Exploring the interaction mechanism of chlorogenic acid and myoglobin: Insights from structure and molecular dynamics simulation.

This study focused on non-covalent complex of myoglobin-chlorogenic acid (Mb-CA) and the changes in conformation, oxidation, and microstructure induced by varying concentrations of CA (10-40 µmol/g Mb). Employing molecular docking and dynamics simulations, further insights into the interaction between Mb and CA were obtained. The findings revealed that different CA concentrations enhanced Mb's thermal stability, while diminishing particle size, solubility, and relative content of metmyoglobin (MetMb%). The optimal interaction occurred at 40 µmol/g Mb. Furthermore, CA exhibited static quenching of Mb, with thermodynamic analysis confirming a 1:1 complex formation. These insights deepen our understanding of interaction between Mb and CA, providing valuable clarity.

Targeting glycogen synthase kinase-3ß for Alzheimer's disease: Recent advances and future Prospects.

Senile plaques induced by ß-amyloid (Aß) abnormal aggregation and neurofibrillary tangles (NFT) caused by tau hyperphosphorylation are important pathological manifestations of Alzheimer's disease (AD). Glycogen synthase kinase-3 (GSK-3) is a conserved kinase; one member GSK-3ß is highly expressed in the AD brain and involved in the formation of NFT. Hence, pharmacologically inhibiting GSK-3ß activity and expression is a good approach to treat AD. As summarized in this article, multiple GSK-3ß inhibitors has been comprehensively summarized over recent five years. However, only lithium carbonate and Tideglusib have been studied in clinical trials of AD. Besides ATP-competitive and non-ATP-competitive inhibitors, peptide inhibitors, allosteric inhibitors and other types of inhibitors have gradually attracted more interest. Moreover, considering the close relationship between GSK-3ß and other targets involved in cholinergic hypothesis, Aß aggregation hypothesis, tau hyperphosphorylation hypothesis, oxidative stress hypothesis, neuro-inflammation hypothesis, etc., diverse multifunctional molecules and multi-target directed ligands (MTDLs) have also been disclosed. We hope that these recent advances and critical perspectives will facilitate the discovery of safe and effective GSK-3ß inhibitors for AD treatment.

SARS-CoV-2 vaccine breakthrough infection in the older adults: a meta-analysis and systematic review.

BACKGROUND: Corona Virus Disease 2019 (COVID-19) mRNA vaccine effectiveness (VE) has recently declined, and reports about COVID-19 breakthrough infection have increased. We aimed to conduct a meta-analysis on population-based studies of the prevalence and incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection amongst older adults worldwide. METHODS: Studies from PubMed, Embase, Cochrane Library, and Web of Science were systematically screened to determine the prevalence and incidence of SARS-CoV-2 breakthrough infection in older adults from inception to November 2, 2022. Our meta-analysis included 30 studies, all published in English. Pooled estimates were calculated using a random-effect model through the inverse variance method. Publication bias was tested through funnel plots and Egger's regression test, and sensitivity analyses were performed to confirm the robustness of the results. This research was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Thirty publications were included in this meta-analysis (17 on prevalence, 17 on incidence, and 4 on both). The pooled prevalence of COVID-19 breakthrough infection among older adults was 7.7 per 1,000 persons (95% confidence interval [95%CI] 4.0-15.0). At the same time, the pooled incidence was 29.1 per 1000 person-years (95%CI 15.2-55.7). CONCLUSIONS: This meta-analysis provides estimates of prevalence and incidence in older adults. We concluded that the prevalence and incidence of SARS-CoV-19 breakthrough infection in older people was low. The prevalence and incidence of breakthrough infection admitted to hospital, severe-critical, and deathly was significantly lower. Otherwise, there was considerable heterogeneity among estimates in this study, which should be considered when interpreting the results.

Intermittent theta burst stimulation vs. high-frequency repetitive transcranial magnetic stimulation for post-stroke cognitive impairment: Protocol of a pilot randomized controlled double-blind trial.

Introduction: Intermittent theta burst stimulation (iTBS), a novel mode of transcranial magnetic stimulation (TMS), has curative effects on patients with post-stroke cognitive impairment (PSCI). However, whether iTBS will be more applicable in clinical use than conventional high-frequency repetitive transcranial magnetic stimulation (rTMS) is unknown. Our study aims to compare the difference in effect between iTBS and rTMS in treating PSCI based on a randomized controlled trial, as well as to determine its safety and tolerability, and to further explore the underlying neural mechanism. Methods: The study protocol is designed as a single-center, double-blind, randomized controlled trial. Forty patients with PSCI will be randomly assigned to two different TMS groups, one with iTBS and the other with 5 Hz rTMS. Neuropsychological evaluation, activities of daily living, and resting electroencephalography will be conducted before treatment, immediately post-treatment, and 1 month after iTBS/rTMS stimulation. The primary outcome is the change in the Montreal Cognitive Assessment Beijing Version (MoCA-BJ) score from baseline to the end of the intervention (D11). The secondary outcomes comprise changes in resting electroencephalogram (EEG) indexes from baseline to the end of the intervention (D11) as well as the Auditory Verbal Learning Test, the symbol digit modality test, the Digital Span Test findings, and the MoCA-BJ scores from baseline to endpoint (W6). Discussion: In this study, the effects of iTBS and rTMS will be evaluated using cognitive function scales in patients with PSCI as well as data from resting EEG, which allows for an in-depth exploration of underlying neural oscillations. In the future, these results may contribute to the application of iTBS for cognitive rehabilitation of patients with PSCI.

Flavor mechanism of micro-nanoparticles and correlation analysis between flavor substances in thermoultrasonic treated fishbone soup.

To study the physicochemical properties of micro-nanoparticles (MNPs) in thermoultrasonic treated fishbone soup, it was subjected to ultra-filtration with a 100 kDa ultrafiltration membrane to obtain large MNPs (LMNPs) and small MNPs (SMNPs). LMNPs and SMNPs were treated with force-breakers, and the interactions of the MNPs with five characteristic volatile compounds were investigated. LMNPs covered most proteins (222.66 mg/mL) and fatty acids (363.76 mg/g), while SMNPs was mostly soluble small molecules with taste substances like total free amino acids (85.26 mg/g), organic acids (2.55 mg/mL), and 5'-nucleotides (169.17 mg/100 mL). The stability of LMNPs is significantly higher than raw bone soup, and SMNPs can exist stably in the solution. Correlation analysis between flavor substance content and flavor suggested that the overall flavor profile of halibut bone soup was closely related to the content changes of 72 significant influence variables. The binding of LMNPs to characteristic flavor compounds was largely affected by hydrophobic interactions, hydrogen bonds, and ionic effects. While the binding of SMNPs to characteristic flavor compounds was largely determined by hydrophobic interaction and hydrogen bonding. This study explores the characteristics of MNPs and provides the possibility to clarify the interaction mechanism between MNPs and flavor.

Evaluating the effects of nanoparticles combined ultrasonic-microwave thawing on water holding capacity, oxidation, and protein conformation in jumbo squid (Dosidicus gigas) mantles.

Magnetic nanoparticles (MNPs) have a dual role in acting as magnetic and sonosensitizer agents, which can combine the synergistic effects of microwave and ultrasonic waves. To study the effects of MNPs combined ultrasonic-microwave thawing (NUMT) on the water holding capacity (WHC), oxidation of protein and lipid, and protein conformation, jumbo squid mantles were subjected to cold storage thawing (CST), MNPs combined ultrasonic thawing (NUT), MNPs combined microwave thawing (NMT) and NUMT. Results showed that NUMT treatment had a higher WHC, lower oxidation, effectively reduced myofibrillar protein aggregation and degradation, and stabilized the structure of the protein of the jumbo squid. The muscle fiber structure of NUMT treated jumbo squid mantles was dense, orderly with a smooth surface, and the fiber network gaps were small and uniformly distributed. This study shows that NUMT can ameliorate the thawing qualities of jumbo squid, and is an effectively thawing method.

Flavonol-Aluminum Complex Formation: Enhancing Aluminum Accumulation in Tea Plants.

Polyphenol-rich tea plants are aluminum (Al) accumulators. Whether an association exists between polyphenols and Al accumulation in tea plants remains unclear. This study revealed that the accumulation of the total Al and bound Al contents were both higher in tea samples with high flavonol content than in low, and Al accumulation in tea plants was significantly and positively correlated with their flavonol content. Furthermore, the capability of flavonols combined with Al was higher than that of epigallocatechin gallate (EGCG) and root proanthocyanidins (PAs) under identical conditions. Flavonol-Al complexes signals (94 ppm) were detected in the tender roots and old leaves of tea plants through solid-state 27Al nuclear magnetic resonance (NMR) imaging, and the strength of the signals in the high flavonol content tea samples was considerably stronger than that in the low flavonol content tea samples. This study provides a new perspective for studying Al accumulation in different tea varieties.

Plant polyphenols regulating myoglobin oxidation and color stability in red meat and certain fish: A review.

Color is an essential criterion for assessing the freshness, quality, and acceptability of red meat and certain fish with red muscle. Myoglobin (Mb), one of the significant pigment substances, is the uppermost reason to keep the color of red meat. Their oxidation and browning are easy to occur throughout the storage and processing period. Natural antioxidants are substances with antioxidant activity extracted from plants, such as plant polyphenols. Consumers prefer natural antioxidants due to safety concerns and limitations on the use of synthetic antioxidants. In recent years, plant polyphenols have been widely used as antioxidants to slow down the deterioration of product quality due to oxidation. As natural antioxidants, it is necessary to strengthen the researches on the antioxidant mechanism of plant polyphenols to solve the discoloration of red meat and certain fish. A fundamental review of the relationship between Mb oxidation and color stability is discussed. The inhibiting mechanisms of polyphenols on lipid and Mb oxidation are presented and investigated. Meanwhile, this review comprehensively outlines applications of plant polyphenols in improving color stability. This will provide reference and theoretical support for the rational application of plant polyphenols in green meat processing.

Preparation, characterization, and gel characteristics of nanoemulsions stabilized with dextran-conjugated clam Meretrix meretrix linnaeus protein isolate.

In this study, the stability and flavor characteristics of nanoemulsions prepared with dextran-conjugated Meretrix meretrix clam protein isolate were studied by characterizing particle size, polydispersity index, zeta potential, turbidity, microstructure, e-tongue, e-nose and HS-GC-IMS. Compared with the NCPI (CPI nanoemulsions) and NCPI-Dex Mix (CPI-Dex Mix nanoemulsions), the NCPI-Dex Con (CPI-Dex Con nanoemulsions) has better stability and flavor. The breaking strength and breaking strain of clam sausages were significantly (P > 0.05) affected by the addition of NCPI-Dex Con. The gel strength with 8% NCPI-Dex Con was the highest (5122.08 g‧mm), a 51.07% increase compared with the control group (3390.58 g‧mm). The clam sausages supplemented with the 8% NCPI-Dex Con had the highest sensory score, with the densest and the most uniform gel structure. Therefore, CPI-Dex Con stabilized nanoemulsions could effectively improve the gel property and flavor of the clam sausages.

Aluminum-tolerant, growth-promoting endophytic bacteria as contributors in promoting tea plant growth and alleviating aluminum stress.

Unlike that of other crops, the growth of tea plants can be promoted by aluminum, but its regulation mechanism remains unclear. Some endophytes can also promote growth of plant hosts. In this paper, tea roots treated with aluminum were used to study the growth-promoting traits and aluminum tolerance of endophytes. Meta-16S rDNA analysis revealed that Burkholderia was enriched in tea roots after aluminum treatment, and it was the dominant strain for hydroponic tea roots and field tea roots. Actinomycetes constituted the dominant strains in hydroponic tea seedlings treated with aluminum. Sixteen endophytic bacteria, including 12 strains of Firmicutes, 2 strains of Proteobacteria and 2 strains of Actinomycetes, were isolated and identified from hydroponic tea roots treated with different aluminum concentrations. Growth-promoting activity analysis showed that the isolated endophytic bacteria all had more than one plant growth-promoting trait. Among them, B4 (Bacillus nealsonii), B8 (Brevibacterium frigoritolerans) and A2 (Nocardia nova) bacteria each had three growth-promoting traits. Aluminum tolerance ability analysis indicated that endophyte A1 (Leifsonia shinshuensis) had the strongest aluminum tolerance ability, up to 200 mg l-1 aluminum. Plant-bacteria interactions showed that endophytes A1, A2 and B4 and their synthetic community all had a growth-promoting effect on the growth of wheat lateral roots. Moreover, endophytes A1 and B4 alleviated aluminum stress in wheat. Endophyte A1 also promoted the growth of tea cuttings, especially lateral roots, with/without aluminum. Taken together, aluminum enhanced the distribution of aluminum-tolerant and growth-promoting bacteria, thereby promoting the growth of tea roots. This study provides a new aspect for research on the mechanism by which aluminum promotes tea plant growth.

A novel mouse model of orthotopic extrahepatic cholangiocarcinoma confirmed with molecular imaging.

BACKGROUND: Cholangiocarcinoma (CCA) is the second most common primary hepatic malignancy in humans. Although early-stage CCA can be managed with surgery, CCA is considered incurable at advanced stages and results in poor quality of life and overall survival. A good orthotopic CCA animal model is essential to perform basic studies investigating CCA in order to understand the molecular pathways that underlie cancer development, and to develop new therapies for the prevention and treatment of CCA. However, to the best of our knowledge, orthotopic extrahepatic CCA animal models have not yet been reported in the literature. METHODS: In this study, we established an orthotopic extrahepatic CCA model in mice using a two-step surgical procedure. RESULTS: The characteristics of this model were confirmed using molecular imaging and histological analysis. CONCLUSIONS: We believe that this CCA animal model, which can be established quickly, easily, and with good reproducibility, will help guide research on novel diagnostic and treatment strategies for extrahepatic CCA.