Causal role of immune cells in uveitis: a Mendelian randomization study.

Background: Uveitis refers to a group inflammation affecting the uvea, retina, retinal blood vessels as well as vitreous body, which is one of the common causes of blindness. There is growing evidence linking different types of immune cells to uveitis, although it remains uncertain if these associations imply causal relationships. Recent advancements in high-density genetic markers like SNPs or CNVs for genotyping, along with the progress in genome-wide association studies (GWAS) technologies, have improved our understanding of the immunological mechanisms involved in ocular diseases. Therefore, our objective was to investigate the potential causal link between immune cells and uveitis using a Mendelian randomization study. Methods: The exposure and outcome GWAS data for this study were sourced from an open-access database (https://gwas.mrcieu.ac.uk/). Two-sample MR analysis was utilized to evaluate the causal relationship between 731 immune cell features and uveitis. Various MR methods were employed to reduce bias and obtain dependable estimates of the causal link between the immune cell variables and the outcomes. Instrumental variable selection criteria were carefully chosen to enhance the accuracy and efficacy of the causal relationship between different immune cell types and the risk of uveitis. Results: Using two-sample MR, IVW modeling showed that GAD had significant effect on immunophenotypes. CD3 levels on CD45RA- CD4+ T cells (OR = 1.087, 95%CI = 1.029 ~ 1.147, p = 0.003) and CD3 levels on CM CD4+ T cells (OR = 1.086, 95%CI = 1.033 ~ 1.141, p = 0.001) were found to be elevated in cases of uveitis. HLA DR levels in CD14- CD16+ monocyte cells (OR = 0.735, 95% CI = 0.635 ~ 0.850, p < 0.001) and HLA DR levels in NK cells (OR = 0.910, 95% CI = 0.851 ~ 0.972, p = 0.005) were observed to be reduced in individuals with uveitis. Furthermore, Two cells were identified to be significantly associated with uveitis risk: HLA DR on in NK cells (OR = 0.938, 95%CI = 0.899 ~ 0.979, p = 0.003), HLA DR on CD14- CD16+ monocytes (OR = 0.924, 95%CI = 0.878 ~ 0.972, p = 0.002). Conclusion: This study highlights the intricate relationship between immune cells and generalized anxiety disorder using genetic methods, offering valuable insights for future clinical investigations.

Near-infrared AIEgens for sulfatase imaging in breast cancer in vivo.

Aggregation-induced emission luminogens (AIEgens) enable highly sensitive and in situ visualization of sulfatase to benefit the early diagnosis of breast cancer (BC), but current sulfatase AIEgens always emit visible light (<650 nm). Herein, a near-infrared (NIR) AIEgen QMT-SFA is developed for sulfatase imaging in vivo. Hydrophilic QMT-SFA is cleaved by sulfatase to yield hydrophobic QMT-OH, which subsequently aggregates into nanoparticles to turn the AIE fluorescence "on", enabling sensitive sulfatase imaging in 4T1 cells and mouse models.

C8-ceramide modulates microglia BDNF expression to alleviate postoperative cognition dysfunction via PKCδ/NF-κB signaling pathway.

Postoperative cognitive dysfunction (POCD) is a kind of serious postoperative complication in surgery with general anesthesia and it may affect patients' normal lives. Activated microglia are thought to be one of the key factors in the regulation of POCD process. Once activated, resident microglia change their phenotype and secrete kinds of cytokines to regulate inflammatory response in tissues. Among these secretory factors, brain-derived neurotrophic factor (BDNF) is considered to be able to inhibit inflammation response and protect nervous system. Therefore, the enhancement of BDNF expression derived from resident microglia is suggested to be potential treatment for POCD. In our study, we focused on the role of C8-ceramide (a kind of interventional drug) and assessed its regulatory effect on improving the expression of BDNF secreted from microglia to treat POCD. According to the results of our study, we observed that C8-ceramide stimulated primary microglia to up-regulate the expression of BDNF mRNA after being treated with lipopolysaccharide (LPS) in vitro. We proved that C8-ceramide had ability to effectively improve POCD of mice after being accepted carotid artery exposure and their abnormal behavior recovered better than that of mice from the surgery group. Furthermore, we also demonstrated that C8-ceramide enhanced the cognitive function of mice via the PKCδ/NF-κB signaling pathway. In general, our study has confirmed a potential molecular mechanism that led to the occurrence of POCD caused by surgery and provided a new clinical strategy to treat POCD.

Biochemical characterization of a novel ß-galactosidase from Pedobacter sp. with strong transglycosylation activity at low lactose concentration.

A novel ß-galactosidase gene (PbBgal35A) from Pedobacter sp. CAUYN2 was cloned and expressed in Escherichia coli. The gene had an open reading frame of 1917 bp, encoding 638 amino acids with a predicted molecular mass of 62.3 kDa. The deduced amino acid sequence of the gene shared the highest identity of 41% with a glycoside hydrolase family 35 ß-galactosidase from Xanthomonas campestris pv. campestris (AAP86763.1). The recombinant ß-galactosidase (PbBgal35A) was purified to homogeneity with a specific activity of 65.9 U/mg. PbBgal35A was optimally active at pH 5.0 and 50 °C, respectively, and it was stable within pH 4.5‒7.0 and up to 45 °C. PbBgal35A efficiently synthesized galacto-oligosaccharides from lactose with a conversion ratio of 32% (w/w) and fructosyl-galacto-oligosaccharides from lactulose with a conversion ratio of 21.9% (w/w). Moreover, the enzyme catalyzed the synthesis of galacto-oligosaccharides from low-content lactose in fresh milk, and the GOS conversion ratios of 17.1% (w/w) and 7.8% (w/w) were obtained when the reactions were performed at 45 and 4 °C, respectively. These properties make PbBgal35A an ideal candidate for commercial use in the manufacturing of GOS-enriched dairy products.

Digital financial inclusion and upgrading of consumption structure: Evidence from rural China.

Based on the perspective of spatial economy, this paper focuses on the primary effects and spatial characteristics of Digital Financial Inclusion (DFI) on the upgrading of rural consumption structure (URCS) in China, conducting a literature review and theoretical analysis. It then uses statistical data collected over the years and the Digital Financial Inclusion Index (DFII) of Peking University to prepare panel data for 31 provinces in China (aside from Hong Kong, Macao, and Taiwan) from 2011 to 2020 for empirical testing. The results are as follows: DFI can considerably boost URCS, and there is a strong spatial neighbor impact, that is, it is affected by random shocks in surrounding provinces via its spatial effect; DFI has nonlinear characteristics in the process of fostering URCS, with the threshold variables of income level and family sizes; the impact of DFI on URCS is spatially heterogeneous, and the promotion of the eastern region is better than other zones. These results can inform policymakers about rural development and provide valuable references to push forward rural vitalization.

Multi-stimulus perception and visualization by an intelligent liquid metal-elastomer architecture.

Multi-stimulus responsive soft materials with integrated functionalities are elementary blocks for building soft intelligent systems, but their rational design remains challenging. Here, we demonstrate an intelligent soft architecture sensitized by magnetized liquid metal droplets that are dispersed in a highly stretchable elastomer network. The supercooled liquid metal droplets serve as microscopic latent heat reservoirs, and their controllable solidification releases localized thermal energy/information flows for enabling programmable visualization and display. This allows the perception of a variety of information-encoded contact (mechanical pressing, stretching, and torsion) and noncontact (magnetic field) stimuli as well as the visualization of dynamic phase transition and stress evolution processes, via thermal and/or thermochromic imaging. The liquid metal-elastomer architecture offers a generic platform for designing soft intelligent sensing, display, and information encryption systems.

Enhanced Bioactivity of Enzyme/MOF Biocomposite via Host Framework Engineering.

This study reports the successful development of a sustainable synthesis protocol for a phase-pure metal azolate framework (MAF-6) and its application in enzyme immobilization. An esterase@MAF-6 biocomposite was synthesized, and its catalytic performance was compared with that of esterase@ZIF-8 and esterase@ZIF-90 in transesterification reactions. Esterase@MAF-6, with its large pore aperture, showed superior enzymatic performance compared to esterase@ZIF-8 and esterase@ZIF-90 in catalyzing transesterification reactions using both n-propanol and benzyl alcohol as reactants. The hydrophobic nature of the MAF-6 platform was shown to activate the immobilized esterase into its open-lid conformation, which exhibited a 1.5- and 4-times enzymatic activity as compared to free esterase in catalyzing transesterification reaction using n-propanol and benzyl alcohol, respectively. The present work offers insights into the potential of MAF-6 as a promising matrix for enzyme immobilization and highlights the need to explore MOF matrices with expanded pore apertures to broaden their practical applications in biocatalysis.

Deep causal feature extraction and inference with neuroimaging genetic data.

Alzheimer's disease (AD) is a severe public health issue in the world. Magnetic Resonance Imaging (MRI) offers a way to study brain differences between AD patients and healthy individuals through feature extraction and comparison. However, in most previous works, the extracted features were not aimed to be causal, hindering biological understanding and interpretation. In order to extract causal features, we propose using instrumental variable (IV) regression with genetic variants as IVs. Specifically, we propose Deep Feature Extraction via Instrumental Variable Regression (DeepFEIVR), which uses a nonlinear neural network to extract causal features from three-dimensional neuroimages to predict an outcome (eg, AD status in our application) while maintaining a linear relationship between the extracted features and IVs. DeepFEIVR not only can handle high dimensional individual-level data for model building, but also is applicable to GWAS summary data to test associations of the extracted features with the outcome in subsequent analysis. In addition, we propose an extension of DeepFEIVR, called DeepFEIVR-CA, for covariate adjustment (CA). We apply DeepFEIVR and DeepFEIVR-CA to the Alzheimer's Disease Neuroimaging Initiative (ADNI) individual-level data as training data for model building, then apply to the UK Biobank neuroimaging and the International Genomics of Alzheimer's Project (IGAP) AD GWAS summary data, showcasing how the extracted causal features are related to AD and various brain endophenotypes.

Spinning Liquid Metal Droplets on Ice.

The non-contact and non-wetting droplet motion isolated from the solid surface has a high degree of freedom and thus can exhibit many peculiar interfacial phenomena. Here, an experimental phenomenon of spinning liquid metal droplets on an ice block is discovered, which adopts the dual solid-liquid phase transition of the liquid metal and the ice. The whole system is somewhat a variant of the classic Leidenfrost effect, which directly uses the latent heat released by the spontaneous solidification of the liquid metal droplet as a heat source to melt the ice and create an intervening lubricant water film. Interestingly, it is found that the droplets on ice become very mobile and undergo rapid spin as the solidification process proceeds. A series of comparative experiments clarify that the circumferential driving force comes from the escaping bubbles as the ice melts. Furthermore, by comparing the motion characteristics of different kinds of liquid metal droplets and solid balls on ice and investigating their physical properties and heat transfer, it is disclosed that the spin effect can be universal for objects of different materials, as long as the two necessary elements of rapid liquid film establishment and gas bubble release can be satisfied simultaneously.