Bioscience trends最新文献

The apolipoprotein E ε4 (APOE ε4) allele, the strongest genetic risk factor for late-onset Alzheimer's disease (AD), induces cell-type-specific disturbances in brain lipid metabolism. Although impacting astrocytes and neurons, its most pronounced effects occur in microglia, where it causes energy metabolism deficits and promotes the formation of lipid droplet-accumulating microglia, triggering a cascade of neurodegenerative responses. This review comprehensively examines how microglial APOE4-driven lipid metabolic dysregulation exacerbates neuroinflammation and compromises phagocytic capacity, particularly in the clearance of amyloid-β, phosphorylated-tau, and pathological synapses. Mechanistically, microglial APOE4 activates neuroinflammation via LilrB3-mediated type I interferon signaling and induces lipid metabolic imbalance through PU.1/NF-κB-driven transcriptional reprogramming and ER stress-SREBP2 activation. These disturbances exacerbate neuroinflammation, promote lipid droplet accumulation and cholesterol overload, impair lysosomal function, and ultimately compromise microglial phagocytosis. The resulting disruption of neuron-microglia interactions further amplifies neurotoxicity in AD. Furthermore, this review summarizes emerging therapeutic strategies targeting APOE4-related pathway in microglia. By synthesizing these insights, this review highlights the multifaceted role of microglial APOE4 in AD pathology, with particular emphasis on the central role of lipid metabolism dysregulation, and provides new intervention ideas for reducing its damage to brain function.

With the accelerating trend of population aging, Japan has become the first country to enter a "super-aged society", where the proportion of people age 65 and over exceeds 21%, making it a global model in addressing aging-related challenges. In response to the various social and healthcare issues arising from this demographic shift, the Japanese Government has implemented a series of policy measures. Among them, "Small-scale Multifunctional In-home Care (Shotaki)" and "Nursing Small-scale Multifunctional In-home Care (Kantaki)" have emerged as key components of the community-based care system. This paper explores the common challenges faced in super-aged populations and provides a comparative analysis of the functions, current status, existing issues, and future prospects of "Shotaki" and "Kantaki". By examining these two service models, the study aims to offer policy recommendations and practical insights to build a sustainable elderly care system.

Despite the continued high prevalence of colorectal cancer in the Western world, recent years have witnessed a decline in its mortality rate, largely attributable to the sustained advancement of multimodal treatment modalities for metastatic patients. One persisting issue is lack of consensus between different centres and multidisciplinary teams regarding definition of resectability, the duration of chemotherapy treatment, and surgical strategy. This narrative review outlines current multimodal treatment of patients with colon cancer metastatic to the liver and/or lung in different clinical scenarios. Currently, there are multiple multimodal strategies that can be employed to enhance resectability in these patients. These include novel and sophisticated target therapies (such as novel immunotherapeutic modalities and micro RNAs), complex resections utilising parenchyma-sparing techniques, liver transplantation, and cytoreductive strategies in patients for whom a curative option is not feasible. It is the responsibility of the scientific community to establish standardised protocols across different centres, based on the most recent evidence, while maintaining a high degree of personalisation of treatment for each individual patient. It seems likely that artificial intelligence (AI) will play a significant role in achieving this goal.

The pre-mRNAs splicing is important mechanisms of hepatocellular carcinoma (HCC) progression. Hence, this study aimed to explore the function and corresponding mechanisms of small nuclear ribonucleoprotein polypeptide A (SNRPA), a vital RNAs splicing molecule, in HCC. Here, the University of Alabama at Birmingham CANcer data analysis portal (UALCAN), western blotting, and immunohistochemistry indicated that SNRPA levels were elevated in HCC tissues. Moreover, high expression of SNRPA was correlated with unfavorable clinicopathologic features and poor survival in HCC patients. A series of in vitro and in vivo gain/loss-of-function experiments reported that SNRPA promoted the proliferation of HCC cells. Integrated nanopore full-length cDNA sequencing and RNA-binding protein immunoprecipitation sequencing revealed that B7 homologue 6 (B7-H6) was a potential target of SNRPA. Subsequently, western blotting and flow cytometry showed that SNRPA activated B7-H6-STAT3/AKT signaling axis in HCC cells with promotion of G1-S transition in the cell cycle and inhibition of cell apoptosis. Mechanistically, RNA-binding protein immunoprecipitation and polymerase chain reaction with using exon-exon and exon-intron junction primers revealed that SNRPA facilitated B7-H6 pre-mRNA maturation by binding to it directly and contributing to its intron 2 splicing. Moreover, drug sensitivity test found that SNRPA induced HCC cell resistance to lenvatinib. Finally, restoration experiments demonstrated that the effects of SNRPA on HCC cells relied on B7- H6 expression. Taken together, SNRPA promotes HCC growth and lenvatinib resistance via B7-H6-STAT3/AKT axis through facilitating B7-H6 pre-mRNA maturation by maintaining its intron 2 splicing. Thus, SNRPA may be a promising target for HCC therapy and lenvatinib resistance reversion.

Stroke remains a leading cause of mortality and long-term disability worldwide, frequently resulting in impairments in motor control, cognition, and emotional regulation. Conventional rehabilitation approaches, while partially effective, often lack individualization and yield suboptimal outcomes. In recent years, brain-computer interface (BCI) technology has emerged as a promising neurorehabilitation tool by decoding neural signals and providing real-time feedback to enhance neuroplasticity. This review systematically explores the use of BCI systems in post-stroke rehabilitation, focusing on three core domains: motor function, cognitive capacity, and emotional regulation. This review outlines the neurophysiological principles underpinning BCI-based motor rehabilitation, including neurofeedback training, Hebbian plasticity, and multimodal feedback strategies. It then examines recent advances in upper limb and gait recovery using BCI integrated with functional electrical stimulation (FES), robotics, and virtual reality (VR). Moreover, it highlights BCI's potential in cognitive and language rehabilitation through EEG-based neurofeedback and the integration of artificial intelligence (AI) and immersive VR environments. In addition, it discusses the role of BCI in monitoring and regulating post-stroke emotional disorders via closed-loop systems. While promising, BCI technologies face challenges related to signal accuracy, device portability, and clinical validation. Future research should prioritize multimodal integration, AI-driven personalization, and large-scale randomized trials to establish long-term efficacy. This review underscores BCI's transformative potential in delivering intelligent, personalized, and cross-domain rehabilitation solutions for stroke survivors.

One of the challenges of laparoscopic liver resection (LLR) is the exposure of the surgical field. We propose a new surgical approach to better expose the right liver, stretching of the ligamentum teres hepatis (SLTH), and we evaluated its clinical feasibility and limitations through a study analyzing relevant cases. Clinicopathologic data on patients who underwent laparoscopic right partial hepatectomy (LRPH) at our center were retrospectively collected, and subjects were 276 patients with liver space-occupying lesions who met the selection criteria and who underwent the new surgical approach (SLTH) or the conventional surgical approach (no stretching of the ligamentum teres hepatis, or NSLTH). After 1:1 propensity score matching (PSM), 102 patients in each cohort were selected for further analysis. There were no significant differences in the operating time or the duration of postoperative hospitalization between the SLTH cohort and the NSLTH cohort. The duration of detachment of the hepatic parenchyma and the duration of hepatic portal occlusion were significantly shorter in the SLTH cohort than in the NSLTH cohort. The intraoperative blood loss in the SLTH cohort was significantly less than that in the NSLTH cohort. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were significantly lower in the SLTH cohort than in the NSLTH cohort on day 5 postoperatively. Results confirmed that SLTH is a simple, safe, effective, and highly reproducible technique for the treatment of LRPH. SLTH may help to perform LRPH by increasing the level of laparoscopic exposure of the right liver and reducing bleeding and operating time.

The prognostic significance of preoperative platelet counts among patients with hepatocellular carcinoma (HCC) undergoing curative resection remains controversial. The objective of the current study was to investigate the impact of preoperative platelet count on long-term outcomes after HCC resection. Patients who underwent curative-intent resection for HCC between 2000 and 2021 at 10 hepatobiliary centers in China were retrospectively analyzed. Patients were categorized based on platelet count within 2 weeks before surgery: thrombocytopenia (< 100 × 10⁹/L), normal platelet count (100-299 × 10⁹/L), and thrombocytosis (≥ 300 × 10⁹/L). The primary outcomes were overall survival (OS) and recurrence-free survival (RFS). Among 3,116 patients, 655 (21.0%) had thrombocytopenia, 2,374 (76.2%) had normal platelet counts, and 87 (2.8%) had thrombocytosis. The 5-year OS was 52.7%, 56.0%, and 40.2% for thrombocytopenia, normal platelet count, and thrombocytosis groups, respectively (p < 0.001 among the three groups); the corresponding 5-year RFS was 39.3%, 39.3%, and 26.9%, respectively (p = 0.001 among the three groups). Multivariable analysis identified both thrombocytopenia (HR 1.215, 95% CI 1.045-1.413, p = 0.011) and thrombocytosis (HR 1.307, 95% CI 1.130-1.511, p < 0.001) as independent risk factors for worse OS, and thrombocytosis was independently associated with worse RFS (HR 1.523, 95% CI 1.196-1.939, p = 0.001). Both thrombocytopenia and thrombocytosis were associated with worse survival after HCC resection, with thrombocytosis also predicting higher risk of recurrence. Routine preoperative platelet count may serve as a valuable and practical prognostic marker for risk stratification among patients with HCC undergoing resection.

Acquired immunodeficiency syndrome (AIDS)/human immunodeficiency virus (HIV) patients experience significant increase in their survival and decline in the mortality with the advent of antiretroviral therapy (ART). Nonetheless, ART alone still cannot completely cure AIDS/HIV patients. Furthermore, the virus remains latent in resting CD4+T cells for extended periods, posing a continuous threat to AIDS/HIV patients. Immune checkpoint blockades (ICBs), as a promising immunotherapy, inaugurate new pathways for AIDS/HIV cure or remission given their capability to break down the latency limit of HIV, and promote the regeneration and activation of HIV-specific T cells. However, not all AIDS/HIV patients respond to immune checkpoint inhibitors (ICIs), similar to that encountered in cancer patients, accompanied by the risk of severe immune-related adverse events (irAEs) in some cases. Accordingly, the present study was conducted to explore the possibility of personalized medicine tailored to the host discrepancy, with purposes of achieving better treatment outcomes, higher objective response rates, and fewer irAEs. Strategies for ICIs based on individual differences are documented to be conducive to improving therapeutic outcomes for patients. Therefore, this study intended to improving the therapeutic efficacy of ICIs in AIDS/HIV patients within the context of precision immunotherapy, including monotherapy and combination strategies, as well as the application of predictive biomarkers.

Indocyanine green (ICG)-C9, a novel cyanine dye developed by the Center for Biosystems Dynamics Research at RIKEN, provides significant advantages over conventional ICG due to its detectability via shortwave-infrared (SWIR) fluorescence imaging. Unlike standard ICG, ICG-C9 facilitates SWIR imaging and displays therapeutic potential when conjugated with antibodies in vivo, suggesting broader applicability across various cancer types. This study evaluated the efficacy of SWIR fluorescence imaging with ICG-C9 in comparison with existing near-infrared (NIR) imaging techniques. We assessed excretion kinetics and the relationship between excitation and fluorescence wavelengths for ICG-C9 and ICG following intravenous administration in BALB/c-nu mice. Tumor uptake was evaluated using a cell-line-derived subcutaneous tumor model from HuH-7 cells, representing hepatocellular carcinoma. Variables including dose, administration route, and exposure time were optimized for comparison. Maximum fluorescence intensity for ICG-C9 was observed with an excitation wavelength of 915 nm and fluorescence emission wavelengths >950 nm within the SWIR spectrum. Both ICG-C9 and ICG followed similar excretion pathways, involving hepatic uptake and biliary excretion. Tumor uptake of ICG-C9 was confirmed under similar conditions to ICG. ICG-C9 demonstrates promising potential as an alternative to NIR fluorescence imaging with ICG, offering unique properties that may enhance imaging capabilities. However, further research is required to establish its clinical applicability and broader therapeutic utility.

Hepatocellular carcinoma (HCC) risk factors and incidence vary globally, but men generally have higher incidence than women. Men also tend to have a worse prognosis in terms of survival period and pathological characteristics. Furthermore, there are notable gender differences in treatment strategies and drug responses. While traditional risk factors such as hepatitis B virus, hepatitis C virus, alcohol consumption, and metabolic syndrome contribute to these differences, the underlying molecular mechanisms remain partly understood. Recent research has focused on elucidating the roles of sex hormones, DNA damage and repair pathways, immune microenvironments, and genetic/epigenetic factors in driving gender-specific disparities. For instance, estrogen receptor signaling has been shown to suppress HCC progression, whereas androgen receptor signaling promotes tumor development. Additionally, immune cells such as tumor-associated macrophages and regulatory T cells exhibit gender-specific patterns, with males typically showing higher levels of immunosuppressive cells. Omics analyses, including genomics, transcriptomics, and proteomics, have further revealed sex-specific differences in gene expression, protein interactions, and metabolic pathways. Despite these advances, significant gaps remain in understanding the interplay between environmental, hormonal, and genetic factors in shaping gender disparities in HCC. Future research should prioritize the identification of novel molecular targets, the development of gender-specific therapeutic strategies, and the integration of multi-omics data to address these disparities. Addressing these challenges will be critical for improving diagnostic, prognostic, and therapeutic outcomes in HCC patients of both sexes.