Search Results (122)

Toxin–antitoxin (TA) systems in bacteria are key regulators of the cell cycle and can activate a death response under stress conditions. Like other bacterial elements, TA modules have been widely exploited for biotechnological purposes in diverse applications, such as molecular cloning and anti-cancer therapies. However, their use in plants has been limited, leaving room for the development of new approaches. In this study, we examined two TA systems previously tested in plants, MazEF and YefM-YoeB, and identified interesting differences between them, likely related to their modes of action. We engineered modifications to these specific modules to transform them into molecular switches that can be activated by a protease, inducing necrosis in the plant cells where they are expressed. Finally, we demonstrated the antiviral potential of the modified TA modules by using, as a proof-of-concept, the potyvirus plum pox virus as an activator of the death phenotype. Full article

Ongoing global research actions seek to comprehensively understand the adverse impact of stress and anxiety on the physical and mental health of both human beings and animals. Niaprazine (NIA) is a chemical compound that belongs to the class of piperazine derivatives. This compound has recently gained renewed attention due to its potential therapeutic properties for treating certain conditions such as anxiety. Despite its potential benefits, the behavioral effects of NIA have not been thoroughly investigated. This study aimed to examine NIA’s potential as an anti-anxiety and anti-stress agent. After administering either vehicle or NIA in their drinking water to mice for 14 days, we conducted behavioral analyses using the Marble Burying Test and the Elevated Plus Maze test. NIA-treated mice spend more time in the open arms and bury fewer marbles. Moreover, a stability study confirmed the linear relationship between NIA concentration and its response across concentrations encompassing the NIA mother solution and the NIA solutions administered to mice. Also, a preliminary synaptic toxicity analysis showed no direct damage to cortical nerve endings. Here, we show that NIA can modulate anxiety-related behaviors without significantly impacting exploratory activity or adverse effects. Our work describes new findings that contribute to the research on safer and more tolerable anxiety management options. Full article

Background: Tafamidis reduces cardiovascular morbidity and mortality in transthyretin amyloid cardiomyopathy (ATTR-CM), yet availability and access to therapy vary. Objective: To determine how availability and access to tafamidis impact time-to-diagnosis, time-to-therapy, and cardiovascular outcomes in ATTR-CM. Methods: Ninety-one consecutive ATTR-CM (~97% wt-TTR) patients diagnosed between June 2019 and June 2021 were evaluated for tafamidis. Access to therapy was regulated by compassionate use [n(CU) = 42] prior to, and insurance [n(IA) = 49] after regulatory approval. Results: Tafamidis was started in 37/42 (88.1%), and 39/49 (79.6%) patients, respectively. At diagnosis, ATTR-CM disease stage (≤stage 2: 88.2% vs. 90.9%, p = 0.92) was similar between groups. Timely access (after tafamidis approval) reduced the median time from first presentation to diagnosis from 6.2 (IQR: 1.3–28.9) to 2.4 (0.7–21.7) months, and from first presentation to therapy from 24.4 (10.7–46.8) to 11.8 (6.4–32.4) months. While RV function significantly worsened between diagnosis and therapy initiation in CU patients diagnosed before tafamidis approval (S’-velocity 10.0 ± 2.2 to 9.2 ± 2.2 cm/s; p = 0.018; TAPSE 17.3 ± 4.7 to 15.7 ± 3.9 mm, p = 0.008), it remained unchanged in IA patients (S’-velocity 9.6 ± 2.6 to 9.4 ± 2.3 cm/s; p = 0.83; TAPSE 15.6 ± 4.2 to 16.3 ± 3.1 mm, p = 0.45). After a median follow-up of 42.3 and 24.9 months in CU and IA patients, respectively, timely availability was associated with a reduction in annual heart failure hospitalizations (0.40 vs. 0.16 per patient, p < 0.001) and improved MACE-free survival (HR = 0.51; 95%CI: 0.26–1.00; p = 0.051). Timely diagnosis (<12-months) prolonged MACE-free survival (HR = 0.424; 95%CI: 0.22–0.81; p = 0.004), and reduced HFH (HR = 0.40; 95%CI: 0.19–0.81); p = 0.011) and all-cause mortality (HR = 0.29; 95%CI: 0.11–0.74); p = 0.009). Conclusions: Availability of tafamidis improves diagnostic efficacy in ATTR-CM patients. Timely diagnosis and initiation of therapy reduces adverse cardiovascular events. Full article

Avoidant/restrictive food intake disorder (ARFID) includes age-inappropriate feeding behaviors in eating patterns, including food neophobia, defined as refusal or reluctance to eat new or unknown foods. This study aimed to assess the prevalence of ARFID and food neophobia among adults and determine the related characteristics of these risks. The study used an anonymous survey questionnaire consisting of three parts as the research tool. The first part of the questionnaire was a metric and concerned socio-demographic data. The Food Neophobia Scale (FNS) and the Nine-Item Avoidance/Restrictive Food Disorder Screen Questionnaire (NIAS) were used to evaluate the eating disorders. The survey included 309 people (60.2% women, 39.8% men) aged 18–77 years. NIAS results indicated that 15.2% of the subjects showed food selectivity, and 11.0% had food anxiety. In the FNS assessment, 42.4% had a low risk of food neophobia, 38.2% a medium risk, and 19.4% a high risk. A higher risk of food neophobia correlated with higher NIAS scores, indicating a higher risk of ARFID (p = 0.00231). The NIAS score increased with the risk of food neophobia (p = 0.000). Respondents at low risk of neophobia were most likely to avoid several products (83.97%), while in the high-risk group, 56.67% did not want to eat a favorite food enriched with a new ingredient. A higher risk of neophobia was correlated with more food avoidance and adverse reactions to new foods (p = 0.000). A higher risk of food neophobia is strongly correlated with a higher risk of ARFID. Although demographics did not significantly impact NIAS results, some trends were noted, such as higher scores among older and underweight people. Those with a higher risk of food neophobia show more food avoidance and a greater reluctance to experiment with new ingredients. Public education should emphasize that eating disorders affect both sexes equally, with tailored interventions for high-risk groups such as the elderly, rural populations, and those with lower education. Health policies should promote access to nutrition education, psychological support, and diverse food options, while further research is needed to improve targeted interventions. Full article

Wine quality and safety is affected by the food contact materials (FCMs) used. These materials are expected to protect the beverage from any chemical, physical, or biological hazard and preserve its composition stable throughout its shelf-life. However, the migration of chemical substances from FCMs is a known phenomenon and requires monitoring. This review distinguishes the migrating chemical substances to those of (i) industrial origin with potential safety effects and those of (ii) natural occurrence, principally in cork (ex. tannins) with organoleptic quality effects. The review focuses on the migration of industrial chemical contaminants. Migration testing has been applied only for cork stoppers and tops, while other materials like polyethylene terephthalate (PET) bottles with aluminum cups, paperboard cartons, stainless steel vats, and oak casks have been examined for the presence of chemical migrating substances only by wine analysis without migration testing. The dominant analytical techniques applied are gas and liquid chromatography coupled to mass spectrometry (MS) for the determination of organic compounds and Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES) and ICP-MS for elemental analysis. Targeted approaches are mostly applied, while limited non-target methodologies are reported. The identified migrating substances include authorized substances like phthalate plasticizers, monomers (bisphenol A), antioxidants (Irganox 1010), known but non-authorized substances (butylparaben), break-down products, oxidation products (nonylphenol), polyurethane adhesive by-products, oligomers, ink photoinitiators, and inorganic elements. A preliminary investigation of microplastics’ migration has also been reported. It is proposed that further research on the development of comprehensive workflows of target, suspect, and non-target analysis is required to shed more light on the chemical world of migration for the implementation of an efficient risk assessment and management of wine contact materials. Full article

Since pig vocalization is an important indicator of monitoring pig conditions, pig vocalization detection and recognition using deep learning play a crucial role in the management and welfare of modern pig livestock farming. However, collecting pig sound data for deep learning model training takes time and effort. Acknowledging the challenges of collecting pig sound data for model training, this study introduces a deep convolutional neural network (DCNN) architecture for pig vocalization and non-vocalization classification with a real pig farm dataset. Various audio feature extraction methods were evaluated individually to compare the performance differences, including Mel-frequency cepstral coefficients (MFCC), Mel-spectrogram, Chroma, and Tonnetz. This study proposes a novel feature extraction method called Mixed-MMCT to improve the classification accuracy by integrating MFCC, Mel-spectrogram, Chroma, and Tonnetz features. These feature extraction methods were applied to extract relevant features from the pig sound dataset for input into a deep learning network. For the experiment, three datasets were collected from three actual pig farms: Nias, Gimje, and Jeongeup. Each dataset consists of 4000 WAV files (2000 pig vocalization and 2000 pig non-vocalization) with a duration of three seconds. Various audio data augmentation techniques are utilized in the training set to improve the model performance and generalization, including pitch-shifting, time-shifting, time-stretching, and background-noising. In this study, the performance of the predictive deep learning model was assessed using the k-fold cross-validation (k = 5) technique on each dataset. By conducting rigorous experiments, Mixed-MMCT showed superior accuracy on Nias, Gimje, and Jeongeup, with rates of 99.50%, 99.56%, and 99.67%, respectively. Robustness experiments were performed to prove the effectiveness of the model by using two farm datasets as a training set and a farm as a testing set. The average performance of the Mixed-MMCT in terms of accuracy, precision, recall, and F1-score reached rates of 95.67%, 96.25%, 95.68%, and 95.96%, respectively. All results demonstrate that the proposed Mixed-MMCT feature extraction method outperforms other methods regarding pig vocalization and non-vocalization classification in real pig livestock farming. Full article

Seed longevity is a crucial trait for the seed industry and genetic resource preservation. To develop excellent cultivars with extended seed lifespans, it is important to understand the mechanism of keeping seed germinability long term and to find useful genetic resources as prospective breeding materials. This study was conducted to identify the best cultivars with a high and stable seed longevity trait in the germplasm of rice (Oryza sativa L.) and to analyze the correlation between seed longevity and embryonic RNA integrity. Seeds from 69 cultivars of the world rice core collection selected by the NIAS in Japan were harvested in different years and subjected to long-term storage or controlled deterioration treatment (CDT). The long-term storage (4 °C, RH under 35%, 10 years) was performed on seeds harvested in 2010 and 2013. The seeds harvested in 2016 and 2019 were used for CDT (36 °C, RH of 80%, 40 days). Seed longevity and embryonic RNA integrity were estimated by a decrease in the germination percentage and RNA integrity number (RIN) after long-term storage or CDT. The RIN value was obtained by the electrophoresis of the total RNA extracted from the seed embryos. Seeds of “Vandaran (indica)”, “Tupa 729 (japonica)”, and “Badari Dhan (indica)” consistently showed higher seed longevity and embryonic RNA integrity both under long-term storage and CDT conditions regardless of the harvest year. A strong correlation (R² = 0.93) was observed between the germination percentages and RIN values of the seeds after the long-term storage or CDT among nine cultivars selected based on differences in their seed longevity. The study findings revealed the relationship between rice seed longevity and embryo RNA stability and suggested potential breeding materials including both japonica and indica cultivars for improving rice seed longevity. Full article

Plant viruses cause severe losses in agricultural production. Parasite-derived resistance (PDR) offers a promising avenue for developing disease-resistant varieties independent of resistance genes. However, for potyviruses with great agricultural importance, such as soybean mosaic virus (SMV), systematic research on viral genes that can be used for PDR has not been conducted. In this study, we transiently expressed the untranslated region (UTR) or each protein-coding cistron of SMV in Nicotiana benthamiana to evaluate their potential role in conferring PDR. A viral suppressor of RNA silencing (VSR) was also applied to investigate the possible mechanisms of the PDR. The results showed that the transient overexpression of UTR and each cistron of SMV could inhibit SMV infection. The expression of VSR in N. benthamiana leaves could compromise UTR and most of the SMV cistron-mediated inhibition of SMV infection, indicating the involvement of RNA silencing in PDR. In comparison, the expression of VSR could not compromise the PDR conferred by coat protein (CP), P3N-PIPO, cylindrical inclusion (CI), and NIa-Pro, suggesting that these viral cistrons may play roles in PDR at the protein level. These results reveal diverse mechanisms in PDR conferred by different viral cistrons and provide potential gene candidates that can be used for transgenic approaches against SMV. Full article

Diabetic neuropathy and nephropathy are common complications of type 1 diabetes (T1D). The symptoms are often elusive in the early stages, and available diagnostic methods can be improved using biomarkers. Matrix metalloproteinase 3 (MMP-3) has been identified in the kidneys and is thought to be involved in diabetic nephropathy. Growth differentiation factor 15 (GDF-15) has been suggested to have positive effects in diabetes, but is otherwise associated with adverse effects such as cardiovascular risk, declined kidney function, and neurodegeneration. This study aims to investigate plasma MMP-3 and GDF-15 as systemic biomarkers for diabetic neuropathy and nephropathy in T1D. The study involves patients with childhood-onset T1D (n = 48, age 38 ± 4 years) and a healthy control group (n = 30, age 38 ± 5 years). Neurophysiology tests, evaluations of albuminuria, and measurements of routine biochemical markers were conducted. The neuropathy impairment assessment (NIA) scoring system, where factors such as loss of sensation and weakened reflexes are evaluated, was used to screen for symptoms of neuropathy. MMP-3 and GDF-15 concentrations were determined in heparinized plasma using ELISA kits. In total, 9 patients (19%) had albuminuria, and 25 (52%) had diabetic neuropathy. No significant differences were found in MMP-3 concentrations between the groups. GDF-15 levels were higher in T1D, with median and interquartile range (IQR) of 358 (242) pg/mL in T1D and 295 (59) in controls (p < 0.001). In the merged patient group, a positive correlation was found between MMP-3 and plasma creatinine, a negative correlation was found between MMP-3 and estimated glomerular filtration rate (eGFR; rho = −0.358, p = 0.012), and there was a positive correlation between GDF-15 and NIA (rho = 0.723, p < 0.001) and high-sensitive C-reactive protein (rho = 0.395, p = 0.005). MMP-3 was increased in macroalbuminuria and correlated positively with NIA only in the nine T1D patients with albuminuria (rho = 0.836, p = 0.005). The present study indicates that high MMP-3 is associated with low eGFR, high plasma creatinine, and macroalbuminuria, and that GDF-15 can be a biomarker for diabetic neuropathy in T1D. MMP-3 may be useful as biomarker for neuropathy in T1D with albuminuria. Full article

In the formerly glaciated terrains in the northern hemisphere and countries such as Finland, till is the most common sediment covering the bedrock. Specifically, indicator or heavy mineral studies utilising till as a vector for mineral deposits undercover have been successful. The pyrite trace-element composition from in situ mineral analyses has been shown to be an effective discriminator between different mineral deposit types, and this has led to research using heavy mineral pyrite in till to identify potential mineral deposits in a given area. However, pyrite is easily oxidised in till beds, and thus, alternative methods should be considered. Goethite pseudomorphs are more commonly found in the till sediments as remnants after pyrite oxidation. This study evaluates trace element compositions of goethitised pyrite recovered in the till beds from central Lapland in northern Finland. Intra-grain trace-elemental variations gathered using laser-ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) between the intact pyrite core and oxidised rim demonstrated complex dynamics and variations between different trace-element values. For example, Cu, V and Mn exhibited elevated trace-element values in the goethite rim compared to the pyrite core. However, elemental ratios such as Ni/As and Co/Ni remain stable between the pyrite core and oxidised rim. Therefore, these ratios have the potential to be used as a discriminating tool between the pyrite core and oxidised rim. In addition, nanoscale variabilities using focused ion beam (FIB) and transmission electron microscopy (TEM) were utilised to inspect possible nano inclusions within the studied heavy mineral grain. The FIB and TEM studies revealed a nanocrystalline pyrite nodule observation within the goethite rim. Full article

The aim of this work was to develop active packaging based on polypropylene (PP) and polylactic acid (PLA) matrices using a high value by-product extracted from orange peel as an active compound for food packaging applications. Different films with and without orange peel extract (OPE) based on PP and PLA were obtained via cast extrusion and characterized in terms of their mechanical, thermal, optical, and sealing properties. The films obtained were transparent, but when OPE was incorporated, the transmittance spectrum decreased, causing slight coloration. Mechanical properties were affected by the incorporation of OPE, as elongation at break and tensile strength increased in the cross-direction of the PP film, although the main differences found were related to the polymer itself. In addition, sealing strength also increased via the incorporation of OPE in the PP matrix. However, thermal properties were not affected by OPE in the PP matrix but slightly decreased stability in PLA. Regarding antimicrobial activity in in vitro studies, no inhibition of the growth of Listeria innocua, Saccharomyces cerevisiae, Aspergillus niger, or Escherichia coli was observed. Finally, antioxidant activity was observed in in vitro studies with 2,2-Diphenyl-1picrylhydrazyl (DPPH) radical. The results of this study showed that the obtention of materials with OPE incorporated into the PLA and PP matrix is feasible. The new materials obtained can be used for applications of oxidation-sensitive fresh products. Full article

Hafnium carbide (HfC) is a refractory compound known for its exceptional mechanical, thermal, and electrical properties. This compound has gained significant attention in materials science and engineering due to its high melting point, extreme hardness, and excellent thermal stability. This study presents crystal structure prediction via energy landscape explorations of pristine hafnium carbide supplemented by data mining. Apart from the well-known equilibrium rock salt phase, we predict eight new polymorphs of HfC. The predicted HfC phases appear in the energy landscape with known structure types such as the WC type, NiAs type, 5-5 type, sphalerite (ZnS) type, TlI type, and CsCl type; in addition, we predict two new structure types denoted as ortho_HfC and HfC_polytype, respectively. Moreover, we have investigated the structural characteristics and mechanical properties of hafnium carbide at the DFT level of computation, which opens diverse applications in various technological domains. Full article

Introduction: Type 2 diabetes mellitus is a major global health concern, but interpreting machine learning models for diagnosis remains challenging. This study investigates combining association rule mining with advanced natural language processing to improve both diagnostic accuracy and interpretability. This novel approach has not been explored before in using pretrained transformers for diabetes classification on tabular data. Methods: The study used the Pima Indians Diabetes dataset to investigate Type 2 diabetes mellitus. Python and Jupyter Notebook were employed for analysis, with the NiaARM framework for association rule mining. LightGBM and the dalex package were used for performance comparison and feature importance analysis, respectively. SHAP was used for local interpretability. OpenAI GPT version 3.5 was utilized for outcome prediction and interpretation. The source code is available on GitHub. Results: NiaARM generated 350 rules to predict diabetes. LightGBM performed better than the GPT-based model. A comparison of GPT and NiaARM rules showed disparities, prompting a similarity score analysis. LightGBM’s decision making leaned heavily on glucose, age, and BMI, as highlighted in feature importance rankings. Beeswarm plots demonstrated how feature values correlate with their influence on diagnosis outcomes. Discussion: Combining association rule mining with GPT for Type 2 diabetes mellitus classification yields limited effectiveness. Enhancements like preprocessing and hyperparameter tuning are required. Interpretation challenges and GPT’s dependency on provided rules indicate the necessity for prompt engineering and similarity score methods. Variations in feature importance rankings underscore the complexity of T2DM. Concerns regarding GPT’s reliability emphasize the importance of iterative approaches for improving prediction accuracy. Full article

Phthalates are the synthetic chemical plasticizers with the most varied uses and are a source of concern due to their toxicity and ubiquity, so much so that even plasticizer-free polymers can contain them as non-intentionally added substances (NIAS). Food packaging is among the materials with the greatest impact. In this study, a simple protocol is proposed for the location and identification of dimethyl phthalate, diethyl phthalate, dipropyl phthalate, and dibutyl phthalate which is applicable to compliance studies of food packaging materials and for the associated risk assessment. Solid phase microextraction gas chromatography/mass spectrometry was used to evaluate the migration of four NIAS from food packaging to release media simulating food substrates. Three plasticizer-free polymers were used: two that were lab-made and based on sodium alginate and a commercial polyethylene film. Linearity ranged from the LOQ to 10 µg/mL; within-day and between-day precision values were between 12.3–25.7% and 21.9–35.8%, respectively; the LOD and LOQ were in the range 0.029–0.073 µg/mL and 0.122–0.970 µg/mL. Migration tests were conducted for different periods of time at room temperature and at 8 °C. Exposure to microwaves (MW) was also evaluated. All packaging materials tested had global migration limits lower than 10 mg/dm² of material surface. Full article

The aspergilli comprise a diverse group of filamentous fungi spanning over 200 million years of evolution. In this work, we report a clarification of the phylogenetic relationship between A. carbonarius and A. tubingensis via the screening of ITS-5.8RDNA, (niiA-niaD), ß-tubulin, and eEF-1 genes. The phylogenetic analysis of aspergilli ITS-5.8rDNA sequences divided A. carbonarius and A. tubingensis into two coherent clusters and showed a close intergeneric relationship, which is in keeping with the existing morphological and taxonomic classification. Herein, A. carbonarius exhibits a complete similarity (100%) for the three target genes: intergenic region of (niiA-niaD), ß-tubulin, and eEF-1. The tree resulting from a bootstrap analysis indicates branch points when the significance is 98% minimum for each gene (ß-tubulin and eEF-1). The phylogenetic analysis of the aspergilli genome structure provided a quantitative evaluation of the forces driving long-term eukaryotic genome evolution. It also led to an experimentally validated model of mating-type locus evolution, suggesting the potential for sexual reproduction in A. carbonarius and A. tubingensis. This is the first work describing the evolutionary relationship between both species. Nevertheless, this discovery might be viewed as typical during the process of new taxonomic evolution. Full article