Communications between Neutrophil-Endothelial Interaction in Immune Defense against Bacterial Infection.

The endothelial barrier plays a critical role in immune defense against bacterial infection. Efficient interactions between neutrophils and endothelial cells facilitate the activation of both cell types. However, neutrophil activation can have dual effects, promoting bacterial clearance on one hand while triggering inflammation on the other. In this review, we provide a detailed overview of the cellular defense progression when neutrophils encounter bacteria, focusing specifically on neutrophil-endothelial interactions and endothelial activation or dysfunction. By elucidating the underlying mechanisms of inflammatory pathways, potential therapeutic targets for inflammation caused by endothelial dysfunction may be identified. Overall, our comprehensive understanding of neutrophil-endothelial interactions in modulating innate immunity provides deeper insights into therapeutic strategies for infectious diseases and further promotes the development of antibacterial and anti-inflammatory drugs.

Remediation of oil-polluted soil using anionic and non-ionic composite biosurfactants.

Petroleum hydrocarbons as pervasive pollutants pose a significant threat to soil ecology and human health. Surfactant washing as an established technique can effectively remediate soils contaminated by hydrocarbons. Biosurfactants, which combine the properties of surfactants and environmental compatibility, have attracted increasing interest. However, due to the high production cost of biosurfactants, their practical application is restricted. This study addressed these limitations by selecting two biosurfactants, ß-cyclodextrin (C1) and sodium carboxymethyl cellulose (C2), and developed a promising cleaning agent formula through compounding and the addition of suitable additives. When the volume ratio of C1 to C2 was 8:2 and an 8 g/L mixture of sodium humate and sodium carbonate electrolyte was added, the surfactant system's surface tension reached a minimum, yielding optimal oil removal. The formation and synergistic behaviour of mixed micelles of surfactants were explained using ideal solution theory and the Rubingh model. By optimising the oil washing process parameters - normal temperature of 25 °C, pH 11, washing time of 2 h, solid-liquid ratio of 1:5, and oscillation frequency of 200 r/min - the oil removal rate achieved 76%. This cleaning agent, characterised by low production cost, straightforward application, environmental compatibility, and rapid, significant cleaning effect, shows potential for field-scale purification of petroleum-contaminated soil.

DDAH-1 maintains endoplasmic reticulum-mitochondria contacts and protects dopaminergic neurons in Parkinson's disease.

The loss of dopaminergic neurons in the substantia nigra is a hallmark of pathology in Parkinson's disease (PD). Dimethylarginine dimethylaminohydrolase-1 (DDAH-1) is the critical enzyme responsible for the degradation of asymmetric dimethylarginine (ADMA) which inhibits nitric oxide (NO) synthase and has been implicated in neurodegeneration. Mitochondrial dysfunction, particularly in the mitochondria-associated endoplasmic reticulum membrane (MAM), plays a critical role in this process, although the specific molecular target has not yet been determined. This study aims to examine the involvement of DDAH-1 in the nigrostriatal dopaminergic pathway and PD pathogenesis. The distribution of DDAH-1 in the brain and its colocalization with dopaminergic neurons were observed. The loss of dopaminergic neurons and aggravated locomotor disability after rotenone (ROT) injection were showed in the DDAH-1 knockout rat. L-arginine (ARG) and NO donors were employed to elucidate the role of NO respectively. In vitro, we investigated the effects of DDAH-1 knockdown or overexpression on cell viability and mitochondrial functions, as well as modulation of ADMA/NO levels using ADMA or ARG. MAM formation was assessed by the Mitofusin2 oligomerization and the mitochondrial ubiquitin ligase (MITOL) phosphorylation. We found that DDAH-1 downregulation resulted in enhanced cell death and mitochondrial dysfunctions, accompanied by elevated ADMA and reduced NO levels. However, the recovered NO level after the ARG supplement failed to exhibit a protective effect on mitochondrial functions and partially restored cell viability. DDAH-1 overexpression prevented ROT toxicity, while ADMA treatment attenuated these protective effects. The declines of MAM formation in ROT-treated cells were exacerbated by DDAH-1 downregulation via reduced MITOL phosphorylation, which was reversed by DDAH-1 overexpression. Together, the abundant expression of DDAH-1 in nigral dopaminergic neurons may exert neuroprotective effects by maintaining MAM formation and mitochondrial function probably via ADMA, indicating the therapeutic potential of targeting DDAH-1 for PD.

Maize ZmHSP90 plays a role in acclimation to salt stress.

Background: Maize is sensitive to salt stress, especially during the germination and seedling stages. Methods: We conducted germination experiments on 60 maize materials under salt stress, and screened out the most salt-tolerant and salt-sensitive varieties based on germination indicators. Afterwards, transcriptome analysis was performed to screen for key regulators in the plumule and flag leaf at the germination and seedling stages, respectively. Following that, transgenic tobacco was developed to expose the roles and mechanisms of the candidate genes, enabling a deeper investigation of their functions. Results: Out of the 60 inbred lines of maize, "975-12" exhibits the highest level of salt tolerance, while "GEMS64" displays the lowest. The application of salt stress resulted in a significant increase in the levels of antioxidant enzymes in both "975-12" and "GEMS64". ABA signal transduction and jasmonic acid pathways were the pathways that mainly affected by salt stress. In addition, a significant finding has been made indicating that when exposed to high levels of salt stress, the expression of ZmHSP90 in '975-12' increased while in 'GEMS64' decreased. Furthermore, in tobacco plants overexpressing ZmHSP90, there was an increase in antioxidant enzyme activity associated with salt tolerance. ZmHSP90 enhanced the expression levels of NtSOS1, NtHKT1, and NtNHX1 as compared to those in the salt treatment, causing the maintenance of Na+ and K+ homeostasis, suggesting that high expression of ZmHSP90 was conducive to regulate Na+ transporters to maintain K+/Na+ balanced in tobacco.

Using High-Throughput Phenotyping Analysis to Decipher the Phenotypic Components and Genetic Architecture of Maize Seedling Salt Tolerance.

Soil salinization is a worldwide problem that limits agricultural production. It is important to understand the salt stress tolerance ability of maize seedlings and explore the underlying related genetic resources. In this study, we used a high-throughput phenotyping platform with a 3D laser sensor (Planteye F500) to identify the digital biomass, plant height and normalized vegetation index under normal and saline conditions at multiple time points. The result revealed that a three-leaf period (T3) was identified as the key period for the phenotypic variation in maize seedlings under salt stress. Moreover, we mapped the salt-stress-related SNPs and identified candidate genes in the natural population via a genome-wide association study. A total of 44 candidate genes were annotated, including 26 candidate genes under normal conditions and 18 candidate genes under salt-stressed conditions. This study demonstrates the feasibility of using a high-throughput phenotyping platform to accurately, continuously quantify morphological traits of maize seedlings in different growing environments. And the phenotype and genetic information of this study provided a theoretical basis for the breeding of salt-resistant maize varieties and the study of salt-resistant genes.

Genomic analysis of a new heterotic maize group reveals key loci for pedigree breeding.

Genome-wide analyses of maize populations have clarified the genetic basis of crop domestication and improvement. However, limited information is available on how breeding improvement reshaped the genome in the process of the formation of heterotic groups. In this study, we identified a new heterotic group (X group) based on an examination of 512 Chinese maize inbred lines. The X group was clearly distinct from the other non-H&L groups, implying that X × HIL is a new heterotic pattern. We selected the core inbred lines for an analysis of yield-related traits. Almost all yield-related traits were better in the X lines than those in the parental lines, indicating that the primary genetic improvement in the X group during breeding was yield-related traits. We generated whole-genome sequences of these lines with an average coverage of 17.35× to explore genome changes further. We analyzed the identity-by-descent (IBD) segments transferred from the two parents to the X lines and identified 29 and 28 IBD conserved regions (ICRs) from the parents PH4CV and PH6WC, respectively, accounting for 28.8% and 12.8% of the genome. We also identified 103, 89, and 131 selective sweeps (SSWs) using methods that involved the π, Tajima's D, and CLR values, respectively. Notably, 96.13% of the ICRs co-localized with SSWs, indicating that SSW signals concentrated in ICRs. We identified 171 annotated genes associated with yield-related traits in maize both in ICRs and SSWs. To identify the genetic factors associated with yield improvement, we conducted QTL mapping for 240 lines from a DH population (PH4CV × PH6WC, which are the parents of X1132X) for ten key yield-related traits and identified a total of 55 QTLs. Furthermore, we detected three QTL clusters both in ICRs and SSWs. Based on the genetic evidence, we finally identified three key genes contributing to yield improvement in breeding the X group. These findings reveal key loci and genes targeted during pedigree breeding and provide new insights for future genomic breeding.

Pollution source identification and abatement for water quality sections in Huangshui River basin, China.

Accurately obtaining the pollution sources and their contribution rates is the basis for refining watershed management. Although many source analysis methods have been proposed, a systematic framework for watershed management is still lacking, including the complete process of pollution source identification to control. We proposed a framework for identification and abatement of pollutants and applied in the Huangshui River Basin. A newer contaminant flux variation method based on a one-dimensional river water quality model was used to calculate the contribution of pollutants. The contributions of various factors to the over-standard parameters of water quality sections at different spatial and temporal scales were calculated. Based on the calculation results, corresponding pollution abatement projects were developed, and the effectiveness of the projects was evaluated through scenario simulation. Our results showed that the large scale livestock and poultry farms and sewage treatment plants were the largest sources of total nitrogen (TP) in Xiaoxia bridge section, with contribution rates of 46.02% and 36.74%, respectively. Additionally, the largest contribution sources of ammonia nitrogen (NH3-N) were sewage treatment plants (36.17%) and industrial sewage (26.33%). Three towns that contributed the most to TP were Lejiawan Town (14.4%), Ganhetan Town (7.3%) and Handong Hui Nationality town (6.6%), while NH3-N mainly from the Lejiawan Town (15.9%), Xinghai Road Sub-district (12.4%) and Mafang Sub-district (9.5%). Further analysis found that point sources in these towns were the main contributor to TP and NH3-N. Accordingly, we developed abatement projects for point sources. Scenario simulation indicated that the TP and NH3-N could be significantly improved by closing down and upgrading relevant sewage treatment plants and building facilities for large scale livestock and poultry farms. The framework adopted in this study can accurately identify pollution sources and evaluate the effectiveness of pollution abatement projects, which is conducive to the refined water environment management.

High-Temperature Metal-Free Molecular Ferroelectrics with Large Spontaneous Polarization.

In the past two decades, numerous molecular ferroelectrics have been reported. However, metal-free molecular ferroelectrics with high working temperatures and large spontaneous polarizations are still uncommon. Herein, we present two metal-free molecular ferroelectrics prepared from monoprotonated hexamethylenetetramine (HMTA), namely (HMTAH)Cl and (HMTAH)Br, which crystallize in a polar point group of 3m. In these crystals, the polar HMTAH+ organic cations can be reoriented 180° along the polar axis because of the quasispherical molecular geometry. As a result of the large shift of the positively charged protonated N atoms, these compounds demonstrate large spontaneous polarizations with values of 8.3 and 8.1 µC cm-2 and high working temperatures of 390 and 435 K, respectively. The ferroelectric property of these compounds is characterized with second-harmonic generation, ferroelectric hysteresis loop, and pyroelectric current measurements.

Genetic basis of the oil biosynthesis in ultra-high-oil maize grains with an oil content exceeding 20.

Vegetable oil is an important part of the human diet and has multiple industrial uses. The rapid increase in vegetable oil consumption has necessitated the development of viable methods for optimizing the oil content of plants. The key genes regulating the biosynthesis of maize grain oil remain mostly uncharacterized. In this study, by analyzing oil contents and performing bulked segregant RNA sequencing and mapping analyses, we determined that su1 and sh2-R mediate the shrinkage of ultra-high-oil maize grains and contribute to the increase in the grain oil content. Functional kompetitive allele-specific PCR (KASP) markers developed for su1 and sh2-R detected su1su1Sh2Sh2, Su1Su1sh2sh2, and su1su1sh2sh2 mutants among 183 sweet maize inbred lines. An RNA sequencing (RNA-seq) analysis indicated that genes differentially expressed between two conventional sweet maize lines and two ultra-high-oil maize lines were significantly associated with linoleic acid metabolism, cyanoamino acid metabolism, glutathione metabolism, alanine, aspartate, and glutamate metabolism, and nitrogen metabolism. A bulk segregant analysis and sequencing (BSA-seq) analysis identified another 88 genomic intervals related to grain oil content, 16 of which overlapped previously reported maize grain oil-related QTLs. The combined analysis of BSA-seq and RNA-seq data enabled the identification of candidate genes. The KASP markers for GRMZM2G176998 (putative WD40-like beta propeller repeat family protein), GRMZM2G021339 (homeobox-transcription factor 115), and GRMZM2G167438 (3-ketoacyl-CoA synthase) were significantly related to maize grain oil content. Another candidate gene, GRMZM2G099802 (GDSL-like lipase/acylhydrolase), catalyzes the final step of the triacylglycerol synthesis pathway and was expressed at significantly higher levels in the two ultra-high-oil maize lines than in the two conventional sweet maize lines. These novel findings will help clarify the genetic basis of the increased oil production in ultra-high-oil maize lines with grain oil contents exceeding 20%. The KASP markers developed in this study may be useful for breeding new high-oil sweet maize varieties.

Effects of microplastics and nitrogen deposition on soil multifunctionality, particularly C and N cycling.

Both nitrogen deposition (ND) and microplastics (MPs) pose global change challenges. The effects of MPs co-existing with ND on ecosystem functions are still largely unknown. Herein, we conducted a 10-month soil incubation experiment to explore the effects of polyethylene (PE) and polylactic acid (PLA) MPs on soil multifunctionality under different ND scenarios. We found that the interactions between ND and MPs affected soil multifucntionality. FAPROTAX function prediction indicated that both ND and MPs affected C and N cycling. ND increased some C-cycling processes, such as cellulolysis, ligninolysis, and plastic degradation. MPs also showed stimulating effects on these processes, particularly in the soil with ND. ND significantly decreased the abundance of functional genes NifH, amoA, and NirK, leading to inhibited N-fixation, nitrification, and denitrification. The addition of MPs also modified N-cycling processes: 0.1% PE enriched the bacterial groups for nitrate reduction, nitrate respiration, nitrite respiration, and nitrate ammonification, and 1% PLA MPs enriched N-fixation bacteria at all ND levels. We found that ND caused lower soil pH but higher soil N, decreased bacterial diversity and richness, and changed the composition and activity of functional bacteria, which explains why ND changed soil functions and regulated the impact of MPs.

Activation of TRPV4 induces intraneuronal tau hyperphosphorylation via cholesterol accumulation.

Transient receptor potential vanilloid 4 (TRPV4) is a non-selective cation channel, whose aberrant function in neurons has been reported to participate in the progression of brain disorders, including Alzheimer's disease (AD). However, the influence of TRPV4 activation on tau hyperphosphorylation in AD has not yet been elucidated. Since disturbed brain cholesterol homeostasis is considered to be related to excessive tau phosphorylation, this study aimed to explore whether dysregulation of TRPV4 affects tau phosphorylation and whether it involves cholesterol unbalance. Our data indicated that TRPV4 activation increased tau phosphorylation in the cortex and hippocampus of P301S tauopathy mouse model and aggravated its cognitive decline. In addition, we detected that TRPV4 activation upregulated cholesterol levels in primary neurons, and the elevation of cholesterol promoted hyperphosphorylation of tau. TRPV4 knockdown improved tau hyperphosphorylation by reducing intracellular cholesterol accumulation. Our results suggest that activation of TRPV4 may take part in the pathological mechanism of AD by promoting intraneuronal tau hyperphosphorylation in a cholesterol-dependent manner.

Inversion of Molecular Chirality Associated with Ferroelectric Switching in a High-Temperature Two-Dimensional Perovskite Ferroelectric.

Controlling molecular chirality by external stimuli is of great significance in both fundamental research and technological applications. Herein, we report a high-temperature (384 K) molecular ferroelectric of a Cu(II) complex whose spontaneous polarization can be switched associated with flipping of molecular chirality. In this two-dimensional perovskite structure, the inorganic layer is separated by (NH3(CH2)2SS(CH2)2NH3)2+ organic cations skewed in a chiral conformation (P- or M-helicity in an individual crystal). As the stereodynamic disulfide bridge determines the molecular dipole moment along the polar axis, the chiral organic cation can be converted to its enantiomer as a consequence of an electric field-induced shift of the S-S moiety relative to its screw axis during the ferroelectric switching. The variation of the molecular chirality is examined with single-crystal X-ray diffraction and circular dichroism spectra. The simultaneous switching of molecular chirality and spontaneous polarization in this perovskite ferroelectric may lead to novel chiral electronic phenomena.

Degradation of metoprolol by UV/sulfite as an advanced oxidation or reduction process: The significant role of oxygen.

The degradation of metoprolol (MTP) by the UV/sulfite with oxygen as an advanced reduction process (ARP) and that without oxygen as an advanced oxidation process (AOP) was comparatively studied herein. The degradation of MTP by both processes followed the first-order rate law with comparable reaction rate constants of 1.50×10-3sec-1 and 1.20×10-3sec-1, respectively. Scavenging experiments demonstrated that both eaq- and H• played a crucial role in MTP degradation by the UV/sulfite as an ARP, while SO4•- was the dominant oxidant in the UV/sulfite AOP. The degradation kinetics of MTP by the UV/sulfite as an ARP and AOP shared a similar pH dependence with a minimum rate obtained around pH 8. The results could be well explained by the pH impacts on the MTP speciation and sulfite species. Totally six transformation products (TPs) were identified from MTP degradation by the UV/sulfite ARP, and two additional ones were detected in the UV/sulfite AOP. The benzene ring and ether groups of MTP were proposed as the major reactive sites for both processes based on molecular orbital calculations by density functional theory (DFT). The similar degradation products of MTP by the UV/sulfite process as an ARP and AOP indicated that eaq-/H• and SO4•- might share similar reaction mechanisms, primarily including hydroxylation, dealkylation, and H abstraction. The toxicity of MTP solution treated by the UV/sulfite AOP was calculated to be higher than that in the ARP by the Ecological Structure Activity Relationships (ECOSAR) software, due to the accumulation of TPs with higher toxicity.

ORF355 confers enhanced salinity stress adaptability to S-type cytoplasmic male sterility maize by modulating the mitochondrial metabolic homeostasis.

Moderate stimuli in mitochondria improve wide-ranging stress adaptability in animals, but whether mitochondria play similar roles in plants is largely unknown. Here, we report the enhanced stress adaptability of S-type cytoplasmic male sterility (CMS-S) maize and its association with mild expression of sterilizing gene ORF355. A CMS-S maize line exhibited superior growth potential and higher yield than those of the near-isogenic N-type line in saline fields. Moderate expression of ORF355 induced the accumulation of reactive oxygen species and activated the cellular antioxidative defense system. This adaptive response was mediated by elevation of the nicotinamide adenine dinucleotide concentration and associated metabolic homeostasis. Metabolome analysis revealed broad metabolic changes in CMS-S lines, even in the absence of salinity stress. Metabolic products associated with amino acid metabolism and galactose metabolism were substantially changed, which underpinned the alteration of the antioxidative defense system in CMS-S plants. The results reveal the ORF355-mediated superior stress adaptability in CMS-S maize and might provide an important route to developing salt-tolerant maize varieties.

Characterization and genetic dissection of maize ear leaf midrib acquired by 3D digital technology.

The spatial morphological structure of plant leaves is an important index to evaluate crop ideotype. In this study, we characterized the three-dimensional (3D) data of the ear leaf midrib of maize at the grain-filling stage using the 3D digitization technology and obtained the phenotypic values of 15 traits covering four different dimensions of the ear leaf midrib, of which 13 phenotypic traits were firstly proposed for featuring plant leaf spatial structure. Cluster analysis results showed that the 13 traits could be divided into four groups, Group I, -II, -III and -IV. Group I contains HorizontalLength, OutwardGrowthMeasure, LeafAngle and DeviationTip; Group II contains DeviationAngle, MaxCurvature and CurvaturePos; Group III contains LeafLength and ProjectionArea; Group IV contains TipTop, VerticalHeight, UpwardGrowthMeasure, and CurvatureRatio. To investigate the genetic basis of the ear leaf midrib curve, 13 traits with high repeatability were subjected to genome-wide association study (GWAS) analysis. A total of 828 significantly related SNPs were identified and 1365 candidate genes were annotated. Among these, 29 candidate genes with the highest significant and multi-method validation were regarded as the key findings. In addition, pathway enrichment analysis was performed on the candidate genes of traits to explore the potential genetic mechanism of leaf midrib curve phenotype formation. These results not only contribute to further understanding of maize leaf spatial structure traits but also provide new genetic loci for maize leaf spatial structure to improve the plant type of maize varieties.

Comparative analysis of mitochondrial genomes of maize CMS-S subtypes provides new insights into male sterility stability.

BACKGROUND: Cytoplasmic male sterility (CMS) is a trait of economic importance in the production of hybrid seeds. In CMS-S maize, exerted anthers appear frequently in florets of field-grown female populations where only complete male-sterile plants were expected. It has been reported that these reversions are associated with the loss of sterility-conferring regions or other rearrangements in the mitochondrial genome. However, the relationship between mitochondrial function and sterility stability is largely unknown. RESULTS: In this study, we determined the ratio of plants carrying exerted anthers in the population of two CMS-S subtypes. The subtype with a high ratio of exerted anthers was designated as CMS-Sa, and the other with low ratio was designated as CMS-Sb. Through next-generation sequencing, we assembled and compared mitochondrial genomes of two CMS-S subtypes. Phylogenetic analyses revealed strong similarities between the two mitochondrial genomes. The sterility-associated regions, S plasmids, and terminal inverted repeats (TIRs) were intact in both genomes. The two subtypes maintained high transcript levels of the sterility gene orf355 in anther tissue. Most of the functional genes/proteins were identical at the nucleotide sequence and amino acid sequence levels in the two subtypes, except for NADH dehydrogenase subunit 1 (nad1). In the mitochondrial genome of CMS-Sb, a 3.3-kilobase sequence containing nad1-exon1 was absent from the second copy of the 17-kb repeat region. Consequently, we detected two copies of nad1-exon1 in CMS-Sa, but only one copy in CMS-Sb. During pollen development, nad1 transcription and mitochondrial biogenesis were induced in anthers of CMS-Sa, but not in those of CMS-Sb. We suggest that the impaired mitochondrial function in the anthers of CMS-Sb is associated with its more stable sterility. CONCLUSIONS: Comprehensive analyses revealed diversity in terms of the copy number of the mitochondrial gene nad1-exon1 between two subtypes of CMS-S maize. This difference in copy number affected the transcript levels of nad1 and mitochondrial biogenesis in anther tissue, and affected the reversion rate of CMS-S maize. The results of this study suggest the involvement of mitochondrial robustness in modulation of sterility stability in CMS-S maize.

Electrified ceramic membrane actuates non-radical mediated peroxymonosulfate activation for highly efficient water decontamination.

Electrified ceramic membranes (ECMs) achieve high water decontamination efficiency mainly through implementing in situ radical-mediated oxidation in membrane filtration, whereas ECMs leveraging non-radical pathways are rarely explored. Herein, we demonstrated a Janus ECM realizing ultra-efficient micropollutant (MP) removal via electro-activating peroxymonosulfate (PMS) in a fast, flow-through single-pass electro-filtration. The Janus ECM features two separate palladium (Pd) functionalized electrocatalytic reaction zones engineered on its two sides. We confirmed that the PMS/electro-filtration system induced non-radical pathways for MP degradation, including singlet oxygenation and mediating direct electron transfer (DET) from MP to PMS. Under the design of the ECM featuring dual electrocatalytic reaction zones in the ceramic membrane intrapores, the Janus ECM showed over one-fold increase in micropollutant removal rate as 94.5% and lower electric energy consumption as 1.78 Wh g-1 MP in the PMS electro-activation process, as compared with the conventional ECM assembly implementing only half-cell reaction. This finding manifested the Janus ECM configuration advantage for maximizing the PMS electro-activation efficiency via singlet oxygenation intensification and direct usage of cathode for DET mediation. The Janus ECM boosted the PMS electro-activation and water decontamination efficiency by enhancing the convective mass transfer and the spatial confinement effect. Our work demonstrated a high-efficiency PMS electro-activation method based on electro-filtration and maximized the non-radical mediated PMS oxidation for MP removal, expanding the ECM filtration strategies for water decontamination.

Transplantation of fecal microbiota from APP/PS1 mice and Alzheimer's disease patients enhanced endoplasmic reticulum stress in the cerebral cortex of wild-type mice.

Background and purpose: The 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 methods: In 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. Results: Excessive 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. Conclusion: The findings indicate that imbalance of the gut microbiota induces ER stress in the cerebral cortex, which may be mediated by TMAO.

Associations of Abdominal Visceral Fat Content and Plasma Adiponectin Level With Intracranial Atherosclerotic Stenosis: A Cross-Sectional Study.

Background: Abdominal obesity and adipocytokines are closely related to atherosclerosis, and adiponectin level is considered one of the important clinical indicators. This study aimed to analyze the associations of abdominal visceral fat content and adiponectin level with intracranial atherosclerotic stenosis (ICAS). Methods: A total of 186 patients were enrolled in this study. Patients were distributed into ICAS and non-ICAS by the degree of artery stenosis. Plasma adiponectin levels and the ratio of visceral adipose tissue (VAT) to subcutaneous adipose tissue (SAT) were measured. The related factors of intracranial atherosclerotic stenosis were determined using multivariable logistic regression analysis. Results: The VAT/SAT ratio (OR, 26.08; 95% CI, 5.92-114.83; p < 0.001) and adiponectin (OR, 0.61; 95% CI, 0.44-0.84; p = 0.002) were found to be the independent predictors of ICAS in a multivariable logistic regression analysis. The prevalence of ICAS increased (T1: 27.4%; T2: 50.0%; T3: 75.8%) as the VAT/SAT ratio tertile increased (p < 0.001). The prevalence of ICAS decreased (T1: 72.6%; T2: 54.8%; T3: 25.8%) as the adiponectin tertile increased (p < 0.001). In ROC curves analysis, VAT/SAT ratio had a sensible accuracy for the prediction of ICAS. The optimal cut-off value of VAT/SAT ratio to predict ICAS in this study was 1.04 (AUC: 0.747; p < 0.001; sensitivity: 67.4%; specificity: 74.7%). The optimal adiponectin cutoff was 3.03 ug/ml (AUC: 0.716; p < 0.001; sensitivity:75.8%; specificity: 61.5%). Conclusion: Higher VAT/SAT ratio and lower plasma adiponectin levels were closely related to the increased risk of intracranial atherosclerotic stenosis.

A newly characterized allele of ZmR1 increases anthocyanin content in whole maize plant and the regulation mechanism of different ZmR1 alleles.

KEY MESSAGE: The novel ZmR1CQ01 allele for maize anthocyanin synthesis was identified, and the biological function and regulatory molecular mechanisms of three ZmR1 alleles were unveiled. Anthocyanins in maize are valuable to human health. The R1 gene family is one of the important regulatory genes for the tissue-specific distribution of anthocyanins. R1 gene allelic variations are abundant and its biological function and regulatory molecular mechanisms are not fully understood. By exploiting genetic mapping and transgenic verification, we found that anthocyanin pigmentation in maize leaf midrib was controlled by ZmR1 on chromosome 10. Allelism test of maize zmr1 EMS mutants confirmed that anthocyanin pigmentation in leaf sheath was also controlled by ZmR1. ZmR1CQ01 was a novel ZmR1 allelic variation obtained from purple maize. Its overexpression caused the whole maize plant to turn purple. ZmR1B73 allele confers anthocyanin accumulation in near ground leaf sheath rather than in leaf midribs. The mRNA expression level of ZmR1B73 was low in leaf midribs, resulting in no anthocyanin accumulation. ZmR1B73 overexpression promoted anthocyanin accumulation in leaf midribs. Loss of exon 5 resulted in ZmR1ZN3 allele function destruction and no anthocyanin accumulation in leaf midrib and leaf sheath. DNA affinity purification sequencing revealed 1010 genes targeted by ZmR1CQ01, including the bz2 in anthocyanin synthesis pathway. RNA-seq analysis showed 55 genes targeted by ZmR1CQ01 changed the expression level significantly, and the expression of genes encoding key enzymes in flavonoid and phenylpropanoid biosynthesis pathways were significantly up-regulated. ZmR1 functional molecular marker was developed. These results revealed the effects of transcriptional regulation and sequence variation on ZmR1 function and identified the genes targeted by ZmR1CQ01 at the genome-wide level.