Sanderbondesen3815

The nemertide toxins from the phylum Nemertea are a little researched family of neurotoxins with potential for development as biopesticides. Here we report the recombinant production of nemertide α-1 (α-1), a 65-residue inhibitor cystine knot (ICK) peptide from Lineus longissimus, known to target insect voltage-gated sodium channels. The insecticidal activity of α-1 was assessed and compared with the well characterised ICK venom peptide, ω-atracotoxin/hexatoxin-Hv1a (Hv1a). α-1 elicited potent spastic paralysis when injected into cabbage moth (Mamestra brassicae) larvae; conferring an ED50 3.90 μg/larva (10.30 nmol/g larva), followed by mortality (60% within 48 h after 10 μg injection). By comparison, injection of M. brassicae larvae with recombinant Hv1a produced short-lived flaccid paralysis with an ED50 over 6 times greater than that of α-1 at 26.20 μg/larva (64.70 nmol/g larva). Oral toxicity of α-1 was demonstrated against two aphid species (Myzus persicae and Acyrthosiphon pisum), with respective LC50 values of 0.35 and 0.14 mg/mL, some 6-fold lower than those derived for recombinant Hv1a. When delivered orally to M. brassicae larvae, α-1 caused both paralysis (ED50 11.93 μg/larva, 31.5 nmol/g larva) and mortality. This contrasts with the lack of oral activity of Hv1a, which when fed to M. brassicae larvae had no effect on feeding or survival. Hv1a has previously been shown to be non-toxic by injection to the beneficial honeybee (Apis mellifera). By contrast, rapid paralysis and 100% mortality was observed following injection of α-1 (31.6 nmol/g insect). These results demonstrate the great potential of naturally occurring non-venomous peptides, such as α-1, for development as novel effective biopesticides, but equally highlights the importance of understanding the phyletic specificity of a given toxin at an early stage in the quest to discover and develop safe and sustainable pesticides.The present report describes the clinical and pathological changes induced by the consumption of oats contaminated with Crotalaria spectabilis seeds by horses. Eighty horses were exposed to oats containing 10 g/kg of C. spectabilis seeds with 0.46% pyrrolizidine alkaloids, and 21 horses died within a 6-month period. Clinical signs included jaundice, apathy, a hypotonic tongue, ataxia, hyporexia, weight loss, aimless wandering, violent behavior, and proprioceptive deficits. Pathological findings were predominant in the liver and included periportal bridging fibrosis, megalocytosis, centrilobular necrosis, and bile stasis. Other findings were Alzheimer's type II astrocytes in the cortex, midbrain, basal nuclei, brainstem and pons; multifocal edema and hemorrhage in the lungs; and degeneration and necrosis of the tubular epithelium of kidneys. Horses are highly sensitive to pyrrolizidine alkaloid-containing plants, and the observed clinical and pathological findings are typical of this poisoning. The seeds were planted, and botanical identification of the adult plants confirmed the diagnosis of C. spectabilis poisoning.Biofilms are rigid and largely impenetrable three-dimensional matrices constituting virulence determinants of various pathogenic bacteria. Here, we demonstrate that molecular tweezers, unique supramolecular artificial receptors, modulate biofilm formation of Staphylococcus aureus. In particular, the tweezers affect the structural and assembly properties of phenol-soluble modulin α1 (PSMα1), a biofilm-scaffolding functional amyloid peptide secreted by S. aureus. The data reveal that CLR01, a diphosphate tweezer, exhibits significant S. aureus biofilm inhibition and disrupts PSMα1 self-assembly and fibrillation, likely through inclusion of lysine side chains of the peptide. In comparison, different peptide binding occurs in the case of CLR05, a tweezer containing methylenecarboxylate units, which exhibits lower affinity for the lysine residues yet disrupts S. aureus biofilm more strongly than CLR01. Our study points to a possible role for molecular tweezers as potent biofilm inhibitors and antibacterial agents, particularly against untreatable biofilm-forming and PSM-producing bacteria, such as methicillin-resistant S. aureus.

Endoscopic submucosal dissection (ESD) and EMR are applied in treating superficial colorectal neoplasms but are contraindicated by deeply invasive colorectal cancer (CRC). The invasion depth of neoplasms can be examined by an automated artificial intelligence (AI) system to determine the applicability of ESD and EMR.

A deep convolutional neural network with a tumor localization branch to guide invasion depth classification was constructed on the GoogLeNet architecture. The model was trained using 7734 nonmagnified white-light colonoscopy (WLC) images supplemented by image augmentation from 657 lesions labeled with histopathologic analysis of invasion depth. An independent testing dataset consisting of 1634 WLC images from 156 lesions was used to validate the model.

For predicting noninvasive and superficially invasive neoplasms, the model achieved an overall accuracy of 91.1% (95% confidence interval [CI], 89.6%-92.4%), with 91.2% sensitivity (95% CI, 88.8%-93.3%) and 91.0% specificity (95% CI, 89.0%-92.7%) at an optimal cutoff of .41 and the area under the receiver operating characteristic (AUROC) curve of .970 (95% CI, .962-.978). learn more Inclusion of the advanced CRC data significantly increased the sensitivity in differentiating superficial neoplasms from deeply invasive early CRC to 65.3% (95% CI, 61.9%-68.8%) with an AUROC curve of .729 (95% CI, .699-.759), similar to experienced endoscopists (.691; 95% CI, .624-.758).

We have developed an AI-enhanced attention-guided WLC system that differentiates noninvasive or superficially submucosal invasive neoplasms from deeply invasive CRC with high accuracy, sensitivity, and specificity.

We have developed an AI-enhanced attention-guided WLC system that differentiates noninvasive or superficially submucosal invasive neoplasms from deeply invasive CRC with high accuracy, sensitivity, and specificity.

Pancreatic cystic fluid (PCF) analysis is useful to distinguish between different cyst types and to guide management. The aim of our study was to compare the diagnostic accuracy of glucose level with carcinoembryonic antigen (CEA) in PCF for mucinous cyst diagnosis.

We identified studies with PCF obtained by EUS before surgery, with cysts classified as mucinous and nonmucinous according to surgical specimens. A random-effects model was used for quantitative meta-analysis. Pooled sensitivities, specificities, and summary receiver operating characteristic (ROC) curve analysis were conducted.

For CEA, we included 31 studies with 5268 patients, of which 2083 were referred for surgery. For glucose, we included 4 studies with 345 patients, of which 275 were referred for surgery. Glucose performed better than CEA for mucinous cysts diagnosis (premalignant and malignant) with sensitivities of .90 (95% confidence interval [CI], .85-.94) and .67 (95% CI, .65-.70), specificities of .82 (95% CI, .72-.89) and .80 (95% CI, 0.