A cellular and spatial map of the choroid plexus across brain ventricles and ages.

The choroid plexus (ChP) in each brain ventricle produces cerebrospinal fluid (CSF) and forms the blood-CSF barrier. Here, we construct a single-cell and spatial atlas of each ChP in the developing, adult, and aged mouse brain. We delineate diverse cell types, subtypes, cell states, and expression programs in epithelial and mesenchymal cells across ages and ventricles. In the developing ChP, we predict a common progenitor pool for epithelial and neuronal cells, validated by lineage tracing. Epithelial and fibroblast cells show regionalized expression by ventricle, starting at embryonic stages and persisting with age, with a dramatic transcriptional shift with maturation, and a smaller shift in each aged cell type. With aging, epithelial cells upregulate host-defense programs, and resident macrophages upregulate interleukin-1ß (IL-1ß) signaling genes. Our atlas reveals cellular diversity, architecture and signaling across ventricles during development, maturation, and aging of the ChP-brain barrier.

The dynamics of B-cell reconstitution post allogeneic hematopoietic stem cell transplantation: A real-world study.

BACKGROUND: The immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is crucial for preventing infections and relapse and enhancing graft-versus-tumor effects. B cells play an important role in humoral immunity and immune regulation, but their reconstitution after allo-HSCT has not been well studied. METHODS: In this study, we analyzed the dynamics of B cells in 252 patients who underwent allo-HSCT for 2 years and assessed the impact of factors on B-cell reconstitution and their correlations with survival outcomes, as well as the development stages of B cells in the bone marrow and the subsets in the peripheral blood. RESULTS: We found that the B-cell reconstitution in the bone marrow was consistent with the peripheral blood (p = 0.232). B-cell reconstitution was delayed by the male gender, age >50, older donor age, the occurrence of chronic and acute graft-versus-host disease, and the infections of fungi and cytomegalovirus. The survival analysis revealed that patients with lower B cells had higher risks of death and relapse. More importantly, we used propensity score matching to obtain the conclusion that post-1-year B-cell reconstitution is better in females. Meanwhile, using mediation analysis, we proposed the age-B cells-survival axis and found that B-cell reconstitution at month 12 posttransplant mediated the effect of age on patient survival (p = 0.013). We also found that younger patients showed more immature B cells in the bone marrow after transplantation (p = 0.037). CONCLUSION: Our findings provide valuable insights for optimizing the management of B-cell reconstitution and improving the efficacy and safety of allo-HSCT.

Magnetic detection under high pressures using designed silicon vacancy centres in silicon carbide.

Pressure-induced magnetic phase transitions are attracting interest as a means to detect superconducting behaviour at high pressures in diamond anvil cells, but determining the local magnetic properties of samples is a challenge due to the small volumes of sample chambers. Optically detected magnetic resonance of nitrogen vacancy centres in diamond has recently been used for the in situ detection of pressure-induced phase transitions. However, owing to their four orientation axes and temperature-dependent zero-field splitting, interpreting these optically detected magnetic resonance spectra remains challenging. Here we study the optical and spin properties of implanted silicon vacancy defects in 4H-silicon carbide that exhibit single-axis and temperature-independent zero-field splitting. Using this technique, we observe the magnetic phase transition of Nd2Fe14B at about 7 GPa and map the critical temperature-pressure phase diagram of the superconductor YBa2Cu3O6.6. These results highlight the potential of silicon vacancy-based quantum sensors for in situ magnetic detection at high pressures.

Arc discharge method to fabricate large concave structures for open-access fiber Fabry-Pérot cavities.

We present a novel micro-fabrication technique for creating concave surfaces on the endfacets of photonic crystal fibers. A fiber fusion splicer is used to generate arc discharges to melt and reshape the fiber endfacet. This technique can produce large spherical concave surfaces with roughness as low as 0.12 nm in various types of photonic crystal fibers. The deviation of fabricated surface and a spherical profile in the region of 70 µm in diameter is less than 50 nm. The center of the concave surface and the fiber mode field are highly coincident with a deviation less than 500 nm. Finesse measurements have shown that a Fabry-Pérot cavity composed of the fiber fabricated using this method and a plane mirror maintains finesse of 20000. This method is easy to replicate, making it a practical and efficient approach to fabricate concave surface on fibers for open-access fiber Fabry-Pérot cavities.

Clinical characteristics of delirium in older patients with first-ever acute myocardial infarction who underwent percutaneous coronary intervention : A retrospective study.

OBJECTIVES: Delirium is a serious complication of cardiac surgery and a common clinical problem. The study aimed to identify the incidence, risk factors, and outcomes of delirium in older patients (≥ 65 years) with first-ever acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI). METHODS: A retrospective cohort study was performed in a hospital in northern China. A total of 1033 older patients with first-ever AMI who underwent PCI between January 2018 and April 2021 were screened for delirium using the CAM-ICU method. Clinical and laboratory data were collected. RESULTS: A total of 134 (12.97%) patients were diagnosed with delirium. Patients with delirium were older. The most common concomitant diseases were cardiac arrest, chronic renal failure, and a history of coronary artery bypass graft (CABG). Delirious patients experienced more times of mechanical ventilation, more intra-aortic balloon pump (IABP) support, high postoperative immediate pain score (VAS), more non-bedside cardiac rehabilitation, and longer total length of stay and cardiac care unit (CCU) time. Multivariable logistic regression showed that age, mechanical ventilation, postoperative immediate pain score, and non-bedside cardiac rehabilitation were independently associated with delirium. Delirium was an independent predictor of prolonged CCU stay, total length of stay, and 1­year mortality. CONCLUSION: Age, mechanical ventilation, postoperative immediate pain score, and non-bedside cardiac rehabilitation were independently closely related to delirium in older patients with first-ever AMI who underwent PCI. Delirium was associated with a higher 1­year all-cause mortality.

Orthogonal genome-wide screens of bat cells identify MTHFD1 as a target of broad antiviral therapy.

Bats are responsible for the zoonotic transmission of several major viral diseases, including those leading to the 2003 SARS outbreak and likely the ongoing COVID-19 pandemic. While comparative genomics studies have revealed characteristic adaptations of the bat innate immune system, functional genomic studies are urgently needed to provide a foundation for the molecular dissection of the viral tolerance in bats. Here we report the establishment of genome-wide RNA interference (RNAi) and CRISPR libraries for the screening of the model megabat, Pteropus alecto. We used the complementary RNAi and CRISPR libraries to interrogate P. alecto cells for infection with two different viruses: mumps virus and influenza A virus, respectively. Independent screening results converged on the endocytosis pathway and the protein secretory pathway as required for both viral infections. Additionally, we revealed a general dependence of the C1-tetrahydrofolate synthase gene, MTHFD1, for viral replication in bat cells and human cells. The MTHFD1 inhibitor, carolacton, potently blocked replication of several RNA viruses, including SARS-CoV-2. We also discovered that bats have lower expression levels of MTHFD1 than humans. Our studies provide a resource for systematic inquiry into the genetic underpinnings of bat biology and a potential target for developing broad-spectrum antiviral therapy.

Ratiometric luminescent simultaneous sensing of aristolochic acids (I-IV) by a novel metal-organic framework and its nanowire.

Aristolochic acids (AAs), which are a group of nitrophenanthrene carboxylic acids formed by Aristolochia plant, have become an increasing serious threat to humans due to their nephrotoxicity and carcinogenicity. Fast and accurate approaches capable of simultaneous sensing of aristolochic acids (I-IV) are vital to avoid intake of such compounds. In this research, the novel ratiometric fluorescence zinc metal-organic framework and its nanowire have been prepared. The two different coordination modes (tetrahedral configuration and twisted triangular bipyramidal configuration) within zinc metal-organic framework lead to the significant double emissions. The ratiometric fluorescence approach based on nanowire provides a broader concentration range (3.00 × 10-7~1.00 × 10-4 M) and lower limit of detection (3.70 × 10-8 M) than that based on zinc metal-organic framework (1.00 × 10-6~1.00 × 10-4 M, 5.91 × 10-7 M). The RSDs of the results are in the range 1.4-3.5% (nanowire). The density functional theory calculations and UV-Vis absorption verify that the sensing mechanism is due to charge transfer and energy transfer. Excellent spiked recoveries for AAs(I-IV) in soil and water support that nanowire is competent to simultaneously detect these targets in real samples, and the proposed approach has potential as a fluorescence sensing platform for the simultaneous detection of AAs (I-IV) in complex systems.

Progress on metabolites of Astragalus medicinal plants and a new factor affecting their formation: Biotransformation of endophytic fungi.

It is generally believed that the main influencing factors of plant metabolism are genetic and environmental factors. However, the transformation and catalysis of metabolic intermediates by endophytic fungi have become a new factor and resource attracting attention in recent years. There are over 2000 precious plant species in the Astragalus genus. In the past decade, at least 303 high-value metabolites have been isolated from the Astragalus medicinal plants, including 124 saponins, 150 flavonoids, two alkaloids, six sterols, and over 20 other types of compounds. These medicinal plants contain abundant endophytic fungi with unique functions, and nearly 600 endophytic fungi with known identity have been detected, but only about 35 strains belonging to 13 genera have been isolated. Among them, at least four strains affiliated to Penicillium roseopurpureum, Alternaria eureka, Neosartorya hiratsukae, and Camarosporium laburnicola have demonstrated the ability to biotransform four saponin compounds from the Astragalus genus, resulting in the production of 66 new compounds, which have significantly enhanced our understanding of the formation of metabolites in plants of the Astragalus genus. They provide a scientific basis for improving the cultivation quality of Astragalus plants through the modification of dominant fungal endophytes or reshaping the endophytic fungal community. Additionally, they open up new avenues for the discovery of specialized, green, efficient, and sustainable biotransformation pathways for complex pharmaceutical intermediates.

VrMYB90 Functions Synergistically with VrbHLHA and VrMYB3 to Regulate Anthocyanin Biosynthesis in Mung Bean.

Mung bean is an important grain-legume crop and its sprout is an economical and nutrient vegetable for the public, but the genetic regulation of anthocyanin production, which is an antioxidant in mung bean, remains elusive. In our study, we characterized a subgroup (SG) 6 R2R3-MYB anthocyanin activator VrMYB90 and a SG 4 R2R3-MYB anthocyanin repressor VrMYB3, which synergistically function in regulating anthocyanin synthesis with VrbHLHA transcription factor. The overexpressed VrMYB90 protein activates the expression of VrMYB3 and VrbHLHA in mung bean hair roots, and also promotes VrDFR and VrANS transcript levels by directly binding to the corresponding promoters at specific motifs (CAACTG and CCGTTG). VrMYB90 interacts with VrbHLHA to enhance its regulatory activities on VrDFR and VrANS. Furthermore, the interaction between VrMYB3 with VrMYB90 and VrbHLHA could result in the restriction of anthocyanin synthesis to prevent excessive anthocyanin accumulation. Our results demonstrate that the VrMYB90 protein, in conjunction with VrMYB3 and VrbHLHA, forms a key regulatory module to fine-tune anthocyanin synthesis in mung bean.

Sugar Signals and R2R3-MYBs Participate in Potassium-Repressed Anthocyanin Accumulation in Radish.

Anthocyanin biosynthesis in plants is influenced by a wide range of environmental factors, such as light, temperature and nutrient availability. In this study, we revealed that the potassium-repressed anthocyanin accumulation in radish hypocotyls was associated with altered sugar distribution and sugar signaling pathways rather than changes in oxidative stress status. Sugar-feeding experiments suggested a hexokinase-independent glucose signal acted as a major contributor in regulating anthocyanin biosynthesis, transport and regulatory genes at the transcriptional level. Several R2R3-MYBs were identified as anthocyanin-related MYBs. Phylogenetic and protein sequence analyses suggested that RsMYB75 met the criteria of subgroup 6 MYB activator, while RsMYB39 and RsMYB82 seemed to be a non-canonical MYB anthocyanin activator and repressor, respectively. Through yeast-one-hybrid, dual-luciferase and transient expression assays, we confirmed that RsMYB39 strongly induced the promoter activity of anthocyanin transport-related gene RsGSTF12, while RsMYB82 significantly reduced anthocyanin biosynthesis gene RsANS1 expression. Molecular models are proposed in the discussion, allowing speculation on how these novel RsMYBs may regulate the expression levels of anthocyanin-related structural genes. Together, our data evidenced the strong impacts of potassium on sugar metabolism and signaling and its regulation of anthocyanin accumulation through different sugar signals and R2R3-MYBs in a hierarchical regulatory system.

A swine arterivirus deubiquitinase stabilizes two major envelope proteins and promotes production of viral progeny.

Arteriviruses are enveloped positive-strand RNA viruses that assemble and egress using the host cell's exocytic pathway. In previous studies, we demonstrated that most arteriviruses use a unique -2 ribosomal frameshifting mechanism to produce a C-terminally modified variant of their nonstructural protein 2 (nsp2). Like full-length nsp2, the N-terminal domain of this frameshift product, nsp2TF, contains a papain-like protease (PLP2) that has deubiquitinating (DUB) activity, in addition to its role in proteolytic processing of replicase polyproteins. In cells infected with porcine reproductive and respiratory syndrome virus (PRRSV), nsp2TF localizes to compartments of the exocytic pathway, specifically endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and Golgi complex. Here, we show that nsp2TF interacts with the two major viral envelope proteins, the GP5 glycoprotein and membrane (M) protein, which drive the key process of arterivirus assembly and budding. The PRRSV GP5 and M proteins were found to be poly-ubiquitinated, both in an expression system and in cells infected with an nsp2TF-deficient mutant virus. In contrast, ubiquitinated GP5 and M proteins did not accumulate in cells infected with the wild-type, nsp2TF-expressing virus. Further analysis implicated the DUB activity of the nsp2TF PLP2 domain in deconjugation of ubiquitin from GP5/M proteins, thus antagonizing proteasomal degradation of these key viral structural proteins. Our findings suggest that nsp2TF is targeted to the exocytic pathway to reduce proteasome-driven turnover of GP5/M proteins, thus promoting the formation of GP5-M dimers that are critical for arterivirus assembly.

RANKL from bone marrow adipose lineage cells promotes osteoclast formation and bone loss.

Receptor activator of NF-κB ligand (RANKL) is essential for osteoclast formation and bone remodeling. Nevertheless, the cellular source of RANKL for osteoclastogenesis has not been fully uncovered. Different from peripheral adipose tissue, bone marrow (BM) adipose lineage cells originate from bone marrow mesenchymal stromal cells (BMSCs). Here, we demonstrate that adiponectin promoter-driven Cre expression (AdipoqCre ) can target bone marrow adipose lineage cells. We cross the AdipoqCre mice with ranklfl/fl mice to conditionally delete RANKL from BM adipose lineage cells. Conditional deletion of RANKL increases cancellous bone mass of long bones in mice by reducing the formation of trabecular osteoclasts and inhibiting bone resorption but does not affect cortical bone thickness or resorption of calcified cartilage. AdipoqCre ; ranklfl/fl mice exhibit resistance to estrogen deficiency and rosiglitazone (ROS)-induced trabecular bone loss but show bone loss induced by unloading. BM adipose lineage cells therefore represent an essential source of RANKL for the formation of trabecula osteoclasts and resorption of cancellous bone during remodeling under physiological and pathological conditions. Targeting bone marrow adiposity is a promising way of preventing pathological bone loss.

Distinguishing common renal cell carcinomas from benign renal tumors based on machine learning: comparing various CT imaging phases, slices, tumor sizes, and ROI segmentation strategies.

OBJECTIVES: To determine whether a CT-based machine learning (ML) can differentiate benign renal tumors from renal cell carcinomas (RCCs) and improve radiologists' diagnostic performance, and evaluate the impact of variable CT imaging phases, slices, tumor sizes, and region of interest (ROI) segmentation strategies. METHODS: Patients with pathologically proven RCCs and benign renal tumors from our institution between 2008 and 2020 were included as the training dataset for ML model development and internal validation (including 418 RCCs and 78 benign tumors), and patients from two independent institutions and a public database (TCIA) were included as the external dataset for individual testing (including 262 RCCs and 47 benign tumors). Features were extracted from three-phase CT images. CatBoost was used for feature selection and ML model establishment. The area under the receiver operating characteristic curve (AUC) was used to assess the performance of the ML model. RESULTS: The ML model based on 3D images performed better than that based on 2D images, with the highest AUC of 0.81 and accuracy (ACC) of 0.86. All three radiologists achieved better performance by referring to the classifier's decision, with accuracies increasing from 0.82 to 0.87, 0.82 to 0.88, and 0.76 to 0.87. The ML model achieved higher negative predictive values (NPV, 0.82-0.99), and the radiologists achieved higher positive predictive values (PPV, 0.91-0.95). CONCLUSIONS: A ML classifier based on whole-tumor three-phase CT images can be a useful and promising tool for differentiating RCCs from benign renal tumors. The ML model also perfectly complements radiologist interpretations. KEY POINTS: • A machine learning classifier based on CT images could be a reliable way to differentiate RCCs from benign renal tumors. • The machine learning model perfectly complemented the radiologists' interpretations. • Subtle variances in ROI delineation had little effect on the performance of the ML classifier.

Asymmetric Syn-Selective Vinylogous Addition of Butenolides to Chromones via Al-Li-BINOL Catalysis.

A gram-scale syn-selective asymmetric vinylogous addition of butenolides to chromones, catalyzed by an Al-Li-BINOL (ALB) complex, was developed in this study. For various combinations of substrates, the observed diastereoselectivity approached 20:1 with 84-98% ee. This protocol is complementary to previously reported ones and improves the selectivity for several chromones. This methodology can be applied to a quinolone substrate, affording another type of heterocyclic scaffolds substituted with five-membered lactones. Computational studies support the role of ALB as a bifunctional catalyst in this reaction and provide insights into the origin of the observed stereoselectivity.

Differential expression of diacylglycerol kinase ζ is involved in inferior parietal lobule-related dysfunction in schizophrenia with cognitive impairments.

BACKGROUND: Cognitive impairment is the main factor in the poor prognosis of schizophrenia, but its mechanism remains unclear. The inferior parietal lobule (IPL) is related to various clinical symptoms and cognitive impairment in schizophrenia. We aimed to explore the relationship between IPL-related functions and cognitive impairment in schizophrenia. METHODS: 136 schizophrenia patients and 146 demographically matched healthy controls were enrolled for a cross-sectional study. High-spatial-resolution structural and resting-state functional images were acquired to demonstrate the alternations of brain structure and function. At the same time, the digit span and digit symbol coding tasks of the Chinese Wechsler Adult Intelligence Test Revised (WAIS-RC) were utilized in assessing the subjects' cognitive function. Patients were divided into cognitive impairment and normal cognitive groups according to their cognitive score and then compared whether there were differences between the three groups in fractional amplitude of low-frequency fluctuation (fALFF). In addition, we did a correlation analysis between cognitive function and the fALFF for the left IPL of patients and healthy controls. Based on the Allen Human Brain Atlas, we obtained genes expressed in the left IPL, which were then intersected with the transcriptome-wide association study results and differentially expressed genes in schizophrenia. RESULTS: Grouping of patients by the backward digit span task and the digit symbol coding task showed differences in fALFF values between healthy controls and cognitive impairment patients (P < 0.05). We found a negative correlation between the backward digit span task score and fALFF of the left IPL in healthy controls (r = - 0.388, P = 0.003), which was not seen in patients (r = 0.203, P = 0.020). In addition, none of the other analyses were statistically significant (P > 0.017). In addition, we found that diacylglycerol kinase ζ (DGKζ) is differentially expressed in the left IPL and associated with schizophrenia. CONCLUSION: Our study demonstrates that the left IPL plays a vital role in cognitive impairment in schizophrenia. DGKζ may act as an essential regulator in the left IPL of schizophrenia patients with cognitive impairment.

Retrospective Analysis of Carotid Body Tumor Surgical Management: Roles of Preoperative Image Investigation and Preoperative Embolization.

BACKGROUND: Carotid body tumors (CBT) surgery is a challenging procedure, and the role of embolization (EMB) in CBT surgery has remained unclear. This study is performed to analyze the management of CBTs, particularly the use of preoperative EMB and image features in minimizing surgical complications. METHODS: A total of 200 CBTs were identified among 184 medical records involving CBT surgery. Regression analysis was used to explore the prognostic predictors of cranial nerve deficit (CND), including image features. In addition, blood loss, operation times, and complication rates were compared between patients who had surgery only versus patients who had surgery along with preoperative EMB. RESULTS: Overall, 96 males and 88 females were identified for inclusion in the study, with a median age of 37.0 years. Computed tomography angiography (CTA) showed the presence of a tiny gap adjacent to the encasement of carotid vessels, which could help minimize carotid arterial injury. High-lying tumors that encased the cranial nerve were usually managed with synchronous cranial nerve resection. Regression analysis revealed that the incidence of CND was positively associated with Shamblin Ⅲ, high-lying, and a maximal CBT diameter of ≥ 5 cm. Among 146 EMB cases, 2 cases of intracranial arterial EMB occurred. No statistical difference was found between the EBM and non-EBM groups in terms of bleeding volume, operation time, blood loss, blood transfusion requirement, stroke, and permanent CND. Subgroup analysis revealed that EMB decreased CND in Shamblin III and low-lying tumors. CONCLUSIONS: CBT surgery should be performed with preoperative CTA to identify favorable factors for minimizing surgical complications. Shamblin Ⅲ or high-lying tumors, as well as CBT diameter, are predictors of permanent CND. EBM does not reduce blood loss or shorten operation time.

Coherent Control and Magnetic Detection of Divacancy Spins in Silicon Carbide at High Pressures.

Spin defects in silicon carbide appear to be a promising tool for various quantum technologies, especially for quantum sensing. However, this technique has been used only at ambient pressure until now. Here, by combining this technique with diamond anvil cell, we systematically study the optical and spin properties of divacancy defects created at the surface of SiC at pressures up to 40 GPa. The zero-field-splitting of the divacancy spins increases linearly with pressure with a slope of 25.1 MHz/GPa, which is almost two-times larger than that of nitrogen-vacancy centers in diamond. The corresponding pressure sensing sensitivity is about 0.28 MPa/Hz-1/2. The coherent control of divacancy demonstrates that coherence time decreases as pressure increases. Based on these, the pressure-induced magnetic phase transition of Nd2Fe14B sample at high pressures was detected. These experiments pave the way to use divacancy in quantum technologies such as pressure sensing and magnetic detection at high pressures.

Targeting the ATG5-ATG16L1 Protein-Protein Interaction with a Hydrocarbon-Stapled Peptide Derived from ATG16L1 for Autophagy Inhibition.

Selective modulation of autophagy is a promising therapeutic strategy, especially for cancer treatment. However, the lack of specific autophagy inhibitors limits this strategy. The formation of the ATG12-ATG5-ATG16L1 complex is essential for targeting the ATG12-ATG5 conjugate to proper membranes and to generate LC3-II for the progression of autophagy. Thus, targeting ATG5-ATG16L1 protein-protein interactions (PPIs) might inhibit early stage autophagy with high specificity. In this paper, we report that a stapled peptide derived from ATG16L1 exhibits potent binding affinity to ATG5, striking resistance to proteolysis, and significant autophagy inhibition activities in cells.

Improving the anthocyanin accumulation of hypocotyls in radish sprouts by hemin-induced NO.

BACKGROUND: The health benefits of anthocyanins impel researchers and food producers to explorer new methods to increase anthocyanin contents in plant foods. Our previous studies revealed a positive role of nitric oxide (NO) in anthocyanin accumulation in radish (Raphanus sativus L.) sprouts. The application of hemin, an inducer of heme oxygenase-1 (HO-1), can effectively elevate NO production in vivo. Hemin treatment also improves plant growth and stress tolerance. This study is aimed to assess the effects of hemin treatment on anthocyanin production in radish sprouts, and to investigate whether NO signalling is involved in this process. RESULTS: The application of hemin significantly up regulated the expressions of many anthocyanins biosynthesis related structure and regulatory genes, leading to increased anthocyanins accumulation in radish hypocotyls. Hemin treatment also raised NO contents in radish sprouts, probably through enhancing nitrate reductase (NR) activity and Nitric Oxide-Associated 1 (NOA1) expression. Comparing the effects of Zinc Protoporphyrin (ZnPP, HO-1 activity inhibitor), Sodium Nitroprusside (SNP, NO donor) and carboxy-PTIO (cPTIO, NO-scavenger) on anthocyanin and NO production, a positive role of NO signalling has been revealed in hemin-derived anthocyanin accumulation. A positive feedback loop between HO-1 and NO may be involved in regulating this process. CONCLUSIONS: Hemin induced anthocyanin accumulation in radish sprouts through HO-1 and NO signalling network.

Bicyclol Alleviates Atherosclerosis by Manipulating Gut Microbiota.

Atherosclerosis (AS) is associated with high morbidity and mortality, thus imposing a growing burden on modern society. Herb-derived bicyclol (BIC) is a versatile bioactive compound that can be used to treat AS. However, its efficacy in AS is not yet described. Here, it is shown that BIC normalizes gut microflora dysbiosis induced by a high fat diet in Apoe(-/-) mice. Metagenome-wide association study analysis verifies that the modulation on carbohydrate-active enzymes and short-chain fatty acid generating genes in gut flora is among the mechanisms. The gut healthiness, especially the gut immunity and integrity, is restored by BIC intervention, leading to improved systemic immune cell dynamic and liver functions. Accordingly, the endothelial activation, macrophage infiltration, and cholesterol ester accumulation in the aortic arch are alleviated by BIC to lessen the plaque onset. Moreover, it is proved that the therapeutic effect of BIC on AS is transmissible by fecal microbiota transplantation. The current study, for the first time, demonstrates the antiatherosclerotic effects of BIC and shows that its therapeutic value can at least partially be attributed to its manipulation of gut microbiota.