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Abstract Background Vascular cognitive impairment (VCI) is a significant contributor to dementia, yet the precise mechanisms underlying the cognitive decline associated with chronic cerebral hypoperfusion (CCH) remain unclear. This study investigated the molecular and epigenetic changes in the striatum, a brain region critical for motor function and cognition, following chronic hypoperfusion using a bilateral common carotid artery stenosis (BCAS) model in mice. Methods RNA-seq was utilized to identify differentially expressed genes (DEGs) associated with hypoperfusion. In parallel, ATAC-seq was used to assess changes in chromatin accessibility within the striatum, providing insight into the epigenome and potential regulatory mechanisms. The integration of these datasets allowed us to correlate chromatin accessibility with transcriptional activity and to identify key transcription factors driving the observed gene expression changes. Results Analysis of striatum-specific transcriptome revealed significant upregulation of immune response genes, particularly type II interferon signaling, and downregulation of neural activation pathways. Analysis of striatum-specific epigenome showed increased chromatin accessibility at promoters of immune-related genes. Integrated analysis highlighted PU.1 as a key transcription factor in upregulated pathways, while neural pathways lacked epigenetic regulation, revealing distinct molecular responses in the striatum following chronic hypoperfusion. Conclusions Our findings indicate that upregulated pathways in the striatum following BCAS-induced CCH are driven by epigenetic changes, while downregulated pathways occur independently of these modifications. Additionally, PU.1 plays a critical role in mediating immune responses, offering a potential target for therapeutic intervention.

Abstract Retinoic acid-inducible gene I (RIG-I) is a pattern recognition receptor involved in innate immunity, but its role in adaptive immunity, specifically in the context of CD8+ T-cell antitumour immunity, remains unclear. Here, we demonstrate that RIG-I is upregulated in tumour-infiltrating CD8+ T cells, where it functions as an intracellular checkpoint to negatively regulate CD8+ T-cell function and limit antitumour immunity. Mechanistically, the upregulation of RIG-I in CD8+ T cells is induced by activated T cells, and directly inhibits the AKT/glycolysis signalling pathway. In addition, knocking out RIG-I enhances the efficacy of adoptively transferred T cells against solid tumours, and inhibiting RIG-I enhances the response to PD-1 blockade. Overall, our study identifies RIG-I as an intracellular checkpoint and a potential target for alleviating inhibitory constraints on T cells in cancer immunotherapy, either alone or in combination with an immune checkpoint inhibitor.

Abstract Hepatocellular carcinoma (HCC) is among the most common malignancies worldwide and is characterized by high rates of morbidity and mortality, posing a serious threat to human health. Interventional embolization therapy is the main treatment against middle- and late-stage liver cancer, but its efficacy is limited by the performance of embolism, hence the new embolic materials have provided hope to the inoperable patients. Especially, hydrogel materials with high embolization strength, appropriate viscosity, reliable security and multifunctionality are widely used as embolic materials, and can improve the efficacy of interventional therapy. In this review, we have described the status of research on hydrogels and challenges in the field of HCC therapy. First, various preparation methods of hydrogels through different cross-linking methods are introduced, then the functions of hydrogels related to HCC are summarized, including different HCC therapies, various imaging techniques, in vitro 3D models, and the shortcomings and prospects of the proposed applications are discussed in relation to HCC. We hope that this review is informative for readers interested in multifunctional hydrogels and will help researchers develop more novel embolic materials for interventional therapy of HCC. Graphical Abstract

Viola yedoensis Makino (Vy) is a well-known traditional Chinese medicine widely used to treat inflammatory diseases. However, the regulatory effects of dietary Vy supplementation on lipopolysaccharide (LPS)-induced intestinal damage in broilers and the underlying molecular mechanisms remain unclear. In this study, broilers were intraperitoneally injected with 1 mg/kg LPS on days 17, 19 and 21 to induce intestinal damage. Vy supplementation at 0.5, 1.5 and 4.5 % in the diet was administered separately for 21 days to investigate the potential protective effects of Vy supplementation against LPS-induced intestinal impairment in broilers. Vy supplementation improved intestinal morphology and restored growth performance. Vy supplementation attenuated intestinal inflammation by regulating the nuclear factor kappa B (NF-κB) / NLR family pyrin domain-containing 3 (NLRP3) signaling pathway and inhibited its downstream pro-inflammatory factor levels. In addition, Vy supplementation relieved intestinal oxidative impairment by regulating the nuclear factor erythroid-2 related factor 2 (Nrf2) / mitogen-activated protein kinase (MAPK) signaling pathway and downstream antioxidant enzyme activity. Vy supplementation reduced LPS-induced mitochondrial damage and apoptosis. Furthermore, Vy supplementation alleviated LPS-induced intestinal inflammation and oxidative damage in chickens by increasing the abundance of protective bacteria (Lactobacillus and Romboutsia) and reducing the number of pathogenic bacteria (unclassified_f_Ruminococcaceae, unclassified_f_Oscillospiraceae and norank_f_norank_o_Clostridia_vadinBB60_group). Overall, Vy supplementation effectively ameliorated LPS-induced intestinal damage by regulating the NF-κB-NLRP3/Nrf2-MAPK signaling pathway and maintaining intestinal microbiota balance. Vy supplementation can be used as a dietary supplement to protect broilers against intestinal inflammation and oxidative damage.

Cancer is a leading cause of death worldwide, and the development of new diagnostic and treatment methods is crucial. Manganese-based nanomaterials (MnNMs) have emerged as a focal point in the field of cancer diagnosis and treatment due to their multifunctional properties. These nanomaterials have been extensively explored as contrast agents for various imaging technologies such as magnetic resonance imaging (MRI), photoacoustic imaging (PAI), and near-infrared fluorescence imaging (NIR-FL). The use of these nanomaterials has significantly enhanced the contrast for precise tumor detection and localization. Moreover, MnNMs have shown responsiveness to the tumor microenvironment (TME), enabling innovative approaches to cancer treatment. This review provides an overview of the latest developments of MnNMs and their potential applications in tumor diagnosis and therapy. Finally, potential challenges and prospects of MnNMs in clinical applications are discussed. We believe that this review would serve as a valuable resource for guiding further research on the application of manganese nanomaterials in cancer diagnosis and treatment, addressing the current limitations, and proposing future research directions.

Abstract This study aimed to evaluate the effect of theaflavins [TFs] on the process of dentin erosion and investigation the potential mechanism. For erosion kinetics of the dentin, 7 experimental groups (n = 5) treated with 10% ethanol [EtOH] (negative control) are erosion for 1, 2, 3, 4, 5, 6, and 7 d erosion cycles (4 cycles/d). For the effect of TFs on dentin erosion, 6 experimental groups (n = 5) were treated with 1% epigallocatechin gallate [EGCG], 1% chlorhexidine [CHX], 1%, 2%, 4%, and 8% TFs for the 30 s and then subjected to erosion cycles (4 cycles/d for 7 d). The erosive dentin wear (μm) and surface morphology were evaluated and compared by laser scanning confocal microscope and scanning electron microscopy. The matrix metalloproteinase inhibition effects of TFs were investigated using in situ zymography and molecular docking. TFs-treated collagen was investigated by ultimate microtensile strength, Fourier-transform infrared spectroscopy, and molecular docking. Data were analyzed by ANOVA, Tukey’s test (P

ABSTRACT: Salmonella, as a common foodborne pathogen in dairy products, poses a great threat to human health. We studied a new detection method based on quantum dots (QD). A fluorescent biosensor with multiple fluorescent signal amplification based on a streptavidin (SA) biotin system and the polyamino linear polymer poly-l-lysine (PLL) were established to detect Salmonella in milk. First, Salmonella was captured on a black 96-well plate with paired Salmonella mAb to form a double-antibody sandwich. Second, SA was immobilized on biotin-modified mAb by SA-biotin specific bond. Then, the biotin-modified polylysine (BT-PLL) was bound on SA and specifically bonded again through the SA-biotin system. Finally, water-soluble CdSe/ZnS QD-labeled SA was added to a black 96-well plate for covalent coupling with BT-PLL. The fluorescent signal was amplified in a dendritic manner by the layer-by-layer overlap of SA and biotin and the covalent coupling of biotinylated PLL. Under optimal conditions, the detection limit was 4.9 × 103 cfu/mL in PBS. The detection limit was 10 times better than that of the conventional sandwich ELISA. In addition, the proposed biosensor was well specific and could be used for detecting Salmonella in milk samples.

ABSTRACT: Foods contaminated by foodborne pathogens have always been a great threat to human life. Herein, we constructed an electrochemical immunosensor for Salmonella detection by using a Fe3O4@graphene modified electrode. Because of the excellent electrical conductivity and mechanical stability of graphene and the large specific surface area of Fe3O4, the Fe3O4@graphene nanocomposite exhibits an excellent electrical signal, which greatly increased the sensitivity of the immunosensor. Gold nanoparticles were deposited on Fe3O4@graphene nanocomposite by electrochemical technology for the immobilization of the antibody. Cyclic voltammetry was selected to electrochemically characterize the construction process of immunosensors. The microstructure and morphology of related nanocomposites were analyzed by scanning electron microscopy. Under optimized experimental conditions, a good linear relationship was achieved in the Salmonella concentration range of 2.4 × 102 to 2.4 × 107 cfu/mL, and the limit of detection of the immunosensor was 2.4 × 102 cfu/mL. Additionally, the constructed immunosensor exhibited acceptable selectivity, reproducibility, and stability and provides a new reference for detecting pathogenic bacteria in milk.

In order to solve the problem that it is difficult for a single sensor to accurately characterize the running state of rotating bearings under complex working conditions, this paper proposes a data-level fusion method based on multi-source isomorphic sensors to monitor spindle bearings. First, new vibration signals in the X,Y,Z direction were obtained through the process of decomposing, de-noise, and reconstructing. Second, the PCA algorithm was used to select the time-domain and frequency-domain features of the vibration signals, construct the feature matrix, and perform dimensionality reduction in the feature matrix. Finally, the entropy weight method was introduced to obtain the initial weights of the three directions as the inputs of the adaptive function. The chaotic particle swarm optimization algorithm proposed in this paper helps particles jump out of the local optimum. Chaotic mapping is used to initialize the velocity and position of the particles, which calculates globally optimal weights in three directions. In order to extract bearing signal features more accurately and efficiently, a DenseNet and Transformer (DAT) feature extraction model is proposed to deal with the complex changes and noise interference of bearing signals. Through the open data set of Jiangnan University and the data collected by our own experimental platform, the maximum accuracy of the DAT model was verified to be 100%.

The artificial ground freezing method has been widely used in shield tunneling breakthrough working shafts. The freezing effect was mainly considered in the previous research, and the heat generation of the shield machine was not considered, which has great influence in actual engineering. In this paper, a coupling calculation model, considering phase change latent heat, is establishes that by containing the freezing process and heat generation of the shield machine, the model is verified. A numerical simulation is carried out for several working conditions that may occur in actual projects, and the following conclusions are obtained. Although the heat dissipated by the normal tunneling of the shield machine will melt the frozen soil curtain that originally meets the design requirements, the thickness of the frozen soil curtain after melting cannot reach the initial design, though it is still within the safe range. In the process of a continuous rotation working condition, the bottom and sides of a cup-shaped frozen soil curtain are partially melted in the early 6 day stay of the shield machine, and the thickness is reduced to a relatively stable value of 0.8 m. In a temporary shutdown working condition, when the contact surface temperature between the shield machine shell and the frozen soil drops to −12 °C after almost 4 days of shutdown, the shield machine may not keep tunneling forward due to the freezing effect. The research results will benefit the freezing design and management of the shield tunneling breakthrough working shaft under extreme conditions.

Nothodoritis zhejiangensis (Orchidaceae) is a rare orchid unique to China of great horticultural value. The complete chloroplast (cp) genome of this species is 143,522 bp in length and the total GC content is 36.8%. It includes a large single copy (LSC) region of 83,830 bp in length, a small single copy (SSC) region of 10,764 bp, and a pair of inverted repeat regions (IRs) with 24,464 bp. The cp genome contains 120 functional genes, including 74 protein-coding genes, 38 tRNA genes, and eight rRNA genes. The phylogenetic tree constructed by the maximum-likelihood method showed that the taxonomic status of N. zhejiangensis was clustered with the species in Phalaenopsis.

Paphiopedilum parishii (Rchb. f.) Stein is an endangered and rare species with highly ornamental value. In this study, we report the complete chloroplast genome of P. parishii using the Illumina sequencing data. The total genome of P. parishii is 154,689 bp in length and the GC content is 35.9%, with a pair of inverted repeats (IRs) regions of 32,690 bp each, a large single-copy region (LSC) of 86,863 bp and a small single-copy region (SSC) of 2,446 bp. The chloroplast genome encoded 127 genes, including 82 protein-coding genes (CDS), 8 rRNA genes and 37 tRNA genes. The phylogenetic tree showed that P. parishii was clustered with other species in Paphiopedilum with strong support based on the complete chloroplast genome.

In the study, an equiatomic CoCrNiCuZn high-entropy alloy (HEA) was prepared by mechanical alloying (MA) and the phases, microstructures, and thermal properties of the alloy powder were explored. The results suggest that a solid solution with body-centered cubic (BCC) phase and a crystalline size of 10 nm formed after 60 h of milling. Subsequently, the alloy powder was consolidated by spark plasma sintering (SPS) at different temperatures (600 °C, 700 °C, 800 °C, and 900 °C). Two kinds of face-centered cubic (FCC) phases co-existed in the as-sintered samples. Besides, Vickers hardness and compressive strength of the consolidated alloy sintered at 900 °C were respectively 615 HV and 2121 MPa, indicating excellent mechanical properties.

The differences in the cross-sectional positions of cells in the detection area have a severe negative impact on achieving accurate characterization of the impedance spectra of cells. Herein, we proposed a threedimensional (3D) inertial focusing based impedance cytometer integrating sheath fluid compression and inertial focusing for the high-accuracy electrical characterization and identification of tumor cells. First, we studied the effects of the particle initial position and the sheath fluid compression on particle focusing. Then, the relationship of the particle height and the signal-to-noise ratio (SNR) of the impedance signal was explored. The results showed that efficient single-line focusing of 7–20 μm particles close to the electrodes was achieved and impedance signals with a high SNR and a low coefficient of variation (CV) were obtained. Finally, the electrical properties of three types of tumor cells (A549, MDA-MB-231, and UMUC-3 cells) were accurately characterized. Machine learning algorithms were implemented to accurately identify tumor cells based on the amplitude and phase opacities at multiple frequencies. Compared with traditional two-dimensional (2D) inertial focusing, the identification accuracy of A549, MDA-MB-231, and UM-UC-3 cells using our 3D inertial focusing increased by 57.5%, 36.4% and 36.6%, respectively. The impedance cytometer enables the detection of cells with a wide size range without causing clogging and obtains high SNR signals, improving applicability to different complex biological samples and cell identification accuracy. [ABSTRACT FROM AUTHOR]