Search Results (33)

Blooms of the marine dinoflagellate Vulcanodinium rugosum have been associated with skin lesion outbreaks in Cuba and elsewhere. In this study, cell growth and toxin production were investigated under laboratory-controlled conditions in two strains isolated from Cienfuegos Bay, Cuba. Strains were cultured with and without a mechanical agitation and toxins were analyzed at two stages of the culture growth (exponential and stationary). Although blooms in Cienfuegos Bay occur in a semi-enclosed system characterized by calm waters with no agitation, the results of this study suggest that V. rugosum cells may also exhibit growth capacity under agitated conditions, or in open waters, comparable to that observed in systems with low hydrodynamic energy. Higher toxin levels, as determined by liquid chromatography with mass spectrometry (LC-MS/MS), were detected after exponential growth. Portimine-A and pinnatoxin-F (PnTX-F) were the dominant toxins (up to 1.75 and 1.0 pg·cell⁻¹, respectively). PnTX-E, -D and Portimine-B were also detected at minor concentrations. This study contributes the first data necessary for a proper interpretation of monitoring programs aiming to assess the impact of V. rugosum blooms, particularly when used alongside forecasting models. Full article

Objective: This study aimed to assess the impact of the number of metastatic lymph nodes (LNs) on survival and propose a subdivision of the N2b category in colorectal cancer (CRC) patients. Methods: We retrospectively analyzed from two sources: clinicopathologic data of CRC patients with stage pTxN2bM0 who initially underwent radical surgery at Cancer Hospital, Chinese Academy of Medical Sciences/National Cancer center (NCC), and patients with stage pTxN0-2bM0-1 in the Surveillance, Epidemiology and End Results (SEER) database from January 2010 to December 2015. The optimal cutoff value of the number of positive lymph nodes (PLNs) was determined based on the principle of maximum chi-square value. We constructed survival curves using the Kaplan–Meier method, assessed survival differences with the log-rank test, and conducted univariate and multivariate analyses using the Cox proportional hazard regression model. Results: A total of 68,335 CRC patients were included: 240 from the NCC cohort, and 68,095 from the SEER cohort. Within the SEER cohort, 65,189 patients had M0 stage disease and 2,906 had M1 stage disease. The optimal PLN cutoff value determined by X-tile software (Version 3.6.1) was 13. According to PLN, stage N2b patients were divided into two groups: stage N2b# (7 ≤ PLN < 13) and stage N3 (PLN ≥ 13). In the NCC cohort, the 5-year overall survival (OS) rates of stage N2b# and N3 patients were 66.0% and 45.7%, respectively (p < 0.001). In the SEER cohort, the 5-year cancer-specific survival (CSS) rate was 57.1% for stage N2b# patients compared with 40.2% for stage N3 patients (p < 0.001). The results of multivariate Cox analysis demonstrated that modified stage pN was the independent prognosis factor of OS in the NCC cohort (HR = 1.869, 95%CI:1.253–2.787, p = 0.002); modified stage pN was also the independent prognosis indicator of CSS in the SEER cohort (N3:N0, HR = 8.170, 95%CI: 7.298–9.146, p < 0.001). There was no survival difference between TxN3M0 and TxN0-2b#M0 (5-year CSS rate: 40.2% vs. 30.1%, p = 0.050; 5-year OS rate: 35.3% vs. 27.8%, p = 0.358). Conclusions: The N category served as a strong independent prognostic indicator in CRC patients. Furthermore, PLN emerged as an independent prognostic factor specifically in stage N2b CRC patients. These findings suggest that clinicians may utilize PLN for prognostic stratification and tailor adjuvant therapeutic strategies accordingly for patients diagnosed with stage N2b CRC. Full article

High-precision 6D pose estimation for pick-and-place operations remains a critical problem for industrial robot arms in manufacturing. This study introduces an analytics-based solution for 6D pose estimation designed for a real-world industrial application: it enables the Staubli TX2-60L (manufactured by Stäubli International AG, Horgen, Switzerland) robot arm to pick up metal plates from various locations and place them into a precisely defined slot on a brake pad production line. The system uses a fixed eye-to-hand Intel RealSense D435 RGB-D camera (manufactured by Intel Corporation, Santa Clara, California, USA) to capture color and depth data. A robust software infrastructure developed in LabVIEW (ver.2019) integrated with the NI Vision (ver.2019) library processes the images through a series of steps, including particle filtering, equalization, and pattern matching, to determine the X-Y positions and Z-axis rotation of the object. The Z-position of the object is calculated from the camera’s intensity data, while the remaining X-Y rotation angles are determined using the angle-of-inclination analytics method. It is experimentally verified that the proposed analytical solution outperforms the hybrid-based method (YOLO-v8 combined with PnP/RANSAC algorithms). Experimental results across four distinct picking scenarios demonstrate the proposed solution’s superior accuracy, with position errors under 2 mm, orientation errors below 1°, and a perfect success rate in pick-and-place tasks. Full article

Owing to high electrical conductivity, layered structure, and abundant surface functional groups, transition metal carbides/nitrides (MXenes) have received enormous interest in the field of gas sensors at room temperature. In this work, we synthesize a heterostructured nanocomposite with indium oxide (In₂O₃) decorated on titanium carbide (Ti₃C₂T_x) nanosheets by electrostatic self-assembly and develop it for high-selectivity NO₂ gas sensing at room temperature. Self-assembly formation of multiple heterojunctions in the In₂O₃/Ti₃C₂T_x composite provide abundant NO₂ gas adsorption sites and high electron transfer activity, which is conducive to improving the gas-sensing response of the In₂O₃/Ti₃C₂T_x gas sensor. Assisted by rich adsorption sites and hetero interface, the as-fabricated In₂O₃/Ti₃C₂T_x gas sensor exhibits the highest response to NO₂ among various interference gases. Meanwhile, a detection limit of 0.3 ppm, and response/recovery time (197.62/93.84 s) is displayed at room temperature. Finally, a NO₂ sensing mechanism of In₂O₃/Ti₃C₂T_x gas sensor is constructed based on PN heterojunction enhancement and molecular adsorption. This work not only expands the gas-sensing application of MXenes, but also demonstrates an avenue for the rational design and construction of NO₂-sensing materials. Full article

This paper presents an optoelectronic transceiver (OTRx) realized in a 180 nm CMOS technology for applications of short-range LiDAR sensors, in which a modified current-mode single-ended VCSEL driver (m-CMVD) is exploited as a transmitter (Tx) and a voltage-mode fully differential transimpedance amplifier (FD-TIA) is employed as a receiver (Rx). Especially for Tx, a concurrent automatic power control (APC) circuit is incorporated to compensate for the inevitable increase in the threshold current in a VCSEL diode. For Rx, two on-chip spatially modulated P⁺/N- well avalanche photodiodes (APDs) are integrated with the FD-TIA to achieve circuit symmetry. Also, an extra APD is added to facilitate the APC operations in Tx, i.e., concurrently adjusting the bias current of the VCSEL diode by the action of the newly proposed APC path in Rx. Measured results of test chips demonstrate that the proposed OTRx causes the DC bias current to increase from 0.93 mA to 1.42 mA as the input current decreases from 250 µA_pp to 3 µA_pp, highlighting its suitability for short-range sensor applications utilizing a cost-effective CMOS process. Full article

The pinnatoxins (PnTXs) and portimines, produced by Vulcanodinium rugosum, have been detected in several countries, raising concerns for human health. Although no human poisoning from these toxins has been reported so far, they have been shown to distribute throughout the rodent body after oral administration. Therefore, we investigated the impact of PnTX analogs (PnTX-A, -E, -F, -G, and -H) and portimine (8, 16, and 32 ng/mL) on intestinal barrier integrity and their oral bioavailability using human Caco-2 cell monolayers treated for 2, 6, and 24 h. Our results demonstrated that all of the toxins could impair barrier integrity after 24 h, with differences observed for PnTX-A, -E, and -F, as well as portimine, the most potent of all. While PnTX-A and -E exhibited poor permeability, the other PnTXs were more penetrative, with a Papp > 1.5 × 10⁻⁶ cm·s⁻¹. Portimine was the only toxin displaying both a time- and concentration-dependent passage, likely involving a passive diffusion process. The experimental results were compared to predictions obtained by QSAR tools. Although only qualitative, our results suggest that some of these compounds may be more likely to be distributed throughout the body. Further in vivo studies are required to estimate oral bioavailability and potential public health concerns. Full article

The combination of two-dimensional material MXene and one-dimensional metal oxide semiconductor can improve the carrier transmission rate, which can effectively improve sensing performance. We prepared a trimethylamine gas sensor based on MoO₃ nanofibers and layered Ti₃C₂T_x MXene. Using electrospinning and chemical etching methods, one-dimensional MoO₃ nanofibers and two-dimensional Ti₃C₂T_x MXene nanosheets were prepared, respectively, and the composites were characterized via XPS, SEM, and TEM. The Ti₃C₂T_x MXene–MoO₃ composite material exhibits excellent room-temperature response characteristics to trimethylamine gas, showing high response (up to four for 2 ppm trimethylamine gas) and rapid response–recovery time (10 s/7 s). Further, we have studied the possible sensitivity mechanism of the sensor. The Ti₃C₂T_x MXene–MoO₃ composite material has a larger specific surface area and more abundant active sites, combined with p–n heterojunction, which effectively improves the sensitivity of the sensor. Because of its low detection limit and high stability, it has the potential to be applied in the detection system of trimethylamine as a biomarker in exhaled air. Full article

Cyclic imines are a class of lipophilic shellfish toxins comprising gymnodimines, spirolides, pinnatoxins, portimines, pteriatoxins, prorocentrolides, spiro-prorocentrimine, symbiomines and kabirimine. They are structurally diverse, but all share an imine moiety as part of a bicyclic ring system. These compounds are produced by marine microalgal species and are characterized by the rapid death that they induce when injected into mice. Cyclic imines have been detected in a range of shellfish species collected from all over the world, which raises the question as to whether they present a food safety risk. The European Food Safety Authority (EFSA) considers them to be an emerging food safety issue, and in this review, the risk posed by these toxins to shellfish consumers is assessed by collating all available occurrence and toxicity data. Except for pinnatoxins, the risk posed to human health by the cyclic imines appears low, although this is based on only a limited dataset. For pinnatoxins, two different health-based guidance values have been proposed at which the concentration should not be exceeded in shellfish (268 and 23 µg PnTX/kg shellfish flesh), with the discrepancy caused by the application of different uncertainty factors. Pinnatoxins have been recorded globally in multiple shellfish species at concentrations of up to 54 times higher than the lower guidance figure. Despite this observation, pinnatoxins have not been associated with recorded human illness, so it appears that the lower guidance value may be conservative. However, there is insufficient data to generate a more robust guidance value, so additional occurrence data and toxicity information are needed. Full article

This study reports the first detection of the marine neurotoxin pinnatoxin-G (PnTX-G) in clams collected in the northwestern Adriatic Sea (Italy). It also represents the first report of the potential toxin-producing dinoflagellate, Vulcanodinium rugosum, in Italian seas. This result, from the coasts of the Emilia-Romagna Region, indicates a successful colonization process, reflecting conditions in France where V. rugosum was initially documented. In this case, the concentration of PnTXs was very low, making further sampling necessary to fully understand the extent of the phenomenon. Discussions on the need to obtain more data to support a proper risk assessment and the need to implement a monitoring program that includes emerging marine biotoxins are also included. Full article

Spirolides (SPXs), gymnodimines (GYMs), and pinnatoxins (PnTXs) have been detected in shellfish from the northwestern Mediterranean coast of Spain. Several samples of bivalves were collected from Fangar Bay and Alfacs Bay in Catalonia over a period of over 7 years (from 2015 to 2021). Shellfish samples were analyzed for cyclic imines (CIs) on an LC1200 Agilent and 3200 QTrap triple–quadrupole mass spectrometer. In shellfish, SPX-1 was detected in two cases (of 26.5 µg/kg and 34 µg/kg), and GYM-A was only detected in trace levels in thirteen samples. Pinnatoxin G (PnTX-G) was detected in 44.6% of the samples, with its concentrations ranging from 2 µg/kg to 38.4 µg/kg. Statistical analyses revealed that seawater temperature influenced the presence or absence of these toxins. PnTX-G showed an extremely significant presence/temperature relationship in both bays in comparison to SPX-1 and GYM-A. The prevalence of these toxins in different bivalve mollusks was evaluated. A seasonal pattern was observed, in which the maximum concentrations were found in the winter months for SPX-1 and GYM-A but in the summer months for PnTX-G. The obtained results indicate that it is unlikely that CIs in the studied area pose a potential health risk through the consumption of a seafood diet. However, further toxicological information about CIs is necessary in order to perform a conclusive risk assessment. Full article

Algal toxins pose a serious threat to human and coastal ecosystem health, even if their potential impacts are poorly documented in New Caledonia (NC). In this survey, bivalves and seawater (concentrated through passive samplers) from bays surrounding Noumea, NC, collected during the warm and cold seasons were analyzed for algal toxins using a multi-toxin screening approach. Several groups of marine microalgal toxins were detected for the first time in NC. Okadaic acid (OA), azaspiracid-2 (AZA2), pectenotoxin-2 (PTX2), pinnatoxin-G (PnTX-G), and homo-yessotoxin (homo-YTX) were detected in seawater at higher levels during the summer. A more diversified toxin profile was found in shellfish with brevetoxin-3 (BTX3), gymnodimine-A (GYM-A), and 13-desmethyl spirolide-C (SPX1), being confirmed in addition to the five toxin groups also found in seawater. Diarrhetic and neurotoxic toxins did not exceed regulatory limits, but PnTX-G was present at up to the limit of the threshold recommended by the French Food Safety Authority (ANSES, 23 μg kg⁻¹). In the present study, internationally regulated toxins of the AZA-, BTX-, and OA-groups by the Codex Alimentarius were detected in addition to five emerging toxin groups, indicating that algal toxins pose a potential risk for the consumers in NC or shellfish export. Full article

Diabetic neuropathic pain is one of the complications that affect a wide variety of the diabetic population and is often difficult to treat. Only a small number of patients experience pain relief, which usually comes with onerous side effects and low levels of satisfaction. The search for new analgesic drugs is necessary, given the limitations that current drugs present. Combining drugs to treat neuropathic pain has been attracting interest to improve their efficacy compared to single-drug monotherapies while also reducing dose sizes to minimize side effects. The aim of our study was to verify the antinociceptive effect of a synthetic peptide, PnPP-15, alone and combined with pregabalin, in male Swiss diabetic mice using the von Frey method. PnPP-15 is a synthetic peptide derived from PnPP19, a peptide representing a discontinuous epitope of the primary structure of the toxin PnTx2-6 from the venom of the spider Phoneutria nigriventer. The antinociceptive activity of both compounds was dose-dependent and showed synergism, which was verified by isobolographic analysis. Treatment with PnPP-15 did not cause spontaneous or forced motor changes and did not cause any damage or signs of toxicity in the analyzed organs (pancreas, lung, heart, kidney, brain, or liver). In conclusion, PnPP-15 is a great candidate for an analgesic drug against neuropathic pain caused by diabetes and exerts a synergistic effect when combined with pregabalin, allowing for even more efficient treatment. Full article

Shellfish accumulate microalgal toxins, which can make them unsafe for human consumption. In France, in accordance with EU regulations, three groups of marine toxins are currently under official monitoring: lipophilic toxins, saxitoxins, and domoic acid. Other unregulated toxin groups are also present in European shellfish, including emerging lipophilic and hydrophilic marine toxins (e.g., pinnatoxins, brevetoxins) and the neurotoxin β-N-methylamino-L-alanine (BMAA). To acquire data on emerging toxins in France, the monitoring program EMERGTOX was set up along the French coasts in 2018. Three new broad-spectrum LC-MS/MS methods were developed to quantify regulated and unregulated lipophilic and hydrophilic toxins and the BMAA group in shellfish (bivalve mollusks and gastropods). A single-laboratory validation of each of these methods was performed. Additionally, these specific, reliable, and sensitive operating procedures allowed the detection of groups of EU unregulated toxins in shellfish samples from French coasts: spirolides (SPX-13-DesMeC, SPX-DesMeD), pinnatoxins (PnTX-G, PnTX-A), gymnodimines (GYM-A), brevetoxins (BTX-2, BTX-3), microcystins (dmMC-RR, MC-RR), anatoxin, cylindrospermopsin and BMAA/DAB. Here, we present essentially the results of the unregulated toxins obtained from the French EMERGTOX monitoring plan during the past five years (2018–2022). Based on our findings, we outline future needs for monitoring to protect consumers from emerging unregulated toxins. Full article

Phα1β (PnTx3–6) is a neurotoxin from the spider Phoneutria nigriventer venom, originally identified as an antagonist of two ion channels involved in nociception: N-type voltage-gated calcium channel (Ca_V2.2) and TRPA1. In animal models, Phα1β administration reduces both acute and chronic pain. Here, we report the efficient bacterial expression system for the recombinant production of Phα1β and its ¹⁵N-labeled analogue. Spatial structure and dynamics of Phα1β were determined via NMR spectroscopy. The N-terminal domain (Ala1–Ala40) contains the inhibitor cystine knot (ICK or knottin) motif, which is common to spider neurotoxins. The C-terminal α-helix (Asn41–Cys52) stapled to ICK by two disulfides exhibits the µs–ms time-scale fluctuations. The Phα1β structure with the disulfide bond patterns Cys1–5, Cys2–7, Cys3–12, Cys4–10, Cys6–11, Cys8–9 is the first spider knottin with six disulfide bridges in one ICK domain, and is a good reference to other toxins from the ctenitoxin family. Phα1β has a large hydrophobic region on its surface and demonstrates a moderate affinity for partially anionic lipid vesicles at low salt conditions. Surprisingly, 10 µM Phα1β significantly increases the amplitude of diclofenac-evoked currents and does not affect the allyl isothiocyanate (AITC)-evoked currents through the rat TRPA1 channel expressed in Xenopus oocytes. Targeting several unrelated ion channels, membrane binding, and the modulation of TRPA1 channel activity allow for considering Phα1β as a gating modifier toxin, probably interacting with S1–S4 gating domains from a membrane-bound state. Full article

A representative of titanium carbide MXene, Ti₃C₂T_x is a promising candidate for high performance gas sensing and has attracted significant attention. However, MXene naturally has a multilayer structure with low porosity, which prevents its gas-sensing activity. Zinc oxide (ZnO) has long been utilized as a gas detector. Despite its good response to multiple gases, high operation temperature has limited its widespread use as a gas-sensing material. In this study, a room-temperature toxic gas sensor was prepared from ZnO/Ti₃C₂T_x MXene nanocomposite consisting of 2D few-layered MXene and 1D ZnO nanoparticles. A simple technique for synthesizing the nanocomposite was established. The physicochemical properties of the nanocomposite were fine-controlled with more active sites and higher porosity. The sensitivity and gas-selectivity of the sensing material were closely examined. The nanocomposite showed enhanced response and recovery behaviors to toxic gases, which outperformed pure Ti₃C₂T_x MXene and pure ZnO. This study offers a practical strategy by which to increase the gas-sensing performance of Ti₃C₂T_x MXene, and expands comprehensive understanding of the gas-sensing process of ZnO/Ti₃C₂T_x p-n heterostructure. Full article