Microglial activation in the lateral amygdala promotes anxiety-like behaviors in mice with chronic moderate noise exposure.

BACKGROUND: Long-term non-traumatic noise exposure, such as heavy traffic noise, can elicit emotional disorders in humans. However, the underlying neural substrate is still poorly understood. METHODS: We exposed mice to moderate white noise for 28 days to induce anxiety-like behaviors, measured by open-field, elevated plus maze, and light-dark box tests. In vivo multi-electrode recordings in awake mice were used to examine neuronal activity. Chemogenetics were used to silence specific brain regions. Viral tracing, immunofluorescence, and confocal imaging were applied to define the neural circuit and characterize the morphology of microglia. RESULTS: Exposure to moderate noise for 28 days at an 85-dB sound pressure level resulted in anxiety-like behaviors in open-field, elevated plus maze, and light-dark box tests. Viral tracing revealed that fibers projecting from the auditory cortex and auditory thalamus terminate in the lateral amygdala (LA). A noise-induced increase in spontaneous firing rates of the LA and blockade of noise-evoked anxiety-like behaviors by chemogenetic inhibition of LA glutamatergic neurons together confirmed that the LA plays a critical role in noise-induced anxiety. Noise-exposed animals were more vulnerable to anxiety induced by acute noise stressors than control mice. In addition to these behavioral abnormalities, ionized calcium-binding adaptor molecule 1 (Iba-1)-positive microglia in the LA underwent corresponding morphological modifications, including reduced process length and branching and increased soma size following noise exposure. Treatment with minocycline to suppress microglia inhibited noise-associated changes in microglial morphology, neuronal electrophysiological activity, and behavioral changes. Furthermore, microglia-mediated synaptic phagocytosis favored inhibitory synapses, which can cause an imbalance between excitation and inhibition, leading to anxiety-like behaviors. CONCLUSIONS: Our study identifies LA microglial activation as a critical mediator of noise-induced anxiety-like behaviors, leading to neuronal and behavioral changes through selective synapse phagocytosis. Our results highlight the pivotal but previously unrecognized roles of LA microglia in chronic moderate noise-induced behavioral changes.

The impact of rivers and lakes on urban transportation expansion: A case study of the century-long evolution of the road network in Wuhan, China.

Throughout history, rivers and lakes have wielded a profound influence on the dynamics of urban transportation expansion. To illustrate this phenomenon, we turn to the century-long evolution of the road network in Wuhan, China, as a case study. The study aims to explore the relationship framework between water bodies and urban transportation, characterized by the sequence of "strong connection" to "weakened connection", then to "mutual restriction", and ultimately to "mutual benefit". Additionally, the analysis of the impact mechanisms of rivers and lakes on urban transportation at different stages of development is also a key research objective. To facilitate our exploration, we select the road networks in Wuhan from four years of 1922, 1969, 1995, and 2023 as the primary research subjects. By establishing water buffers, we scrutinize the evolving characteristics of riverside and lakeside transportation amidst the city's expansion. Based on the modified shortest path model, we introduce the innovative concepts of "Detour Index" and "Weighted Detour Index" to assess the road accessibility of each node in the city based on its inherent environmental conditions. This allows for the effective analysis of the potential impact of water bodies as "obstacles" on the road network at different stages of urban development. The study found that in the areas adjacent to the rivers and lakes in Wuhan, there is insufficient road accessibility based on their inherent environmental conditions. Particularly, some areas along the rivers may become "terminals" in the urban road network. Furthermore, during the process of urban expansion, the correlation between the urban road network and rivers continues to weaken, while the correlation with lakes continues to strengthen. These conclusions can provide valuable insights for the planning of urban roads near water bodies.

Reviving: restoring depression-like behaviour through glial cell-derived neurotrophic factor treatment in the medial prefrontal cortex.

BACKGROUND: Depression is a prevalent nonmotor symptom in Parkinson disease and can greatly reduce the quality of life for patients; the dopamine receptors found in glutamatergic pyramidal cells in the medial prefrontal cortex (mPFC) play a role in regulating local field activity, which in turn affects behavioural and mood disorders. Given research showing that glial cell-derived neurotrophic factor (GDNF) may have an antidepressant effect, we sought to evaluate the impact of exogenous GDNF on depression-like behaviour in mouse models of Parkinson disease. METHODS: We used an established subacute model of Parkinson disease in mice involving intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), followed by brain stereotaxic injection of GDNF into the mPFC region. Subsequently, we assessed depression-like behaviour using the sucrose preference test, forced swimming test and tail suspension test, while also evaluating protein expression in the mPFC. RESULTS: We included 60 mice, divided into 3 groups, including a control group (saline injection), an MPTP plus saline injection group and an MPTP plus GDNF injection group. We found that exogenous GDNF injection into the mPFC led to an increase in dopamine receptor D1 (DRD1) protein levels. We also observed that activating the protein kinase A pathway through DRD1 produced a prolonged antidepressant response. Under GDNF stimulation, the expression of dopamine receptor D2 (DRD2) remained constant, suggesting that the DRD2 signal was ineffective in alleviating depression-like symptoms. Moreover, our investigation involved Golgi staining and Western blot techniques, which found enhanced synaptic plasticity, including increased dendritic branches, dendritic spines and retrograde protection after GDNF treatment in Parkinson disease models. LIMITATIONS: A subtle motor phenotype became evident only toward the conclusion of the behavioural testing period. The study exclusively involved male mice, and no separate control group receiving only GDNF treatment was included in the experimental design. CONCLUSION: Our findings support a positive effect of exogenous GDNF on synaptic plasticity, mediated by DRD1 signalling in the mPFC, which could facilitate depression remission in Parkinson disease.

PBA alleviates cadmium-induced mouse spermatogonia apoptosis by suppressing endoplasmic reticulum stress.

OBJECTIVE: Endoplasmic reticulum (ER) stress mediates Cd-caused germ cell apoptosis in testis. The effects of 4-phenylbutyric acid (PBA), a classical chaperone, were investigated on Cd-induced apoptosis in mouse GC-1 spermatogonia cells. METHODS: The cells were pretreated with PBA before Cd exposure. TUNEL and flow cytometry assays were applied to determine apoptosis. Some key biomarkers of ER stress were analyzed using RT-PCR and western blot. RESULTS: as expected, the apoptotic cells exposed to Cd apparently increased. The mRNA and protein expression levels of GRP78 and ATF6α, were elevated in the Cd groups. Additional experiments displayed that Cd notably increased IRE1α and JNK phosphorylation, and upregulated XBP-1 mRNA and protein expression. Moreover, p-eIF2α and CHOP expressions were clearly elevated in the Cd groups. Interestingly, PBA almost completely inhibited ER stress and protected spermatogonia against apoptosis induced by Cd. CONCLUSION: PBA alleviated Cd-induced ER stress and spermatogonia apoptosis, and may have the therapeutic role in Cd-induced male reproductive toxicity.

The Abnormal Accumulation of Lipopolysaccharide Secreted by Enriched Gram-Negative Bacteria Increases the Risk of Rotavirus Colonization in Young Adults.

Human rotavirus (HRV) is an enteric virus that causes infantile diarrhea. However, the risk factors contributing to HRV colonization in young adults have not been thoroughly investigated. Here, we compared the differences in dietary habits and composition of gut microbiota between asymptomatic HRV-infected young adults and their healthy counterparts and investigated potential risk factors contributing to HRV colonization. Our results indicated that asymptomatic HRV-infected adults had an excessive intake of milk and dairy and high levels of veterinary antibiotics (VAs) and preferred veterinary antibiotic (PVAs) residues in urine samples. Their gut microbiota is characterized by abundant Gram-negative (G-) bacteria and high concentrations of lipopolysaccharide (LPS). Several opportunistic pathogens provide discriminatory power to asymptomatic, HRV-infected adults. Finally, we observed an association between HRV colonization and disrupted gut microbiota caused by the exposure to VAs and PVAs. Our study reveals the traits of disrupted gut microbiota in asymptomatic HRV-infected adults and provides a potential avenue for gut microbiota-based prevention strategies for HRV colonization.

Cadmium exposure during puberty damages testicular development and spermatogenesis via ferroptosis caused by intracellular iron overload and oxidative stress in mice.

Cadmium (Cd) is a widespread environmental pollutant and a reproductive toxicant. It has been proved that Cd can reduce male fertility, however, the molecular mechanisms remain unveiled. This study aims to explore the effects and mechanisms of pubertal Cd exposure on testicular development and spermatogenesis. The results showed that Cd exposure during puberty could cause pathological damage to testes and reduce sperm counts in mice in adulthood. Moreover, Cd exposure during puberty reduced GSH content, induced iron overload and ROS production in testes, suggesting that Cd exposure during puberty may induce testicular ferroptosis. The results in vitro experiments further strengthened that Cd caused iron overload and oxidative stress, and decreased MMP in GC-1 spg cells. In addition, Cd disturbed intracellular iron homeostasis and peroxidation signal pathway based on transcriptomics analysis. Interestingly, these changes induced by Cd could be partially suppressed by pretreated with ferroptotic inhibitors, Ferrostatin-1 and Deferoxamine mesylate. In conclusion, the study demonstrated that Cd exposure during puberty maybe disrupted intracellular iron metabolism and peroxidation signal pathway, triggered ferroptosis in spermatogonia, and ultimately damaged testicular development and spermatogenesis in mice in adulthood.

Cadmium induced mouse spermatogonia apoptosis via mitochondrial calcium overload mediated by IP3R-MCU signal pathway.

Cadmium (Cd) is a toxic metal and also a well-known reproductive toxicant. Cd could induce germ cells apoptosis in mouse testes, however, the mechanism remains unclear. This study designed in vitro using GC-1 spermatogonial (spg) cells to explore the cytotoxicity and the molecular mechanisms induced by cadmium chloride(CdCl2). As expected, CdCl2 elevated the levels of reactive oxygen species (ROS) and induced the release of AIF and Cyt-c from the mitochondria to the cytosol in spermatogonia. Correspondingly, CdCl2 apparently increased the apoptotic rate in spermatogonia. Further researches found that CdCl2 could activate IP3R-MCU pathway, trigger Ca2+ transfer from endoplasmic reticulum to mitochondria, and cause mitochondrial Ca2+ overload. BAPTA acetoxymethyl ester (BAPTA-AM), a calcium chelator, almost completely attenuated IP3R phosphorylation, inhibited the mRNA and protein expression levels of VDAC1, MCU and MCUR1 upregulated by CdCl2, reduced the calcium ion content in the mitochondria. Moreover, BAPTA-AM could decrease the level of ROS, antagonize CdCl2-induced release of AIF and Cyt-c from the mitochondria to the cytosol and alleviate CdCl2-induced apoptosis in spermatogonia. As above, these results provided the evidence that CdCl2 might induce apoptosis of spermatogonia via mitochondrial Ca2+ overload mediated by IP3R-MCU signal pathway.

Crosstalk between imbalanced gut microbiota caused by antibiotic exposure and rotavirus replication in the intestine.

Objective: Rotavirus (RV), one of non-enveloped double-strained RNA viruses, can cause infantile diarrheal illness. It is widely accepted that RV is transmitted mainly via feces-oral route. However, infected asymptomatic adults are becoming the source of infection. It is necessary to explore the underlying mechanism of RV replication in adult's intestine. Methods: After recruiting healthy volunteers and RV asymptomatic carriers, we firstly investigated the association of animal-derived food intake with antibiotic level in urine samples. Secondly, we compared the difference in the structure of gut microbiota, and identified the taxa that most likely explained the difference. Finally, we investigated the impact of lipopolysaccharide (LPS), produced by gram-negative bacteria, on RV replication in vivo and in vitro. Results: We found that 10% of participants were RV asymptomatic carriers in our study. High intake of animal-derived food was positively correlated to antibiotic level in urine samples. The disrupted gut microbiota in RV carriers was characterized by high abundance of antibiotic resistant gram-negative bacteria and high level of LPS. The disrupted gut microbiota caused by penicillin treatment was benefit to RV replication in vivo. LPS enhanced RV thermal stability in vitro. Conclusions: Our findings suggest that the imbalanced gut microbiota caused by antibiotic exposure plays an important role in RV replication, and brings risk to health complications.

Blunt dopamine transmission due to decreased GDNF in the PFC evokes cognitive impairment in Parkinson's disease.

Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson's disease. However, there have not been any studies conducted on the potential relationship between glial cell line-derived neurotrophic factor and cognitive performance in Parkinson's disease. We first performed a retrospective case-control study at the Affiliated Hospital of Xuzhou Medical University between September 2018 and January 2020 and found that a decreased serum level of glial cell line-derived neurotrophic factor was a risk factor for cognitive disorders in patients with Parkinson's disease. We then established a mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analyzed the potential relationships among glial cell line-derived neurotrophic factor in the prefrontal cortex, dopamine transmission, and cognitive function. Our results showed that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex weakened dopamine release and transmission by upregulating the presynaptic membrane expression of the dopamine transporter, which led to the loss and primitivization of dendritic spines of pyramidal neurons and cognitive impairment. In addition, magnetic resonance imaging data showed that the long-term lack of glial cell line-derived neurotrophic factor reduced the connectivity between the prefrontal cortex and other brain regions, and exogenous glial cell line-derived neurotrophic factor significantly improved this connectivity. These findings suggested that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex leads to neuroplastic degeneration at the level of synaptic connections and circuits, which results in cognitive impairment in patients with Parkinson's disease.

Exposure to Veterinary Antibiotics via Food Chain Disrupts Gut Microbiota and Drives Increased Escherichia coli Virulence and Drug Resistance in Young Adults.

Exposure to veterinary antibiotics (VAs) and preferred as veterinary antibiotics (PVAs) via the food chain is unavoidable for their extensive use not only for treating bacterial infections, but also for use as growth promoters in livestock and aquaculture. One of the consequences is the disturbance of gut microbiota. However, its impact on the virulence and drug resistance of opportunistic pathogens is still unclear. In this study, a total of 26 antibiotics were detected in the urine of 300 young undergraduates in Anhui Province. We found that excessive intake of milk was positively correlated to high levels of VAs and PVAs. It led to the dysbiosis of gut microbiota characterized by high abundance of Bacteroidetes and Proteobacteria. The increase in Proteobacteria was mainly due to a single operational taxonomic unit (OTU) of Escherichia coli (E. coli). We isolated several E. coli strains from participants and compared their drug resistance and virulence using PCR assay and virulence-related assays. We observed that exposure to high levels of VAs and PVAs induced more resistant genes and drove E. coli strain to become more virulent. At last, we conducted transcriptome analysis to investigate the molecular mechanism of virulent and drug-resistant regulators in the highly virulent E. coli strain. We noted that there were multiple pathways involved in the drug resistance and virulence of the highly virulent strain. Our results demonstrated that participants with high-level VAs and PVAs exposure have a disrupted gut microbiota following the appearance of highly drug-resistant and virulent E. coli and, therefore may be at elevated risk for long-term health complications.

Excess copper promotes catabolic activity of gram-positive bacteria and resistance of gram-negative bacteria but inhibits fungal community in soil.

The extensive use of copper fungicides has resulted in significant non-target effects on soil microbial communities. However, the documented effects are often variable and contradictory, depending on the methods used to assess them. In this study, we examined the effects of copper accumulation in surface soils on microbial catabolic activity, active biomass and composition, and sensitive bacterial species. The community-level catabolic profiles (CLCPs) showed that both normal (50 mg CuSO4 kg-1 soil) and high dosages (tenfold rate) of CuSO4 significantly increased the catabolic diversity of gram-positive bacteria, while the high dosage increased the overall catabolic activity of gram-negative bacteria. The phospholipid fatty acid (PLFA) analysis showed that the high dosage reduced the biomass of gram-positive bacteria by 27% but did not affect that of gram-negative bacteria. In comparison, the normal and high dosages decreased the fungal biomass by 34% and 58%, respectively. Furthermore, 16S rRNA-denaturing gradient gel electrophoresis (DGGE) fingerprint revealed that more than two-thirds of identified bands belonged to gram-negative bacteria. Some Cu-resistant gram-negative bacterial genera, such as Actinobacterium, Pseudomonas, and Proteobacterium, were detected in the soil to which the high dosage of CuSO4 had been applied. In conclusion, an excess application of CuSO4 increased the catabolic diversity of gram-positive bacteria and induced resistance in gram-negative bacteria, whereas the active fungal community displayed a dosage-dependent response to CuSO4 and can thus be used as a sensitive indicator of copper contamination.

The Dysbiosis of Gut Microbiota Caused by Low-Dose Cadmium Aggravate the Injury of Mice Liver through Increasing Intestinal Permeability.

Cadmium (Cd), widely present in food and drinking water at low doses, can cause health risks. However, the mechanistic effects of long-term Cd exposure at low dose through dietary intake is poorly studied. The aim of this study is to elucidate whether the dysbiosis of gut microbiota caused by Cd at an environmental low dose can aggravate the injury of mice liver, and the possible mechanism is investigated. In order to explore the potential underlying mechanism, the analyses of the variation of gut microbiota composition, intestinal permeability, and hepatic transcriptome were conducted. Our results showed that gut microbiota was disturbed. The rise of intestinal permeability induced by the dysbiosis of gut microbiota resulted in more Cd ions accumulating in mice liver, but it could be restored partly through depleting gut microbiota by antibiotics cocktail. Transcriptomic analyses indicated that 162 genes were significantly differentially expressed including 59 up-regulated and 103 down-regulated in Cd treatment. These genes were involved in several important pathways. Our findings provide a better understanding about the health risks of cadmium in the environment.

Walnut Shell Powder Can Limit Acid Mine Drainage Formation by Shaping the Bacterial Community Structure.

The formation of acid mine drainage (AMD), which results from the oxidation of sulfur minerals by air and water, can be accelerated by acidophilic and chemolithotrophic bacteria such as Acidithiobacillus ferrooxidans. Our previous study revealed that walnut shell powder and its phenolic component inhibit the growth of A. ferrooxidans. However, their inhibitory effect on AMD formation in the environment needs verification. We established a bioleaching system to test whether walnut shell powder and its phenolic component can limit AMD formation. Our results showed that lignin and cellulose isolated from walnut shell decreased metal ion concentrations through absorption, whereas the phenolic component increased pH by downregulating the expression of Fe2+-oxidizing genes and rus operon genes of A. ferrooxidans. Only walnut shell powder showed an excellent ability to curb AMD by binding metal ions and increasing the pH value. On probing deeper into the alteration of the bacterial community structure in the bioleaching system, we found that the bacterial community became more diverse-the amount of A. ferrooxidans decreased and that of some non-acidophilic bacteria increased. The bacterial community in samples treated with walnut shell powder or its phenolic component had low abundance in the pathways of metabolism and energy production, as determined by phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt). In other words, preponderant microbes, mainly A. ferrooxidans, lacked energy to grow well in the treated samples. Our findings provide a practical applicability of walnut shell powder to reduce leaching from a complex environmental community.

Glyphosate application increased catabolic activity of gram-negative bacteria but impaired soil fungal community.

Glyphosate is a non-selective organophosphate herbicide that is widely used in agriculture, but its effects on soil microbial communities are highly variable and often contradictory, especially for high dose applications. We applied glyphosate at two rates: the recommended rate of 50 mg active ingredient kg-1 soil and 10-fold this rate to simulate multiple glyphosate applications during a growing season. After 6 months, we investigated the effects on the composition of soil microbial community, the catabolic activity and the genetic diversity of the bacterial community using phospholipid fatty acids (PLFAs), community level catabolic profiles (CLCPs), and 16S rRNA denaturing gradient gel electrophoresis (DGGE). Microbial biomass carbon (Cmic) was reduced by 45%, and the numbers of the cultivable bacteria and fungi were decreased by 84 and 63%, respectively, under the higher glyphosate application rate. According to the PLFA analysis, the fungal biomass was reduced by 29% under both application rates. However, the CLCPs showed that the catabolic activity of the gram-negative (G-) bacterial community was significantly increased under the high glyphosate application rate. Furthermore, the DGGE analysis indicated that the bacterial community in the soil that had received the high glyphosate application rate was dominated by G- bacteria. Real-time PCR results suggested that copies of the glyphosate tolerance gene (EPSPS) increased significantly in the treatment with the high glyphosate application rate. Our results indicated that fungi were impaired through glyphosate while G- bacteria played an important role in the tolerance of microbiota to glyphosate applications.

Perinatal sulfamonomethoxine exposure influences physiological and behavioral responses and the brain mTOR pathway in mouse offspring.

Sulfamonomethoxine (SMM) is widely used in the veterinary field in China. Although some clinical surveys have revealed that sulfonamide antibiotics cause adverse nervous system symptoms, the related mechanisms of maternal SMM exposure on the neurobehavioral development of offspring remain unclear. Here, we investigated the effects of perinatal SMM exposure on the physiological and behavioral responses of pubertal offspring mice and the underlying mechanisms. We randomly allocated pregnant mice into the groups treated with SMM at different doses and the saline-treated groups. Maternal mice were orally administered SMM daily from gestational day 1 to postpartum day 21. On postnatal day (PND) 22, the parameters of growth, endocrine hormones, and brain amino acid composition were assessed, as well as the brain transcript levels of key genes involved in the mammalian target of rapamycin (mTOR) signaling pathway. From PND 50 to 55, a battery of behavioral tests relevant to anxiety and memory were then administered. Analysis of the results indicated that the pups, particularly the pubertal female offspring, showed anxiety-like behavior. Moreover, the pubertal offspring showed cognitive impairments and fat accumulation. Furthermore, the relative mRNA expression of genes involved in the mTOR signaling pathway in females on PND 22 was elevated, whereas the expression of N-methyl-d-aspartate receptor 2B (NR2B) was reduced. Together, the results showed that perinatal SMM exposure perturbs neuroendocrine functions, and further alters gene expression in the mTOR pathway and NR2B gene expression early in life, which may contribute to brain dysfunction in pubertal life.

The mode of delivery affects the diversity and colonization pattern of the gut microbiota during the first year of infants' life: a systematic review.

BACKGROUND: The human gut is the habitat for diverse and dynamic microbial ecosystem. The human microbiota plays a critical role in functions that sustain health and is a positive asset in host defenses. Establishment of the human intestinal microbiota during infancy may be influenced by multiple factors including delivery mode. Present review compiles existing evidences on the effect of delivery mode on the diversity and colonization pattern of infants gut microbiota. METHODS: Two investigators searched for relevant scientific publications from four databases (Pubmed, Medline, Embase, and Web of Science). The last search was performed on September 21, 2015, using key terms ((delivery mode OR caesarean delivery OR cesarean section OR vaginal delivery) AND (gut microbiota OR gut microbiome OR gut microflora OR intestinal microflora OR microbial diversity) AND (infants OR children)). All included studies described at least two types of gut microbiota in relation to delivery mode (caesarean section vs vaginal delivery) and used fecal samples to detect gut microbiota. RESULTS: Seven out of 652 retrieved studies met inclusion criteria, were included in systematic analysis. Caesarean Section (CS) was associated with both lower abundance and diversity of the phyala Actinobacteria and Bacteroidetes, and higher abundance and diversity of the phylum Firmicute from birth to 3 months of life. At the colonization level, Bifidobacterium, and Bacteroides genera seems to be significantly more frequent in vaginally delivered infants compared with CS delivered. These infants were more colonized by the Clostridium, and Lactobacillus genera. From the reports, it is tempting to say that delivery mode has less effect on colonization and diversity of Bifidobacteria, Bacteroides, Clostridium, and Lactobacillus genera from the age of 6 to 12 months of life. CONCLUSION: The diversity and colonization pattern of the gut microbiota were significantly associated to the mode of delivery during the first three months of life, however the observed significant differences disappears after 6 months of infants life. The healthy gut microbiota is considered to promote development and maturation of the immune system while abnormal gut is considered as the major cause of severe gastrointestinal infections during the infancy. Further studies should investigate the diversity and colonization levels of infant gut microbiota in relation to the mode of delivery and its broad impact on infants' health at each stage of life.

Wheat bran intake can attenuate chronic cadmium toxicity in mice gut microbiota.

Environmental exposure to pollutants such as heavy metals is responsible for various altered physiological functions that are detrimental to health. Cadmium (Cd) is one of the most representative toxic, non-essential elements that can contaminate food and water. This study evaluated the protective effects of wheat bran, a selected prebiotic with good Cd binding ability, against Cd toxicity in mice. Thirty mice were divided into control and therapeutic groups. The control group was fed a low dietary fiber diet with no Cd for 8 weeks. In the therapeutic group, 100 mg L(-1) Cd was administered along with a diet of 10% wheat bran. First, the binding ability of wheat bran for Cd was measured along with the protection of cell growth in vitro by wheat bran. Second, the effectiveness of wheat bran in preventing Cd from entering mice organs was evaluated. Finally, restoration of gut microbiota from alterations caused by Cd was investigated. The results showed that wheat bran could bind most of the Cd ions and restore the growth rate of cells in vitro. The wheat bran treatment group showed that the bran effectively prevented Cd from entering mice organs. In addition, the bacterial community structure was restored because the toxicity of Cd to gut microbiota was eliminated by the wheat bran. Our results suggest that wheat bran is more effective against chronic Cd toxicity than traditional treatments because of its special physiological functions, and it can be considered as a new dietary, therapeutic strategy against Cd toxicity.

Use of Walnut Shell Powder to Inhibit Expression of Fe(2+)-Oxidizing Genes of Acidithiobacillus Ferrooxidans.

Acidithiobacillus ferrooxidans is a Gram-negative bacterium that obtains energy by oxidizing Fe(2+) or reduced sulfur compounds. This bacterium contributes to the formation of acid mine drainage (AMD). This study determined whether walnut shell powder inhibits the growth of A. ferrooxidans. First, the effects of walnut shell powder on Fe(2+) oxidization and H⁺ production were evaluated. Second, the chemical constituents of walnut shell were isolated to determine the active ingredient(s). Third, the expression of Fe(2+)-oxidizing genes and rus operon genes was investigated using real-time polymerase chain reaction. Finally, growth curves were plotted, and a bioleaching experiment was performed to confirm the active ingredient(s) in walnut shells. The results indicated that both walnut shell powder and the phenolic fraction exert high inhibitory effects on Fe(2+) oxidation and H⁺ production by A. ferrooxidans cultured in standard 9K medium. The phenolic components exert their inhibitory effects by down-regulating the expression of Fe(2+)-oxidizing genes and rus operon genes, which significantly decreased the growth of A. ferrooxidans. This study revealed walnut shell powder to be a promising substance for controlling AMD.

Physiological and behavioral responses in offspring mice following maternal exposure to sulfamonomethoxine during pregnancy.

Sulfamonomethoxine (SMM), a veterinary antibiotic, is widely used in China. However, the impacts of maternal SMM exposure on neurobehavioral development in early life remain little known. In this study, we investigated the effects of maternal SMM exposure during pregnancy on behavioral and physiological responses in offspring mice. Pregnant mice were randomly divided into three SMM-treated groups, namely low-(10mg/kg/day), medium-(50mg/kg/day), and high-dose (200mg/kg/day), and a control group. The pregnant mice in the SMM-treated groups received SMM by gavage daily from gestational day 1-18, whereas those in the control received normal saline. On postnatal day (PND) 50, spatial memory was assessed using the Morris water maze test, and anxiety was measured using the elevated plus-maze and open field tests. The results showed significantly increased blood glucose in pups whose mothers received a high SMM dose. In addition, maternal SMM exposure increased anxiety-related activities among the offspring; spatial learning and memory were impaired more severely in the male offspring. The contents of tetrahydrobiopterin (BH4) and brain-derived neurotrophic factors (BDNF) on PND 22 were significantly reduced in the male offspring of the high-dose group compared with the controls. These findings indicate that SMM may be identified as a risk factor for cognitive and behavioral development on the basis of gender and that it may be associated with diminished BH4 and BDNF levels early in life.

Exposing to cadmium stress cause profound toxic effect on microbiota of the mice intestinal tract.

Cadmium (Cd), one of the heavy metals, is an important environmental pollutant and a potent toxicant to organism. It poses a severe threat to the growth of the organism, and also has been recognized as a human carcinogen. However, the toxicity of cadmium and its influences on microbiota in mammal's intestine are still unclear. In our experiment, the changes of intestinal microbiota in two groups of mice were investigated, which were supplied with 20 and 100 mg kg(-1) cadmium chloride respectively for 3 weeks. The control group was treated with water free from cadmium chloride only. This study demonstrated that Cd accumulated in some tissues of mice after Cd administration and the gut barrier was impaired. Cd exposure also significantly elevated the colonic level of TNF-α. On the other hand, Cd-treatment could slow down the growth of gut microbiota and reduced the abundance of total intestinal bacteria of the mice. Among them, the growth of Bacteroidetes was significantly suppressed while Firmicutes growth was not. The probiotics including Lactobacillus and Bifidobacterium were notably inhibited. We also observed that the copies of key genes involved in the metabolism of carbohydrates to short-chain fatty acids (SCFAs) were lower in Cd-treated groups than control. As a result, the levels of short-chain fatty acids in colonic decreased significantly. In summary, this study provides valuable insight into the effects of Cd intake on mice gut microbiota.