Bioscience trends最新文献

Aging constitutes a major risk factor for pan-cancer development, with epidemiological studies indicating that 60% of new malignancies occur in adults age 65 and older. This review synthesizes cutting-edge insights from single-cell sequencing databases (e.g., TCGA and GEO) that decipher how aging reprograms the tumor microenvironment (TME) to fuel carcinogenesis. Single-cell RNA sequencing (scRNA-seq) has revealed that senescent cell subpopulations (e.g., CDKN2A⁺/LMNB1^- cells) accumulate in aged tissues at frequencies up to 15%, driving genomic instability and secrete pro-tumorigenic senescence-associated secretory phenotype (SASP) factors (IL-6 and TGF-β). These factors remodel the TME by inducing fibroblast activation and extracellular matrix degradation, accelerating metastasis by 40-70% in murine models. Crucially, immunosenescence diminishes anti-tumor immunity, with scRNA-seq profiling showing 40-60% increases in exhausted PD-1⁺ T cells and immunosuppressive myeloid cells in aged TMEs. Pan-cancer analyses have identified conserved aging gene signatures (e.g., p16INK4a upregulation in 12+ cancer types) that correlate with 30-50% poorer survival. While technical challenges persist - including batch effects in scRNA-seq data and low senescent cell abundance (< 5%) - emerging solutions like deep learning can enhance detection sensitivity. Therapeutically, senolytic strategies deplete senescent cells, improving drug response by 3.5-fold in preclinical trials. Future research must integrate multi-omics and AI to examine aging-related targets, advancing personalized interventions for aging-associated malignancies.

The medical metaverse, with its potential for efficient care delivery, improved patient outcomes, and reduced healthcare costs, is profoundly impacting global healthcare systems. Scholars researching this topic primarily focus on exploring specific scenarios for its use. This article aims to analyze the development trajectory, potential applications, and directions for management optimization within the medical metaverse. Through a case study of China, we review the current status of use of the medical metaverse and systematically examine its future prospects and challenges. We contend that the medical metaverse offers significant value in enabling equitable distribution of healthcare resources, enhancing medical care efficiency, promoting the integration of medical education, research, and clinical practice, and assisting in public health management. To ensure sustainable development, however, the imperative task is to proactively devise technical standards and legal regulatory frameworks and to dynamically monitor the effectiveness of medical metaverse technologies, with the ultimate aim of maximizing the value of the medical metaverse.

Early-stage diagnosis offers the greatest survival advantage in oncology, and yet conventional liquid-biopsy markers - circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) - depend on cell death or mechanical shedding and therefore appear late in disease progression. Exosomes, 40-160 nm lipid-bilayer vesicles secreted by viable cells, emerge earlier, outnumber CTCs by several orders of magnitude, and preserve multi-omic cargo that mirrors intratumor heterogeneity. Rapid advances in enabling technologies are driving continual breakthroughs in exosome-based liquid biopsy, laying a solid foundation for its accelerated translation into clinical practice. Key hurdles remain: standardizing exosome isolation, defining quantitative cut-offs that separate malignant from inflammatory EV surges, and building probabilistic multi-omic models to pinpoint tissue origin. Eliminating these obstacles could advance detection by months and shift care from late salvage to true early interception.

Neurotropin, a non-protein extract widely used for the treatment of neuropathic pain, has recently been reported to protect against ischemic brain injury, enhance remyelination in demyelinating diseases, and ameliorate neuroinflammation and memory deficits. However, its role in microglial polarization and mitochondrial dysfunction in Alzheimer's disease (AD) remains poorly understood. In this study, we investigated the therapeutic potential of Neurotropin in the 5xFAD mouse model of AD. Neurotropin administration alleviated cognitive decline, reduced amyloid-β (Aβ) deposition, suppressed neuroinflammation, and preserved neuronal density. Mechanistically, Neurotropin improved mitochondrial morphology, restored ATP production, increased mitochondrial DNA copy number, and reduced oxidative stress while promoting a shift in microglial polarization from the pro-inflammatory M1 phenotype toward the anti-inflammatory M2 phenotype. Transcriptomic and molecular analyses revealed that calcium homeostasis modulator family member 2 (Calhm2) was markedly upregulated in 5xFAD mice, colocalized with microglia, and transcriptionally regulated by fused in sarcoma (FUS), while Calhm2 interacted with EF-hand domain containing protein D2 (EFhd2). Neurotropin suppressed FUS-mediated Calhm2 transcription and attenuated Calhm2-EFhd2 interaction. Importantly, overexpression of Calhm2 in both microglial cells and 5xFAD mice abolished the beneficial effects of Neurotropin, leading to exacerbated mitochondrial dysfunction, oxidative stress, and inflammatory cytokine release. Together, these findings identify Calhm2 as a critical mediator of Neurotropin's neuroprotective effects and demonstrate that Neurotropin alleviates AD pathology by suppressing FUS-dependent Calhm2 transcription and blocking the Calhm2/EFhd2 interaction. This study provides new insights into the mechanism of Neurotropin action and highlights its therapeutic potential for AD.

The persistent mutation of the novel coronavirus (SARS-CoV-2) not only remains a threat to human health but also continues to challenge existing antiviral therapeutic strategies. In current clinical practice, the resistance of novel coronavirus to antivirals, the rebound of viral load after treatment with drugs such as nirmatrelvir/ritonavir (NTV/r), and the urgent need for rapid clearance of the virus in the management of critically and emergently ill patients suggest that the existing single-drug regimens may have limitations and that the intensity of suppression may be insufficient in some cases. In clinical practice, we have observed that a combination of antivirals with different mechanisms of action can result in better efficacy and not significantly increase adverse drug reactions (ADRs). For some immunosuppressed, post-transplantation, or other special patients in particular, such as those in whom COVID-19 nucleic acids tended not to be negative after conventional treatment, when virus clearance is still the main goal, the combination of small-molecule antivirals can help to clear the virus as early as possible and attempt to improve the success rate of salvage. Based on evidence-based medicine and in light of the current situation of China, we assembled experts from disciplines such as infectious diseases, respiratory medicine, critical care medicine, and clinical pharmacy into a group to carry out a systematic literature search and identify key issues and to put forward relevant recommendations to reach an Expert Consensus on Combined Use of Oral Small-molecule Antivirals to Treat COVID-19, which is intended to serve as a reference for clinical practice.

Faced with the global challenges of population aging and a surge in dementia cases, healthcare models worldwide are undergoing profound transformation. The Netherlands' "dementia villages" concept simulates living environments, with their antipsychotic drug usage rate (11%) being significantly lower than in traditional facilities (52%). Japan has established over 12,000 "small-scale multi-functional" care facilities, striving to achieve "life in the community." Meanwhile, China is promoting community-embedded elderly care models, exemplified by Shanghai's plan to increase the number of daycare centers from 720 in 2019 to 919 by 2024, establishing a "15-minute elderly care circle." This commentary compares the Netherlands, Japan, and China across four dimensions: aging trends, innovative care models, the development of multifunctional healthcare systems, and end-of-life care philosophies. It assesses current policy developments and practical challenges, proposing that future sustainable care systems should integrate healthcare with community resources, institutional frameworks with ethical considerations, technological advancements with humanistic values, and education on death with the preservation of life with dignity.

Aging of the population has become a critical challenge globally. The proportion of individuals age 60 years and older is projected to increase from 12% in 2015 to 22% by 2050, representing more than 2.1 billion older adults globally. This demographic transition is advancing particularly rapidly in Japan, which has become the first nation to become a "super-aged society". Projections indicate that by 2060, the number of older adults living with dementia will reach approximately 6.45 million (more than 17% of the elderly population), making it one of the country's most urgent health and social care challenges. Japan has developed a comprehensive response system that integrates medical, community, and family-based care. Key initiatives include a national dementia strategy, mechanisms for early screening and diagnosis, the establishment of memory clinics, and the implementation of the community-based integrated care system, which emphasizes coordination between healthcare and long-term care services. These measures have alleviated part of the burden on patients and families while enhancing social awareness of dementia and inclusion of those with that condition. Nevertheless, Japan continues to face significant structural challenges, such as severe shortages of healthcare personnel and professional caregivers, increasing fiscal pressure on long-term care financing, insufficient dissemination of innovative therapies and digital diagnostic tools, and disparities in social support between urban and rural areas. Cross-national comparisons indicate that Japan's experience offers valuable lessons for other rapidly aging societies, particularly in policy design, the integration of community-based care, and the promotion of a dementia-inclusive society. Summarizing and adapting Japan's approaches may therefore provide globally applicable strategies to build sustainable and equitable systems for dementia prevention, management, and care.

Colorectal liver metastasis (CRLM) remains lethal, and the convergence of cellular senescence with metabolic reprogramming via epigenomic rewiring is poorly understood. We integrated genome-wide DNA methylation and RNA-seq data from 10 paired primary tumors and liver metastases (GSE213402). After calling differentially methylated genes (3,399 hyper- and 9,519 hypomethylated) and differentially expressed genes (406 DEGs), we intersected them with curated senescence (n = 866) and metabolic reprogramming (n = 948) gene sets, yielding 28 differentially expressed cellular-senescence-related genes (DE-CSRGs) and 24 metabolic-reprogramming-related genes (DE-MRRGs). Machine-learning pipelines (LASSO + SVM-RFE) converged on a five-gene signature: CXCL1, SERPINE1, NDRG1, SRM and GATM, most of which are hypomethylated and over-expressed in metastases. Gene-set enrichment analysis revealed that these genes are involved in pathways such as oxidative phosphorylation, focal adhesion, complement-coagulation cascades, and PPAR signaling. Immune de-convolution revealed strong positive correlations between signature genes and immunosuppressive subsets (MDSCs, Tregs, type-1 T-helper cells; p < 0.05). Elevated IC₅₀ values for oxaliplatin and 5-fluorouracil in metastatic samples were positively associated with NDRG1 and negatively with SRM, indicating chemo-resistance modulation. This five-gene epigenetic-transcriptomic hub identifies a molecular signature that warrants prospective validation as a potential biomarker for patient stratification and combination therapy in CRLM.

The high performance of core members of social organizations (SOs) caring for the elderly can enhance the quality of management and services, thereby improving the life satisfaction of older adults residing there. However, the factors influencing the performance of core members and their pathways remain unclear. This research seeks to uncover how social support mediates and self-efficacy moderates the association between a social network and individual performance of core members of SOs caring for the elderly. A cross-sectional survey was conducted from June to August 2023 in Shanghai, China, and data on participants' demographics, social network, social support, individual performance, and self-efficacy were collected. Hierarchical stepwise regression, bootstrap analysis, and simple slope method analysis were used to test potential mediating and moderating effects. After adjusting for confounders, the total effect of a social network on core members' individual performance (β = 0.078, 95% CI: 0.052-0.103) consisted of a direct effect (β = 0.059, 95% CI: 0.030-0.087) as well as an indirect effect mediated through social support (β = 0.019, 95% CI: 0.006-0.033). In addition, self-efficacy was identified as a moderating factor in the relationship between a social network and individual performance, with higher levels of self-efficacy diminishing the influence of a social network on performance outcomes. An extensive social network can enhance social support for core members of SOs caring for the elderly, thereby improving individual performance. Concurrently, targeted interventions should be developed to draw on self-efficacy to activate social network resources and to have a synergistic effect on individual performance.

Surgical resection of the caudate lobe of the liver remains the final hurdle for liver surgeons, not only in open hepatectomy but also in recent minimally invasive hepatectomy. In the dawn of liver surgery, Prof. Kumon made hepatic casts and showed the anatomy of the caudate lobe of the liver based on the portal segmentation in the National Cancer Center Hospital, Tokyo. Meanwhile, liver surgeons in the center successfully performed isolated caudate lobectomy of the liver for liver cancers one after another. Prof. Kumon is still dissecting hepatic casts to demonstrate the right border of the paracaval portion of the caudate lobe against segment VIII of the liver. An approach to right hemihepatectomy preserving the paracaval portion of the caudate lobe was developed thanks to the detailed anatomical knowledge of the liver based on hepatic casts.