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Molecular autopsy is a very important tool in forensic toxicology. However, many determinants, such as co-medication and physiological parameters, should be considered for optimal results. These determinants could cause phenoconversion (PC), a discrepancy between the real metabolic profile after phenoconversion and the phenotype determined by the genotype. This study’s objective was to assess the PC of drug-metabolizing enzymes, namely CYP2D6, 2C19, and 3A4, in 45 post-mortem cases where medications that are substrates, inducers, or inhibitors of these enzymes were detected. It also intended to evaluate how PC affected the drug’s metabolic ratio (MR) in four cases. Blood samples from 45 cases of drug-related deaths were analyzed to detect and determine drug and metabolite concentrations. Moreover, all the samples underwent genotyping utilizing the HaloPlex Target Enrichment System for CYP2D6, 2C19, and 3A4. The results of the present study revealed a statistically significant rate of PC for the three investigated enzymes, with a higher frequency of poor metabolizers after PC. A compatibility was seen between the results of the genomic evaluation after PC and the observed MRs of venlafaxine, citalopram, and fentanyl. This leads us to focus on the determinants causing PC that may be mainly induced by drug interactions. This complex phenomenon can have a significant impact on the analysis, interpretation of genotypes, and accurate conclusions in forensic toxicology. Nevertheless, more research with more cases in the future is needed to confirm these results.

The prevalence of multidrug-resistant (MDR) bacteria has recently increased dramatically, seriously endangering human health. Herein, amoxicillin (Amoxi)-conjugated gold nanoparticles (AuNPs) were created as a novel drug delivery system to overcome MDR bacteria. MDR bacteria were isolated from a variety of infection sources. Phenotype, biotype, and 16S rRNA gene analyses were used for isolate identification. Additionally, Juniperus excelsa was used for the production of AuNPs. The conjugation of AuNPs with Amoxi using sodium tri-polyphosphate (TPP) as a linker to produce Amoxi-TPP-AuNPs was studied. The AuNP and Amoxi-TPP-AuNP diameters ranged from 15.99 to 24.71 nm, with spherical and hexagonal shapes. A total of 83% of amoxicillin was released from Amoxi-TPP-AuNPs after 12 h, and after 3 days, 90% of the medication was released. The Amoxi-TPP-AuNPs exhibited superior antibacterial effectiveness against MRSA and MDR E. coli strains. Amoxi-TPP-AuNPs had MICs of 3.6–8 µg mL−1 against the tested bacteria. This is 37.5–83 fold higher compared to values reported in the literature. Amoxi-TPP-AuNPs exhibit a remarkable ability against MRSA and E. coli strains. These results demonstrate the applicability of Amoxi-TPP-AuNPs as a drug delivery system to improve therapeutic action.

Lead (Pb), mercury (Hg), and cadmium (Cd) are identified as potent developmental neurotoxicants. Neonates are the main group receiving multiple blood transfusions. The exposure of neonates to these heavy metals (HMs) can occur through blood transfusions. This study aimed to determine the concentrations of lead (Pb), mercury (Hg), and cadmium (Cd) in various blood products (plasma, platelets, packed red blood cells (pRBCs), and whole blood (WB)) to explore the probability of concurrent exposure of these HMs and to identify the metal load per transfusion with risk assessment. Residual bloods from blood bank bags were collected after neonatal transfusion. Pb, Hg, and Cd concentrations were determined in 120 samples of blood products by inductively coupled plasma mass spectrometry (ICP-MS). Pb and Cd levels were over the normal levels in 19.2 and 5.9% of all blood units, respectively. In 35 and 0.8% of blood units, the Pb and Cd concentrations, respectively, were higher than that recommended for transfusions in premature neonates. The anticipated safe value was surpassed by 2.5% for Cd of all transfusions, primarily because of WB. However, Hg was detected only in 5.8% of all samples and their concentrations were within the normal range. The concurrent neonatal exposure to Pb, Hg, and Cd was statistically significant. Hazard quotients of Hg and Cr were >1 and Pb cancer risk was 2.41 × 10−4. To the best of our knowledge, this study is the first report examining Pb, Hg, and Cd in blood products other than WB and pRBCs using ICP-MS. This study demonstrated the exposure of neonates to Pb, Hg, and Cd during transfusion with a considerable amount of Pb. It confirms the significant concurrent exposure to the three HMs, which maximize their potential developmental neurotoxicity with a high probability of developing non-carcinogenic and carcinogenic health effects.

Colon cancer is a major cause of cancer-related death, with significantly increasing rates of incidence worldwide. The current study was designed to evaluate the anti-carcinogenic effects of hesperetin (HES) alone and in combination with capecitabine (CAP) on 1,2 dimethylhydrazine (DMH)-induced colon carcinogenesis in Wistar rats. The rats were given DMH at 20 mg/kg body weight (b.w.)/week for 12 weeks and were orally treated with HES (25 mg/kg b.w.) and/or CAP (200 mg/kg b.w.) every other day for 8 weeks. The DMH-administered rats exhibited colon-mucosal hyperplastic polyps, the formation of new glandular units and cancerous epithelial cells. These histological changes were associated with the significant upregulation of colon Ki67 expression and the elevation of the tumor marker, carcinoembryonic antigen (CEA), in the sera. The treatment of the DMH-administered rats with HES and/or CAP prevented these histological cancerous changes concomitantly with the decrease in colon-Ki67 expression and serum-CEA levels. The results also indicated that the treatments with HES and/or CAP showed a significant reduction in the serum levels of lipid peroxides, an elevation in the serum levels of reduced glutathione, and the enhancement of the activities of colon-tissue superoxide dismutase, glutathione reductase and glutathione-S-transferase. Additionally, the results showed an increase in the mRNA expressions of the anti-inflammatory cytokine, IL-4, as well as the proapoptotic protein, p53, in the colon tissues of the DMH-administered rats treated with HES and/or CAP. The TGF-β1 decreased significantly in the DMH-administered rats and this effect was counteracted by the treatments with HES and/or CAP. Based on these findings, it can be suggested that both HES and CAP, singly or in combination, have the potential to exert chemopreventive effects against DMH-induced colon carcinogenesis via the suppression of oxidative stress, the stimulation of the antioxidant defense system, the attenuation of inflammatory effects, the reduction in cell proliferation and the enhancement of apoptosis.

The oxidation of food emulsions causes rancidity, which reduces their shelf life. To prevent rancidity, synthetic antioxidants are widely used in the food industry. However, due to their potential health risks, researchers are exploring natural alternatives. This study aimed to investigate whether Rosa canina fruit extract (RCFE) could be used as a natural antioxidant to extend the shelf life of mayonnaise. Mayonnaise containing varying concentrations of RCFE [0.125% (T1), 0.25% (T2), 0.50% (T3), 0.75% (T4)] was compared to a mayonnaise control sample (C1) and a mayonnaise sample containing 0.02% BHT (C2) for 60 days of storage at 4 °C. RCFE was found to have high levels of total phenols content (52.06 ± 1.14 mg GAE g−1), total flavonoids content (26.31 ± 1.03 mg QE g−1), and free radical scavenging activity. The GC–MS analysis of RCFE revealed 39 different peaks, whereas the HPLC analysis showed the presence of 13 polyphenolic compounds in RCFE. The pH values of T2, T3, and T4 mayonnaise samples substantially declined as storage progressed; however, the reduction was less than that of C1 and C2. After 60 days, mayonnaise samples T2, T3, and T4 had greatly reduced peroxide and free fatty acid levels compared to C1 and C2. The mayonnaise enriched with RCFE (T3 and T4) had the most potent antioxidative ability and the lowest value of lipid hydroperoxides (peroxide value, POV) and the lowest value of thiobarbituric-acid-reactive substances (TBARS). The sensory evaluation revealed that the T3 sample exhibited the highest overall acceptability. In conclusion, this study recommends that RCFE could be used as a natural preservative to enhance the shelf life of functional foods.

To date, the effectiveness of COVID-19 vaccines and booster doses has yet to be evaluated in longitudinal head-to-head studies. This single-center longitudinal study assessed the effectiveness of ChAdOx1 nCoV-19, BNT162b2, and mRNA-1273 vaccines and assessed two BNT162b2 boosters in 1550 participants, of whom 26% had comorbidities. In addition, the SARS-CoV-2 antibody dynamics was monitored. A group of 1500 unvaccinated subjects was included as the controls. The study’s endpoint was the development of virologically-proven COVID-19 cases after vaccine completion, while the secondary endpoint was hospitalizations due to severe COVID-19. Overall, 23 (4.6%), 16 (3%), and 18 (3.8%) participants vaccinated with ChAdOx1 nCoV-19, BNT162b2, and mRNA-1273, respectively, developed COVID-19 after vaccine completion, with an effectiveness of 89%, 92%, and 90%. Ten COVID-19 cases were reported in participants with comorbidities, three of whom were hospitalized. No hospitalizations occurred after boosters. SARS-CoV-2 antibody levels peaked 2–4 weeks after the second vaccine dose but declined after a mean of 28.50 ± 3.48 weeks. Booster doses significantly enhanced antibody responses. Antibody titers ≤ 154 U/mL were associated with a higher risk of COVID-19 emergence. Thus, COVID-19 vaccines effectively reduced COVID-19 and prevented severe disease. The vaccine-induced SARS-CoV-2 antibody responses declined after 28–32 weeks. Booster doses induced significant maintained responses. SARS-CoV-2 antibody levels may help determine the timing and need for vaccine booster doses.

Paratuberculosis (PTB) has been reported in the Sudan in cattle and goats for more than 50 years but has never been reported in sheep. However, suspicion of the disease in a breeding flock of sheep in Khartoum North locality was made due to a history of unknown cause of loss of weight. Blood and faecal samples were collected from all animals (N = 59): harvested sera were tested for anti-Mycobacterium avium subsp. paratuberculosis (MAP) antibodies by Enzyme Linked Immunosorbent Assay (ELISA); faeces were screened for acid-fast bacilli by Ziehl–Neelsen staining, tested for MAP DNA by recombinase polymerase amplification (RPA) and some faecal samples were cultured for MAP isolation. Typical MAP acid-fast bacilli were seen in 10.2% (6/59) of the faecal smears, 37.5% of the tested faecal samples (12/32) were positive for MAP DNA and only 3 (5.1%) animals were seropositive for MAP. MAP positive cultures were obtained from 2 out the 6 samples showing typical MAP acid-fast bacilli; the isolates were confirmed by real-time PCR and sequencing. As sheep are animals of utmost economic importance as the main export animals for the country, this first report of ovine PTB warrants special considerations and more investigations for planning control programmes of the disease.

Research on adolescent substance use is of utmost importance. Using local toxicological data, both prevalence and pattern of substance use (SU) and substance-related death (SRD) can be assessed to design effective prevention programs. A retrospective study of toxicology investigations of all adolescents referred to the medico-legal section of the Toxicology Unit of the University Hospital of Lille, France, for a 2-year period from 2017 to 2018. In the total sample of 1961 cases, adolescents accounted for 3.3% of the cases (n = 65). Among the adolescents, 16.9% were aged 10–14 years and 83.1% were aged >14–19 years. About 69.2% were males. Less than 70% of all presented adolescents used substances. More than two-thirds (74%) of positive detections were male. Illicit substances (43%) were the most detected substance followed by alcohol (20%) and prescription substances (20%). Tetrahydrocannabinol (THC) was extremely common as it was found in 29% of all adolescents. Cocaine and amphetamines were detected in 13.8% of total tested adolescents. Polysubstance use was common between alcohol and THC and among males. About one-third of deaths were due to substance use. About 54% of SRD was associated with polysubstance detection. It is recommended that illicit substances, ethanol, and prescription substances are targeted for testing among adolescents in order to provide appropriate prevention.

Caries lesions during cement repairs are a severe issue, and developing a unique antimicrobial restorative biomaterial can help to reduce necrotic lesion recurrence. As a result, Thymus vulgaris extract was used to biosynthesize copper nanoparticles (TVE-CuNPs) exhibiting different characteristics (TVE). Along with TVE-CuNPs, commercial silver nanoparticles (AgNPs) and metronidazole were combined with glass ionomer cement (GIC) to test its antibacterial efficacy and compressive strength. FTIR, XRD, UV-Vis spectrophotometry, and TEM were applied to characterize the TVE-CuNPs. Additionally, AgNPs and TVE-CuNPs were also combined with metronidazole and GIC. The modified GIC samples were divided into six groups, where groups 1 and 2 included conventional GIC and GIC with 1.5% metromidazole, respectively; group 3 had GIC with 0.5% TVE-CuNPs, while group 4 had 0.5% TVE-CuNPs with metronidazole in 1.5%; group 5 had GIC with 0.5% AgNPs, and group 6 had 0.5% AgNPs with metronidazole at 1.5%. An antimicrobial test was performed against Staphylococcus aureus (S. aureus) and Streptococcus mutans (S. mutans) by the disc diffusion method and the modified direct contact test (MDCT). GIC groups 4 and 6 demonstrated a greater antimicrobial efficiency against the two tested strains than the other groups. In GIC groups 4 and 6, the combination of GIC with two antimicrobial agents, 1.5% metronidazole and 0.5% TVE-CuNPs or AgNPs, enhanced the antimicrobial efficiency when compared to that of the other groups with or without a single agent. GIC group specimens combined with nanosilver and nanocopper had similar mean compressive strengths when compared to the other GIC groups. Finally, the better antimicrobial efficacy of GIC boosted by metronidazole and the tested nanoparticles against the tested strains may be relevant for the future creation of more efficient and modified restorations to reduce dental caries lesions.

In the present study, Zingiber officinale is used for the synthesis of Zingiber officinale capped silver nanoparticles (ZOE-AgNPs) and compares the antimicrobial efficacy and compressive strength of conventional glass ionomer cement (GIC) combined with ZOE-AgNPs, lyophilized miswak, and chlorhexidine diacetate (CHX) against oral microbes. Five groups of the disc-shaped GIC specimens were prepared. Group A: lyophilized miswak and GIC combination, Group B: ZOE-AgNPs and GIC combinations, Group C: CHX and GIC combination, Group D: ZOE-AgNPs + CHX + GIC; Group E: Conventional GIC. Results confirmed the successful formation of ZOE-AgNPs that was monitored by UV-Vis sharp absorption spectra at 415 nm. The X-ray diffractometer (XRD) and transmission electron microscope (TEM) results revealed the formation of ZOE-AgNPs with a mean size 10.5–14.12 nm. The peaks of the Fourier transform infrared spectroscopy (FTIR) were appearing the involvement of ZOE components onto the surface of ZOE-AgNPs which played as bioreducing, and stabilizing agents. At a 24-h, one-week and three-week intervals, Group D showed the significantly highest mean inhibitory zones compared to Group A, Group B, and Group C. At microbe-level comparison, Streptococcus mutans and Staphylococcus aureus were inhibited significantly by all the specimens tested except group E when compared to Candida albicans. Group D specimens showed slightly higher (45.8 ± 5.4) mean compressive strength in comparison with other groups. The combination of GIC with ZOE-AgNPs and chlorhexidine together enhanced its antimicrobial efficacy and compressive strength compared to GIC with ZOE-AgNPs or lyophilized miswak or chlorhexidine combination alone. The present study revealed that The combination of GIC with active components of ZOE-AgNPs and chlorhexidine paves the way to lead its effective nano-dental materials applications.

Paratuberculosis (PTB) is a contagious and chronic enteric disease of ruminants and many non-ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP), and is characterised by diarrhoea and progressive emaciation with consequent serious economic losses due to death, early culling, and reduced productivity. In addition, indirect economic losses may arise from trade restrictions. Besides being a production limiting disease, PTB is a potential zoonosis; MAP has been isolated from Crohn’s disease patients and was associated with other human diseases, such as rheumatoid arthritis, Hashimoto’s thyroiditis, Type 1 diabetes, and multiple sclerosis. Paratuberculosis in sheep and goats may be globally distributed though information on the prevalence and economic impact in many developing countries seem to be scanty. Goats are more susceptible to infection than sheep and both species are likely to develop the clinical disease. Ingestion of feed and water contaminated with faeces of MAP-positive animals is the common route of infection, which then spreads horizontally and vertically. In African countries, PTB has been described as a “neglected disease”, and in small ruminants, which support the livelihood of people in rural areas and poor communities, the disease was rarely reported. Prevention and control of small ruminants’ PTB is difficult because diagnostic assays demonstrate poor sensitivity early in the disease process, in addition to the difficulties in identifying subclinically infected animals. Further studies are needed to provide more insight on molecular epidemiology, transmission, and impact on other animals or humans, socio-economic aspects, prevention and control of small ruminant PTB.

Polyhydroxybutyrates (PHBs) are macromolecules synthesized by bacteria. Because of their fast degradability under natural environmental conditions, PHBs were selected as alternatives for the production of biodegradable plastics. Sixteen PHB-accumulating strains were selected and compared for their ability to accumulate PHB granules inside their cells. Isolate AS-02 was isolated from cattle manure and identified as Bacillus wiedmannii AS-02 OK576278 by means of 16S rRNA analysis. It was found to be the best producer. The optimum pH, temperature, and incubation period for the best PHB production by the isolate were 7, 35 °C, and 72 h respectively. PHB production was the best with peptone and glucose as nitrogen and carbon sources at a C/N ratio of (2:1). The strain was able to accumulate 423, 390, 249, 158, and 144 mg/L PHB when pretreated orange, mango, banana, onion peels, and rice straw were used as carbon sources, respectively. The extracted polymer was characterized by Fourier transform infrared (FTIR), nuclear magnetic resonance (NMR), and GC-MS spectroscopy, which confirmed the structure of the polymer as PHB. The isolate B. wiedmannii AS-02 OK576278 can be considered an excellent candidate for industrial production of PHB from agricultural wastes.

Dental caries results from the bacterial pathogen Streptococcus mutans (S. mutans) and is the maximum critical reason for caries formation. Consequently, the present study aims to evaluate the antibacterial activity of a newly synthesized nanoantibiotic–Biodentine formulation. The silver nanoparticles (ROE-AgNPs) were biosynthesized from the usage of Rosmarinus officinalis L. extract (ROE) and conjugated with cefuroxime to form Cefuroxime-ROE-AgNPs. Using Biodentine™ (BIOD), five groups of dental materials were prepared, in which Group A included conventional BIOD, Group B included BIOD with ROE-AgNPs, Groups C and D included BIOD with Cefuroxime-ROE-AgNPs at concentrations of 0.5% and 1.5% cefuroxime, respectively, and Group E included BIOD with 1.5% cefuroxime. The synthesized ROE-AgNPs or Cefuroxime-ROE-AgNPs were characterized for conjugating efficiency, morphology, particle size, and in vitro release. Minimum inhibitory concentration (MIC) of the cefuroxime, ROE-AgNPs, and Cefuroxime-ROE-AgNPs were additionally evaluated against cefuroxime resistant S. mutans, which furthered antibacterial efficacy of the five groups of dental materials. The UV-Visible spectrum showed the ROE-AgNPs or Cefuroxime-ROE-AgNPs peaks and their formation displayed through transmission electron microscopy (TEM), X-ray diffraction (XRD) pattern, and Fourier transforms infrared (FTIR) analysis. The end result of Cefuroxime-ROE-AgNPs showed conjugating efficiency up to 79%. Cefuroxime-ROE-AgNPs displayed the highest antibacterial efficacy against S. mutans as compared to cefuroxime or ROE-AgNPs alone. Moreover, the MIC of ROE-AgNPs and Cefuroxime-ROE-AgNPs was detected against S. mutans to be 25 and 8.5 μg/mL, respectively. Consequently, Cefuroxime-ROE-AgNPs displayed that a decrease in the MIC reached to more than three-fold less than MIC of ROE-AgNPs on the tested strain. Moreover, Cefuroxime-ROE-AgNPs/BIOD was employed as a novel dental material that showed maximum antimicrobial activity. Groups C and D of novel materials showed inhibitory zones of 19 and 26 mm, respectively, against S. mutans and showed high antimicrobial rates of 85.78% and 91.17%, respectively. These data reinforce the utility of conjugating cefuroxime with ROE-AgNPs to retrieve its efficiency against resistant S. mutant. Moreover, the nanoantibiotic delivered an advantageous antibacterial effect to BIOD, and this may open the door for future conjugation therapy of dental materials against bacteria that cause dental caries.

Paratuberculosis, caused by Mycobacterium avium subspecies paratuberculosis (MAP), is a chronic wasting disease mainly of domestic and wild ruminants. It occurs worldwide, causing significant economic losses through decreased productivity, low fertility, increased cull rates and mortality. It is listed by the OIE (World Organization for Animal Health) as a disease of concern to trade in animals. Prevalence of this disease can be studied by detecting anti-MAP antibodies by Enzyme linked immunosorbent Assay (ELISA). The aim of this study was to investigate the current prevalence of MAP infection in cattle in Khartoum State. The overall apparent prevalence of MAP infection was found to be 6.3% and 18.9% at animal and herd levels, respectively. All seropositive animals were cross-bred females of good body condition; most of them (>90%) were >3 years old and >50% were from medium-sized herds in Omdurman. No significant association (p > 0.05) was found between seropositivity and animal herd size. The prevalence of MAP infection in Khartoum State is still low to medium compared to other parts of the world, but it is comparable to those reported from other African countries. Further studies with the view of designing nationwide surveys in domestic ruminants and camels in other states of the country are needed for establishing control programmes.

One of the challenges in the preparation of poly(methyl methacrylate) (PMMA) is to develop new catalytic systems with improved efficiency. A hybrid iron oxide silver catalyst holds promise in solving this issue. Catalysts were prepared at room temperature by a two-step technique. First, iron oxide nanoparticles were prepared by the reduction of FeCl3 using sodium borohydride (NaBH4) at room temperature. Second, magnetic nanoparticles doped with a series of Ag nanoparticles (Ag, Ag/3 –amino propyltriethoxysilane (APTES) and Ag/poly(ethyleneimine) (PEI)). The prepared catalysts were characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), dynamic light scattering (DLS), scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDX), and Fourier-transform infrared spectroscopy (FTIR). The catalytic activity of Fe, Ag/Fe, PEI–Ag/Fe, and APTES–Ag/Fe in methyl methacrylate (MMA) polymerization was investigated in the presence of O2, N2, NaHSO3, and benzoyl peroxide in bulk or solution conditions. The produced polymer was characterized by gel permeation chromatography (GPC) and proton nuclear magnetic resonance spectroscopy (1HNMR). The structures of PEI–Ag/Fe and APTES–Ag/Fe are assumed. The conversion efficiency was 100%, 100%, 97.6%, and 99.1% using Fe, Ag/Fe, PEI–Ag/Fe, and APTES–Ag/Fe catalysts at the optimum conditions, respectively. Hybrid iron oxide silver nanoparticles are promising catalysts for PMMA preparation.

Chiral pincer complexes, characterized by their rigid tridentate coordination framework, have emerged as powerful catalysts in asymmetric synthesis. This review provides a comprehensive overview of recent advancements in the development of chiral pincer-type ligands and their corresponding transition metal complexes. We highlight the latest progress in their application across a range of catalytic asymmetric reactions, including the (transfer) hydrogenation of polar and non-polar bonds, hydrophosphination, alkynylation, Friedel-Crafts reactions, enantioselective reductive cyclization of alkynyl-tethered cyclohexadienones, enantioselective hydrosilylation, as well as Aza–Morita–Baylis–Hillman reactions. The structural rigidity and tunability of chiral pincer complexes enable precise control over stereoselectivity, resulting in high enantioselectivity and efficiency in complex molecular transformations. As the field advances, innovations in ligand design and the exploration of new metal centers are expected to expand the scope and utility of these catalysts, bearing significant implications for the synthesis of enantioenriched compounds in pharmaceuticals, materials science, and beyond.

In recent years, extensive research has focused on cannabidiol (CBD), a well-studied non-psychoactive component of the plant-derived cannabinoids. CBD has shown significant therapeutic potential for treating various diseases and disorders, including antioxidants and anti-inflammatory effects. Due to the promising therapeutic effect of CBD in a wide variety of diseases, synthetic derivatization of this compound has attracted the attention of drug discovery in both industry and academia. In the current research, we focused on the derivatization of CBD by introducing Schiff base moieties, particularly (thio)-semicarbazide and aminoguanidine motifs, at the 3-position of the olivetolic ring. We have designed, synthesized, and characterized new derivatives based on CBD’s framework, specifically aminoguanylhydrazone- and (thio)-semicarbazones-CBD-aldehyde compounds. Their antioxidant potential was assessed using FRAP and DPPH assays, alongside an evaluation of their effect on LDL oxidation induced by Cu2+ and AAPH. Our findings suggest that incorporating the thiosemicarbazide motif into the CBD framework produces a potent antioxidant, warranting further investigation.

In recent years, research on mushrooms belonging to the Hericium genus has attracted considerable attention due to their unique appearance and well-known medicinal properties. These mushrooms are abundant in bioactive chemicals like polysaccharides, hericenones, erinacines, hericerins, resorcinols, steroids, mono- and diterpenes, and corallocins, alongside essential nutrients. These compounds demonstrate beneficial bioactivities which are related to various physiological systems of the body, including the digestive, immune, and nervous systems. Extensive research has been conducted on the isolation and identification of numerous bioactive chemicals, and both in vitro and in vivo studies have confirmed their antimicrobial, antioxidant, immunomodulatory, antidiabetic, anticholesterolemic, anticancer, and neuroprotective properties. Therefore, this review aims to provide a comprehensive summary of the latest scientific literature on the chemical composition and secondary metabolites profile of Hericium spp. through an introduction to their chemical characteristics, speculated biosynthesis pathways for key chemical families, potential toxicological aspects, and a detailed description of the recent updates regarding the bioactivity of these metabolites.

The current study examines the moderating role of R&D expenditures by the government on the relationship between entrepreneurship and per capita output in GCC countries. Using secondary quantitative data, panel data analysis was conducted for six GCC countries (Saudi Arabia, Kuwait, Oman, Bahrain, Qatar, and UAE) based on their scores on the Global Entrepreneurship Index, Ease of Doing Business, and R&D expenditure as a percentage of GDP. Descriptive statistics and regression analysis were conducted using Eviews 12. The study found that a supportive business environment and entrepreneurship ecosystem can lead to higher per capita output and that laboratory force and capital are significant positive contributors to per capita output. However, both Ease of Doing Business and the Global Entrepreneurship Index have a significant negative impact on per capita output. The study did not find significant moderation of the relationship between entrepreneurship and per capita output by R&D expenditures. These findings have important implications for policy-makers and academia, emphasizing the significant labour force and capital for per capita output. Future research should explore the relationship between entrepreneurship and growth further and investigate the role of R&D. Policy recommendations include reducing regulatory burdens and providing tax incentives to create a supportive environment for entrepreneurship and increasing R&D funding to promote per capita output. Overall, this study contributes to the state of the art through examining the moderating role of R&D expenditures on the relationship between entrepreneurship and per capita output in the context of GCC countries.

Yttrium-doped barium zirconate is one of the fastest solid-state proton conductors. While previous studies suggest that proton–tuples move as pairs in yttrium-doped barium zirconate, a systematic catalog of possible close proton–tuple moves is missing. Such a catalog is essential to simulating dual proton conduction effects. Density functional theory with the Perdew–Burke–Ernzerhof functional is utilized to obtain the total electronic energy for each proton–tuple. The conjugate gradient and nudged elastic band methods are used to find the minima and transition states for proton–tuple motion. In the lowest-energy configuration, protons are in close proximity to each other and the dopant, significantly affecting the backbone structure. The map of moves away from the global minimum proton–tuple shows that the most critical move for long-range proton conduction is a rotation with a barrier range of 0.31–0.41 eV when the two protons are in close proximity.

Paraoxonase 1 (PON1) plays a role in regulating reverse cholesterol transport and has antioxidative, anti-inflammatory, antiapoptotic, vasodilative, and antithrombotic activities. Scientists are currently focused on the modulation of PON1 expression using different pharmacological, nutritional, and lifestyle approaches. We previously isolated a novel active compound from Nannochloropsis microalgae—lyso-diacylglyceryltrimethylhomoserine (lyso-DGTS)—which increased PON1 activity, HDL-cholesterol efflux, and endothelial nitric oxide release. Here, to explore this important lipid moiety’s effect on PON1 activities, we examined the effect of synthesized lipid derivatives and endogenous analogs of lyso-DGTS on PON1 lactonase and arylesterase activities and LDL oxidation using structure–activity relationship (SAR) methods. Six lipids significantly elevated recombinant PON1 (rePON1) lactonase activity in a dose-dependent manner, and four lipids significantly increased rePON1 arylesterase activity. Using tryptophan fluorescence-quenching assay and a molecular docking method, lipid–PON1 interactions were characterized. An inverse correlation was obtained between the lactonase activity of PON1 and the docking energy of the lipid–PON1 complex. Furthermore, five of the lipids increased the LDL oxidation lag time and inhibited its propagation. Our findings suggest a beneficial effect of lyso-DGTS or lyso-DGTS derivatives through increased PON1 activity and prevention of LDL oxidation.

Covalent binding between nitric oxide (NO) and a protein’s free thiol group (SH) is termed protein S-nitrosylation. Protein S-nitrosylation is involved in cellular regulation mechanisms that underlie a wide range of critical functions, such as apoptosis, alteration of enzyme activities, and transcription-factor stability. Impaired protein S-nitrosylation is associated with a growing list of pathophysiological conditions, such as cardiovascular disease, multiple sclerosis, pulmonary hypertension, and sickle cell disease. The enzyme paraoxonase 1 (PON1) binds to high-density lipoprotein to provide many of its antiatherogenic properties. The enzyme has a strong antioxidant capacity, which protects fats, lipids, and lipoproteins from oxidation, in addition to breaking down oxidized fats. We investigated the effect of S-S transnitrosylation on PON1 activities. Incubation of recombinant PON1 (rePON1) with nitrosylated human serum albumin (HSA-NO) resulted in S-nitrosylation of about 70% of the rePON1, as measured by Q-TOF LC/MS. S-nitrosylation significantly increased rePON1 hydrolytic activities. It also increased rePON1’s ability to inhibit low-density lipoprotein oxidation induced by Cu2+. Finally, it increased the enzyme’s penetration into macrophage cells by 31%. Our findings suggest that S-nitrosylation of rePON1 improves its biological functions which may positively affect atherosclerosis disease progression.

Background: Stipa tenacissima L. (S. tenacissima), called Esparto grass, is a cultivated species used for industrial purposes, including textile production. This species has never been studied for its medical potential before, nor has it been used in traditional medicines. It is thus fitting that the present study aimed to investigate the pharmacological potential of S. tenacissima. To achieve this goal, this work was conducted to study the chemical composition, antioxidant properties, and antiproliferative effects of S. tenacissima against cancerous cell lines, including the human colorectal adenocarcinoma cell line (HT-29) and human breast adenocarcinoma cell line (MDA-MB-231). Fractionation and characterization of S. tenacissima extract showed the presence of promising bioactive fractions. The fractions obtained from S. tenacissima extract exhibited interesting antioxidant properties, with IC50 values ranging from 1.26 to 1.85 mg/mL. All fractions, such as F1, F2, F3, and F4, induced an important antiproliferative effect on the cancer cell lines MDA-MB-231, scoring IC50 values ranging from 63.58 ± 3.14 to 99.880 ± 0.061 µg/mL. These fractions (F1, F2, F3, and F4) also exhibited a potent antiproliferative effect versus HT-29 cell lines, with IC50 values ranging from 71.50 ± 4.97 to 87.500 ± 1.799 µg/mL. Therefore, S. tenacissima could constitute a new natural source of bioactive compounds that can be used for therapeutic purposes to fight cancer and free radical damage.

A review of quantitative risk assessment (QRA) models of Listeria monocytogenes in produce was carried out, with the objective of appraising and contrasting the effectiveness of the control strategies placed along the food chains. Despite nine of the thirteen QRA models recovered being focused on fresh or RTE leafy greens, none of them represented important factors or sources of contamination in the primary production, such as the type of cultivation, water, fertilisers or irrigation method/practices. Cross-contamination at processing and during consumer's handling was modelled using transfer rates, which were shown to moderately drive the final risk of listeriosis, therefore highlighting the importance of accurately representing the transfer coefficient parameters. Many QRA models coincided in the fact that temperature fluctuations at retail or temperature abuse at home were key factors contributing to increasing the risk of listeriosis. In addition to a primary module that could help assess current on-farm practices and potential control measures, future QRA models for minimally processed produce should also contain a refined sanitisation module able to estimate the effectiveness of various sanitisers as a function of type, concentration and exposure time. Finally, L. monocytogenes growth in the products down the supply chain should be estimated by using realistic time-temperature trajectories, and validated microbial kinetic parameters, both of them currently available in the literature.

Better knowledge regarding the Listeria monocytogenes dose-response (DR) model is needed to refine the assessment of the risk of foodborne listeriosis. In 2018, the European Food Safety Agency (EFSA) derived a lognormal Poisson DR model for 14 different age-sex sub-groups, marginally to strain virulence. In the present study, new sets of parameters are developed by integrating the EFSA model for these sub-groups together with three classes of strain virulence characteristics ("less virulent", "virulent", and "more virulent"). Considering classes of virulence leads to estimated relative risks (RRs) of listeriosis following the ingestion of 1000 bacteria of "less virulent" vs. "more virulent" strains ranging from 21.6 to 24.1, depending on the sub-group. These relatively low RRs when compared with RRs linked to comorbidities described in the literature suggest that the influence of comorbidity on the occurrence of invasive listeriosis for a given exposure is much more important than the influence of the virulence of the strains. The updated model parameters allow better prediction of the risk of invasive listeriosis across a population of interest, provided the necessary data on population demographics and the proportional contribution of strain virulence classes in food products of interest are available. An R package is made available to facilitate the use of these dose-response models.

Invasive listeriosis, due to its severe nature in susceptible populations, has been the focus of many quantitative risk assessment (QRA) models aiming to provide a valuable guide in future risk management efforts. A review of the published QRA models of Listeria monocytogenes in seafood was performed, with the objective of appraising the effectiveness of the control strategies at different points along the food chain. It is worth noting, however, that the outcomes of a QRA model are context-specific, and influenced by the country and target population, the assumptions that are employed, and the model architecture itself. Studies containing QRA models were retrieved through a literature search using properly connected keywords on Scopus and PubMed ® . All 13 QRA models that were recovered were of short scope, covering, at most, the period from the end of processing to consumption; the majority (85%) focused on smoked or gravad fish. Since the modelled pathways commenced with the packaged product, none of the QRA models addressed cross-contamination events. Many models agreed that keeping the product's temperature at 4.0-4.5 °C leads to greater reductions in the final risk of listeriosis than reducing the shelf life by one week and that the effectiveness of both measures can be surpassed by reducing the initial occurrence of L. monocytogenes in the product (at the end of processing). It is, therefore, necessary that future QRA models for RTE seafood contain a processing module that can provide insight into intervention strategies that can retard L. monocytogenes ' growth, such as the use of bacteriocins, ad hoc starter cultures and/or organic acids, and other strategies seeking to reduce cross-contamination at the facilities, such as stringent controls for sanitation procedures. Since risk estimates were shown to be moderately driven by growth kinetic parameters, namely, the exponential growth rate, the minimum temperature for growth, and the maximum population density, further work is needed to reduce uncertainties.

A review of the published quantitative risk assessment (QRA) models of L. monocytogenes in meat and meat products was performed, with the objective of appraising the intervention strategies deemed suitable for implementation along the food chain as well as their relative effectiveness. A systematic review retrieved 23 QRA models; most of them (87%) focused on ready-to-eat meat products and the majority (78%) also covered short supply chains (end processing/retail to consumption, or consumption only). The processing-to-table scope was the choice of models for processed meats such as chorizo, bulk-cooked meat, fermented sausage and dry-cured pork, in which the effects of processing were simulated. Sensitivity analysis demonstrated the importance of obtaining accurate estimates for lag time, growth rate and maximum microbial density, in particular when affected by growth inhibitors and lactic acid bacteria. In the case of deli meats, QRA models showed that delicatessen meats sliced at retail were associated with a higher risk of listeriosis than manufacture pre-packed deli meats. Many models converged on the fact that (1) controlling cold storage temperature led to greater reductions in the final risk than decreasing the time to consumption and, furthermore, that (2) lower numbers and less prevalence of L. monocytogenes at the end of processing were far more effective than keeping low temperatures and/or short times during retail and/or home storage. Therefore, future listeriosis QRA models for meat products should encompass a processing module in order to assess the intervention strategies that lead to lower numbers and prevalence, such as the use of bio-preservation and novel technologies. Future models should be built upon accurate microbial kinetic parameters, and should realistically represent cross-contamination events along the food chain.

A review of the published quantitative risk assessment (QRA) models of L. monocytogenes in dairy products was undertaken in order to identify and appraise the relative effectiveness of control measures and intervention strategies implemented at primary production, processing, retail, and consumer practices. A systematic literature search retrieved 18 QRA models, most of them (9) investigated raw and pasteurized milk cheeses, with the majority covering long supply chains (4 farm-to-table and 3 processing-to-table scopes). On-farm contamination sources, either from shedding animals or from the broad environment, have been demonstrated by different QRA models to impact the risk of listeriosis, in particular for raw milk cheeses. Through scenarios and sensitivity analysis, QRA models demonstrated the importance of the modeled growth rate and lag phase duration and showed that the risk contribution of consumers' practices is greater than in retail conditions. Storage temperature was proven to be more determinant of the final risk than storage time. Despite the pathogen's known ability to reside in damp spots or niches, re-contamination and/or cross-contamination were modeled in only two QRA studies. Future QRA models in dairy products should entail the full farm-to-table scope, should represent cross-contamination and the use of novel technologies, and should estimate L. monocytogenes growth more accurately by means of better-informed kinetic parameters and realistic time-temperature trajectories.

The foodborne disease burden (FBDB) related to 26 major biological hazards in France was attributed to foods and poor food-handling practices at the final food preparation step, in order to develop effective intervention strategies, especially food safety campaigns. Campylobacter spp. and non-typhoidal Salmonella accounted for more than 60% of the FBDB. Approximately 30% of the FBDB were attributed to 11 other hazards including bacteria, viruses and parasites. Meats were estimated as the main contributing food category causing (50-69%) (CI90) of the FBDB with (33-44%), (9-21%), (4-20%) (CI90) of the FBDB for poultry, pork and beef, respectively. Dairy products, eggs, raw produce and complex foods caused each approximately (5-20%) (CI90) of the FBDB. When foods are contaminated before the final preparation step, we estimated that inadequate cooking, cross-contamination and inadequate storage contribute for (19-49%), (7-34%) and (9-23%) (CI90) of the FBDB, respectively; (15-33%) (CI90) of the FBDB were attributed to the initial contamination of ready-to-eat foods-without any contribution from final food handlers. The thorough implementation of good hygienic practices (GHPs) at the final food preparation step could potentially reduce the FBDB by (67-85%) (CI90) (mainly with the prevention of cross-contamination and adequate cooking and storage).

Entomophagy has been part of human diets for a long time in a significant part of the world, but insects are considered to be a novel food everywhere else. It would appear to be a strategic alternative in the future of human diet to face the challenge of ensuring food security for a growing world population, using more environmentally sustainable production systems than those required for the rearing of other animals. Tenebrio molitor , called yellow mealworm, is one of the most interesting insect species in view of mass rearing, and can be processed into a powder that ensures a long shelf life for its use in many potential products. When considering insects as food or feed, it is necessary to guarantee their safety. Therefore, manufacturers must implement a Hazard Analysis Critical Control plan (HACCP), to limit risks for consumers' health. The aim of this case study was to develop a HACCP plan for Tenebrio molitor larvae powders for food in a risk-based approach to support their implementation in industry. Specific purposes were to identify related significant biological hazards and to assess the efficiency of different manufacturing process steps when used as Critical Control Points. Then, combinations of four different processes with four potential uses of powders by consumers in burger, protein shake, baby porridge, and biscuits were analyzed with regard to their safety.