Bibliometric and visualized analysis of the applications of exosomes based drug delivery.

Exosomes, endogenous vesicles secreted by cells, possess unique properties like high biocompatibility, low immunogenicity, targeting ability, long half-life, and blood-brain barrier permeability. They serve as crucial intercellular communication vectors in physiological processes and disease occurrence. Our comprehensive analysis of exosome-based drug delivery research from 2013 to 2023 revealed 2,476 authors from 717 institutions across 33 countries. Keyword clustering identified five research areas: drug delivery, mesenchymal stem cells, cancer immunotherapy, targeting ligands, surface modifications, and macrophages. The combination of exosome drug delivery technology with a proven clinical model enables the precise targeting of tumors with chemotherapy or radiosensitising agents, as well as facilitating gene therapy. This bibliometric analysis aims to characterize the current state and advance the clinical application of exosome-based drug delivery systems.

Generalized latent multi-view clustering with tensorized bipartite graph.

Tensor-based multi-view spectral clustering algorithms use tensors to model the structure of multi-dimensional data to take advantage of the complementary information and high-order correlations embedded in the graph, thus achieving impressive clustering performance. However, these algorithms use linear models to obtain consensus, which prevents the learned consensus from adequately representing the nonlinear structure of complex data. In order to address this issue, we propose a method called Generalized Latent Multi-View Clustering with Tensorized Bipartite Graph (GLMC-TBG). Specifically, in this paper we introduce neural networks to learn highly nonlinear mappings that encode nonlinear structures in graphs into latent representations. In addition, multiple views share the same latent consensus through nonlinear interactions. In this way, a more comprehensive common representation from multiple views can be achieved. An Augmented Lagrangian Multiplier with Alternating Direction Minimization (ALM-ADM) framework is designed to optimize the model. Experiments on seven real-world data sets verify that the proposed algorithm is superior to state-of-the-art algorithms.

Neurobiological Underpinnings of Hyperarousal in Depression: A Comprehensive Review.

Patients with major depressive disorder (MDD) exhibit an abnormal physiological arousal pattern known as hyperarousal, which may contribute to their depressive symptoms. However, the neurobiological mechanisms linking this abnormal arousal to depressive symptoms are not yet fully understood. In this review, we summarize the physiological and neural features of arousal, and review the literature indicating abnormal arousal in depressed patients. Evidence suggests that a hyperarousal state in depression is characterized by abnormalities in sleep behavior, physiological (e.g., heart rate, skin conductance, pupil diameter) and electroencephalography (EEG) features, and altered activity in subcortical (e.g., hypothalamus and locus coeruleus) and cortical regions. While recent studies highlight the importance of subcortical-cortical interactions in arousal, few have explored the relationship between subcortical-cortical interactions and hyperarousal in depressed patients. This gap limits our understanding of the neural mechanism through which hyperarousal affects depressive symptoms, which involves various cognitive processes and the cerebral cortex. Based on the current literature, we propose that the hyperconnectivity in the thalamocortical circuit may contribute to both the hyperarousal pattern and depressive symptoms. Future research should investigate the relationship between thalamocortical connections and abnormal arousal in depression, and explore its implications for non-invasive treatments for depression.

Tracking a spin-polarized superconducting bound state across a quantum phase transition.

The magnetic exchange coupling between magnetic impurities and a superconductor induce so-called Yu-Shiba-Rusinov (YSR) states which undergo a quantum phase transition (QPT) upon increasing the exchange interaction beyond a critical value. While the evolution through the QPT is readily observable, in particular if the YSR state features an electron-hole asymmetry, the concomitant change in the ground state is more difficult to identify. We use ultralow temperature scanning tunneling microscopy to demonstrate how the change in the YSR ground state across the QPT can be directly observed for a spin-1/2 impurity in a magnetic field. The excitation spectrum changes from featuring two peaks in the doublet (free spin) state to four peaks in the singlet (screened spin) ground state. We also identify a transition regime, where the YSR excitation energy is smaller than the Zeeman energy. We thus demonstrate a straightforward way for unambiguously identifying the ground state of a spin-1/2 YSR state.

Effects of obesity-related anthropometric indices and body composition on erectile dysfunction mediated by coronary artery disease: A Mendelian randomization study.

BACKGROUND: The causal relationship between obesity-related anthropometric indicators/body composition and erectile dysfunction has not been established in previous observational studies. METHOD: We screened single nucleotide polymorphisms significantly associated with exposure from genome-wide association studies as instrumental variables (p < 5.0 × 10-8 ). The summary statistics for erectile dysfunction were collected from a genome-wide association study with a sample size of 223,805. Exposure and outcome populations included are of European ancestry. We used univariate and multivariate Mendelian randomization (i) to investigate the causal relationship between genetically predicted obesity-related anthropometric indicators/body composition and erectile dysfunction and (ii) to examine the mediating role of coronary artery disease. Mendelian randomization analysis was conducted using an inverse variance weighted method. A series of sensitivity analyses validated the results of the Mendelian randomization analysis. Causal estimates are expressed as odds ratios with 95% confidence intervals. RESULTS: Obesity-related anthropometric indicators/body composition were associated with an increased risk of erectile dysfunction in univariate Mendelian randomization analyses. For the 1-SD increase in body mass index, the odds ratio was 1.841 (95% confidence interval: 1.049-1.355, p = 0.006). For the 1-SD increase in waist circumference and hip circumference, the odds ratios were 1.275 (95% confidence interval: 1.101-1.478, p = 0.001) and 1.156 (95% confidence interval: 1.015-1.317, p = 0.009), respectively. The odds ratio for the 1-SD increase in whole body fat mass was 1.221 (95% confidence interval: 1.047-1.388, p = 0.002). For the 1-SD increase in leg fat percentage (left and right), the odds ratios were 1.256 (95% confidence interval: 1.006-1.567, p = 0.044) and 1.285 (95% confidence interval: 1.027-1.608, p = 0.028), respectively. For the 1-SD increase in leg fat mass (left and right), the odds ratios were 1.308 (95% confidence interval: 1.108-1.544, p = 0.001) and 1.290 (95% confidence interval: 1.091-1.524, p = 0.003), respectively. For the 1-SD increase in arm fat mass (left and right), the odds ratios were 1.269 (95% confidence interval: 1.113-1.447, p < 0.001) and 1.254, respectively. Multivariate Mendelian randomization analysis showed that after adjusting for coronary artery disease, some genetic predispositions to obesity-related anthropometric indicators and body composition were still associated with an increased risk of erectile dysfunction. Significant associations were found for waist circumference-erectile dysfunction (odds ratio: 1.218, 95% confidence interval: 1.036-1.432), leg fat percentage (left)-erectile dysfunction (odds ratio: 1.245, 95% confidence interval: 1.035-1.497), leg fat mass (left)-erectile dysfunction (odds ratio: 1.264, 95% confidence interval: 1.051-1.521), arm fat mass (right)-erectile dysfunction (odds ratio: 1.186, 95% confidence interval: 1.024-1.373), and arm fat mass (left)-erectile dysfunction (odds ratio: 1.17, 95% confidence interval: 1.018-1.360). Meanwhile, coronary artery disease mediated the effects of fat on erectile dysfunction, and the proportion of coronary artery disease-mediated cases ranged from 10% to 22%. CONCLUSION: There is a potential causal relationship between obesity-related anthropometric indicators/body composition and erectile dysfunction. Higher waist circumference, leg fat percentage, and arm fat mass may increase the risk of erectile dysfunction, and coronary artery disease partly mediates this overall effect. Understanding the causal relationship between obesity and erectile dysfunction and the mediating role of coronary artery disease may provide more information for erectile dysfunction intervention and prevention strategies.

Electric control of spin transitions at the atomic scale.

Electric control of spins has been a longstanding goal in the field of solid state physics due to the potential for increased efficiency in information processing. This efficiency can be optimized by transferring spintronics to the atomic scale. We present electric control of spin resonance transitions in single TiH molecules by employing electron spin resonance scanning tunneling microscopy (ESR-STM). We find strong bias voltage dependent shifts in the ESR signal of about ten times its line width. We attribute this to the electric field in the tunnel junction, which induces a displacement of the spin system changing the g-factor and the effective magnetic field of the tip. We demonstrate direct electric control of the spin transitions in coupled TiH dimers. Our findings open up new avenues for fast coherent control of coupled spin systems and expands on the understanding of spin electric coupling.

Microwave excitation of atomic scale superconducting bound states.

Magnetic impurities on superconductors lead to bound states within the superconducting gap, so called Yu-Shiba-Rusinov (YSR) states. They are parity protected, which enhances their lifetime, but makes it more difficult to excite them. Here, we realize the excitation of YSR states by microwaves facilitated by the tunnel coupling to another superconducting electrode in a scanning tunneling microscope (STM). We identify the excitation process through a family of anomalous microwave-assisted tunneling peaks originating from a second-order resonant Andreev process, in which the microwave excites the YSR state triggering a tunneling event transferring a total of two charges. We vary the amplitude and the frequency of the microwave to identify the energy threshold and the evolution of this excitation process. Our work sets an experimental basis and proof-of-principle for the manipulation of YSR states using microwaves with an outlook towards YSR qubits.

Comprehensive Multiview Representation Learning via Deep Autoencoder-Like Nonnegative Matrix Factorization.

Learning a comprehensive representation from multiview data is crucial in many real-world applications. Multiview representation learning (MRL) based on nonnegative matrix factorization (NMF) has been widely adopted by projecting high-dimensional space into a lower order dimensional space with great interpretability. However, most prior NMF-based MRL techniques are shallow models that ignore hierarchical information. Although deep matrix factorization (DMF)-based methods have been proposed recently, most of them only focus on the consistency of multiple views and have cumbersome clustering steps. To address the above issues, in this article, we propose a novel model termed deep autoencoder-like NMF for MRL (DANMF-MRL), which obtains the representation matrix through the deep encoding stage and decodes it back to the original data. In this way, through a DANMF-based framework, we can simultaneously consider the multiview consistency and complementarity, allowing for a more comprehensive representation. We further propose a one-step DANMF-MRL, which learns the latent representation and final clustering labels matrix in a unified framework. In this approach, the two steps can negotiate with each other to fully exploit the latent clustering structure, avoid previous tedious clustering steps, and achieve optimal clustering performance. Furthermore, two efficient iterative optimization algorithms are developed to solve the proposed models both with theoretical convergence analysis. Extensive experiments on five benchmark datasets demonstrate the superiority of our approaches against other state-of-the-art MRL methods.

Current status and prospects of diabetes mellitus induced erectile dysfunction: A bibliometric and visualization study.

Background: The prevalence of diabetes mellitus-induced erectile dysfunction (DMED) has recently increased, which has prompted numerous DMED studies. Here, we conduct a bibliometric analysis of relevant literature in the field of DMED and to discuss the research hotspots and future development directions. Methods: The Web of Science Core Collection database was searched for literature on DMED, and literature characterization including the number of articles, journals, countries/regions, institutions, authors, keywords, and other information was performed using VOS viewer and CiteSpace software. In addition, Pajek software was used for visual map adjustment, and GraphPad Prism was used to generate line graphs. Results: A total of 804 articles concerning DMED were included in this study. The Journal of Sexual Medicine issued the most documents(92 articles). The United States and China were in the leading position in the field of DMED research, and cross-institutional collaboration on DMED research worldwide needs to be further strengthened. Ryu JK were the authors with the highest number of documents issued (22 articles) while Bivalacqua TJ was the author with the most co-citated(249 co-citated). The keywords analysis shows that the main research hotspots in the field of DMED were mechanism discussions and disease treatment and management. Conclusions: Global research on DMED is expected to increase further. The investigation of the mechanism of DMED and the exploration of new therapeutic means and targets are the focus of future research.

GNAEMDA: Microbe-Drug Associations Prediction on Graph Normalized Convolutional Network.

The importance of microbe-drug associations (MDA) prediction is evidenced in research. Since traditional wet-lab experiments are both time-consuming and costly, computational methods are widely adopted. However, existing research has yet to consider the cold-start scenarios that commonly seen in real-world clinical research and practices where data of confirmed microbe-drug associations are highly sparse. Therefore, we aim to contribute by developing two novel computational approaches, the GNAEMDA (Graph Normalized Auto-Encoder to predict Microbe-Drug Associations), and a variational extension of the GNAEMDA (called VGNAEMDA), to provide effective and efficient solutions for well-annotated cases and cold-start scenarios. Multi-modal attribute graphs are constructed by collecting multiple features of microbes and drugs, and then input into a graph normalized convolutional network, where a l2-normalization is introduced to avoid the norm-towards-zero tendency of isolated nodes in embedding space. Then the reconstructed graph output by the network is used to infer undiscovered MDA. The difference between the proposed two models lays in the way to generate the latent variables in network. To verify the effectiveness of the two proposed models, we conduct a series of experiments on three benchmark datasets in comparison with six state-of-the-art methods. The comparison results indicate that both GNAEMDA and VGNAEMDA have strong prediction performances in all cases, especially in identifying associations for new microbes or drugs. In addition, we conduct case studies on two drugs and two microbes and find that more than 75% of the predicted associations have been reported in PubMed. The comprehensive experimental results validate the reliability of our models in accurately inferring potential MDA.

Fluoride disrupts intestinal epithelial tight junction integrity through intracellular calcium-mediated RhoA/ROCK signaling and myosin light chain kinase.

Fluoride is a common contaminant of groundwater and agricultural commodity, which poses challenges to animal and human health. A wealth of research has demonstrated its detrimental effects on intestinal mucosal integrity; however, the underlying mechanisms remain obscure. This study aimed to investigate the role of the cytoskeleton in fluoride-induced barrier dysfunction. After sodium fluoride (NaF) treatment of the cultured Caco-2 cells, both cytotoxicity and cytomorphological changes (internal vacuoles or massive ablation) were observed. NaF lowered transepithelial electrical resistance (TEER) and enhanced paracellular permeation of fluorescein isothiocyanate dextran 4 (FD-4), indicating Caco-2 monolayers hyperpermeability. In the meantime, NaF treatment altered both the expression and distribution of the tight junction protein ZO-1. Fluoride exposure increased myosin light chain II (MLC2) phosphorylation and triggered actin filament (F-actin) remodeling. While inhibition of myosin II by Blebbistatin blocked NaF-induced barrier failure and ZO-1 discontinuity, the corresponding agonist Ionomycin had effects comparable to those of fluoride, suggesting that MLC2 serves as an effector. Given the mechanisms upstream of p-MLC2 regulation, further studies demonstrated that NaF activated RhoA/ROCK signaling pathway and myosin light chain kinase (MLCK), strikingly increasing the expression of both. Pharmacological inhibitors (Rhosin, Y-27632 and ML-7) reversed NaF-induced barrier breakdown and stress fiber formation. The role of intracellular calcium ions ([Ca2+]i) in NaF effects on Rho/ROCK pathway and MLCK was investigated. We found that NaF elevated [Ca2+]i, whereas chelator BAPTA-AM attenuated increased RhoA and MLCK expression as well as ZO-1 rupture, thus, restoring barrier function. Collectively, abovementioned results suggest that NaF induces barrier impairment via Ca2+-dependent RhoA/ROCK pathway and MLCK, which in turn triggers MLC2 phosphorylation and rearrangement of ZO-1 and F-actin. These results provide potential therapeutic targets for fluoride-induced intestinal injury.

Molecular docking and molecular dynamics study Lianhua Qingwen granules (LHQW) treats COVID-19 by inhibiting inflammatory response and regulating cell survival.

Purpose: 2019 Coronavirus disease (COVID-19) is endangering health of populations worldwide. Latest research has proved that Lianhua Qingwen granules (LHQW) can reduce tissue damage caused by inflammatory reactions and relieve patients' clinical symptoms. However, the mechanism of LHQW treats COVID-19 is currently lacking. Therefore, we employed computer simulations to investigate the mechanism of LHQW treats COVID-19 by modulating inflammatory response. Methods: We employed bioinformatics to screen active ingredients in LHQW and intersection gene targets. PPI, GO and KEGG was used to analyze relationship of intersection gene targets. Molecular dynamics simulations validated the binding stability of active ingredients and target proteins. Binding free energy, radius of gyration and the solvent accessible surface area were analyzed by supercomputer platform. Results: COVID-19 had 4628 gene targets, LHQW had 1409 gene targets, intersection gene targets were 415. Bioinformatics analysis showed that intersection targets were closely related to inflammation and immunomodulatory. Molecular docking suggested that active ingredients (including: licopyranocoumarin, Glycyrol and 3-3-Oxopropanoic acid) in LHQW played a role in treating COVID-19 by acting on CSF2, CXCL8, CCR5, NLRP3, IFNG and TNF. Molecular dynamics was used to prove the binding stability of active ingredients and protein targets. Conclusion: The mechanism of active ingredients in LHQW treats COVID-19 was investigated by computer simulations. We found that active ingredients in LHQW not only reduce cell damage and tissue destruction by inhibiting the inflammatory response through CSF2, CXCL8, CCR5 and IFNG, but also regulate cell survival and growth through NLRP3 and TNF thereby reducing apoptosis.

Bibliometrics and visualisation analysis of literature on varicocele: From 2002 to 2021.

Varicocele is a common disease in men, with a global incidence of approximately 25%. A comprehensive and systematic analysis of the knowledge map on it will help in assessing frontier research and identify knowledge gaps. In total, 4103 articles published from 2002 to 2021 in 1066 journals were included. They represent the current research status worldwide, potential hotspots and future research directions. In the past decades, the number of publications and citations of varicocele-related studies have increased steadily. Academic institutions in the United States played a leading role in varicocele research. The country, institution, journal and author with the most publications were the United States (779), Cleveland Clinic Foundation (132), Andrologia (246) and Agarwal A (106), respectively. The most frequently used keywords were Varicocele (1620), Male Infertility (944), Varicocelectomy (288), Testis (245), Sperm (166), Oxidative Stress (144), Azoospermia (119), Semen Analysis (118), Laparoscopy (116) and Adolescent (97). Currently, the main focus of current varicocele research is its surgical treatment method and effect on sperm quality. The frontier research hotspot is the specific mechanism of varicocele-induced decrease in sperm quality.

Fangchinoline inhibits non-small cell lung cancer metastasis by reversing epithelial-mesenchymal transition and suppressing the cytosolic ROS-related Akt-mTOR signaling pathway.

Few drugs alleviate non-small cell lung cancer (NSCLC) metastasis effectively. Small molecular screening demonstrated that fangchinoline (Fan) reversed epithelial-mesenchymal transition (EMT) in NSCLC cells, inhibiting cell invasion and migration. RNA sequencing (RNA-seq) of Fan-treated NSCLC cells revealed that Fan potently quenched the NADP+ metabolic process. Molecular docking analysis revealed that Fan directly and specifically targeted NOX4. NOX4 was associated with poor prognosis in NSCLC in both The Cancer Genome Atlas (TCGA) and Hong Kong cohorts. In mitochondrial DNA-depleted ρ0 NSCLC cells, Fan decreased cytosolic reactive oxygen species (ROS) to inhibit the Akt-mTOR signaling pathway by directly promoting NOX4 degradation. In TCGA and Hong Kong cohorts, NOX4 upregulation acted as a driver event as it positively correlated with metastasis and oxidative stress. Single-cell RNA-seq indicated that NOX4 was overexpressed, especially in cancer cells, cancer stem cells, and endothelial cells. In mice, Fan significantly impeded subcutaneous xenograft formation and reduced metastatic nodule numbers in mouse lung and liver. Drug sensitivity testing demonstrated that Fan suppressed patient-derived organoid growth dose-dependently. Fan is a potent small molecule for alleviating NSCLC metastasis by directly targeting NOX4 and is a potential novel therapeutic agent.

Case Report: Disseminated Nocardiosis Caused by Nocardia vulneris in a Patient With Macroglobulinemia.

This report describes a case of disseminated nocardiosis, caused by Nocardia vulneris, in a 61-year-old man with macroglobulinemia and presenting with repeated fever, cough, shortness of breath, and muscle pain. The isolated Nocardia strain was resistant to ciprofloxacin, but susceptible to amikacin, gentamicin, tobramycin, linezolid, trimethoprim-sulfamethoxazole, amoxicillin/clavulanic, moxifloxacin, ceftriaxone, cefotaxim, and imipenem. The patient was started on combined meropenem and doxycycline treatment, followed by trimethoprim-sulfamethoxazole, which was subsequently switched to a combination treatment of linezolid, amikacin, and trimethoprim-sulfamethoxazole. The patient recovered, and his condition remained stable. Although infection by Nocardia vulneris is rare, and it is easy to miss detection in clinical practice, clinicians should be aware of the possibility of this infection. In addition, the MIC value of the drug sensitivity test should be ascertained when there is a wide choice of medicines. The current case was treated successfully with linezolid, amikacin, and trimethoprim-sulfamethoxazole. In cases of disseminated nocardiosis, the patient should be treated with antimicrobial therapy for at least 12 months. Furthermore, bacteriological examination and antimicrobial susceptibility testing should be performed regularly.

Application of a New Mesh Fixation Method in Laparoscopic Incisional Hernia Repair.

Laparoscopic incisional hernia repair using intraperitoneal onlay mesh (IPOM) is one of the most widely used minimally invasive methods for repairing incisional hernias. The laparoscopic IPOM involves implanting the mesh into the abdominal cavity through laparoscopy to repair an abdominal wall hernia. In the IPOM surgery, after the closure of the hernia ring, an anti-adhesion mesh is placed laparoscopically. The correct placement of this mesh is critical to the success of the method, and surgical skills are required to achieve perfect placement. If the mesh placement is not mastered properly, the operation and anesthesia time will be prolonged. In addition, improper placement of the mesh can lead to serious consequences, such as intestinal obstruction and mesh infection. A "contraposition and alignment" mesh fixation method is described in this study, which involves pre-marking the fixation position of the mesh to reduce the difficulty of mesh placement. A properly placed mesh is completely flat on the peritoneum, the edges are not curled or wrapped, and the mesh is adhered firmly such that there is no displacement after removing the pneumoperitoneum pressure. The "contraposition and alignment" mesh fixation technique offers the advantages of reliable placement of the mesh and fewer complications than other techniques, and it is easy to learn and master. It also allows for positioning the nail gun in advance based on the anatomy of the incisional hernia. This enables the use of the minimum number of nails possible while still ensuring good fixation, which can reduce the occurrence of complications and reduce the cost of surgery. Thus, the mesh fixation method described here is highly suitable for clinical applications based on the aforementioned advantages.

Preventive effects of Lactobacillus johnsonii on the renal injury of mice induced by high fluoride exposure: Insights from colonic microbiota and co-occurrence network analysis.

Fluoride (F) exposure was widely reported to be associated with renal diseases. Since absorbed F enters the organism from drinking water mostly through the gastrointestinal tract, investigating changes of gut microbes may have profound implications for the prevention of chronic F exposure because increasing evidence supported the existence of the gut-kidney axis. In the present study, we aimed to explore the potential positive effects of probiotics on high F exposure-induced renal lesions and dysfunction in mice by the modulation of the colonic microbiota. Mice were fed with normal (Ctrl group) or sodium-fluoride (F and Prob groups; 100 mg/L sodium fluoride (NaF)) drinking water with or without Lactobaillus johnsonii BS15, a probiotic strain proven to be preventive for F exposure. Mice fed with sodium-fluoride drinking water alone exhibited renal tissue damages, decreased the renal antioxidant capability and dysfunction. In contrast, L. johnsonii BS15 reversed these F-induced renal changes. 16S rRNA gene sequencing shows that L. johnsonii BS15 alleviated the increased community diversity (Shannon diversity) and richness index (number of observed features) as well as the distured structure of colon microbiota in F-exposed mice. A total of 13 OTUs with increased relative abundance were identified as the keystone OTUs in F-exposed mice based on the analysis of degree of co-occurrence and abundance of OTUs. Moreover, Spearman's rank correlation shows that the 13 keystone OTUs had negative effect on renal health and intestinal integrity. L. johnsonii BS15 reversed four of keystone OTUs (OTU 5, OTU 794, OTU 1035, and OTU 868) changes which might be related to the underlying protected mechanism of L. johnsonii BS15 against F-induced renal damages.

Endophytic Bacterial Communities of Ginkgo biloba Leaves During Leaf Developmental Period.

Plant-specialized secondary metabolites have ecological functions in mediating interactions between plants and their entophytes. In this study, high-throughput gene sequencing was used to analyze the composition and abundance of bacteria from Ginkgo leaves at five different sampling times. The results indicated that the bacterial community structure varied during leaf developmental stage. Bacterial diversity was observed to be the highest at T2 stage and the lowest at T1 stage. Proteobacteria, Firmicutes, Actinobacteria, Chloroflexi, Cyanobacteria, and Bacteroidetes were found as the dominant phyla. The major genera also showed consistency across sampling times, but there was a significant variation in their abundance, such as Bacillus, Lysinibacillus, and Staphylococcus. Significant correlations were observed between endophytic bacteria and flavonoids. Especially, Staphylococcus showed a significant positive correlation with quercetin, and changes in the abundance of Staphylococcus also showed a strong correlation with flavonoid content. In order to determine the effect of flavonoids on endophytic bacteria of Ginkgo leaves, an extracorporeal culture of related strains (a strain of Staphylococcus and a strain of Deinococcus) was performed, and it was found that the effect of flavonoids on them remained consistent. The predicted result of Tax4Fun2 revealed that flavonoids might lead to a lower abundance of endophytic microorganisms, which further proved the correlation between bacterial communities and flavonoids. This study provided the first insight into the bacterial community composition during the development of Ginkgo leaves and the correlation between the endophytic bacteria and flavonoids.

Root Endophytes and Ginkgo biloba Are Likely to Share and Compensate Secondary Metabolic Processes, and Potentially Exchange Genetic Information by LTR-RTs.

Ginkgo biloba is a pharmaceutical resource for terpenes and flavonoids. However, few insights discussed endophytes' role in Ginkgo, and whether genetic exchange happens between Ginkgo and endophytes remains unclear. Herein, functional gene profiles and repetitive sequences were analyzed to focus on these issues. A total of 25 endophyte strains were isolated from the Ginkgo root and distributed in 16 genera of 6 phyla. Significant morphological diversities lead to the diversity in the COG functional classification. KEGG mapping revealed that endophytic bacteria and fungi potentially synthesize chalcone, while endophytic fungi might also promote flavonoid derivatization. Both bacteria and fungi may facilitate the lignin synthesis. Aspergillus sp. Gbtc_1 exhibited the feasibility of regulating alcohols to lignans. Although Ginkgo and the endophytes have not observed the critical levopimaradiene synthase in ginkgolides synthesis, the upstream pathways of terpenoid precursors are likely intact. The MVK genes in Ginkgo may have alternative non-homologous copies or be compensated by endophytes in long-term symbiosis. Cellulomonas sp. Gbtc_1 became the only bacteria to harbor both MEP and MVA pathways. Endophytes may perform the mutual transformation of IPP and DMAPP in the root. Ginkgo and bacteria may lead to the synthesis and derivatization of the carotenoid pathway. The isoquinoline alkaloid biosynthesis seemed lost in the Ginkgo root community, but L-dopa is more probably converted into dopamine as an essential signal-transduction substance. So, endophytes may participate in the secondary metabolism of the Ginkgo in a shared or complementary manner. Moreover, a few endophytic sequences predicted as Ty3/Gypsy and Ty1/Copia superfamilies exhibited extremely high similarity to those of Ginkgo. CDSs in such endophytic LTR-RT sequences were also highly homologous to one Ginkgo CDS. Therefore, LTR-RTs may be a rare unit flowing between the Ginkgo host and endophytes to exchange genetic information. Collectively, this research effectively expanded the insight on the symbiotic relationship between the Ginkgo host and the endophytes in the root.

The Macleaya cordata Symbiont: Revealing the Effects of Plant Niches and Alkaloids on the Bacterial Community.

Endophytes are highly associated with plant growth and health. Exploring the variation of bacterial communities in different plant niches is essential for understanding microbe-plant interactions. In this study, high-throughput gene sequencing was used to analyze the composition and abundance of bacteria from the rhizospheric soil and different parts of the Macleaya cordata. The results indicated that the bacterial community structure varied widely among compartments. Bacterial diversity was observed to be the highest in the rhizospheric soil and the lowest in fruits. Proteobacteria, Actinobacteria, and Bacteroidetes were found as the dominant phyla. The genera Sphingomonas (∼47.77%) and Methylobacterium (∼45.25%) dominated in fruits and leaves, respectively. High-performance liquid chromatography (HPLC) was employed to measure the alkaloid content of different plant parts. Significant correlations were observed between endophytic bacteria and alkaloids. Especially, Sphingomonas showed a significant positive correlation with sanguinarine and chelerythrine. All four alkaloids were negatively correlated with the microbiota of stems. The predicted result of PICRUST2 revealed that the synthesis of plant alkaloids might lead to a higher abundance of endophytic microorganisms with genes related to alkaloid synthesis, further demonstrated the correlation between bacterial communities and alkaloids. This study provided the first insight into the bacterial community composition in different parts of Macleaya cordata and the correlation between the endophytic bacteria and alkaloids.