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Background Liver cancer stem cells (LCSCs) significantly impact chemo-resistance and recurrence in liver cancer. Dopamine receptor D4 (DRD4) is known to enhance the cancer stem cell (CSC) phenotype in glioblastoma and correlates with poor prognosis in some non-central nervous system tumors; however, its influence on LCSCs remains uncertain. Methods To investigate the gene and protein expression profiles of DRD4 in LCSCs and non-LCSCs, we utilized transcriptome sequencing and Western blotting analysis. Bioinformatics analysis and immunohistochemistry were employed to assess the correlation between DRD4 expression levels and the pathological characteristics of liver cancer patients. The impact of DRD4 on LCSC phenotypes and signaling pathways were explored using pharmacological or gene-editing techniques. Additionally, the effect of DRD4 on the protein expression and intracellular localization of β-catenin were examined using Western blotting and immunofluorescence. Results DRD4 expression is significantly elevated in LCSCs and correlates with short survival in liver cancer. The expression and activity of DRD4 are positive to resistance, self renewal and tumorigenicity in HCC. Mechanistically, DRD4 stabilizes β-catenin and promotes its entry into the nucleus via activating the PI3K/Akt/GSK-3β pathway, thereby enhancing LCSC phenotypes. Conclusions Inhibiting DRD4 expression and activation offers a promising targeted therapy for eradicating LCSCs and relieve chemo-resistance.

Network intrusion detection plays a crucial role in ensuring network security by distinguishing malicious attacks from normal network traffic. However, imbalanced data affects the performance of intrusion detection system. This paper utilizes few-shot learning to solve the data imbalance problem caused by insufficient samples in network intrusion detection, and proposes a few-shot intrusion detection method based on prototypical capsule network with the attention mechanism. Our method is mainly divided into two parts, a temporal-spatial feature fusion method using capsules for feature extraction and a prototypical network classification method with attention and vote mechanisms. The experimental results demonstrate that our proposed model outperforms state-of-the-art methods on imbalanced datasets.

Social stress in adolescents precipitates stress-related emotional disorders. In this study we aimed to investigate oligodendrogenesis in three stress-associated brain regions, medial prefrontal cortex (mPFC), habenula, and amygdala in adolescent mice exposed to social defeat stress. Four-week-old adolescent mice were subjected to social defeat for 10 days, followed by behavioral tests and evaluations of oligodendroglial proliferation and differentiation. Stressed mice showed reduced social interaction, more stretched approach posture, lower sucrose preference, but no changes in the forced swimming test. EdU labeled proliferative cells, newly formed NG2 EdU + oligodendrocyte precursor cells (OPCs), and Olig2 EdU oligodendrocyte lineage cells (OLLs) were significantly decreased in the mPFC and the lateral habenula, but not in the amygdala and the medial habenula in socially defeated mice. APC Edu newly-generated mature oligodendrocytes (OLs) were decreased in the mPFC in stressed mice. However, the total number of NG2 OPCs, APC mature OLs, and Olig2 OLLs were comparable in all the brain regions examined between stressed and control mice except for a decrease of APC mature OLs in the prelimbic cortex of stressed mice. Our findings indicate that adolescent social stress causes emotion-related behavioral changes and region-specific impairment of oligodendrogenesis.

In comparison to conventional rTMS, theta burst stimulation is stronger and more effective as a brain stimulation approach within short periods of time. Although this deep rTMS technique is being applied in treating neuropsychiatric disorders, few animal studies have attempted to clarify the neurobiological mechanisms underlying its beneficial effects. This animal study examined effects of deep rTMS on the cuprizone-induced neuropathologic and behavioral anomalies and explored the underlying mechanism. Adolescent male C57BL/6 mice were fed a rodent chow without or with cuprizone (CPZ; 0.2% w/w) for 5 weeks. Another two groups of mice were subjected to deep rTMS or sham rTMS once a day during weeks 2-5 of the CPZ-feeding period. The behaviors of all mice were assessed after withdrawal of CPZ prior to neuropathological and immunological analyses. Compared to CNT group, mice in CPZ and CPZ+Sham groups showed deficits in social recognition and spatial working memory as well as anxiety-like behavior, in addition to myelin breakdown and OL loss in corpus callosum, caudate putamen, cerebral cortex, and hippocampus of the brain. Deep rTMS effectively reduced behavioral anomalies and blocked myelin breakdown and OL loss in CPZ-fed mice. In addition, it also dampened microglia activation at lesion sites and rectified cytokines levels (IL-1β, IL-6, and IL-10) in CPZ-affected regions. The most significant effect was seen in cerebral cortex where alleviated neuropathology co-existed with less microglia activation and higher IL-10 level. These data provided experimental evidence for the beneficial effects of deep rTMS in CPZ-fed mice and revealed a neurobiological mechanism of the modality.

Over the past few decades, the number of patients with neurological diseases has increased significantly, posing huge challenges and opportunities for the development of brain imaging technology. As a hybrid imaging method combining optical excitation and acoustic detection techniques, photoacoustic tomography (PAT), has experienced rapid development, due to high optical contrast and spatial resolution at depth inside tissues. With the development of lasers, ultrasonic detectors, and data computations, PAT has been widely applied for the diagnosis of oncology, dermatosis, etc. However, the energy of light and ultrasound would be greatly attenuated while penetrating the skull, due to the reflection, absorption, and scattering effects, resulting in limited application of PAT in brain imaging. In this review, we summarized the achievements of PAT and its application in the detection of brain diseases including glioma, stroke, traumatic brain injury, Alzheimer's disease, epilepsy, and Parkinson's disease. Moreover, various PAT systems and multi‐modality photoacoustic imaging are introduced for potential clinical applications. Finally, the challenges and current limitations of PAT for further brain imaging are also discussed. As a hybrid imaging method combining optical excitation and acoustic detection techniques, photoacoustic tomography (PAT), has experienced a rapid development, due to high optical contrast and spatial resolution at depth inside tissues. This review has summarized the current progress of PAT and its application in the detection of brain diseases such as glioma, stroke, traumatic brain injury, Alzheimer's disease, epilepsy and Parkinson's disease.

Acute respiratory distress syndrome (ARDS) is a common cause of death in ICU patients and its underlying mechanism remains unclear, which leads to its high mortality rate. This study aimed to identify candidate genes potentially implicating in the pathogenesis of ARDS and provide novel therapeutic targets. Using bioinformatics tools, we searched for differentially expressed genes (DEGs) in an ARDS microarray dataset downloaded from the Gene Expression Omnibus (GEO) database. Afterwards, functional enrichment analysis of GO, KEGG, GSEA and WGCNA were carried out to investigate the potential involvement of these DEGs. Moreover, the Protein-protein interaction (PPI) network was constructed and molecular complexes and hub genes were identified, followed by prognosis analysis of the hub genes. Further, we performed qRT-PCR, Western Blot and flow cytometry analysis to detect candidate genes of CCR2 and FPR3 in macrophage model of LPS-induced ARDS and primary alveolar macrophages(AMs). Macrophage chemotaxis was evaluated using Transwell assay. DEGs mainly involved in myeloid leukocyte activation, cell chemotaxis, adenylate cyclase-modulating G protein-coupled receptor signaling pathway and cytokine-cytokine receptor interaction. Basing on the constructed PPI network, we identified five molecular complexes and 10 hub genes potentially participating in the pathogenesis of ARDS. It was observed that candidate genes of CCR2 and FPR3 were significantly over-expressed in primary alveolar macrophages from ARDS patients and macrophgae model of LPS-induced ARDS. Moreover, transwell assay demonstrated that CCR2 and FPR3 down-regulation, respectively, inhibited LPS-triggered macrophage chemotaxis toward CCL2. Finally, a positive correlation between FPR3 and CCR2 expression was confirmed using pearson correlation analysis and Western Blot assay. Our study identified CCR2 and FPR3 as the candidate genes which can promote macrophage chemotaxis through a possible interaction between FPR3 and CCL2/CCR2 axis and provided novel insights into ARDS pathogenesis.

Piezoelectric materials provide a unique platform for bioelectronic interfaces, enabling dynamic sensing and electroactive therapies through bidirectional transduction between biomechanical and bioelectrical signals. However, the development of bioresorbable piezoelectric materials that combine high functional performance with mechanical compliance remains a critical challenge for seamless integration with soft biological tissues, while eliminating the need for retrieval surgeries and long-term material retention. Here, we report a bioresorbable, flexible piezoelectric composite composed of Rochelle salt (RS) crystals embedded within poly(L-lactic acid) (PLLA) nanofibers. Fabricated via electrospinning and uniaxial compression, centimeter-scale biodegradable nanofiber films are achieved, exhibiting excellent effective piezoelectric coefficient of 43.1 pC N and piezoelectric voltage coefficient of 1909.2 mV m N , surpassing the piezoelectric performance of previously reported biodegradable flexible materials. Ultrasound-driven scaffold devices derived from these bioresorbable piezoelectric materials markedly enhance sciatic nerve regeneration in rodents. Additionally, a biodegradable piezoelectric strain sensor enables wireless, real-time monitoring of intestinal motility, facilitating diagnosis of colonic dysfunction. Together, these findings establish a prominent materials paradigm for biodegradable piezoelectric electronics, offering a versatile platform for bioelectronic applications in regenerative medicine, neuromodulation, and physiological monitoring.

Network intrusion detection plays a crucial role in ensuring network security by distinguishing malicious attacks from normal network traffic. However, imbalanced data affects the performance of intrusion detection system. This paper utilizes few-shot learning to solve the data imbalance problem caused by insufficient samples in network intrusion detection, and proposes a few-shot intrusion detection method based on prototypical capsule network with the attention mechanism. Our method is mainly divided into two parts, a temporal-spatial feature fusion method using capsules for feature extraction and a prototypical network classification method with attention and vote mechanisms. The experimental results demonstrate that our proposed model outperforms state-of-the-art methods on imbalanced datasets.

As a hybrid imaging method combining optical excitation and acoustic detection techniques, photoacoustic tomography (PAT), has experienced a rapid development, due to high optical contrast and spatial resolution at depth inside tissues. This review has summarized the current progress of PAT and its application in the detection of brain diseases such as glioma, stroke, traumatic brain injury, Alzheimer's disease, epilepsy and Parkinson's disease.