Quantitative Analysis of Bioaccessible Phenolic Compounds in Aegean Bee Bread Using LC-HRMS Coupled with a Human Digestive System Model.

Bee bread, a valuable bee product that has recently attracted significant public interest as a nutritional supplement. The aim of this study was to evaluate the presence of phenolic compounds in bee bread samples from the Aegean Region and assess their bioaccessibility using a simulated human digestion model. Various extraction techniques, such as maceration, ultrasound-assisted extraction, and supercritical fluid extraction were employed to obtain extracts of bee bread. The antioxidant capabilities of these extracts were carried out using assays like DPPH⋅, ABTS⋅+ , CUPRAC, and ß-carotene linoleic acid bleaching, and their effectiveness was quantified through IC50 values. The bioaccessibility of phenolic compounds was analysed by using LC-HRMS in a simulated human digestive system using ethanol extracts obtained from bee bread samples of each season by ultrasound-assisted extraction, which has the highest antioxidant activity. In the Aegean bee bread, a total of 25 phenolic compounds which were major phenolics including quercetin, ascorbic acid, isorhamnetin, kaempferol, and hyperoside were identified and quantified. Also, ascorbic acid was the one of the most bioaccessible compounds with the bioaccessibility index 35.38 % for 2021, 16.79 % for 2022. These findings underscore the substantial transformation of the phenolic profile of bee bread as it traverses the human digestive system.

Characteristics of 210Po in Asian overbite clam (Potamocorbula laevis) from the coastal area at Thai Binh province, Vietnam.

210Po concentration in the edible muscle tissue and digestive diverticulum organs of Asian overbite clam at the near-shore Thai Binh, Vietnam was analyzed using alpha detectors. The 210Po activity in muscle tissue and digestive diverticulum organs ranged from 5 ± 1 to 178 ± 10 and from 118 ± 7 to 812 ± 12 Bq.kg-1 with the average value of 25 and 324 Bq.kg-1, respectively. Results showed that 210Po activity in the digestive diverticulum was significantly higher than in the muscle tissue. There was a slightly inverse correlation between 210Po activity in muscle tissue, digestive diverticulum, and clam weight and size. The annual committed effective dose was calculated from 210Po due to the consumption of Asian overbite clam for adults in the study area was higher than the guideline value of 0.2 - 1 mSv.y-1.

Effect of different cadmium levels in Boletus griseus on bioaccessibility, bioavailability, and intestinal flora by establishing a complete bionic digestion system in vitro.

The bioaccessibility and bioavailability of different cadmium (Cd) levels (low: 7.31 mg/kg, medium: 24.20 mg/kg, high: 41.64 mg/kg) in Boletus griseus were evaluated by establishing a bionic digestive system in vitro. The results showed that the bioaccessibility of high Cd level by gastrointestinal digestion was significantly higher than other two levels. Further, colonic digestion significantly increased the bioaccessibilities of low Cd level (p < 0.05). After intestinal flora fermentation, the bioaccessibilities of different Cd levels significantly decreased (p < 0.05), and high and medium Cd levels had no significant difference (p > 0.05). A Caco-2 monolayer cell model was established to evaluate the bioavailability of Cd. The bioavailabilities of low and high Cd levels by gastrointestinal digestion were 8.75 and 10.58%, and the bioavailabilities increased by 38.17% and 5.20% after colonic digestion, respectively. Furthermore, Cd could affect diversity, composition, and balance of intestinal flora, and the relative abundances of several genera were correlation with Cd levels in B. griseus.

First evidence of presence of plastic debris in digestive system of Mola mola (L.) from western Mediterranean Sea.

Ingestion of marine debris by ocean sunfishes is not very well documented. As the feeding behaviour of these giants of the seas is very similar to marine turtles, it is expected that the accidental ingestion of plastics could be registered in these species of fish. With this work it is noticed for the first time the presence of a blue plastic fragment, classified by its size as a mesoplastic, in the digestive system of Mola mola (L.) (Molidae) from western Mediterranean Sea.

An arithmetic correction for the effect of lipid on carbon stable isotope ratios in muscle and digestive glands of the American lobster (Homarus americanus).

RATIONALE: Lipid correction models use elemental carbon-to-nitrogen ratios to estimate the effect of lipids on δ13 C values and provide a fast and inexpensive alternative to chemically removing lipids. However, the performance of these models varies, especially in whole-body invertebrate samples. The generation of tissue-specific lipid correction models for American lobsters, both an ecologically and an economically important species in eastern North America, will aid ecological research of this species and our understanding of the function of these models in invertebrates. METHOD: We determined the δ13 C and δ15 N values before and after lipid extraction in muscle and digestive glands of juvenile and adult lobster. We assessed the performance of four commonly used models (nonlinear, linear, natural logarithm (LN) and generalized linear model (GLM)) at estimating lipid-free δ13 C values based on the non-lipid-extracted δ13 C values and elemental C:N ratios. The accuracy of model predictions was tested using paired t-tests, and the performance of the different models was compared using the Akaike information criterion score. RESULTS: Lipid correction models accurately estimated post-lipid-extraction δ13 C values in both tissues. The nonlinear model was the least accurate for both tissues. In muscle, the three other models performed well, and in digestive glands, the LN model provided the most accurate estimates throughout the range of C:N values. In both tissues, the GLM estimates were not independent of the post-lipid-extraction δ13 C values, thus reducing their transferability to other datasets. CONCLUSIONS: Whereas previous work found that whole-body models poorly estimated the effect of lipids in invertebrates, we show that tissue-specific lipid correction models can generate accurate and precise estimates of lipid-free δ13 C values in lobster. We suggest that the tissue-specific logarithmic models presented here are the preferred models for accounting for the effect of lipid on lobster isotope ratios.

Occurrence and characterization of microplastic content in the digestive system of riverine fishes.

In the present study, the occurrence and characterization of microplastics (MPs) content in the fishes of the river was studied. Therefore, six sampling stations were considered for fishing. Then, the entire stomach of fishes was investigated by visual stereomicroscope, FTIR, SEM, and EDX to analyze the content of the samples, by MPs type, shape, color, and size. The most frequency of MPs was observed in Ghazanchi (Siii) and Kermanshah (Siv) stations which were close to urban and industrial areas. Most types of detected MPs included polystyrene, polyethylene, and nylon with the highest frequency observed in Luciobarbus caspius and Alburnus chalcoides fishes. Overall, the frequency of detected MPs in the caught fishes was 93.8%. Indeed, MPs with a size of 0.025-1 mm (25-1000 µm) were the most frequency of MPs in fishes. The frequency of MPs shapes was fiber (85.12%), fragment (12.32%), foam (0.77%), film (1.21%), and microbead (0.56%), respectively. The highest and lowest percentage of MPs belonged to black and green with an abundance of 63% and 2%, respectively. The result implies that lots of riverine fishes are polluted with MPs, those which can move into the food chain.

Physical and Chemical Barriers in the Larval Midgut Confer Developmental Resistance to Virus Infection in Drosophila.

Insects can become lethally infected by the oral intake of a number of insect-specific viruses. Virus infection commonly occurs in larvae, given their active feeding behaviour; however, older larvae often become resistant to oral viral infections. To investigate mechanisms that contribute to resistance throughout the larval development, we orally challenged Drosophila larvae at different stages of their development with Drosophila C virus (DCV, Dicistroviridae). Here, we showed that DCV-induced mortality is highest when infection initiates early in larval development and decreases the later in development the infection occurs. We then evaluated the peritrophic matrix as an antiviral barrier within the gut using a Crystallin-deficient fly line (Crys-/-), whose PM is weakened and becomes more permeable to DCV-sized particles as the larva ages. This phenotype correlated with increasing mortality the later in development oral challenge occurred. Lastly, we tested in vitro the infectivity of DCV after incubation at pH conditions that may occur in the midgut. DCV virions were stable in a pH range between 3.0 and 10.5, but their infectivity decreased at least 100-fold below (1.0) and above (12.0) this range. We did not observe such acidic conditions in recently hatched larvae. We hypothesise that, in Drosophila larvae, the PM is essential for containing ingested virions separated from the gut epithelium, while highly acidic conditions inactivate the majority of the virions as they transit.

Genetic architecture of 11 organ traits derived from abdominal MRI using deep learning.

Cardiometabolic diseases are an increasing global health burden. While socioeconomic, environmental, behavioural, and genetic risk factors have been identified, a better understanding of the underlying mechanisms is required to develop more effective interventions. Magnetic resonance imaging (MRI) has been used to assess organ health, but biobank-scale studies are still in their infancy. Using over 38,000 abdominal MRI scans in the UK Biobank, we used deep learning to quantify volume, fat, and iron in seven organs and tissues, and demonstrate that imaging-derived phenotypes reflect health status. We show that these traits have a substantial heritable component (8-44%) and identify 93 independent genome-wide significant associations, including four associations with liver traits that have not previously been reported. Our work demonstrates the tractability of deep learning to systematically quantify health parameters from high-throughput MRI across a range of organs and tissues, and use the largest-ever study of its kind to generate new insights into the genetic architecture of these traits.

Distribution of Domoic Acid in the Digestive Gland of the King Scallop Pecten maximus.

The king scallop Pecten maximus retains the amnesic shellfish poisoning toxin, domoic acid (DA), for a long time. Most of the toxin is accumulated in the digestive gland, but this organ contains several cell types whose contribution to the accumulation of the toxin is unknown. Determining the time-course of the depuration by analyzing whole organs is difficult because the inter-individual variability is high. A sampling method, using biopsies of the digestive gland, has been developed. This method allows for repetitive sampling of the same scallop, but the representativeness of the samples obtained in this way needs to be validated. In this work, we found that the distribution of DA in the digestive gland of the scallops is mostly homogeneous. Only the area closest to the gonad, and especially its outer portion, had a lower concentration than the other ones, probably due to a transfer of the toxin to the intestinal loop. Samples obtained by biopsies can therefore be considered to be representative. Most of the toxin was accumulated in large cells (mostly digestive cells), which could be due to differences during the toxin absorption or to the preferential depuration of the toxin from the small cells (mostly secretory).

Rosai-Dorfman Disease of the Digestive System-Beware Vasculopathy: A Clinicopathologic Analysis.

Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytic proliferation that occurs in nodal and extranodal sites. Rare examples of the disease involving the digestive system have been described. To characterize the digestive tract manifestations of this disease, 12 specimens from 11 patients with extranodal RDD affecting the digestive organs were analyzed. Hematoxylin and eosin sections and available immunohistochemical stains were reviewed, and the clinical information was obtained from patients' electronic or submitted records. Eight patients were female and 3 male (median age, 65 y; range, 17 to 76 y). Abdominal pain was the most frequent symptom. Six patients had an associated immunologic or malignant disease. Nine lesions arose in the gastrointestinal tract (1 involving the appendix, 2 right colon, 6 left colon), 2 in the pancreas, and 1 in the liver. Two patients had the coexistent nodal disease, and 1 had bone and soft-tissue involvement. The lesions were generally composed of polygonal to spindle-shaped histiocytes with eosinophilic to clear cytoplasm admixed with lymphoplasmacytic cells. The inflammatory cells formed lymphoid aggregates in 7 cases and included focally scattered or small collections of neutrophils in 6 cases. Fibrosis was variable, and 4 cases had a storiform pattern. Vasculopathy in the form of a thickened capillary wall, medium-sized arterial wall infiltration by lesional and inflammatory cells and phlebitis was seen in 10, 5, and 2 cases, respectively. All cases were reactive for S100-protein. Of the 5 patients with follow-up, 1 developed immunoglobulin A nephropathy and died of renal failure.

Anti-complement activity in salivary glands and midgut of Chagas disease vector, Panstrongylus megistus (Hemiptera, Triatominae).

The triatomine insect Panstrongylus megistus , one of the most important Chagas disease vectors in Brazil, presents salivary molecules pharmacologically active to counteract homeostatic responses from the host, including inhibitors of the human complement system, a major effector of immune responses. The aim of the present study was to investigate the effect of P. megistus salivary gland extract (SGE) on the complement system from different host species and characterize the inhibitory effect of SGE and intestinal contents on human complement. Glands and midguts from fourth instar nymphs were used. Hemolytic assays were performed with sheep erythrocytes as complement activators by using human, rats and chickens sera in the presence or absence of SGE. An ELISA assay was carried out detect deposition of the C3b component on IgG- or agarose-sensitized microplates, in the presence or absence of SGE or midgut contents. P. megistus SGE was able to significantly inhibit the complement of the three studied species (human, rat and chiken). Both, SGE and midgut contents inhibited C3b deposition in either the classical or the alternative pathways. As conclusions, SGE and midgut from P. megistus possess anti-complement activity. The inhibitors are effective against different host species and act on the initial steps of the complement system cascade. These inhibitors may have a role in blood feeding and Trypanosoma cruzi transmission by the vector.

Semi-quantitative analysis of morphological changes in bee tissues: A toxicological approach.

During foraging, bees are exposed to sublethal doses of insecticides, which can cause morphological changes to various organs, such as the midgut, Malpighian tubules, and mushroon body. Thus, the purpose of this study was to establish a scoring system to evaluate these alterations based on the damage caused and its reversibility. Therefore, a grade 1 score indicates a minimal and easily reversible lesion, increased apocrine secretion, increased cell elimination into the lumen, and a larger quantity of spherocrystals; grade 2 was assigned to moderate and typically reversible injuries, such as changes in the brush border, vacuolation/loss of cytoplasmic material, presence/height of the brush border, and cell swelling; and grade 3 was assigned to serious and irreversible, loss of cell nests of regenerative cells, pyknosis, and loss of contact between Kenyon cells. In addition, frequency values were assigned since the alterations can occur at different frequencies according to the insecticide and the bees exposed; the frequency ranges from 0 to 6, with 0 representing the absence of an alteration and 6 representing a high-frequency occurrence. Based on the analyses, we conclude that each change causes morphological damage, which may or may not be irreversible and could affect the health of the colony.

Metal Concentration in Muscle and Digestive Gland of Common Octopus (Octopus vulgaris) from Two Coastal Site in Southern Tyrrhenian Sea (Italy).

Octopus vulgaris constitute an important part of most suitable marine resources for human consumption, however, they can represent a source in chemical contaminants intake such as heavy metals. In this scenario, the aim of the study was the evaluation of the concentration of lead (Pb), cadmium (Cd) and mercury (Hg) in the muscle and digestive gland of octopus caught from two different locations along Campania coast (Castellammare di Stabia and Napoli) and the estimation of their weekly human intake derived from the ingestion of octopus. Analysing 38 samples showed a higher concentration of Pb in the muscle of octopus in Castellammare di Stabia than in Napoli. No statistical differences were reported for Cd, Pb and Hg concentrations in the digestive gland of octopus between two sampling sites. Differences were observed between the two tissue types, with a higher level of Cd and Pb observed in the digestive gland compared with the muscle. Noteworthy, the consumption of muscle from Castellammare di Stabia could increase Pb intake in heavy consumers of local octopus. In conclusion, the present work determines that it is important to improve strategies to minimize environmental pollution sources in these areas.

Prominent Stereoselectivity of NNAL Glucuronidation in Upper Aerodigestive Tract Tissues.

Tobacco specific nitrosamines (TSNAs) are among the most potent carcinogens found in cigarettes and smokeless tobacco products. Decreases in TSNA detoxification, particularly 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), have been associated with tobacco-related cancer incidence. NNK is metabolized by carbonyl reduction to its major carcinogenic metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), which is detoxified by glucuronidation at the nitrogen within the pyridine ring or at the chiral alcohol to form four glucuronide products: (R)-NNAL-O-Gluc, (S)-NNAL-O-Gluc, (R)-NNAL-N-Gluc, (S)-NNAL-N-Gluc. Stereoselective NNAL-Gluc formation and the relative expression of NNAL-glucuronidating UGTs (1A4, 1A9, 1A10, 2B7, 2B10, 2B17) were analyzed in 39 tissue specimens from the upper aerodigestive tract (esophagus (n = 13), floor of mouth (n = 4), larynx (n = 9), tongue (n = 7), and tonsil (n = 6)). All pooled tissue types preferentially formed (R)-NNAL-O-Gluc in the presence of racemic-NNAL; only esophagus exhibited any detectable formation of (S)-NNAL-O-Gluc. For every tissue type examined, UGT1A10 exhibited the highest relative expression levels among the NNAL-O-glucuronidating UGTs, ranging from 36% (tonsil) to 49% (esophagus), followed by UGT1A9 > UGT2B7 > UGT2B17. UGT1A10 also exhibited similar or higher levels of expression as compared to both NNAL-N-glucuronidating UGTs, 1A4 and 2B10. In a screening of cells expressing individual UGT enzymes, all NNAL glucuronidating UGTs exhibited some level of stereospecific preference for individual NNAL enantiomers, with UGTs 1A10 and 2B17 forming primarily (R)-NNAL-O-Gluc. These data suggest that UGTs 1A10 and 2B17 may be important enzymes in the detoxification of TSNAs like NNK in tissues of the upper aerodigestive tract.

Multivesicular Liposomes for the Sustained Release of Angiotensin I-Converting Enzyme (ACE) Inhibitory Peptides from Peanuts: Design, Characterization, and In Vitro Evaluation.

The multivesicular liposome (MVL) provides a potential delivery approach to avoid the destruction of the structure of drugs by digestive enzymes of the oral cavity and gastrointestinal system. It also serves as a sustained-release drug delivery system. In this study, we aimed to incorporate a water-soluble substance into MVLs to enhance sustained release, prevent the destruction of drugs, and to expound the function of different components and their mechanism. MVLs were prepared using the spherical packing model. The morphology, structure, size distribution, and zeta potential of MVLs were examined using an optical microscope (OM), confocal microscopy (CLSM), transmission electron cryomicroscope (cryo-EM) micrograph, a Master Sizer 2000, and a zeta sizer, respectively. The digestion experiment was conducted using a bionic mouse digestive system model in vitro. An in vitro release and releasing mechanism were investigated using a dialysis method. The average particle size, polydispersity index, zeta potential, and encapsulation efficiency are 47.6 nm, 1.880, -70.5 ± 2.88 mV, and 82.00 ± 0.25%, respectively. The studies on the controlled release in vitro shows that MVLs have excellent controlled release and outstanding thermal stability. The angiotensin I-converting enzyme (ACE) inhibitory activity of ACE-inhibitory peptide (AP)-MVLs decreased only 2.84% after oral administration, and ACE inhibitory activity decreased by 5.03% after passing through the stomach. Therefore, it could serve as a promising sustained-release drug delivery system.

Evaluation of microplastic ingestion by tropical fish from Moorea Island, French Polynesia.

Microplastics are ubiquitous throughout the oceans, yet few studies have documented their occurrence in marine organisms associated with coral reefs. Four genera of adult fish were sampled (Myripristis spp., Siganus spp., Epinephelus merra and Cheilopogon simus) from different trophic guilds around the tropical island of Moorea, French Polynesia. Digestive tracts from 133 adult fish were surveyed and microplastics were found in 28 tracts (21%). Abundance of ingested microplastic pieces per individual fish varied from 1 to 3 pieces, with an average of 1.25 ±â€¯0.13 ingested microplastic pieces. Microplastics size ranged from 0.031 to 2.44 mm and 70% of microplastics did not exceed 0.3 mm in size. Overall, this study shows that the number and size of microplastic ingested per trophic groups are independent of trophic guild. Additional studies are needed to sample in other tropical regions in order to have a better assessment of microplastic occurrence in coral reefs.

Microplastic ingestion by Atlantic chub mackerel (Scomber colias) in the Canary Islands coast.

In recent years, due to the increasing concerns about their negative impact on wildlife and possible toxicity to living organisms (including humans), microplastics have become the subject of intense investigations. In the ocean, microplastics can be easily ingested by numerous marine organisms because of their small size (<5 mm). The Northwest African upwelling system is an important fishery area, and the present study is the first one in the region to reveal the presence of microplastic particles in the digestive tract of Atlantic chub mackerel (Scomber colias). From the 120 examined fish gastrointestinal tracts, 78.3% contained some type of microplastics, 74.2% contained fibres, 17.5% plastic fragments, and 16.7% paint. More studies are needed on fish, but S. colias is a candidate for being a good indicator of microplastic contamination in the region.

An assessment of the ability to ingest and excrete microplastics by filter-feeders: A case study with the Mediterranean mussel.

Plastic debris has been recognized as a growing threat to marine biota due to its widespread distribution and possible interactions with marine species. Concerns over the effects of plastic polymers in marine ecosystems is reflected in the high number of toxicological studies, regarding microplastics (<5 mm) and marine fauna. Although several studies reported that organisms ingest and subsequently eliminate microplastics (MP), the potential effects at organ and tissue level remain unclear, especially considering exposure to different microplastic sizes and concentrations. The present study aimed at investigating potential pathophysiological effects of the ingestion of MP by marine filter-feeders. For the purpose, Mediterranean mussel (Mytilus galloprovincialis) was exposed to spherical polystyrene MP (2 and 10 µm Ø) over short- and medium-term exposure periods, under single and combined concentrations that represent high, yet realistic doses (10 and 1000 MP mL-1). Overall, results suggest rapid MP' clearance from water column by filtering, regardless of MP size. Ingestion occurred, identified by MP in the lumen of the gut (mostly in midgut region), followed by excretion through faeces. However, no MP were found in gills or digestive gland diverticula. Biochemical indicators for oxidative stress were generally irresponsive regardless of organ and time of exposure. Small foci of haemocytic infiltration in gastric epithelia were found, albeit not clearly related to MP ingestion. Globally, no evident histopathological damage was recorded in whole-body sections of exposed animals. The present findings highlight the adaptative ability of filter-feeding bivalves to cope with filtration of suspended MP, resulting in rapid elimination and reduced internal damage following ingestion of spherical MP. Nevertheless, the fact that the animals are able to translocate MP to the gut reveals that filter feeding organisms may indeed became a target of concern for fragmented materials with smaller, mixed sizes and sharper edges.

Microplastic pollution in rice-fish co-culture system: A report of three farmland stations in Shanghai, China.

Microplastics are emerging contaminants of increasing concern. Despite the occurrence of microplastics in farmland soils, the knowledge on microplastics in rice-fish co-culture ecosystems is limited. In this study, we investigated the distribution of microplastics in three rice-fish culture stations in Shanghai. During non-rice and rice-planting periods, microplastics in water, soils and aquatic animals (eel, loach and crayfish) were systematically assayed using methods of NaCl density extraction, H2O2 digestion and micro-fourier transform infrared spectroscopy. Results showed that average microplastic abundances were 0.4 ±â€¯0.1 items L-1, 10.3 ±â€¯2.2 items kg-1, 1.7 ±â€¯0.5 items individual-1 in water, soils and aquatic animal samples, respectively. We found an increasing trend in microplastic abundances in water, soil and animal samples from non-rice period to rice-planting period. Almost all of microplastics were found in digestive tracts of animals. Major microplastics were small (<1 mm) polyethylene and polypropylene fibers, with color of white and translucent. Size, shape, color and polymer type distributions of microplastics were similarly found in environmental and animal samples. Moreover, microplastic abundances in aquatic animals correlated to abundance in farmland soils. This study, for the first time, reveals the occurrence and characteristics of microplastic pollution in rice-fish culture ecosystem which suggests the potential ecological risks of microplastics in the agroecosystem.

SLC30A10 transporter in the digestive system regulates brain manganese under basal conditions while brain SLC30A10 protects against neurotoxicity.

The essential metal manganese becomes neurotoxic at elevated levels. Yet, the mechanisms by which brain manganese homeostasis is regulated are unclear. Loss-of-function mutations in SLC30A10, a cell surface-localized manganese efflux transporter in the brain and liver, induce familial manganese neurotoxicity. To elucidate the role of SLC30A10 in regulating brain manganese, we compared the phenotypes of whole-body and tissue-specific Slc30a10 knockout mice. Surprisingly, unlike whole-body knockouts, brain manganese levels were unaltered in pan-neuronal/glial Slc30a10 knockouts under basal physiological conditions. Further, although transport into bile is a major route of manganese excretion, manganese levels in the brain, blood, and liver of liver-specific Slc30a10 knockouts were only minimally elevated, suggesting that another organ compensated for loss-of-function in the liver. Additional assays revealed that SLC30A10 was also expressed in the gastrointestinal tract. In differentiated enterocytes, SLC30A10 localized to the apical/luminal domain and transported intracellular manganese to the lumen. Importantly, endoderm-specific knockouts, lacking SLC30A10 in the liver and gastrointestinal tract, had markedly elevated manganese levels in the brain, blood, and liver. Thus, under basal physiological conditions, brain manganese is regulated by activity of SLC30A10 in the liver and gastrointestinal tract, and not the brain or just the liver. Notably, however, brain manganese levels of endoderm-specific knockouts were lower than whole-body knockouts, and only whole-body knockouts exhibited manganese-induced neurobehavioral defects. Moreover, after elevated exposure, pan-neuronal/glial knockouts had higher manganese levels in the basal ganglia and thalamus than controls. Therefore, when manganese levels increase, activity of SLC30A10 in the brain protects against neurotoxicity.