Genomic profiling of cell-free DNA from dogs with benign and malignant tumors.

OBJECTIVE: Cancer is currently the most common cause of death in adult dogs. Like humans, dogs have a one-third chance of developing cancer in their lifetime. We used shallow whole-genome sequencing (sWGS) to analyze blood cell-free DNA (cfDNA) from four tumor-bearing dogs (one with benign and three with malignant tumors) and 38 healthy dogs. RESULTS: Similar to the results observed in the healthy dogs, no copy number aberration (CNA) was detected in the dog with benign lipomas, and the distribution of cfDNA fragment size (FS) closely resembled that of the healthy dogs. However, among the three dogs diagnosed with malignant tumors, two dogs exhibited varying degrees and quantities of CNAs. Compared to the distribution of FS in the healthy dogs, the cancer dogs exhibited a noticeable shift towards shorter lengths. These findings indicated that CNA and FS profiles derived from sWGS data can be used for non-invasive cancer detection in dogs.

Exercise-promoted adiponectin secretion activates autolysosomes to protect the liver of ApoE-/- mice from a high-fat diet.

Fat is a "double-edged sword": while it is a necessary substance for the body, the long-term intake of excessive fat will cause obesity, with the liver subjected to lipotoxicity as it accumulates. It will then continue to deteriorate, eventually leading to liver failure, which is a negative impact of high-fat food intake. Research has shown that exercise can reverse the side effects of a chronic high-fat diet and help the body to mitigate the harmful effects of lipotoxicity. In our study, it was found that moderate-intensity cardio-training (MICT) and high-intensity interval exercise (HIIT) effectively protected the livers of high-fat diet (HFD) ApoE-/- mice against lipotoxicity. Previous results demonstrated that 12 weeks of HFD resulted in a significant elevation of CD36 in the livers of C57BL/6J mice, while knockdown of CD36 did not reduce the accumulation of fat in the liver. Therefore, we used ApoE-/- mice as experimental subjects. Although HFD caused the development of hyperlipidemia and atherosclerosis, it is interesting to note that, due to the knockdown of ApoE, the livers of ApoE-/- mice in the non-exercise group did not show significant lipid deposition; however, after 12 weeks of MICT and HIIT, the livers of ApoE-/- mice showed significant lipid deposition. After we analyzed the lipid metabolism in their livers, we found that this was caused by the promotion of transport of peripheral fat into the liver due to exercise. Moreover, 12 weeks of exercise effectively reduced atherosclerosis, and the livers of ApoE-/- mice in the exercise group were not damaged by lipotoxicity. The results showed that a 12-week exercise treatment activated AMPK in the livers of HFD ApoE-/- mice through the APN-AdipoR1 signaling pathway, improved hepatic lipid metabolism disorders, and promoted the nuclear translocation of TFEB to enhance autophagic-lysosomal lipid scavenging. After the peripheral lipid is input into the liver due to exercise, the energy generated through gluconeogenesis can be used to replenish the energy consumed by exercise and maintain the normal operation of various functions in the liver, based on which the high autophagic flux in the liver can be maintained and the lipid clearance rate can be enhanced to protect the liver from lipotoxicity.

Optimized irrigation and fertilization can mitigate negative CO2 impacts on seed yield and vigor of hybrid maize.

Seed yield and vigor of hybrid maize determine the planting, yield, and quality of maize, and consequently affect food, nutrition, and livelihood security; however, the response of seed yield and vigor to climate change is still unclear. We established an optimization-simulation framework consisting of a water­nitrogen crop production function, a seed vigor and a gridded process-based model to optimize irrigation and nitrogen fertilization management, and used it to evaluate seed yield and vigor in major seed production locations of China, the USA, and Mexico. This framework could reflect the influence of water and nitrogen inputs at different stages on seed yield and vigor considering the spatio-temporal variability of climate and soil properties. Projected seed yield and vigor decreased by 5.8-9.0 % without adaptation by the 2050s, due to the 1.3-5.8 % decrease in seed number and seed protein concentration. Seed yield was positively correlated with CO2 and negatively correlated with temperature, while seed vigor depended on the response of components of seed vigor to climatic factors. Under optimized management, the direct positive effects of temperature on seed protein concentration and CO2 on seed number were strengthened, and the direct negative effects of temperature on seed number and CO2 on seed protein concentration were weakened, which mitigated the reductions in both seed yield and vigor. Elevated CO2 was projected to exacerbate the 2.6 % seed vigor reduction and mitigate the 2.9 % seed yield loss without adaptation, while optimized management could increase seed yield by 4.1 % and mitigate the 2.2 % seed vigor reduction in the Hexi Corridor of China, and decrease the seed yield and vigor reduction by 2.4-5.8 % in the USA and Mexico. Optimized management can strengthen the positive and mitigate the negative effects of climate change on irrigated hybrid maize and inform high-yield and high-quality seed production globally.

Guest-Induced Helical Superstructure from a Gold Nanocluster-Based Supramolecular Organic Framework Enables Efficient Catalysis.

Mimicking hierarchical assembly in nature to exploit atomically precise artificial systems with complex structures and versatile functions remains a long-standing challenge. Herein, we report two single-crystal supramolecular organic frameworks (MSOF-4 and MSOF-5) based on custom-designed atomically precise gold nanoclusters Au11(4-Mpy)3(PPh3)7, showing distinct and intriguing host-guest adaptation behaviors toward 1-/2-bromopropane (BPR) isomers. MSOF-4 exhibits sev topology and cylindrical channels with 4-mercaptopyridine (4-Mpy) ligands matching well with guest 1-BPR. Due to the confinement effect, solid MSOF-4 undergoes significant structural change upon selective adsorption of 1-BPR vapor over 2-BPR, resulting in strong near-infrared fluorescence. Single-crystal X-ray diffraction reveals that Au11(4-Mpy)3(PPh3)7 in MSOF-4 transforms into Au11Br3(PPh3)7 upon ligand exchange with 1-BPR, resulting in 1-BPR@MSOF-6 single crystals with a rarely reported helical assembly structure. Significantly, the double-helical structure of MSOF-6 facilitates efficient catalysis of the electron transfer (ET) reaction, resulting in a nearly 6 times increase of catalytic rates compared with MSOF-4. In sharp contrast, solid MSOF-5 possesses chb topology and cage-type channels with narrow windows, showing excellent selective physical adsorption toward 1-BPR vapor but a nonfluorescent feature upon guest adsorption. Our results demonstrate a powerful strategy for developing advanced assemblies with high-order complexity and engineering their functions in atomic precision.

DDR2/STAT3 Positive Feedback Loop Mediates the Immunosuppressive Microenvironment by Upregulating PD-L1 and Recruiting MDSCs in Oxaliplatin-Resistant HCC.

BACKGROUND AND AIMS: Transcriptome sequencing revealed high expression of DDR2 in oxaliplatin-resistant hepatocellular carcinoma (HCC). This study aimed to explore the role of DDR2 in oxaliplatin resistance and immune evasion in HCC. METHODS: Oxaliplatin-resistant HCC cell lines were established. The interaction between DDR2 and STAT3 was investigated, along with the mechanisms involved in DDR2/STAT3-mediated PD-L1 upregulation and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) accumulation both in vitro and in vivo. RESULTS: DDR2 was found to induce the phosphorylation of STAT3, leading to its nuclear translocation. Conversely, the activation of STAT3 enhanced DDR2 expression. A positive feedback loop involving DDR2/STAT3 was identified in oxaliplatin-resistant HCC, which was associated with PD-L1 upregulation and PMN-MDSCs accumulation. Knockdown of DDR2 and STAT3 sensitized oxaliplatin-resistant HCC cells to oxaliplatin and resulted in decreased PMN-MDSCs and increased CD8+ T cells in the tumor microenvironment. Enzyme-linked immunosorbent array and MDSC transwell migration assays indicated that oxaliplatin-resistant HCC cells recruited PMN-MDSCs through CCL20. Dual luciferase reporter assays demonstrated that STAT3 can directly enhance the transcription of PD-L1 and CCL20. Furthermore, treatment with a PD-L1 antibody in combination with CCL20 blockade had significant antitumor effects on oxaliplatin-resistant HCC. CONCLUSIONS: Our findings revealed a positive feedback mechanism involving DDR2 and STAT3 that mediates the immunosuppressive microenvironment and promotes oxaliplatin resistance and immune evasion via PD-L1 upregulation and PMN-MDSC recruitment. Targeting the DDR2/STAT3 pathway may be a promising therapeutic strategy to overcome immune escape and chemoresistance in HCC.

Association between ambient fine particular matter components and subsequent cognitive impairment in community-dwelling older people: a prospective cohort study from eastern China.

BACKGROUND: Fine particular matter (PM2.5) has been associated with dementia, but limited information is available regarding the association between PM2.5 components and dementia. AIMS: We aimed to identify the major components of PM2.5 that affect cognitive function to further investigate its mechanism of action, and develop a prevention strategy for dementia. METHODS: In this study, we included 7804 participants aged ≥ 60 years recruited from seven counties in Zhejiang province, eastern China. The participants completed the baseline survey between 2014 and 2015, and were followed up until the end of 2020. We adopted single-component robust Poisson regression models for analyses, and estimated relative risks and 95% confidence intervals describing associations between the chemical constituents of PM2.5 exposure and incident cognitive impairment in those who were free from cognitive impairment at baseline. RESULTS: Significantly positive associations were observed between sulfate, nitrate, ammonium, and organic matter in PM2.5 and incident cognitive impairment across different exposure periods; the relative risks of 10-year exposure before enrollment ranged from 1.01 to 1.02. However, we did not find a significant association between black carbon and cognitive impairment. The point estimates of the relative risk values did not change substantially after performing the sensitivity analyses. CONCLUSIONS: Our findings strengthen the idea that long-term exposure to PM2.5 mass and its chemical components is associated with an elevated risk of incident cognitive impairment among older adults.

CD276 Promotes an Inhibitory Tumor Microenvironment in Hepatocellular Carcinoma and is Associated with Poor Prognosis.

Background: CD276 is an emerging immune checkpoint molecule that has been implicated in various cancers. However, its specific role in hepatocellular carcinoma (HCC) remains unclear. This study examined the impact of CD276 on patient prognosis and the tumor microenvironment (TME). Methods: The Cancer Genome Atlas (TCGA) database was utilized to evaluate CD276 expression in HCC and the association between CD276 and immune indicators was also analyzed. The signaling pathways correlated with CD276 expression were identified by gene set enrichment analysis (GSEA). Different algorithms were used to assess immune cell infiltration. The effect of CD276 knockdown on HCC cell phenotypes and its relationship with macrophage polarization was examined using the cell counting kit 8 (CCK-8) assay and co-culture system. Results: CD276 was upregulated in HCC and associated with unfavorable clinical outcomes. Hgh CD276 expression was associated with enrichment of the G2/M checkpoint, E2F targets, and mitotic spindles. CD276 expression was correlated with the infiltration of immune cells, including high level of tumor-associated macrophages and low levels of CD8+ T cells. Knockdown of CD276 decreased HCC cell proliferation and increased apoptosis. CD276 silencing in HCC cells and co-culture with THP-1-derived macrophages had a regulatory effect on macrophage polarization and macrophage-mediated cell proliferation and migration. Conclusion: CD276 expression in HCC is associated with unfavorable clinical outcomes and may contribute to the development of an immunosuppressive microenvironment. Specifically, CD276 was associated with alterations in immune cell infiltration, immune marker expression, and macrophage polarization during HCC progression, suggesting its potential as a prognostic indicator and promising target for immunotherapeutic intervention in HCC.

High-precision spatiotemporal three-dimensional ultrashort pulse synchronization with optical Kerr effect.

In studying the interaction of multiple ultrashort pulses with matter, high requirements are put forward for spatiotemporal synchronization accuracy. Limited by the response time and bandwidth of existing devices, the synchronization of multiple ultrashort pulses still faces significant difficulties. By observing the transient phenomena of the optical Kerr effect, high-precision, three-dimensional (x, y, t) synchronization of ultrashort pulses at different angles was achieved. In the optical Kerr effect, the polarization state of the signal pulse changes only when it coincides with the pump pulse, at which point the signal pulse passes through the analyzer. The changes in the intensity and phase of the signal pulse is positively correlated with the degree of spatiotemporal coincidence. In this study, 10-ps pulses were used in the experiments. By observing the intensity and phase distribution of the signal pulses, a time synchronization accuracy between two pulses of less than 1 ps and spatial synchronization accuracy of ±125 µm and ±3 µm in the x and y directions, respectively, were achieved. Moreover, the synchronization of two pulses at an angle of 90 ° was measured, further proving that the method can achieve the spatiotemporal synchronization of pulses with large angles. Therefore, this method has important application prospects in the study of multi-beam interactions with matter and other ultrafast physical phenomena.

Elevating Discharge Voltage of Li2CO3-Routine Li-CO2 Battery over 2.9†V at an Ultra-Wide Temperature Window.

The Li-CO2 batteries utilizing greenhouse gas CO2 possess advantages of high energy density and environmental friendliness. However, these batteries following Li2CO3-product route typically exhibit low work voltage (<2.5 V) and energy efficiency. Herein, we have demonstrated for the first time that cobalt phthalocyanine (CoPc) as homogeneous catalyst can elevate the work plateau towards 2.98 V, which is higher than its theoretical discharge voltage without changing the Li2CO3-product route. This unprecedented discharge voltage is illustrated by mass spectrum and electrochemical analyses that CoPc has powerful adsorption capability with CO2 (-7.484 kJ mol-1) and forms discharge intermediate of C33H16CoN8O2. Besides high discharge capacity of 18724 mAh g-1 and robust cyclability over 1600 hours (1000 mAh g-1 cut-off) at a current density of 100 mA g-1, the batteries show high temperature adaptability (-30-80 °C). Our work is paving a promising avenue for the progress of high-efficiency Li-CO2 batteries.

High-intensity interval training and medium-intensity continuous training may affect cognitive function through regulation of intestinal microbial composition and its metabolite LPS by the gut-brain axis.

AIMS: The gut-brain axis is the communication mechanism between the gut and the central nervous system, and the intestinal flora and lipopolysaccharide (LPS) play a crucial role in this mechanism. Exercise regulates the gut microbiota composition and metabolite production (i.e., LPS). We aimed to investigate the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on cognitive function in C57BL/6 J mice through gut-brain axis regulation of gut microbiota composition and LPS displacement. MAIN METHODS: C57BL/6 J male mice were randomly divided into sedentary, HIIT, and MICT groups. After 12 weeks of exercise intervention, the cognitive function of the brain and mRNA levels of related inflammatory factors were measured. RNA sequencing, Golgi staining, intestinal microbial 16 s rDNA sequencing, and ELISA were performed. KEY FINDINGS: HIIT and MICT affect brain cognitive function by regulating the gut microbiota composition and its metabolite, LPS, through the gut microbiota-gut-brain axis. HIIT is suspected to have a risk: it can induce "intestinal leakage" by regulating intestinal permeability-related microbiota, resulting in excessive LPS in the blood and brain and activating M1 microglia in the brain, leading to reduced dendritic spine density and affecting cognitive function. SIGNIFICANCE: This study revealed a potential link between changes in the gut microbiota and cognitive function. It highlighted the possible risk of HIIT in reducing dendritic spine density and affecting cognitive function.

High-Entropy Configuration Strategy to Build High Performance Na-Ion Layered Oxide Cathodes Derived from Simple Techniques.

Layered transition metal oxides are commonly used as the cathode materials in sodium-ion batteries due to their low cost and easy manufacturing. However, the application is hindered by poor rate performance and complex phase transitions. To address these challenges, a new seven-component high-entropy layered oxide cathode material, O3-NaNi0.25Fe0.15Mn0.3Ti0.1Sn0.05Co0.05Li0.1O2 (HEO) has been developed. The entropy stabilization effect plays a crucial role in improving the performance of electrochemical systems and the stability of structures. The HEO exhibits a specific discharge capacity of 154.1 mA h g-1 at 0.1 C and 94.5 mA h g-1 at 7 C. In-situ and ex-situ XRD results demonstrate that the HEO effectively retards complex phase transitions. This work provides a high-entropy design for the storage materials with a high energy density. Meanwhile, it eliminates industry doubts about the performance of sodium ion layered oxide cathode materials.

Giant dielectric tunability in ferroelectric ceramics with ultralow loss by ion substitution design.

Due to their responsiveness to modulation by external direct current fields, dielectric tunable materials are extensively utilized in integrated components, such as ferroelectric phase shifters. Barium strontium titanate ceramics have been considered the most potential tunable materials for a long time. However, the significant dielectric loss and high voltage drive have limited their further applications. Recently, Bi6Ti5WO22 ceramic has regained attention for its high dielectric tunability with low loss. In this study, we judiciously introduce Nb5+ with a larger ionic radius, replacing Ti4+ and W6+. This successful substitution enables the modulation of the phase transition temperature of Bi6Ti5WO22 ceramics to room temperature, resulting in superior tunable properties. Specifically, the 0.7Bi6Ti5WO22-0.3Bi6Ti4Nb2O22 ceramics exhibit giant tunability (~75.6%) with ultralow loss (<0.002) under a low electric field (1.5 kV/mm). This tunability is twice that of barium strontium titanate ceramics with a similar dielectric constant and only one-tenth of the loss. Neutron powder diffraction and transmission-electron-microscopy illustrate the nanodomains and micro-strains influenced by ion substitution. Density functional theory simulation calculations reveal the contribution of ion substitution to polarization. The research provides an ideal substitute for tunable material and a general strategy for adjusting phase transition temperature to improve dielectric properties.

Nickel-catalyzed switchable arylative/endo-cyclization of 1,6-enynes.

Carbo- and heterocycles are frequently used as crucial scaffolds in natural products, fine chemicals, and biologically and pharmaceutically active compounds. Transition-metal-catalyzed cyclization of 1,6-enynes has emerged as a powerful strategy for constructing functionalized carbo- and heterocycles. Despite significant progress, the regioselectivity of alkyne functionalization is entirely substrate-dependent. And only exo-cyclization/cross-coupling products can be obtained, while endo-selective cyclization/cross-coupling remains elusive and still poses a formidable challenge. In this study, we disclose a nickel-catalyzed switchable arylation/cyclization of 1,6-enynes in which the nature of the ligand dictates the regioselectivity of alkyne arylation, while the electrophilic trapping reagents determine the selectivity of the cyclization mode. Specifically, using a commercially available 1,10-phenanthroline as a ligand facilitates trans-arylation/cyclization to obtain seven-membered ring products, while a 2-naphthyl-substituted bisbox ligand promotes cis-arylation/cyclization to access six-membered ring products. Diastereoselective cyclizations have also been developed for the synthesis of enantioenriched piperidines and azepanes, which are core structural elements of pharmaceuticals and natural products possessing important biological activities. Furthermore, experimental and density functional theory studies reveal that the regioselectivity of the alkyne arylation process is entirely controlled by the steric hindrance of the ligand; the reaction mechanism involves exo-cyclization followed by Dowd-Beckwith-type ring expansion to form endo-cyclization products.

Identification of clinically relevant subsets CD39+PD-1+CD8+ T cells and CD39+ regulatory T cells in intrahepatic cholangiocarcinoma using single-cell CyTOF.

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive liver malignancy with limited treatment options and a dismal prognosis. The tumor immune microenvironment (TIME) is crucial for iCCA progression, yet its comprehensive characterization remains incomplete. This study utilized mass cytometry by time of flight (CyTOF) to comprehensively analyze immune cell populations in fresh iCCA tumor samples and adjacent peritumor liver tissues. Notably, NK cell percentages significantly decreased in iCCA lesions compared to peritumor liver tissues. Conversely, an enrichment of immunosuppressive CD39+Foxp3+CD4+ regulatory T cells (CD39+T-regs) and exhausted-like CD8+T cells (with pronounced CD39 and PD-1 expression) within TIME was identified and confirmed by multiplex immunofluorescence staining in an independent patient cohort (n = 140). Crucially, tumor-infiltrating CD39+T-regs and CD39+PD-1+CD8+T cells emerged as independent prognostic indicators associated with an unfavorable prognosis in iCCA. These findings unveil the intricate immune landscape within iCCA, offering valuable insights for disease management and novel cancer immunotherapies.

Real-world study of hepatic artery infusion chemotherapy combined with anti-PD-1 immunotherapy for hepatocellular carcinoma patients with portal vein tumor thrombus.

Background: Patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) present a poor prognosis. Current systemic therapies offer limited benefits. Hepatic artery infusion chemotherapy (HAIC) is a local regional treatment for advanced HCC, particularly in selected patients such as patients with PVTT or high intrahepatic tumor burden. Objectives: The purpose of this study is to retrospectively evaluate the efficacy and safety of HAIC combined with anti-PD-1 immunotherapy for HCC patients with PVTT, and explore factors related to survival prognosis, providing clues for treatment decisions for HCC patients. Design: This is a single-center retrospective study conducted over 2 years on consecutive PVTT patients receiving HAIC combined anti-PD-1 antibodies. Methods: The primary endpoint was overall survival (OS). Univariate and multivariate analyses were performed to identify prognostic factors affecting OS. Treatment-associated adverse events were evaluated as well. Results: A total of 119 patients were analyzed. The median OS and PFS were 14.9 months and 6.9 months. A total of 31.1% of grade 3-4 adverse events were reported, with elevated transaminase and total bilirubin being the most common. The independent variables correlated with survival include treatment-related alpha-fetoprotein (AFP) response, the presence of extrahepatic organ metastasis, absolute value of platelet (PLT), neutrophil-to-lymphocyte ratio, and combined usage of tyrosine kinase inhibitors (TKIs). Conclusion: In HCC patients with PVTT, combination therapy with HAIC and anti-PD-1 antibodies might be a promising therapy. The efficacy and safety of this combination protocol on patients with HCC complicated by PVTT warrants further investigation prospectively, especially in combination with TKIs.

Preoxidation and Prilling Combined with Doping Strategy to Build High-Performance Recycling Spent LiFePO4 Materials.

Direct regeneration has gained much attention in LiFePO4 battery recycling due to its simplicity, ecofriendliness, and cost savings. However, the excess carbon residues from binder decomposition, conductive carbon, and coated carbon in spent LiFePO4 impair electrochemical performance of direct regenerated LiFePO4. Herein, we report a preoxidation and prilling collaborative doping strategy to restore spent LiFePO4 by direct regeneration. The excess carbon is effectively removed by preoxidation. At the same time, prilling not only reduces the size of the primary particles and shortens the diffusion distance of Li+ but also improves the tap density of the regenerated materials. Besides, the Li+ transmission of the regenerated LiFePO4 is further improved by Ti4+ doping. Compared with commercial LiFePO4, it has excellent low-temperature performance. The collaborative strategy provides a new insight into regenerating high-performance spent LiFePO4.

UFObow: A single-wavelength excitable Brainbow for simultaneous multicolor ex-vivo and in-vivo imaging of mammalian cells.

Brainbow is a genetic cell-labeling technique that allows random colorization of multiple cells and real-time visualization of cell fate within a tissue, providing valuable insights into understanding complex biological processes. However, fluorescent proteins (FPs) in Brainbow have distinct excitation spectra with peak difference greater than 35 nm, which requires sequential imaging under multiple excitations and thus leads to long acquisition times. In addition, they are not easily used together with other fluorophores due to severe spectral bleed-through. Here, we report the development of a single-wavelength excitable Brainbow, UFObow, incorporating three newly developed blue-excitable FPs. We have demonstrated that UFObow enables not only tracking the growth dynamics of tumor cells in vivo but also mapping spatial distribution of immune cells within a sub-cubic centimeter tissue, revealing cell heterogeneity. This provides a powerful means to explore complex biology in a simultaneous imaging manner at a single-cell resolution in organs or in vivo.

Monocular vision-based dynamic calibration method for determining the sensitivities of low-frequency tri-axial vibration sensors.

Low-frequency vibrations exist widely in the natural environment and in human activities. Low-frequency tri-axial vibration sensors are enormously applied in the fields of seismic monitoring, building structure health monitoring, aerospace navigating, etc. Their sensitivity calibration accuracy directly determines whether their applications can work reliably. Although the laser interferometry recommended by the International Standardization Organization (ISO) is commonly used to achieve the vibration calibration, it suffers from the shortages of low-frequency range, high cost, low efficiency, and limited applicable environment. In this study, a novel monocular vision-based dynamic calibration method is proposed, which determines the whole sensitivities of tri-axial sensors by the monocular vision method to accurately measure the spatial input excitation. This method improves the calibration performance by eliminating the installation error and enhancing calibration efficiency via decreasing reinstallations. The experimental results compared with the laser interferometry demonstrate that the investigated method can obtain similar calibration accuracy in the range of 0.16-2 Hz with more efficiency. The corresponding maximum relative deviations of X-, Y-, and Z-axial sensitivities were approximately 2.5%, 1.8%, and 0.4%. In addition, the maximum relative standard deviation of the investigated method was only about 0.3% in this range.

Lactate/Hydroxycarboxylic Acid Receptor 1 in Alzheimer's Disease: Mechanisms and Therapeutic Implications-Exercise Perspective.

Lactate has a novel function different from previously known functions despite its traditional association with hypoxia in skeletal muscle. It plays various direct and indirect physiological functions. It is a vital energy source within the central nervous system (CNS) and a signal transmitter regulating crucial processes, such as angiogenesis and inflammation. Activating lactate and its associated receptors elicits effects like synaptic plasticity and angiogenesis alterations. These effects can significantly influence the astrocyte-neuron lactate shuttle, potentially impacting cognitive performance. Decreased cognitive function relates to different neurodegenerative conditions, including Alzheimer's disease (AD), ischemic brain injury, and frontotemporal dementia. Therefore, lactic acid has significant potential for treating neurodegenerative disorders. Exercise is a method that induces the production of lactic acid, which is similar to the effect of lactate injections. It is a harmless and natural way to achieve comparable results. Animal experiments demonstrate that high-intensity intermittent exercise can increase vascular endothelial growth factor (VEGF) levels, thus promoting angiogenesis. In vivo, lactate receptor-hydroxycarboxylic acid receptor 1 (HCAR1) activation can occur by various stimuli, including variations in ion concentrations, cyclic adenosine monophosphate (cAMP) level elevations, and fluctuations in the availability of energy substrates. While several articles have been published on the benefits of physical activity on developing Alzheimer's disease in the CNS, could lactic acid act as a bridge? Understanding how HCAR1 responds to these signals and initiates associated pathways remains incomplete. This review comprehensively analyzes lactate-induced signaling pathways, investigating their influence on neuroinflammation, neurodegeneration, and cognitive decline. Consequently, this study describes the unique role of lactate in the progression of Alzheimer's disease.

Oral administration of egg ovalbumin allergen induces dysregulation of tryptophan metabolism in sensitized BALB/c mice.

Food allergy (FA), triggered by specific dietary allergens, has emerged as a substantial global concern for food safety and public health. While studies have elucidated changes in immune cells and cytokines associated with allergen exposure, a comprehensive analysis of the host's metabolic features and the interaction between metabolites and the gut microbiota has not been conducted. In this study, egg allergen ovalbumin (OVA) was administered by the oral route to sensitized BALB/c mice to faithfully replicate key aspects of human FA, including severe allergic diarrhea, mast cell infiltration, and elevated levels of serum IgE, mMCPT-1, and Th2 cell hallmark cytokines (such as IL-4, IL-5, and IL-13). Furthermore, the untargeted and targeted metabolomic analyses indicated that FA in mice precipitated a substantial decrease in the tryptophan metabolites indole-3-acrylic acid (IA) and indole-3-lactic acid (ILA). The integration of shotgun metagenome and metabolome data further unveiled that the dysregulation of indole metabolism is related to a decline in the abundance of beneficial bacteria such as Lactobacillus and Bifidobacterium. Additionally, disruption of the tryptophan indole derivative pathway compromises the maintenance of intestinal mucosal function through the AHR signaling pathway, manifested by decreased expression of Reg3g and IL22. Taken together, this study demonstrated that the anaphylaxis triggered by oral ingestion of food allergens can lead to disruptions in tryptophan metabolism, consequently impairing intestinal immune homeostasis.