Parent material influences soil properties to shape bacterial community assembly processes, diversity, and enzyme-related functions.

Soil parent material is the second most influential factor in pedogenesis, influencing soil properties and microbial communities. Different assembly processes shape diverse functional microbial communities. The question remains unresolved regarding how these ecological assembly processes affect microbial communities and soil functionality within soils on different parent materials. We collected soil samples developed from typical parent materials, including basalt, granite, metamorphic rock, and marine sediments across soil profiles at depths of 0-20, 20-40, 40-80, and 80-100 cm, within rubber plantations on Hainan Island, China. We determined bacterial community characteristics, community assembly processes, and soil enzyme-related functions using 16S rRNA high-throughput sequencing and enzyme activity analyses. We found homogeneous selection, dispersal limitation, and drift processes were the dominant drivers of bacterial community assembly across soils on different parent materials. In soils on basalt, lower pH and higher moisture triggered a homogeneous selection-dominated assembly process, leading to a less diverse community but otherwise higher carbon and nitrogen cycling enzyme activities. As deterministic process decreased, bacterial community diversity increased with stochastic process. In soils on marine sediments, lower water, carbon, and nutrient content limited the dispersal of bacterial communities, resulting in higher community diversity and an increased capacity to utilize relative recalcitrant substrates by releasing more oxidases. The r-strategy Bacteroidetes and genera Sphingomonas, Bacillus, Vibrionimonas, Ochrobactrum positively correlated with enzyme-related function, whereas k-strategy Acidobacteria, Verrucomicrobia and genera Acidothermus, Burkholderia-Caballeronia-Paraburkholderia, HSB OF53-F07 showed negative correlations. Our study suggests that parent material could influence bacterial community assembly processes, diversity, and soil enzyme-related functions via soil properties.

Acoustic Levitation Synthesis of Ultrahigh-Density Spherical Nucleic Acid Architectures for Specific SERS Analysis.

Controllably regulating the electrostatic bilayer of nanogold colloids is a significant premise for synthesizing spherical nucleic acid (SNA) and building ordered plasmonic architectures. We develop a facile acoustic levitation reactor to universally synthesize SNAs with an ultra-high density of DNA strands, which is even higher than those of various state-of-the-art methods. Results reveal a new mechanism of DNA grafting via acoustic wave that can reconfigure the ligands on colloidal surfaces. The acoustic levitation reactor enables substrate-free three-dimentional (3D) spatial assembly of SNAs with controllable interparticle nanogaps through regulating DNA lengths. This kind of architecture may overcome the plasmonic enhancement limits by blocking electron tunneling and breaking electrostatic shielding in dried aggregations. Finite element simulations support the architecture with 3D spatial plasmonic hotspot matrix, and its ultrahigh surface-enhanced Raman scattering (SERS) capability is evidenced by in situ untargeted tracking of biomolecular events during photothermal stimulation (PTS)-induced cell death process. For biomarker diagnosis, the conjugation of adenosine triphosphate (ATP) aptamer onto SNAs enables in situ targeted tracking of ATP during PTS-induced cell death process. Particularly, the CD71 receptor and integrin α3ß1 protein on PL45 cell membrance could be well distinguished by label-free SERS fingerprints when using specific XQ-2d and DML-7 aptamers, respectively, to synthesize SNA architectures. Our current acoustic levitation reactor offers a new method for synthesizing SNAs and enables both targeted and untargeted SERS analysis for tracking molecular events in living systems. It promises great potentials in biochemical synthesis and sensing in future.

Virtual histological staining of unlabeled autopsy tissue.

Traditional histochemical staining of post-mortem samples often confronts inferior staining quality due to autolysis caused by delayed fixation of cadaver tissue, and such chemical staining procedures covering large tissue areas demand substantial labor, cost and time. Here, we demonstrate virtual staining of autopsy tissue using a trained neural network to rapidly transform autofluorescence images of label-free autopsy tissue sections into brightfield equivalent images, matching hematoxylin and eosin (H&E) stained versions of the same samples. The trained model can effectively accentuate nuclear, cytoplasmic and extracellular features in new autopsy tissue samples that experienced severe autolysis, such as COVID-19 samples never seen before, where the traditional histochemical staining fails to provide consistent staining quality. This virtual autopsy staining technique provides a rapid and resource-efficient solution to generate artifact-free H&E stains despite severe autolysis and cell death, also reducing labor, cost and infrastructure requirements associated with the standard histochemical staining.

Virtual Staining of Nonfixed Tissue Histology.

Surgical pathology workflow involves multiple labor-intensive steps, such as tissue removal, fixation, embedding, sectioning, staining, and microscopic examination. This process is time-consuming and costly and requires skilled technicians. In certain clinical scenarios, such as intraoperative consultations, there is a need for faster histologic evaluation to provide real-time surgical guidance. Currently, frozen section techniques involving hematoxylin and eosin (H&E) staining are used for intraoperative pathology consultations. However, these techniques have limitations, including a turnaround time of 20 to 30 minutes, staining artifacts, and potential tissue loss, negatively impacting accurate diagnosis. To address these challenges, researchers are exploring alternative optical imaging modalities for rapid microscopic tissue imaging. These modalities differ in optical characteristics, tissue preparation requirements, imaging equipment, and output image quality and format. Some of these imaging methods have been combined with computational algorithms to generate H&E-like images, which could greatly facilitate their adoption by pathologists. Here, we provide a comprehensive, organ-specific review of the latest advancements in emerging imaging modalities applied to nonfixed human tissue. We focused on studies that generated H&E-like images evaluated by pathologists. By presenting up-to-date research progress and clinical utility, this review serves as a valuable resource for scholars and clinicians, covering some of the major technical developments in this rapidly evolving field. It also offers insights into the potential benefits and drawbacks of alternative imaging modalities and their implications for improving patient care.

Genome-Wide Comparative Analysis of SRCR Gene Superfamily in Invertebrates Reveals Massive and Independent Gene Expansions in the Sponge and Sea Urchin.

Without general adaptative immunity, invertebrates evolved a vast number of heterogeneous non-self recognition strategies. One of those well-known adaptations is the expansion of the immune receptor gene superfamily coding for scavenger receptor cysteine-rich domain containing proteins (SRCR) in a few invertebrates. Here, we investigated the evolutionary history of the SRCR gene superfamily (SRCR-SF) across 29 metazoan species with an emphasis on invertebrates. We analyzed their domain architectures, genome locations and phylogenetic distribution. Our analysis shows extensive genome-wide duplications of the SRCR-SFs in Amphimedon queenslandica and Strongylocentrotus purpuratus. Further molecular evolution study reveals various patterns of conserved cysteines in the sponge and sea urchin SRCR-SFs, indicating independent and convergent evolution of SRCR-SF expansion during invertebrate evolution. In the case of the sponge SRCR-SFs, a novel motif with seven conserved cysteines was identified. Exon-intron structure analysis suggests the rapid evolution of SRCR-SFs during gene duplications in both the sponge and the sea urchin. Our findings across nine representative metazoans also underscore a heightened expression of SRCR-SFs in immune-related tissues, notably the digestive glands. This observation indicates the potential role of SRCR-SFs in reinforcing distinct immune functions in these invertebrates. Collectively, our results reveal that gene duplication, motif structure variation, and exon-intron divergence might lead to the convergent evolution of SRCR-SF expansions in the genomes of the sponge and sea urchin. Our study also suggests that the utilization of SRCR-SF receptor duplication may be a general and basal strategy to increase immune diversity and tissue specificity for the invertebrates.

In Situ Spatiotemporal SERS Profiling of Bacterial Quorum Sensing by Hierarchical Hydrophobic Plasmonic Arrays in Agar Medium.

A feedback inhibition effect of high autoinducer levels on metabolite secretion in Chromobacterium subtsugae (C. subtsugae) was evidenced by in situ spatiotemporal surface-enhanced Raman spectroscopy (SERS) profiling. The hierarchical hydrophobic plasmonic array in agar medium is structured by oil/water/oil (OL/W/OH) triphasic interfacial self-assembly. The hydrophobic layer acts as a "door curtain" to selectively permit adsorption of a quorum sensing (QS)-regulated fat-soluble metabolite, i.e., violacein (Vio), and significantly blocks nonspecific adsorption of water-soluble proteins, etc. The SERS profiling clearly evidences that the diffusion of N-hexanoyl-l-homoserine lactone (C6-HSL) in agar medium quickly triggers the initial synthesis of Vio in C. subtsugae CV026 but surprisingly inhibits the intrinsic synthesis of Vio in C. subtsugae ATCC31532. The latter negative response might be related to the VioS repressor of ATCC31532, which negatively controls violacein production without influencing the expression of the CviI/R QS system. Moreover, two sender-receiver systems are constructed by separately coculturing CV026 or ATCC31532 with Hafnia alvei H4 that secretes large amounts of C6-HSL. Expectedly, the cocultivation similarly triggers the initial synthesis of Vio in CV026 but seems to have a quite weak negative effect on the intrinsic synthesis in ATCC31532. In fact, the negative regulation in ATCC31532 might be affected by a diffusion-dependent concentration effect. The H4 growth and its secretion of C6-HSL are a slow and continuous process, thereby avoiding the gathering of local high concentrations. Overall, our study put forward an in situ SERS strategy as an alternative to traditional bioluminescent tools for highly sensitively analyzing the spatiotemporal communication and cooperation in live microbial colonies.

Assessing the Settling Velocity of Biofilm-Encrusted Microplastics: Accounting for Biofilms as an Equivalent to Surface Roughness.

While it is well established that a biofilm contributes to the sinking of plastics, the underlying mechanisms of how it influences the vertical transport of plastics have not been well explained. In this context, our study dives into the intricate effects of biofouling on the settling velocity (Ws) of microplastics (MPs) within the fluid. We adopt the perspective that the biofilm is a form of surface roughness impacting the drag coefficient (Cd) and vertical settling of MPs. By advancing the biofouling process model, we simulate the temporal variations of density and biofilm thickness of biofouled floating MPs, accounting for realistic parameters and assuming a layer-by-layer growth of biofilm on plastisphere surfaces. MPs of polyethylene (PE) exhibit a quicker initiation of descent compared to their polypropylene (PP) counterparts. Furthermore, leveraging computational fluid dynamics (CFD) simulation, the method to predict the Cd of spherical MPs with surface roughness is established. By treating the thickness of the biofilm as roughness height, an explicit method to predict the Ws of biofouled MPs is derived. The settling experiments for biofouled MPs conducted not only support the combination of the biofouling model and the explicit method to predict the Ws of biofouled MPs but also enhance the prediction accuracy by introducing a ratio parameter Co to better relate the equivalent surface roughness height (k) to the biofilm thickness (σ), i.e., k = Co·σ, where the recommended value of Co for spherical PP and PE MPs is between 0.5 to 0.8. This study, thus, provides new insights into the dynamics of biofouled MPs in hydraulic ecosystems.

Irritable Bowel Syndrome Is Associated With Brain Health by Neuroimaging, Behavioral, Biochemical, and Genetic Analyses.

BACKGROUND: Irritable bowel syndrome (IBS) interacts with psychopathology in a complex way; however, little is known about the underlying brain, biochemical, and genetic mechanisms. METHODS: To clarify the phenotypic and genetic associations between IBS and brain health, we performed a comprehensive retrospective cohort study on a large population. Our study included 171,104 participants from the UK Biobank who underwent a thorough assessment of IBS, with the majority also providing neuroimaging, behavioral, biochemical, and genetic information. Multistage linked analyses were conducted, including phenome-wide association analysis, polygenic risk score calculation, and 2-sample Mendelian randomization analysis. RESULTS: The phenome-wide association analysis showed that IBS was linked to brain health problems, including anxiety and depression, and poor cognitive performance. Significantly lower brain volumes associated with more severe IBS were found in key areas related to emotional regulation and higher-order cognition, including the medial orbitofrontal cortex/ventromedial prefrontal cortex, anterior insula, anterior and mid-cingulate cortices, dorsolateral prefrontal cortex, and hippocampus. Higher triglycerides, lower high-intensity lipoprotein, and lower platelets were also related (p < 1 × 10-10) to more severe IBS. Finally, Mendelian randomization analyses demonstrated potential causal relationships between IBS and brain health and indicated possible mediating effects of dyslipidemia and inflammation. CONCLUSIONS: For the first time, this study provides a comprehensive understanding of the relationship between IBS and brain health phenotypes, integrating perspectives from neuroimaging, behavioral performance, biochemical factors, and genetics, which is of great significance for clinical applications to potentially address brain health impairments in patients with IBS.

Subtyping treatment response of tirofiban in acute ischemic stroke based on neuroimaging features.

In a previously published clinical trial, we demonstrated that tirofiban was effective and safe in acute ischemic stroke (AIS) patients who did not undergo early recanalization treatments. We aimed to evaluate neuroimaging characteristics and their clinical significance to guide tirofiban treatment. In this post hoc analysis, location of infarcts (anterior circulation stroke [ACS] vs. posterior circulation stroke [PCS]), degree of cerebral artery stenosis (≤69% vs. ≥70% or occlusion), total infarct volume, and ASPECTS were used to predict the treatment effects of tirofiban, defined as the proportions of excellent and favorable functional outcome (modified Rankin Scale [mRS] score of 0-1, 0-2) at 90 days. ACS patients were more likely to achieve excellent (OR 2.08; 95% CI 1.25-3.45; p = 0.004) and favorable functional outcome (OR 2.28; 95% CI 1.24-4.22; p = 0.008) when treated with tirofiban. However, there was no significant difference in PCS patients between tirofiban and the control group. For patients with severe stenosis (≥70% or occlusion), tirofiban treatment improved the proportion of good outcomes (OR 2.84; 95% CI 1.44-5.60; p = 0.002 for mRS 0-1; OR 2.42; 95% CI 1.22-4.77; p = 0.011 for mRS 0-2). Meanwhile, we found that tirofiban improved outcome in patients with ASPECTS 8-10 and was independent of total infarct volume. These findings support the hypothesis that patients with ACS and severe stenosis may be recommended for tirofiban treatment, which can be predicted independent of total infarct volume.

Socioeconomic status, lifestyle and risk of incident dementia: a prospective cohort study of 276730 participants.

Healthy lifestyle might alleviate the socioeconomic inequities in health, but the extent of the joint and interactive effects of these two factors on dementia are unclear. This study aimed to detect the joint and interactive associations of socioeconomic status (SES) and lifestyle factors with incident dementia risk, and the underlying brain imaging alterations. Cox proportional hazards analysis was performed to test the joint and interactive associations. Partial correlation analysis was performed to reflect the brain imaging alterations. A total of 276,730 participants with a mean age of 55.9 (±8.0) years old from UK biobank were included. Over 8.5 (±2.6) years of follow-up, 3013 participants were diagnosed with dementia. Participants with high SES and most healthy lifestyle had a significantly lower risk of incident dementia (HR=0.19, 95% CI=0.14 to 0.26, P<2×10-16), Alzheimer's disease (AD, HR=0.19, 95% CI=0.13 to 0.29, P=8.94×10-15), and vascular dementia (HR=0.24, 95% CI=0.12 to 0.48, P=7.57×10-05) compared with participants with low SES and an unhealthy lifestyle. Significant interactions were found between SES and lifestyle on dementia (P=0.002) and AD (P=0.001) risks; the association between lifestyle and dementia was stronger among those of high SES. The combination of high SES and healthy lifestyle was positively associated with higher volumes in brain regions vulnerable to dementia-related atrophy. These findings suggest that SES and lifestyle significantly interact and influence dementia with its related brain structure phenotypes.

In vitro and in†vivo biological evaluation of Lappaconitine derivatives as potential anti-inflammatory agents.

Natural products and their derivatives are a precious treasure in the pursuit of potent anti-inflammatory drugs. In this work, we measured the toxicity of 78 LA derivatives at 20 µM using MTT, then we evaluated the NO release of compounds without obvious toxicity in LPS-induced RAW.264.7 by Griess reagent, we identified three compounds, namely compounds 6, 19, 70, which exhibited promising anti-inflammatory potential. These compounds exhibited IC50 values of 10.34±2.05 µM, 18.18±4.80 µM and 15.66±0.88 µM. In addition, through ELISA kits, compounds 6, 19, 70 significantly reduce the production of inflammatory factors (TNF-α, IL-6, IL-1ß). Real-time PCR and western blot analysis showed that compounds 6, 19, 70 inhibited the mRNA and protein expression of iNOS and COX-2. Notably, compound 6 exhibited the most potent inhibitory activity. In vitro, it inhibits LPS-induced phosphorylation of NF-κB p65, IκBα, ERK1/2, JNK, and p38 MAPKs in RAW264.7 cells. In vivo, compound 6 potently inhibits the secretion of inflammatory mediators and neutrophil activation in ALI mice. Our findings suggest that compound 6 may be a potential anti-inflammatory drug.

Dopaminergic-related Anatomical Pattern of Dorsal Striatum in Schizophrenia.

Striatal dopaminergic overactivity was hypothesized as the core pathophysiology of schizophrenia. However, morphological alterations of striatum in schizophrenia remains exclusive, largely because brain regional heterogeneity limited traditional group-mean based approach. Leveraging third-party brain maps of neurotransmitter and cognition behaviours, we developed a pattern-based representation feature score (ReFS) to investigate structural spatial pattern variation in schizophrenia. Structural ReFS of subcortical regions, particularly the striatum, were linked to schizophrenia diagnosis, symptom severity, and genetic susceptibility. Dopaminergic-ReFS of striatum was increased in schizophrenia patients and reliably reproduced across 13 datasets. The pattern-based ReFS effectively captured the shared genetic pathways underlying both schizophrenia and striatum. The results provide convergent, multimodal suggest the central role of striatal spatial patterns in schizophrenia psychopathologies and and open new avenues to develop individualized treatments for psychotic disorders.

Circulating metabolites and risk of incident dementia: A prospective cohort study.

Identifying circulating metabolites associated with dementia, cognition, and brain volume may improve the understanding of dementia pathogenesis and provide novel insights for preventive and therapeutic interventions. This cohort study included a total of 87 885 participants (median follow-up of 9.1 years, 54% female) without dementia at baseline from the UK Biobank. A total of 249 plasma metabolites were measured using nuclear magnetic resonance spectroscopy at baseline. Cox proportional regression was used to examine the associations of each metabolite with incident dementia (cases = 1134), Alzheimer's disease (AD; cases = 488), and vascular dementia (VD; cases = 257) during follow-up. Dementia-associated metabolites were further analyzed for association with cognitive deficits (N = 87 885) and brain volume (N = 7756) using logistic regression and linear regression. We identified 26 metabolites associated with incident dementia, of which 6 were associated with incident AD and 5 were associated with incident VD. These 26 dementia-related metabolites were subfractions of intermediate-density lipoprotein, large low-density lipoprotein (L-LDL), small high-density lipoprotein (S-HDL), very-low-density lipoprotein, fatty acids, ketone bodies, citrate, glucose, and valine. Among them, the cholesterol percentage in L-LDL (L-LDL-C%) was associated with lower risk of AD (HR [95% CI] = 0.92 [0.87-0.97], p = 0.002), higher brain cortical (ß = 0.047, p = 3.91 × 10-6 ), and hippocampal (ß = 0.043, p = 1.93 × 10-4 ) volume. Cholesteryl ester-to-total lipid ratio in L-LDL (L-LDL-CE%) was associated with lower risk of AD (HR [95% CI] = 0.93 [0.90-0.96], p = 1.48 × 10-4 ), cognitive deficits (odds ratio = 0.98, p = 0.009), and higher hippocampal volume (ß = 0.027, p = 0.009). Cholesteryl esters in S-HDL (S-HDL-CE) were associated with lower risk of VD (HR [95% CI] = 0.81 [0.71-0.93], p = 0.002), but not AD. Taken together, circulating levels of L-LDL-CE% and L-LDL-C% were robustly associated with risk of AD and AD phenotypes, but not with VD. S-HDL-CE was associated with lower risk of VD, but not with AD or AD phenotypes. These metabolites may play a role in the advancement of future intervention trials. Additional research is necessary to gain a complete comprehension of the molecular mechanisms behind these associations.

Comparison of anti-thymocyte globulin-based immunosuppressive therapy and allogeneic hematopoietic stem cell transplantation in patients with transfusion-dependent non-severe aplastic anaemia: a retrospective study from a single centre.

OBJECTIVES: The selection and timing of anti-thymocyte globulin (ATG)-based immunosuppressive therapy (IST) or allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with transfusion-dependent non-severe aplastic anemia (TD-NSAA) pose significant clinical challenges. This study aims to compare the efficacy and long-term outcomes of the two treatments in TD-NSAA. METHODS: Patients who underwent ATG-based IST or allo-HSCT between July 2011 and December 2019 were reviewed. We gathered their clinical information, treatment response, survival data, and subsequently analysed the associated risk factors. RESULTS: A total of 97 TD-NSAA patients were reviewed, and 55 patients who underwent either ATG-based IST (n = 27) or allo-HSCT (n = 28) were enrolled. We observed a significant disparity in the 12-month overall response rate (ORR) (48.1% in IST vs 78.6% in HSCT, p < 0.05), but not in five-year overall survival (OS) and event-free survival (EFS). Multivariate Cox regression analysis identified the transfusion of ≥78.75 units of red blood cells (RBCs) as the sole independent risk factor for OS (HR: 17.04, p = 0.039) in the IST group. For the HSCT group, disease duration (DD) ≥20 months and transfusion of ≥78.75 units of RBCs predicted an adverse EFS. Frontline IST exhibited superior 12-month ORR (68.8% vs 18.2%, p = 0.018) and five-year EFS when compared to non-frontline. Patients with a DD ranging from 6 to 20 months displayed a better EFS (p = 0.016) in HSCT group than those in the ATG-based IST group. CONCLUSIONS: Prior treatment history, disease duration, and serum ferritin levels should be carefully weighed when making the choice between ATG-based IST and allo-HSCT for TD-NSAA.

The selection and timing of anti-thymocyte globulin (ATG)-based immunosuppressive therapy (IST) or allogeneic hematopoietic stem cell transplantation (allo-HSCT) present notable clinical challenges for individuals with transfusion-dependent non-severe aplastic anaemia (TD-NSAA).In terms of treatment outcomes, allo-HSCT exhibited a higher 12-month overall response rate (ORR) in comparison to ATG-based IST among TD-NSAA patients. Nevertheless, comparable rates of 5-year overall survival (OS) and event-free survival (EFS) were observed between the two therapeutic approaches.Several factors warrant consideration when deliberating between ATG-based IST and allo-HSCT for TD-NSAA. These factors include the patient's prior treatment history, disease duration, number of packed red cell transfusions received, and serum ferritin levels.

Artificial intelligence-enabled quantitative phase imaging methods for life sciences.

Quantitative phase imaging, integrated with artificial intelligence, allows for the rapid and label-free investigation of the physiology and pathology of biological systems. This review presents the principles of various two-dimensional and three-dimensional label-free phase imaging techniques that exploit refractive index as an intrinsic optical imaging contrast. In particular, we discuss artificial intelligence-based analysis methodologies for biomedical studies including image enhancement, segmentation of cellular or subcellular structures, classification of types of biological samples and image translation to furnish subcellular and histochemical information from label-free phase images. We also discuss the advantages and challenges of artificial intelligence-enabled quantitative phase imaging analyses, summarize recent notable applications in the life sciences, and cover the potential of this field for basic and industrial research in the life sciences.

The role of regulatory T cells in the pathogenesis of acute kidney injury.

The incidence of acute kidney injury (AKI) is on the rise and is associated with high mortality; however, there are currently few effective treatments. Moreover, the relationship between Tregs and other components of the immune microenvironment (IME) in the pathogenesis of AKI remains unclear. We downloaded four publicly accessible AKI datasets, GSE61739, GSE67401, GSE19130, GSE81741, GSE19288 and GSE106993 from the gene expression omnibus (GEO) database. Additionally, we gathered two kidney single-cell sequencing (scRNA-seq) samples from the Department of Organ Transplantation at Zhujiang Hospital of Southern Medical University to investigate chronic kidney transplant rejection (CKTR). Moreover, we also collected three samples of normal kidney tissue from GSE131685. By analysing the differences in immune cells between the AKI and Non-AKI groups, we discovered that the Non-AKI group contained a significantly greater number of Tregs than the AKI group. Additionally, the activation of signalling pathways, such as inflammatory molecules secretion, immune response, glycolytic metabolism, NOTCH, FGF, NF-κB and TLR4, was significantly greater in the AKI group than in the Non-AKI group. Additionally, analysis of single-cell sequencing data revealed that Tregs in patients with chronic kidney rejection and in normal kidney tissue have distinct biology, including immune activation, cytokine production, and activation fractions of signalling pathways such as NOTCH and TLR4. In this study, we found significant differences in the IME between AKI and Non-AKI, including differences in Tregs cells and activation levels of biologically significant signalling pathways. Tregs were associated with lower activity of signalling pathways such as inflammatory response, inflammatory molecule secretion, immune activation, glycolysis.

Er:YAG Laser Physical Etching and Ultra-High-Molecular-Weight Cross-Linked Sodium Polyacrylate Chemical Etching for a Reliable Dentin Dry Bonding.

Dentin bond interface stability is the key issue of dental adhesion in present clinical dentistry. The concept of selective extrafibrillar demineralization has opened a new way to maintain intrafibrillar minerals to prevent interface degradation. Here, using ultra-high-molecular-weight sodium polyacrylate [Carbopol (Carbo) > 40 kDa] as a calcium chelator, we challenge this concept and propose a protocol for reliable dentin dry bonding. The results of high-resolution transmission electron microscopy revealed periodic bands of 67 nm dentin collagen fibrils after Carbo etching, and the hydroxyproline concentration increasing with prolonged chelating time denied the concept of extrafibrillar demineralization. The results that wet and dry bonding with Carbo-based demineralization produced a weaker bond strength than the traditional phosphoric acid wet adhesion suggested that the Carbo-based demineralization is an unreliable adhesion strategy. A novel protocol of Er:YAG laser physical etching followed by Carbo chemical etching for dentin adhesion revealed that a micro-/nano-level rough, rigid, and non-collagen exposed dentin surface was produced, the micro-tensile bond strength was maintained after aging under dry and wet bonding modes, and in situ zymography and nanoleakage within the hybrid layers presented lower signals after aging. Cell culture in vitro and a rabbit deep dentin adhesion model in vivo proved that this protocol is safe and biocompatible. Taken together, the concept of extrafibrillar demineralization is limited and insufficient to use in the clinic. The strategy of Er:YAG laser physical etching followed by Carbo chemical etching for dentin adhesion produces a bonding effect with reliability, durability, and safety.

Association between polygenic risk for Alzheimer's disease and brain structure in children and adults.

BACKGROUND: The correlations between genetic risk for Alzheimer's disease (AD) with comprehensive brain regions at a regional scale are still not well understood. We aim to explore whether these associations vary across different age stages. METHODS: This study used large existing genome-wide association datasets to calculate polygenic risk score (PRS) for AD in two populations from the UK Biobank (N ~ 23 000) and Adolescent Brain Cognitive Development Study (N ~ 4660) who had multimodal macrostructural and microstructural magnetic resonance imaging (MRI) metrics. We used linear mixed-effect models to assess the strength of the association between AD PRS and multiple MRI metrics of regional brain structures at different stages of life. RESULTS: Compared to those with lower PRSs, adolescents with higher PRSs had thinner cortex in the caudal anterior cingulate and supramarginal. In the middle-aged and elderly population, AD PRS had correlations with regional structure shrink primarily located in the cingulate, prefrontal cortex, hippocampus, thalamus, amygdala, and striatum, whereas the brain expansion was concentrated near the occipital lobe. Furthermore, both adults and adolescents with higher PRSs exhibited widespread white matter microstructural changes, indicated by decreased fractional anisotropy (FA) or increased mean diffusivity (MD). CONCLUSIONS: In conclusion, our results suggest genetic loading for AD may influence brain structures in a highly dynamic manner, with dramatically different patterns at different ages. This age-specific change is consistent with the classical pattern of brain impairment observed in AD patients.