Neuroprotective effect of GJ-4 against cognitive impairments in vascular dementia by improving white matter damage.

BACKGROUND: White matter lesions (WMLs) are increasingly linked to the pathological process of chronic vascular dementia (VaD). An effective crocins fraction extracted from Gardenia Fructus, GJ-4, has been shown to improve cognitive function in several Alzheimer's disease models and VaD models. OBJECTIVES: To explore the potential mechanisms of GJ-4 on WMLs in a chronic VaD mouse model. METHODS: The chronic VaD mouse model was established, and WMLs were characterized by cerebral blood flow (CBF), behavioral tests, LFB staining, and immunohistochemistry. The anti-oxidative effect of GJ-4 was validated by examining biochemical parameters (SOD, MDA, and GSH) and the Keap1-Nrf2/HO-1 pathway. The impact of GJ-4 on lipid metabolism in WM was further investigated through lipidomic analysis. RESULTS: GJ-4 significantly attenuated cognitive impairments and improved the CBF of BCAS (bilateral common carotid artery stenosis)-induced mice. Mechanism research showed that GJ-4 could enhance cognition by promoting the repair of WMLs by inhibiting oxidative stress. Furthermore, GJ-4 treatment significantly reduced chronic cerebral hypoperfusion (CCH)-induced WMLs via improving lipid metabolism disorder in the WM. CONCLUSION: This research has provided valuable insights into the significance of WMLs in CCH-induced VaD and underscored the potential of GJ-4 as a therapeutic agent for improving cognitive function by targeting WMLs. These findings suggest that GJ-4 is a promising candidate for the treatment of VaD.

Magnetic compression anastomosis gastrojejunostomy: feasibility and efficacy of a novel device in a swine model.

BACKGROUND: Means of addressing technical challenges in forming gastrojejunostomy (GJ) anastomoses and maintaining their patency are sought. OBJECTIVES: Evaluation of preclinical feasibility and healing efficacy of a novel linear magnetic compression anastomosis (MCA) device to form a patent GJ versus sutured jejunal enterotomy (JE) sites in swine. SETTING: Single-center veterinary testing facility. METHODS: Feasibility of 3 prototype sizes (4, 6, and 8 cm) of a metal MCA device (MCAD) to form a patent GJ was evaluated over 6 weeks. A distal magnet was laparoscopically inserted in the jejunum, a proximal magnet was placed gastroscopically in the stomach; magnets were aligned to gradually form an anastomosis, self-detached, and be expelled. At necropsy, MCAs were assessed for patency and compared with JE tissues to evaluate wound healing. RESULTS: MCADs aligned at the GJ location without complications. In 5/6 MCAD pairs, dislodgement occurred between 7 and 26 days; expulsion 13-31 days; 1 MCAD pair was retained in the stomach. At necropsy, all pigs were healthy, gaining a mean 15.0 kg. Anastomoses were not adequately patent in 2/4 pigs receiving the 4-cm or 6-cm MCADs because their linear length was too small. But, anastomoses of both pigs receiving the 8-cm MCADs maintained full patency. Minimal inflammation and fibrosis were seen in MCA specimens versus sutured enterotomies. CONCLUSIONS: A novel linear MCA device was feasible and effectively created a patent GJ anastomosis in swine with minimal inflammation and fibrosis. The MCAD may be appropriate for clinical evaluation.

Endoscopic ultrasound-guided gastrojejunostomy for benign gastric outlet obstruction (GOO): a retrospective analysis of patients and outcomes.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound-guided gastrojejunostomy (EUS-GJ) has been well utilized in treating malignant gastric outlet obstructions (GOO) given its efficacy and lower risk profile compared to surgery. However, its efficacy and potential for use in patients with benign GOO who are poor surgical candidates is not well documented. The aim of this study was to examine the role of EUS-GJ in treatment of benign GOO in select patients. PATIENTS AND METHODS: This is a single-center, open-label, retrospective descriptive study that included all consecutive patients undergoing EUS-GJ to treat benign causes of GOO. Direct antegrade and direct retrograde methods were utilized. RESULTS: A total of 18 patients were included, 38.9% female with an average age of 63.3 years. Extrinsic GOO was present in (10 of 18) 55.5% of patients and intrinsic etiology was present in (8 of 18) 45.5% of patients. Technical success was achieved in 100% (18 of 18) patients and clinical success was achieved in 94% (17 of 18) patients. In total, 13 patients had follow-up endoscopy, 2 patients were treated relatively recently in time, 1 patient was lost to follow-up, and 2 patients died of other chronic illnesses. Stents remained in place for a median of 286 days (range 88-1444 days). In patients whose stents were removed, 75% (3 of 4) had extrinsic etiologies of GOO. CONCLUSIONS: This study reports a favorable long-term patency with excellent technical and clinical success of EUS-GJ in patients with benign GOO. Despite the limitations of sample size and retrospective nature, it adds to the extremely limited literature of EUS-GJ in management of patients with benign GOO.

The Therapeutic Potential of Targeting the Connexin43 as a New Approach to Reducing Post-surgical Adhesion

Post-surgical peritoneal adhesions are a serious problem causing complications, such as bowel obstruction, infertility, and pain. There are currently no effective ways of preventing post-surgical adhesions. Excess secretion of proinflammatory cytokines and profibrotic molecules by immune cells and adherent fibroblasts are the main mechanism that promotes post-operative fibrotic scars. Although many studies have been conducted on the pathological causes of this disorder, there are still many unknown facts in this matter, so assessment of the role of different molecules in causing inflammation and adhesion can lead to the creation of new treatment methods. Connexins are a group of proteins related to gap junctions that have a role in cell communication and transmitted signaling between adjacent cells. Between different types of connexin protein isoforms, connexin43 is known to be involved in pathological conditions related to inflammation and fibrosis. Recent studies have reported that inhibition of connexin43 has the potential to reduce inflammation and fibrosis by reducing the expression of molecules like α-SMA and plasminogen activator inhibitor (PAI) that are involved in the early stages of adhesion formation. As well as, inhibition of connexin43 may have therapeutic potential as a target to prevent post-surgical peritoneal adhesions.

Amelioration activity of the high bioaccessible chrysanthemum (Gongju) phenolics on alcohol-induced oxidative injury in AML-12 cells.

The main bioavailable phenolics from of Gongju (GJ) and their mechanism for hepato-protection remain unclear. To select the GJ phenolics with high bioavailability, chrysanthemum digestion and Caco-2 cells were used and their hepato-protective potential were examined by using AML-12 cells. The digestive recovery and small intestinal transit rate of the main phenolic compounds ranged from 28.52 to 69.53% and 6.57% âˆ¼ 15.50%, respectively. Among them, chlorogenic acid, 3,5-dicaffeoylquinic acid, and 1,5-dicaffeoylquinic acid, showed higher small intestinal transit rates and digestive recoveries. Furthermore, we found that by increasing intracellular Catalase (CAT) and Superoxide dismutase (SOD) viability and lowering Malondialdehyde (MDA) level (P < 0.05), 3,5-dicaffeoylquinic acid significantly mitigated the oxidative damage of AML-12 liver cells more than the other two phenolics. Our results demonstrated that 3,5-dicaffeoylquninic acid was the primary phenolic compounds in GJ that effectively reduced liver damage, providing a theoretical basis for the development of GJ as a potentially useful resource for hepatoprotective diet.

Impact of Gastrojejunostomy Anastomosis Diameter on Weight Loss Following Laparoscopic Gastric Bypass: A Systematic Review.

Laparoscopic Roux-en-Y gastric bypass (RYGB) is crucial for significant weight reduction and treating obesity-related issues. However, the impact of gastrojejunostomy (GJ) anastomosis diameter on weight loss remains unclear. We investigate this influence on post-RYGB weight loss outcomes. A systematic search was conducted. Six studies met the inclusion criteria, showing varied GJ diameters and follow-up durations (1-5 years). Smaller GJ diameters generally correlated with greater short-to-medium-term weight loss, with a threshold beyond which complications like stenosis increased. Studies had moderate-to-low bias risk, emphasizing the need for precise GJ area quantification post-operation. This review highlights a negative association between smaller GJ diameters and post-RYGB weight loss, advocating for standardized measurement techniques. Future research should explore intra-operative and AI-driven methods for optimizing GJ diameter determination.

Isolation, identification, molecular and pathogenicity characteristics of an infectious laryngotracheitis virus from Hubei province, China.

Multiple outbreaks of avian infectious laryngotracheitis (ILT) in chickens, both domestically and internationally, have been directly correlate to widespread vaccine use in affected countries and regions. Phylogenetic and recombination event analyses have demonstrated that avian infectious laryngotracheitis virus (ILTV) field strains are progressively evolving toward the chicken embryo-origin (CEO) vaccine strain. Even with standardized biosecurity measures and effective prevention and control strategies implemented on large-scale farms, continuous ILT outbreaks result in significant economic losses to the poultry industry worldwide. These outbreaks undoubtedly hinder efforts to control and eradicate ILTV in the future. In this study, an ILTV isolate was successfully obtained by laboratory PCR detection and virus isolation from chickens that exhibited dyspnea and depression on a broiler farm in Hubei Province, China. The isolated strain exhibited robust propagation on chorioallantoic membranes of embryonated eggs, but failed to establish effective infection in chicken hepatocellular carcinoma (LMH) cells. Phylogenetic analysis revealed a unique T441P point mutation in the gJ protein of the isolate. Animal experiments confirmed the virulence of this strain, as it induced mortality in 6-wk-old chickens. This study expands current understanding of the epidemiology, genetic variations, and pathogenicity of ILTV isolates circulating domestically, contributing to the elucidate of ILTV molecular basis of pathogenicity and development of vaccine.

Cooperative cell-cell actin network remodeling to perform Gap junction endocytosis.

BACKGROUND: The endocytosis of Gap junction plaques (GJP) requires cytoskeletal forces to internalize such large membranous structures. Actin, which partners the connexin proteins constituting Gap junctions and is located close to Annular Gap Junctions (AGJ), could be actively involved in this physiological process. RESULTS: Electron Microscopy and Light Microscopy images, associated with time-lapse analysis and 3D reconstruction, used at high resolution and enhanced using ImageJ based software analysis, revealed that: i) actin cables, originating from Donor cells, insert on the edge of GJP and contribute to their invagination, giving rise to AGJ, whereas actin cables on the Acceptor cell side of the plaque are not modified; ii) actin cables from the Donor cell are continuous with the actin network present over the entire GJP surface. These actin cables fuse at a single point distant from the plaque, which then detaches itself from the membrane, condensing to form an actin mass during the final internalization process; iii) the Acceptor cell participates in the last step of the endocytic invagination process by forming an annular actin structure known as an actin ring. CONCLUSIONS: Together, these data suggest that the endocytosis of GJP is an example of a unique cooperative mechanism between the Donor (the traction of its actin cables) and the Acceptor cells (forming the actin ring).

RéSUMé: CONTEXTE: L'endocytose des plaques de jonctions communicantes ou jonctions gap (GJP) nécessite les forces du cytosquelette pour internaliser ces grandes structures membranaires. L'actine, partenaire des connexines, proteins constitutives des jonctions gap (Gj), localisée proche des jonctions gap annulaires (GJA), pourrait être impliquée dans ce processus physiologique. RéSULTATS: L' imagerie par microscopie optique et électronique, associées avec des analyses vidéo et des reconstructions en relief/3D, examinées à haute résolution et améliorées après traitement par des logiciels développés sous ImageJ, montrent que: i) des câbles d'actine, originaires des cellules donneuses, s'insèrent sur le bord des plaques jonctionnelles et facilitent leur invagination pour former les GJA tandis que les câbles d'actine des cellules receveuses ne sont pas modifies; ii) les câbles d'actine des cellules donneuses sont en continuité avec le réseau d'actine qui couvre la totalité de la surface de la plaque. De plus, ces câbles fusionnent en un point unique, à distance de la plaque, qui se détache de la région membranaire pour former une masse d'actine à la fin du processus d'endocytose; iii) la cellule receveuse participe à l'étape ultime du processus d'endocytose de la plaque en formant un anneau d'actine. CONCLUSIONS: L'ensemble de nos résultats montrent que l'endocytose des plaques jonctionnelles est un exemple de coopération unique entre la cellule donneuse (grâce à la traction des câbles d'actine) et la cellule receveuse (anneau d'actine).

Intussusception in an elderly female and its management: A case report and literature review.

Intussusception is the telescoping or invagination of the proximal part of the gastrointestinal tract into an adjacent section. It is rare in adults, accounting for 1% of adult bowel obstruction. Adult presentation of intussusception is variable, with nonspecific, vague symptoms like abdominal pain, nausea, vomiting, and rectal bleeding. Abdominal computed tomography (CT) scans have the highest sensitivity in the diagnosis of intussusception. The classical findings of intussusception are the target sign and mesenteric vessels lined within the bowel lumen. An abdominal CT scan can reveal a cloverleaf figuration, fluid-filled ileal loops, superior mesenteric venous (SMV) occlusion, and concerns about ongoing sealed perforation or fistulization. Our patient is an 86-year-old female who was diagnosed with a jejunal-jejunal long-segment intussusception, gastro-enteric fistula, and SMV occlusion with distal reconstitution. The patient responded well to conservative treatment and was discharged for follow-up.

Retrospective cohort comparison between fluoroscopic and radiograph-only exams for evaluation of gastrostomy and gastrojejunostomy tubes.

BACKGROUND: Gastrostomy (G) tube or gastrojejunostomy (GJ) tube checks are radiographic procedures that are frequently ordered to confirm tube positioning. OBJECTIVE: To characterize the sensitivity and specificity of radiograph-only examinations and traditional radiologist-performed fluoroscopy exams for G-tube or GJ-tube malposition and other adverse events detectable by imaging. MATERIALS AND METHODS: We performed a retrospective cohort study at a single tertiary pediatric center that included all subjects who underwent G-tube or GJ-tube checks using fluoroscopy or radiograph-only exams between January 1, 2008, and January 1, 2019. Radiograph-only examinations were defined as checks that consist of frontal and lateral abdominal radiographs after injection of contrast through the G-tube or GJ-tube. Fluoroscopy exams were defined as exams performed by a radiologist in the fluoroscopy suite. Radiology reports were evaluated for reported tube malposition and for other adverse events that are detectable by imaging. Clinical notes from the day of the procedure and longer-term clinical follow-up notes were used as a reference standard for adverse events. The sensitivity and specificity of the two procedures were calculated. RESULTS: A total of 212 exams, including 86 (41%) fluoroscopy exams and 126 (59%) radiograph-only exams, were evaluated. The most common correctly identified adverse event was tube malposition (9 true positives). The most commonly missed adverse event was leakage around the tube (8 false negatives). Fluoroscopy exams had a sensitivity of 100% (6/6; 95% CI: 100%, 100%) and a specificity of 100% (80/80; 95% CI: 100%, 100%) for tube malposition, while radiograph-only exams had 75% sensitivity (3/4; 95% CI: 33%,100%) and 100% specificity (112/112; 95% CI: 100%, 100%). CONCLUSIONS: Fluoroscopy and radiograph-only exams have similar sensitivity and specificity for detecting G-tube or GJ-tube malposition.

Volatile Organic Compounds of Bacillus velezensis GJ-7 against Meloidogyne hapla through Multiple Prevention and Control Modes.

The Bacillus velezensis GJ-7 strain isolated from the rhizosphere soil of Panax notoginseng showed high nematicidal activity and therefore has been considered a biological control agent that could act against the root-knot nematode Meloidogyne hapla. However, little was known about whether the GJ-7 strain could produce volatile organic compounds (VOCs) that were effective in biocontrol against M. hapla. In this study, we evaluated the nematicidal activity of VOCs produced by the fermentation of GJ-7 in three-compartment Petri dishes. The results revealed that the mortality rates of M. hapla J2s were 85% at 24 h and 97.1% at 48 h after treatment with the VOCs produced during GJ-7 fermentation. Subsequently, the VOCs produced by the GJ-7 strain were identified through solid-phase micro-extraction gas chromatography mass spectrometry (SPME-GC/MS). Six characteristic VOCs from the GJ-7 strain fermentation broth were identified, including 3-methyl-1-butanol, 3-methyl-2-pentanone, 5-methyl-2-hexanone, 2-heptanone, 2,5-dimethylpyrazine, and 6-methyl-2-heptanone. The in vitro experimental results from 24-well culture plates showed that the six volatiles had direct-contact nematicidal activity against M. hapla J2s and inhibition activity against egg hatching. In addition, 3-methyl-1-butanol and 2-heptanone showed significant fumigation effects on M. hapla J2s and eggs. Furthermore, all six of the VOCs repelled M. hapla J2 juveniles in 2% water agar Petri plates. The above data suggested that the VOCs of B. velezensis GJ-7 acted against M. hapla through multiple prevention and control modes (including direct-contact nematicidal activity, fumigant activity, and repellent activity), and therefore could be considered as potential biocontrol agents against root-knot nematodes.

Iatrogenic perforation during lumen-apposing metal stent deployment closed using an over-the-scope stent fixation clip device.

Video 1Endoscopic closure of an iatrogenic perforation caused during EUS-guided gastrojejunostomy for malignant gastric outlet obstruction treated with an over-the-scope stent fixation clip device.

Structural basis of the oncogenic KRAS mutant and GJ101 complex.

KRAS mutations occur in a quarter of all human cancers. When activated in its GTP-bound form, RAS stimulates diverse cellular systems, such as cell division, differentiation, growth, and apoptosis through the activations of various signaling pathways, which include mitogen-activated protein kinase (MAPK), phosphoinositide 3 kinases (PI3K), and RAL-GEFs pathways. We found that GJ101 (65LYDVA69) binds directly to the KRAS mutant (G12V) and showed tumor-suppressive activity. In addition, the GJ101 peptide inhibited KRAS mutant as determined by a [α-32P] guanosine triphosphate (GTP) binding assay and suppressed pancreatic cell line in a cell proliferation assay. Herein, the complex structure of KRAS and GJ101 was clarified by X-ray crystallography. Isothermal titration calorimetry showed that GJ101 binds highly with KRAS mutant and the complex structure of KRAS G12V.GJ101 complex presented that the residue of Q61 directly interacted with L65 of GJ101. Overall, the results suggest GJ101 be considered a developmental starting point for KRAS G12V inhibitor.

Gardenia jasminoides Extract GJ-4 Alleviates Memory Deficiency of Vascular Dementia in Rats through PERK-Mediated Endoplasmic Reticulum Stress Pathway.

Endoplasmic reticulum stress (ERS) is involved in the pathological process of vascular dementia (VD). GJ-4 is extracted from Gardenia jasminoides J. Ellis and has been reported to have protective roles in ischemia-related brain damage. However, the role of GJ-4 in ERS has not been elucidated. We established a VD rat model through bilateral common carotid arteries occlusion (2-VO). The rats were intragastrically administrated with GJ-4 (10, 25, and 50[Formula: see text]mg/kg) and nimodipine (10[Formula: see text]mg/kg). Data from a Morris water maze test showed that GJ-4 could significantly alleviate learning and memory deficits in VD rats. Nissl and cleaved caspase-3 staining revealed that GJ-4 can inhibit apoptosis and thus exert a protective role in the brain of 2-VO rats. Western blot results suggested that GJ-4 significantly reduced ERS-related protein expression and inhibited apoptosis through suppression of the PERK/eIF2[Formula: see text]/ATF4/CHOP signaling pathway. For in vitro studies, the oxygen-glucose deprivation (OGD) SH-SY5Y model was employed. Western blot and Hoechst 33342/PI double staining were utilized to explore the effects of crocetin, the main active metabolite of GJ-4. Like GJ-4 in vivo, crocetin in vitro also decreased ERS-related protein expression and inhibited the activation of the PERK/eIF2[Formula: see text]/ATF4/CHOP signaling pathway. Thus, crocetin exerted similar protective roles on OGD challenged SH-SY5Y cells in vitro. In summary, GJ-4 and crocetin reduce the ERS in the brain of VD rats and SY5Y cells subjected to OGD and inhibit neuronal apoptosis through suppression of the PERK/eIF2[Formula: see text]/ATF4/CHOP pathway, suggesting that GJ-4 may be useful for the treatment of VD.

Endoscopic management of gastrojejunocolic fistula after endoscopic gastrojejunostomy.

Video 1Endoscopic repair of gatstrojejunocolic fistala using tandem stent placement with a long covered metal stent.

EUS-directed transenteric ERCP-assisted internalization of a percutaneous biliary drain in Roux-en-Y anatomy.

Video 1EUS-directed transenteric ERCP-assisted internalization of percutaneous biliary drain in Roux-en-Y hepaticojejunostomy anatomy.

EUS-guided gastrojejunostomy for management of malignant gastric outlet obstruction in a patient with Roux-en-Y anatomy.

Video 1Endoscopic ultrasound-guided gastrojejunostomy.

Gardenia jasminoides J. Ellis extract GJ-4 attenuates hyperlipidemic vascular dementia in rats via regulating PPAR-γ-mediated microglial polarization.

Background: GJ-4 is extracted from Gardenia jasminoides J. Ellis (Fructus Gardenia) with crocin composition and has been demonstrated to improve memory deficits in several dementia models in our previous studies. Objective: This study aimed to evaluate the effects of GJ-4 on hyperlipidemic vascular dementia (VD) and explore the underlying mechanisms. Design: In the current study, we employed a chronic hyperlipidemic VD rat model by permanent bilateral common carotid arteries occlusion (2-VO) based on high-fat diet (HFD), which is an ideal model to mimic the clinical pathogenesis of human VD. Results: Our results showed that GJ-4 could significantly reduce serum lipids level and improve cerebral blood flow in hyperlipidemic VD rats. Additionally, treatment with GJ-4 remarkedly ameliorated memory impairment and alleviated neuronal injury. Mechanistic investigation revealed that the neuroprotective effects of GJ-4 might be attributed to the inhibition of microglia-mediated neuro-inflammation via regulating the M1/M2 polarization. Our data further illustrated that GJ-4 could regulate the phenotype of microglia through activating the peroxisome proliferator-activated receptor-γ (PPAR-γ) and subsequently inhibited nuclear factor-κB (NF-κB) nuclear translocation and increased CCAAT/enhancer-binding protein ß (C/EBPß) expression. Conclusion: Our results implied that GJ-4 might be a promising drug to improve VD through the regulation of microglial M1/M2 polarization and the subsequent inhibition of neuro-inflammation.

Gardenia jasminoides J.Ellis extract GJ-4 alleviated cognitive deficits of APP/PS1 transgenic mice.

BACKGROUND: Accumulating evidence demonstrates that traditional Chinese medicines that act on multiple targets could effectively treat various multi-etiological diseases, including cerebrovascular diseases, Alzheimer's disease (AD), Parkinson's disease (PD) and so on. Previous studies have shown that crocin richments (GJ-4), Gardenia jasminoides J.Ellis extract, provide neuroprotective effects on cognitive impairments in AD mouse models. However, the mechanism how GJ-4 improves cognition remains still unclear. PURPOSE: The aim of this study was to uncover the protective effects and underlying mechanism of GJ-4 on PrP-hAßPPswe/PS1ΔE9 (APP/PS1) transgenic mice. METHODS: APP/PS1 mice were given GJ-4 (10, 20, and 50 mg/kg), donepezil (5 mg/kg) and memantine (5 mg/kg) orally at eight months of age for 12 consecutive weeks. Morris water maze and novel object recognition were conducted to assess the cognitive ability of mice. The release of inflammatory cytokines was determined by RT-PCR assay, and the pathological features of neurons and microglia were assayed by immunohistochemistry and immunofluorescence assay. The expression of Aß-related proteins and signaling pathways were determined by Western blot. RESULTS: The behavioral results revealed that GJ-4 ameliorated the cognitive deficits of APP/PS1 mice measured by Morris water maze and novel object recognition tests. Mechanism studies indicated that GJ-4 significantly decreased ß-amyloid (Aß) level through reducing Aß production and promoting Aß degradation. It has been reported that Aß plaques trigger the hyper-phosphorylation of tau protein in APP/PS1 mice. Consistent with previous studies, hyper-phosphorylation of tau was also occurred in APP/PS1 mice in the present study, and GJ-4 inhibited Tau phosphorylation at different sites. Overwhelming evidence indicates that neuroinflammation stimulated by Aß and hyperphosphorylated tau is involved in the pathological progression of AD. We found that GJ-4 suppressed neuroinflammatory responses in the brain through regulating phosphatidylinositide 3-kinase/AKT (PI3K/AKT) signaling pathway activation, and subsequent expression of inflammatory proteins and release of inflammatory cytokines. CONCLUSION: Altogether, GJ-4 ameliorated cognition of APP/PS1 transgenic mice through multiple targets, including Aß, tau and neuroinflammation. This study provides a solid research basis for further development of GJ-4 as a potential candidate for the treatment of AD.

Fusarium: more than a node or a foot-shaped basal cell.

Recent publications have argued that there are potentially serious consequences for researchers in recognising distinct genera in the terminal fusarioid clade of the family Nectriaceae. Thus, an alternate hypothesis, namely a very broad concept of the genus Fusarium was proposed. In doing so, however, a significant body of data that supports distinct genera in Nectriaceae based on morphology, biology, and phylogeny is disregarded. A DNA phylogeny based on 19 orthologous protein-coding genes was presented to support a very broad concept of Fusarium at the F1 node in Nectriaceae. Here, we demonstrate that re-analyses of this dataset show that all 19 genes support the F3 node that represents Fusarium sensu stricto as defined by F. sambucinum (sexual morph synonym Gibberella pulicaris). The backbone of the phylogeny is resolved by the concatenated alignment, but only six of the 19 genes fully support the F1 node, representing the broad circumscription of Fusarium. Furthermore, a re-analysis of the concatenated dataset revealed alternate topologies in different phylogenetic algorithms, highlighting the deep divergence and unresolved placement of various Nectriaceae lineages proposed as members of Fusarium. Species of Fusarium s. str. are characterised by Gibberella sexual morphs, asexual morphs with thin- or thick-walled macroconidia that have variously shaped apical and basal cells, and trichothecene mycotoxin production, which separates them from other fusarioid genera. Here we show that the Wollenweber concept of Fusarium presently accounts for 20 segregate genera with clear-cut synapomorphic traits, and that fusarioid macroconidia represent a character that has been gained or lost multiple times throughout Nectriaceae. Thus, the very broad circumscription of Fusarium is blurry and without apparent synapomorphies, and does not include all genera with fusarium-like macroconidia, which are spread throughout Nectriaceae (e.g., Cosmosporella, Macroconia, Microcera). In this study four new genera are introduced, along with 18 new species and 16 new combinations. These names convey information about relationships, morphology, and ecological preference that would otherwise be lost in a broader definition of Fusarium. To assist users to correctly identify fusarioid genera and species, we introduce a new online identification database, Fusarioid-ID, accessible at www.fusarium.org. The database comprises partial sequences from multiple genes commonly used to identify fusarioid taxa (act1, CaM, his3, rpb1, rpb2, tef1, tub2, ITS, and LSU). In this paper, we also present a nomenclator of names that have been introduced in Fusarium up to January 2021 as well as their current status, types, and diagnostic DNA barcode data. In this study, researchers from 46 countries, representing taxonomists, plant pathologists, medical mycologists, quarantine officials, regulatory agencies, and students, strongly support the application and use of a more precisely delimited Fusarium (= Gibberella) concept to accommodate taxa from the robust monophyletic node F3 on the basis of a well-defined and unique combination of morphological and biochemical features. This F3 node includes, among others, species of the F. fujikuroi, F. incarnatum-equiseti, F. oxysporum, and F. sambucinum species complexes, but not species of Bisifusarium [F. dimerum species complex (SC)], Cyanonectria (F. buxicola SC), Geejayessia (F. staphyleae SC), Neocosmospora (F. solani SC) or Rectifusarium (F. ventricosum SC). The present study represents the first step to generating a new online monograph of Fusarium and allied fusarioid genera (www.fusarium.org).