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Background and purposeThe gut-brain axis is bidirectional and the imbalance of the gut microbiota usually coexists with brain diseases, including Alzheimer’s disease (AD). Accumulating evidence indicates that endoplasmic reticulum (ER) stress is a core lesion in AD and persistent ER stress promotes AD pathology and impairs cognition. However, whether the imbalance of the gut microbiota is involved in triggering the ER stress in the brain remains unknown.Materials and methodsIn the present study, fecal microbiota transplantation (FMT) was performed with gut microbiota from AD patients and APP/PS1 mice, respectively, resulting in two mouse models with dysregulated gut microbiota. The ER stress marker protein levels in the cerebral cortex were assessed using western blotting. The composition of the gut microbiota was assessed using 16S rRNA sequencing.ResultsExcessive ER stress was induced in the cerebral cortex of mice after FMT. Elevated ER stress marker proteins (p-perk/perk, p-eIF2α/eIF2α) were observed, which were rescued by 3,3-dimethyl-1-butanol (DMB). Notably, DMB is a compound that significantly attenuates serum trimethylamine-N-oxide (TMAO), a metabolite of the gut microbiota widely reported to affect cognition.ConclusionThe findings indicate that imbalance of the gut microbiota induces ER stress in the cerebral cortex, which may be mediated by TMAO.

Southern corn rust (SCR) caused by Puccinia polysora Underw. poses a major threat to maize production worldwide. The utilization of host SCR-resistance genes and the cultivation of resistant cultivars are the most effective, economical strategies for controlling SCR. Here, we identified and cloned a new SCR resistance gene, RppM, from the elite maize inbred line Jing2416K. RppM was found to encode a typical CC-NBS-LRR protein localized in both the nucleus and cytoplasm. This gene was constitutively expressed at all developmental stages and in all tissues examined, with the strongest expression detected in leaves at the mature stage. A transcriptome analysis provided further evidence that multiple defense systems were initiated in Jing2416K, including pathogen-associated molecular pattern-triggered immunity and effector-triggered immunity, reinforcement of cell walls, accumulation of antimicrobial compounds, and activation of phytohormone signaling pathways. Finally, we developed functional Kompetitive allele-specific PCR markers for RppM using two conserved SNP sites and successfully applied these functional markers for the detection of RppM and the cultivation of resistant maize cultivars, demonstrating their great potential utility in maize breeding.

The rapid development of high-throughput phenotypic detection techniques makes it possible to obtain a large number of crop phenotypic information quickly, efficiently, and accurately. Among them, image-based phenotypic acquisition method has been widely used in crop phenotypic identification and characteristic research due to its characteristics of automation, non-invasive, non-destructive and high throughput. In this study, we proposed a method to define and analyze the traits related to leaf sheaths including morphology-related, color-related and biomass-related traits at V6 stage. Next, we analyzed the phenotypic variation of leaf sheaths of 418 maize inbred lines based on 87 leaf sheath-related phenotypic traits. In order to further analyze the mechanism of leaf sheath phenotype formation, 25 key traits (2 biomass-related, 19 morphology-related and 4 color-related traits) with heritability greater than 0.3 were analyzed by genome-wide association studies (GWAS). And 1816 candidate genes of 17 whole plant leaf sheath traits and 1,297 candidate genes of 8 sixth leaf sheath traits were obtained, respectively. Among them, 46 genes with clear functional descriptions were annotated by single nucleotide polymorphism (SNPs) that both Top1 and multi-method validated. Functional enrichment analysis results showed that candidate genes of leaf sheath traits were enriched into multiple pathways related to cellular component assembly and organization, cell proliferation and epidermal cell differentiation, and response to hunger, nutrition and extracellular stimulation. The results presented here are helpful to further understand phenotypic traits of maize leaf sheath and provide a reference for revealing the genetic mechanism of maize leaf sheath phenotype formation.

We prove that the group $\mathrm{QI}^{+}(\mathbb{R})$ of orientation-preserving quasi-isometries of the real line is a left-orderable, non-simple group, which cannot act effectively on the real line $\mathbb{R}.$, Minor changes; final version, to appear in Algebraic and Geometric Topology

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The determination of the total amount of water pollutant emission in different regions is a difficult problem faced by managers and researchers. Previous studies mostly focused on operability and fairness with little attention paid to local water quality. In order to make total emission pollutant control (TEPC) truly serve the improvement of water quality, a water total emission pollutant allocation model was built based on water environmental carrying capacity (WECC) in this paper. This model was used to construct a water pollutant emission control allocation scheme for 28 cities in Henan Province, China. The results showed that the chemical oxygen demand (COD) reduction rates for these cities ranged from 16.8 to 38.6% and ammonia-nitrogen (NH3-N) reduction rates ranged from 5.7 to 43.5% in 2020, which were different from the previous targets for these cities without considering their current status of water quality. The largest COD reduction rates for different types of point sources (industrial, urban, and large-scale livestock sources) were 35.4%, 39.0%, and 38.0%, respectively, and the largest NH3-N reduction rates were 62.2%, 42.5%, and 43.5%, respectively. This study solves the problem of long-term disconnection between TEPC and water quality improvement in China. The results can also be applied to implement the TEPC to improve water quality in other regions with a similar problem.

Additional file 5: Fig. S5. sEV miRNA expression profile. (A–C) sEVs were isolated from glutamate (15 μM), GABA (500 μM), or PBS-treated neurons, and the miRNA composition of sEVs was compared by miRNA-sequencing. (A) miRNA sequencing showed 41 upregulated miRNAs in GABA sEVs and 14 downregulated miRNAs in glutamate sEVs compared to Ctrl sEVs. 4 repeated miRNAs were identified in both groups. (B) There were 64 downregulated miRNAs in GABA sEVs and 47 upregulated miRNAs in glutamate sEVs compared with Ctrl sEVs. A total of 12 miRNAs overlapped in both groups. (C) An aggregate of 16 miRNAs (p < 0.05).

Additional file 7: Fig. S7. sEVs with inhibited or over-expressed miR-132 abrogated Glutamate/GABA sEVs induced alterations of apoptotic molecules and synapse-related proteins in APP/PS1 mice, respectively. (A) Cy3-labeled agomir-132 was loaded into sEVs and injected into mice. Twenty-four hours later, the brain slices showed overlapped Cy3-labeled agomir-132-loaded sEVs (red) and NeuN+-neurons (green). (B-O) The mice were injected with glutamate sEVs/Ctrl sEVs and agomir-132/agomir ctrl (B-H) and GABA sEVs/Ctrl sEVs and antagomir-132/antagomir ctrl (I-O)-loaded sEVs at every other day for seven consecutive injections. The expression of apoptotic molecules (cleaved Caspase-3, Bax, and Bcl-2) and synapse-related proteins (Synapsin I, Synapsin I (phospho S9), postsynaptic density-95 (PSD-95)) in the brain lysate of mice was examined by Western blot. n = 3. Data are presented as the mean ± SEM, *p

Additional file 4: Fig. S4. Internalization of PKH-26 labeled sEVs by neurons in APP/PS1 mice. (A) sEVs were labeled with PKH26 (red) and injected via the tail vein in mice. Brain slices were harvested and subjected to the immunostaining of the neuron marker NeuN (green) and visualized. The control group mice were injected with PKH26 only without sEVs. n = 3.

Additional file 1: Fig. S1. sEVs-depleted medium had no effect on the cell viability of Aβ-treated neurons. (A) Image of cultured primary cortical neurons on DIV 15. (B) Immunostaining of cortical cultures on DIV 15 for the detection of GFAP+ glial cells (red) vs. NeuN+ neurons (green). (C) The morphology of sEVs from glutamate or GABA-treated neurons was observed under a transmission electron microscope. Glutamate sEVs = sEVs derived from 10 μM glutamate-treated neurons, GABA sEVs = sEVs derived from 300 μM GABA-treated neurons. (D-F) Neurons were incubated with PBS (the same amount as the solvent of the sEVs), sEVs and sEV-depleted medium (Negative control, NC), then with Aβ as before. Neuronal viability in Ctrl-sEV-treated group (D), glutamate-sEV-treated group (E), GABA-sEV-treated group (F) and NC group were compared using CCK-8. n = 3. Data are presented as the mean ± SEM, ***p

Additional file 3: Fig. S3. Function of sEVs from neurons treated by various concentrations of glutamate or GABA. (A) Primary neurons on DIV 15 were treated with a gradient concentration of Aβ1–42 for 48 h. Cell viability was measured using a CCK-8 assay. (B–I) sEVs were isolated from low concentrations of glutamate (5 μM)/GABA (100 μM), or high concentrations of glutamate (15 μM)/GABA (500 μM) and added to the culture media. Cell viability was measured using CCK-8 (D, E, H, I) and TUNEL assays (B, C, F, G). Glutamate5 sEVs = sEVs derived from 5 μM glutamate treated neurons, GABA100 sEVs = sEVs derived from 100 μM GABA-treated neurons, Glutamate15 sEVs = sEVs derived from 15 μM glutamate-treated neurons, GABA500 sEVs = sEVs derived from 500 μM GABA treated neurons, Ctrl sEVs = sEVs derived from PBS-treated neurons. n = 3. Data are presented as the mean ± SEM, *p

Additional file 6: Fig. S6. sEVs with inhibited or over-expressed miR-132 abrogated Glutamate/GABA sEVs induced alterations of apoptotic molecules in Aβ treated neurons, respectively. (A, B) TUNEL- positive rate of neurons in Fig. 6C and D were calculated. (C–J) Neurons were cotreated with glutamate sEVs and miR-132 mimic-loaded sEVs (C, E–G) or GABA sEVs and miR-132 inhibitor-loaded sEVs (D, H–J). 24 h later, neurons were subjected to Aβ treatment for another 48 h. Then, the expression of apoptotic molecules (cleaved Caspase-3, Bax, and Bcl-2). (K, L) The proportion of TUNEL-positive cells in brain slices in Fig. 6E and F was detected. n = 3. Data are presented as the mean ± SEM, *p

Additional file 2: Fig. S2. Internalization of PKH26 labeled sEVs in primary cultured neurons. (A) sEVs were labeled with PKH26 (red) and added to primary neurons. A control group (only PKH26 without sEVs) was established to exclude false-positive staining caused by the dye. Then, the neurons were immunostained with βIII-tubulin (green) and visualized under a confocal microscope. PKH26 -labeled sEVs were indicated by white arrows. n = 3.

Background Sodium toxicity and potassium insufficient are important factors affecting the growth and development of maize in saline soil. The monovalent cation proton antiporter (CPA) superfamily comprises Na + /H + exchanger (NHX), K + efflux antiporter (KEA), and cation/H + exchanger (CHX) subfamily proteins, which play vital functions in maize salt tolerance. Results A total of 35 ZmCPA genes were identified in maize, and they were phylogenetically classified into 13 ZmNHXs , 16 ZmCHXs and 6 ZmKEAs . ZmCPA genes have a conserved gene structure, with the determined introns range from 11 to 25, 0 to 5 and 16 to 19 in ZmNHXs, ZmCHXs, ZmKEAs , respectively. All proteins have transmembrane domains, with an average transmembrane number of 8, 10, and 10 in ZmNHX, ZmCHX and ZmKEA proteins, respectively. Transient expression in maize protoplasts showed that ZmCHX16 and ZmNHX8 are located in the cell membrane. All ZmCHX subfamily genes showed lower expression compared to ZmNHX and ZmKEA subfamilies. Diverse expression in the 60 tissues and modulated expression in response to salt stress suggested ZmCPAs’ role in maize development and salt stress. Yeast complementary experiment revealed the function of ZmNHX8 , ZmCHX8 , - 12 , - 14 , - 16 and ZmKEA6 in salt tolerance. Maize mutants zmnhx8 and zmkea6 further validated the important function of ZmNHX8 and ZmKEA6 in salt tolerance. Phosphorylation sites and cis -acting regulation elements analyses indicated that phosphorylation and transcriptional regulation may be involved in salt tolerance of ZmCPA genes. Conclusions Our study provides comprehensive information about ZmCPA gene superfamily, which would be useful in their future functional characterization.

Alzheimer’s disease (AD) is the most common cause of dementia. Despite numerous studies on the subject, the pathologies for AD are still unclear and there is still no ideal biomarker for diagnosis. The present study aimed to investigate clinical significance of human complement factor H (CFH) in patients with late-onset AD. Methods: The present prospective study included 187 late-onset AD patients who went to our hospital from January 2015 to December 2017. One hundred patients with mild cognitive impairment (MCI) and 80 healthy individuals who were age and gender matched to AD patients were enrolled as controls. Demographic data such as age, gender, and education duration were recorded. Blood samples were collected and serum levels of C-reactive protein (CRP), CFH, and brain-derived neurotrophic factor (BDNF) were determined by Enzyme-linked immunosorbent assay (ELISA). The mini-mental state examination (MMSE) score was measured for all patients. Results: No significant difference was found in age, gender, and education duration for all participants. The MMSE scores showed AD patients had lower MMES scores than the other two groups. All factors of CFH, CRP, and BDNF were dramatically decreased in AD patients compared with the MCI and the ealthy control. Levels of CFH were found to be positively correlated with levels of CRP; however, no significant correlation was found between CFH and BDNF, nor CFH and MMSE. Conclusion: CFH was decreased in late-onset AD patients, and serum levels of CFH was correlated with serum levels of CRP, but not MMSE and BDNF. These results may provide more clinical evidences for the role of CFH in AD patients. Resumo A doença de Alzheimer (DA) é a causa mais comum de demência. Apesar de inúmeros estudos sobre DA, suas patologias ainda não são claras e ainda não existe um biomarcador ideal para o diagnóstico da condição. O presente estudo teve como objetivo investigar a significância clínica do fator H do complemento humano (CFH) em pacientes com DA de início tardio. Métodos: O presente estudo prospectivo incluiu um total de 187 pacientes com DA de início tardio que foram ao nosso hospital entre janeiro de 2015 e dezembro de 2017. Cem pacientes com comprometimento cognitivo leve (CCL) e 80 indivíduos saudáveis com idade e sexo pareados com pacientes com DA foram incluídos como controle. Dados demográficos como idade, sexo e duração da educação foram registrados. As amostras de sangue foram coletadas e os níveis séricos de proteína C-reativa (PCR), CFH e fator neurotrófico derivado do cérebro (BDNF) foram determinados pelo ensaio imunoabsorvente ligado à enzima (ELISA). O escore do miniexame do estado mental (MEEM) foi medido para todos os pacientes. Resultados: Não foram encontradas diferenças significativas em idade, sexo e duração da educação para todos os participantes. Pacientes com DA tinham os menores escores de MEEM em relação aos outros dois grupos. Todos os fatores de CFH, PCR e BDNF diminuíram drasticamente em pacientes com DA em comparação com o CCL e o controle saudável. Os níveis de CFH mostraram correlação positiva com os níveis de PCR; no entanto, não foi encontrada correlação significativa entre CFH e BDNF, nem CFH e MEEM. Conclusão: A CFH diminuiu nos pacientes com DA de início tardio e os níveis séricos de CFH foram correlacionados com os níveis séricos de PCR, mas não o MEEM e o BDNF. Esses resultados podem fornecer mais evidências clínicas do papel da CFH em pacientes com DA.

Sigma receptor is an endoplasmic reticulum protein and belongs to non-opioid receptor. Increasing evidence shows that Sigma receptor activation can significantly attenuate AD induced neurological dysfunction and the functional deficiency of Sigma receptor plays an important role in the Aβ induced neuronal loss. This study aimed to investigate the influence of extracellular accumulation of Aβ on the Sigma receptor expression. Our results showed the increase in extracellular Aβ had little influence on the mRNA expression of Sigma receptor, but gradually reduced its protein expression. Co-immunoprecipitation was employed to evaluate the interaction of Sigma receptor with other proteins. Results showed BIP could bind to Sigma receptor to affect the ubiquitination of Sigma receptor. Further investigation showed there was a NFAT binding site at the promoter of BIP. Then, Western blot assay was performed to detect NFAT expression. Results showed extracellular Aβ affected the nuclear translocation of NFAT and the CaN activity of NFAT also increased with the accumulation of extracellular Aβ. In this study, NFAT-BIP luciferase reporter gene system was constructed. Results showed NFAT was able to regulate the transcription of BIP. Thus, we speculate that extracellular Aβ accumulation may activate CaN/NFAT signaling pathway to induce chaperone BIP expression, which results in Sigma receptor ubiquitination and its degradation.

Background: Diabetes is proved to be one of the independent risk factors for cognitive dysfunction. The pathophysiologic changes caused by diabetes including hyperglycemia and tissue hypoxia may contribute greatly to cognitive decline. In the present study, we demonstrate E3 Ubiquitin Ligase Siah-1 downregulates the key synaptic protein Synaptophysin expression under high glucose and hypoxia condition which may be the underlying factor leading to cognitive dysfunction in diabetic patients. Methods: In this study, hypoxia (2% oxygen) and high glucose (50 mM) were used to treat primary neuronal culture. By using quantitative PCR and western blotting we determined the influence of hypoxia and high glucose on the expression of synaptophysin and Siah-1 and the phosphorylated forms of extracellular signal-regulated kinase (ERK). Knockdown of Siah-1, inhibitors for proteasome, lysosome and ERK kinase was employed to evaluate the role of Siah-1 and ERK activity on the expression of synaptophysin. By immunoprecipitation we also examined the role of Siah-1 in the ubiquitination of synaptophysin under hypoxic and hyperglycemic condition. Results: We demonstrated that hypoxia and high glucose together but not hypoxia or high glucose along mediated posttranscriptional reduction of synaptophysin with increased ERK phosphorylation and Siah-1 expression. The downregulation of synaptophysin was reversed by inhibition of ERK and Siah-1 knockdown. Overexpression of Siah-1 accelerated the degradation of synaptophysin under hypoxia and high glucose conditions and promoted the ubiquitination of synaptophysin. Conclusions: The present results demonstrate that Siah-1 is the key factor that contributes to hypoxia and high glucose mediated synaptophysin degradation.

Selecting an appropriate air-conditioning system for villa is important for maintaining a comfortable indoor environment, energy saving and environmental protection, etc. The paper gives a study on selection of air-conditioning system for villa based on value engineering methodology. According to the principle of value engineering, a mathematical model for selection of villa air-conditioning system is constructed. The model mainly deals with the function analysis of villa air-conditioning system and formulates a value engineering method to evaluate villa air-conditioning system schemes. Value index which combines the technical and economic characters of schemes is used as an evaluation parameter to select the optimal scheme. An application case is studied using the evaluation model, and the selected scheme is in line with the actual engineering.

By technical-economic calculation of the gas pipeline network, the economic diameter can be determined and the project investment can be saved. According to the principle of value engineering, a mathematical model is constructed for technical-economic calculation of the gas pipeline network. The function of gas pipeline network is analyzed and is divided into four parts: gas transport, gas distribution, pressure transport and gas storage, and the measurement method of each part is given. 0-4 grade method is used to determine the functions’ weight. By calculating the function coefficients and cost coefficients, the value index of gas pipeline is determined. The value index provides some good advice for technical-economic calculation of the gas pipeline network. A case of branched gas pipeline network is studied using the value engineering model, the results show the investment of the network can be saved about 4.76 percent under the premise of meeting the technical requirements.

Water-source heat pump system is an air-conditioning device using water as heat source/heat-exhaust source for heating/cooling cycle. The relative stabilization of water temperature ensures the higher coefficient of performance (COP). Using water-source heat pump system can reduce the pollution emission, which is benefit for the environment. Comparing with the traditional systems for heating and cooling, the investment and operating costs of the water-source heat pump system is lower and the system can be a multi-purpose machine for heating, air-conditioning and the provision of domestic hot water. Water-source heat pump system has the advantages of running stably and control and maintenance expediently. So the water-source heat pump system should be promoted as green environmentally friendly products.