Analysis of the mechanism of fibrauretine alleviating Alzheimer's disease based on transcriptomics and proteomics.

The dried rattan stem of the Fibraurea Recisa Pierre plant contains the active ingredient known as fibrauretine (FN). Although it greatly affects Alzheimer's disease (AD), the mechanism of their effects still remains unclear. Proteomics and transcriptomics analysis methods were used in this study to determine the mechanism of FN in the treatment of AD. AD model is used through bilateral hippocampal injection of Aß1-40. After successful modeling, FN was given for 30 days. The results showed that FN could improve the cognitive dysfunction of AD model rats, reduce the expression of Aß and P-Tau, increase the content of acetylcholine and reduce the activity of acetylcholinesterase. The Kyoto Encyclopedia of Genes and Genomes enriched differentially expressed genes and proteins are involved in signaling pathways including metabolic pathway, AD, pathway in cancer, PI3K-AKT signaling pathway, and cAMP signaling pathway. Transcriptomics and proteomics sequencing resulted in 19 differentially expressed genes and proteins. Finally, in contrast to the model group, after FN treatment, the protein expressions and genes associated with the PI3K-AKT pathway were significantly improved in RT-qPCR and Western blot and assays. This is consistent with the findings of transcriptomic and proteomic analyses. Our study found that, FN may improve some symptoms of AD model rats through PI3K-AKT signaling pathway.

Coronary microvascular dysfunction and myocardial area at risk assessed by cadmium zinc telluride single photon emission computed tomography after primary percutaneous coronary intervention in acute myocardial infarction patients.

Background: A high proportion of coronary microvascular dysfunction (CMD) has been observed in patients with acute myocardial infarction (AMI) who have received primary percutaneous coronary intervention (PCI), which may affect their prognosis. This study used cadmium zinc telluride (CZT) single photon emission computed tomography (SPECT) to evaluate the prevalence and characteristics of CMD and myocardial area at risk (AAR) in AMI patients who had undergone primary PCI. Methods: We conducted a single-center cross-sectional retrospective study at TEDA International Cardiovascular Hospital from September 2021 to June 2022. A total of 83 patients received primary PCI for AMI. Subsequently, a rest/stress dynamic and routine gated myocardial perfusion imaging (MPI) were performed 1 week after PCI. The CMD group was defined as having a residual stenosis of infarct-related artery (IRA) <50% and myocardial flow reserve (MFR) <2.0 in this corresponding territory, whereas MFR ≥2.0 of IRA pertained to the normal control group. Rest-AAR of infarction (%) and stress-AAR (%) were expressed by the percentage of measured rest-defect-size and stress-defect-size in the left ventricular area, respectively. Logistic regression analyses were performed to identify significant predictors of CMD. Results: A total of 53 patients with a mean age of 57.06±11.99 years were recruited, of whom 81.1% were ST-segment elevation myocardial infarction (STEMI). The proportion of patients with CMD was 79.2% (42/53). The time of pain to SPECT imaging was 7.50±1.27 days in the CMD group and 7.45±1.86 days among controls. CMD patients had a higher body mass index (BMI) than controls (26.48±3.26 vs. 24.36±2.73 kg/m2, P=0.053), and a higher proportion of STEMI, thrombolysis in myocardial infarction (TIMI) 0 grade of IRA prior PCI than controls (88.1% vs. 54.5%, P=0.011; 61.9% vs. 18.2%, P=0.004, respectively). No significant difference was identified in the rest-myocardial blood flow (MBF) of IRA between the 2 groups, whereas the stress-MBF and MFR of IRA, rest-AAR, and stress-AAR in the CMD group were remarkably lowered. Higher BMI [odds ratio (OR): 1.332, 95% confidence interval (CI): 1.008-1.760, P=0.044] and stress-AAR (OR: 1.994, 95% CI: 1.122-3.543, P=0.019) were used as independent predictors of CMD occurrence. Conclusions: The prevalence of CMD is high in AMI patients who received primary PCI. Each 1 kg/m2 increase in BMI was associated with a 1.3-fold increase in CMD risk. A 5% increase in stress-AAR was associated with a nearly 2-fold increase in CMD risk. Increased BMI and stress-AAR predicts decreased coronary reserve function.

BICC1 drives pancreatic cancer stemness and chemoresistance by facilitating tryptophan metabolism.

Pancreatic adenocarcinoma is the fourth leading cause of malignancy-related deaths, with rapid development of drug resistance driven by pancreatic cancer stem cells. However, the mechanisms sustaining stemness and chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Here, we demonstrate that Bicaudal C homolog 1 (BICC1), an RNA binding protein regulating numerous cytoplasmic mRNAs, facilitates chemoresistance and stemness in PDAC. Mechanistically, BICC1 activated tryptophan catabolism in PDAC by up-regulating indoleamine 2,3-dioxygenase-1 (IDO1) expression, a tryptophan-catabolizing enzyme. Increased levels of tryptophan metabolites contribute to NAD+ synthesis and oxidative phosphorylation, leading to a stem cell-like phenotype. Blocking BICC1/IDO1/tryptophan metabolism signaling greatly improves the gemcitabine (GEM) efficacy in several PDAC models with high BICC1 level. These findings indicate that BICC1 is a critical tryptophan metabolism regulator that drives the stemness and chemoresistance of PDAC and thus a potential target for combinatorial therapeutic strategy against chemoresistance.

Paeoniflorin alleviates depression by inhibiting the activation of NLRP3 inflammasome via promoting mitochondrial autophagy.

Depression ranks among the most common neuropsychiatric disorders globally. Current studies examining the roles of inflammation and mitochondrial autophagy in the antidepressant efficacy of paeoniflorin (PF) are sparse. This study aimed to elucidate PF's antidepressant mechanism by promoting autophagy and inhibiting NLRP3 inflammasome activation using chronic unpredictable mild stimulation (CUMS)-induced C57BL/6 mouse models in vivo and corticosterone (CORT)-induced HT22 cell models in vitro. Results demonstrated that PF enhanced the viability of HT22 cells following CORT exposure, restored mitochondrial membrane potential (MMP), reduced reactive oxygen species accumulation, increased LC3 fluorescence intensity, and suppressed inflammatory cytokine secretion and inflammation activation. Additionally, PF ameliorated depressive behaviors induced by CUMS and improved damage in hippocampal neurons. It also reduced the expression of NLRP3, ASC, Caspase-1, IL-1ß, and the assembly of the NLRP3 inflammasome. Moreover, PF upregulated the expression of autophagy-related proteins in the hippocampus, facilitating the clearance of damaged mitochondria and enhancing autophagy. The role of autophagy in PF's antidepressant effects was further confirmed through the use of the autophagy inhibitor 3-methyladenine (3-MA), which reduced the efficacy of PF. In conclusion, PF effectively improved depressive behaviors in CUMS-induced mice and reduced NLRP3-mediated inflammation both in vivo and in vitro, likely via the induction of autophagy.

Molecular evolution and functional diversification of metal tolerance protein families in cereals plants and function of maize MTP protein.

Plants employ metal tolerance proteins (MTPs) to confer tolerance by sequestering excess ions into vacuoles. MTPs belong to the cation diffusion facilitator (CDF) family, which facilitates the transport of divalent transition metal cations. In this study, we conducted a comprehensive analysis of the MTP gene families across 21 plant species, including maize (Zea mays). A total of 247 MTP genes were identified within these plant genomes and categorized into distinct subgroups, namely Zn-CDF, Mn-CDF, and Fe/Zn-CDF, based on phylogenetic analyses. This investigation encompassed the characterization of genomic distribution, gene structures, cis-regulatory elements, collinearity relationships, and gene ontology functions associated with MTPs. Transcriptomic analyses unveiled stress-specific expression patterns of MTP genes under various abiotic stresses. Moreover, quantitative RT-PCR assays were employed to assess maize MTP gene responses to diverse heavy metal stress conditions. Functional validation of metal tolerance roles was achieved through heterologous expression in yeast. This integrated evolutionary scrutiny of MTP families in cereals furnishes a valuable framework for the elucidation of MTP functions in subsequent studies. Notably, the prioritized MTP gene ZmMTP6 emerged as a positive regulator of plant Cd tolerance, thereby offering a pivotal genetic asset for the development of Cd-tolerant crops, particularly maize cultivars.

Mangiferin alleviated poststroke cognitive impairment by modulating lipid metabolism in cerebral ischemia/reperfusion rats.

INTRODUCTION: Mangiferin is a Chinese herbal extract with multiple biological activities. Mangiferin can penetrate the blood‒brain barrier and has potential in the treatment of nervous system diseases. These findings suggest that mangiferin protects the neurological function in ischemic stroke rats by targeting multiple signaling pathways. However, little is known about the effect and mechanism of mangiferin in alleviating poststroke cognitive impairment. METHODS: Cerebral ischemia/reperfusion (I/R) rats were generated via middle cerebral artery occlusion. Laser speckle imaging was used to monitor the cerebral blood flow. The I/R rats were intraperitoneally (i.p.) injected with 40 mg/kg mangiferin for 7 consecutive days. Neurological scoring, and TTC staining were performed to evaluate neurological function. Behavioral experiments, including the open field test, elevated plus maze, sucrose preference test, and novel object recognition test, were performed to evaluate cognitive function. Metabolomic data from brain tissue with multivariate statistics were analyzed by gas chromatography‒mass spectrometry and liquid chromatography‒mass spectrometry. RESULTS: Mangiferin markedly decreased neurological scores, and reduced infarct areas. Mangiferin significantly attenuated anxiety-like and depression-like behaviors and enhanced learning and memory in I/R rats. According to the metabolomics results, 13 metabolites were identified to be potentially regulated by mangiferin, and the differentially abundant metabolites were mainly involved in lipid metabolism. CONCLUSIONS: Mangiferin protected neurological function and relieved poststroke cognitive impairment by improving lipid metabolism abnormalities in I/R rats.

Dysfunctional circadian clock accelerates cancer metastasis by intestinal microbiota triggering accumulation of myeloid-derived suppressor cells.

Circadian homeostasis in mammals is a key intrinsic mechanism for responding to the external environment. However, the interplay between circadian rhythms and the tumor microenvironment (TME) and its influence on metastasis are still unclear. Here, in patients with colorectal cancer (CRC), disturbances of circadian rhythm and the accumulation of monocytes and granulocytes were closely related to metastasis. Moreover, dysregulation of circadian rhythm promoted lung metastasis of CRC by inducing the accumulation of myeloid-derived suppressor cells (MDSCs) and dysfunctional CD8+ T cells in the lungs of mice. Also, gut microbiota and its derived metabolite taurocholic acid (TCA) contributed to lung metastasis of CRC by triggering the accumulation of MDSCs in mice. Mechanistically, TCA promoted glycolysis of MDSCs epigenetically by enhancing mono-methylation of H3K4 of target genes and inhibited CHIP-mediated ubiquitination of PDL1. Our study links the biological clock with MDSCs in the TME through gut microbiota/metabolites in controlling the metastatic spread of CRC, uncovering a systemic mechanism for cancer metastasis.

Post-translational Regulation of BRI1-EMS Suppressor 1 and Brassinazole-resistant 1.

BRI1-EMS Suppressor 1 (BES1) and Brassinazole resistant 1 (BZR1) are two highly similar master transcription factors of the brassinosteroid (BR) signaling pathway that regulate a variety of plant growth and development processes as well as stress responses. Previous genetic and biochemical analyses have established a complex regulatory network to control the two transcription factors. This network includes coordination with other transcription factors and interactors, multiple post-translational modifications (PTMs), and differential subcellular localizations. In this review, we systematically detail the functions and regulatory mechanisms of various PTMs: phosphorylation/dephosphorylation, ubiquitination/deubiquitination, SUMOylation/deSUMOylation, oxidation/reduction, in regulating the subcellular localization, protein stability, and the transcriptional activity of BES1/BZR1. We also discuss the current knowledge about the BES1/BZR1-interactors mediating the dynamic nucleocytoplasmic shuttling of BES1 and BZR1.

Understanding the cascade heterojunction of CuPc/Bi-MOF for photoelectrochemical nitrate reduction.

Herein, a CuPc/Bi-MOF cascade heterojunction is synthesized exhibiting an excellent NH3 yield (7.13 µg h-1 cm-2) and stability. Characterization studies show that the cascade heterostructure with a unique morphology and oxygen vacancies offers new insights into future photoelectrocatalytic material design.

Establishment of a real-time fluorescent quantitative PCR detection method and phylogenetic analysis of BoAHV-1.

BACKGROUND: Infectious bovine rhinotracheitis (IBR), caused by Bovine alphaherpesvirus-1 (BoAHV-1), is an acute, highly contagious disease primarily characterized by respiratory tract lesions in infected cattle. Due to its severe pathological damage and extensive transmission, it results in significant economic losses in the cattle industry. Accurate detection of BoAHV-1 is of paramount importance. In this study, we developed a real-time fluorescent quantitative PCR detection method for detecting BoAHV-1 infections. Utilizing this method, we tested clinical samples and successfully identified and isolated a strain of BoAHV-1.1 from positive samples. Subsequently, we conducted a genetic evolution analysis on the isolate strain's gC, TK, gG, gD, and gE genes. RESULTS: The study developed a real-time quantitative PCR detection method using SYBR Green II, achieving a detection limit of 7.8 × 101 DNA copies/µL. Specificity and repeatability analyses demonstrated no cross-reactivity with other related pathogens, highlighting excellent repeatability. Using this method, 15 out of 86 clinical nasal swab samples from cattle were found to be positive (17.44%), which was higher than the results obtained from conventional PCR detection (13.95%, 12/86). The homology analysis and phylogenetic tree analysis of the gC, TK, gG, gD, and gE genes of the isolated strain indicate that the JL5 strain shares high homology with the BoAHV-1.1 reference strains. Amino acid sequence analysis revealed that gC, gE, and gG each had two amino acid mutations, while the TK gene had one synonymous mutation and one H to Y mutation, with no amino acid mutations observed in the gD gene. Phylogenetic tree analysis indicated that the JL5 strain belongs to the BoAHV-1.1 genotype and is closely related to American strains such as C33, C14, and C28. CONCLUSIONS: The established real-time fluorescent quantitative PCR detection method exhibits good repeatability, specificity, and sensitivity. Furthermore, genetic evolution analysis of the isolated BoAHV-1 JL-5 strain indicates that it belongs to the BoAHV-1.1 subtype. These findings provide a foundation and data for the detection, prevention, and control Infectious Bovine Rhinotracheitis.

Tumors cells with mismatch repair deficiency induce hyperactivation of pyroptosis resistant to cell membrane damage but are more sensitive to co-treatment of IFN-γ and TNF-α to PANoptosis.

Hypermutated neoantigens in cancers with DNA mismatch repair deficiency (dMMR) are prerequisites for favorable clinical responses to immune-checkpoint blockade (ICB) therapy. However, TMB is not significantly associated with favorable prognosis from Preclinical and clinical studies. It implies that except for TMB, other mechanisms should be needed to contribute to successful cancer immunotherapy. We found that the hyperactivation of PANoptotic effective molecules in dMMR tumor cells caused cell membrane damage, induced ESCRT-mediated membrane repair, and protected tumor cells from the damage caused by Triton X-100, while DNA mismatch repair proficient (pMMR) tumor cells were sensitive to Triton X-100 mediating cell membrane damage due to the lack of ESCRT-mediated membrane repair. There was hyperactivation of GSDMD, GSDME, and p-MLKL in dMMR tumor cells. Co-treatment of IFN-γ and TNF-α induced rapid death of dMMR tumor cells by inducing PANoptosis including pyroptosis, apoptosis, and no necrosis. pMMR tumor cells had defects in the PANoptosis pathway and were resistant to co-treatment of IFN-γ and TNF-α. In conclusion, we can activate immune cells to release IFN-γ and TNF-α to overcome resistance to ICB treatment.

Transcriptomic Profiling in Low-Risk Thyroid Cancer Induced by Microwave Ablation.

Background: Peripheral blood mononuclear cells (PBMCs) serve as the immune system's primary transportation hub outside of the affected ablated tissue. This study aims to explore the transcriptomic profiling of the immune response in PBMCs induced by microwave ablation (MWA) in low-risk thyroid cancer. Methods: For eight patients diagnosed with low-risk thyroid cancer, 10 ml of peripheral venous blood was collected before MWA as well as one day and one month after MWA. mRNA was extracted from PBMCs for transcriptome next-generation gene sequencing and qRT-PCR analyses. The plasma samples were used for chemokine detection purposes. Results: One day and one month after MWA, there were significant changes in GSEA, particularly in the NF-kappa B-TNFα pathway, inflammatory response, and early and late estrogen response. Common changes in differently expressed genes resulted in a significant downregulation of tumor-promoting genes (BCL3, NR6A1, and PFKFB3). One day after low-risk thyroid cancer MWA, GO enrichment analysis mainly revealed processes related to oxygen transport and other pathways. One month after MWA, GO enrichment analysis mainly revealed regulation of toll-like receptor signaling and other pathways. Furthermore, inflammation-related cytokines and regulatory genes, as well as tumor-promoting cytokines and regulatory genes, were downregulated after MWA. Conclusions: This study presents a comprehensive profile of the systemic immune response induced by thermal ablation for treating low-risk thyroid cancer. More significantly, this study provides valuable insight into potential references for systemic antitumor immunity of ablation against low-risk thyroid cancer. This trial is registered with ChiCTR1900024544.

Protein degrons and degradation: Exploring substrate recognition and pathway selection in plants.

Proteome composition is dynamic and influenced by many internal and external cues, including developmental signals, light availability, or environmental stresses. Protein degradation, in synergy with protein biosynthesis, allows cells to respond to various stimuli and adapt by reshaping the proteome. Protein degradation mediates the final and irreversible disassembly of proteins, which is important for protein quality control and to eliminate misfolded or damaged proteins, as well as entire organelles. Consequently, it contributes to cell resilience by buffering against protein or organellar damage caused by stresses. Moreover, protein degradation plays important roles in cell signaling, as well as transcriptional and translational events. The intricate task of recognizing specific proteins for degradation is achieved by specialized systems that are tailored to the substrate's physicochemical properties and subcellular localization. These systems recognize diverse substrate cues collectively referred to as "degrons", which can assume a range of structural configurations. They are molecular surfaces recognized by E3 ligases of the ubiquitin-proteasome system, but can also be considered as general features recognized by other degradation systems, including autophagy or even organellar proteases. Here we provide an overview of the newest developments in the field, delving into the intricate processes of protein recognition and elucidating the pathways through which they are recruited for degradation.

VPAC2 Receptor Signaling Promotes Growth and Immunosuppression in Pancreatic Cancer.

Pancreatic cancer (PDAC) harbors a complex tumor microenvironment (TME), and crosstalk between cells in the TME can contribute to drug resistance and relapse. Vasoactive intestinal peptide (VIP) is overexpressed in PDAC, and VIP receptors expressed on T cells are a targetable pathway that sensitizes PDAC to immunotherapy. In this study, we showed that pancreatic cancer cells engage in autocrine VIP signaling through VIP receptor 2 (VPAC2). High co-expression of VIP with VPAC2 correlated with reduced relapse-free survival in PDAC patients. VPAC2 activation in PDAC cells upregulated piwi-like RNA-mediated gene silencing 2 (Piwil2), which stimulated cancer cell clonogenic growth. In addition, VPAC2 signaling increased expression of TGF-ß1 to inhibit T cell function. Loss of VPAC2 on PDAC cells led to reduced tumor growth and increased sensitivity to anti-PD1 immunotherapy in mouse models of PDAC. Overall, these findings expand our understanding of the role of VIP/VPAC2 signaling in PDAC and provide the rationale for developing potent VPAC2-specific antagonists for treating PDAC patients.

Regeneration in Mice of Injured Skin, Heart, and Spinal Cord by α-Gal Nanoparticles Recapitulates Regeneration in Amphibians.

The healing of skin wounds, myocardial, and spinal cord injuries in salamander, newt, and axolotl amphibians, and in mouse neonates, results in scar-free regeneration, whereas injuries in adult mice heal by fibrosis and scar formation. Although both types of healing are mediated by macrophages, regeneration in these amphibians and in mouse neonates also involves innate activation of the complement system. These differences suggest that localized complement activation in adult mouse injuries might induce regeneration instead of the default fibrosis and scar formation. Localized complement activation is feasible by antigen/antibody interaction between biodegradable nanoparticles presenting α-gal epitopes (α-gal nanoparticles) and the natural anti-Gal antibody which is abundant in humans. Administration of α-gal nanoparticles into injuries of anti-Gal-producing adult mice results in localized complement activation which induces rapid and extensive macrophage recruitment. These macrophages bind anti-Gal-coated α-gal nanoparticles and polarize into M2 pro-regenerative macrophages that orchestrate accelerated scar-free regeneration of skin wounds and regeneration of myocardium injured by myocardial infarction (MI). Furthermore, injection of α-gal nanoparticles into spinal cord injuries of anti-Gal-producing adult mice induces recruitment of M2 macrophages, that mediate extensive angiogenesis and axonal sprouting, which reconnects between proximal and distal severed axons. Thus, α-gal nanoparticle treatment in adult mice mimics physiologic regeneration in amphibians. These studies further suggest that α-gal nanoparticles may be of significance in the treatment of human injuries.

Responses of runoff and sediment yield to slope length and gravel content of Lou soil engineering accumulation slope in Guanzhong region, Northwest China.

With the economic development, a large number of engineering accumulation bodies with Lou soil as the main soil type were produced in Guanzhong area, Northwest China. We examined the characteristics of runoff and sediment yield of Lou soil accumulation bodies with earth (gravel content 0%) and earth-rock (gravel content 30%) under different rainfall intensities (1.0, 1.5, 2.0, 2.5 mm·min-1) and different slope lengths (3, 5, 6.5, 12 m) by the simulating rainfall method. The results showed that runoff rate was relatively stable when rainfall intensity was 1.0-1.5 mm·min-1, while runoff rate fluctuated obviously when rainfall intensity was 2.0-2.5 mm·min-1. The average runoff rate varied significantly across different rainfall intensities on the same slopes, and the difference of average runoff rate of the two slopes was significantly increased with rainfall intensity. Under the same rainfall intensity, the difference in runoff rate between the slope lengths of the earth-rock slope was more obvious than that of the earth slope. When the slope length was 3-6.5 m, flow velocity increased rapidly at first and then increased slowly or tended to be stable. When the slope length was 12 m, flow velocity increased significantly. In general, with the increases of rainfall intensity, inhibition effect of gravel on the average flow velocity was enhanced. When rainfall intensity was 2.5 mm·min-1, the maximum reduction in the average flow velocity of earth-rock slope was 61.5% lower than that of earth slope. When rainfall intensity was less than 2.0 mm·min-1, sediment yield rate showed a trend of gradual decline or stable change, while that under the other rainfall intensities showed a trend of rapid decline and then fluctuated sharply. The greater the rainfall intensity, the more obvious the fluctuation. There was a significant positive correlation between the average sediment yield rate and runoff parameters, with the runoff rate showing the best fitting effect. Among the factors, slope length had the highest contribution to runoff velocity and rainfall erosion, which was 51.8% and 35.5%, respectively. This study can provide scientific basis for soil and water erosion control of engineering accumulation in Lou soil areas.

Fish swim bladders as valve leaflets enhance the durability of transcatheter aortic valve replacement devices.

Transcatheter aortic valve replacement (TAVR) has emerged as an effective therapy for inoperable patients with severe aortic stenosis (AS). However, calcification-induced limited durability restricts its application. Fish swim bladders (FSB), which are resistant to calcific degeneration, offer a viable solution to this challenge. In this study, we developed a new TAVR device using FSB as the valve leaflet. Furthermore, the in vitro durability, in vivo performance, and size selection of this TAVR device were assessed by an experimental study and finite element analysis. A self-expandable TAVR device was fabricated by suturing the FSB films into a 23 mm nitinol alloy frame. Further, hemodynamic performance, such as effective orifice area, transvalvular pressure difference and regurgitant fraction, the durability was tested by the pulsatile flow test and accelerated fatigue test, according to the ISO 5840-3. The effect of release size on hydrodynamic performance was also investigated. Finally, the in vivo performance of the TAVR device were examined using a porcine implantation model. The results showed that the strength of the FSB films satisfied the requirements for valve leaflets. The hemodynamic performance of the FSB TAVR device met the requirements of ISO 5840-3 standards. After 400 million cycles, the FSB showed no fiber loss, torn, perforation, or other valve failure phenomena. In porcine models, the devices were well-positioned, functioned well with no stenosis immediately after the operation. Collectively, we successfully developed a TAVR device with FSB as valve leaflets that exhibited good fatigue resistance. STATEMENT OF SIGNIFICANCE: The source of material for the leaflets of commercialized biological heart valves (BHVs) is mainly bovine pericardium, but this material suffers the following problems: large and uneven thickness of the material, the presence of α-Gal and Neu5Gc antigens, and the susceptibility to structural valve degradation (SVD). New material for BHVs leaflets is rarely reported. In this study, we prepared a transcatheter aortic valve (TAV) and performed long-term in vitro and short-term in vivo studies using fish swim bladder (FSB) as the leaflets. The study confirmed that FSB TAV device can complete 400 million fatigue tests and maintain the good morphology of the leaflets, and that it still maintains good functionality after a certain amount of compression, indicating that FSB is a promising material for leaflets.

Left atrial size modify the association between uric acid and atrial fibrillation in patients with coronary artery disease.

BACKGROUND AND AIMS: The potential influence of left atrial size on the relationship between uric acid and atrial fibrillation has not been fully investigated. This study aims to evaluate the interaction effect of left atrial size on the association between uric acid and atrial fibrillation in patients with coronary artery disease. METHODS AND RESULTS: This retrospective cohort study, conducted from January 2018 to October 2022, included 2004 patients undergoing Drug-Eluting Stent implantation for coronary artery disease. Utilizing logistic regression models with the product of left atrial enlargement (LAE) and uric acid, interaction effects were assessed. Among the participants, 383 had LAE, and 159 experienced atrial fibrillation. After adjusting for covariates, continuous uric acid levels were associated with an increased risk of atrial fibrillation in patients without LAE (OR:1.631, 95% CI: 1.284-2.072), but not in those with LAE (OR:1.069, 95% CI: 0.848-1.348). A significant interaction of uric acid levels was observed between groups with and without LAE (p = 0.046). Restricted cubic spline curves indicated a J-shaped relationship between uric acid and atrial fibrillation in the absence of LAE. However, the association between uric acid levels and atrial fibrillation in the LAE group remained unchanged with increasing uric acid levels. CONCLUSION: The study suggested that left atrial size modified the association between uric acid and atrial fibrillation in patients with coronary artery disease. Uric acid serves as a potential biomarker for atrial fibrillation risk, especially in individuals without LAE.

Palmatine improves cognitive dysfunction in Alzheimer's disease model rats through autophagy pathway and regulation of gut microbiota.

Alzheimer's disease (AD) is a primary degenerative encephalopathy that first appeared as a decline in memory and learning skills. Over time, the condition's severity grew. Palmatine (Pal) alleviates Alzheimer's disease symptoms, which has neuroprotective benefits. Numerous investigations have demonstrated a close relationship among AD and gut structure changes. The aim of the research was investigating whether the improvement of Pal on AD is linked to regulating gut flora and autophagy. First, we used Aß1-40 to induce apoptosis in HT22 cells. After Pal treatment, apoptosis can be improved. Then, We used bilateral intracranial hippocampal injection of Aß1-40 for establishing the AD model, after treatment with Pal, the morris water maze experiment and eight-arm maze test demonstrated that Pal enhanced the AD rats' capacity for learning and memory, HE staining illustrated that Pal improved the morphological abnormalities of brain cells and gut tissue damage. Pal reduced the death of hippocampus neurons, as shown by Nissl staining. Pal substantially reduced Tau hyperphosphorylation and Aß accumulation in the brain, according to immunohistochemical labelling. Pal improved the expression of LC3, Beclin 1, AMPK, and suppressed the expression of mTOR and P62, as validated by RT-qPCR and immunofluorescence labelling. This suggests that Pal's treatment of AD may be associated with the control of the AMPK/mTOR autophagy signalling system. 16S rRNA sequencing and short-chain fatty acids (SCFAs) content detection analysis illustrated that Pal has the potential to enhance the content of SCFAs, reverse the alterations in gut microorganisms. It has been showed by the study that Pal could improve AD by activating autophagy signaling pathway and improving gut barrier changes.