-
Journal of Agricultural and Food... Jul 2024Corn ear rot and fumonisin caused by pose a serious threat to food security. To find more highly active fungicidal and antitoxic candidates with structure diversity...
Corn ear rot and fumonisin caused by pose a serious threat to food security. To find more highly active fungicidal and antitoxic candidates with structure diversity based on naturally occurring lead xanthatin, a series of novel spiropiperidinyl-α-methylene-γ-butyrolactones were rationally designed and synthesized. The bioassay results indicated that compound showed broad-spectrum activity with EC values falling from 3.51 to 24.10 μg/mL against and , which was more active than the positive controls xanthatin and oxathiapiprolin. In addition, compound also showed good antitoxic efficacy against fumonisin with a 48% inhibition rate even at a concentration of 20 μg/mL. Fluorescence quenching and the molecular docking validated both and oxathiapiprolin targeting at FvoshC. RNA sequencing analysis discovered that FUM gene cluster and protein processing in endoplasmic reticulum were downregulated. Our studies have discovered spiropiperidinyl-α-methylene-γ-butyrolactone as a novel FvoshC target-based scaffold for fungicide lead with antitoxin activity.
PubMed: 38949855
DOI: 10.1021/acs.jafc.4c02848 -
Drug Delivery and Translational Research Jun 2024Parkinson's disease (PD), affecting millions of people worldwide and expected to impact 10 million by 2030, manifests a spectrum of motor and non-motor symptoms linked...
Parkinson's disease (PD), affecting millions of people worldwide and expected to impact 10 million by 2030, manifests a spectrum of motor and non-motor symptoms linked to the decline of dopaminergic neurons. Current therapies manage PD symptoms but lack efficacy in slowing disease progression, emphasizing the urgency for more effective treatments. Resveratrol (RSV), recognized for its neuroprotective and antioxidative properties, encounters challenges in clinical use for PD due to limited bioavailability. Researchers have investigated lipid-based nanoformulations, specifically solid lipid nanoparticles (SLNs), to enhance RSV stability. Oral drug delivery via SLNs faces obstacles, prompting exploration into transdermal delivery using SLNs integrated with microneedles (MNs) for improved patient compliance. In this study, an RSV-loaded SLNs (RSV -SLNs) incorporated into the MN patch was developed for transdermal RSV delivery to improve its stability and patient compliance. Characterization studies demonstrated favorable physical properties of SLNs with a sustained drug release profile of 78.36 ± 0.74%. The developed MNs exhibited mechanical robustness and skin penetration capabilities. Ex vivo permeation studies displayed substantial drug permeation of 68.39 ± 1.4% through the skin. In an in vivo pharmacokinetic study, the RSV-SLNs delivered through MNs exhibited a significant increase in C, T, and AUC values, alongside a reduced elimination rate in blood plasma in contrast to the administration of pure RSV via MNs. Moreover, an in vivo study showcased enhanced behavioral functioning and increased brain antioxidant levels in the treated animals. In-vivo skin irritation study revealed no signs of irritation till 24 h which permits long-term MNs application. Histopathological analysis showed notable changes in the brain regions of the rat, specifically the striatum and substantia nigra, after the completion of the treatment. Based on these findings, the development of an RSV-SLN loaded MNs (RSVSNLMP) patch presents a novel approach, with the potential to enhance the drug's efficiency, patient compliance, and therapeutic outcomes for PD, offering a promising avenue for advanced PD therapy.
PubMed: 38949746
DOI: 10.1007/s13346-024-01656-0 -
Methods in Molecular Biology (Clifton,... 2024Tuberculosis (TB) is the most common cause of death from an infectious disease. Although treatment has been available for more than 70 years, it still takes too long and...
Tuberculosis (TB) is the most common cause of death from an infectious disease. Although treatment has been available for more than 70 years, it still takes too long and many patients default risking relapse and the emergence of resistance. It is known that lipid-rich, phenotypically antibiotic-tolerant, bacteria are more resistant to antibiotics and may be responsible for relapse necessitating extended therapy. Using a microfluidic system that acoustically traps live mycobacteria, M. smegmatis, a model organism for M. tuberculosis we can perform optical analysis in the form of wavelength-modulated Raman spectroscopy (WMRS) on the trapped organisms. This system can allow observations of the mycobacteria for up to 8 h. By adding antibiotics, it is possible to study the effect of antibiotics in real-time by comparing the Raman fingerprints in comparison to the unstressed condition. This microfluidic platform may be used to study any microorganism and to dynamically monitor its response to many conditions including antibiotic stress, and changes in the growth media. This opens the possibility of understanding better the stimuli that trigger the lipid-rich downregulated and phenotypically antibiotic-resistant cell state.
Topics: Spectrum Analysis, Raman; Mycobacterium smegmatis; Microfluidics; Anti-Bacterial Agents; Acoustics; Lab-On-A-Chip Devices; Microfluidic Analytical Techniques; Humans
PubMed: 38949705
DOI: 10.1007/978-1-0716-3981-8_11 -
Analytical and Bioanalytical Chemistry Jun 202417α-Hydroxyprogesterone (17α-OHP) quantification in dried blood spots (DBS) is essential for newborn screening for congenital adrenal hyperplasia (CAH), which is...
Development and evaluation of a candidate reference measurement procedure for detecting 17α-hydroxyprogesterone in dried blood spots using isotope dilution liquid chromatography tandem mass spectrometry.
17α-Hydroxyprogesterone (17α-OHP) quantification in dried blood spots (DBS) is essential for newborn screening for congenital adrenal hyperplasia (CAH), which is challenging due to its low physiological concentration. The high false-positive rates of immunoassays necessitate the development of more accurate methods. Liquid chromatography tandem mass spectrometry (LC-MS/MS) offers increased specificity and sensitivity, yet standardized procedures for 17α-OHP measurement are required for clinical application. A candidate reference measurement procedure (cRMP) using isotope dilution LC-MS/MS was developed for 17α-OHP quantification in DBS. By utilizing stable isotope-labeled D8-17α-OHP as an internal standard, the cRMP was optimized, covering sample preparation, calibration, and LC-MS/MS analysis. The method performance was validated across several parameters, including precision, accuracy, specificity, detection limits, and matrix effects. Clinical applicability was further assessed through the establishment of reference intervals for healthy newborns. The developed cRMP exhibited a linear range of 1.00 to 80.00 ng/mL for 17α-OHP, with detection and quantification limits of 0.14 ng/mL and 0.52 ng/mL, respectively. Inter- and intraday precision demonstrated coefficients of variation within 1.27 to 5.69%. The recovery rates and matrix effects were well within acceptable limits, ensuring method reliability. Clinical application showed distinct reference intervals for healthy newborns that were unaffected by sex but influenced by weight and gestational age. This method significantly enhances CAH diagnostic accuracy in newborns, providing a valuable tool for clinical laboratories and improving newborn screening program standardization and traceability.
PubMed: 38949681
DOI: 10.1007/s00216-024-05411-9 -
Natural Product Research Jul 2024Recent research has indicated that saponins (PNS) extracted from the radix of (Burkill) F. H. Chen exert antidepressant effects. This study aimed to assess the...
Recent research has indicated that saponins (PNS) extracted from the radix of (Burkill) F. H. Chen exert antidepressant effects. This study aimed to assess the antidepressive effects of ginsenoside Rg1 and PNS in a depression model induced by chronic unpredictable mild stress (CUMS). Over a period of three weeks, rats were administered ginsenoside Rg1 at a dose of 30 mg/kg and PNS at dosages ranging from 100 to 200 mg/kg body weight per day. To assess how ginsenoside Rg1 and PNS influence depression-like behaviours in rats, various assessments were conducted, including coat state evaluation, forced swim test, and elevated plus maze test. The levels of cortisol and testosterone in serum samples were analysed using the liquid chromatography-electrospray ionisation tandem mass spectrometry (LC-ESI-MS/MS) method. LC-ESI-MS/MS method provides precise and accurate results. The lower limit of quantification values for cortisol and testosterone were determined as 100 and 2 pg/mL, respectively. Our data demonstrated that both ginsenoside Rg1 and PNS significantly reversed depression-like behaviour in rats by improving coat condition, reducing immobility time in the forced swim test, and increasing time spent in the open arms of the elevated plus maze test. Furthermore, ginsenoside Rg1 and PNS exhibited a regulatory effect on cortisol and testosterone levels in plasma. These findings suggest that ginsenoside Rg1 and PNS may be potential antidepressants in clinical treatment.
PubMed: 38949646
DOI: 10.1080/14786419.2024.2371997 -
Analytical Chemistry Jul 2024The number of possible candidate formulas for high molecular weight unknown compounds (e.g., 7000-8000 Da for common 20-mer oligonucleotides) by high-resolution mass...
The number of possible candidate formulas for high molecular weight unknown compounds (e.g., 7000-8000 Da for common 20-mer oligonucleotides) by high-resolution mass spectrometry is in the order of several hundred thousand even at the highest level of experimental accuracy. In demanding analytical applications involving new chemistries and synthetic routes where little is known about the chemical nature or mechanisms of formation of the unknown compounds (e.g., impurities), the generation of a short list of the most plausible formulas would be highly desirable. Such an approach has been developed in the current work. The concept of mass difference from a reference compound is introduced to simplify the approach and greatly reduce the number of possible formulas. The approach allows for the generation of candidate formulas by both the addition and subtraction of atoms to account for all possible molecular changes from the parent compound. A reduction of 3 orders of magnitude in the number of possible formulas has been achieved by the approach. Ranking of the formulas by the product of the sums of the absolute changes in the total number of all atoms and all heteroatoms in the proposed difference formula successfully ranked the correct formula within the top 10 from a list of 200-250 best candidate formulas. There is a tendency for the impurities to be formed involving the least change in the number of atoms and heteroatoms. Δ Δ values can be used as a complementary ranking system of the top candidates. The approach is applicable to unknowns in any other systems of high MW compounds.
PubMed: 38949572
DOI: 10.1021/acs.analchem.4c00621 -
Journal of Clinical and Experimental... Jul 2024Prior research on the Noise Pareidolia Test (NPT) has demonstrated its clinical utility in detecting patients with mild cognitive impairment and dementia due to Lewy...
Neuropsychological and neuroanatomical underpinnings of the face pareidolia errors on the noise pareidolia test in patients with mild cognitive impairment and dementia due to Lewy bodies.
OBJECTIVE
Prior research on the Noise Pareidolia Test (NPT) has demonstrated its clinical utility in detecting patients with mild cognitive impairment and dementia due to Lewy Body Disease (LBD). However, few studies to date have investigated the neuropsychological factors underlying pareidolia errors on the NPT across the clinical spectrum of LBD. Furthermore, to our knowledge, no research has examined the relationship between cortical thickness using MRI data and NPT subscores. As such, this study sought to explore the neuropsychological and neuroanatomical factors influencing performance on the NPT utilizing the National Alzheimer's Coordinating Center Lewy Body Dementia Module.
METHODS
Our sample included participants with normal cognition (NC; = 56), LBD with mild cognitive impairment (LBD-MCI; = 97), and LBD with dementia (LBD-Dementia; = 94). Archival data from NACC were retrospectively analyzed for group differences in neuropsychological test scores and cognitive and psychiatric predictors of NPT scores. Clinicoradiological correlates between NPT subscores and a small subsample of the above LBD participants were also examined.
RESULTS
Analyses revealed significant differences in NPT scores among groups. Regression analysis demonstrated that dementia severity, attention, and visuospatial processing contributed approximately 24% of NPT performance in LBD groups. Clinicoradiological analysis suggests a potential contribution of the right fusiform gyrus, but not the inferior occipital gyrus, to NPT pareidolia error scores.
CONCLUSIONS
Our findings highlight the interplay of attention and visuoperceptual functions in complex pareidolia in LBD. Further investigation is needed to refine the utility of NPT scores in clinical settings, including identifying patients at risk for visual illusions and hallucinations.
PubMed: 38949538
DOI: 10.1080/13803395.2024.2372876 -
Autism Research : Official Journal of... Jul 2024Securing an accurate autism-spectrum-condition diagnosis, particularly among women, remains challenging for autistic adults. Building upon previous research highlighting...
Securing an accurate autism-spectrum-condition diagnosis, particularly among women, remains challenging for autistic adults. Building upon previous research highlighting the short-story task (SST) as a promising tool for detecting fiction-based mentalizing difficulties in autistic adults, this study expands its scope. We investigated the SST's discriminative capacity across three distinct groups: autistic individuals (n = 32), nonautistic individuals without mental health problems (n = 32), and nonautistic individuals with clinical depression (n = 30). All three groups differed significantly from each other in their SST mentalizing score with the nonautistic group having the highest scores, the nonautistic but depressed group having medium scores and the autistic group showing the lowest scores. Receiver operator curve (ROC) analysis reaffirmed the SST's efficacy as a discriminator. Moreover, a linear regression analysis identified the SST mentalizing score, the SST comprehension score, and the number of books read per month as significant predictors of autism-spectrum-condition diagnosis. These findings bolster the SST's potential as a valuable adjunct in autism diagnostics, highlighting its discriminatory ability across diverse samples.
PubMed: 38949479
DOI: 10.1002/aur.3191 -
Isotopes in Environmental and Health... Jul 2024For a detailed characterization of the 5.7 10 mt phosphogypsum (PG) stack in the vicinity of Bacau city, Romania, the air dose rate (ADR) was measured in 72 points...
For a detailed characterization of the 5.7 10 mt phosphogypsum (PG) stack in the vicinity of Bacau city, Romania, the air dose rate (ADR) was measured in 72 points covering the stack surface, while 10 samples of stack material were collected for future analysis. Radiometric determinations showed for the ADR values varying between 364 ± 53 and 489 ± 8 nSv/h, with some extreme values of 2775 ± 734 nSv/h, significantly exceeding 90 nSv/h, the average value reported for the Romanian territory. High-resolution gamma-ray spectroscopy (HRGS), performed on 10 samples collected from the entire PG stack evidenced only the presence of Ra as the major radioactive element with a specific activity varied between 820 ± 150 and 5278 ± 264 Bq/kg for hot spots. Further analysis performed on a similar number of samples by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), X-ray fluorescence (XRF), scanning electron microscopy (SEM) and energy dispersive X-ray spectrometry (EDX), evidenced, beside gypsum as the main component, traces of brushite (CaHPO·2HO) and ardealite (Ca(POOH)(SO)·4HO), as well as the presence of small acicular celestine (SrSO) agglomerates. XRF determinations of the mass fractions of major elements evidenced values such as SiO (2.31 ± 0.73 %), TiO (0.07 ± 0.01 %), AlO (0.17 ± 0.04 %), FeO (0.87 ± 0.18 %), MnO (0.01 ± 0.01 %), MgO (0.17 ± 0.02 %), CaO (32.5 ± 0.82 %), NaO (0.04 ± 0.04 %), KO (0.05 ± 0.01 %), PO (2.12 ± 0.51 %), LOI (20.2 ± 0.3 %), i.e. closer to literature reported data for PG of different provenience while the data concerning the distribution of 20 trace elements, including incompatible Sc, La, Ce, and Th were relatively closer to the upper continental crust (UCC).
PubMed: 38949391
DOI: 10.1080/10256016.2024.2365684 -
Addiction Biology Jul 2024In recent years, electronic cigarettes (e-cigs) have gained popularity as stylish, safe, and effective smoking cessation aids, leading to widespread consumer acceptance....
In recent years, electronic cigarettes (e-cigs) have gained popularity as stylish, safe, and effective smoking cessation aids, leading to widespread consumer acceptance. Although previous research has explored the acute effects of combustible cigarettes or nicotine replacement therapy on brain functional activities, studies on e-cigs have been limited. Using fNIRS, we conducted graph theory analysis on the resting-state functional connectivity of 61 male abstinent smokers both before and after vaping e-cigs. And we performed Pearson correlation analysis to investigate the relationship between alterations in network metrics and changes in craving. E-cig use resulted in increased degree centrality, nodal efficiency, and local efficiency within the executive control network (ECN), while causing a decrease in these properties within the default model network (DMN). These alterations were found to be correlated with reductions in craving, indicating a relationship between differing network topologies in the ECN and DMN and decreased craving. These findings suggest that the impact of e-cig usage on network topologies observed in male smokers resembles the effects observed with traditional cigarettes and other forms of nicotine delivery, providing valuable insights into their addictive potential and effectiveness as aids for smoking cessation.
Topics: Humans; Male; Vaping; Adult; Electronic Nicotine Delivery Systems; Executive Function; Craving; Spectroscopy, Near-Infrared; Young Adult; Default Mode Network; Brain; Smoking Cessation; Nerve Net
PubMed: 38949205
DOI: 10.1111/adb.13423