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PurposeOlfactory dysfunction (OD) is a debilitating symptom frequently reported by patients with chronic rhinosinusitis (CRS) and it is associated with a dysregulated sinonasal inflammation. However, little information is available about the effect of the inflammation-related nasal microbiota and related metabolites on the olfactory function in these patients. Therefore, the current study aimed to investigate the nasal microbiota-metabolites-immune interactions and their role in the pathogenesis of OD in CRS patients.Methods23 and 19 CRS patients with and without OD, respectively, were enrolled in the present study. The “Sniffin’ Sticks” was used to measure the olfactory function, while the metagenomic shotgun sequencing and the untargeted metabolite profiling were performed to assess the differences in terms of the nasal microbiome and metabolome between the two groups. The levels of nasal mucus inflammatory mediators were investigated by a multiplex flow Cytometric Bead Array (CBA).ResultsA decreased diversity in the nasal microbiome from the OD group compared to the NOD group was evidenced. The metagenomic analysis revealed a significant enrichment of Acinetobacter johnsonii in the OD group, while Mycoplasma arginini, Aeromonas dhakensis, and Salmonella enterica were significantly less represented (LDA value > 3, p < 0.05). The nasal metabolome profiles were significantly different between the OD and NOD groups (P < 0.05). The purine metabolism was the most significantly enriched metabolic subpathway in OD patients compared with NOD patients (P < 0.001). The expressions of IL-5, IL-8, MIP-1α, MCP-1, and TNF were statistically and significantly increased in the OD group (P < 0.05). All these data, including the dysregulation of the nasal microbiota, differential metabolites, and elevated inflammatory mediators in OD patients demonstrated a clear interaction relationship.ConclusionThe disturbed nasal microbiota-metabolite-immune interaction networks may be implicated in the pathogenesis of OD in CRS patients and the underlying pathophysiological mechanisms need to be further investigated in future studies.

Developmental abnormalities and hippocampal aging leads to alteration in cognition. In the brain, N6-methyladenosine (m6A) is a common and reversible mRNA alteration that is essential for both neurodevelopment and neurodegeneration. However, its function in the postnatal hippocampus and the specific mechanisms regulating hippocampus-related neurodegeneration still awaits elucidate. We identified dynamic m6A modifications in postnatal hippocampus at different stages (at 10 days postnatally, and at 11 and 64 weeks of age). m6A shows a definite cell-specific methylation profile and m6A modification displays temporal dynamic during neurodevelopment and aging. Differentially methylated transcripts in the aged (64-week-old) hippocampus were enriched in microglia. The PD-1/PD-L1 pathways was identified that may participate in the cognitive dysfunction associated with an aged hippocampus. Furthermore, Mettl3 was spatiotemporally expressed in the postnatal hippocampus, which was highly expressed at the age of 11 weeks compared with the other two timepoints. Ectopic expression of METTL3 in mice hippocampus mediated by lentiviral infection resulted in high expression of genes related to PD-1/PD-L1 pathway and significant spatial cognitive deficit. Together, our data show that m6A dysregulation, which is mediated by METTL3, most likely contributes to cognitive deficits linked to the hippocampus via the PD-1/PD-L1 pathway.

With increasing attention on sibling relationship studies in China, one problem that has been neglected is the limited validation of instruments used to assess these relationships. The present study evaluated the psychometric properties of the Sibling Inventory of Behavior to measure Chinese children’s sibling relationships using a stratified random sample of 590 parents of three- to six-year-olds in three economic regions. The confirmatory factor analysis obtained an adequate fit, suggesting that the Chinese version of the instrument had a six-factor structure (i.e., Companionship, Empathy, Teaching, Rivalry, Aggression, and Avoidance). It demonstrated satisfactory internal consistency as well as test–retest reliability. Results of discriminant, convergent, and criterion-related validity test also fulfilled psychometric requirements. Furthermore, the residual measurement invariance across regions was discovered. Given the importance, emergence, and tendency of sibling studies in China, having a reliable and valid instrument with robust psychometric properties is essential and impactful.

Wheat has a specific preference for NO3- and shows toxicity symptoms under high NH4+ concentrations. Increasing the nitrate supply may alleviate ammonium stress. Nevertheless, the mechanisms underlying the nitrate regulation of wheat root growth to alleviate ammonium toxicity remain unclear. In this study, we integrated physiological and weighted gene co-expression network analysis (WGCNA) to identify the hub genes involved in nitrate alleviation of ammonium toxicity at the wheat seedling stage. Five NH4+/NO3- ratio treatments, including 100/0 (Na), 75/25 (Nr1), 50/50 (Nr2), 25/75 (Nr3), and 0/100 (Nn) were tested in this study. The results showed that sole ammonium treatment (Na) increased the lateral root number but reduced root biomass. Increasing the nitrate supply significantly increased the root biomass. Increasing nitrate levels decreased abscisic acid (ABA) content and increased auxin (IAA) content. Furthermore, we identified two modules (blue and turquoise) using transcriptome data that were significantly related to root physiological growth indicators. TraesCS6A02G178000 and TraesCS2B02G056300 were identified as hub genes in the two modules which coded for plastidic ATP/ADP-transporter and WRKY62 transcription factors, respectively. Additionally, network analysis showed that in the blue module, TraesCS6A02G178000 interacts with downregulated genes that coded for indolin-2-one monooxygenase, SRG1, DETOXIFICATION, and wall-associated receptor kinase. In the turquoise module, TraesCS2B02G056300 was highly related to the genes that encoded ERD4, ERF109, CIGR2, and WD40 proteins, and transcription factors including WRKY24, WRKY22, MYB30, and JAMYB, which were all upregulated by increasing nitrate supply. These studies suggest that increasing the nitrate supply could improve root growth and alleviate ammonium toxicity through physiological and molecular regulation networks, including ROS, hormonal crosstalk, and transcription factors.

To clarify the influences of shading stress and planting density on the lignin monomer composition of wheat stems and their relationship with lodging resistance, Lodging resistant variety Shannong 23 (SN23) and lodging sensitive variety Shannong 16 (SN16) were grown during 2018−2019 and 2019−2020 growing seasons. The planting densities were 150 × 104 plants ha-1 (D1), 225 × 104 plants ha-1 (D2) and 300 × 104 plants ha-1 (D3). At the jointing stage, an artificial shading shed was used to simulate shading stress. Then the effects of shading on stem morphological characteristics, lignin monomer composition and lodging resistance of wheat under different planting densities were studied. Results indicate that shading at the jointing stage increased the length of basal internodes and the plant height and moved the height of center of gravity (CG) upward. Moreover, the stem diameter and the wall thickness decreased by 0.10−0.53 mm and 0.18−0.40 mm, respectively. The stem filling degree was reduced accordingly. As indicated by the correlation analysis and the stepwise regression analysis, shading-induced lodging mainly resulted from changes in the stem morphological characteristics and lignin accumulation. The influential magnitude of these factors was ordered as follows: stem filling degree, wall thickness, lignin content, contents and proportions of monomers S and H, and length of the second internode. The expression abundance of TaPAL, TaCOMT, TaCCR, and TaCAD declined in response to shading stress and high planting density. As a result, the distribution ratios of photosynthetic carbon sources to lignin monomers S, G and H were changed. The lignin content of stems on the day 42 after the jointing stage decreased by 18.48%. The monomer S content decreased, while the content and proportion of monomer H increased, thus weakening the breaking strength of wheat stems.

Natural fractures in continental shale oil reservoirs of the Fengcheng Formation in the Mahu Sag show multi-scale characteristics, which leads to complex seismic responses and difficult identification. In order to establish fracture prediction models with good performance in these reservoirs, this study uses seismic attributes such as post-stack coherence, curvature, likelihood, and pre-stack AVAz to predict the multi-scale fractures, including main-secondary faults, large-scale fractures, and medium-small scale fractures in continental shale oil reservoirs. The final prediction results are superimposed on the plane to clarify the multi-scale fracture distribution law of the Fengcheng Formation in the Mahu Sag. Seismic prediction results show that natural fractures in the upper sweet spot of the Fengcheng Formation are more developed, especially in the northern and central platform areas, and they are mainly near E-W strikes. With the increase of the primary-secondary fault distance, the fracture density gradually decreases. Natural fractures obtained by seismic prediction are consistent with the fractures interpreted by image logs, which can be used to effectively predict fractures for continental shale oil reservoirs in the Mahu Sag of the Junggar Basin and other areas with a similar geological background.

Wheat growth and nitrogen (N) uptake gradually decrease in response to high NH4+/NO3– ratio. However, the mechanisms underlying the response of wheat seedling roots to changes in NH4+/NO3– ratio remain unclear. In this study, we investigated wheat growth, transcriptome, and proteome profiles of roots in response to increasing NH4+/NO3– ratios (Na: 100/0; Nr1: 75/25, Nr2: 50/50, Nr3: 25/75, and Nn: 0/100). High NH4+/NO3– ratio significantly reduced leaf relative chlorophyll content, Fv/Fm, and ΦII values. Both total root length and specific root length decreased with increasing NH4+/NO3– ratios. Moreover, the rise in NH4+/NO3– ratio significantly promoted O2– production. Furthermore, transcriptome sequencing and tandem mass tag-based quantitative proteome analyses identified 14,376 differentially expressed genes (DEGs) and 1,819 differentially expressed proteins (DEPs). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that glutathione metabolism and phenylpropanoid biosynthesis were the main two shared enriched pathways across ratio comparisons. Upregulated DEGs and DEPs involving glutathione S-transferases may contribute to the prevention of oxidative stress. An increment in the NH4+/NO3– ratio induced the expression of genes and proteins involved in lignin biosynthesis, which increased root lignin content. Additionally, phylogenetic tree analysis showed that both A0A3B6NPP6 and A0A3B6LM09 belong to the cinnamyl-alcohol dehydrogenase subfamily. Fifteen downregulated DEGs were identified as high-affinity nitrate transporters or nitrate transporters. Upregulated TraesCS3D02G344800 and TraesCS3A02G350800 were involved in ammonium transport. Downregulated A0A3B6Q9B3 is involved in nitrate transport, whereas A0A3B6PQS3 is a ferredoxin-nitrite reductase. This may explain why an increase in the NH4+/NO3– ratio significantly reduced root NO3–-N content but increased NH4+-N content. Overall, these results demonstrated that increasing the NH4+/NO3– ratio at the seedling stage induced the accumulation of reactive oxygen species, which in turn enhanced root glutathione metabolism and lignification, thereby resulting in increased root oxidative tolerance at the cost of reducing nitrate transport and utilization, which reduced leaf photosynthetic capacity and, ultimately, plant biomass accumulation.

The low red/far-red (R/FR) light proportion at the base of the high-density wheat population leads to poor stem quality and increases lodging risk. We used Shannong 23 and Shannong 16 as the test materials. By setting three-light quality treatments: normal light (CK), red light (RL), and far-red light (FRL), we irradiated the base internodes of the stem with RL and FRL for 7h. Our results showed that RL irradiation enhanced stem quality, as revealed by increased breaking strength, stem diameter, wall thickness and, dry weight per unit length, and the total amount of lignin and related gene expression increased, at the same time. The composition of lignin subunits was related to the lodging resistance of wheat. The proportion of S+G subunits and H subunits played a key role in wheat lodging resistance. RL could increase the content of S subunits and G subunits and the proportion of S+G subunits, reduce the proportion of H subunits. We described here, to the best of our knowledge, the systematic study of the mechanism involved in the regulation of stem breaking strength by light quality, particularly the effect of light quality on lignin biosynthesis and its relationship with lodging resistance in wheat.

In two independent yet complementary studies, the current research explored the developmental changes of young children’s conceptualization of learning, focusing the role of knowledge change and learning intention, and its association with their developing theory of mind (ToM) ability. In study 1, 75 children between 48 and 86 months of age (M = 65.45, SD = 11.45, 36 girls) judged whether a character with or without a genuine knowledge change had learned. The results showed that younger children randomly attributed learning between genuine knowledge change and accidental coincidence that did not involve knowledge change. Children’s learning judgments in familiar contexts improved with age and correlated with their ToM understanding. However, the correlation was no longer significant once age was held constant. Another sample of 72 children aged between 40 and 90 months (M = 66.87, SD = 11.83, 31 girls) participated in study 2, where children were asked to judge whether the story protagonists intended to learn and whether they eventually learned. The results suggested that children over-attributed learning intention to discovery and implicit learning. Stories with conflict between the learning intention and outcome appeared to be most challenging for children. Children’s intention judgment was correlated with their ToM understanding, and ToM marginally predicted intention judgment when the effect of age was accounted for. The implication of the findings for school readiness was discussed. Training studies and longitudinal designs in the future are warranted to better understand the relation between ToM development and children’s learning understanding.

Repair and reconstruction of critical-sized bone defects has always been a difficult task in orthopedics. Hypoxia inducible factor-1α (HIF-1α) plays an important role in bone defect repair, it has the dual function of promoting osteogenesis and vascular regeneration, but it is quickly degraded by the body under normoxic conditions. Previously we prepared mutant HIF-1α, which has been shown to efficiently maintain cellular expression under normoxic conditions. In this study, we evaluated for the first time the role of exosomes of rat bone marrow mesenchymal stem cell carry mutant HIF-1α (BMSC-Exos-HIF1α) in repairing critical-sized bone defects. Evaluation of the effects of BMSC-Exos-HIF1α on bone marrow mesenchymal stem cells (BMSCs) proliferation and osteogenic differentiation by cell proliferation assay, alkaline phosphatase activity assay, alizarin red staining, real-time quantitative polymerase chain reaction. BMSC-Exos-HIF1α was loaded onto the β-TCP stent implanted in the bone defect area using a rat cranial critical-sized bone defect model, and new bone formation and neovascularization were detected in vivo by micro-CT, fluorescence labeling analysis, Microfil perfusion, histology and immunohistochemical analysis. In vitro results showed that BMSC-Exos-HIF1α stimulated the proliferation of BMSCs and up-regulated the expression level of bone-related genes, which was superior to bone marrow MSC exosomes (BMSC-Exos). In vivo results showed that BMSC-Exos-HIF1α combined with β-TCP scaffold promoted new bone regeneration and neovascularization in the bone defect area, and the effect was better than that of BMSC-Exos combined with β-TCP scaffold. In this study, the results showed that BMSC-Exos-HIF1α stimulated the proliferation and osteogenic differentiation of BMSCs and that BMSC-Exos-HIF1α combined with β-TCP scaffolds could repair critical-sized bone defects by promoting new bone regeneration and neovascularization.

Playing chess requires perspective taking in order to consistently infer the opponent’s next moves. The present study examined whether long-term chess players are more advanced in visual perspective taking tasks than their counterparts without chess training during laboratory visual perspective taking tasks. Visual perspective taking performance was assessed among 11- to 12-year-old experienced chess players (n = 15) and their counterparts without chess training (n = 15) using a dot perspective task. Participants judged their own and the avatar’s visual perspective that were either consistent with each other or not. The results indicated that the chess players out-performed the non-chess players (Experiment 1), yet this advantage disappeared when the task required less executive functioning (Experiment 2). Additionally, unlike the non-chess players whose performance improved in Experiment 2 when the executive function (EF) demand was reduced, the chess players did not show better perspective taking under such condition. These findings suggested that long-term chess experience might be associated with children’s more efficient perspective taking of other people’s viewpoints without exhausting their cognitive resources.

Children's understanding of the concepts of teaching and learning is closely associated with their theory of mind (ToM) ability and vital for school readiness. This study aimed to develop and validate a Preschool Teaching and Learning Comprehension Index (PTLCI) across cultures and examine the causal relationship between children's comprehension of teaching and learning and their mental state understanding. Two hundred and twelve children from 3 to 6 years of age from Hong Kong and the United States participated in study. The results suggested strong construct validity of the PTLCI, and its measurement and structural equivalence within and across cultures. ToM and PTLCI were significantly correlated with a medium effect size, even after controlling for age, and language ability. Hong Kong children outperformed their American counterparts in both ToM and PTLCI. Competing structural equation models suggested that children's performance on the PTLCI causally predicted their ToM across countries.

Purpose: Olfactory dysfunction (OD) is a debilitating symptom frequently reported by patients with chronic rhinosinusitis (CRS) and it is associated with a dysregulated sinonasal inflammation. However, little information is available about the effect of the inflammation-related nasal microbiota and related metabolites on the olfactory function in these patients. Therefore, the current study aimed to investigate the nasal microbiota-metabolites-immune interactions and their role in the pathogenesis of OD in CRS patients. Methods: 23 and 19 CRS patients with and without OD, respectively, were enrolled in the present study. The "Sniffin' Sticks" was used to measure the olfactory function, while the metagenomic shotgun sequencing and the untargeted metabolite profiling were performed to assess the differences in terms of the nasal microbiome and metabolome between the two groups. The levels of nasal mucus inflammatory mediators were investigated by a multiplex flow Cytometric Bead Array (CBA). Results: A decreased diversity in the nasal microbiome from the OD group compared to the NOD group was evidenced. The metagenomic analysis revealed a significant enrichment of Acinetobacter johnsonii in the OD group, while Mycoplasma arginini, Aeromonas dhakensis, and Salmonella enterica were significantly less represented (LDA value > 3, p < 0.05). The nasal metabolome profiles were significantly different between the OD and NOD groups (P < 0.05). The purine metabolism was the most significantly enriched metabolic subpathway in OD patients compared with NOD patients (P < 0.001). The expressions of IL-5, IL-8, MIP-1a, MCP-1, and TNF were statistically and significantly increased in the OD group (P < 0.05). All these data, including the dysregulation of the nasal microbiota, differential metabolites, and elevated inflammatory mediators in OD patients demonstrated a clear interaction relationship. Conclusion: The disturbed nasal microbiota-metabolite-immune interaction networks may be implicated in the pathogenesis of OD in CRS patients and the underlying pathophysiological mechanisms need to be further investigated in future studies. [ABSTRACT FROM AUTHOR]

Developmental abnormalities and hippocampal aging leads to alteration in cognition. In the brain, N6-methyladenosine (m6 A) is a common and reversible mRNA alteration that is essential for both neurodevelopment and neurodegeneration. However, its function in the postnatal hippocampus and the specific mechanisms regulating hippocampus-related neurodegeneration still awaits elucidate. We identified dynamic m6 A modifications in postnatal hippocampus at different stages (at 10 days postnatally, and at 11 and 64 weeks of age). m6 A shows a definite cell-specific methylation profile and m6 A modification displays temporal dynamic during neurodevelopment and aging. Differentially methylated transcripts in the aged (64-week-old) hippocampus were enriched in microglia. The PD-1/PD-L1 pathways was identified that may participate in the cognitive dysfunction associated with an aged hippocampus. Furthermore, Mettl3 was spatiotemporally expressed in the postnatal hippocampus, which was highly expressed at the age of 11 weeks compared with the other two timepoints. Ectopic expression of METTL3 in mice hippocampus mediated by lentiviral infection resulted in high expression of genes related to PD-1/PD-L1 pathway and significant spatial cognitive deficit. Together, our data show that m6 A dysregulation, which is mediated by METTL3, most likely contributes to cognitive deficits linked to the hippocampus via the PD-1/PD-L1 pathway. [ABSTRACT FROM AUTHOR]

Wheat has a specific preference for NO3 - and shows toxicity symptoms under high NH4 + concentrations. Increasing the nitrate supply may alleviate ammonium stress. Nevertheless, the mechanisms underlying the nitrate regulation of wheat root growth to alleviate ammonium toxicity remain unclear. In this study, we integrated physiological and weighted gene coexpression network analysis (WGCNA) to identify the hub genes involved in nitrate alleviation of ammonium toxicity at the wheat seedling stage. Five NH4 +/NO3 - ratio treatments, including 100/0 (Na), 75/25 (Nr1), 50/50 (Nr2), 25/75 (Nr3), and 0/100 (Nn) were tested in this study. The results showed that sole ammonium treatment (Na) increased the lateral root number but reduced root biomass. Increasing the nitrate supply significantly increased the root biomass. Increasing nitrate levels decreased abscisic acid (ABA) content and increased auxin (IAA) content. Furthermore, we identified two modules (blue and turquoise) using transcriptome data that were significantly related to root physiological growth indicators. TraesCS6A02G178000 and TraesCS2B02G056300 were identified as hub genes in the two modules which coded for plastidic ATP/ADP-transporter and WRKY62 transcription factors, respectively. Additionally, network analysis showed that in the blue module, TraesCS6A02G178000 interacts with downregulated genes that coded for indolin-2-one monooxygenase, SRG1, DETOXIFICATION, and wallassociated receptor kinase. In the turquoise module, TraesCS2B02G056300 was highly related to the genes that encoded ERD4, ERF109, CIGR2, and WD40 proteins, and transcription factors including WRKY24, WRKY22, MYB30, and JAMYB, which were all upregulated by increasing nitrate supply. These studies suggest that increasing the nitrate supply could improve root growth and alleviate ammonium toxicity through physiological and molecular regulation networks, including ROS, hormonal crosstalk, and transcription factors. [ABSTRACT FROM AUTHOR]