Spatial Multi-Omics in Alzheimer's Disease: A Multi-Dimensional Approach to Understanding Pathology and Progression.

Alzheimer's Disease (AD) presents a complex neuropathological landscape characterized by hallmark amyloid plaques and neurofibrillary tangles, leading to progressive cognitive decline. Despite extensive research, the molecular intricacies contributing to AD pathogenesis are inadequately understood. While single-cell omics technology holds great promise for application in AD, particularly in deciphering the understanding of different cell types and analyzing rare cell types and transcriptomic expression changes, it is unable to provide spatial distribution information, which is crucial for understanding the pathological processes of AD. In contrast, spatial multi-omics research emerges as a promising and comprehensive approach to analyzing tissue cells, potentially better suited for addressing these issues in AD. This article focuses on the latest advancements in spatial multi-omics technology and compares various techniques. Additionally, we provide an overview of current spatial omics-based research results in AD. These technologies play a crucial role in facilitating new discoveries and advancing translational AD research in the future. Despite challenges such as balancing resolution, increasing throughput, and data analysis, the application of spatial multi-omics holds immense potential in revolutionizing our understanding of human disease processes and identifying new biomarkers and therapeutic targets, thereby potentially contributing to the advancement of AD research.

Tiny Organs, Big Impact: How Microfluidic Organ-on-Chip Technology Is Revolutionizing Mucosal Tissues and Vasculature.

Organ-on-chip (OOC) technology has gained importance for biomedical studies and drug development. This technology involves microfluidic devices that mimic the structure and function of specific human organs or tissues. OOCs are a promising alternative to traditional cell-based models and animals, as they provide a more representative experimental model of human physiology. By creating a microenvironment that closely resembles in vivo conditions, OOC platforms enable the study of intricate interactions between different cells as well as a better understanding of the underlying mechanisms pertaining to diseases. OOCs can be integrated with other technologies, such as sensors and imaging systems to monitor real-time responses and gather extensive data on tissue behavior. Despite these advances, OOCs for many organs are in their initial stages of development, with several challenges yet to be overcome. These include improving the complexity and maturity of these cellular models, enhancing their reproducibility, standardization, and scaling them up for high-throughput uses. Nonetheless, OOCs hold great promise in advancing biomedical research, drug discovery, and personalized medicine, benefiting human health and well-being. Here, we review several recent OOCs that attempt to overcome some of these challenges. These OOCs with unique applications can be engineered to model organ systems such as the stomach, cornea, blood vessels, and mouth, allowing for analyses and investigations under more realistic conditions. With this, these models can lead to the discovery of potential therapeutic interventions. In this review, we express the significance of the relationship between mucosal tissues and vasculature in organ-on-chip (OOC) systems. This interconnection mirrors the intricate physiological interactions observed in the human body, making it crucial for achieving accurate and meaningful representations of biological processes within OOC models. Vasculature delivers essential nutrients and oxygen to mucosal tissues, ensuring their proper function and survival. This exchange is critical for maintaining the health and integrity of mucosal barriers. This review will discuss the OOCs used to represent the mucosal architecture and vasculature, and it can encourage us to think of ways in which the integration of both can better mimic the complexities of biological systems and gain deeper insights into various physiological and pathological processes. This will help to facilitate the development of more accurate predictive models, which are invaluable for advancing our understanding of disease mechanisms and developing novel therapeutic interventions.

MI-MZI based distributed optical fiber sensor for location and pattern recognition.

This research addressed the drawbacks of the conventional hybrid structure and processing technique by presenting a novel distributed fiber optic sensor based on a hybrid Michelson and Mach-Zehnder interferometer. The sensor can achieve blind spot free positioning and has a wide response frequency, additionally its structure is not complex. It can obtain two phase signals from each of the two interferometers by using a demodulation method that uses a 3 × 3 optical coupler. To determine the position of the disturbance, we computed cross-correlations on the two signals following basic mathematical techniques. Markov Transition Field was used to transform the phase signals-which had been filtered by a band pass filter-into two-dimensional images. Tagged photos built a dataset, which is then fed into a neural network to identify patterns. Experiments have shown that the frequency response capacity of the structure was verified, and it was able to achieve location within 0-30 km with location errors of ±85 m. In a six-category pattern recognition, the testing set accuracy was 98.74%.

Roles of physical exercise-induced MiR-126 in cardiovascular health of type 2 diabetes.

Although physical activity is widely recommended for preventing and treating cardiovascular complications of type 2 diabetes mellitus (T2DM), the underlying mechanisms remain unknown. MicroRNA-126 (miR-126) is an angiogenetic regulator abundant in endothelial cells (ECs) and endothelial progenitor cells (EPCs). It is primarily involved in angiogenesis, inflammation and apoptosis for cardiovascular protection. According to recent studies, the levels of miR-126 in the myocardium and circulation are affected by exercise protocol. High-intensity interval training (HIIT) or moderate-and high-intensity aerobic exercise, whether acute or chronic, can increase circulating miR-126 in healthy adults. Chronic aerobic exercise can effectively rescue the reduction of myocardial and circulating miR-126 and vascular endothelial growth factor (VEGF) in diabetic mice against diabetic vascular injury. Resistance exercise can raise circulating VEGF levels, but it may have a little influence on circulating miR-126. The Several targets of miR-126 have been suggested for cardiovascular fitness, such as sprouty-related EVH1 domain-containing protein 1 (SPRED1), phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2), vascular cell adhesion molecule 1 (VCAM1), high-mobility group box 1 (HMGB1), and tumor necrosis factor receptor-associated factor 7 (TRAF7). Here, we present a comprehensive review of the roles of miR-126 and its downstream proteins as exercise mechanisms, and propose that miR-126 can be applied as an exercise indicator for cardiovascular prescriptions and as a preventive or therapeutic target for cardiovascular complications in T2DM.

Performance enhancement of polyurethane foam applied to optical fiber microphones.

The application of polyurethane foam to optical fiber microphone sensitization is proposed. In this experiment, the Michelson interference system is used, and polyurethane foam is coated on the optical fiber of the signal arm. By changing the optical fiber material of the signal arm and the reference arm, four sets of comparative experiments are designed to test the sensitivity of the optical microphone. Through a scanning electron microscope (SEM) test and a pore size distribution test, the porous structure and non-closed cell structure characteristics, pore size range, etc., of the polyurethane foam were determined. The average sound absorption coefficient of the polyurethane foam is 0.66 through the sound absorption coefficient and sound insulation test. The sound absorption coefficient of each frequency band is above 0.2, the sound insulation is below 30 dB, and the overall sound insulation performance is poor, which can be regarded as an ideal sound absorption material. The sound-absorbing effect of polyurethane foam is better than that of nylon tight-packed materials in the frequency range of 500-2800 Hz, and it has a significant sensitization effect in this frequency band. In the frequency band above 2800 Hz, the sound-absorbing effect of nylon tight-packed optical fiber is better than that of polyurethane foam, and the optimal combination is determined by lateral comparison as signal arm (nylon tight-packed fiber + polyurethane foam) + reference arm (bare fiber). Finally, with different coating thicknesses as variables, the results show that the optical fiber microphone has the best sound collection effect when the coating thickness of polyurethane foam is 1.5 cm.

Disturbance location and pattern recognition of a distributed optical fiber sensor based on dual-Michelson interferometers.

A distributed fiber optic sensor based on dual-Michelson interferometers for disturbance localization and pattern recognition is proposed. The system obtains the phase difference of each of the two interferometers using a passive demodulating algorithm based on a 3×3 coupler. Two correlation signals with disturbance position information are obtained by delaying and subtracting the phase difference signals through which the disturbance location can be obtained. This method has the same frequency response over the whole sensing path, and there is no localization blind spot. The pattern recognition method of this sensing system is to obtain the spectral signal by fast Fourier transform of the demodulated interferometer phase information and input it as a feature vector into a one-dimensional convolutional neural network to verify the correct rate of pattern recognition for four behaviors: stepping, shearing, sweeping, and shaking. The total transmission distance of the system can reach 100 km; the location errors are within ±35m, and the correct rate of four pattern recognitions is higher than 97%. The sensing system has good polarization stability, which can ensure the stability of long-term operation and has a broad application prospect in long-distance perimeter security.

The CYP3A5 and ABCB1 Gene Polymorphisms in Kidney Transplant Patients and Establishment of Initial Daily Tacrolimus Dosing Formula.

BACKGROUND: Tacrolimus is an immunosuppressive drug used to prevent organ rejections. Many factors could influence blood concentration of tacrolimus. OBJECTIVE: To detect genotypes of cytochrome P450 3A5 (CYP3A5) and ABCB1 in kidney transplant patients and establish initial daily tacrolimus dosing formula based on genotypes of CYP3A5 and ABCB1 and patients' clinical parameters. METHODS: Sequence specific primer polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism were used to detect genotypes of CYP3A5 and ABCB1. The blood cell, procalcitonin, C-reactive protein, height, weight, age, gender and other clinical parameters were recorded. Multiple linear regression analysis and Pearson correlation analysis were used to conduct date analysis. RESULTS: 102 cases were enrolled in cohort 1, and there were 10 cases of CYP3A5 *1/*1 (9.8%), 28 cases of CYP3A5 *1/*3 (27.5%), and 64 cases of CYP3A5 *3/*3 (62.7%). The distributions of ABCB1 C3435T genotype were CC 36 (35.3%), CT 52 (51.0%), and TT 14 (13.7%). The distributions of ABCB1 G2677T/A genotype were GG 39 (38.2%), GT 40 (39.2%), and TT 23 (22.5%). The formula was 7.499 + (0.053 × Weight) - (0.029 × Hemoglobin concentration) - (1.045 × CYP3A5 genotype) (CYP3A5 genotype: *1/*1 type inputs 0, *1/*3 type inputs 1, *3/*3 type inputs 2). The predicted doses from the established formula had a significant correlation (r = 0.605) with actual clinical doses (P < 0.05). CONCLUSION AND RELEVANCE: Hemoglobin concentration, weight, and CYP3A5 genotype should be considered using tacrolimus. The initial daily tacrolimus dosing formula established can make a good prediction.

Enhancing Hydrogen Productivity of Photosynthetic Bacteria from the Formulated Carbon Source by Mixing Xylose with Glucose.

To develop an efficient photofermentative process capable of higher rate biohydrogen production using carbon components of lignocellulosic hydrolysate, a desired carbon substrate by mixing xylose with glucose was formulated. Effects of crucial process parameters affecting cellular biochemical reaction of hydrogen by photosynthetic bacteria (PSB), i.e., variation in initial concentration of total carbon, glucose content in initial carbon substrate, and light intensity, were experimentally investigated using response surface methodology (RSM) with a Box-Behnken design (BBD). Hydrogen production rate (HPR) in the maximum value of 30.6 mL h-1 L-1 was attained under conditions of 39 mM initial concentration of total carbon, 59% (mol/mol) glucose content in initial carbon substrate, and 12.6 W m-2 light intensity at light wavelength of 590 nm. Synergic effects of metabolizing such a well-formulated carbon substrate for sustaining the active microbial synthesis to sufficiently accumulate biomass in bioreactor, as well as stimulating enzyme activity of nitrogenase for the higher rate biohydrogen production, were attributed to this carbon substrate that can enable PSB to maintain the relatively consistent microenvironment in suitable culture pH condition during the optimized photofermentative process.

The efficacy and safety of Yijinjing exercise in the adjuvant treatment of ankylosing spondylitis: A protocol of randomized controlled trial.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic systemic autoimmune disease with high disability rate. Conventional treatment regimens have long medication cycles and are associated with adverse reactions. Therapeutic exercise is also considered to be an effective treatment for AS. Evidence suggests that Yijinjing as a low-energy exercise has advantages in adjuncting AS, but there is a lack of standard clinical studies to evaluate its efficacy and safety. METHODS: This is a prospective randomized controlled trial to investigate the efficacy and safety of Yijinjing in the adjuvant treatment of AS. Approved by the Clinical Research Ethics Association of our hospital, patients were randomly divided into treatment or control groups in a ratio of 1:1. The treatment group received 4-month Yijinjing training on the basis of conventional treatment, while the control group received conventional treatment and maintained their current lifestyle. The outcome indicators included: activity index, functional ability, Bath Ankylosing Spondylitis Metrology Index, adverse reaction, etc. Finally, SPASS 22.0 software was used for statistical analysis of the data. DISCUSSION: This study evaluated the clinical efficacy of Yijinjing exercise in the adjuvant treatment of AS, and the results of our study will provide a reference for the clinical use of Yijinjing exercise as an effective complementary alternative for the treatment of AS.

AttPNet: Attention-Based Deep Neural Network for 3D Point Set Analysis.

Point set is a major type of 3D structure representation format characterized by its data availability and compactness. Most former deep learning-based point set models pay equal attention to different point set regions and channels, thus having limited ability in focusing on small regions and specific channels that are important for characterizing the object of interest. In this paper, we introduce a novel model named Attention-based Point Network (AttPNet). It uses attention mechanism for both global feature masking and channel weighting to focus on characteristic regions and channels. There are two branches in our model. The first branch calculates an attention mask for every point. The second branch uses convolution layers to abstract global features from point sets, where channel attention block is adapted to focus on important channels. Evaluations on the ModelNet40 benchmark dataset show that our model outperforms the existing best model in classification tasks by 0.7% without voting. In addition, experiments on augmented data demonstrate that our model is robust to rotational perturbations and missing points. We also design a Electron Cryo-Tomography (ECT) point cloud dataset and further demonstrate our model's ability in dealing with fine-grained structures on the ECT dataset.

Chromatin Remodeling and Immediate Early Gene Activation by SLFN11 in Response to Replication Stress.

Schlafen 11 (SLFN11) was recently discovered as a cellular restriction factor against replication stress. Here, we show that SLFN11 increases chromatin accessibility genome wide, prominently at active promoters in response to replication stress induced by the checkpoint kinase 1 (CHK1) inhibitor prexasertib or the topoisomerase I (TOP1) inhibitor camptothecin. Concomitantly, SLFN11 selectively activates cellular stress response pathways by inducing the transcription of the immediate early genes (IEGs), including JUN, FOS, EGR1, NFKB2, and ATF3, together with the cell cycle arrest genes CDKN1A (p21WAF1) and GADD45. Both chromatin remodeling and IEG activation require the putative ATPase and helicase activity of SLFN11, whereas canonical extrinsic IEG activation is SLFN11 independent. SLFN11-dependent IEG activation by camptothecin is also observed across 55 non-isogenic NCI-60 cell lines. We conclude that SLFN11 acts as a global regulator of chromatin structure and an intrinsic IEG activator with the potential to engage the innate immune activation in response to replicative stress.

Formation mechanism of the oolong tea characteristic aroma during bruising and withering treatment.

To elucidate formation mechanism of oolong tea aroma, the released and remaining volatiles during bruising and withering treatment were analyzed using head space solid-phase microextraction/gas chromatography-mass spectrometry. An increase in proportion of the released terpenoid volatiles (TVs) along with a decrease in proportion of the released C6 green leaf volatiles (GLVs) was observed in both cultivars 'Zhejiang139' and 'Foshou'. Proportion of remaining TVs also fluctuated reversely with GLVs although the level of these volatiles increased remarkably. High ratio of TVs to GLVs was the key chemical foundation of oolong tea characteristic aroma and could be regarded as a good indicator in screening cultivar for suitably producing high quality oolong tea. Combining with transcriptome analysis, increased TVs and GLVs during the treatment might be largely generated through de novo synthesis and modulated at transcript level through up-regulation of genes involved in terpenoids metabolism and enzymatic cleavage of long-chain fatty acids.

Different Catabolism Pathways Triggered by Various Methylxanthines in Caffeine-Tolerant Bacterium Pseudomonas putida CT25 Isolated from Tea Garden Soil.

The degradation efficiency and catabolism pathways of the different methylxanthines (MXs) in isolated caffeine-tolerant strain Pseudomonas putida CT25 were comprehensively studied. The results showed that the degradation efficiency of various MXs varied with the number and position of the methyl groups on the molecule (i.e., xanthine > 7-methylxanthine ≈ theobromine > caffeine > theophylline > 1-methylxanthine). Multiple MX catabolism pathways coexisted in strain CT25, and a different pathway would be triggered by various MXs. Demethylation dominated in the degradation of N-7-methylated MXs (such as 7-methylxanthine, theobromine, and caffeine), where C-8 oxidation was the major pathway in the catabolism of 1-methylxanthine, whereas demethylation and C-8 oxidation are likely both involved in the degradation of theophylline. Enzymes responsible for MX degradation were located inside the cell. Both cell culture and cell-free enzyme assays revealed that N-1 demethylation might be a rate-limiting step for the catabolism of the MXs. Surprisingly, accumulation of uric acid was observed in a cell-free reaction system, which might be attributed to the lack of activity of uricase, a cytochrome c-coupled membrane integral enzyme.

Neuroprotective Effects and Mechanisms of Tea Bioactive Components in Neurodegenerative Diseases.

As the population ages, neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD) impose a heavy burden on society and families. The pathogeneses of PD and AD are complex. There are no radical cures for the diseases, and existing therapeutic agents for PD and AD have diverse side effects. Tea contains many bioactive components such as polyphenols, theanine, caffeine, and theaflavins. Some investigations of epidemiology have demonstrated that drinking tea can decrease the risk of PD and AD. Tea polyphenols can lower the morbidity of PD and AD by reducing oxidative stress and regulating signaling pathways and metal chelation. Theanine can inhibit the glutamate receptors and regulate the extracellular concentration of glutamine, presenting neuroprotective effects. Additionally, the neuroprotective mechanisms of caffeine and theaflavins may contribute to the ability to antagonize the adenosine receptor A2AR and the antioxidant properties, respectively. Thus, tea bioactive components might be useful for neuronal degeneration treatment in the future. In the present paper, the neuro protection and the mechanisms of tea and its bioactive components are reviewed. Moreover, the potential challenges and future work are also discussed.