Metal Ion-Regulated Fluorescent Sensor Array Based on Gold Nanoclusters for Physiological Phosphate Sensing.

The detection of physiological phosphates (PPs) is of great importance due to their essential roles in numerous biological processes, but the efficient detection of different PPs simultaneously remains challenging. In this work, we propose a fluorescence sensor array for detecting PPs based on metal-ion-regulated gold nanoclusters (AuNCs) via an indicator-displacement assay. Zn2+ and Eu3+ are selected to assemble with two different AuNCs, resulting in quenching or enhancing their fluorescence. Based on the competitive interaction of metal ions with AuNCs and PPs, the fluorescence of AuNCs will be recovered owing to the disassembly of AuNC-metal ion ensembles. Depending on different PPs' distinct fluorescence responses, a four-channel sensor array was established. The array not only exhibits good discrimination capability for eight kinds of PPs (i.e., ATP, ADP, AMP, GTP, CTP, UTP, PPi, and Pi) via linear discriminant analysis but also enables quantitative detection of single phosphate (e.g., ATP) in the presence of interfering PPs mixtures. Moreover, potential application of the present sensor array for the discrimination of different PPs in real samples (e.g., cell lysates and serum) was successfully demonstrated with a good performance. This work illustrates the great potential of a metal ion-regulated sensor array as a new and efficient sensing platform for differential sensing of phosphates as well as other disease-related biomolecules.

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.

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.

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.

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.

Inhibitory effect of liriopesides B in combination with gemcitabine on human pancreatic cancer cells.

Gemcitabine (GEM) is a standard chemotherapeutic agent for patients with pancreatic cancer; however, GEM-based chemotherapy has a high rate of toxicity. A combination of GEM and active constituents from natural products may enhance its therapeutic efficacy and reduce its toxicity. This study investigated the synergistic effects of the combination of liriopesides B (LirB) from Liriope spicata var. prolifera and GEM on human pancreatic cancer cells. The results of our study showed that the combination of LirB and GEM synergistically decreased the viability of pancreatic cancer cells. The combination also caused a strong increase in apoptosis and a strong decrease in cell migration and invasion. Furthermore, LirB combined with GEM had potent inhibitory effects on pancreatic cancer stem cells (CSCs). Studies on the mechanisms of action showed that the combination more potently inhibited protein kinase B (Akt) and nuclear factor kappa B (NF-κB), as well as the downstream antiapoptotic molecules B-cell lymphoma 2 (Bcl-2) and survivin than either agent used alone. The results of this study suggest that the combination of LirB with GEM may improve the efficacy of GEM for the treatment of pancreatic cancer.

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.

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.

Optimization of doping design for planar P-N homologous junction perovskite solar cells.

In this study, we used the solar cell capacitance simulator (SCAPS) to analyse numerically the performance of perovskite solar cells (PSCs) containing CH3NH3PbI3. The findings indicate that P-N homologous junction processing based on traditional P-I-N PSCs can enhance the photoelectric conversion efficiency (PCE). Furthermore, the authors analyzed the effect of uniform P-N doping of CH3NH3PbI3, concluding that the photoelectric efficiency can be improved from 16.10% to 19.03% after doping. In addition, the optical properties of PSCs under solar irradiation are simulated using finite difference time-domain (FDTD) software under AM1.5. This method is applied to investigate the effect of the P-N uniform junction on the internal electric field generated within the cell. The generation of this electric field promotes carrier separation and transmission, ultimately increasing the open circuit voltage (VOC) of the solar cell from 1.03 to 1.12 V. The usage of P-N junctions enhances PSCs performance and exhibits vast potential for designing and developing PSCs.

Nickel-catalyzed electrophiles-controlled enantioselective reductive arylative cyclization and enantiospecific reductive alkylative cyclization of 1,6-enynes.

Transition metal-catalyzed asymmetric cyclization of 1,6-enynes is a powerful tool for the construction of chiral nitrogen-containing heterocycles. Despite notable achievements, these transformations have been largely limited to the use of aryl or alkenyl metal reagents, and stereoselective or stereospecific alkylative cyclization of 1,6-enynes remains unexploited. Herein, we report Ni-catalyzed enantioselective reductive anti-arylative cyclization of 1,6-enynes with aryl iodides, providing enantioenriched six-membered carbo- and heterocycles in good yields with excellent enantioselectivities. Additionally, we have realized Ni-catalyzed enantiospecific reductive cis-alkylative cyclization of 1,6-enynes with alkyl bromides, furnishing chiral five-membered heterocycles with high regioselectivity and stereochemical fidelity. Mechanistic studies reveal that the arylative cyclization of 1,6-enynes is initiated by the oxidative addition of Ni(0) to aryl halides and the alkylative cyclization is triggered by the oxidative addition of Ni(0) to allylic acetates. The utility of this strategy is further demonstrated in the enantioselective synthesis of the antiepileptic drug Brivaracetam.

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.

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.

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.

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 and associated with PD-L1 upregulation, and PMN-MDSCs accumulation was identified in oxaliplatin-resistant HCC. 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.

Inhibiting PLA2G7 reverses the immunosuppressive function of intratumoral macrophages and augments immunotherapy response in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is an exceptionally immunosuppressive malignancy characterized by limited treatment options and a dismal prognosis. Macrophages constitute the primary and heterogeneous immune cell population within the HCC microenvironment. Our objective is to identify distinct subsets of macrophages implicated in the progression of HCC and their resistance to immunotherapy. METHODS: Intratumoral macrophage-specific marker genes were identified via single-cell RNA sequencing analyses. The clinical relevance of phospholipase A2 Group VII (PLA2G7), a pivotal enzyme in phospholipid metabolism, was assessed in patients with HCC through immunohistochemistry and immunofluorescence. Flow cytometry and an in vitro co-culture system were used to elucidate the specific role of PLA2G7 in macrophages. Orthotopic and subcutaneous HCC mouse models were employed to evaluate the potential of the PLA2G7 inhibitor in complementing immune checkpoint blockade (ICB) therapy. RESULTS: Single-cell RNA sequencing analyses disclosed predominant PLA2G7 expression in intratumoral macrophages within the HCC microenvironment. The macrophage-specific PLA2G7 was significantly correlated with poorer prognosis and immunotherapy resistance in patients with HCC. PLA2G7high macrophages represent a highly immunosuppressive subset and impede CD8 T-cell activation. Pharmacological inhibition of PLA2G7 by darapladib improved the therapeutic efficacy of anti-programmed cell death protein 1 antibodies in the HCC mouse models. CONCLUSIONS: Macrophage-specific PLA2G7 serves as a novel biomarker capable of prognosticating immunotherapy responsiveness and inhibiting PLA2G7 has the potential to enhance the efficacy of ICB therapy for HCC.

Discovering novel biomarkers for diagnosis and treatment monitoring of active pulmonary tuberculosis by ion metabolism analysis.

Tuberculosis (TB) is a highly lethal infectious disease that poses a global threat. Timely and accurate biomarker for TB diagnosis and treatment monitoring remains a pressing need. Ions, the crucial trace element for humans, may be potential targets for TB diagnosis and the forecasting of TB development. To explore the potential of ions as biomarkers, we measured and compared the levels of various ions in whole blood and plasma samples from healthy control (HC), pulmonary TB patients (TB), cured pulmonary TB patients (RxTB), and other non-TB pneumonia patients (PN) by using ultra-high performance liquid chromatography-tandem mass spectrometry. Our study demonstrated that Cu (AUC = 0.670), Pb (AUC = 0.660), and Zn (AUC = 0.701) in whole blood exhibited promising diagnostic performance for TB. Then we used a neural network (NNET) for TB prediction, the AUC values used to differentiate definite TB from HC or PN in plasma were 0.867 and 0.864, respectively. The AUC values used to differentiate definite TB from HC or PN in whole blood were 0.818 and 0.660, respectively. Our correlation analysis showed that Zn (r= 0.356, p=0.001) and Cu (r= 0.361, p=0.0004) in plasma are most closely related to disease severity. Additionally, six ions (Cu, Sb, V, Mn, Fe, Sr) in plasma and whole blood were altered following anti-TB therapy. These results showed that ions could be diagnostic biomarkers for TB. Furthermore, the level of particular ions can forecast the degree of lung damage and the success of the TB treatment. In conclusion, this study highlights the possibility of using ions from blood samples to enable rapid tuberculosis diagnosis.

Mitigating nitrogen losses with almost no crop yield penalty during extremely wet years.

Climate change-induced precipitation anomalies during extremely wet years (EWYs) result in substantial nitrogen losses to aquatic ecosystems (Nw). Still, the extent and drivers of these losses, and effective mitigation strategies have remained unclear. By integrating global datasets with well-established crop modeling and machine learning techniques, we reveal notable increases in Nw, ranging from 22 to 56%, during historical EWYs. These pulses are projected to amplify under the SSP126 (SSP370) scenario to 29 to 80% (61 to 120%) due to the projected increases in EWYs and higher nitrogen input. We identify the relative precipitation difference between two consecutive years (diffPr) as the primary driver of extreme Nw. This finding forms the basis of the CLimate Extreme Adaptive Nitrogen Strategy (CLEANS), which scales down nitrogen input adaptively to diffPr, leading to a substantial reduction in extreme Nw with nearly zero yield penalty. Our results have important implications for global environmental sustainability and while safeguarding food security.

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.

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-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.