Improving precision management of anxiety disorders: a Mendelian randomization study targeting specific gut microbiota and associated metabolites.

Background: There is growing evidence of associations between the gut microbiota and anxiety disorders, where changes in gut microbiotas may affect brain function and behavior via the microbiota-gut-brain axis. However, population-level studies offering a higher level of evidence for causality are lacking. Our aim was to investigate the specific gut microbiota and associated metabolites that are closely related to anxiety disorders to provide mechanistic insights and novel management perspectives for anxiety disorders. Method: This study used summary-level data from publicly available Genome-Wide Association Studies (GWAS) for 119 bacterial genera and the phenotype "All anxiety disorders" to reveal the causal effects of gut microbiota on anxiety disorders and identify specific bacterial genera associated with anxiety disorders. A two-sample, bidirectional Mendelian randomization (MR) design was deployed, followed by comprehensive sensitivity analyses to validate the robustness of results. We further conducted multivariable MR (MVMR) analysis to investigate the potential impact of neurotransmitter-associated metabolites, bacteria-associated dietary patterns, drug use or alcohol consumption, and lifestyle factors such as smoking and physical activity on the observed associations. Results: Bidirectional MR analysis identified three bacterial genera causally related to anxiety disorders: the genus Eubacterium nodatum group and genus Ruminococcaceae UCG011 were protective, while the genus Ruminococcaceae UCG011 was associated with an increased risk of anxiety disorders. Further MVMR suggested that a metabolite-dependent mechanism, primarily driven by tryptophan, tyrosine, phenylalanine, glycine and cortisol, which is consistent with previous research findings, probably played a significant role in mediating the effects of these bacterial genera to anxiety disorders. Furthermore, modifying dietary pattern such as salt, sugar and processed meat intake, and adjusting smoking state and physical activity levels, appears to be the effective approaches for targeting specific gut microbiota to manage anxiety disorders. Conclusion: Our findings offer potential avenues for developing precise and effective management approaches for anxiety disorders by targeting specific gut microbiota and associated metabolites.

Cross-modality mapping using image varifolds to align tissue-scale atlases to molecular-scale measures with application to 2D brain sections.

This paper explicates a solution to building correspondences between molecular-scale transcriptomics and tissue-scale atlases. This problem arises in atlas construction and cross-specimen/technology alignment where specimens per emerging technology remain sparse and conventional image representations cannot efficiently model the high dimensions from subcellular detection of thousands of genes. We address these challenges by representing spatial transcriptomics data as generalized functions encoding position and high-dimensional feature (gene, cell type) identity. We map onto low-dimensional atlas ontologies by modeling regions as homogeneous random fields with unknown transcriptomic feature distribution. We solve simultaneously for the minimizing geodesic diffeomorphism of coordinates through LDDMM and for these latent feature densities. We map tissue-scale mouse brain atlases to gene-based and cell-based transcriptomics data from MERFISH and BARseq technologies and to histopathology and cross-species atlases to illustrate integration of diverse molecular and cellular datasets into a single coordinate system as a means of comparison and further atlas construction.

Whole-cortex in situ sequencing reveals input-dependent area identity.

The cerebral cortex is composed of neuronal types with diverse gene expression that are organized into specialized cortical areas. These areas, each with characteristic cytoarchitecture1,2, connectivity3,4 and neuronal activity5,6, are wired into modular networks3,4,7. However, it remains unclear whether these spatial organizations are reflected in neuronal transcriptomic signatures and how such signatures are established in development. Here we used BARseq, a high-throughput in situ sequencing technique, to interrogate the expression of 104 cell-type marker genes in 10.3 million cells, including 4,194,658 cortical neurons over nine mouse forebrain hemispheres, at cellular resolution. De novo clustering of gene expression in single neurons revealed transcriptomic types consistent with previous single-cell RNA sequencing studies8,9. The composition of transcriptomic types is highly predictive of cortical area identity. Moreover, areas with similar compositions of transcriptomic types, which we defined as cortical modules, overlap with areas that are highly connected, suggesting that the same modular organization is reflected in both transcriptomic signatures and connectivity. To explore how the transcriptomic profiles of cortical neurons depend on development, we assessed cell-type distributions after neonatal binocular enucleation. Notably, binocular enucleation caused the shifting of the cell-type compositional profiles of visual areas towards neighbouring cortical areas within the same module, suggesting that peripheral inputs sharpen the distinct transcriptomic identities of areas within cortical modules. Enabled by the high throughput, low cost and reproducibility of BARseq, our study provides a proof of principle for the use of large-scale in situ sequencing to both reveal brain-wide molecular architecture and understand its development.

Reimagining Cortical Connectivity by Deconstructing Its Molecular Logic into Building Blocks.

Comprehensive maps of neuronal connectivity provide a foundation for understanding the structure of neural circuits. In a circuit, neurons are diverse in morphology, electrophysiology, gene expression, activity, and other neuronal properties. Thus, constructing a comprehensive connectivity map requires associating various properties of neurons, including their connectivity, at cellular resolution. A commonly used approach is to use the gene expression profiles as an anchor to which all other neuronal properties are associated. Recent advances in genomics and anatomical techniques dramatically improved the ability to determine and associate the long-range projections of neurons with their gene expression profiles. These studies revealed unprecedented details of the gene-projection relationship, but also highlighted conceptual challenges in understanding this relationship. In this article, I delve into the findings and the challenges revealed by recent studies using state-of-the-art neuroanatomical and transcriptomic techniques. Building upon these insights, I propose an approach that focuses on understanding the gene-projection relationship through basic features in gene expression profiles and projections, respectively, that associate with underlying cellular processes. I then discuss how the developmental trajectories of projections and gene expression profiles create additional challenges and necessitate interrogating the gene-projection relationship across time. Finally, I explore complementary strategies that, together, can provide a comprehensive view of the gene-projection relationship.

Dietary Factors and Risk of Gout: A Two-Sample Mendelian Randomization Study.

BACKGROUND: Dietary intervention is the preferred approach for the prevention and clinical management of gout. Nevertheless, the existing evidence regarding the influence of specific foods on gout is insufficient. METHODS: We used two-sample Mendelian randomization for genetic prediction to analyze the relationship between the intake of more than a dozen daily food items, such as pork, beef, cheese, and poultry, and dietary macronutrient intake (fat, protein, carbohydrates, and sugar) and the risk of developing gout and elevating the serum uric acid level. Inverse-variance weighted MR analyses were used as the main evaluation method, and the reliability of the results was tested by a sensitivity analysis. RESULTS: Cheese intake was associated with lower serum uric acid levels, and tea intake (OR = 0.523, [95%CI: 0.348~0.784], p = 0.002), coffee intake (OR = 0.449, [95%CI: 0.229~0.882], p = 0.020), and dried fruit intake (OR = 0.533, [95%CI: 0.286~0.992], p = 0.047) showed a preventive effect on the risk of gouty attacks. In contrast, non-oily fish intake (ß = 1.08, [95%CI: 0.24~1.92], p = 0.012) and sugar intake (ß = 0.34, [95%CI: 0.03~0.64], p = 0.030) were risk factors for elevated serum uric acid levels, and alcohol intake frequency (OR = 1.422, [95%CI: 1.079~1.873], p = 0.012) was a risk factors for gout predisposition. CONCLUSIONS: These results will significantly contribute to the formulation and refinement of nutritional strategies tailored to patients afflicted with gout.

Rabies virus-based barcoded neuroanatomy resolved by single-cell RNA and in situ sequencing.

Mapping the connectivity of diverse neuronal types provides the foundation for understanding the structure and function of neural circuits. High-throughput and low-cost neuroanatomical techniques based on RNA barcode sequencing have the potential to map circuits at cellular resolution and a brain-wide scale, but existing Sindbis virus-based techniques can only map long-range projections using anterograde tracing approaches. Rabies virus can complement anterograde tracing approaches by enabling either retrograde labeling of projection neurons or monosynaptic tracing of direct inputs to genetically targeted postsynaptic neurons. However, barcoded rabies virus has so far been only used to map non-neuronal cellular interactions in vivo and synaptic connectivity of cultured neurons. Here we combine barcoded rabies virus with single-cell and in situ sequencing to perform retrograde labeling and transsynaptic labeling in the mouse brain. We sequenced 96 retrogradely labeled cells and 295 transsynaptically labeled cells using single-cell RNA-seq, and 4130 retrogradely labeled cells and 2914 transsynaptically labeled cells in situ. We found that the transcriptomic identities of rabies virus-infected cells can be robustly identified using both single-cell RNA-seq and in situ sequencing. By associating gene expression with connectivity inferred from barcode sequencing, we distinguished long-range projecting cortical cell types from multiple cortical areas and identified cell types with converging or diverging synaptic connectivity. Combining in situ sequencing with barcoded rabies virus complements existing sequencing-based neuroanatomical techniques and provides a potential path for mapping synaptic connectivity of neuronal types at scale.

In the brain, messages are relayed from one cell to the next through intricate networks of axons and dendrites that physically interact at junctions known as synapses. Mapping out this synaptic connectivity ­ that is, exactly which neurons are connected via synapses ­ remains a major challenge. Monosynaptic tracing is a powerful approach that allows neuroscientists to explore neural networks by harnessing viruses which spread between neurons via synapses, in particular the rabies virus. This pathogen travels exclusively from 'postsynaptic' to 'presynaptic' neurons ­ from the cell that receives a message at a synapse, back to the one that sends it. A modified variant of the rabies virus can therefore be used to reveal the presynaptic cells connecting to a population of neurons in which it has been originally introduced. However, this method does not allow scientists to identify the exact postsynaptic neuron that each presynaptic cell is connected to. One way to bypass this issue is to combine monosynaptic tracing with RNA barcoding to create distinct versions of the modified rabies virus, which are then introduced into separate populations of neurons. Tracking the spread of each version allows neuroscientists to spot exactly which presynaptic cells signal to each postsynaptic neuron. So far, this approach has been used to examine synaptic connectivity in neurons grown in the laboratory, but it remains difficult to apply it to neurons in the brain. In response, Zhang, Jin et al. aimed to demonstrate how monosynaptic tracing that relies on barcoded rabies viruses could be used to dissect neural networks in the mouse brain. First, they confirmed that it was possible to accurately detect which version of the virus had spread to presynaptic neurons using both in situ and single-cell RNA sequencing. Next, they described how this information could be analysed to build models of potential neural networks, and what type of additional experiments are required for this work. Finally, they used the approach to identify neurons that tend to connect to the same postsynaptic cells and then investigated what these have in common, showing how the technique enables a finer understanding of neural circuits. Overall, the work by Zhang, Jin et al. provides a comprehensive review of the requirements and limitations associated with monosynaptic tracing experiments based on barcoded rabies viruses, as well as how the approach could be optimized in the future. This information will be of broad interest to scientists interested in mapping neural networks in the brain.

Short-Term Ambient Air Pollution and Urticaria in Guangzhou, China: Estimating the Association and Population Attributable Fraction.

Limited evidence is available regarding the association between acute exposure to ambient air pollutants and the risk of urticaria, even though the skin is an organ with direct contact with the external environment. This study utilized generalized additive models to investigate the association between particulate matter with an aerodynamic diameter smaller than 10 µm (PM10) and 2.5 µm (PM2.5), nitrogen dioxide (NO2) and sulfur dioxide (SO2), and daily outpatient visits for urticaria in Guangzhou, China from 2013 to 2017. We also estimated the attributable fraction of urticaria outpatient visits due to air pollution. A total of 216,648 outpatient visits due to urticaria occurred during the study period. All air pollutants were significantly associated with an increased excess risk of urticaria. Each 10 µg/m3 increase in PM2.5, PM10, NO2, and SO2 was associated with an increase of 1.23% (95% CI: 0.42%, 2.06%), 0.88% (95% CI: 0.28%, 1.49%), 3.09% (95% CI: 2.16%, 4.03%), and 2.82% (95% CI: 0.93%, 4.74%) in hospital visits for urticaria at lag05, respectively. It was estimated that 3.77% (95% CI: 1.26%, 6.38%), 1.91% (95% CI: 0.60%, 3.26%), 6.36% (95% CI: 4.38%, 8.41%), and 0.08% (95% CI: 0.03%, 0.14%) of urticaria outpatient visits were attributable to PM2.5, PM10, NO2, and SO2 using the World Health Organization's air quality guideline as the reference. Relatively stronger associations were observed during the cold season. This study indicates that short-term air pollution may play a significant role in outpatient visits for urticaria, and that such relationships could be modified by season.

The gut-lung axis in influenza A: the role of gut microbiota in immune balance.

Influenza A, the most common subtype, induces 3 to 5 million severe infections and 250,000 to 500,000 deaths each year. Vaccination is traditionally considered to be the best way to prevent influenza A. Yet because the Influenza A virus (IAV) is highly susceptible to antigenic drift and Antigenic shift, and because of the lag in vaccine production, this poses a significant challenge to vaccine effectiveness. Additionally, much information about the resistance of antiviral drugs, such as Oseltamivir and Baloxavir, has been reported. Therefore, the search for alternative therapies in the treatment of influenza is warranted. Recent studies have found that regulating the gut microbiota (GM) can promote the immune effects of anti-IAV via the gut-lung axis. This includes promoting IAV clearance in the early stages of infection and reducing inflammatory damage in the later stages. In this review, we first review the specific alterations in GM observed in human as well as animal models regarding IAV infection. Then we analyzed the effect of GM on host immunity against IAV, including innate immunity and subsequent adaptive immunity. Finally, our study also summarizes the effects of therapies using probiotics, prebiotics, or herbal medicine in influenza A on intestinal microecological composition and their immunomodulatory effects against IAV.

1,8-cineole ameliorates colon injury by downregulating macrophage M1 polarization via inhibiting the HSP90-NLRP3-SGT1 complex.

Ulcerative colitis (UC) is characterized by chronic relapsing intestinal inflammation. Currently, there is no effective treatment for the disease. According to our preliminary data, 1,8-cineole, which is the main active compound of Amomum compactum Sol. ex Maton volatile oil and an effective drug for the treatment of pneumonia, showed remarkable anti-inflammatory effects on colitis pathogenesis. However, its mechanism of action and direct targets remain unclear. This study investigated the direct targets and mechanism through which 1,8-cineole exerts its anti-inflammatory effects using a dextran sulfate sodium salt-induced colitis mouse model. The effects of 1,8-cineole on macrophage polarization were investigated using activated bone marrow-derived macrophages and RAW264.7 cells. In addition, 1,8-cineole targets were revealed by drug affinity responsive target stability, thermal shift assay, cellular thermal shift assay, and heat shock protein 90 (HSP90) adenosine triphosphatases (ATPase) activity assays. The results showed that 1,8-cineole exhibited powerful anti-inflammatory properties in vitro and in vivo by inhibiting the macrophage M1 polarization and protecting intestinal barrier function. Mechanistically, 1,8-cineole directly interacted with HSP90 and decreased its ATPase activity, also inhibited nucleotide-binding and oligomerization domain-, leucine rich repeat-, and pyrin domain-containing 3 (NLRP3) binding to HSP90 and suppressor of G-two allele of SKP1 (SGT1) and suppressed NLRP3 inflammasome activation in macrophages. These results demonstrated that 1,8-cineole is a potential drug candidate for UC treatment.

Shikonin inhibits immune checkpoint PD-L1 expression on macrophage in sepsis by modulating PKM2.

Sepsis, a life-threatening condition whereby immune dysregulation develops, is one of the major causes of death worldwide. To date, there is still no clinically effective therapeutic method for sepsis. As a natural product from traditional Chinese medicine, Shikonin has been demonstrated to have pleiotropic medical effects, including anti-tumor, anti-inflammation, and relieving sepsis. PD-L1, as the receptor of PD-1, was also involved in exacerbating sepsis by inducing immunosuppression, but the relationship between them is still unclear. In this study, we aimed to evaluate the effect of Shikonin on modulating PD-L1 expression and its contact with PKM2. The results showed that Shikonin significantly decreased the levels of sepsis mice serum inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interferon-γ (IFN-γ), interleukin-1ß (IL-1ß) and maintain the percentage of T cells from the spleen and significantly reduce the apoptosis of splenocytes in LPS-induced sepsis mice. Our data also demonstrated that Shikonin significantly decreased PD-L1 expression on macrophages, not PD-1 expression on T cells in vivo and in vitro. Additionally, we revealed that Shikonin attenuated PD-L1 expression on macrophages and was associated with downregulating phosphorylation and nuclear import of PKM2, which could bind to the HRE-1 and HRE-4 sites of the PD-L1 promoter. As the present research was conducted in sepsis mice model and macrophage cell line, further study is required to evaluate Shikonin to regulate PD-L1 by targeting PKM2 in clinical samples.

Study of the Relationship between Mucosal Immunity and Commensal Microbiota: A Bibliometric Analysis.

This study presents the first bibliometric evaluation and systematic analysis of publications related to mucosal immunity and commensal microbiota over the last two decades and summarizes the contribution of countries, institutions, and scholars in the study of this field. A total of 1423 articles related to mucosal immunity and commensal microbiota in vivo published in 532 journals by 7774 authors from 1771 institutions in 74 countries/regions were analyzed. The interaction between commensal microbiota in vivo and mucosal immunity is essential in regulating the immune response of the body, maintaining communication between different kinds of commensal microbiota and the host, and so on. Several hot spots in this field have been found to have received extensive attention in recent years, especially the effects of metabolites of key strains on mucosal immunity, the physiopathological phenomena of commensal microbiota in various sites including the intestine, and the relationship between COVID-19, mucosal immunity and microbiota. We hope that the full picture of the last 20 years in this research area provided in this study will serve to deliver necessary cutting-edge information to relevant researchers.

Rabies virus-based barcoded neuroanatomy resolved by single-cell RNA and in situ sequencing.

Mapping the connectivity of diverse neuronal types provides the foundation for understanding the structure and function of neural circuits. High-throughput and low-cost neuroanatomical techniques based on RNA barcode sequencing have the potential to map circuits at cellular resolution and a brain-wide scale, but existing Sindbis virus-based techniques can only map long-range projections using anterograde tracing approaches. Rabies virus can complement anterograde tracing approaches by enabling either retrograde labeling of projection neurons or monosynaptic tracing of direct inputs to genetically targeted postsynaptic neurons. However, barcoded rabies virus has so far been only used to map non-neuronal cellular interactions in vivo and synaptic connectivity of cultured neurons. Here we combine barcoded rabies virus with single-cell and in situ sequencing to perform retrograde labeling and transsynaptic labeling in the mouse brain. We sequenced 96 retrogradely labeled cells and 295 transsynaptically labeled cells using single-cell RNA-seq, and 4,130 retrogradely labeled cells and 2,914 transsynaptically labeled cells in situ. We found that the transcriptomic identities of rabies virus-infected cells can be robustly identified using both single-cell RNA-seq and in situ sequencing. By associating gene expression with connectivity inferred from barcode sequencing, we distinguished long-range projecting cortical cell types from multiple cortical areas and identified cell types with converging or diverging synaptic connectivity. Combining in situ sequencing with barcoded rabies virus complements existing sequencing-based neuroanatomical techniques and provides a potential path for mapping synaptic connectivity of neuronal types at scale.

Massive Multiplexing of Spatially Resolved Single Neuron Projections with Axonal BARseq.

Neurons in the cortex are heterogenous, sending diverse axonal projections to multiple brain regions. Unraveling the logic of these projections requires single-neuron resolution. Although a growing number of techniques have enabled high-throughput reconstruction, these techniques are typically limited to dozens or at most hundreds of neurons per brain, requiring that statistical analyses combine data from different specimens. Here we present axonal BARseq, a high-throughput approach based on reading out nucleic acid barcodes using in situ RNA sequencing, which enables analysis of even densely labeled neurons. As a proof of principle, we have mapped the long-range projections of >8000 mouse primary auditory cortex neurons from a single brain. We identified major cell types based on projection targets and axonal trajectory. The large sample size enabled us to systematically quantify the projections of intratelencephalic (IT) neurons, and revealed that individual IT neurons project to different layers in an area-dependent fashion. Axonal BARseq is a powerful technique for studying the heterogeneity of single neuronal projections at high throughput within individual brains.

Poria cocos Polysaccharide Ameliorated Antibiotic-Associated Diarrhea in Mice via Regulating the Homeostasis of the Gut Microbiota and Intestinal Mucosal Barrier.

Poria cocos polysaccharides (PCP) have been validated for several biological activities, including antitumor, anti-inflammatory, antioxidant, immunomodulatory, hepatoprotective and modulation on gut microbiota. In this research, we aim to demonstrate the potential prebiotic effects and the therapeutic efficacies of PCP in the treatment of antibiotic-associated diarrhea (AAD), and confirm the beneficial effects of PCP on gut dysbiosis. Antibiotic-associated diarrhea mice models were established by treating them with broad-spectrum antibiotics in drinking water for seven days. Mice in two groups treated with probiotics and polysaccharide were given Bifico capsules (4.2 g/kg/d) and PCP (250 mg/kg/d) for seven days using intragastric gavage, respectively. To observe the regulatory effects of PCP on gut microbiota and intestinal mucosal barrier, we conducted the following experiments: intestinal flora analysis (16S rDNA sequencing), histology (H&E staining) and tight junction proteins (immunofluorescence staining). The levels of mRNA expression of receptors associated with inflammation and gut metabolism were assessed by real-time reverse transcription-polymerase chain reaction (RT-PCR). The study revealed that PCP can comprehensively improve the clinical symptoms of AAD mice, including fecal traits, mental state, hair quality, etc., similar to the effect of probiotics. Based on histology observation, PCP significantly improved the substantial structure of the intestine of AAD mice by increasing the expression levels of colonic tight junction protein zonula-occludens 1 (ZO-1) and its mRNA. Moreover, PCP not only increased the abundance of gut microbiota, but also increased the diversity of gut microbiota in AAD mice, including alpha diversity and beta diversity. Further analysis found that PCP can modulate seven characteristic species of intestinal flora in AAD mice, including Parabacteroides_distasonis, Akkermansia_muciniphila, Clostridium_saccharolyticum, Ruminoc-occus_gnavus, Lactobacillus_salivarius, Salmonella_enterica and Mucispirillum_schaedleri. Finally, enrichment analysis predicted that PCP may affect intestinal mucosal barrier function, host immune response and metabolic function by regulating the microbiota. RT-PCR experiments showed that PCP can participate in immunomodulatory and modulation on metabolic by regulating the mRNA expression of forkhead-box protein 3 (FOXP3) and G protein-coupled receptor 41 (GPR41). These results indicated that Poria cocos polysaccharide may ameliorate antibiotic-associated diarrhea in mice by regulating the homeostasis of the gut microbiota and intestinal mucosal barrier. In addition, polysaccharide-derived changes in intestinal microbiota were involved in the immunomodulatory activities and modulation of the metabolism.

Proanthocyanidins attenuates ferroptosis against influenza-induced acute lung injury in mice by reducing IFN-γ.

BACKGROUND: Acute lung injury (ALI) is associated with high morbidity and mortality and is partly driven promoted by ferroptosis. Proanthocyanidins (PAs) is a natural bioactive flavonoid with anti-inflammatory and antioxidant activities. PAs can also significantly protect against acute lung inflammation and ferroptosis in alveolar epithelial cells. However, it is unclear whether PAs can alleviate ALI by reducing ferroptosis. This study aimed to evaluate the protective effects of PAs and the potential mechanisms against Influenza A virus (IAV)-induced ALI. METHODS: Mice were inoculated nasally with IAV to induce ALI. IAV-induced pulmonary inflammation and ferroptosis was tested by measuring the levels of malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11) and acyl-CoA synthetase long-chain family member (ACSL4) in lung tissue. The potential targets that PAs protect against IAV-induced ALI were determined via a systemic pharmacological analysis. The molecular mechanism of PAs in ALI treatment was investigated by assessing the level of inflammation and ferroptosis markers using Western Blot and quantitative real-time PCR. RESULTS: Systemic pharmacological analysis suggested that PAs protect against IAV-induced pneumonia thorough TGF-ß1 and its relative signaling pathway. PAs effectively alleviated histopathological lung injury, reduced inflammatory cytokines and chemokines secretion, which were increased in IAV-infected mice. Meanwhile, PAs further prevented mouse airway inflammation in ALI, concomitant with the decreased expression TGF-ß1, smad2/3, p-Smad2, p-Smad3 and ferroptosis mediator IFN-γ. Furthermore，IFN-γ promotes cell lipid peroxidation and ferroptosis，PAs significantly reduced MDA and ACSL4 levels and upregulated GSH, GPX4, and SLC7A11. CONCLUSION: Overall, PAs can attenuate ferroptosis against IAV-induced ALI via the TGF-ß1/Smad2/3 pathway and is a promising novel therapeutic candidate for ALI.

Multiple/Two-Way Shape Memory Poly(urethane-urea-amide) Elastomers.

Multiple and two-way reversible shape memory polymers (M/2W-SMPs) are highly promising for many fields due to large deformation, lightweight, strong recovery stress, and fast response rates. Herein, a semi-crystalline block poly(urethane-urea-amide) elastomers (PUUAs) are prepared by the copolymerization of isocyanate-terminated polyurethane (OPU) and amino-terminated oligomeric polyamide-1212 (OPA). PUUAs, composed of OPA as stationary phase and PTMEG as reversible phase, exhibit excellent rigidity, flexibility, and resilience, and cPUUA-C7 -S25 exhibits the best tensile property with strength of 10.3 MPa and elongation at break of 360.2%. Besides, all the PUUAs possess two crystallization/melting temperatures and a glass transition temperature, which endow PUUAs with multiple and reversible two-way shape memory effect (M/2W-SME). Physically crosslinked PUUA-C0 -S25 exhibits excellent dual and triple shape memory, and micro chemically crosslinked cPUUA-C7 -S25 further shows quadruple shape memory behavior. Additionally, both PUUA-C0 -S25 and cPUUA-C7 -S25 have 2W-SME. Intriguingly, cPUUA-C7 -S25 can achieve a higher temperature (up to 165 °C) SME, which makes it suitable for more complex and changeable applications. Based on the advantages of M/2W-SME, a temperature-responsive application scenario where PUUAs can transform spontaneously among different shapes is designed. These unique M/2W-SME and high-temperature SME will enable the applications of high-temperature sensors, actuators, and aerospace equipment.

The 'perfect' lens: Perfectionism and early adolescents' math self-efficacy development.

BACKGROUND: Self-efficacy, or the beliefs learners hold about what they can do, develops largely from how learners perceive and interpret four main sources of information: mastery experiences, vicarious experiences, social persuasions and physiological and affective states. Although the relationship between these sources and self-efficacy is well-established, less is known about the factors that may influence how early adolescent learners perceive and interpret information from these sources. AIMS: The purpose of this study was to investigate how the predisposition of perfectionism might predict how learners perceive efficacy-relevant information in the domain of math. METHODS: Using a correlational design, this study considered whether perfectionism was associated with how middle school students (N = 1683) perceive information from the four hypothesized sources of self-efficacy. Participants completed a paper-based survey at two time points. Perfectionism was measured at Time 1. Self-efficacy and its sources were measured at Time 2. Structural equation modelling techniques were used to examine the relationship between factors. RESULTS AND CONCLUSIONS: Students who held themselves to high standards (i.e., greater self-oriented perfectionism) reported higher levels of mastery experiences, vicarious experiences, social messages and self-efficacy. Conversely, students who felt external pressure to be perfect (i.e., socially prescribed perfectionism) reported lower levels of mastery experiences, vicarious experiences and self-efficacy, as well as higher levels of negative physiological and affective states. The relationship between perfectionism and self-efficacy was partially mediated by students' perceptions of mastery. This study extends the current literature on the sources of math self-efficacy in early adolescence by showing how a predisposition like perfectionism is associated with how adolescent learners perceive and interpret efficacy-relevant information.

Adlay (Coix lacryma-jobi L.) Polyphenol Improves Hepatic Glucose and Lipid Homeostasis through Regulating Intestinal Flora via AMPK Pathway.

SCOPE: Non-alcoholic fatty liver disease (NAFLD) is a type of metabolic syndrome characterized of abnormal lipid deposition in the liver. Adlay polyphenol (AP), an effective component extracted from Coix lacryma-jobi L., has been reported that it can be used as a dietary supplement to prevent NAFLD. In this study, the mechanism and action of AP on lipid metabolism and regulation of intestinal flora are investigated. METHODS AND RESULTS: AP significantly decreases the lipid accumulation in free fatty acid-treated HepG2 cells. Western blot results indicate that AP improves lipid metabolism via activating the p-AMPK/p-ACC pathway. In vivo experiments show AP treatment significantly decreases the body weight, liver weight, hepatic triglyceride, and total cholesterol contents, as well as the serum glucose levels in high fat diet-fed mice, which may affect lipid accumulation by activating AMPK pathway and changing intestinal bacterial communities and intestinal microbiome metabolism. CONCLUSION: AP can be used as a food supplement for improving lipid metabolic dysfunction and reducing the incidence of metabolic diseases.

High-throughput sequencing of single neuron projections reveals spatial organization in the olfactory cortex.

In most sensory modalities, neuronal connectivity reflects behaviorally relevant stimulus features, such as spatial location, orientation, and sound frequency. By contrast, the prevailing view in the olfactory cortex, based on the reconstruction of dozens of neurons, is that connectivity is random. Here, we used high-throughput sequencing-based neuroanatomical techniques to analyze the projections of 5,309 mouse olfactory bulb and 30,433 piriform cortex output neurons at single-cell resolution. Surprisingly, statistical analysis of this much larger dataset revealed that the olfactory cortex connectivity is spatially structured. Single olfactory bulb neurons targeting a particular location along the anterior-posterior axis of piriform cortex also project to matched, functionally distinct, extra-piriform targets. Moreover, single neurons from the targeted piriform locus also project to the same matched extra-piriform targets, forming triadic circuit motifs. Thus, as in other sensory modalities, olfactory information is routed at early stages of processing to functionally diverse targets in a coordinated manner.

Copepods as Indicators of Different Water Masses during the Northeast Monsoon Prevailing Period in the Northeast Taiwan.

During this research, the average surface temperature, salinity, dissolved oxygen, and pH were 24.65 ± 1.53 (°C), 34.21 ± 0.07 (PSU), 6.85 ± 0.18 (mg/L), and 8.36 ± 0.03, respectively. Based on these environmental parameters, stations were arranged into three groups. Group A represents stations located around Keelung Island with the relative highest average dissolved oxygen, lowest average temperature, and pH values. Instead, the lowest average dissolved oxygen and highest average temperature, salinity, and pH values were recorded at the offshore stations. Keelung Island area was charged by cold water masses, which were driven by the Northeast monsoon, and stations in group C were affected by the Kuroshio Current. Kueishan Island area was mainly affected by mixed water masses resulting from the Kuroshio intrusion and monsoon-derived cold water. In this study, a total of 108 copepod species were identified, with an average abundance of 774.24 ± 289.42 (inds. m-3). Most species belong to the orders Calanoida and Poecilostomatoida, with an average relative abundance (RA) of 62.96% and 30.56%, respectively. Calanoid copepodites were the most dominant group, with a RA of 28.06%. This was followed by Paracalanus aculeatus, with a RA of 18.44%. The RA of Clausocalanus furcatus and Canthocalanus pauper was 4.80% and 3.59%, respectively. The dominant species P. aculeatus, C. pauper, Paracalanus parvus, and Temora turbinata were positively correlated with dissolved oxygen and negatively correlated with temperature in the surface waters. pH showed a negative correlation with P. parvus and T. turbinata, while the temperature was negatively correlated with these two dominant species. Indicator species were selected by an indicator value higher than 50%. Temora turbinata, Calanopia elliptica, C. pauper, Euchaeta concinna, Temora discaudata, Acartia pacifica, Macrosetella gracilis, Corycaeus speciosus, and P. parvus were considered as monsoonal cold water indicator species in Group A. Indicator copepod species for the Kuroshio Current were Farranula concinna, Copilia mirabilis, Candacia aethiopica, Corycaeus agilis, Farranula gibbula and Acrocalanus monachus in the study area. Paracandacia truncata, Oncaea clevei, P. aculeatus, and Centropages furcatus were considered suitable indicators for mixed water masses.