Computer-aided diagnosis system for optical diagnosis of colorectal polyps under white light imaging.

OBJECTIVES: This study presents a novel computer-aided diagnosis (CADx) designed for optically diagnosing colorectal polyps using white light imaging (WLI).We aimed to evaluate the effectiveness of the CADx and its auxiliary role among endoscopists with different levels of expertise. METHODS: We collected 2,324 neoplastic and 3,735 nonneoplastic polyp WLI images for model training, and 838 colorectal polyp images from 740 patients for model validation. We compared the diagnostic accuracy of the CADx with that of 15 endoscopists under WLI and narrow band imaging (NBI). The auxiliary benefits of CADx for endoscopists of different experience levels and for identifying different types of colorectal polyps was also evaluated. RESULTS: The CADx demonstrated an optical diagnostic accuracy of 84.49%, showing considerable superiority over all endoscopists, irrespective of whether WLI or NBI was used (P < 0.001). Assistance from the CADx significantly improved the diagnostic accuracy of the endoscopists from 68.84% to 77.49% (P = 0.001), with the most significant impact observed among novice endoscopists. Notably, novices using CADx-assisted WLI outperform junior and expert endoscopists without such assistance. CONCLUSIONS: The CADx demonstrated a crucial role in substantially enhancing the precision of optical diagnosis for colorectal polyps under WLI and showed the greatest auxiliary benefits for novice endoscopists.

Relative Localization and Circumnavigation of a UGV0 Based on Mixed Measurements of Multi-UAVs by Employing Intelligent Sensors.

Relative localization (RL) and circumnavigation is a highly challenging problem that is crucial for the safe flight of multi-UAVs (multiple unmanned aerial vehicles). Most methods depend on some external infrastructure for positioning. However, in some complex environments such as forests, it is difficult to set up such infrastructures. In this paper, an approach to infrastructure-free RL estimations of multi-UAVs is investigated for circumnavigating a slowly drifting UGV0 (unmanned ground vehicle 0), where UGV0 serves as the RL and circumnavigation target. Firstly, a discrete-time direct RL estimator is proposed to ascertain the coordinates of each UAV relative to the UGV0 based on intelligent sensing. Secondly, an RL fusion estimation method is proposed to obtain the final estimate of UGV0. Thirdly, an integrated estimation control scheme is also proposed for the application of the RL fusion estimation method to circumnavigation. The convergence and the performance are analyzed. The simulation results validate the effectiveness of the proposed algorithm for RL fusion estimations and of the integrated scheme.

Cellular and molecular mechanisms of oroxylin A in cancer therapy: Recent advances.

Seeking an effective and safe scheme is the common goal of clinical treatment of tumor patients. In recent years, traditional Chinese medicine has attracted more and more attention in order to discover new drugs with good anti-tumor effects. Oroxylin A (OA) is a compound found in natural Oroxylum indicum and Scutellaria baicalensis Georgi plants and has been used in the treatment of various cancers. Studies have shown that OA has a wide range of powerful biological activities and plays an important role in neuroprotection, anti-inflammation, anti-virus, anti-allergy, anti-tumor and so on. OA shows high efficacy in tumor treatment. Therefore, it has attracted great attention of researchers all over the world. This review aims to discuss the anti-tumor effects of OA from the aspects of cell cycle arrest, induction of cell proliferation and apoptosis, induction of autophagy, anti-inflammation, inhibition of glycolysis, angiogenesis, invasion, metastasis and reversal of drug resistance. In addition, the safety and toxicity of the compound were also discussed. As a next step, to clarify the benefits and adverse effects of Oroxylin A in cancer patients further experiments, especially clinical trials, are needed.

Enhancing singlet oxygen production of dioxygen activation on the carbon-supported rare-earth oxide nanocluster and rare-earth single atom catalyst to remove antibiotics.

Singlet oxygen (1O2) is extensively employed in the fields of chemical, biomedical and environmental. However, it is still a challenge to produce high- concentration 1O2 by dioxygen activation. Herein, a system of carbon-supported rare-earth oxide nanocluster and single atom catalysts (named as RE2O3/RE-C, RE=La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Sc and Y) with similar morphology, structure, and physicochemical characteristic are constructed to activate dissolved oxygen (DO) to enhance 1O2 production. The catalytic activity trends and mechanisms are revealed experimentally and are also proven by theoretical analyses and calculations. The 1O2 generation activity trend is Gd2O3/Gd-C>Er2O3/Er-C>Sm2O3/Sm-C>pristine carbon (C). More than 95.0% of common antibiotics (ciprofloxacin, ofloxacin, norfloxacin and carbamazepine) can be removed in 60 min by Gd2O3/Gd-C. Density functional theory calculations indicate that Gd2O3 nanoclusters and Gd single atoms exhibit the moderate adsorption energy of ·O2- to enhance 1O2 production. This study offers a universal strategy to enhance 1O2 production in dioxygen activation for future application and reveals the natural essence of basic mechanisms of 1O2 production via rare-earth oxide nanoclusters and rare-earth single atoms.

Advancing document-level event extraction: Integration across texts and reciprocal feedback.

The primary objective of document-level event extraction is to extract relevant event information from lengthy texts. However, many existing methods for document-level event extraction fail to fully incorporate the contextual information that spans across sentences. To overcome this limitation, the present study proposes a document-level event extraction model called Integration Across Texts and Reciprocal Feedback (IATRF). The proposed model constructs a heterogeneous graph and employs a graph convolutional network to enhance the connection between document and entity information. This approach facilitates the acquisition of semantic information enriched with document-level context. Additionally, a Transformer classifier is introduced to transform multiple event types into a multi-label classification task. To tackle the challenge of event argument recognition, this paper introduces the Reciprocal Feedback Argument Extraction strategy. Experimental results conducted on both our COSM dataset and the publicly available ChFinAnn dataset demonstrate that the proposed model outperforms previous methods in terms of F1 value, thus confirming its effectiveness. The IATRF model effectively solves the problems of long-distance document context-aware representation and cross-sentence argument dispersion.

Aging effects on residential biomass burning emissions under quasi-real atmospheric conditions.

Emissions from biomass burning (BB) vastly contribute to the atmospheric trace gases and particles, which affect air quality and human health. After emission, the chemical evolution changes the mass and composition of organic aerosol (OA) in the diluted and aged plume. In this study, we used a quasi-real atmospheric smog chamber system to conduct aging experiments and investigated the multiphase oxidation of primary organic aerosol (POA) and the formation of secondary organic aerosols (SOA) in residential biomass burning plumes. We found that the emissions in the gas and particle phases were interlinked during the plume evolution. During photochemical aging, more oxidized OA was produced, and SOA formation increased by a factor of 2 due to functionalization reactions of gaseous precursors such as furans, phenols, and carbonyls. On the other hand, dark aging resulted in a lower OA mass enhancement by a factor of 1.2, with weaker oxidation from gaseous reactions. Dark aging experiments resulted in the generation of substantial quantities of nitrogen-containing organic compounds in both gas and particulate phases, while photochemical aging led to a notable increase in the concentration of gaseous carboxylic acids. Our observations show that the properties of SOA are influenced by exposure to sunlight radiation and oxidants such as OH or NO3 radicals. These results reflect the aging process of BB plumes in real-world atmospheric conditions and highlight the importance of considering various aging mechanisms.

Injectable Zn2+ and Paeoniflorin Release Hydrogel for Promoting Wound Healing.

As more and more superbugs emerge, wounds are struggling to heal due to the inflammation that accompanies infection. Therefore, there is an urgent need to reduce the abuse of antibiotics and find nonantibiotic antimicrobial methods to counter infections to accelerate wound healing. In addition, common wound dressings struggle to cover irregular wounds, causing bacterial invasion or poor drug release, which reduces the wound healing rate. In this study, Chinese medicinal monomer paeoniflorin which can inhibit inflammation is loaded in mesoporous zinc oxide nanoparticles (mZnO), while Zn2+ released from mZnO degradation can kill bacteria and facilitate wound healing. The drug-loaded mZnO was encapsulated by a hydrogel formed from oxidized konjac glucomannan and carboxymethyl chitosan via rapid Schiff base reaction to obtain an injectable drug-releasing hydrogel wound dressing. The immediate-formation hydrogel allows the dressing to cover any wound shape. In vitro and in vivo studies have demonstrated that the dressing has good biocompatibility and superior antibacterial properties, which can promote wound healing and tissue regeneration by promoting angiogenesis and collagen production, providing a promising perspective for the further development of multifunctional wound dressings.

Enhanced selective separation of vanadium(V) and chromium(VI) using the CeO2 nanorod containing oxygen vacancies.

Adsorption of vanadium from wastewater defends the environment from toxic ions and contributes to recover the valuable metal. However, it is still challenging for the separation of vanadium (V5+) and chromium (Cr6+) because of their similar properties. Herein, a kind of CeO2 nanorod containing oxygen vacancies is facilely synthesized which displays ultra-high selectivity of V5+ against various competitive ions (i.e., Fe, Mn, Cr, Ni, Cu, Zn, Ga, Cd, Ba, Pb, Mg, Be, and Co). Moreover, a large separation factor (SFV/Cr) of 114,169.14 for the selectivity of V5+ is achieved at the Cr6+/V5+ ratio of 80 with the trace amount of V5+ (~ 1 mg/L). The results show that the process of V5+ uptake is the monolayer homogeneous adsorption and is controlled by external and intraparticle diffusions. In addition, it also shows that V5+ is reduced to V3+ and V4+ and then formation of V-O complexation. This work offers a novel CeO2 nanorod material for efficient separation of V5+ and Cr6+ and also clarifies the mechanism of the V5+ adsorption on the CeO2 surface.

Statistic and Network Features of RGB and Hyperspectral Imaging for Determination of Black Root Mold Infection in Apples.

Apples damaged by black root mold (BRM) lose moisture, vitamins, and minerals as well as carry dangerous toxins. Determination of the infection degree can allow for customized use of apples, reduce financial losses, and ensure food safety. In this study, red-green-blue (RGB) imaging and hyperspectral imaging (HSI) are combined to detect the infection degree of BRM in apple fruits. First, RGB and HSI images of healthy, mildly, moderately, and severely infected fruits are measured, and those with effective wavelengths (EWs) are screened from HSI by random frog. Second, the statistic and network features of images are extracted by using color moment and convolutional neural network. Meanwhile, random forest (RF), K-nearest neighbor, and support vector machine are used to construct classification models with the above two features of RGB and HSI images of EWs. Optimal results with the 100% accuracy of training set and 96% accuracy of prediction set are obtained by RF with the statistic and network features of the two images, outperforming the other cases. The proposed method furnishes an accurate and effective solution for determining the BRM infection degree in apples.

A D-cysteine desulfhydrase, SlDCD2, participates in tomato fruit ripening by modulating ROS homoeostasis and ethylene biosynthesis.

Hydrogen sulfide (H2S) is involved in multiple processes during plant growth and development. D-cysteine desulfhydrase (DCD) can produce H2S with D-cysteine as the substrate; however, the potential developmental roles of DCD have not been explored during the tomato lifecycle. In the present study, SlDCD2 showed increasing expression during fruit ripening. Compared with the control fruits, the silencing of SlDCD2 by pTRV2-SlDCD2 accelerated fruit ripening. A SlDCD2 gene-edited mutant was constructed by CRISPR/Cas9 transformation, and the mutant exhibited accelerated fruit ripening, decreased H2S release, higher total cysteine and ethylene contents, enhanced chlorophyll degradation and increased carotenoid accumulation. Additionally, the expression of multiple ripening-related genes, including NYC1, PAO, SGR1, PDS, PSY1, ACO1, ACS2, E4, CEL2, and EXP was enhanced during the dcd2 mutant tomato fruit ripening. Compared with the wild-type fruits, SlDCD2 mutation induced H2O2 and malondialdehyde (MDA) accumulation in fruits, which led to an imbalance in reactive oxygen species (ROS) metabolism. A correlation analysis indicated that H2O2 content was strongly positively correlated with carotenoids content, ethylene content and ripening-related gene expression and negatively correlated with the chlorophyll content. Additionally, the dcd2 mutant showed earlier leaf senescence, which may be due to disturbed ROS homeostasis. In short, our findings show that SlDCD2 is involved in H2S generation and that the reduction in endogenous H2S production in the dcd2 mutant causes accelerated fruit ripening and premature leaf senescence. Additionally, decreased H2S in the dcd2 mutant causes excessive H2O2 accumulation and increased ethylene release, suggesting a role of H2S and SlDCD2 in modulating ROS homeostasis and ethylene biosynthesis.

ß-Cryptoxanthin Attenuates Cigarette-Smoke-Induced Lung Lesions in the Absence of Carotenoid Cleavage Enzymes (BCO1/BCO2) in Mice.

High dietary intake of ß-cryptoxanthin (BCX, an oxygenated provitamin A carotenoid) is associated with a lower risk of lung disease in smokers. BCX can be cleaved by ß-carotene-15,15'-oxygenase (BCO1) and ß-carotene-9',10'-oxygenase (BCO2) to produce retinol and apo-10'-carotenoids. We investigated whether BCX has protective effects against cigarette smoke (CS)-induced lung injury, dependent or independent of BCO1/BCO2 and their metabolites. Both BCO1-/-/BCO2-/- double knockout mice (DKO) and wild type (WT) littermates were supplemented with BCX 14 days and then exposed to CS for an additional 14 days. CS exposure significantly induced macrophage and neutrophil infiltration in the lung tissues of mice, regardless of genotypes, compared to the non-exposed littermates. BCX treatment significantly inhibited CS-induced inflammatory cell infiltration, hyperplasia in the bronchial epithelium, and enlarged alveolar airspaces in both WT and DKO mice, regardless of sex. The protective effects of BCX were associated with lower expression of IL-6, TNF-α, and matrix metalloproteinases-2 and -9. BCX treatment led to a significant increase in hepatic BCX levels in DKO mice, but not in WT mice, which had significant increase in hepatic retinol concentration. No apo-10'-carotenoids were detected in any of the groups. In vitro BCX, at comparable doses of 3-OH-ß-apo-10'-carotenal, was effective at inhibiting the lipopolysaccharide-induced inflammatory response in a human bronchial epithelial cell line. These data indicate that BCX can serve as an effective protective agent against CS-induced lung lesions in the absence of carotenoid cleavage enzymes.

Local Regulator AcrR Regulates Persister Formation by Repression of AcrAB Efflux Pump during Exponential Growth in Aeromonas veronii.

Bacterial persisters refer to a small fraction of dormant variants that survive treatment with high concentrations of antibiotics. Increasing research indicates that multidrug efflux pumps play a major role in persister formation in many Gram-negative organisms. In the present study, the roles of the repressor of the AcrAB efflux pump, AcrR, in the regulation of the activity and function of the efflux, as well as in the production of persisters, were investigated in the pathogen Aeromonas veronii, which causes huge economic losses in the aquatic industry and threatens human health. We observed that exclusively in exponential-phase cells, not in stationary-phase cells, the deletion of the acrR gene significantly (P < 0.05) promoted the expression of the acrA and acrB genes and reduced the intracellular accumulation of the efflux substrate Hoechst 33342. Moreover, overexpression of acrR triggered decreased transcription of the promoter of the acrAB operon. The persister assay indicated that the loss of the AcrAB pump decreased the formation of persisters under challenge with all tested antibiotic types of chloramphenicol, fluoroquinolone, tetracycline, and ß-lactam, while deletion of acrR caused an exponential-phase-specific increase in persister formation against chloramphenicol, tetracycline, and ß-lactam. Our results provide molecular insights into the mechanism of bacterial persistence by demonstrating for the first time that the local regulator AcrR is involved in the modulation of persister formation in A. veronii through its repressive activity on the function of the AcrAB efflux pump during the exponential growth period.

Relative decline in serum albumin help to predict anastomotic leakage for female patients following sphincter-preserving rectal surgery.

BACKGROUND: Patients with normal preoperative serum albumin still suffer from a significant reduction in serum albumin after major abdominal surgery. The current study aims to explore the predictive value of ∆ALB for AL in patients with normal serum albumin and examine whether there is a gender difference in the prediction of AL. METHODS: Medical reports of consecutive patients undergoing elective sphincter-preserving rectal surgery between July 2010 and June 2016 were reviewed. Receiver operating characteristic (ROC) analysis was adopted to examine the predictive ability of ∆ALB and determine the cut-off value according to the Youden index. The logistic regression model was performed identify independent risk factors for AL. RESULTS: Out of the 499 eligible patients, 40 experienced AL. Results of the ROC analyses showed that ΔALB displayed a significant predictive value for females, and the AUC value was 0.675 (P = 0.024), with a sensitivity of 93%. In male patients, the AUC was 0.575 (P = 0.22), but did not reach a significant level. In the multivariate analysis, ∆ALB ≥ 27.2% and low tumor location prove to be independent risk factors for AL in female patients. CONCLUSIONS: The current study suggested that there may be a gender difference in the prediction of AL and ∆ ALB can serve as a potential predictive biomarker for AL in females. A cut-off value of the relative decline in serum albumin can help predict AL in female patients as early as postoperative day 2. Although our study needs further external validation, our findings may provide an earlier, easier and cheaper biomarker for the detection of AL.

Dynamic Electric Field Alignment Determines the Water Rotational Motion around Protein.

Water rotational dynamics in biomolecular solution is crucial to evaluating and controlling biomolecule stability. In this molecular dynamics simulation (MD) study on lysozyme solutions, we present how the exerted internal electric field determines water rotational dynamics. We find that the relaxation time of water rotation is equivalent to that of the reorientation of the exerted overall electric field for every single water molecule, regardless of its translation mode. Namely, water molecular rotation synchronizes with the exerted field reorientation. We also map the reorientation process of the electric field at fixed points relative to protein in the solution, which displays the local hydration dynamics commensurate with the reported time-dependent fluorescence Stokes shift (TDFSS) measurements. Comparing the spatial distribution of local field reorientation relaxation time with that of rotational relaxation time, we further suggest that water rotation dynamics are subject to the reorientation of the local overall field within the hydration layer. While outside the hydration layer, the relaxation time of the local electric field reorientation is short enough (subpicosecond) to assume the δ function, showing the electric force with randomly changing orientation is applied to each water molecule.

E3 ligase BRG3 persulfidation delays tomato ripening by reducing ubiquitination of the repressor WRKY71.

Hydrogen sulfide (H2S) is a gaseous signaling molecule reported to play multiple roles in fruit ripening. However, the molecular mechanisms underlying H2S-mediated delay in fruit ripening remain to be established. Here, the gene encoding a WRKY transcription factor, WRKY71, was identified as substantially upregulated in H2S-treated tomato (Solanum lycopersicum) via transcriptome profiling. The expression of WRKY71 was negatively associated with that of CYANOALANINE SYNTHASE1 (CAS1). Transient and stable genetic modification experiments disclosed that WRKY71 acts as a repressor of the tomato ripening process. CAS1 appears to play an opposite role, based on the finding that the ripening process was delayed in the cas1 mutant and accelerated in CAS1-OE tomatoes. Dual-luciferase reporter assay, yeast one-hybrid, electrophoretic mobility shift assay, and transient transformation experiments showed that WRKY71 bound to the CAS1 promoter and suppressed its activation. Moreover, the persulfidation of WRKY71 enhanced its binding ability to the CAS1 promoter. Data from luciferase complementation and Y2H assays confirmed that WRKY71 interacts with a BOI-related E3 ubiquitin-protein ligase 3 (BRG3) and is ubiquitinated in vitro. Further experiments showed that modification of BRG3 via persulfidation at Cys206 and Cys212 led to reduced ubiquitination activity. Our findings support a model whereby BRG3 undergoes persulfidation at Cys206 and Cys212, leading to reduced ubiquitination activity and decreased interactions with the WRKY71 transcript, with a subsequent increase in binding activity of the persulfidated WRKY71 to the CAS1 promoter, resulting in its transcriptional inhibition and thereby delayed ripening of tomatoes. Our collective findings provide insights into a mechanism of H2S-mediated regulation of tomato fruit ripening.

Source characterization of volatile organic compounds in urban Beijing and its links to secondary organic aerosol formation.

Volatile organic compounds (VOCs) are precursors for ozone and secondary organic aerosol (SOA) formation, thereby playing a vital role in atmospheric chemistry and urban air quality. To characterize the relationship between VOCs and SOA, organics both in gas and particulate phases were concurrently measured in urban Beijing. The VOCs and organic aerosol (OA) were apportioned into factors with different oxidation levels by applying the factorization analysis on their detailed mass spectra. Six factors of VOCs were identified, including four primary VOCs (PVOC) factors and two secondary VOCs (SVOC) factors. The PVOC factors dominated the total VOCs when the air mass originated in the cleaner northern areas, while SVOC factors dominated for polluted southern air masses. The normalized concentrations of PVOC and primary OA factors showed consistent diurnal variations regardless of air mass directions, owing to the relatively stable local emissions during the experimental period. This contrasted with the secondary factors due to more complex transformation processes. The traffic-related VOCs and solid fuel combustion VOCs negatively correlated with SOA, implying that they may have contributed to the SOA formation through photooxidation. The VOCs in lower oxidation levels were found to have poor correlations with the less oxidized SOA, whereas they correlated strongly to the more oxidized SOA. This implied that the less oxidized SOA may be in a transition state, where its production and loss rates were balanced. These served as products of VOCs oxidation and reactants of more oxidized SOA formation, playing important roles on the VOC to SOA transformation. The identified VOC emission sources and their photochemical production of SOA should be considered in air quality policy planning.

Clinical and prognostic features of E-cadherin in adenocarcinoma of the esophagogastric junction patients.

OBJECTIVE: The expression, activity, and functional role of E-cadherin in adenocarcinoma of the esophagogastric junction (AEG) are unclear. In this research, we evaluated the expression of E-cadherin in AEG, as well as its clinicopathological significance and prognostic value. METHODS: A total of 65 AEG samples and 10 normal paracancerous tissues undergoing AEG resection in thoracic surgery were collected. The samples were immunohistochemically examined for expression levels of E-cadherin. The Chi-square test was used to determine if E-cadherin expression correlated with the clinicopathological features of AEG patients. The link between clinicopathological features and 5-year survival rates was investigated using Kaplan-Meier survival curves and multifactorial Cox regression analysis. RESULTS: In AEG tissues, E-cadherin expression was considerably reduced. Differentiation grade ( P = 0.013), infiltration depth ( P = 0.033), and clinicopathological stage ( P = 0.045) were substantially linked to the level of E-cadherin expression. Five-year survival rates of AEG patients were affected by E-cadherin expression ( P = 0.037), tumor differentiation ( P = 0.010), lymph node metastasis ( P < 0.001), and clinicopathological stage ( P = 0.037). Tumor differentiation ( P = 0.033) and lymph node metastasis ( P = 0.001) were independent risk factors for shorter overall survival. CONCLUSION: E-cadherin expression in AEG was significantly decreased, which was strongly related to tumor differentiation, infiltration, and clinicopathological stage. An E-cadherin deficiency would lead to poor prognosis in AEG patients. E-cadherin may play a crucial role in AEG invasion and metastasis. Low expression of E-cadherin may be a potential early biomarker and overall survival predictor for AEG patients.

A Coculture of Enterobacter and Comamonas Species Reduces Cadmium Accumulation in Rice.

The accumulation of cadmium (Cd) in plants is strongly impacted by soil microbes, but its mechanism remains poorly understood. Here, we report the mechanism of reduced Cd accumulation in rice by coculture of Enterobacter and Comamonas species. In pot experiments, inoculation with the coculture decreased Cd content in rice grain and increased the amount of nonbioavailable Cd in Cd-spiked soils. Fluorescence in situ hybridization and scanning electron microscopy detection showed that the coculture colonized in the rhizosphere and rice root vascular tissue and intercellular space. Soil metagenomics data showed that the coculture increased the abundance of sulfate reduction and biofilm formation genes and related bacterial species. Moreover, the coculture increased the content of organic matter, available nitrogen, and potassium and increased the activities of arylsulfatase, ß-galactosidase, phenoloxidase, arylamidase, urease, dehydrogenase, and peroxidase in soils. In subsequent rice transcriptomics assays, we found that the inoculation with coculture activated a hypersensitive response, defense-related induction, and mitogen-activated protein kinase signaling pathway in rice. Heterologous protein expression in yeast confirmed the function of four Cd-binding proteins (HIP28-1, HIP28-4, BCP2, and CID8), a Cd efflux protein (BCP1), and three Cd uptake proteins (COPT4, NRAM5, and HKT6) in rice. Succinic acid and phenylalanine were subsequently proved to inhibit rice divalent Cd [Cd(II)] uptake and activate Cd(II) efflux in rice roots. Thus, we propose a model that the coculture protects rice against Cd stress via Cd immobilization in soils and reducing Cd uptake in rice. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.