Bat-derived oligopeptide LE6 inhibits the contact-kinin pathway and harbors anti-thromboinflammation and stroke potential.

Thrombosis and inflammation are primary contributors to the onset and progression of ischemic stroke. The contact-kinin pathway, initiated by plasma kallikrein (PK) and activated factor XII (FXIIa), functions bidirectionally with the coagulation and inflammation cascades, providing a novel target for therapeutic drug development in ischemic stroke. In this study, we identified a bat-derived oligopeptide from Myotis myotis (Borkhausen, 1797), designated LE6 (Leu-Ser-Glu-Glu-Pro-Glu, 702 Da), with considerable potential in stroke therapy due to its effects on the contact kinin pathway. Notably, LE6 demonstrated significant inhibitory effects on PK and FXIIa, with inhibition constants of 43.97 µmol/L and 6.37 µmol/L, respectively. In vitro analyses revealed that LE6 prolonged plasma recalcification time and activated partial thromboplastin time. In murine models, LE6 effectively inhibited carrageenan-induced mouse tail thrombosis, FeCl 3-induced carotid artery thrombosis, and photochemically induced intracerebral thrombosis. Furthermore, LE6 significantly decreased inflammation and stroke injury in transient middle cerebral artery occlusion models. Notably, the low toxicity, hemolytic activity, and bleeding risk of LE6, along with its synthetic simplicity, underscore its clinical applicability. In conclusion, as an inhibitor of FXIIa and PK, LE6 offers potential therapeutic benefits in stroke treatment by mitigating inflammation and preventing thrombus formation.

Evaluation of Phenazine Derivatives from the Lichen-Associated Streptomyces flavidovirens as Potent Antineuroinflammatory Agents In Vitro and In Vivo.

Eighteen nitrogen-containing compounds (1-18) were isolated from cultures of the lichen-associated Streptomyces flavidovirens collected from the Qinghai-Tibet Plateau, including seven phenazine derivatives with three new ones, named subphenazines A-C (2-4), two new furan pyrrolidones (8-9), and nine known alkaloids. The structures were elucidated by spectroscopic data analysis, and absolute configurations were determined by single-crystal X-ray diffraction and ECD calculations. The phenazine-type derivatives, in particular compound 3, exhibited significantly better antineuroinflammatory activity than other isolated compounds (8-18). Compound 3 inhibited the release of proinflammatory cytokines including IL-6, TNF-α, and PGE2, and the nuclear translocation of NF-κB; it also reduced the oxidative stress and activated the Nrf2 signaling pathway in LPS-induced BV2 microglia cells. In vivo anti-inflammatory activity in zebrafish indicated that 3 inhibited LPS-stimulated ROS generation. These findings suggested that compound 3 might be a potent antineuroinflammatory agent through the regulation of the NF-κB/Nrf2 signaling pathways.

Constrained motion of self-propelling eccentric disks linked by a spring.

It has been supposed that the interplay of elasticity and activity plays a key role in triggering the non-equilibrium behaviors in biological systems. However, the experimental model system is missing to investigate the spatiotemporally dynamical phenomena. Here, a model system of an active chain, where active eccentric-disks are linked by a spring, is designed to study the interplay of activity, elasticity, and friction. Individual active chain exhibits longitudinal and transverse motions; however, it starts to self-rotate when pinning one end and self-beat when clamping one end. In addition, our eccentric-disk model can qualitatively reproduce such behaviors and explain the unusual self-rotation of the first disk around its geometric center. Furthermore, the structure and dynamics of long chains were studied via simulations without steric interactions. It was found that a hairpin conformation emerges in free motion, while in the constrained motions, the rotational and beating frequencies scale with the flexure number (the ratio of self-propelling force to bending rigidity), χ, as ∼(χ)4/3. Scaling analysis suggests that it results from the balance between activity and energy dissipation. Our findings show that topological constraints play a vital role in non-equilibrium synergy behaviors.

A new neuroprotective candidate TJ1 targeting amyloidogenesis in 5xFAD Alzheimer's disease mice.

As one of the main pathmechanisms of Alzheimer's disease (AD), amyloid-ß (Aß) is widely considered to be the prime target for the development of AD therapy. Recently, imidazolylacetophenone oxime ethers or esters (IOEs) have shown neuroprotective effects against neuronal cells damage, suggesting their potential use in the prevention and treatment of AD. Thirty IOEs compounds from our lab in-house library were constructed and screened for the inhibitory effects on Aß42-induced cytotoxicity. Among them, TJ1, as a new IOEs hit, preliminarily showed the effect on inhibiting Aß42-induced cytotoxicity. Furthermore, the inhibitory effects of TJ1 on Aß42 aggregation were tested by ThT assays and TEM. The neuroprotective effects of TJ1 were evaluated in Aß42-stimulated SH-SY5Y cells, LPS-stimulated BV-2 cells, and H2O2- and RSL3-stimulated PC12 cells. The cognitive improvement of TJ1 was assessed in 5xFAD (C57BL/6J) transgenic mouse. These results showed that TJ1 had strong neuroprotective effects and high blood-brain barrier (BBB) permeability without obvious cytotoxicity. TJ1 impeded the self-accumulation process of Aß42 by acting on Aß oligomerization and fibrilization. Besides, TJ1 reversed Aß-, H2O2- and RSL3-induced neuronal cell damage and decreased neuroinflammation. In 5xFAD mice, TJ1 improved cognitive impairment, increased GSH level, reduced the level of Aß42 and Aß plaques, and attenuated the glia reactivation and inflammatory response in the brain,. Taken together, our results demonstrate that TJ1 improves cognitive impairments as a new neuroprotective candidate via targeting amyloidogenesis, which suggests the potential of TJ1 as a treatment for AD.

Structure, anti-inflammatory and anti-bacterial activities of novel pentacyclic triterpenoids and other constituents from the leaves of Pittosporum elevaticostatum.

The investigation of the leaves of Pittosporum elevaticostatum Chang et Yan led to the isolation of fifteen pentacyclic triterpenoids (1-15), including five previously undescribed ones (1-5), and nine others (16-24). The structures of compounds 1-5 were elucidated based on comprehensive spectroscopic techniques, including one dimension (1D) and 2D nuclear magnetic resonance (NMR), high resolution electrospray ionization mass spectroscopy (HR-ESI-MS), and other methods. Compounds 2 and 13 demonstrated significant inhibitory activity against Listeria monocytogenes (L. monocytogenes) with minimum inhibitory concentration (MIC) values of 32 µM. Scanning electron microscopy (SEM) observations revealed insights into the antibacterial mechanism, indicating that compounds 2 and 13 either prevent biofilm formation of dispersed the preformed cell membranes. Additionally, compounds 1, 5, 7, and 12 exhibited anti-inflammatory activity on lipopolysaccharide (LPS)-stimulated BV-2 microglial cells with IC50 values ranging from 11.27 to 17.80 µM.

Internal iliac artery ligation as a damage control method in hemodynamically unstable pelvic fractures: A systematic review of the literature.

PURPOSE: Internal iliac artery ligation (IIAL) has been used as a damage control procedure to treat hemodynamically unstable pelvic fracture for many years. However, there is ongoing debate regarding the effectiveness and safety of this hemostatic method. Therefore, we performed a systematic literature review to assess the efficacy and safety of IIAL for pelvic fracture hemostasis. METHODS: Three major databases, PubMed, Embase, and Google Scholar, were searched to screen eligible original studies published in English journals. Two reviewers independently read the titles, abstracts, and full texts of all literature. Articles were included if they reported the use and effects of IIAL. RESULTS: A total of 171 articles were initially identified, with 22 fully meeting the inclusion criteria. Among the analyzed cases, up to 66.7% of patients had associated abdominal and pelvic organ injuries, with the urethra being the most frequently injured organ, followed by the bowel. The outcomes of IIAL for achieving hemostasis in pelvic fractures were found to be satisfactory, with an effective rate of 80%. Hemorrhagic shock was the leading cause of death, followed by craniocerebral injury. Notably, no reports of ischemic complications involving the pelvic organs due to IIAL were found. CONCLUSION: IIAL has a good effect in treating hemodynamically unstable pelvic fracture without the risk of pelvic organ ischemia. This procedure should be considered a priority for hemodynamically unstable pelvic fracture patients with abdominal organ injuries.

Distinguishing Sanghuangporus from sanghuang-related fungi: a comparative and phylogenetic analysis based on mitogenomes.

The Chinese medicinal fungi "Sanghuang" have been long recognized for their significant and valued medicinal properties, as documented in ancient medical literature. However, in traditional folk medicine, various macrofungi sharing similar appearance, habitat, and therapeutic effects with Sanghuang were erroneously used. These Sanghuang-like fungi mainly belong to the Porodaedalea, Phellinus, and Inonotus genera within the Hymenochaetaceae family. Despite the establishment of the Sanghuangporus genus and the identification of multiple species, the emerging taxonomic references based on morphological, ITS, and mycelial structural features have been inadequate to differentiate Sanghuangporus and Sanghuang-like fungi. To address this limitation, this study presents the first comparative and phylogenetic analysis of Sanghuang-related fungi based on mitogenomes. Our results show that Sanghuangporus species show marked convergence in mitochondrial genomic features and form a distinct monophyletic group based on phylogenetic analyses of five datasets. These results not only deepen our understanding of Sanghuang-like fungi but also offer novel insights into their mitochondrial composition and phylogeny, thereby providing new research tools for distinguishing members of the Sanghuangporus genus. KEY POINTS: • Sanghuangporus, Inonotus, and Porodaedalea are monophyly in sanghuang-like species. • Mitogenome-based analysis exhibits high resolution in sanghuang-like genus. • The mitogenomes provide strong evidence for reclassifying Phellinus gilvus S12 as Sanghuangporus vaninii.

First report of PST-producing Microseira wollei from China reveals its novel toxin profile.

Microseira wollei, a globally distributed freshwater bloom-forming benthic cyanobacterium, is known for its production of cyanotoxins and taste and odor (T&O). While CYN (Cylindrospermopsin)-producing populations of M. wollei are confined to Australia, PST (Paralytic shellfish toxins)-producing populations have been exclusively documented in North America. In this study, four benthic cyanobacterial strains, isolated from West Lake in China, were identified as M. wollei based on morphological and phylogenetic analyses. Detection of sxtA gene and UPLC-MS/MS analysis conclusively confirmed the PST-producing capability of M. wollei CHAB5998. In the phylogenetic tree of 16S rDNA, M. wollei strains formed a monophyletic group with two subclades. Notably, non-PST-producing Chinese strains clustered with Australian strains in Clade II, while all other strains, including PST-producing ones, clustered in Clade I. Additionally, CHAB5998 contains ten PST variants, of which STX, NEO, GTX2, GTX3, GTX5 and C1 were identified for the first time in M. wollei. Sequence analysis of PST biosynthetic gene cluster (sxt) genes indicated potential base variations, gene rearrangements, insertions, and deletions in the strain CHAB5998. Also, sxt gene has a longer evolutionary history in M. wollei than that in cyanobacteria from Nostocales. Multiple recombination breakpoints detected in sxt genes and the inconsistency in the topology of the phylogenetic trees between sxt and 16S rDNA suggested that multiple horizontal gene transfers (HGT) have occurred. Overall, the present study marks the first documented occurrence of PST-producing M. wollei outside of North America and identifies it as the first toxic freshwater benthic cyanobacterium in China. This revelation implies that benthic cyanobacteria may pose a higher environmental risk in China than previously acknowledged.

Ganoderic Acid A Mitigates Inflammatory Bowel Disease through Modulation of AhR Activity by Microbial Tryptophan Metabolism.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a complex gastrointestinal condition influenced by genetic, microbial, and environmental factors, among which the gut microbiota plays a crucial role and has emerged as a potential therapeutic target. Ganoderic acid A (GAA), which is a lanostane triterpenoid compound derived from edible mushroom Ganoderma lucidum, has demonstrated the ability to modulate gut dysbiosis. Thus, we investigated the impact of GAA on IBD using a dextran sodium sulfate (DSS)-induced colitis mouse model. GAA effectively prevented colitis, preserved epithelial and mucus layer integrity, and modulated the gut microbiota. In addition, GAA promoted tryptophan metabolism, especially 3-IAld generation, activated the aryl hydrocarbon receptor (AhR), and induced IL-22 production. Fecal microbiota transplantation validated the mediating role of the gut microbiota in the IBD protection conferred by GAA. Our study suggests that GAA holds potential as a nutritional intervention for ameliorating IBD by influencing the gut microbiota, thereby regulating tryptophan metabolism, enhancing AhR activity, and ultimately improving gut barrier function.

Functional Characterization of Six Eukaryotic Translation Initiation Factors of Toxoplasma gondii Using the CRISPR-Cas9 System.

Eukaryotic translation initiation factors (eIFs) are crucial for initiating protein translation and ensuring the correct assembly of mRNA-ribosomal subunit complexes. In this study, we investigated the effects of deleting six eIFs in the apicomplexan parasite Toxoplasma gondii using the CRISPR-Cas9 system. We determined the subcellular localization of these eIFs using C-terminal endogenous tagging and immunofluorescence analysis. Four eIFs (RH::315150-6HA, RH::286090-6HA, RH::249370-6HA, and RH::211410-6HA) were localized in the cytoplasm, while RH::224235-6HA was localized in the apicoplast. Additionally, RH::272640-6HA was found in both the basal complex and the cytoplasm of T. gondii. Functional characterization of the six RHΔeIFs strains was conducted using plaque assay, cell invasion assay, intracellular growth assay and egress assay in vitro, and virulence assay in mice. Disruption of five eIF genes (RHΔ315150, RHΔ272640, RHΔ249370, RHΔ211410, and RHΔ224235) did not affect the ability of the T. gondii RH strain to invade, replicate, form plaques and egress in vitro, or virulence in Kunming mice (p > 0.05). However, the RHΔ286090 strain showed slightly reduced invasion efficiency and virulence (p < 0.01) compared to the other five RHΔeIFs strains and the wild-type strain. The disruption of the TGGT1_286090 gene significantly impaired the ability of tachyzoites to differentiate into bradyzoites in both type I RH and type II Pru strains. These findings reveal that the eukaryotic translation initiation factor TGGT1_286090 is crucial for T. gondii bradyzoite differentiation and may serve as a potential target for drug development and an attenuated vaccine against T. gondii.

Research on ride comfort optimization of the vehicle considering the subframe.

When the vehicle is in motion, the elastic deformation of the flexible subframe significantly influences ride comfort. Therefore, it is crucial to investigate the impact of flexible subframes on vehicle ride comfort. In order to enhance the reliability and optimization efficiency of our research, this paper incorporates the concept of elastic deformation in the flexible subframe into the investigation of vehicle ride comfort, and proposes a multi-objective optimization approach to enhance the overall vehicle ride comfort. The vibration mathematical model elucidates how flexible subframes affect vehicle ride comfort and establishes a rigid-flexible coupling model for a specific vehicle with a flexible subframe to analyze the impact of its elastic deformation on vehicle ride comfort through simulation experiments. Subsequently, a radial basis function approximation model is established, and the multi-objective particle swarm optimization and non-dominated sorting genetic algorithm II algorithms are employed to conduct multi-objective optimization of the stiffness of the subframe bushing with the aim of enhancing vehicle ride comfort. The findings indicate that the flexible subframe has a significant impact on vehicle ride comfort. Specifically, on bump roads, peak values of vertical and longitudinal seat accelerations decrease while lateral seat acceleration increases. On random roads, peak values of longitudinal and lateral seat accelerations increase while vertical acceleration decreases. Furthermore, the stiffness of the subframe bushing optimized by the non-dominated sorting genetic algorithm II algorithm further enhances vehicle ride comfort and aligns more closely with the optimization requirements in this study.

Mechanism of Zhishi Xiebai Guizhi decoction to treat atherosclerosis: Insights into experiments, network pharmacology and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhishi Xiebai Guizhi Decoction (ZSXBGZD) is a traditional herbal manuscript used to treat cardiovascular disease, including atherosclerosis and coronary heart disease. The decoction has demonstrated its capability to protect arteries and resist atherosclerosis. Its mechanisms for anti-atherosclerosis effect, nevertheless, remain unknown. AIMS OF THE STUDY: The goal of the present study is to explore the effectiveness of ZSXBGZD acting on atherosclerosis and its key components based on experimental verification and network pharmacology analysis. MATERIALS AND METHODS: The ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and databases were used to identify chemical components in ZSXBGZD. Network pharmacological analysis and molecular docking were implemented in order to reveal the possible therapeutic targets of ZSXBGZD. To form the model of atherosclerosis, we gave Apolipoprotein E knocked out mice a high-fat diet. H&E staining was performed to observe the effects of ZSXBGZD on atherosclerosis. Immunofluorescence and Western blot were used to investigate whether ZSXBGZD could affect autophagy, apoptosis, AGE-RAGE signaling pathway and other related mechanisms. RESULTS: In total, 30 core compounds were screened through intersecting UPLC-Q-TOF-MS and the databases. The anti-atherosclerotic effect of ZSXBGZD might relate to the AGE-RAGE signaling pathway via network pharmacology analysis. ZSXBGZD could inhibit apoptosis, activate autophagy and ease inflammation by modifying AGE-RAGE signaling pathway to reduce the area of atherosclerotic plaque. CONCLUSION: ZSXBGZD could treat atherosclerosis by regulating autophagy and apoptosis via adjusting the AGE-RAGE signaling pathway.

Discovery of anti-melanogenic components in persimmon (Diospyros kaki) leaf using LC-MS/MS-MN, AlphaFold2-enabled virtual screening and biological validation.

Persimmon (Diospyros kaki) leaf is widely used as a tea substitute in East Asia, offering potential health benefits. Although studies have highlighted their effects on hyperpigmentation disorders, the active components remain unidentified. This study introduces a novel approach combining LC-MS/MS-based molecular networking with AlphaFold2-enabled virtual screening to expedite the identification of bioactive components in persimmon leaf. A total of 105 compounds were identified by MS/MS analysis. Further, virtual screening identified five flavonoids with potential anti-melanogenic properties. Bioassays confirmed myricetin, quercetin, and kaempferol inhibited melanogenesis in human melanocytes in a dose-dependent manner. Biolayer interferometry assays revealed strong binding affinity between these flavonols and hsTYR, with KD values of 23.26 ± 11.77 for myricetin, 12.43 ± 0.37 for quercetin, and 14.99 ± 3.80 µM for kaempferol. Molecular dynamics simulations provided insights into the binding interactions of these flavonols with hsTYR, particularly highlighting the essential role of the 3-OH group on the C-ring. This study elucidates the bioactive components responsible for the anti-melanogenic effects of persimmon leaf, supporting their use in product development.

Amino-Acid-Encoded Supramolecular Nanostructures for Persistent Bioluminescence Imaging of Tumor.

Bioluminescence imaging (BLI) is a powerful technique for noninvasive monitoring of biological processes and cell transplantation. Nonetheless, the application of D-luciferin, which is widely employed as a bioluminescent probe, is restricted in long-term in vivo tracking due to its short half-life. This study presents a novel approach using amino acid-encoded building blocks to accumulate and preserve luciferin within tumor cells, through a supramolecular self-assembly strategy. The building block platform called Cys(SEt)-X-CBT (CXCBT, with X representing any amino acid) utilizes a covalent-noncovalent hybrid self-assembly mechanism to generate diverse luciferin-containing nanostructures in tumor cells after glutathione reduction. These nanostructures exhibit efficient tumor-targeted delivery as well as sequence-dependent well-designed morphologies and prolonged bioluminescence performance. Among the selected amino acids (X = Glu, Lys, Leu, Phe), Cys(SEt)-Lys-CBT (CKCBT) exhibits the superior long-lasting bioluminescence signal (up to 72 h) and good biocompatibility. This study demonstrates the potential of amino-acid-encoded supramolecular self-assembly as a convenient and effective method for developing BLI probes for long-term biological tracking and disease imaging.

Mechanistic Insights from the Crystal Structure and Computational Analysis of the Radical SAM Deaminase DesII.

Radical S-adenosyl-L-methionine (SAM) enzymes couple the reductive cleavage of SAM to radical-mediated transformations that have proven to be quite broad in scope. DesII is one such enzyme from the biosynthetic pathway of TDP-desosamine where it catalyzes a radical-mediated deamination. Previous studies have suggested that this reaction proceeds via direct elimination of ammonia from an α-hydroxyalkyl radical or its conjugate base (i.e., a ketyl radical) rather than 1,2-migration of the amino group to form a carbinolamine radical intermediate. However, without a crystal structure, the active site features responsible for this chemistry have remained largely unknown. The crystallographic studies described herein help to fill this gap by providing a structural description of the DesII active site. Computational analyses based on the solved crystal structure are consistent with direct elimination and indicate that an active site glutamate residue likely serves as a general base to promote deprotonation of the α-hydroxyalkyl radical intermediate and elimination of the ammonia group.

Comparative toxicology of algal cell extracts and pure cyanotoxins: insights into toxic effects and mechanisms of harmful cyanobacteria Raphidiopsis raciborskii.

Ongoing research on cyanotoxins, driven by the socioeconomic impact of harmful algal blooms, emphasizes the critical necessity of elucidating the toxicological profiles of algal cell extracts and pure toxins. This study comprehensively compares Raphidiopsis raciborskii dissolved extract (RDE) and cylindrospermopsin (CYN) based on Daphnia magna assays. Both RDE and CYN target vital organs and disrupt reproduction, development, and digestion, thereby causing acute and chronic toxicity. Disturbances in locomotion, reduced behavioral activity, and weakened swimming capability in D. magna have also been reported for both RDE and CYN, indicating the insufficiency of conventional toxicity evaluation parameters for distinguishing between the toxic effects of algal extracts and pure cyanotoxins. Additionally, chemical profiling revealed the presence of highly active tryptophan-, humic acid-, and fulvic acid-like fluorescence compounds in the RDE, along with the active constituents of CYN, within a 15-day period, demonstrating the chemical complexity and dynamics of the RDE. Transcriptomics was used to further elucidate the distinct molecular mechanisms of RDE and CYN. They act diversely in terms of cytotoxicity, involving oxidative stress and response, protein content, and energy metabolism, and demonstrate distinct modes of action in neurofunctions. In essence, this study underscores the distinct toxicity mechanisms of RDE and CYN and emphasizes the necessity for context- and objective-specific toxicity assessments, advocating nuanced approaches to evaluate the ecological and health implications of cyanotoxins, thereby contributing to the precision of environmental risk assessments.

Three New Ionone Glycosides from Rhododendron capitatum Maxim.

Six ionone glycosides (1-3 and 5-7), including three new ones, named capitsesqsides A-C (1-3), together with an eudesmane sesquiterpenoid glycoside (4) and three known triterpenoid saponins (8-10) were isolated from Rhododendron capitatum. The structures of these compounds were determined by extensive spectroscopic techniques (MS, UV, 1D-NMR, and 2D-NMR) and comparison with data reported in the literature. The absolute configurations were determined by comparison of the experimental and theoretically calculated ECD curves and LC-MS analyses after acid hydrolysis and derivatization. The anti-inflammatory activities of these compounds were evaluated in the LPS-induced RAW264.7 cells. Molecular docking demonstrated that 2 has a favorable affinity for NLRP3 and iNOS.

Synthetic Sialosides Terminated with 8-N-Substituted Sialic Acid as Selective Substrates for Sialidases from Bacteria and Influenza Viruses.

Sialosides containing C8-modified sialic acids are challenging synthetic targets but potentially useful probes for diagnostic substrate profiling of sialidases and elucidating the binding specificity of sialic acid-interacting proteins. Here, we demonstrate efficient chemoenzymatic methods for synthesizing para-nitrophenol-tagged α2-3- and α2-6-linked sialyl galactosides containing C8-acetamido, C8-azido, or C8-amino derivatized N-acetylneuraminic acid (Neu5Ac). High-throughput substrate specificity studies showed that the C8-modification of sialic acid significantly changes its recognition by sialidases from humans, various bacteria, and different influenza A and B viruses. Sialosides carrying Neu5Ac with a C8-azido modification were generally well tolerated by all the sialidases we tested, whereas sialosides containing C8-acetamido-modified Neu5Ac were only cleaved by selective bacterial sialidases. In contrast, sialosides with C8-amino-modified Neu5Ac were cleaved by a combination of selective bacterial and influenza A virus sialidases. These results indicate that sialosides terminated with a C8-amino or C8-acetamido-modified sialic acid can be used with other sialosides for diagnostic profiling of disease-causing sialidase-producing pathogens.

Normal Values for Atrial Deformation Measured by Feature-Tracking Cardiac MRI: A Meta-Analysis.

BACKGROUND: A consensus on normal atrial deformation measurements by feature-tracking cardiac MRI remained absent. PURPOSE: Provide reference ranges for atrial strain parameters in normal subjects, evaluating the influence of field strength and analysis software on the measurements. STUDY TYPE: Meta-analysis. POPULATION: 2708 subjects from 42 studies undergoing cardiac MRI. ASSESSMENT: A systematic search was conducted from database (PubMed, Web of Science, ScienceDirect, and EMBASE) inception through August 2023. The random-effects model was used to pool the means of biatrial strain parameters. Heterogeneity and clinical variable effects were assessed. Strain measurements among different field strengths and analysis software were compared. STATISTICAL TESTS: The inverse-variance method, Cochrane Q statistic, and I2 value, meta-regression analysis, and ANOVA were used; P < 0.05 was considered statistically significant. RESULTS: The pooled means of left atrial (LA) total strain (εs), passive strain (εe), and active strain (εa) were 37.46%, 22.73%, and 16.24%, respectively, and the pooled means of LA total strain rate (SRs), passive strain rate (SRe), and active strain rate (SRa) were 1.66, -1.95, and -1.83, indicating significant heterogeneity. The pooled means of right atrial (RA) εs, εe, and εa were 44.87%, 26.05%, and 18.83%. RA SRs, SRe, and SRa were 1.66, -1.95, and -1.83, respectively. The meta-regression identified age as significantly associated with LA εs, εe and SRe, field strength was associated with LA SRa (all P < 0.05). ANOVA revealed differences in LA εa and SRa among different analysis software and in LA εs and all LA strain rates (all P < 0.05) among field strengths. No significant differences were identified in RA strain across analysis software (RA strain: P = 0.145-0.749; RA strain rates: P = 0.073-0.744) and field strengths (RA strain: P = 0.641-0.794; RA strain rates: P = 0.204-0.458). DATA CONCLUSION: This study demonstrated the pooled reference values of biatrial strain. Age, analysis software, and field strength were attributed to differences in LA strain, whereas RA strain showed consistency across different field strengths and analysis software. Limited study subjects may account for the absence of influence on RA strain. TECHNICAL EFFICACY: Stage 5.

Chemical Structures, Biological Activities, and Biosynthetic Analysis of Secondary Metabolites from Agaricus Mushrooms: A Review.

Agaricus mushrooms are an important genus in the Agaricaceae family, belonging to the order Agaricales of the class Basidiomycota. Among them, Agaricus bisporus is a common mushroom for mass consumption, which is not only nutritious but also possesses significant medicinal properties such as anticancer, antibacterial, antioxidant, and immunomodulatory properties. The rare edible mushroom, Agaricus blazei, contains unique agaricol compounds with significant anticancer activity against liver cancer. Agaricus blazei is believed to expel wind and cold, i.e., the pathogenic factors of wind and cold from the body, and is an important formula in traditional Chinese medicine. Despite its nutritional richness and outstanding medicinal value, Agaricus mushrooms have not been systematically compiled and summarized. Therefore, the present review compiles and classifies 70 natural products extracted from Agaricus mushrooms over the past six decades. These compounds exhibit diverse biological and pharmacological activities, with particular emphasis on antitumor and antioxidant properties. While A. blazei and A. bisporus are the primary producers of these compounds, studies on secondary metabolites from other Agaricus species remain limited. Further research is needed to explore and understand the anticancer and nutritional properties of Agaricus mushrooms. This review contributes to the understanding of the structure, bioactivity, and biosynthetic pathways of Agaricus compounds and provides insights for the development of functional foods using these mushrooms.