.09±57.81) mm(3), P<0.05; (0.94±0.21) g vs. (0.60±0.13) g, P<0.05]. High-throughput sequencing results showed that miR-148a-3p, miR-100-5p, miR-143-3p, miR-21-5p and miR-92a-3p were highly expressed. GO and KEGG analysis showed that the target genes of these miRNAs were mainly involved in the regulation of glucosaldehylation, and the main metabolic pathways were ascorbic acid and aldehyde acid metabolism, which were closely related to the development of pancreatic cancer. Conclusion: Exosomes derived from human umbilical cord mesenchymal stem cells can promote the growth of pancreatic cancer cells and the mechanism is related to miRNAs that are highly expressed in exosomes.

It is of great significance to sensitively and selectively detect uranyl ion (UO22+) in environmental and biological samples due to the high risks of UO22+ to human health. However, such suitable sensors are still scarce. A novel fluorescence sensor based on a dansyl-modified peptide, Dansyl-Glu-Glu-Pro-Glu-Trp-COOH (D-P5), was efficiently synthesized by Fmoc solid phase peptide synthesis. As the first linear peptide-based fluorescence sensor for UO22+, D-P5 exhibited high selectivity and sensitivity to UO22+ over 27 metal ions (UO22+, Cr3+, Cu2+, Ba2+, Hg2+, Pb2+, Co2+, Ag+, Fe3+, Ca2+, K+, Mg2+, Mn2+, Na+, Ni2+, Cd2+, Zn2+, Al3+, Dy3+, Er3+, Gd2+, Ho3+, La3+, Lu3+, Pr3+, Sm3+, Tm3+) by a turn-off fluorescence response in 10 mM HEPES buffer (pH 6.3). The effects of anions such as S2-, NO3-, SO42- CO32-, HCOO-, antioxidant ascorbic acid and 4-nitrophenyl acetate on the selectivity for UO22+ detection were also studies. D-P5 sensor could be used for detecting UO22+ in a good linear relationship with concentration in the range of 0-8.0 μM with a low limit of detection of 83.2 nM. Furthermore, the interaction of the sensor with UO22+ was characterized by ESI-MS, IR, XPS and ITC measurements. The 1:1 binding stoichiometry between the sensor and UO22+ was measured by the job's plot and further verified by ESI-MS. The binding constant of the sensor with UO22+ was calculated to be 9.8 × 104 M-1 by modified Benesi-Hildebrand equation. ITC results showed that theΔHθ andΔSθ for the interaction of D-P5 with UO22+ were -(7.167 ± 1.25) kJ·mol-1 and 66.5 J·mol-1·K-1, respectively. Time-resolved fluorescence spectroscopy indicated that the mechanism of fluorescence quenching of D-P5 by UO22+ ion was static quenching process. In addition, this sensor displayed a good practicality for UO22+ detection in lake water sample without tedious sample pretreatment.

Ascorbic acid, as one of the basic exogenous vitamins, is known for its tremendous antioxidant properties. This review has been prepared to show not only the importance of ascorbic acid as a free radical scavenger, but also to summarize its antioxidant action based on other mechanisms, including activation of intracellular antioxidant systems. Ascorbic acid interacts with small molecule antioxidants, including tocopherol, glutathione and thioredoxin, but also can stimulate the biosynthesis and activation of antioxidant enzymes, such as superoxide dismutase, catalase or glutathione peroxidase. Moreover, ascorbic acid promotes the activity of several transcription factors (Nrf2, Ref-1, AP-1), which enables the expression of genes encoding antioxidant proteins. Additionally, it supports the action of other exogenous antioxidants, mainly polyphenols. In this connection, both DNA, protein and lipids are protected against oxidation. Although ascorbic acid has strong antioxidant properties, it can also have pro-oxidant effects in the presence of free transition metals. However, its role in prevention of DNA mutation and cellular apoptosis, especially in relation to cancer cells is controversial.

Noninvasive human health monitoring requires the development of efficient electrochemical sensors for the quantitative analysis of infinitesimal biomolecules. In this work, we reported a novel hierarchical nanosheet assemblies (HSA) of copper-based metal-organic frameworks (MOFs) as an electrochemical sensor for ascorbic acid (AA) detection. Copper 1,4-benzenedicarboxylate (CuBDC) HSA was constructed by three steps of in situ growth on stone paper, including hydrolysis, anion exchange, and heteroepitaxy growth. The monodispersed two-dimensional MOFs nanosheet units were aligned in an orderly manner and arranged into three-dimensional hierarchical assemblies. The CuBDC HSA-based AA sensor displayed a high sensitivity of 396.8 μA mM-1 cm-2 and a low detection limit of 0.1 μM. Excellent selectivity, stability and reproducibility were also obtained. Benefiting from the advantages of ultrathin nanosheets and nature-inspired hierarchy, this unique architecture facilitated reactant dispersion and maximized the accessible active sites and charge-transport capability and thus had superior catalytic ability for the electro-oxidation of ascorbic acid compared to bulk MOFs. Moreover, the CuBDC HSA sensor performed AA level detection in juice samples with acceptable accuracy and verified the feasibility for sweat AA sensing. This novel MOFs architecture holds great potential as an electrochemical sensor to detect AA for noninvasive human health monitoring in the future.

Salmonella Typhimurium infection of the gastrointestinal tract leads to damage that compromises the integrity of the intestinal epithelium and results in enterocolitis and inflammation. Salmonella infection promotes the expression of inflammasome NLRP3, leading to activation and release of proinflammatory cytokines such as IL-1β, and the infected host often displays altered nutrient levels. To date, the effect of Salmonella infection and proinflammatory cytokine IL-1β on the intestinal uptake of ascorbic acid (AA) is unknown. Our results revealed a marked decrease in the rate of AA uptake in mouse jejunum infected with Salmonella wild type (WT). However, the nonpathogenic mutant (Δ invA Δ spiB) strain did not affect AA uptake. The decrease in AA uptake due to Salmonella WT infection is accompanied by significantly lower expression of mouse (m)SVCT1 protein, mRNA, and hnRNA levels. NLRP3 and IL-1β expression levels were markedly increased in Salmonella-infected mouse jejunum. IL-1β-exposed Caco-2 cells displayed marked inhibition in AA uptake and significantly decreased hSVCT1 expression at both protein and mRNA levels. Furthermore, the activity of the SLC23A1 promoter was significantly inhibited by IL-1β exposure. In addition, GRHPR (a known SVCT1 interactor) protein and mRNA expression levels were significantly reduced in Salmonella-infected mouse jejunum. These results indicate that Salmonella infection inhibits AA absorption in mouse jejunum and IL-1β-exposed Caco-2 cells. The observed inhibitory effect may partially be mediated through transcriptional mechanisms.

Rosa roxburghii Tratt. is an important commercial horticultural crop endemic to China, which is recognized for its extremely high content of L-ascorbic acid (AsA). To understand the mechanisms underlying AsA overproduction in fruit of R. roxburghii, content levels, accumulation rate, and the expression of genes putatively in the biosynthesis of AsA during fruit development have been characterized. The content of AsA increased with fruit weight during development, and AsA accumulation rate was found to be highest between 60 and 90 days after anthesis (DAA), with approximately 60% of the total amount being accumulated during this period. In vitro incubating analysis of 70DAA fruit flesh tissues confirmed that AsA was synthesized mainly via the L-galactose pathway although L-Gulono-1, 4-lactone was also an effective precursor elevating AsA biosynthesis. Furthermore, in transcript level, AsA content was significantly associated with GDP-L-galactose phosphorylase (RrGGP2) gene expression. Virus-induced RrGGP2 silencing reduced the AsA content in R. roxburghii fruit by 28.9%. Overexpressing RrGGP2 increased AsA content by 8-12-fold in tobacco leaves and 2.33-3.11-fold in tomato fruit, respectively, and it showed enhanced resistance to oxidative stress caused by paraquat in transformed tobacco. These results further justified the importance of RrGGP2 as a major control step to AsA biosynthesis in R. roxburghii fruit.

Medicinal and aromatic plants are known to have a number of biologically active compounds. Since ancient times, such plants have been used in ethnopharmacology. A number of medicines have been developed from plant origin by researchers and Researchers continue to be interested in plant-based medicines.. Zingiberaceae is a well-known plant family for such types of medicinal and aromatic plants. Zingiber is the third largest genus of this family and Zingiber roseum (Roxb.) Roscoe is a medicinal and aromatic Z. roseum is a rhizomatous perennial herbaceous plant of this genus, popularly known as "Rosy Ginger" and "Jangli Adrak," utilized in the Siddha arrangement of medication, and its rhizomes have been used to treat injury, cough, asthma, skin illnesses, gastric ulcers, liver diseases, and heartburn in tradition. It also has ethnopharmacological uses, such as the rhizome of Z. roseum is used for digestion, relieving giddiness, and as a stimulant. Apart from this, it has been reported for several pharmacological activities such as antispasmodic, hepatoprotective, antimicrobial, and anticancer activities, etc. Z. roseum is a reservoir of several chemical constituents such as terpenes and terpenoids such as linalool, α-pinene, β-pinene, limonene, terpinen-4-ol, α-terpineol, etc., phenols, flavonoids, alkaloids, saponins, and ascorbic acid along with important unique constituents such as zerumbone which are responsible for its medicinal and other biological activities. In this review article, we discussed the thorough knowledge published by researchers regarding the phytochemistry, ethnopharmacological, and mediational properties of Z. roseum and its botanical descriptions.

Chemical-based syntheses of metallic nanoparticles (MNPs) has become a major topic of research exploration in the field of nanotechnology. The utilization of folic acid (FA) as stabilizing and capping agent has been reported as a novel route for the synthesis of bimetallic nanomaterials. The present study includes novel research and brief discussion about preparation of UV light assisted ZnO-Ag nanobars (NBs) using FA as stabilizing agent and its catalytic applications on the reduction of organic pollutants (4-NP and Cr+6) using NBs as a catalyst alongwith ascorbic acid (AA). Analytical techniques including UV-visible spectroscopy, XRD, SEM, EDX and FT-IR were used for the characterizing synthesized ZnO-Ag NBs. Hexagonal structure of ZnO-Ag NBs were found having crystallite size 5.6 nm and SEM studies revealed the nanobar width 33.2 nm and length 133.5 nm. The prepared ZnO-Ag NBs were tested for their catalytic activity for the reduction of 4-nitrophenol (4-NP) and Cr+6. In the presence of ZnO-Ag NBs and AA, an effective reduction of 4-nitrophenol (4-NP) and Cr+6 was achieved up to 93% and 90% in 17 and 26 min with respectively. The successful and efficient catalytic activity of NBs may be attributed to the size of NBs or the concentration of FA employed for synthesis.

In this work, dual-template molecularly imprinted polymer surfaces imprinted on blue fluorescent Cr-based MOF (Cr-MOF) functionalized with yellow emissive carbon dots (Y-CDs) were prepared using l-ascorbic acid (AA) and uric acid (UA) as templates for simultaneous selective recognition of AA and UA. The as-prepared nanocomposite probe (Y-CDs/Cr-MOF@MIP) contains two recognition site cavities and emits a dual well-resolved fluorescence spectra when excited at 390 nm; blue emission (λem 450 nm) is due to Cr-MOF, and yellow emission (λem 560 nm) is due to Y-CDs. The yellow fluorescence emission of Y-CDs was quenched upon the addition of ascorbic acid, while Cr-MOF's emission remained unaffected. In the same way, the blue fluorescence emission of the Cr-MOFs was quenched in the presence of uric acid, while the yellow emission remained constant. Both emissions were quenched in a sample containing both AA and UA. This can be exploited to design a dual-template biosensor to detect UA and AA simultaneously. The Y-CDs/Cr-MOF@MIP sensor displayed a dynamic linear response for AA in the range 25.0 µM - 425.0 µM with a detection limit of 1.30 µM, and for UA in the range 25.0 µM - 425.0 µM with a detection limit of 1.10 µM. The dual-target probe Y-CDs/Cr-MOF@MIP was highly selective and sensitive for the detection of UA and AA in human urine samples due to the selectivity of the two recognition sites.

One of the major challenges for in vivo electrochemical measurements of dopamine (DA) is to achieve selectivity in the presence of interferents, such as ascorbic acid (AA) and uric acid (UA). Complicated multimaterial structures and ill-defined pretreatments have been frequently utilized to enhance selectivity. The lack of control over the realized structures has prevented establishing associations between the achieved selectivity and the electrode structure. Owing to their easily tailorable structure, carbon nanofiber (CNF) electrodes have become promising materials for neurobiological applications. Here, a novel yet simple strategy to control the sensitivity and selectivity of CNF electrodes toward DA is reported. It consists of adjusting the lengths of CNF by modulating the growth phase during the fabrication process while keeping the surface chemistries similar. It was observed that the sensitivity of the CNF electrodes toward DA was enhanced with the increase in the fiber lengths. More importantly, the increase in the fiber length induced (i) an anodic shift in the DA oxidation peak and (ii) a cathodic shift in the AA oxidation peak. As the UA oxidation peak remained unaffected at high anodic potentials, the electrodes with long CNFs showed excellent selectivity. Electrodes without proper fibers showed only a single broad peak in the solution of AA, DA, and UA, completely lacking the ability to discriminate DA. Hence, the simple strategy of controlling CNF length without the need to carry out any complex chemical treatments provides us a feasible and robust route to fabricate electrode materials for neurotransmitter detection with excellent sensitivity and selectivity.

Sepsis is a substantial healthcare burden, and its management continues to be a major challenge. Prior studies demonstrate conflicting evidence regarding the utility of vitamin C in sepsis. This systematic review and meta-analysis aim to collect data among critically ill patients (sepsis/septic shock), comparing the efficacy of parenteral vitamin C with standard care. A literature review was conducted using databases including PubMed, Web of Science, Google Scholar, and the Cochrane Library to identify randomized controlled trials (RCTs) and observational studies comparing intravenous vitamin C alone or in combination with thiamine or glucocorticoids to the standard of care. We identified 11 RCTs and seven retrospective cohort studies. The primary outcome was 28-day mortality. Secondary outcomes included intensive care unit (ICU) length of stay, change in Sequential Organ Failure Assessment (SOFA) score, duration of vasopressor use, and duration of mechanical ventilation. A total of 18 studies with 4078 patients were included in our final analysis. Overall, we found no mortality reduction in patients treated with vitamin C compared to standard of care (odds ratio (OR) 0.92; 95% confidence interval (CI) 0.78 to 1.09; p = 0.34). Studies that reported a change in SOFA scores, ICU length of stay, duration of mechanical ventilation, or duration of vasopressor use did not show any significant difference between groups. Subgroup analysis with RCT versus observational studies and vitamin C dosage regimens did not show any difference. Among patients with sepsis or septic shock, treatment with vitamin C was not associated with a reduction in mortality, ICU length of stay, change in SOFA score, duration of vasopressor use, or duration of mechanical ventilation. Further studies are needed to demonstrate the potential role of vitamin C in the management of sepsis.

The new concept of functional foods has led to the varieties in the production of foods that provide not only basic nutrition, but can also warrant good health and longevity. This study deals with the production and evaluation of fortified yogurts' with Cinnamomum verum, Elettaria cardamomum, Beta vulgaris and Brassica oleracea. The qualitative and quantitative phytochemical analysis of above mentioned plant extracts before using them into the preparation of functional yoghurt was carried out. The sensory evaluation of enriched yogurts with plant extracts carried out using 9 point hedonic scale. Comparative analysis between enriched yogurts and plain yogurt was carried. The results indicated increase in ash contents, water holding capacity, titratable acidity, total soluble solids, total phenolic content, tannin content, and total flavonoid content in fortified yogurt as compared to plain yogurt. In addition to this fortified yogurts showed greater antioxidant and antibacterial activity in contrast to plain yogurt. However, moisture contents, pH and susceptibility to syneresis of yogurt decreases with the addition of plant extracts. Shelf life of plain and fortified yogurt was determined both at room and refrigerated temperature. The results revealed that shelf life of fortified yogurt was greater as compared to plain yogurt. In silico analysis was carried out by using the galaxy web software. The results indicated that bioactive compounds including ascorbic acid, sinapinic acid, cinnamaldehyde and linalool acetate present in the flavored yogurts binds with angiotensin converting enzyme. All enriched yogurts showed higher anti-Angiotensin converting enzyme activity as compared to plain-yogurt.

Dimethyl nitrosamine (DMN) is a known hepatotoxin, carcinogen, and mutagen. This study is therefore carried out to investigate the therapeutic effects of syringic acid (SYRA) and ascorbic acid (ASCA) in DMN-induced hepatic injury in rats. Following DMN administrations, malondialdehyde (MDA), nitric oxide (NO) and reduced glutathione (GSH) as well as activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) were significantly increased. Also significantly increased were levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Following treatment with SYRA and ASCA, the activities of ALT, AST, GPx, CAT and SOD, as well as MDA, GSH, TNF-α, IL-1β, and NFkB levels were significantly reduced. Overall, both treatments were effective, but SYRA had a better therapeutic effect than ASCA. Therefore, this promising potential of SYRA can be taken advantage of in the treatment of DMN-induced hepatic injury.

Ascorbic acid (AA; vitamin C) plays a crucial role in the biosynthesis and secretion of collagen to produce the organic matrix of hard tissues. Nevertheless, the detailed mechanism by which AA induces reparative dentinogenesis is still unknown. This study aimed to investigate the pathway and function of AA during wound healing in a rat pulpotomy model. Sodium-dependent vitamin C transporter (SVCT) 2 and glucose transporter (GLUT) 1 were detected in odontoblasts, endothelial cells, and nerve fibers in normal pulp tissues. SVCT2 and GLUT1 were also expressed in odontoblast-like cells in pulpotomized tissues of Wistar rats, and immunopositive cells of SVCT2 were significantly increased at 5 days after pulpotomy (p < 0.05). By contrast, osteogenic disorder Shionogi (ODS) rats, which cannot generate AA, also expressed SVCT2 and GLUT1 in normal and wound healing conditions. However, in ODS rats, when compared with the AA-addition group, the formation of dentin bridges in the AA-loss group was not evident, a layer of osteopontin was significantly increased beneath the wound surface (p < 0.05), and alpha smooth muscle actin at the odontoblast-like cells observed along this layer was significantly increased (p < 0.05), but not Nestin. Moreover, the amounts of type 1 collagen generated in the reparative dentin and beneath the wound healing site were significantly diminished (p < 0.05). Macrophages expressing CD68 and CD206 increased beneath the wound site. Hence, AA may be involved in odontoblast-like cell differentiation and anti-inflammatory response during dental pulp wound healing. Our results provide new insights into the function of AA through SVCT2 and GLUT1 in reparative dentinogenesis and may help in developing new therapeutic targets for dental pulpal disease.

In this study, site saturation mutagenesis was performed on the - 3 (R44, D86, S90, and D192) and - 6 subsite (Y163, G175, G176, and N189) of Bacillus stearothermophilus NO2 cyclodextrin glucosyltransferase to enhance its specificity for the donor substrate maltodextrin for 2-O-α-D-glucopyranosyl-L-ascorbic acid (AA-2G) preparation. The AA-2G yields produced by the mutants S90D, G176H, and S90D/G176H were 181, 171, and 185 g/L, respectively. Our previous study found that the mutant K228R/M230L also increased the AA-2G yield. Therefore, the mutants S90D, G176H, S90D/G176H, and K228R/M230L were further used to generate combinatorial mutants. Among these mutants, the highest AA-2G yield (217 g/L) was produced by S90D/K228R/M230L with 500 g/L maltodextrin as the glucosyl donor, which was 56 g/L higher than that produced by wild-type CGTase. In addition, AA-2G was prepared by adding isoamylase to hydrolyze α-1,6 glucosidic linkages in maltodextrin that could not be utilized by CGTase to improve the utilization rate of maltodextrin. The addition of isoamylase reduced the concentration of maltodextrin from 500 to 350 g/L, while the AA-2G yield remained high (208 g/L). The preparation of AA-2G by complexing isoamylase with mutant S90D/K228R/M230L reduced the maltodextrin concentration by 150 g/L, while the AA-2G yield increased by 47 g/L than preparation with wild-type CGTase alone, which laid a foundation for the large-scale preparation of AA-2G. KEY POINTS: • Mutants exhibited improved maltodextrin specificity. • Mutant S90D/K228R/M230L produced high yield of AA-2G with maltodextrin as substrate. • AA-2G was first synthesized by a combination of isoamylase and CGTase.

Although helpful in treating cancer, exposure to ionizing radiation can sometimes cause severe side effects, negating its benefit. In addition to its use in clinics, a nontoxic radioprotective agent can also be beneficial in occupational settings where humans are occupationally exposed for prolonged periods to low doses of radiation. Scientific studies using laboratory animals have shown that the fruits Aegle marmelos, Capsicum annuum, Citrus aurantium, Citrullus lanatus, Crataegus microphylla, Eugenia jambolana, Emblica officinalis, Garcinia kola, Grewia asiatica, Hippophae rhamnoides, Malus baccata, Malpighia glabra or Malpighia emarginata, Mangifera indica, Prunus domestica, Prunus avium, Prunus armeniaca, Psoralea corylifolia, Punica granatum, Solanum lycopersicum, Terminalia chebula, Vaccinium macrocarpon, Vitis vinifera and Xylopia aethiopica, and the phytochemicals gallic acid, ellagic acid, quercetin, geraniin, corilagin, ascorbic acid, hesperetin, ursolic acid, lycopene, naringin, hesperidin, rutin, resveratrol, β-sitosterol, apigenin, luteolin, chlorogenic acid, caffeic acid, mangiferin, diosmin, ferulic acid, and kaempferol are effective in preventing radiation-induced ill effects. Clinical studies with Emblica officinalis and Punica granatum have also shown that fruits help mitigate radiation-induced mucositis, dermatitis, and cystitis. For the first time, the current review summarizes the beneficial effects of fruits and phytochemicals in mitigating radiation-induced damage, the underlying mechanisms and the existing lacunae for future studies to be undertaken for the benefit of humans and the nutraceutical and agri-based industries.

Black Tibetan sheep is one of the primitive sheep breeds in China that is famous for its great eating quality and nutrient value but with little attention to the relationship between feeding regimes and rumen metabolome along with its impact on the muscle metabolism and meat quality.

Hydroxychloroquine (HCQ) is a potential drug molecule for treating malaria. Recently it has also been tried as adjustment in Covid 19 therapy. Interaction of HCQ with free radicals is very important, which controls its stability in the environment where free radicals are generated unintentionally. In this report, we present detailed investigation on the reactions of hydrated electrons (eaq -) and hydroxyl radical (•OH) with HCQ in aqueous solution through electron pulse radiolysis technique and computational studies. The degradation of HCQ was found to be faster in the case of reaction with •OH radicals. However, the degradation could be substantially slowed down in the presence of antioxidants like ascorbic acid and gallic acid. This revealed that the stability of HCQ could be enhanced in an oxidative environment in the presence of these two compounds, which are easily available through food supplements. Various global and local reactivity parameters are also determined to understand the reactivity trend using Hard-Soft Acid-Base (HSAB) principle in the realm of the DFT methods. Computational studies were performed to elucidate the site-specific reactivity trend towards the electrophilic and nucleophilic attack by calculating the condensed Fukui index for various species of HCQ.

Despite the widespread use of silver nanoparticles (NPs), these NPs can accumulate and have toxic effects on various organs. However, the effects of silver nanostructures (Ag-NS) with alginate coating on the male reproductive system have not been studied. Therefore, this study aimed to investigate the impacts of this NS on sperm function and testicular structure. After the synthesis and characterization of Ag-NS, the animals were divided into five groups (n = 8), including one control group, two sham groups (received 1.5 mg/kg/day alginate solution for 14 and 35 days), and two treatment groups (received Ag-NS at the same dose and time). Following injections, sperm parameters, apoptosis, and autophagy were analyzed by the TUNEL assay and measurement of the mRNA expression of Bax, Bcl-2, caspase-3, LC3, and Beclin-1. Fertilization rate was assessed by in vitro fertilization (IVF), and testicular structure was analyzed using the TUNEL assay and hematoxylin and eosin (H&E) staining. The results showed that the NS was rod-shaped, had a size of about 60 nm, and could reduce sperm function and fertility. Gene expression results demonstrated an increase in the apoptotic markers and a decrease in autophagy markers, indicating apoptotic cell death. Moreover, Ag-NS invaded testicular tissues, especially in the chronic phase (35 days), resulting in tissue alteration and epithelium disintegration. The results suggest that sperm parameters and fertility were affected. In addition, NS has negative influences on testicular tissues, causing infertility in men exposed to these NS.

A revival of interest in traditional varieties reflects the change in consumer preferences and the greater awareness of the quality of locally grown products. As ancient cultivars, heirlooms have been selected for decades in specific habitats and represent nowadays potential germplasm sources to consider for breeding high-quality products and cultivation in sustainable agriculture. In this study, 60 heirloom tomato (Solanum lycopersicum L.) accessions, including diverse varietal types (beefsteak, globe, oxheart, plum, and cherry), were profiled over two seasons for the main chemical and biochemical fruit traits. A medium-high level of heritability was found for all traits ranging from 0.52 for soluble solids to 0.99 for fruit weight. The average content of ascorbic acid was ~31 mg 100 g-1 of fw in both seasons, while the greatest variability was found for carotenoids with peaks of 245.65 μg g-1 of fw for total lycopene and 32.29 μg g-1 of fw for β-carotene. Dissection of genotypic (G) and seasonal (Y) factors highlighted genotype as the main source of variation for all traits. No significant effect of Y and G × Y was found for ascorbic acid and fruit weight, respectively, whereas a high influence of Y was found on the variation of lycopene. Molecular fingerprinting was performed using the 10K SolCAP array, yielding a total of 7,591 SNPs. Population structure, phylogenetic relationships, and principal components analysis highlighted a differentiation of plum and cherry genotypes with respect to the beefsteak and globe types. These results were confirmed by multivariate analysis of phenotypic traits, shedding light on how breeding and selection focused on fruit characteristics have influenced the genetic and phenotypic makeup of heirlooms. Marker-trait association showed 11 significantly associated loci for β-carotene and fruit weight. For β-carotene, a single variant on chromosome 8 was found at 12 kb to CCD8, a cleavage dioxygenase playing a key role in the biosynthesis of apocarotenoids. For fruit weight, a single association was located at less than 3 Mbp from SLSUN31 and fw11.3, two candidates involved in the increasing of fruit mass. These results highlight the potentiality of heirlooms for genetic improvement and candidate gene identification.

Phosphate-solubilizing bacteria play a key role in increasing plant growth as potential suppliers of soluble phosphorus and have great potential for the remediation of heavy metal-polluted soils. However, the soil and microbiological mechanisms by which phosphate-solubilizing bacteria prevent heavy metal absorption in radish have not been adequately studied. Here, the mechanisms of phosphorus solubilization, Cd and Pb immobilization, and the inhibition of heavy metal absorption by phosphate-solubilizing bacteria were studied in radish through solution adsorption and pot experiments. Two phosphate-solubilizing bacteria with high Cd and Pb removal rates (46.9-97.12 %), Klebsiella sp. M2 and Kluyvera sp. M8, were isolated. The soluble phosphorus content released by strains M2 and M8 was 265-277 mg L-1, achieved by secreting oxalic acid, ascorbic acid, citric acid, and succinic acid in an inorganic phosphorus medium containing 3 mg L-1 Cd and 5 mg L-1 Pb. Furthermore, these two functional strains induced the formation of Pb2(PO4)2, Cd(PO3)2, Fe2Pb3(PO4)2, CdS, and PbS precipitates that immobilized Cd and Pb in the solution. In general, strains M2 and M8 inhibited the absorption of Cd and Pb by radish by the following mechanisms: i) bacterial cell wall adsorption, ii) induction of Pb2(PO4)2, Cd(PO3)2, Fe2Pb3(PO4)2, CdS, and PbS precipitation in the solution/soil, iii) increases in the Ca2P and FeP contents in the radish rhizosphere, and iv) the promotion of bacterial community enrichment toward phosphorus-solubilizing and plant growth-promoting properties (Ramlibacter, Enterobacter, Bacillus, Gemmatimonas, and Lysinibacillusin) in the radish rhizosphere. These results provide bacterial resources and technical approaches to heavy metal pollution amelioration and efficient phosphorus fertilizer use in farmland.

Plants that are pharmacologically significant require intensive phytochemical characterization for bioactive profiling of the compounds, which has enabled their safe use in ayurvedic medicine. The present study is focused on the phytochemical analyses, quantitative estimation and profiling of secondary metabolites of leaf extract, as well as the antioxidant and cytotoxic activity of the potent halophytes such as Avicennia marina, Ceriops tagal, Ipomoea pes-caprae, and Sonneratia apetala. The in vitro antioxidant property was investigated using DPPH, ferric reducing antioxidant capacity (FRAP) assay. Bioactive compounds such as phenols, flavonoids, saponin and alkaloids were quantitatively estimated from the extracts of A.marina, C.tagal, I.pes-capra and S.apetala, which possessed higher phenol content than the other studied halophytes. The extracts at 200 µg/ml revealed higher antioxidant activity than the standard ascorbic acid and it functions as a powerful oxygen free radical scavenger with 77.37%, 75.35% and 72.84% for S.apetala, I.pes-caprae and C.tagal respectively and with least IC50 for I.pes-caprae (11.95 µg/ml) followed by C.tagal (49.94 µg/ml). Cell viability and anti-proliferative activity of different polyphenolic fractions of C.tagal (CT1 and CT2) and I.pes-caprae fraction (IP) against LN229, SNB19 revealed Ipomoea as the promising anti-cytotoxic fraction. IP-derived polyphenols was further subjected to apoptosis, migration assay, ROS and caspase - 3 and - 7 to elucidate its potentiality as a therapeutic drug. IP-polyphenols was found to have higher percentage of inhibition than the CT1 and CT2 polyphenols of C.tagal on comparison with TMZ. All the above-mentioned in-vitro analysis further validated the ability of IP-polyphenols inducing cell death via ROS-mediated caspase dependent pathway. Further, proteomic and phospho-proteomic analysis revealed the potential role of IP-polyphenols in the regulation of cell proliferation through MMK3, p53, p70 S6 kinase and RSK1 proteins involved in mitogen-activated protein kinase signaling pathway. Our analysis confirmed the promising role of I.pes-caprae derived polyphenols as an anti-metastatic compound against GBM cells.

The rapid softening of hardy kiwifruit (Actinidia arguta) fruit significantly reduces its marketing potential. Therefore, the effect of 1-methylcyclopropene (1-MCP) on the softening of A. arguta fruit was investigated. Results indicated that A. arguta fruit treated with 1-MCP maintained a higher level of firmness, titratable acidity, ascorbic acid, total phenolics, and flavonoids content, relative to non-treated fruit. Fruit treated with 1-MCP and placed in long-term cold storage had higher sensory scores, as determined by a taste panel and supported by electronic nose and tongue data. Notably, 1-MCP delayed the degradation of cell wall components, including pectin, cellulose, and hemicellulose, by reducing the activity of cell-wall-modifying enzymes. In addition, 1-MCP reduced the activity of carbohydrate metabolism-related enzymes, resulting in fruit with higher levels of starch and sucrose and lower levels of glucose, fructose and sorbitol. Collectively, these results indicate that 1-MCP can be used to delay the softening of A. arguta fruit and extend its storage and shelf life.

This article presents a novel and selective electrochemical bioassay with antibody and laccase for the determination of free thyroid hormone (free triiodothyronine, fT3). The biosensor was based on a glassy carbon electrode modified with a Fe3O4@graphene nanocomposite with semiconducting properties, an antibody (anti-PDIA3) with high affinity for fT3, and laccase, which was responsible for catalyzing the redox reaction of fT3. The electrode modification procedure was investigated using a cyclic voltammetry technique, based on the response of the peak current after modifications. All characteristic working parameters of the developed biosensor were analyzed using differential pulse voltammetry. Obtained experimental results showed that the biosensor revealed a sensitive response to fT3 in a concentration range of 10-200 µM, a detection limit equal to 27 nM, and a limit of quantification equal to 45.9 nM. Additionally, the constructed biosensor was selective towards fT3, even in the presence of interference substances: ascorbic acid, tyrosine, and levothyroxine, and was applied for the analysis of fT3 in synthetic serum samples with excellent recovery results. The designed biosensor also exhibited good stability and can find application in future medical diagnostics.

Pancreatic cancer (PC) is one of the most aggressive solid malignancies with poor treatment response and low survival rates. Herbal medicines such as betulinic acid (BA) have shown potential in treating various solid tumours, but with limitations that can be circumvented by polymer-drug conjugation. Polyethylene glycol-BA (PEG-BA) polymer-drug conjugate has previously shown selective anticancer activity against PC cells. Here, we elucidate the mechanism of cell death and the cell death pathway, anti-inflammatory and antioxidant activities of PEG-BA. PEG-BA induced apoptotic cell death by arresting MIA-PaCa-2 cells in the Sub-G1 phase of the cell cycle compared with BA and untreated cells (39.50 ± 5.32% > 19.63 ± 4.49% > 4.57 ± 0.82%). NFκB/p65 protein expression was moderately increased by PEG-BA (2.70 vs. 3.09 ± 0.42 ng/mL; p = 0.1521). However, significant (p < 0.05) overexpression of the proapoptotic genes TNF (23.72 ± 1.03) and CASPASE 3 (12,059.98 ± 1.74) compared with untreated cells was notable. The antioxidant potential of PEG-BA was greater (IC50 = 15.59 ± 0.64 µM) compared with ascorbic acid (25.58 ± 0.44 µM) and BA-only (>100 µM) and further confirmed with the improved reduction of hydroperoxide levels compared with BA-only (518.80 ± 25.53 µM vs. 542.43 ± 9.70 µM). In conclusion, PEG-BA activated both the intrinsic and extrinsic pathways of apoptosis and improved antioxidant activities in PC cells, suggesting enhanced anticancer activity upon conjugation.

The management of food waste and by-products has become a challenge for the agri-food sector and an example are whey by-products produced in dairy industries. Seeking other whey valorisation alternatives and applications, whey protein films for food packaging applications were developed in this study. Films containing different amounts (0, 5, 10, and 15 wt%) of ascorbic acid were manufactured via compression-moulding and their physicochemical, thermal, barrier, optical, and mechanical properties were analysed and related to the film structure. Additionally, the environmental assessment of the films was carried out to analyse the impact of film manufacture. Regarding physicochemical properties, both FTIR and water uptake analyses showed the presence of non-covalent interactions, such as hydrogen bonding, between whey protein and ascorbic acid as band shifts at the 1500-1700 cm-1 region as well as a water absorption decrease from 380% down to 240% were observed. The addition of ascorbic acid notably improved the UV-Vis light absorbance capacity of whey protein films up to 500 nm, a relevant enhancement for protecting foods susceptible to UV-Vis light-induced lipid oxidation. In relation to the environmental assessment, it was concluded that scaling up film manufacture could lead to a reduction in the environmental impacts, mainly electricity consumption.