Animal Tissues Research Articles

Insights into tissue accumulation, depletion, and health risk assessment of clopidol in poultry

Clopidol is extensively used in livestock farming and residues of this antibiotic can persist in animal tissues, posing a risk to humans and the environment. In this study, we investigated the depletion of clopidol in various edible tissues of chickens (muscle, liver, kidney, fat, and eggs) using liquid chromatography–tandem mass spectrometry after the administration of a clopidol-contaminated diet (at 250 mg kg−1 for the high (1x) dose). After 14 d of exposure, the clopidol concentrations were highest in eggs (median: 9.83 mg/kg), followed by liver (3.56 mg/kg), kidney (3.01 mg/kg), muscle (1.56 mg/kg), and fat (0.727 mg/kg) at low exposure group, indicating that clopidol accumulated primarily in eggs rather than the other edible tissues. In addition, the maternal transfer ratios were estimated, and the transfer efficiencies of clopidol in muscle (egg-to-tissue ratio, ETR:1.81) and fat (2.06–58.2) were higher than those in liver (0.731–31.1) and kidney (0.832–38.9). Furthermore, we conducted a cumulative risk assessment for clopidol in edible chicken tissues using the hazard quotient (HQ) method. This assessment revealed that the exposure levels for Korean consumers pose an acceptable risk. However, for eggs from the 1x dose exposure group, the HQ values were greater than 1 for all age groups, particularly for young children (<18 y), suggesting that the higher daily consumption of eggs combined with the higher clopidol residues in eggs resulted in higher HQ values, which requires further attention. The findings of this study can assist in the management and monitoring of clopidol residues in chicken tissues and eggs

Evaluation optimum ratio of synthetic bone graft material and platelet rich fibrin mixture in a metal 3D printed implant to enhance bone regeneration

BackgroundThis study aims to evaluate the optimal ratio of synthetic bone graft (SBG) material and platelet rich fibrin (PRF) mixed in a metal 3D-printed implant to enhance bone regeneration.MethodsSpecialized titanium hollow implants (5 mm in diameter and 6 mm in height for rabbit; 6 mm in diameter and 5 mm in height for pig) were designed and manufactured using 3D printing technology. The implants were divided into three groups and filled with different bone graft combinations, namely (1) SBG alone; (2) PRF to SBG in 1:1 ratio; (3) PRF to SBG in 2:1 ratio. These three groups were replicated tightly into each bone defect in distal femurs of rabbits (nine implants, n = 3) and femoral shafts of pigs (fifteen implants, n = 5). Animal tissue sections were obtained after euthanasia at the 8th postoperative week. The rabbit specimens were stained with analine blue, while the pig specimens were stained with Masson–Goldner’s trichrome stain to perform histologically examination. All titanium hollow implants were well anchored, except in fracture specimens (three in the rabbit and one fracture in the pig).ResultRabbit specimens under analine blue staining showed that collagen tissue increased by about 20% and 40% in the 1:1 ratio group and the 2:1 ratio group, respectively. Masson–Goldner's trichrome stain results showed that new bone growth increased by 32% in the 1:1 ratio PRF to SBG, while − 8% in the 2:1 ratio group.ConclusionThis study demonstrated that placing a 1:1 ratio combination of PRF and SBG in a stabilized titanium 3D printed implant resulted in an optimal increase in bone growth.

Blockade of the ADAM8-Fra-1 complex attenuates neuroinflammation by suppressing the Map3k4/MAPKs axis after spinal cord injury

BackgroundMechanical spinal cord injury (SCI) is a deteriorative neurological disorder, causing secondary neuroinflammation and neuropathy. ADAM8 is thought to be an extracellular metalloproteinase, which regulates proteolysis and cell adherence, but whether its intracellular region is involved in regulating neuroinflammation in microglia after SCI is unclear.MethodsUsing animal tissue RNA-Seq and clinical blood sample examinations, we found that a specific up-regulation of ADAM8 in microglia was associated with inflammation after SCI. In vitro, microglia stimulated by HMGB1, the tail region of ADAM8, promoted microglial inflammation, migration and proliferation by directly interacting with ERKs and Fra-1 to promote activation, then further activated Map3k4/JNKs/p38. Using SCI mice, we used BK-1361, a specific inhibitor of ADAM8, to treat these mice.ResultsThe results showed that administration of BK-1361 attenuated the level of neuroinflammation and reduced microglial activation and recruitment by inhibiting the ADAM8/Fra-1 axis. Furthermore, treatment with BK-1361 alleviated glial scar formation, and also preserved myelin and axonal structures. The locomotor recovery of SCI mice treated with BK-1361 was therefore better than those without treatment.ConclusionsTaken together, the results showed that ADAM8 was a critical molecule, which positively regulated neuroinflammatory development and secondary pathogenesis by promoting microglial activation and migration. Mechanically, ADAM8 formed a complex with ERK and Fra-1 to further activate the Map3k4/JNK/p38 axis in microglia. Inhibition of ADAM8 by treatment with BK-1361 decreased the levels of neuroinflammation, glial formation, and neurohistological loss, leading to favorable improvement in locomotor functional recovery in SCI mice.Graphical

OphthalMimic: A new alternative apparatus without animal tissue for the evaluation of topical ophthalmic drug products

The necessity of animal-free performance tests for novel ophthalmic formulation screening is challenging. For this, we developed and validated a new device to simulate the dynamics and physical–chemical barriers of the eye for in vitro performance tests of topic ophthalmic formulations. The OphthalMimic is a 3D-printed device with an artificial lacrimal flow, a cul-de-sac area, a support base, and a simulated cornea comprised of a polymeric membrane containing poly-vinyl alcohol 10 % (w/v), gelatin 2.5 % (w/v), and different proportions of mucin and poloxamer, i.e., 1:1 (M1), 1:2 (M2), and 2:1 (M3) w/v, respectively. The support base is designed to move between 0° and 50° to replicate the movement of an eyelid. We challenged the model by testing the residence performance of poloxamer®407 16 % and poloxamer®407 16 % + chitosan 1 % (PLX16CS10) gels containing fluconazole. The test was conducted with a simulated tear flow of 1.0 mL.min−1 for 5 min. The OphthalMimic successfully distinguished PLX16 and PLX16C10 formulations based on their fluconazole drainage (M1: 65 ± 14 % and 27 ± 10 %; M2: 58 ± 6 % and 38 ± 9 %; M3: 56 ± 5 % and 38 ± 18 %). In conclusion, the OphthalMimic is a promising tool for comparing the animal-free performance of ophthalmic formulations.

Maternal transfer of per- and polyfluoroalkyl substances (PFAS) in wild birds: A systematic review and meta-analysis

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals widely used in consumer products. PFAS can accumulate in animal tissues, resulting in biomagnification and adverse effects on wildlife, such as reproductive impairment. In bird species, PFAS are transferred from mothers to eggs along with essential nutrients and may affect embryo development. However, the extent of maternal PFAS transfer across different species and compounds remains poorly understood. Here, we conducted a systematic review and meta-analysis to quantify maternal PFAS transfer in wild birds and investigate potential sources of variation. We tested the moderating effects of compounds’ physicochemical properties and biological traits of studied birds. The dataset included 505 measurements of PFAS concentration and 371 effect sizes derived from 13 studies on 16 bird species and 25 compounds. Overall, across all studies and species, we found a 41% higher concentration of PFAS in offspring than in mothers. Specifically, contaminants were concentrated in the yolk, longer and heavier compounds showed preferential transfer, larger clutch size was associated with decreased PFAS transfer and a higher transfer rate was shown in species with piscivorous and opportunistic/diverse diets. A validation assessment showed good robustness of the overall meta-analytic result. Given the crucial role of birds in maintaining ecological balance, this research article has relevant implications for modelling the impacts of PFAS on wildlife, ecosystems, and human health.

MRI-only based material mass density and relative stopping power estimation via deep learning for proton therapy: a preliminary study

Magnetic Resonance Imaging (MRI) is increasingly being used in treatment planning due to its superior soft tissue contrast, which is useful for tumor and soft tissue delineation compared to computed tomography (CT). However, MRI cannot directly provide mass density or relative stopping power (RSP) maps, which are required for calculating proton radiotherapy doses. Therefore, the integration of artificial intelligence (AI) into MRI-based treatment planning to estimate mass density and RSP directly from MRI has generated significant interest. A deep learning (DL) based framework was developed to establish a voxel-wise correlation between MR images and mass density as well as RSP. To facilitate the study, five tissue substitute phantoms were created, representing different tissues such as skin, muscle, adipose tissue, 45% hydroxyapatite (HA), and spongiosa bone. The composition of these phantoms was based on information from ICRP reports. Additionally, two animal tissue phantoms, simulating pig brain and liver, were prepared for DL training purposes. The phantom study involved the development of two DL models. The first model utilized clinical T1 and T2 MRI scans as input, while the second model incorporated zero echo time (ZTE) MRI scans. In the patient application study, two more DL models were trained: one using T1 and T2 MRI scans as input, and another model incorporating synthetic dual-energy computed tomography (sDECT) images to provide accurate bone tissue information. The DECT empirical model was used as a reference to evaluate the proposed models in both phantom and patient application studies. The DECT empirical model was selected as the reference for evaluating the proposed models in both phantom and patient application studies. In the phantom study, the DL model based on T1, and T2 MRI scans demonstrated higher accuracy in estimating mass density and RSP for skin, muscle, adipose tissue, brain, and liver. The mean absolute percentage errors (MAPE) were 0.42%, 0.14%, 0.19%, 0.78%, and 0.26% for mass density, and 0.30%, 0.11%, 0.16%, 0.61%, and 0.23% for RSP, respectively. The DL model incorporating ZTE MRI further improved the accuracy of mass density and RSP estimation for 45% HA and spongiosa bone, with MAPE values of 0.23% and 0.09% for mass density, and 0.19% and 0.07% for RSP, respectively. These results demonstrate the feasibility of using an MRI-only approach combined with DL methods for mass density and RSP estimation in proton therapy treatment planning. By employing this approach, it is possible to obtain the necessary information for proton radiotherapy directly from MRI scans, eliminating the need for additional imaging modalities.

Arachis pintoi Krapov. &amp; W.C. Greg.–A multifunctional legume

AbstractArachis pintoi, commonly known as pinto or forage peanut, is used mainly in consortia with grass pastures and as cover plant. In addition to increasing the productivity of livestock and plantations, it contributes to the mitigation of environmental impacts (reduction of greenhouse gas emissions) and soil improvement (nitrogen fixation, reduction of fertilizers use), as well as to pests and disease management. Several cultivars that are tolerant to specific climates and soil conditions are suitable to be used as ground covers in agroforestry and silvopastoral systems, orchards, and plantations. Biotechnological and phytochemical investigations revealed the potential of pinto peanut as a sustainable source of resveratrol and other stilbenoids. Extracts from plants grown under natural conditions and from materials obtained in vitro displayed allelopathic, anthelmintic, or antioxidant activities. Other studies revealed the potential of pinto peanut for erosion control, phytoremediation, seed and essential oils production, materials for animal tissue engineering, synthesis of nanoparticles for drug delivery, and as green biorefineries to produce proteins, biochemicals, and biomaterials.

Antifungal activity of Carica papaya fruit extract against Microsporum canis: in vitro and in vivo study.

Tinea capitis (T. capitis), commonly known as scalp ringworm, is a fungal infection affecting the scalp and hair. Among the causative agents, Microsporum canis (M. canis) stands out, often transmitted from cats to humans (zoonotic disease). In this study, we investigated the efficacy of Carica papaya (C. papaya), fruit extract against dermatophytes, particularly M. canis, both in vitro and in vivo. Additionally, we aimed to identify the active compounds responsible for suppressing fungal growth and assess the toxicity of C. papaya on human cells. It conducted in two parts. First, In Vitro Study include the preparation of C. papaya fruit extract using methanol as the solvent, Phytochemical analysis of the plant extract including Gas chromatography-mass spectrometry (GC-MS) and Fourier-transform infrared spectroscopy (FTIR) was conducted, Cytotoxicity assays were performed using HUH-7 cells, employing the MTT assay (1-(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), Antimicrobial activity against M. canis was evaluated, including: Zone of inhibition (ZI), Minimum inhibitory concentration (MIC), Minimum fungicidal concentration (MFC), M. canis cell alterations were observed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Second, In Vivo, Albino Wistar male rats were included. The phytochemical analysis of the methanolic extract from papaya revealed several functional groups, including hydroxyl, ammonia, alkane, carbonate, and alcohol. Additionally, the GC-MS analysis identified 15 compounds, with xanthosine and decanoic acid being the predominant components. The methanolic extract of papaya fruits demonstrated potent antifungal activity: ZI = 37 mm, MIC = 1,000 μg/mL, MFC = 1900 μg/mL, MTT results indicated lower cytotoxicity of the fruit extract at concentrations of 20 μg/mL, 50 μg/mL, 100 μg/mL, 150 μg/mL, and 200 μg/mL, The IC50 revealed a significant decrease in cell viability with increasing extract concentration. Notably, papaya extract induced considerable alterations in the morphology of M. canis hyphae and spores. In animal tissue, improvements were observed among the group of rats which treated with Papaya extract. This study highlights the potential of C. papaya fruits as a natural antifungal agent, warranting further exploration for clinical applications.

A Study on Mineral Oil Hydrocarbons (MOH) Contamination in Pig Diets and Its Transfer to Back Fat and Loin Tissues.

This study assessed saturated mineral oil hydrocarbons (MOSH) and aromatic mineral oil hydrocarbons (MOAH) levels in grower-finisher feeds for pigs supplemented with 5% crude palm oil (CP), crude olive pomace oil (COP), olive pomace acid oil (OPA), or a blend of CP and OPA (50:50, w/w); the contribution of the lipid source to that contamination; and the ability of pigs to accumulate MOH in back fat and loin tissues after 60 days of trial. MOSH and MOAH were analyzed with liquid chromatography (LC)-gas chromatography (GC)-flame ionization detection (FID) after sample preparation. Among the lipid sources, CP had the lowest MOH levels, but CP feeds showed the highest contamination. This, along with the different MOSH profiles, indicated the presence of more significant contamination sources in the feeds than the lipid source. The higher MOH contamination in CP feeds was reflected in the highest MOSH levels in pig back fat, whereas MOAH were not detected in animal tissues. Also, MOSH bioaccumulation in pig tissues was influenced by the carbon chain length. In conclusion, feed manufacturing processes can determine the MOSH contamination present in animal adipose tissues that can be included in human diets.

Diversity and Molecular Evolution of Nonvisual Opsin Genes across Environmental, Developmental, and Morphological Adaptations in Frogs.

Nonvisual opsins are transmembrane proteins expressed in the eyes and other tissues of many animals. When paired with a light-sensitive chromophore, nonvisual opsins form photopigments involved in various nonvisual, light-detection functions including circadian rhythm regulation, light-seeking behaviors, and seasonal responses. Here, we investigate the molecular evolution of nonvisual opsin genes in anuran amphibians (frogs and toads). We test several evolutionary hypotheses including the predicted loss of nonvisual opsins due to nocturnal ancestry and potential functional differences in nonvisual opsins resulting from environmental light variation across diverse anuran ecologies. Using whole-eye transcriptomes of 81 species, combined with genomes, multitissue transcriptomes, and independently annotated genes from an additional 21 species, we identify which nonvisual opsins are present in anuran genomes and those that are also expressed in the eyes, compare selective constraint among genes, and test for potential adaptive evolution by comparing selection between discrete ecological classes. At the genomic level, we recovered all 18 ancestral vertebrate nonvisual opsins, indicating that anurans demonstrate the lowest documented amount of opsin gene loss among ancestrally nocturnal tetrapods. We consistently found expression of 14 nonvisual opsins in anuran eyes and detected positive selection in a subset of these genes. We also found shifts in selective constraint acting on nonvisual opsins in frogs with differing activity periods, habitats, distributions, life histories, and pupil shapes, which may reflect functional adaptation. Although many nonvisual opsins remain poorly understood, these findings provide insight into the diversity and evolution of these genes across anurans, filling an important gap in our understanding of vertebrate opsins and setting the stage for future research on their functional evolution across taxa.

Effect of Lactiplantibacillus plantatum HFY11 on Colitis in Mice.

This study aimed to examine the potential impact of the intervention of Lactiplantibacillus plantatum HFY11 (LP-HFY11) on colitis using in vivo animal trials. The impact of LP-HFY11 intervention on colitis was determined by measuring the levels of relevant indicators in the intestine, colon, and blood after oxazolone-induced colitis in BALB/c mice. The results of the trial show that LP-HFY11 improved the colon weight-to-length ratio, reduced the colitis-induced colon length shortening, and reduced colonic abstinence. Furthermore, it decreased the levels of myeloperoxidase, nitric oxide, and malondialdehyde activities while increasing the glutathione content in the colon tissue of colitis-affected animals. LP-HFY11 lowered the interleukin-10 (IL-10) level and increased the IL-2 level in the serum of colitis mice. LP-HFY11 also upregulated the expression of neuronal nitric oxide synthase, endothelial nitric oxide synthase, c-Kit, and stem cell factor (SCF), and downregulated the expression of IL-8, C-X-C chemokine receptor type 2 (CXCR2), and inducible nitric oxide synthase (iNOS) in the colon tissue of mice with colitis. LP-HFY11 decreased the expression of Firmicutes in the gut while increasing the expression of Bacteroidetes, Bifidobacteria, and Lactobacillus. This indicates that LP-HFY11 could control physiological alterations in the serum and colon tissue, as well as the expression of gut microorganism.

Binucleated human hepatocytes arise through late cytokinetic regression during endomitosis M phase.

Binucleated polyploid cells are common in many animal tissues, where they arise by endomitosis, a non-canonical cell cycle in which cells enter M phase but do not undergo cytokinesis. Different steps of cytokinesis have been shown to be inhibited during endomitosis M phase in rodents, but it is currently unknown how human cells undergo endomitosis. In this study, we use fetal-derived human hepatocyte organoids (Hep-Orgs) to investigate how human hepatocytes initiate and execute endomitosis. We find that cells in endomitosis M phase have normal mitotic timings, but lose membrane anchorage to the midbody during cytokinesis, which is associated with the loss of four cortical anchoring proteins, RacGAP1, Anillin, SEPT9, and citron kinase (CIT-K). Moreover, reduction of WNT activity increases the percentage of binucleated cells in Hep-Orgs, an effect that is dependent on the atypical E2F proteins, E2F7 and E2F8. Together, we have elucidated how hepatocytes undergo endomitosis in human Hep-Orgs, providing new insights into the mechanisms of endomitosis in mammals.

Quercetin promotes the proportion and maturation of NK cells by binding to MYH9 and improves cognitive functions in aged mice

BackgroundQuercetin is a flavonol compound widely distributed in plants that possesses diverse biological properties, including antioxidative, anti-inflammatory, anticancer, neuroprotective and senescent cell-clearing activities. It has been shown to effectively alleviate neurodegenerative diseases and enhance cognitive functions in various models. The immune system has been implicated in the regulation of brain function and cognitive abilities. However, it remains unclear whether quercetin enhances cognitive functions by interacting with the immune system.ResultsIn this study, middle-aged female mice were administered quercetin via tail vein injection. Quercetin increased the proportion of NK cells, without affecting T or B cells, and improved cognitive performance. Depletion of NK cells significantly reduces cognitive ability in mice. RNA-seq analysis revealed that quercetin modulated the RNA profile of hippocampal tissues in aging animals towards a more youthful state. In vitro, quercetin significantly inhibited the differentiation of Lin−CD117+ hematopoietic stem cells into NK cells. Furthermore, quercetin promoted the proportion and maturation of NK cells by binding to the MYH9 protein.ConclusionsIn summary, our findings suggest that quercetin promotes the proportion and maturation of NK cells by binding to the MYH9 protein, thereby improving cognitive performance in middle-aged mice.Graphical abstract

APPLICATIONS OF NANOTECHNOLOGY IN ANIMAL NUTRITION: A REVIEW

Nanoparticles are commonly used in human medicine but their applications in agriculture, animal nutrition and veterinary medicine are quite new. To meet the increasing demands on the livestock industry, synthetic antibiotics are the major substances that are used as growth promoters. However, the use of antibiotics as feed additives is risky due to cross-resistance among bacterial strains and residues in tissues of the animals which could be deposited in man after consumption of animal tissues. Thus, the use of most synthetic antibiotics has been banned in many countries in the world, leading to a reduction in usage and the search for alternative growth promoters with minimal or no residual effect has been intense in recent times. Many reports have suggested that nanoparticles may be good substances for animal growth promotion and antimicrobials because some nanomaterials can remove toxins and pathogens. They can also be better absorbed by animals, improving their performance and the quality of products. Nanotechnology can potentially transform the livestock sector because of better bioavailability, small dose rate, and stable interaction of the nanomaterials with other components. Therefore, using nanoparticles is a good alternate approach that is safe and cost-effective for the control of pathogenic microbes and production improvement in livestock. In view of recent developments, this review was undertaken to discuss issues relating to the use of nanomaterials in animal feeds

Domestic dogs as environmental sentinel in comparative toxicologic pathology: Assessment of metals and rare earth elements concentrations in healthy and neoplastic mammary glands

Quantification of trace element concentrations in human and animal tissues has acquired great importance in the last few years, considering the pivotal role of these elements in several physiological and pathological processes. Variations in their concentrations appear to have a role in the development and advancement of diseases in both humans and animals, for example, cancer. The purpose of this study was to investigate the concentration of rare earth elements and metals in healthy and neoplastic Formalin-Fixed Paraffin-Embedded (FFPE) mammary gland tissue of dogs. All samples were processed to have a quantitative determination of inorganic elements including metals of known toxicological interest such as Pb, Cd, Tl, As, Hg, the trace elements Mn, Fe, Co, Cu, Zn, Se, and other elements including Cr, V, Mo, Ni, Sb, W, Sn. Moreover, rare earth elements (REEs) (Sc, Y, Lu, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb) were also investigated. Cu and Mo concentrations in mammary cancerous tissue were greater than those in normal mammary glands (p < 0.05). In non-neoplastic tissue increased concentrations of Cd, Co, Ni, Tl, and V were also reported (p < 0.05). The mammary tissue of healthy individuals had greater concentrations of REEs than the neoplastic mammary glands (p < 0.05). The results of our study confirmed differences in mammary inorganic element concentrations between healthy and neoplastic groups, highlighting the potential relevance of these fluctuations in toxicologic pathology.

Systematic analysis of ocular features and responses of cultured spotted wolffish (Anarhichas minor).

A better understanding of unique anatomical and functional features of the visual systems of teleost fish could provide key knowledge on how these systems influence the health and survival of these animals in both wild and culture environments. We took a systematic approach to assess some of the visual systems of spotted wolffish (Anarhichas minor), a species of increasing importance in North Atlantic aquaculture initiatives. The lumpfish (Cyclopterus lumpus) was included in these studies in a comparative manner to provide reference. Histology, light and electron microscopy were used to study the spatial distribution and occurrence of cone photoreceptor cells and the nature of the retinal tissues, while immunohistochemistry was used to explore the expression patterns of two photoreceptor markers, XAP-1 and XAP-2, in both species. A marine bacterial infection paradigm in lumpfish was used to assess how host-pathogen responses might impact the expression of these photoreceptor markers in these animals. We define a basic photoreceptor mosaic and present an ultrastructural to macroscopic geographical configuration of the retinal pigment tissues in both animals. Photoreceptor markers XAP-1 and XAP-2 have novel distribution patterns in spotted wolffish and lumpfish retinas, and exogenous pathogenic influences can affect the normal expression pattern of XAP-1 in lumpfish. Live tank-side ophthalmoscopy and spectral domain optical coherence tomography (SD-OCT) revealed that normal cultured spotted wolffish display novel variations in the shape of the retinal tissue. These two complementary imaging findings suggest that spotted wolffish harbour unique ocular features not yet described in marine teleosts and that visual function might involve specific retinal tissue shape dynamics in these animals. Finally, extensive endogenous biofluorescence is present in the retinal tissues of both animals, which raises questions about how these animals might use retinal tissue in novel ways for visual perception and/or communication. This work advances fundamental knowledge on the visual systems of two economically important but now threatened North Atlantic teleosts and provides a basic foundation for further research on the visual systems of these animals in health versus disease settings. This work could also be useful for understanding and optimizing the health and welfare of lumpfish and spotted wolffish in aquaculture towards a one health or integrative perspective.

The complex regulation of Slo1 potassium channels from a structural perspective.

Fast and regulated potassium efflux by Slo1 channels is crucial in many tissues in animals including neurons, the kidney and smooth muscle. During the last decade, structures have revealed many details about the gating mechanism and regulation of these large and complex molecular machines. This review summarizes these findings and the current knowledge about the intricate regulation of these important channels. Slo1 integrates sensing of the membrane potential via a voltage-sensor domain that undergoes subtle but significant structural rearrangements with a calcium-induced expansion of parts of the intracellular gating ring. Together, these two signals synergistically lead to changes in the conformation and chemical nature of the pore domain, allowing potassium ions to be translocated. In many native tissues, Slo1 channels are assembled with at least three classes of auxiliary subunits that change the gating kinetics or allow the channel to open also in absence of one of the two signals. Finally, Slo1 is inhibited, activated or deregulated by natural toxins and synthetic compounds, underlining the importance of the channel for the organism and as a potential target for drugs and other molecules.

MPIGAN: An end-to-end deep based generative framework for high-resolution magnetic particle imaging reconstruction.

Magnetic particle imaging (MPI) is a recently developed, non-invasive in vivo imaging technique to map the spatial distribution of superparamagnetic iron oxide nanoparticles (SPIONs) in animal tissues with high sensitivity and speed. It is a challenge to reconstruct images directly from the received signals of MPI device due to the complex physical behavior of the nanoparticles. System matrix and X-space are two commonly used MPI reconstruction methods, where the former is extremely time-consuming and the latter usually produces blurry images. Currently, we proposed an end-to-end machine learning framework to reconstruct high-resolution MPI images from 1-D voltage signals directly and efficiently. The proposed framework, which we termed "MPIGAN", was trained on a large MPI simulation dataset containing 291597 pairs of high-resolution 2-D phantom images and each image's corresponding voltage signals, so that it was able to accurately capture the nonlinear relationship between the spatial distribution of SPIONs and the received voltage signal, and realized high-resolution MPI image reconstruction. Experiment results showed that, MPIGAN exhibited remarkable abilities in high-resolution MPI image reconstruction. MPIGAN outperformed the traditional methods of system matrix and X-space in recovering the fine-scale structure of magnetic nanoparticles' spatial distribution and achieving enhanced reconstruction performance in both visual effects and quantitative assessments. Moreover, even when the received signals were severely contaminated with noise, MPIGAN could still generate high-quality MPI images. Our study provides a promising AI solution for end-to-end, efficient, and high-resolution magnetic particle imaging reconstruction.

Development and evaluation of a multi-target droplet digital PCR assay for highly sensitive and specific detection of Yersinia pestis.

Plague, caused by the bacterium Yersinia pestis, is a zoonotic disease that poses considerable threats to human health. Nucleic acid tests are crucial for plague surveillance and the rapid detection of Y. pestis. However, inhibitors in complex samples such as soil and animal tissues often hamper nucleic acid detection, leading to a reduced rate of identifying low concentrations of Y. pestis. To address this challenge, we developed a sensitive and specific droplet digital polymerase chain reaction (ddPCR) assay for detecting Y. pestis DNA from soil and animal tissue samples. Three genes (ypo2088, caf1, and pla) from Y. pestis were used to develop a multi-target ddPCR assay. The limits of detection (LoD), reproducibility, and specificity were assessed for bacterial genomic DNA samples. The ability of the assay to detect low concentrations of Y. pestis DNA from simulated soil and mouse liver tissue samples was respectively evaluated and compared with that of quantitative real-time PCR (qPCR). The results showed that the ddPCR LoDs ranged from 6.2 to 15.4 copies/reaction for the target genes, with good reproducibility and high specificity for Y. pestis. By testing 130 soil and mouse liver tissue samples spiked with Y. pestis, the ddPCR assay exhibited a better sensitivity than that of the qPCR assay used in the study, with LoDs of 102 colony forming units (CFU)/100 mg soil and 103 CFU/20 mg liver. Moreover, the assay presented good quantitative linearity (R2 = 0.99) for Y. pestis at 103-106 CFU/sample for soil and liver samples. The ddPCR assay presented good performance for detecting Y. pestis DNA from soil and mouse tissue samples, showing great potential for improving the detection rate of low concentrations of Y. pestis in plague surveillance and facilitating the early diagnosis of plague cases.

Novel foods, food enzymes, and food additives derived from food by-products of plant or animal origin: principles and overview of the EFSA safety assessment.

The European Union (EU) is committed to transitioning toward a circular economy model, with food waste being one of the areas to be targeted. To close the loop of food waste generated during food processing and discarded at the retail or consumption phases, research and innovation parties proposed to valorize agro-food by-products to produce novel foods and food improvement agents (food additives, food enzymes, and food flavorings). In the EU, the authorization of such novel foods and food improvement agents is governed by different regulatory frameworks. A centralized safety assessment by the European Food Safety Authority (EFSA) is the prerequisite for their authorization through the so-called Union Lists. Up to December 2023, EFSA published 45 scientific opinions on the safety of novel foods, food enzymes, and food additives derived from by-products of plant and animal origin. The current study illustrates examples of these by-products for the production of novel foods or food improvement agents and the data requirements behind their respective safety assessments conducted by EFSA. In this review, applications on novel foods, food enzymes, and food additives received by EFSA were screened and analyzed to find the common scientific requirements and differences in terms of the safety evaluation of such products. Various by-products (i.e., corncobs, coffee husks, spent grains of barley and rice, grape pomace, pumpkin peels, bovine whey, eggshells, shrimp heads, and animal organs or tissues) were described in the applications as being processed (extraction, physical treatments, and chemical and enzymatic reactions) to obtain novel foods and food improvement agents. The heterogeneity and complexity of these products emphasize the challenge of their safety assessment, depending on the characteristics of each product. However, as this study shows, the scientific requirements underpinning their safety do not differ substantially in the different regulated product areas considered, with similar information needed to assess their safety in terms of identity, production process, compositional characterization, proposed/intended uses and exposure assessment, toxicological information, and allergenicity data. Additional nutritional information and data on the history of use are required in the case of novel foods.