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Abstract Clastic rock aquifer of the coal seam roof often constitutes the direct water-filling aquifer of the coal seam and its water-richness is closely related to the risk of roof water inrush. Therefore, the evaluation of the water-richness of clastic rock aquifer is the basic work of coal seam roof water disaster prevention. This article took the 4th coal seam in Huafeng mine field as an example. It combined the empirical formula method and generalized regression neural network (GRNN) to calculate the development height of water-conducting fracture zone, determined the vertical spatial range of water-richness evaluation. Depth of the sandstone floor, brittle rock ratio, lithological structure index, fault strength index, and fault intersections and endpoints density were selected as the main controlling factors. A combination weighting method based on the analytic hierarchy process (AHP), rough set theory (RS), and minimum deviation method (MD) was proposed to determine the weight of the main controlling factors. Introduced the theory of unascertained measures and confidence recognition criteria to construct an evaluation model for the water-richness of clastic rock aquifers, the study area was divided into three zones: relatively weak water-richness zones, medium water-richness zones, and relatively strong water-richness zones. By comparing with the water inrush points and the water inflow of workfaces, the evaluation model's water yield zoning was consistent with the actual situation, and the prediction effect was good. This provided a new idea for the evaluation of the water-richness of the clastic rock aquifer on the roof of the mining coal seam.

Abstract Animal‐derived anti‐IgG secondary antibodies are currently employed to stain and screen of human monoclonal antibody(mAb)‐producing cells, but using animal‐derived antibodies may raise the concerns of high cost, complicated operations and biological safety issues in biopharmaceutical manufacturing. Nanobodies(VHHs) are attractive forms of antibodies for their straightforward engineering and expression in both eukaryotic and prokaryotic systems. Using phage‐displayed immune llama VHH library, we identified new anti‐Fc VHHs that could bind to human Fc with high affinity. In GFP fusion format, the anti‐Fc VHH‐GFP generated dramatically stronger FACS signals than AF488 conjugated anti‐IgG antibodies when used for staining mAb‐producing CHO cells. Furthermore, preparative sorting of CHO cells based on anti‐Fc VHH‐GFP staining resulted in the enrichment of cell lines capable of synthesizing mAb at high productivity. This safe and cost‐efficient anti‐Fc VHH‐GFP may optimize the process of generating highly productive cell lines for therapeutic mAb production compared to conventional animal‐derived fluorescent antibodies.

Analyzing and fusing information layers of exploratory parameters is a critical step for enhancing the accuracy of identifying mineral potential zones during the reconnaissance stage of mineral exploration. The Qixia area in Shandong Province is characterized by intricate geological structures and abundant mineral resources. Numerous gold polymetallic deposits have been discovered in this region, highlighting the potential for discovering more such deposits in the ore concentration zone and its adjacent areas. In this study, we focus on the Qixia area and employ the box dimension method to analyze the fractal dimension of fault structures. We investigate the relationship between orebody occurrence and fault incidence within the mining region. Furthermore, we combine fractal analysis with Fry analysis to comprehensively predict the metallogenic potential in the area. This study reveals the fractal dimension values of fault structures, demonstrating that fault structures govern the distribution of ore bodies, with NE and NW fault structures being the primary ore-hosting features. Based on thorough analysis, we hypothesize that gold deposits in this area are generally distributed along the northeastern direction. By considering mineral distribution characteristics, this study identifies five potential metallogenic prospect areas within the study region. Capitalizing on advancements in information technology and big data, digital geology has gained prominence in prospecting and prediction. To this end, we construct a multi-information comprehensive prospecting model based on the structure-geochemical anomaly-mineralization alteration, employing the convolutional neural network (CNN) model for quantitative estimation of regional gold mineral resources. The findings validate the CNN model’s robust prediction performance in this area, leading to the determination of five prediction prospects. We observe a notable congruence between the two methods, offering significant insights for subsequent exploration endeavors in the region.

Inrush of limestone karst water through the mine floor occurs frequently in the Carboniferous–Permian coalfield in northern China. The unascertained measurement evaluation and set pair analysis methods are proposed to evaluate water inflow, by using eight indices. Firstly, ordered binary comparison quantization method and interval number fuzzy decision matrix of EA-TOPSIS ordering were used to obtain weights for these eight factors. Secondly, conflicting evidence theory is applied to couple of these weights calculated by ordered binary comparison quantization and EA-TOPSIS ordering, to ensure the effective evaluation of the relative importance with respect to each indicator for the dynamic model. Lastly, the unapprehend measurement evaluation and set pair analysis methods were utilized to evaluate the risk of limestone karst water influx from coal seam floor. Based on the type of index value, the state classification is carried out through quantitative analysis, and single index measure functions including linear and non-linear patterns, are constructed. The process is described as follows: first, the 8 index values collected from 30 water inrush points in Xinwen coalfield are substituted into the measurement function to construct the multi index comprehensive evaluation matrix. Second, the credibility identification criterion is introduced to determine the risk level of water incurred point XiFinally, the general situation of water inflow risk from coal seam floor during coal mining in Xinwen coalfield is illustrated by using set pair potential analysis method. The production practice in Xinwen coalfield has proved that the evaluation results are consistent with the actual situation.

ABSTRACT Fusarium oxysporum is ubiquitous and can easily contaminate food during processing and storage, potentially producing T-2 toxin, which can pose a severe health risk to public health. Previous research on the presence of T-2 has focused on starch-rich foods, while protein- and amino acid-rich foods have received relatively little attention. In this study, the effects of amino acids on the growth of F. oxysporum and its T-2 production were investigated by gene deletion and complementation experiments. The results showed that amino acids, including aspartic acid, methionine, isoleucine, serine, phenylalanine, and cysteine, significantly inhibited the growth of F. oxysporum, while promoting T-2 synthesis, with cysteine having the most pronounced effect. The target of rapamycin complex 1 (TORC1) is a key pathway in response to a variety of amino acids, including cysteine. gtr2 and tap42 were found to be negative regulators of T-2 synthesis. The study highlights the elevated risk of T-2 production by F. oxysporum in cysteine-rich foods and the need to take appropriate measures to prevent and control the potential harm that such foods may present to public health. IMPORTANCE F. oxysporum and its T-2 contamination of food not only leads to food wastage but also poses a major food safety challenge to humans. The growth and T-2 production characteristics of F. oxysporum in high-protein substrates are considerably different from those in grains. Here, we show that the abundant free amino acids in a protein-rich food matrix are a key regulatory factor for the growth of, and toxin production by, F. oxysporum. Cysteine has the most pronounced effect on inhibiting mycelial growth and promoting T-2 synthesis through the TORC1 pathway. This implies that consumers tend to overlook T-2 contamination due to the poor growth of F. oxysporum in food rich in protein and amino acids, especially cysteine. Therefore, particular attention should be paid to the protection of those products.

Fusarium oxysporum (F. oxysporum) is a common contaminant of dried fish, and the T-2 synthesis by this organism in dried fish products poses a serious public health risk. In this study, we investigated the effects of iturin A, a cyclic lipopeptide produced by Bacillus subtilis, on the growth and synthesis of the T-2 toxin of F. oxysporum, and transcriptomics was conducted. Results showed that the inhibitory effect of iturin A on F. oxysporum was significantly enhanced with an increase in iturin A concentrations. More specifically, compared with the control group, all indexes in the iturin A treatment group with 50 μg/mL were decreased to 24.84 mm, 0.33 × 106 cfu/mL, and 5.86 ng/mL for the colony diameter, number of spores, and concentration of T-2 toxin, respectively. Furthermore, iturin A was proven to destroy the integrity of cell membranes and cause a significant increase in ROS at 25 μg/mL or 50 μg/mL. Transcriptomic analysis revealed that with the treatment of iturin A, the genes of the oxidation-reduction process were up-regulated, while the gene expression of mycelial growth, cell integrity, transmembrane transport, energy metabolism, and others were down-regulated. More importantly, the Tri5 gene cluster was significantly inhibited. This study provided new insights into the mechanism for the inhibitory effect of iturin A on the growth and T-2 toxin synthesis of F. oxysporum and theoretical guidance for the application of iturin A in the preservation of dried aquatic products.

Abstract Background Nucleos(t)ide analogues (NAs) are the first-line option against chronic hepatitis B (CHB). NAs produce potent suppression of viral replication with a small chance of HBsAg seroclearance and a high risk of virological relapse after discontinuation. The combined therapy of NAs plus traditional Chinese medicine (TCM) is widely accepted and has been recognized as a prospective alternative approach in China. Based on preliminary works, this study was designed to observe the therapeutic effect of TCM plus entecavir (ETV) against HBeAg-positive chronic hepatitis B with respect to reducing the recurrence risk after NA withdrawal. Methods/design The study is a nationwide, multicenter, double-blind, randomized, placebo-controlled trial with a duration of 120 weeks. A total of 18 hospitals and 490 eligible Chinese HBeAg-positive CHB patients will be enrolled and randomly allocated into the experimental group and control group in a 1:1 ratio. Patients in the experimental group will be prescribed TCM formulae (Tiaogan-BuXu-Jiedu granules) plus ETV 0.5 mg per day for consolidation therapy for 96 weeks. Patients in the control group will be prescribed TCM granule placebo plus ETV 0.5 mg per day for the same course. After consolidation therapy, all patients will discontinue their trial drugs and be closely monitored over the next 24 weeks. Once clinical recurrence (CR) occurs, ETV treatment will be restarted. The primary outcome is the cumulative rate of CR at the end of this trial. Conclusion This study is the first of its kind to observe therapeutic effects with respect to reducing recurrence after NA withdrawals after unified integrative consolidation therapy in the CHB population. Trial registration Chinese Clinical Trial Registry No. ChiCTR1900021232 . Registered on February 2, 2019

Recently, Lin and colleagues assessed the safety of sodium-glucose cotransporter 2 inhibitors (SGLT2is) by a meta-analysis [1], in which the authors assessed 16 kinds of adverse events (AE) reported in the published articles based on 10 randomized controlled trials. We conducted a further meta-analysis and targeted the association between use of SGLT2is and occurrences of various kinds of serious AE published in the Clinical Trials website (clinicaltrials.gov). Our meta-analysis revealed that use of SGLT2is was not significantly associated with occurrences of 980 kinds of serious AE but was significantly associated with lower risks of 29 kinds of serious AE, especially including several important respiratory diseases (e.g., asthma, chronic obstructive pulmonary disease, sleep apnoea syndrome, and pneumonia). These findings may cause more studies to evaluate the possibilities of gliflozins being used for prevention of these specific diseases.

Lin et al. recently did a network meta-analysis based on cardiovascular (CV) outcome trials (CVOTs) of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and those of glucagon-like peptide-1 receptor agonists (GLP1RAs). Due to the absence of CVOTs directly comparing SGLT2is with GLP1RAs, Lin et al.'s network meta-analysis identified the indirect evidence that SGLT2is vs. GLP1RAs reduced hospitalization for heart failure (HHF) but did not reduce CV death and all-cause mortality (ACM) in patients with type 2 diabetes (T2D). We did another meta-analysis incorporating those CV outcome cohort studies directly comparing SGLT2is with GLP1RAs, and identified that SGLT2is vs. GLP1RAs were significantly associated with the lower risks of not only HHF but also CV death and ACM. These findings may suggest that SGLT2is should be considered over GLP1RAs in terms of preventing CV and all-cause death and HHF in T2D patients.

Background: The effects of sodium-glucose transporter 2 (SGLT2) inhibitors on cardiovascular death (CV death) and all-cause death (AC death) in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) are currently under intensive investigation. We intended to conduct an updated meta-analysis including the SCORED trial to evaluate the effects of SGLT2 inhibitors on death and cardiorenal events in this vulnerable population. Methods: Cardiorenal outcome trials of SGLT2 inhibitors were included. Primary outcomes were CV death and AC death, while secondary outcomes were hospitalization for heart failure (HHF), myocardial infarction (MI), CKD progression, cardiovascular death or hospitalization for heart failure (CV death or HHF), major adverse cardiovascular events (MACE), and stroke. Meta-analysis was conducted for each outcome. Results: Eight trials were included for meta-analysis. Compared with placebo, SGLT2 inhibitors significantly lowered the risk of CV death (HR = 0.86, 95% CI = 0.75–0.98), AC death (HR = 0.87, 95% CI = 0.79–0.96), HHF (HR = 0.64, 95% CI = 0.56–0.74), MI (HR = 0.76, 95% CI = 0.65–0.89), CKD progression (HR = 0.62, 95% CI = 0.54–0.72), and CV death or HHF (HR = 0.73, 95% CI = 0.67–0.80). No heterogeneity existed in the above meta-analyses (all I 2 values = 0%), whereas moderate heterogeneity existed in the meta-analyses for MACE and stroke (I 2 = 31.6% and 44.5%, respectively). Conclusions: Our findings suggest that SGLT2 inhibitors versus placebo significantly lower death, heart failure, renal failure, and MI events in patients with T2D and CKD. Head-to-head trials are needed to examine the possible differences in the effects of various gliflozins on MACE and stroke.

The association between sodium-glucose cotransporter 2 inhibitors (SGLT2is) and various cardiovascular and respiratory diseases is unestablished. This meta-analysis aimed to explore whether use of SGLT2is is significantly associated with the occurrences of 80 types of cardiovascular diseases and 55 types of respiratory diseases. Large randomized trials of SGLT2is were included in analysis. Meta-analysis was conducted to synthesize risk ratio (RR) and 95% confidence interval (CI). Nine large trials were included in analysis. Compared to placebo, SGLT2is were associated with the reduced risks of 9 types of cardiovascular diseases (e.g., atrial fibrillation [RR 0.78, 95% CI 0.67-0.91], bradycardia [RR 0.60, 95% CI 0.40-0.89], and hypertensive emergency [RR 0.29, 95% CI 0.12-0.72]) and 11 types of respiratory diseases (e.g., chronic obstructive pulmonary disease [RR 0.77, 95% CI 0.61-0.97], asthma [RR 0.57, 95% CI 0.35-0.95], and sleep apnoea syndrome [RR 0.36, 95% CI 0.15-0.87]). The results of random-effects meta-analysis were similar with those of fixed-effects meta-analysis. No heterogeneity or only little heterogeneity was found in most meta-analyses. No publication bias was observed in most of the meta-analyses conducted in this study. SGLT2is were not significantly associated with the other 115 cardiovascular and respiratory diseases. SGLT2is are associated with the reduced risks of 9 types of cardiovascular diseases (e.g., atrial fibrillation, bradycardia, and hypertensive emergency) and 11 types of respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma, and sleep apnoea syndrome). This proposes the potential of SGLT2is to be used for prevention of these cardiovascular and respiratory diseases.

The cardiorenal benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) are established, whereas those in patients without T2DM are not established. We sought to assess the cardiorenal efficacy and safety of SGLT2 inhibitors in non-T2DM patients by performing a meta-analysis based on the subgroup data of non-T2DM patients from relevant secondary analysis articles in which subgroup analyses were done according to the status of diabetes. Compared to placebo, SGLT2 inhibitors significantly reduced heart failure hospitalization [risk ratio (RR) 0.70, 95% confidence interval (CI) 0.59–0.83] and kidney-specific composite outcome (RR 0.55, 95% CI 0.40–0.75) and increased Kansas City Cardiomyopathy Questionnaire total score by 1.15 (95% CI 1.05–1.25) in patients without T2DM with heart failure (HF) or chronic kidney disease (CKD), whereas gliflozins did not significantly affect cardiovascular death, all-cause mortality, volume depletion, fracture, and amputation in this vulnerable population. There was no event of major hypoglycemia or diabetic ketoacidosis observed in the non-T2DM subgroup in included trials. These findings will further prompt gliflozins to be used for the prevention of HF and renal failure events and for the improvement of life quality in patients without T2DM with HF or CKD.

Here, Zimmer et al. analyze the natural killer (NK) cell response in a patient cohort with acute dengue virus infection showing early NK cell activation and proliferation, and the data suggest that NK cell proliferation depends on IL-18 signaling, and that responding NK cells have a skin-homing phenotype.

Tricothecenes-2 toxin (T-2) is a major mycotoxin that is widely distributed in aquatic feeds and poses a huge challenge to the aquatic industry, but there is scant information on the toxicokinetics of T-2 in aquatic animals. Here, we describe the development of a three-compartment toxicokinetic model for the absorption, distribution, metabolism and elimination (ADME) of T-2 in shrimp. The three compartments were central (the hemolymph), slow metabolizing and fast metabolizing compartments to account for the varying ADME rates of T-2 in different shrimp organs. The toxicokinetic model was solved by the blindfold particle swarm optimization algorithm, and the values for the model equation parameters were obtained by applying the experimental data of T-2 concentrations in shrimp. The model had a good fit with the experimental data. It was revealed through the model that after i.m. administration, T-2 was rapidly absorbed into the hemolymph and distributed into shrimp organs. The hepatopancreas and intestine belonged to the fast and muscle to the slow metabolizing compartments, respectively, while the hemolymph had no capacity to metabolize T-2. The T-2 elimination rates in the hepatopancreas and intestine were similar and quite high while that in the muscle was very low. The methods used in developing and solving the model could be used for similar toxicokinetic and pharmacokinetic studies of other animals.

Fungal contamination of food, especially by mycotoxigenic fungi, not only reduces the quality of the food, but can also cause serious diseases, thus posing a major food safety challenge to humans. Apart from sound food control systems, there is also a continual need to explore antifungal agents that can inhibit fungal growth and mycotoxin production in food. Many types of fatty acids (FAs) and their oxidized derivatives, oxylipins, have been found to exhibit such effects. In this review, we provide an update on the most recent literature on the occurrence and formation of FAs and oxylipins in food, their effects on fungal growth and mycotoxin synthesis, as well as the genetic and molecular mechanisms of actions. Research gaps in the field and needs for further studies in order to realizing the potential of FAs and oxylipins as natural antifungal preservatives in food are also discussed.

Nanosizedceria (n-CeO2) was synthesized by a facile method in 2-methylimidazolesolution. The characterization results of XRD, N2 adsorption-desorption, Raman and TEM indicate that n-CeO2 shows a regular size of 10 ± 1 nm, a high surface area of 130 m2·g−1 and oxygen vacancies on the surface. A series of CuO/n-CeO2 catalysts (CuCeOX) with different copper loading were prepared for the preferential oxidation of CO in H2-rich gases (CO-PROX). All CuCeOX catalysts exhibit a high catalytic activity due to the excellent structural properties of n-CeO2, over which the 100% conversion of CO is obtained at 120 °C. The catalytic activity of CuCeOX catalysts increases in the order of CuCeO12 < CuCeO3 < CuCeO6 < CuCeO9. It is in good agreement with the order of the amount of active Cu+ species, Ce3+ species and oxygen vacancies on these catalysts, suggesting that the strength of interaction between highly dispersed CuO species and n-CeO2 is the decisive factor for the activity. The stronger interaction results in the formation of more readily reducible copper species on CuCeO9, which shows the highest activity with high stability and the broadest temperature “window” for complete CO conversion (120–180 °C).

The need for inclusive and equitable approaches to teaching and learning is a persistent theme in recent literature. In spite of relatively widespread agreement about this objective, inclusion remains elusive, and opinions about how best to achieve it proliferate. To provide a landscape view of the field and offer recommendations for research and practice, this article provides a focussed review of literature connected to inclusive teaching and learning published since 2010. Drawing from a framework advanced by Hockings (2010), we synthesize key findings from recent scholarship and argue for the value of a whole-of-institution approach that considers the activities and interactions of educational actors operating at different institutional levels. We also extend this argument to consider the need for greater attention to factors that move beyond the individual institution and to advocate for further international research in particular.

Zika virus (ZIKV), a flavivirus with homology to dengue virus (DENV), is spreading to areas of DENV hyper-endemicity. Heterologous T cell immunity, whereby virus-specific memory T cells are activated by variant peptides derived from a different virus, can lead to enhanced viral clearance or diminished protective immunity and altered immunopathology. In mice, CD8+ T cells specific for DENV provide in vivo protective efficacy against subsequent ZIKV infection. In humans, contrasting studies report complete absence or varying degrees of DENV/ZIKV T cell cross-reactivity. Moreover, the impact of cross-reactive T cell recognition on the anti-viral capacity of T cells remains unclear. Here, we show that DENV-specific memory T cells display robust cross-reactive recognition of ZIKV NS3 ex vivo and after in vitro expansion in respectively n = 7/10 and n = 9/9 dengue-immune individuals tested. In contrast, cross-reactivity toward ZIKV capsid is low or absent. Cross-reactive recognition of DENV or ZIKV NS3 peptides elicits similar production of the anti-viral effector mediators IFN-γ, TNF-α, and CD107a. We identify 9 DENV/ZIKV cross-reactive epitopes, 7 of which are CD4+ and 2 are CD8+ T cell epitopes. We also show that cross-reactive CD4+ and CD8+ T cells targeting novel NS3 epitopes display anti-viral effector potential toward ZIKV-infected cells, with CD8+ T cells mediating direct lyses of these cells. Our results demonstrate that DENV NS3-specific memory T cells display anti-viral effector capacity toward ZIKV, suggesting a potential beneficial effect in humans of pre-existing T cell immunity to DENV upon ZIKV infection.

BackgroundDengue is a major public health problem worldwide. Assessment of adaptive immunity is important to understanding immunopathology and to define correlates of protection against dengue virus (DENV). To enable global assessment of CD4+ T cell responses, we mapped HLA-DRB1-restricted DENV-specific CD4+ T cell epitopes in individuals previously exposed to DENV in the general population of the dengue-endemic region of Managua, Nicaragua.MethodsHLA class II epitopes in the population of Managua were identified by an in vitro IFNγ ELISPOT assay. CD4+ T cells purified by magnetic bead negative selection were stimulated with HLA-matched epitope pools in the presence of autologous antigen-presenting cells, followed by pool deconvolution to identify specific epitopes. The epitopes identified in this study were combined with those previously identified in the DENV endemic region of Sri Lanka, to generate a “megapool” (MP) consisting of 180 peptides specifically designed to achieve balanced HLA and DENV serotype coverage. The DENV CD4MP180 was validated by intracellular cytokine staining assays.ResultsWe detected responses directed against a total of 431 epitopes, representing all 4 DENV serotypes, restricted by 15 different HLA-DRB1 alleles. The responses were associated with a similar pattern of protein immunodominance, overall higher magnitude of responses, as compared to what was observed previously in the Sri Lanka region. Based on these epitope mapping studies, we designed a DENV CD4 MP180 with higher and more consistent coverage, which allowed the detection of CD4+ T cell DENV responses ex vivo in various cohorts of DENV exposed donors worldwide, including donors from Nicaragua, Brazil, Singapore, Sri Lanka, and U.S. domestic flavivirus-naïve subjects immunized with Tetravalent Dengue Live-Attenuated Vaccine (TV005). This broad reactivity reflects that the 21 HLA-DRB1 alleles analyzed in this and previous studies account for more than 80% of alleles present with a phenotypic frequency ≥5% worldwide, corresponding to 92% phenotypic coverage of the general population (i.e., 92% of individuals express at least one of these alleles).ConclusionThe DENV CD4 MP180 can be utilized to measure ex vivo responses to DENV irrespective of geographical location.

Synaptic activity increases the resistance of neurons to diverse apoptotic insults; however, the underlying mechanisms remain less well understood. Zinc promotes cell survival under varied conditions, but the role of synaptically released zinc in the activity-dependent anti-apoptotic effect is unknown. Using cultured hippocampal slices and primary neurons we show that a typical apoptosis inducer-staurosporine (STP) was able to cause concentration-dependent apoptotic cell death in brain slices; Enhanced synaptic activity by bicuculline (Bic)/4-Aminopyridine (AP) treatment effectively prevented neurons from STP-induced cell apoptosis, as indicated by increased cell survival and suppressed caspase-3 activity. Application of Ca-EDTA, a cell membrane-impermeable zinc chelator which can efficiently capture the synaptically released zinc, completely blocked the neuronal activity-dependent anti-apoptotic effect. Same results were also observed in cultured primary hippocampal neurons. Therefore, our results indicate that synaptic activity improves neuronal resistance to apoptosis via synaptically released zinc.

Zinc ions highly concentrate in hippocampus and play a key role in modulating spatial learning and memory. At a time when dietary fortification and supplementation of zinc have increased the zinc consuming level especially in the youth, the toxicity of zinc overdose on brain function was underestimated. In the present study, weaning ICR mice were given water supplemented with 15 ppm Zn (low dose), 60 ppm Zn (high dose) or normal lab water for 3 months, the behavior and brain zinc homeostasis were tested. Mice fed high dose of zinc showed hippocampus-dependent memory impairment. Unexpectedly, zinc deficiency, but not zinc overload was observed in hippocampus, especially in the mossy fiber-CA3 pyramid synapse. The expression levels of learning and memory related receptors and synaptic proteins such as NMDA-NR2A, NR2B, AMPA-GluR1, PSD-93 and PSD-95 were significantly decreased in hippocampus, with significant loss of dendritic spines. In keeping with these findings, high dose intake of zinc resulted in decreased hippocampal BDNF level and TrkB neurotrophic signaling. At last, increasing the brain zinc level directly by brain zinc injection induced BDNF expression, which was reversed by zinc chelating in vivo. These results indicate that zinc plays an important role in hippocampus-dependent learning and memory and BDNF expression, high dose supplementation of zinc induces specific zinc deficiency in hippocampus, which further impair learning and memory due to decreased availability of synaptic zinc and BDNF deficit.