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During the life activities of microorganisms, a variety of secondary metabolites are produced, including antimicrobials and antitumor drugs, which are widely used in clinical practice. In addition to exploring new antibiotics, this makes it one of the research priorities of Actinomycetes to effectively increase the yield of antibiotics in production strains by various means. Most antibiotic-producing strains have a variety of functional regulatory factors that regulate their growth, development, and secondary metabolite biosynthesis processes. Through the study of precursor substances in antibiotic biosynthesis, researchers have revealed the precursor biosynthesis process and the mechanism by which precursor synthesis regulators affect the biosynthesis of secondary metabolites, which can be used to obtain engineered strains with high antibiotic production. This paper summarizes the supply of antibiotic biosynthesis precursors and the progress of research on the role of regulators in the process of precursors in biosynthesis. This lays the foundation for the establishment of effective breeding methods to improve antibiotic yields through the manipulation of precursor synthesis genes and related regulators. [ABSTRACT FROM AUTHOR]

Particulate amorphous solid dispersions (ASDs) have been recognised for their potential to enhance the performance of various solid dose forms, especially oral bioavailability and macromolecule stability. However, the inherent nature of spray-dried ASDs leads to their surface cohesion/adhesion, including hygroscopicity, which hinders their bulk flow and affects their utility and viability in terms of powder production, processing, and function. This study explores the effectiveness of L-leucine (L-leu) coprocessing in modifying the particle surface of ASD-forming materials. Various contrasting prototype coprocessed ASD excipients from both the food and pharmaceutical industries were examined for their effective coformulation with L-leu. The model/prototype materials included maltodextrin, polyvinylpyrrolidone (PVP K10 and K90), trehalose, gum arabic, and hydroxypropyl methylcellulose (HPMC E5LV and K100M). The spray-drying conditions were set such that the particle size difference was minimised, so that it did not play a substantial role in influencing powder cohesion. Scanning electron microscopy was used to evaluate the morphology of each formulation. A combination of previously reported morphological progression typical of L-leu surface modification and previously unreported physical characteristics was observed. The bulk characteristics of these powders were assessed using a powder rheometer to evaluate their flowability under confined and unconfined stresses, flow rate sensitivities, and compactability. The data showed a general improvement in maltodextrin, PVP K10, trehalose and gum arabic flowability measures as L-leu concentrations increased. In contrast, PVP K90 and HPMC formulations experienced unique challenges that provided insight into the mechanistic behaviour of L-leu. Therefore, this study recommends further investigations into the interplay between L-leu and the physico-chemical properties of coformulated excipients in future amorphous powder design. This also revealed the need to enhance bulk characterisation tools to unpack the multifactorial impact of L-leu surface modification. [ABSTRACT FROM AUTHOR]

To evaluate the effects of donor ages on growth and stress resistance of 6-year-old seedlings propagated from 5-, 2000-, and 3000-year-old Platycladus orientalis donors with grafting, cutting, and seed sowing, growth indicators and physiological and transcriptomic analyses were performed in 6-year-old seedlings in winter. Results showed that basal stem diameters and plant heights of seedlings of the three propagation methods decreased with the age of the donors, and the sown seedlings were the thickest and tallest. The contents of soluble sugar, chlorophyll, and free fatty acid in apical leaves of the three propagation methods were negatively correlated with donor ages in winter, while the opposite was true for flavonoid and total phenolic. The contents of flavonoid, total phenolic, and free fatty acid in cutting seedlings were highest in the seedlings propagated in the three methods in winter. KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis of differentially expressed genes showed phenylpropanoid biosynthesis and fatty acid metabolism pathways, and their expression levels were up-regulated in apical leaves from 6-year-old seedlings propagated from 3000-year-old P. orientalis donors. In addition, hub genes analysis presented that C4H, OMT1, CCR2, PAL, PRX52, ACP1, AtPDAT2, and FAD3 were up-regulated in cutting seedlings, and the gene expression levels decreased in seedlings propagated from 2000- and 3000-year-old donors. These findings demonstrate the resistance stability of cuttings of P. orientalis and provide insights into the regulatory mechanisms of seedlings of P. orientalis propagated from donors at different ages in different propagation methods against low-temperature stress. [ABSTRACT FROM AUTHOR]

Dementia is characterized as a decline in cognitive function, including memory, language and problem-solving abilities. In this paper, we conducted a Genome-Wide Association Study (GWAS) using data from the electronic Medical Records and Genomics (eMERGE) network. This study has two aims, (1) to investigate the genetic mechanism of dementia and (2) to discuss multiple p-value thresholds used to address multiple testing issues. Using the genome-wide significant threshold ( p ≤ 5 × 10 − 8 ), we identified four SNPs. Controlling the False Positive Rate (FDR) level below 0.05 leads to one extra SNP. Five SNPs that we found are also supported by QQ-plot comparing observed p-values with expected p-values. All these five SNPs belong to the TOMM40 gene on chromosome 19. Other published studies independently validate the relationship between TOMM40 and dementia. Some published studies use a relaxed threshold ( p ≤ 1 × 10 − 5 ) to discover SNPs when the statistical power is insufficient. This relaxed threshold is more powerful but cannot properly control false positives in multiple testing. We identified 13 SNPs using this threshold, which led to the discovery of extra genes (such as ATP10A-DT and PTPRM). Other published studies reported these genes as related to brain development or neuro-development, indicating these genes are potential novel genes for dementia. Those novel potential loci and genes may help identify targets for developing new therapies. However, we suggest using them with caution since they are discovered without proper false positive control. [ABSTRACT FROM AUTHOR]

Simple Summary: Changes in prey biology driven by predation threats that do not involve direct consumption are referred to as non-consumptive effects (NCEs). In general, NCEs are considered common and can affect herbivores sometimes stronger than the direct consumptive effects. However, how the NCEs of predators affect the development, survival, fecundity, and population growth of prey has not been well documented, which is the primary consideration for the compatibility of prey with its natural enemies in agricultural ecosystems. We examined the NCEs of the predator Coccinella septempunctata on the life-history traits and population growth of Sitobion miscanthi via caged predator (i.e., S. miscanthi co-existed with caged C. septempunctata) and caged prey (i.e., C. septempunctata co-existed with caged S. miscanthi) treatments by employing the age-stage, two-sex life table. The findings indicate that S. miscanthi could respond to the predation risk of caged predators by either accelerating the developmental rate or reducing the net reproductive rate, while S. miscanthi might reduce their fitness in response to the predation risk of caged prey. Furthermore, S. miscanthi might also increase the number of winged morphs under both of the above treatments. The results have practical ramifications on managing this economically important pest on wheat production with reduced insecticide applications. How the non-consumptive effects (NCEs) of predators influence the development, survival, fecundity, and population growth of prey has not been well documented, which is the primary consideration for the compatibility of prey with its natural enemies in agricultural ecosystems. We herein employed the age-stage, two-sex life table to examine the NCEs of the predator Coccinella septempunctata on the life-history traits and population growth of prey Sitobion miscanthi via caged predator (prey co-existing with caged predator) and caged prey (predator co-existing with caged prey) treatments with daily different exposure times (i.e., 0 h (control), 12 h, and 24 h). The results indicated that the predation risk of a caged predator could reduce the first nymphal duration and net reproductive rate (R0) of S. miscanthi at 12 h, and the first nymphal duration, preadult duration, and mean generation time (T) at 24 h. However, the predation risk of the caged prey resulted in the prolongation of the pre-adult development time and total pre-reproductive period (TPRP) as well as lowered the intrinsic rate of increase (r), finite rate of increase (), R0, life expectancy, and reproductive value of S. miscanthi after both 12 h and 24 h. Furthermore, the predation risk of both the caged predator and caged prey could increase the percent of winged morph at 24 h. These findings indicate that S. miscanthi could respond to the predation risk of the caged predator by either accelerating the developmental rate or reducing the net reproductive rate, while S. miscanthi might reduce their fitness in response to the predation risk of caged prey. Furthermore, S. miscanthi might also alter to winged morphs for dispersal under both of the above treatments. The findings obtained have practical ramifications for managing this economically important pest in wheat production with reduced insecticide applications. [ABSTRACT FROM AUTHOR]

Regular monitoring of blood α-fetoprotein (AFP) and/or carcino-embryonic antigen (CEA) levels is important for the routine screening of liver cancer. However, AFP and CEA have a much lower specificity than des-γ-carboxyprothrombin (DCP) to detect liver cancer. Therefore, the study reported here was designed, to develop a screen-printed DCP immunosensor incorporating zinc oxide nanoparticles, for accurate determination of DCP. The designed immunosensor shows low detection limits for the detection of DCP: 0.440 ng/mL (based on impedance measurement), 0.081 ng/mL (based on real part of impedance measurement) and 0.078 ng/mL (based on imaginary part of impedance measurement), within the range of 3.125 ng/mL to 2000 ng/mL. In addition, there was little interference to DCP determination by molecules such as Na+, K+, Ca2+, Cl-, glucose, urea, and uric acid. It is therefore concluded that the DCP immunosensor developed and reported here is simple, inexpensive and effective, and shows promise in the rapid screening of early-stage liver cancer at home with a point-of-care approach. [ABSTRACT FROM AUTHOR]

There are limited data on exposure to mycotoxins in Pakistan. Here, we measured exposure to deoxynivalenol (DON), a common contaminant of wheat, and aflatoxin B1 (AFB1), a known contaminant of rice, using biomarkers of exposure. Wheat (n = 195) and rice (n = 62) samples were analyzed for AFB1 and DON levels, and the corresponding urinary biomarkers were analyzed in urine samples from a rural population (n = 264, aged 4–80 years, male 58%) using ultra-sensitive liquid chromatography–tandem mass spectrometry. AFB1 was detected in 66% of rice (5.04 ± 11.94 µg/kg) and 3% of wheat samples. AFM1 (hydroxylated form of AFB1) was detected in 69% of urine samples, mean 0.023 ± 0.048 ng/mL and DON was detected in 20% of urine samples, mean 0.170 ± 0.129 ng/mL. The maximum probable daily intake for DON derived from the urinary biomarker was 59.8 ng/kg b.w./day, which is below the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives' tolerable daily intake (1000 ng/kg b.w./day). However, for aflatoxin, the derived margin of exposure (MoE) of (13.2) was well below the safe MoE (10,000) suggested by the European Food Safety Authority. The calculated aflatoxin-associated cancer risk of 0.514/105 individuals/year suggests that measures should be taken to reduce the AFB1 contamination in food, particularly rice, in Pakistan. [ABSTRACT FROM AUTHOR]

To explore the flavonoids from Morus alba L. leaves (MLF), the process of extracting was optimized by a response surface methodology and the antimicrobial and antioxidant activities were evaluated in vitro. The yield of flavonoids reached 50.52 mg g−1 under the optimized extraction conditions (i.e., extraction temperature, 70.85 °C; solvent concentration, 39.30%; extraction time, 120.18 min; and liquid/solid ratio, 34.60:1). The total flavonoids were extracted in organic solvents with various polarities, including petroleum ether (MLFp), ethyl acetate (MLFe), and n-butanol (MLFb). In vitro, the four MLF samples exhibited good antioxidant activities for scavenging of 2, 2′-azinobis-(3-ethylbenz-thiazoline-6-sulphonate) radical, 1, 1-diphenyl-2-picrylhydrazyl radical, and total reducing power. Regarding antimicrobial efficacy, the MLF samples suppressed the development of Staphylococcus aureus, Bacillus subtilis, and Bacillus pumilus. The MLF samples inhibited α-amylase activity to a certain extent. The analytical hierarchy process (AHP) was used to evaluate comprehensively the bioactivities of the MLF samples. The AHP results revealed that the bioactivity comprehensive score (78.83 μg mL−1) of MLFe was optimal among the four MLF samples. Morus alba L. leaves also exhibited non-hemolytic properties. All bioactivities suggested the potential of MLFe as a candidate resource in the food and drug industries. [ABSTRACT FROM AUTHOR]