Biofluid biomarkers for Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease, with a complex pathogenesis and an irreversible course. Therefore, the early diagnosis of AD is particularly important for the intervention, prevention, and treatment of the disease. Based on the different pathophysiological mechanisms of AD, the research progress of biofluid biomarkers are classified and reviewed. In the end, the challenges and perspectives of future research are proposed.

Establishment of a pMCAO model in SD rats and screening for behavioral indicators suitable for long-term monitoring.

OBJECTIVE: This study aimed to establish a permanent middle cerebral artery occlusion (pMCAO) model in rats to simulate the pathological process of stroke patients with no reperfusion. And screen highly sensitive items that could be used to detect long-term behavioral abilities in rat of intraluminal suture models. METHOD: Established the pMCAO model then tested the rats for the bilateral asymmetry, modified neurological severity score, grid-walking, cylinder, rotating, and water maze test from week 1 to week 16. RESULTS: The infarct volume of the model rats was stable (26.72% ±1.86%). The sensorimotor test of bilateral asymmetry, grid-walking, cylinder, and mNSS test showed significant differences from week 1 to week 16 after injury. The water maze test at week 16 showed significant differences in spatial exploration and learning ability between the two groups. We confirmed that there was no significant difference between MRI and TTC staining in detecting the degree of brain injury, which facilitated the diversity of subsequent detection methods. We also confirmed that at multiple time points, grid, cylinder and water maze test were significantly positively correlated with rat brain infarct volume. CONCLUSION: They are suitable for the long-term observation of behaviors in the sequela stage of stroke in rat.

Vaginal microbiota transplantation is a truly opulent and promising edge: fully grasp its potential.

Vaginal microbiota transplantation (VMT) is a cutting-edge treatment modality that has the potential to revolutionize the management of vaginal disorders. The human vagina is a complex and dynamic ecosystem home to a diverse community of microorganisms. These microorganisms play a crucial role in maintaining the health and well-being of the female reproductive system. However, when the balance of this ecosystem is disrupted, it can lead to the development of various vaginal disorders. Conventional treatments, such as antibiotics and antifungal medications, can temporarily relieve the symptoms of vaginal disorders. However, they often fail to address the underlying cause of the problem, which is the disruption of the vaginal microbiota. In recent years, VMT has emerged as a promising therapeutic approach that aims to restore the balance of the vaginal ecosystem. Several studies have demonstrated the safety and efficacy of VMT in treating bacterial vaginosis, recurrent yeast infections, and other vaginal conditions. The procedure has also shown promising results in reducing the risk of sexually transmitted infections and preterm birth in pregnant women. However, more research is needed to establish optimal donor selection, preparation, and screening protocols, as well as long-term safety and efficacy. VMT offers a safe, effective, and minimally invasive treatment option for women with persistent vaginal problems. It could improve the quality of life for millions of women worldwide and become a standard treatment option shortly. With further research and development, it could potentially treat a wide range of other health problems beyond the scope of vaginal disorders.

Quantitative Assessment of Breast Tumor: Comparison of Four Methods of Positioning Region of Interest for Synthetic Relaxometry and Diffusion Measurement.

RATIONALE AND OBJECTIVES: To compare the differences in apparent diffusion coefficient (ADC) and synthetic magnetic resonance (MR) measurements of four region of interest (ROI) placement methods for breast tumor and to investigate their diagnostic performance. METHODS: 110 (70 malignant, 40 benign) newly diagnosed breast tumors were evaluated. The patients underwent 3.0 T MR examinations including diffusion-weighted imaging and synthetic MR. Two radiologists independently measured ADCs, T1 relaxation time (T1), T2 relaxation time (T2), and proton density (PD) using four ROI methods: round, square, freehand, and whole-tumor volume (WTV). The interclass correlation coefficient (ICC) was used to assess their measurement reliability. Diagnostic performance was evaluated using multivariate logistic regression analysis and the receiver operating characteristic (ROC) curves. RESULTS: The mean values of all ROI methods showed good or excellent interobserver reproducibility (0.79-0.99) and showed the best diagnostic performance compared to the minimum and maximum values. The square ROI exhibited superior performance in differentiating between benign from malignant breast lesions, followed by the freehand ROI. T2, PD, and ADC values were significantly lower in malignant breast lesions compared to benign ones for all ROI methods (p < 0.05). Multiparameters of T2 + ADC demonstrated the highest AUC values (0.82-0.95), surpassing the diagnostic efficacy of ADC or T2 alone (p < 0.05). CONCLUSION: ROI placement significantly influences ADC and synthetic MR values measured in breast tumors. Square ROI and mean values showed superior performance in differentiating benign and malignant breast lesions. The multiparameters of T2 + ADC surpassed the diagnostic efficacy of a single parameter.

Harnessing the power of goat milk-derived extracellular vesicles for medical breakthroughs: A review.

Research into goat milk-derived extracellular vesicles (GMVs) has grown in popularity in recent years owing to their potential uses in several sectors, including medicine. GMVs are tiny, lipid-bound structures that cells secrete and use to transport bioactive substances like proteins, lipids, and nucleic acids. They may be extracted from different body fluids, including blood, urine, and milk, and have been found to play crucial roles in cell-to-cell communication. GMVs are a promising field of study with applications in preventing and treating various disorders. Their immune-modulating properties, for instance, have been investigated, and they have shown promise in treating autoimmune illnesses and cancer. They may be loaded with therapeutic compounds and directed to particular cells or tissues, but they have also been studied for their potential use as drug-delivery vehicles. Goat milk extracellular vesicles are an intriguing study topic with many possible benefits. Although more study is required to thoroughly understand their functioning and prospective applications, they provide a promising path for creating novel medical treatments and technology.

A novel major accidents evolution model and its application in Chinese industrial accident.

The accident mortality rate of major accidents (MAs) show that China is still in the bottleneck period of accident prevention and control. To further promote the MAs prevention and control, this paper presents a novel major accidents evolution model from the theoretical perspective of information processing (IP). Firstly, based on the safety science paradigm of accident prevention and the emergency management paradigm of accident control, a safety information processing (SIP) process is proposed. Secondly, established the SIP model for different stages of accident prevention and control, which involves danger information processing (DIP), potential hazard information processing (PHIP), risk information processing (RIP), and emergency information processing (EIP). Thirdly, revealed the SIP of various management subject and the failure principle of accident prevention and control, that is, MAs occur under the premise of continuous failures of DIP, PHIP, RIP, and EIP under the social-technical system. Finally, the DPRE-IP model is proposed from the whole evolution path of "danger-potential hazard-risk-accident". To demonstrate the viability of the model, this model is applied to the "6·13" Wenling major explosion accident. The results show that the proposed DPRE-IP model can provide new ideas for the formulation of accident prevention and control measures and accident analysis.

Road Traffic Sign Detection Method Based on RTS R-CNN Instance Segmentation Network.

With the rapid development of the autonomous driving industry, there is increasing research on related perception tasks. However, research on road surface traffic sign detection tasks is still limited. There are two main challenges to this task. First, when the target object's pixel ratio is small, the detection accuracy often decreases. Second, the existing publicly available road surface traffic sign datasets have limited image data. To address these issues, this paper proposes a new instance segmentation network, RTS R-CNN, for road surface traffic sign detection tasks based on Mask R-CNN. The network can accurately perceive road surface traffic signs and provide important information for the autonomous driving decision-making system. Specifically, CSPDarkNet53_ECA is proposed in the feature extraction stage to enhance the performance of deep convolutional networks by increasing inter-channel interactions. Second, to improve the network's detection accuracy for small target objects, GR-PAFPN is proposed in the feature fusion part, which uses a residual feature enhancement module (RFA) and atrous spatial pyramid pooling (ASPP) to optimize PAFPN and introduces a balanced feature pyramid module (BFP) to handle the imbalanced feature information at different resolutions. Finally, data augmentation is used to generate more data and prevent overfitting in specific scenarios. The proposed method has been tested on the open-source dataset Ceymo, achieving a Macro F1-score of 87.56%, which is 2.3% higher than the baseline method, while the inference speed reaches 23.5 FPS.

Fecal microbiota transplantation holds the secret to youth.

Aging shows itself not just at the cellular level, with shortened telomeres and cell cycle arrest, but also at the organ and organismal level, with diminished brainpower, dry eyes, intestinal inflammation, muscular atrophy, wrinkles, etc. When the gut microbiota, often called the "virtual organ of the host," fails to function normally, it can lead to a cascade of health problems including, but not limited to, inflammatory bowel disease, obesity, metabolic liver disease, type II diabetes, cardiovascular disease, cancer, and even neurological disorders. An effective strategy for restoring healthy gut bacteria is fecal microbiota transplantation (FMT). It can reverse the effects of aging on the digestive system, the brain, and the vision by transplanting the functional bacteria found in the excrement of healthy individuals into the gut tracts of patients. This paves the way for future research into using the microbiome as a therapeutic target for disorders associated with aging.

Molecular Characterization of Nine TRAF Genes in Yellow Catfish (Pelteobagrus fulvidraco) and Their Expression Profiling in Response to Edwardsiella ictaluri Infection.

The yellow catfish (Pelteobagrus fulvidraco) is an economic fish with a large breeding scale, and diseases have led to huge economic losses. Tumor necrosis factor receptor-associated factors (TRAFs) are a class of intracellular signal transduction proteins that play an important role in innate and adaptive immune responses by mediating NF-κB, JNK and MAPK signaling pathways. However, there are few studies on the TRAF gene family in yellow catfish. In this study, the open reading frame (ORF) sequences of TRAF1, TRAF2a, TRAF2b, TRAF3, TRAF4a, TRAF4b, TRAF5, TRAF6 and TRAF7 genes were cloned and identified in yellow catfish. The ORF sequences of the nine TRAF genes of yellow catfish (Pf_TRAF1-7) were 1413-2025 bp in length and encoded 470-674 amino acids. The predicted protein structures of Pf_TRAFs have typically conserved domains compared to mammals. The phylogenetic relationships showed that TRAF genes are conserved during evolution. Gene structure, motifs and syntenic analyses of TRAF genes showed that the exon-intron structure and conserved motifs of TRAF genes are diverse among seven vertebrate species, and the TRAF gene family is relatively conserved evolutionarily. Among them, TRAF1 is more closely related to TRAF2a and TRAF2b, and they may have evolved from a common ancestor. TRAF7 is quite different and distantly related to other TRAFs. Real-time quantitative PCR (qRT-PCR) results showed that all nine Pf_TRAF genes were constitutively expressed in 12 tissues of healthy yellow catfish, with higher mRNA expression levels in the gonad, spleen, brain and gill. After infection with Edwardsiella ictaluri, the expression levels of nine Pf_TRAF mRNAs were significantly changed in the head kidney, spleen, gill and brain tissues of yellow catfish, of which four genes were down-regulated and one gene was up-regulated in the head kidney; four genes were up-regulated and four genes were down-regulated in the spleen; two genes were down-regulated, one gene was up-regulated, and one gene was up-regulated and then down-regulated in the gill; one gene was up-regulated, one gene was down-regulated, and four genes were down-regulated and then up-regulated in the brain. These results indicate that Pf_TRAF genes might be involved in the immune response against bacterial infection. Subcellular localization results showed that all nine Pf_TRAFs were found localized in the cytoplasm, and Pf_TRAF2a, Pf_TRAF3 and Pf_TRAF4a could also be localized in the nucleus, uncovering that the subcellular localization of TRAF protein may be closely related to its structure and function in cellular mechanism. The results of this study suggest that the Pf_TRAF gene family plays important roles in the immune response against pathogen invasion and will provide basic information to further understand the roles of TRAF gene against bacterial infection in yellow catfish.

Unexpected worsening of doxorubicin cardiotoxicity upon intermittent fasting.

Recently in Cell Metabolism, Ozcan et al. used preclinical and clinical data to suggest that alternate-day fasting may exacerbate the cardiotoxic effects of doxorubicin through the TFEB/GDF15 pathway, leading to myocardial atrophy and impaired cardiac function. The link between caloric intake, chemotherapy-induced cachexia, and cardiotoxicity warrants more clinical attention.

Bacteria associated with glioma: a next wave in cancer treatment.

Malignant gliomas occur more often in adults and may affect any part of the central nervous system (CNS). Although their results could be better, surgical excision, postoperative radiation and chemotherapy, and electric field therapy are today's mainstays of glioma care. However, bacteria can also exert anti-tumor effects via mechanisms such as immune regulation and bacterial toxins to promote apoptosis, inhibit angiogenesis, and rely on their natural characteristics to target the tumor microenvironment of hypoxia, low pH, high permeability, and immunosuppression. Tumor-targeted bacteria expressing anticancer medications will go to the cancer site, colonize the tumor, and then produce the therapeutic chemicals that kill the cancer cells. Targeting bacteria in cancer treatment has promising prospects. Rapid advances have been made in the study of bacterial treatment of tumors, including using bacterial outer membrane vesicles to load chemotherapy drugs or combine with nanomaterials to fight tumors, as well as the emergence of bacteria combined with chemotherapy, radiotherapy, and photothermal/photodynamic therapy. In this study, we look back at the previous years of research on bacteria-mediated glioma treatment and move forward to where we think it is headed.

Increasing Accessible Active Site Density of Non-Precious Metal Oxygen Reduction Reaction Catalysts through Ionic Liquid Modification.

Non-precious metal catalysts show great promise to replace the state-of-the-art Pt-based catalysts for catalyzing the oxygen reduction reaction (ORR), while their catalytic activity still needs to be greatly improved before their broad-based application. Here, we report a facile approach to improving the performance of zeolitic imidazolate framework-derived carbon (ZDC) toward the ORR by incorporating a small amount of ionic liquid (IL). The IL would preferentially fill the micropores of ZDC and greatly enhance the utilization of the active sites within the micropores, which are initially not accessible due to insufficient surface wetting. It is also disclosed that the ORR activity in terms of kinetic current at 0.85 V depends on the loading amount of the IL, and the maximum activity is obtained at a mass ratio of IL to ZDC at 1.2. The optimum stems from the counterbalance between the enhanced utilization of the active sites within the micropores and the retarded diffusion of the reactants within the IL phase due to its high viscosity.

Investigating the mechanism of the flavor formation in Sichuan sun vinegar based on flavor-orientation and metagenomics.

Fermentation and aging are the key stages of flavor formation in Sichuan sun vinegar (SSV), but the generation mechanisms of the flavor produced by these processes are unknown. However, complex microbial metabolism is critical to the flavor development of SSV. In this study, we analyzed the key flavor compounds present in SSV. Combined with odor activity value (OAV), the main aroma components of SSV were screened, and the relationship between microorganisms and key flavor formation was predicted using metagenomic sequencing technology. The results revealed 38 key flavor compounds in SSV. Lactobacillus, Weissella, Acetobacter, Lichtheimia, Pediococcus, Oenococcus, Brettanomyces, Kazachstania, Pichia, Xanthomonas, Lenconostoc are widely involved in the production of key flavor compounds such as 2,3-butanediol, 2-Furanmethanol, phenylethanol, 3-(Methylthio)-1-propanol, acetic acid, lactic acid, butyric acid, isovaleric acid and other organic acids. Among them, Lichtheimia and Lactobacillus are important genera for the degradation of starch, arabinoxylan and cellulose. The acetaldehyde,4-ethyl-2-methoxy-phenol and 2-methoxy-4-methyl-phenol production pathway may be related to Lactobacillus, Acetobacter and Brettanomyces. This study provides a new understanding of the key flavor-formation stage and flavor compound generation mechanism of SSV and provides a reference for the screening and isolation of functional strains and the reconstruction of microbial communities.

Imaging glucose metabolism to reveal tumor progression.

Purpose: To analyze and review the progress of glucose metabolism-based molecular imaging in detecting tumors to guide clinicians for new management strategies. Summary: When metabolic abnormalities occur, termed the Warburg effect, it simultaneously enables excessive cell proliferation and inhibits cell apoptosis. Molecular imaging technology combines molecular biology and cell probe technology to visualize, characterize, and quantify processes at cellular and subcellular levels in vivo. Modern instruments, including molecular biochemistry, data processing, nanotechnology, and image processing, use molecular probes to perform real-time, non-invasive imaging of molecular and cellular events in living organisms. Conclusion: Molecular imaging is a non-invasive method for live detection, dynamic observation, and quantitative assessment of tumor glucose metabolism. It enables in-depth examination of the connection between the tumor microenvironment and tumor growth, providing a reliable assessment technique for scientific and clinical research. This new technique will facilitate the translation of fundamental research into clinical practice.

Information Delayering Safety Management (IDSM): A New Method of System Safety in Urgent Situations Needs to Be Established.

Organizational safety decisions rely heavily on safety information in today's data-driven era, but there is a significant danger of information distortion that can compromise system safety. To address the issue of information distortion and enhance system safety, a new approach called information delayering safety management (IDSM) has been developed and implemented. The IDSM method combines delayering management mode and graph theory to study the relationship between information distortion management and delayering management. By using the delayering mode as a theoretical foundation for safety information management, information distortion can be reduced. The implementation of this approach from a graph theory perspective has been tested using a case study and has been proven to effectively enhance the reliability of safety information and ensure system safety. The minimum control set of the directed graph algorithm can be used to realize the whole network management of safety information distortion. The amount of safety information and signal noise can be controlled by adjusting connectivity, and safety information distortion can be regulated through the adjustment of structural holes and flow direction. Overall, IDSM offers a new, effective method for accident analysis and safety management, allowing safety professionals to make informed decisions based on robust advanced evidence.

Identification of Quinone Outside Inhibitor Fungicide-Resistant Isolates of Parastagonospora nodorum from Illinois and Kentucky.

Stagonospora leaf and glume blotch, caused by Parastagonospora nodorum, is a major disease of winter wheat (Triticum aestivum) in the United States capable of significantly reducing grain yield and quality. Pathogens such as P. nodorum that overwinter in crop residue are often an increased concern in cropping systems that utilize no-till farming. In addition, the lack of wheat cultivars with complete resistance to P. nodorum has led to the reliance on foliar fungicides for disease management. Quinone outside inhibitor (QoI) fungicides (Fungicide Resistance Action Committee group 11) are one of the major classes used to manage foliar diseases in wheat. Use of the QoI class of fungicides tends to select isolates of fungal pathogens with resistance due to mutations in the fungal cytochrome b gene. Isolates of P. nodorum were collected from Illinois in 2014 and Kentucky in 2018, 2019, and 2020. Amplification and sequencing of a segment of the cytochrome b gene from these isolates revealed a mutation at codon 143 that confers a change from glycine to alanine in the amino acid sequence (known as the G143A mutation). In vitro plate assays and greenhouse trials were used to confirm and characterize the QoI resistance caused by the G143A mutation. The frequency of the tested isolates with the G143A mutation was 46% (57 of 123 isolates) and 5% (3 of 60 isolates) for Kentucky and Illinois, respectively. This research is the first to identify the G143A mutation in P. nodorum isolates with resistance to QoI fungicides in Illinois and Kentucky.

Unique Probiotic Properties and Bioactive Metabolites of Saccharomyces boulardii.

Saccharomyces boulardii (S. boulardii) is a probiotic and is widely used to improve the nutritional and functional value of food. This study aimed to compare the probiotic properties of S. boulardii and Saccharomyces cerevisiae. A series of in vitro probiotic experiments was performed, including simulated gastrointestinal digestion, bile salt tolerance, hydrophobicity, self-aggregation, and antioxidant and antibacterial properties. Self-aggregation and hydrophobic properties of S. boulardii were relatively poor, but they showed high tolerance, antioxidant properties, and broad antibacterial properties. In addition, non-targeted metabolomics was used to comprehensively analyze the active metabolites of S. boulardii and the metabolic differences between S. boulardii and S. cerevisiae were compared. Saccharomyces boulardii produced many bioactive metabolites, which generally showed antioxidant, antibacterial, antitumor, anti-inflammatory, and other properties. In contrast to S. cerevisiae, S. boulardii produced phenyllactic acid and 2-hydroxyisocaproic acid. There were also significant differences in their metabolic pathways. These results may be of great significance in the medical and food industries and provide a basis for understanding the metabolism of S. boulardii. It also shows that metabolomics is an effective and novel method for screening microbial functional metabolites and identifying functional differences between similar microorganisms.

Role of bacterial community succession in flavor formation during Sichuan sun vinegar grain (Cupei) fermentation.

Sichuan sun vinegar (SSV) is a traditional Chinese vinegar with a unique flavor and it is fermented with bran as the main raw material. In the present study, we explored the bacterial community succession in fermented grains (Cupei) during SSV production. High-throughput sequencing results showed that bacterial community richness and diversity peaked on day 7 of fermentation. Lactobacillus and Acetobacter were the dominant bacteria throughout the fermentation process. However, Acetobacter, Cupriavidus, Sphingomonas, Pelomonas, and Lactobacillus were the most abundant genera in the late phase of fermentation on day 17. The boundaries of trilateral co-fermentation were determined through cluster analysis. Days 1-3 were considered the early fermentation stage (starch saccharification), days 5-11 were the middle fermentation stage (alcoholic fermentation), and days 13-17 represented the late fermentation stage (acetic acid fermentation). Changes in flavor compounds during Cupei fermentation were subsequently analyzed and a total of 86 volatile compounds, 9 organic acids, and 17 amino acids were detected. Although acetic acid, lactic acid, alcohols, and esters were the main metabolites, butyrate was also detected. Correlation analysis indicated that 20, 21, and 28 microorganisms were positively correlated with the abundance of amino acids, organic acids, and volatile flavor compounds, respectively. We further explored the microbial and metabolic mechanisms associated with the dominant volatile flavor compounds during SSV fermentation. Collectively, the findings of the current study provide detailed insights regarding the fermentation mechanisms of SSV, which may prove relevant for producing high-quality fermented products.

Immune cells and RBCs derived from human induced pluripotent stem cells: method, progress, prospective challenges.

Blood has an important role in the healthcare system, particularly in blood transfusions and immunotherapy. However, the occurrence of outbreaks of infectious diseases worldwide and seasonal fluctuations, blood shortages are becoming a major challenge. Moreover, the narrow specificity of immune cells hinders the widespread application of immune cell therapy. To address this issue, researchers are actively developing strategies for differentiating induced pluripotent stem cells (iPSCs) into blood cells in vitro. The establishment of iPSCs from terminally differentiated cells such as fibroblasts and blood cells is a straightforward process. However, there is need for further refinement of the protocols for differentiating iPSCs into immune cells and red blood cells to ensure their clinical applicability. This review aims to provide a comprehensive overview of the strategies and challenges facing the generation of iPSC-derived immune cells and red blood cells.

Approaches for neutrophil imaging: an important step in personalized medicine.

Neutrophils are the most abundant circulating leukocytes and the first line of defense against invading pathogens. They are key components of the innate immune system. Neutrophils also cause tissue damage in various autoimmune and inflammatory diseases and play an important role in cancer progression. Due to the complex relationship between various diseases and neutrophils, these cells have become potentially important targets for therapeutic interventions. Monitoring neutrophils in the tumor microenvironment is critical for tumor treatment and prognostic analysis but remains challenging. Molecular imaging technology has made great progress as a valuable tool for noninvasively visualizing biological events and establishing effective cancer diagnoses and treatment methods. Molecular probes designed based on the characteristics of neutrophils, such as their flexible morphology, the abundance of surface receptors, and the absence of immunogenicity, have shown great potential. This has created an opportunity for novel ideas and research methods for the diagnosis and targeted therapy of inflammatory diseases and tumors, with the goal of integrated diagnosis and treatment. This review discusses the diverse tumor detection and diagnostic imaging strategies based on neutrophils. It is anticipated that neutrophil-based imaging will soon be gradually integrated into clinical applications.

Neutrophils play a role in promoting/inhibiting tumor growth in the tumor microenvironment.To be more conducive to discovering neutrophils in tumors and guiding treatment, medical imaging technology has developed stepwise.In the context of the intersection of imaging technology, great breakthroughs have been made in the individualized research of tumor diagnosis.This article contributes to the promotion of new multimodal molecular imaging technology and the application of rapid diagnosis individualization.