[Whole Process Analysis and Fate Behavior of Microplastics in Urban Wastewater Treatment Plants, Including their Occurrence Forms, Components, and Removal Efficiency].

Microplastics are among the most difficult new pollutants to remove in wastewater treatment plants. In order to explore the occurrence form, size distribution, composition, removal efficiency, migration law, and fate behavior characteristics of microplastic particles in sewage plants, taking a sewage treatment plant in Hohhot as an example, a total of 17 sampling sites were set up. The LAS X software counted the shape, abundance, and size of microplastics and conducted a full-process analysis. The results showed that： fibrous microplastics had the highest abundance and widest distribution and were the main form of existence, accounting for 61.8% of the total abundance； the size of microplastics ranged mainly between 0 and 1.00 mm, and among the four sizes, the abundance of microplastics 0.25 to 0.50 mm in China was the highest, accounting for 32.9%. Among the eight types of plastic components detected, polyester substances （PET, PBT）, cellulose, and polypropylene （PP） were the main components, accounting for 25%, 21%, and 17%, respectively. The influent abundance of the sewage plant was （73 ±5） n·L-1, the effluent abundance was （14 ±2） n·L-1, and the overall removal rate was （80.8 ±12.1）%. Among the three treatment stages of the sewage plant, only the primary treatment played a role in removal, and the abundance of microplastics surged in the secondary treatment. Different structures playing a major role in the removal of microplastics were fine grids （49.2 ±7.4）% and secondary sedimentation tanks （92.4 ±13.9）%. Microplastics mainly existed in the form of fibers, fragments, and films. The proportion of fibers was approximately 70%, and the size of fragments was mainly concentrated between 0.50 and 5.00 mm. Most fragments were in the range of 5.00 mm, accounting for 50%, making them the main form apart from fibrous. The film-like size was mostly concentrated in the range of less than 0.50 mm, accounting for more than 10%. Therefore, improving the removal of small-sized fibrous and film-like microplastics and large-sized fragmented microplastic particles can effectively reduce the pollution risk of microplastics in the environment caused by sewage plant drainage.

Systems Genetics Analyses Reveals Key Genes Related to Behavioral Traits in the Striatum of CFW Mice.

The striatum plays a central role in directing many complex behaviors ranging from motor control to action choice and reward learning. In our study, we used 55 male CFW mice with rapid decay linkage disequilibrium to systematically mine the striatum-related behavioral functional genes by analyzing their striatal transcriptomes and 79 measured behavioral phenotypic data. By constructing a gene coexpression network, we clustered the genes into 13 modules, with most of them being positively correlated with motor traits. Based on functional annotations as well as Fisher's exact and hypergeometric distribution tests, brown and magenta modules were identified as core modules. They were significantly enriched for striatal-related functional genes. Subsequent Mendelian randomization analysis verified the causal relationship between the core modules and dyskinesia. Through the intramodular gene connectivity analysis, Adcy5 and Kcnma1 were identified as brown and magenta module hub genes, respectively. Knock outs of both Adcy5 and Kcnma1 lead to motor dysfunction in mice, and KCNMA1 acts as a risk gene for schizophrenia and smoking addiction in humans. We also evaluated the cellular composition of each module and identified oligodendrocytes in the striatum to have a positive role in motor regulation.

New insights into the interplay between autophagy, gut microbiota and insulin resistance in metabolic syndrome.

Metabolic syndrome (MetS) is a widespread and multifactorial disorder, and the study of its pathogenesis and treatment remains challenging. Autophagy, an intracellular degradation system that maintains cellular renewal and homeostasis, is essential for maintaining antimicrobial defense, preserving epithelial barrier integrity, promoting mucosal immune response, maintaining intestinal homeostasis, and regulating gut microbiota and microbial metabolites. Dysfunctional autophagy is implicated in the pathological mechanisms of MetS, involving insulin resistance (IR), chronic inflammation, oxidative stress, and endoplasmic reticulum (ER) stress, with IR being a predominant feature. The study of autophagy represents a valuable field of research with significant clinical implications for identifying autophagy-related signals, pathways, mechanisms, and treatment options for MetS. Given the multifactorial etiology and various potential risk factors, it is imperative to explore the interplay between autophagy and gut microbiota in MetS more thoroughly. This will facilitate the elucidation of new mechanisms underlying the crosstalk among autophagy, gut microbiota, and MetS, thereby providing new insights into the diagnosis and treatment of MetS.

Association between visceral obesity index and diabetes: a systematic review and meta-analysis.

CONTENT: The correlation between visceral obesity index (VAI) and diabetes and accuracy of early prediction of diabetes are still controversial. OBJECTIVE: This study aims to review the relationship between high level of VAI and diabetes, and early predictive value of diabetes. DATA SOURCES: The databases of PubMed, Cochrane, Embase, and Web of Science were searched until October 17, 2023. STUDY SELECTION: After adjusting for confounding factors, the original study on the association between VAI and diabetes was analyzed. DATA EXTRACTION: We extracted odds ratio (OR) between VAI and diabetes management after controlling for mixed factors, and the sensitivity, specificity and diagnostic four grid table for early prediction of diabetes. DATA SYNTHESIS: 53 studies, comprising 595,946 participants were included. The findings of the meta-analysis elucidated that in cohort studies, a high VAI significantly increased the risk of diabetes mellitus in males (OR = 2.83 (95% CI: 2.30-3.49)) and females (OR = 3.32 (95% CI: 2.48-4.45)). The ROC, sensitivity, and specificity of VAI for early prediction of diabetes in males were 0.64 (95% CI: 0.62-0.66), 0.57 (95% CI: 0.53-0.61), and 0.65 (95% CI: 0.61-0.69), respectively, and 0.67 (95% CI: 0.65-0.69), 0.66 (95% CI: 0.60-0.71), and 0.61 (95% CI: 0.57-0.66) in females, respectively. CONCLUSIONS: VAI is an independent predictor of the risk of diabetes, yet its predictive accuracy remains limited. In future studies, determine whether VAI can be utilized in conjunction with other related indicators to early predict the risk of diabetes, to enhance the accuracy of prediction of the risk of diabetes.

ViroISDC: a method for calling integration sites of hepatitis B virus based on feature encoding.

BACKGROUND: Hepatitis B virus (HBV) integrates into human chromosomes and can lead to genomic instability and hepatocarcinogenesis. Current tools for HBV integration site detection lack accuracy and stability. RESULTS: This study proposes a deep learning-based method, named ViroISDC, for detecting integration sites. ViroISDC generates corresponding grammar rules and encodes the characteristics of the language data to predict integration sites accurately. Compared with Lumpy, Pindel, Seeksv, and SurVirus, ViroISDC exhibits better overall performance and is less sensitive to sequencing depth and integration sequence length, displaying good reliability, stability, and generality. Further downstream analysis of integrated sites detected by ViroISDC reveals the integration patterns and features of HBV. It is observed that HBV integration exhibits specific chromosomal preferences and tends to integrate into cancerous tissue. Moreover, HBV integration frequency was higher in males than females, and high-frequency integration sites were more likely to be present on hepatocarcinogenesis- and anti-cancer-related genes, validating the reliability of the ViroISDC. CONCLUSIONS: ViroISDC pipeline exhibits superior precision, stability, and reliability across various datasets when compared to similar software. It is invaluable in exploring HBV infection in the human body, holding significant implications for the diagnosis, treatment, and prognosis assessment of HCC.

Anthocyanins from Lycium ruthenicum Murray attenuates high-fat diet-induced hypercholesterolemia in ApoE-/- mice are related to the modulation of gut microbiota and the ratio of conjugated to unconjugated bile acids in fecal bile acid profile.

Previous findings showed that anthocyanins from Lycium ruthenicum Murray (ACN) reduced HFD-induced hypercholesterolemia by regulating gut microbiota, but the mechanism has not been fully understood. The objective of this research was to know whether the cholesterol-lowering impact of ACN in HFD-induced ApoE-/- mice is related to the gut microbiota-bile acid (BA) metabolism. Twenty-four male ApoE-/- mice were divided into three groups: the Control group, the HFD group, and the HFD + ACN group. Here, we showed that ACN intervention reduced HFD-induced body weight serum concentrations of TC and LDL-C and ameliorated lipid accumulation in the liver and adipose tissues. Besides, ACN altered gut microbiota composition in HFD-fed ApoE-/- mice. Moreover, UHPLC-MS/MS analysis revealed that ACN intervention significantly increased the ratio of conjugated to unconjugated BAs in feces induced by HFD, attributed to the increase in conjugated BAs and decrease in unconjugated BAs. Finally, the correlation analysis indicated that the above changes in fecal BA profile were linked with an increase in Bifidobacterium, Allobaculum and a decrease in Ileibacterium, Helicobacter, Rikenellaceae_RC9_gut_group, Blautia, Odoribacter, and Colidextribacter. In summary, ACN could alleviate HFD-induced hypercholesterolemia in ApoE-/- mice, which was associated with the improvement of gut microbiota and modulation of fecal BA profile.

A new species of Populus and the extensive hybrid speciation arising from it on the Qinghai-Tibet Plateau.

While the diversity of species formation is broadly acknowledged, significant debate exists regarding the universal nature of hybrid species formation. Through an 18-year comprehensive study of all Populus species on the Qinghai-Tibet Plateau, 23 previously recorded species and 8 new species were identified. Based on morphological characteristics, these can be classified into three groups: species in section Leucoides, species with large leaves, and species with small leaves in section Tacamahaca. By conducting whole-genome re-sequencing of 150 genotypes from these 31 species, 2.28 million single nucleotide polymorphisms (SNPs) were identified. Phylogenetic analysis utilizing these SNPs not only revealed a highly intricate evolutionary network within the large-leaf species of section Tacamahaca but also confirmed that a new species, P. curviserrata, naturally hybridized with P. cathayana, P. szechuanica, and P. ciliata, resulting in 11 hybrid species. These findings indicate the widespread occurrence of hybrid species formation within this genus, with hybridization serving as a key evolutionary mechanism for Populus on the plateau. A novel hypothesis, "Hybrid Species Exterminating Their Ancestral Species (HSEAS)," is introduced to explain the mechanisms of hybrid species formation at three different scales: the entire plateau, the southeastern mountain region, and individual river valleys.

Evolutionary law and regulatory technology of roof migration on gob-side entry retaining.

In order to study the evolutionary law of roof migration on Gob-Side Entry Retaining, this paper takes the gob-side entry retaining in the comprehensive mining face of the Ningtiaota coal mine as the engineering background, and analyzes the evolutionary law of the overlying rock layer on the roof at different locations during the roadway stay and the stress distribution around the roadway through numerical simulation software, which shows that there is a concentration of stress inside the Flexible formwork concrete wall, and therefore the maximum settlement of the roof on the side of Flexible formwork concrete wall is 35.35 mm, due to the existence of "arch-shaped" decompression area from the working face. Therefore, the maximum settlement of the roof slab on the side of flexible formwork concrete wall was 35.35 mm. Due to the existence of "arch-shaped" decompression area on the roof and floor of roadway, the settlement of the roof slab on both sides of the roadway gradually increased when it was from - 20 to 10 m away from the working face, and the central position had the following pattern of firstly decreasing and then gradually increasing, and then exceeding the top of the roadway. After decreasing and then gradually increasing, after 10 m ahead of the working face, the two sides of the roadway roof subsidence law and the central part of the roadway to maintain the same; the use of cutting the top of the flexible mold concrete wall support technology as a means of controlling the top of the roof along the empty roadway subsidence, the analysis shows that the roof after roof cutting of the amount of subsidence have been reduced, the maximum difference in the rate of change of the displacement is 0.011%, and the maximum difference in the amount of subsidence of 4.98 mm; through the field monitoring data analysis of the pressure of mining The peak value of the influence curve of the working face is located at 19 m of the working face, 9 m of the lagging working face and 19 m of the roadway outside the working face are less affected by the additional mining stress field, comparing the fracture brokenness of the roadway roof before and after the roof cutting, the fracture area in the uncut section is much larger than that in the section of the roof cutting.

Characteristics of surrounding rock damage and control technology of a facing-mining excavating roadway in north Shaanxi mining area.

In a coal mine in the northern region of Shaanxi Province, China, a facing-mining excavating roadway exists, which is intended to be retained for subsequent working face safety services. This paper investigates the deformation and damage characteristics of the surrounding rock in different stages using FLAC 3D numerical simulation, taking the facing-mining excavating roadway of this coal mine as the research context. At 20 m ahead of the working face, a discontinuous plastic zone appears in the surrounding rock of the roadway, a phenomenon attributed to the varying hardness of the lithologyand termed 'plastic zone jumping.' The numerical simulation results have been were verified using drill hole peeping. Real-time monitoring of the roadway's stability is conducted on-site, showing that the roadway is significantly affected by mining at the 50 m point ahead of the working face. Based on the numerical simulation and on-site monitoring results, the support strength was increased at 50 m from the working face along the roadway, and a new support scheme was adopted. In the lagging section of the roadway, where mining pressure is strongly evident, differentiated reinforcement using anchor rods, anchor ropes, and W steel belts has been employed, resulting in a satisfactory on-site effect.

Corrigendum: Microbiota dynamics, metabolic and immune interactions in the cervicovaginal environment and their role in spontaneous preterm birth.

[This corrects the article DOI: 10.3389/fimmu.2023.1306473.].

TEAD1, MYO7A and NDUFC2 are novel functional genes associated with glucose metabolism in BXD recombinant inbred population.

AIM: The liver is an important metabolic organ that governs glucolipid metabolism, and its dysfunction may cause non-alcoholic fatty liver disease, type 2 diabetes mellitus, dyslipidaemia, etc. We aimed to systematic investigate the key factors related to hepatic glucose metabolism, which may be beneficial for understanding the underlying pathogenic mechanisms for obesity and diabetes mellitus. MATERIALS AND METHODS: Oral glucose tolerance test (OGTT) phenotypes and liver transcriptomes of BXD mice under chow and high-fat diet conditions were collected from GeneNetwork. QTL mapping was conducted to pinpoint genomic regions associated with glucose homeostasis. Candidate genes were further nominated using a multi-criteria approach and validated to confirm their functional relevance in vitro. RESULTS: Our results demonstrated that plasma glucose levels in OGTT were significantly affected by both diet and genetic background, with six genetic regulating loci were mapped on chromosomes 1, 4, and 7. Moreover, TEAD1, MYO7A and NDUFC2 were identified as the candidate genes. Functionally, siRNA-mediated TEAD1, MYO7A and NDUFC2 knockdown significantly decreased the glucose uptake and inhibited the transcription of genes related to insulin and glucose metabolism pathways. CONCLUSIONS: Our study contributes novel insights to the understanding of hepatic glucose metabolism, demonstrating the impact of TEAD1, MYO7A and NDUFC2 on mitochondrial function in the liver and their regulatory role in maintaining in glucose homeostasis.

Systems genetics analysis reveals the common genetic basis for pain sensitivity and cognitive function.

BACKGROUND: There is growing evidence of a strong correlation between pain sensitivity and cognitive function under both physiological and pathological conditions. However, the detailed mechanisms remain largely unknown. In the current study, we sought to explore candidate genes and common molecular mechanisms underlying pain sensitivity and cognitive function with a transcriptome-wide association study using recombinant inbred mice from the BXD family. METHODS: The pain sensitivity determined by Hargreaves' paw withdrawal test and cognition-related phenotypes were systematically analyzed in 60 strains of BXD mice and correlated with hippocampus transcriptomes, followed by quantitative trait locus (QTL) mapping and systems genetics analysis. RESULTS: The pain sensitivity showed significant variability across the BXD strains and co-varies with cognitive traits. Pain sensitivity correlated hippocampual genes showed a significant involvement in cognition-related pathways, including glutamatergic synapse, and PI3K-Akt signaling pathway. Moreover, QTL mapping identified a genomic region on chromosome 4, potentially regulating the variation of pain sensitivity. Integrative analysis of expression QTL mapping, correlation analysis, and Bayesian network modeling identified Ring finger protein 20 (Rnf20) as the best candidate. Further pathway analysis indicated that Rnf20 may regulate the expression of pain sensitivity and cognitive function through the PI3K-Akt signaling pathway, particularly through interactions with genes Ppp2r2b, Ppp2r5c, Col9a3, Met, Rps6, Tnc, and Kras. CONCLUSIONS: Our study demonstrated that pain sensitivity is associated with genetic background and Rnf20-mediated PI3K-Akt signaling may involve in the regulation of pain sensitivity and cognitive functions.

Glucagon Enhances Chemotherapy Efficacy By Inhibition of Tumor Vessels in Colorectal Cancer.

Chemotherapy is widely used to treat colorectal cancer (CRC). Despite its substantial benefits, the development of drug resistance and adverse effects remain challenging. This study aimed to elucidate a novel role of glucagon in anti-cancer therapy. In a series of in vitro experiments, glucagon inhibited cell migration and tube formation in both endothelial and tumor cells. In vivo studies demonstrated decreased tumor blood vessels and fewer pseudo-vessels in mice treated with glucagon. The combination of glucagon and chemotherapy exhibited enhanced tumor inhibition. Mechanistic studies demonstrated that glucagon increased the permeability of blood vessels, leading to a pronounced disruption of vessel morphology. Signaling pathway analysis identified a VEGF/VEGFR-dependent mechanism whereby glucagon attenuated angiogenesis through its receptor. Clinical data analysis revealed a positive correlation between elevated glucagon expression and chemotherapy response. This is the first study to reveal a role for glucagon in inhibiting angiogenesis and vascular mimicry. Additionally, the delivery of glucagon-encapsulated PEGylated liposomes to tumor-bearing mice amplified the inhibition of angiogenesis and vascular mimicry, consequently reinforcing chemotherapy efficacy. Collectively, the findings demonstrate the role of glucagon in inhibiting tumor vessel network and suggest the potential utility of glucagon as a promising predictive marker for patients with CRC receiving chemotherapy.

A model of hybrid speciation process drawn from three new poplar species originating from distant hybridization between sections.

Although numerous studies have been conducted on hybrid speciation, our understanding of this process remains limited. Through an 18-year systematic investigation of all taxa of Populus on the Qinghai-Tibet Plateau, we discovered three new taxa with clear characteristics of sect. Leucoides. Further evidence was gathered from morphology, whole-genome bioinformatics, biogeography, and breeding to demonstrate synthetically that they all originated from distant hybridization between sect. Leucoides and sect. Tacamahaca. P. gonggaensis originated from the hybridization of P. lasiocarpa with P. cathayana, P. butuoensis from the hybridization of P. wilsonii with P. szechuanica, and P. dafengensis from the hybridization of P. lasiocarpa with P. szechuanica. Due to heterosis, the three hybrid taxa possess greater ecological adaptability than their ancestral species. We propose a hybrid speciation process model that incorporates orthogonal, reverse, and backcrossing events. This model can adequately explain some crucial evolutionary concerns, such as the nuclear-cytoplasmic conflict on phylogeny and the extinction of ancestral species within the distribution range of hybrid species.

The polysaccharides from the fruits of Lycium barbarum ameliorate high-fat and high-fructose diet-induced cognitive impairment via regulating blood glucose and mediating gut microbiota.

High-fat and high-fructose diet (HFFD) consumption can induce cognitive dysfunction and gut microbiota disorder. In the present study, the effects of the polysaccharides from the fruits of Lycium barbarum L. (LBPs) on HFFD-induced cognitive deficits and gut microbiota dysbiosis were investigated. The results showed that intervention of LBPs (200 mg/kg/day) for 14 weeks could significantly prevent learning and memory deficits in HFFD-fed mice, evidenced by a reduction of latency and increment of crossing parameters of platform quadrant in Morris water maze test. Moreover, oral administration of LBPs enhanced the expression of postsynaptic density protein 95 and brain-derived neurotrophic factor and reduced the activation of glial cells in hippocampus. Besides, LBPs treatment enriched the relative abundances of Allobaculum and Lactococcus and reduced the relative abundance of Proteobacteria in gut bacterial community of HFFD-fed mice, accompanied by increased levels of short-chain fatty acids (SCFAs) as well as expression of associated G protein-coupled receptors. Furthermore, LBPs intervention prevented insulin resistance, obesity and colonic inflammation. Finally, a significant correlation was observed among neuroinflammation associated parameters, gut microbiota and SCFAs through Pearson correlation analysis. Collectively, these findings suggested that the regulation of gut microbiota might be the potential mechanism of LBPs on preventing cognitive dysfunction induced by HFFD.

MaxCLK: discovery of cancer driver genes via maximal clique and information entropy of modules.

MOTIVATION: Cancer is caused by the accumulation of somatic mutations in multiple pathways, in which driver mutations are typically of the properties of high coverage and high exclusivity in patients. Identifying cancer driver genes has a pivotal role in understanding the mechanisms of oncogenesis and treatment. RESULTS: Here, we introduced MaxCLK, an algorithm for identifying cancer driver genes, which was developed by an integrated analysis of somatic mutation data and protein-protein interaction (PPI) networks and further improved by an information entropy index. Tested on pancancer and single cancers, MaxCLK outperformed other existing methods with higher accuracy. About pancancer, we predicted 154 driver genes and 787 driver modules. The analysis of co-occurrence and exclusivity between modules and pathways reveals the correlation of their combinations. Overall, our study has deepened the understanding of driver mechanism in PPI topology and found novel driver genes. AVAILABILITY AND IMPLEMENTATION: The source codes for MaxCLK are freely available at https://github.com/ShandongUniversityMasterMa/MaxCLK-main.

A comprehensive review of goji berry processing and utilization.

Goji berry (wolfberry, Lycium), is a genus of Solanaceae, in which the roots, stems, leaves, and fruits are for both food and medicinal uses. In recent years, the demand for health food and research purposes has led to increasing attention being paid to the application of goji berry nutrients and resources. There are three general strategies to process and utilize the goji berry plant. First, the primary processing of goji berry products, such as dried goji berry pulp, and fruit wine with its by-products. Second, deep processing of sugar-peptides, carotenoids, and the extraction of other efficacy components with their by-products. Third, the utilization of plant-based by-products (roots, stems, leaves, flowers, and fruit residuals). However, the comprehensive use of goji berry is hampered by the non-standardized production technology of resource utilization and the absence of a multi-level co-production and processing technology systems. On the basis of this, we review some novel techniques that are made to more effectively use the resources found in goji berry or its by-products in order to serve as a guide for the thorough use of these resources and the high-quality growth of the goji berry processing industry.

Water extract of goji berries improves neuroinflammation induced by a high-fat and high-fructose diet based on the bile acid-mediated gut-brain axis pathway.

The high-fat and high-fructose diet (HFFD) is a common diet in westernized societies, which worsens disturbances in gut microbiota and bile acid (BA) metabolism. Herein, the present study aimed to investigate the effects of the water extract of Lycium barbarum fruits (LBE) on gut microbiota and BA metabolism in mice with HFFD-induced neuroinflammation. The results showed that supplementation of LBE for 14 weeks remarkably ameliorated weight gain and insulin resistance and suppressed microglial activation and neural neuroinflammation induced by HFFD. The results of Morris water maze and Y-maze tests demonstrated that LBE attenuated HFFD-induced cognitive impairment. Moreover, LBE elevated hepatic BA biosynthesis and excretion of BAs and increased elimination of BAs via the feces. Notably, LBE supplementation resulted in the enrichment of tauroursodeoxycholic acid in the cortex and hippocampus. Furthermore, the 16S rDNA sequencing results showed that LBE could modulate the structure of gut microbiota, and in the meantime decrease the relative abundance of Clostridium_XlVa, which is associated with BA homeostasis. Additionally, LBE exerted neuroprotective effects involving the increment of Lactococcus, known as a potentially beneficial bacterium. These results demonstrated that LBE could ameliorate neuroinflammation and cognitive impairment in HFFD-induced mice through the gut-liver-brain axis, which might be due to the regulation of BA homeostasis and gut microbiota in mice.

Regulation of insulin secretion by the post-translational modifications.

Post-translational modification (PTM) has a significant impact on cellular signaling and function regulation. In pancreatic ß cells, PTMs are involved in insulin secretion, cell development, and viability. The dysregulation of PTM in ß cells is clinically associated with the development of diabetes mellitus. Here, we summarized current findings on major PTMs occurring in ß cells and their roles in insulin secretion. Our work provides comprehensive insight into understanding the mechanisms of insulin secretion and potential therapeutic targets for diabetes from the perspective of protein PTMs.

VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway.

Although VEGF-B was discovered as a VEGF-A homolog a long time ago, the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups. Notwithstanding, drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases. It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms. Using comprehensive in vitro and in vivo methods and models, we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway when the latter is abundantly expressed. Mechanistically, we unveil that VEGF-B binds to FGFR1, induces FGFR1/VEGFR1 complex formation, and suppresses FGF2-induced Erk activation, and inhibits FGF2-driven angiogenesis and tumor growth. Our work uncovers a previously unrecognized novel function of VEGF-B in tethering the FGF2/FGFR1 pathway. Given the anti-angiogenic nature of VEGF-B under conditions of high FGF2/FGFR1 levels, caution is warranted when modulating VEGF-B activity to treat neovascular diseases.