Core Insights - The article discusses a significant breakthrough in anti-aging research, demonstrating that Therapeutic Plasma Exchange (TPE) can effectively reverse biological age in healthy adults by an average of 2.61 years after three months of treatment [2][10]. Study Overview - The study, led by scientists from the Buck Institute for Research on Aging and Global Apheresis, involved 44 healthy volunteers aged 50 and above, assessing the safety and impact of TPE on biological age [5]. - Participants were divided into four groups with varying treatment frequencies and a placebo control group [5]. Methodology - TPE is designed to replace harmful aging-related molecules in the blood, such as inflammatory factors and senescent cell secretions [6]. - The process includes blood collection, plasma separation, plasma replacement with sterile fluids, and reinfusion of the treated blood [11]. Results - The study found that TPE is safe, with only two participants experiencing adverse events leading to treatment interruption [10]. - The most effective treatment was TPE combined with intravenous immunoglobulin (IVIG), which improved immune function and reduced chronic inflammation [10][14]. - Participants receiving TPE every two weeks showed the most significant biological age reduction, while those treated monthly also experienced benefits, albeit to a lesser extent [13]. Mechanisms of Action - TPE significantly improved age-related immune system decline and regulated immune cell composition towards a younger state [14]. - The therapy also reduced aging-promoting proteins and "rebooted" aging signal networks, affecting multiple aging-related signaling pathways [18]. Implications - This research marks a major advancement in aging studies, providing scientific evidence that biological aging can be measured, intervened, and potentially reversed [17]. - The findings suggest the potential for TPE to be used not only for disease treatment but also for health aging and preventive interventions [19]. - The study lays the groundwork for personalized anti-aging strategies based on individual biological markers [19].

Core Viewpoint - The study highlights the role of gut microbiota, specifically the metabolite urocanic acid (UCA), in enhancing the efficacy of cancer immunotherapy when combined with tyrosine kinase inhibitors (TKIs) [3][8][11]. Group 1: Research Findings - The research demonstrates that TKIs increase the abundance of the gut bacterium Muribaculum gordoncarteri and its metabolite UCA, which enhances the response to immune checkpoint blockade (ICB) therapy [8][9]. - UCA interacts with IκBα to inhibit NF-κB activation in endothelial cells, thereby reducing the recruitment of myeloid-derived suppressor cells (MDSCs) mediated by CXCL1 [9][11]. - Higher levels of UCA and Muribaculum gordoncarteri are found in the feces of patients who respond to ICB therapy compared to non-responders, suggesting their potential as predictive biomarkers for treatment response [8][9][11]. Group 2: Implications for Cancer Treatment - The findings indicate that the interaction between TKIs and gut microbiota could be a crucial factor in improving cancer treatment outcomes, particularly for patients who currently do not respond well to existing therapies [7][9]. - Understanding the mechanisms by which UCA enhances ICB therapy could lead to new strategies for increasing the effectiveness of cancer immunotherapy [3][11].

Core Viewpoint - The study reveals that radiotherapy induces the secretion of spermidine synthase from tumor cells, leading to skeletal muscle weakness due to changes in polyamine metabolism and collagen accumulation in muscle tissue [2][4][6]. Group 1: Mechanism of Action - Radiotherapy stress activates the metabolism of phospholipids in tumor cell membranes, resulting in increased levels of free arachidonic acid (ArA), which enhances the ISGylation of spermidine synthase (SRM) [4][5]. - The accumulation of ArA promotes the packaging of SRM into small extracellular vesicles (sEV), which are then absorbed by skeletal muscle, leading to muscle weakness [4][6]. Group 2: Clinical Implications - The study suggests that the antihypertensive drug Losartan can effectively inhibit the ISGylation of SRM, blocking its secretion and significantly improving pathological changes in skeletal muscle post-radiotherapy [5][7]. - This provides a theoretical basis and potential intervention target for developing new radioprotective agents to alleviate the side effects of radiotherapy [5][7].

Core Viewpoint - The research identifies a unique subset of liver portal macrophages (LPAM) that play a crucial role in maintaining liver immune homeostasis and have neuroprotective functions [3][6]. Group 1: Research Findings - The study published in Nature Immunology reveals the existence of a distinct LPAM network characterized by CX3CR1+ CD63+ cells, which differ significantly in transcription and spatial distribution from CX3CR1+ CD207+ liver capsule macrophages [5]. - LPAM survival is dependent on the colony-stimulating factor-1 receptor (CSF1R), and these cells are established in the liver portal area post-birth, supplemented by bone marrow-derived cells during liver homeostasis [5]. - During non-alcoholic steatohepatitis (NASH), the absence of LPAM leads to increased neutrophil infiltration and exacerbates sympathetic nerve degeneration [5]. Group 2: Implications for Liver Health - The findings suggest that the liver portal area is a critical region for regulating liver homeostasis and disease, with tissue macrophages capturing antigens, protecting sympathetic nerves, and limiting neutrophil recruitment during inflammation [7].

Core Viewpoint - The research highlights the role of religious temples in China as long-term refuges for ancient trees in human-dominated landscapes, emphasizing their importance in biodiversity conservation and cultural heritage [4][11][15]. Group 1: Research Background - The study was conducted by researchers from Yunnan University, Peking University, Chongqing University, and the Australian National University, focusing on the relationship between ancient trees and human cultural practices [5][9]. - The research was published in the journal Current Biology, indicating its significance in the field of ecology and conservation [4]. Group 2: Findings on Ancient Trees - A database was created encompassing 51,25 Buddhist temples and 1,420 Taoist temples, documenting 46,966 ancient trees [10]. - The study found that ancient trees within temples in eastern China have a significantly higher density compared to those outside, with some trees being thousands of times more abundant [11]. - Temples serve as crucial refuges for 61 endangered tree species, with 8 species found exclusively within temple grounds, highlighting their role in preserving biodiversity [11]. Group 3: Cultural Influence on Tree Distribution - The distribution of ancient trees associated with Buddhist culture is notably greater than that of non-Buddhist species, indicating a strong cultural influence on the propagation of certain tree species [12]. - Important Buddhist tree species have been introduced and cultivated in many temples far from their natural habitats, showcasing the impact of cultural practices on biodiversity [12]. Group 4: Visual Documentation - The article includes visual documentation of ancient trees in various temples, illustrating the richness and diversity of tree species preserved in these cultural sites [14][17].

Core Viewpoint - The research led by Professor Pan Qiwei from Erasmus University Medical Center focuses on developing macrophage-augmented organoids (MaugO) that replicate the complex pathophysiology of viral diseases, aiding in the development of multitarget therapeutics [1][6]. Group 1: Research Background - The study addresses the complexity of acute viral disease pathophysiology, characterized by strong inflammatory responses driven by immune cells, leading to tissue damage [5]. - Current in vitro models primarily replicate the viral life cycle but fail to simulate immune cell-mediated disease mechanisms [5]. Group 2: Development of MaugO - The research team integrated macrophages into primary organoids cultured from human liver tissue to construct MaugO [6]. - MaugO was tested for infections from two RNA viruses (Hepatitis E virus and SARS-CoV-2) and one DNA virus (monkeypox virus), all of which can infect and affect human liver [8]. Group 3: Findings and Implications - MaugO successfully replicated the infections and the resulting inflammatory responses across all three acute viral infection models, albeit with varying degrees [8]. - The study demonstrated the multifunctional role of human bile in the replication of Hepatitis E virus and the inflammatory response [8]. - MaugO also exhibited characteristics of inflammatory cell death induced by Hepatitis E virus infection when integrated with pro-inflammatory macrophages [8]. - The research validated the concept of developing multitarget therapies that can simultaneously address the virus, inflammatory response, and the resultant inflammatory cell death [8].

Group 1 - The article highlights the publication of six research papers by Chinese scholars in the prestigious journal Cell, covering various topics in biology and evolution [2] - The studies include the reconstruction of the ant phylogenetic tree, octopus sensory perception of environmental microbes, skin microbiomes of Indigenous Malaysians, new strategies for disease-resistant crop breeding, digital reconstruction of full embryos, and insights into the appearance of Denisovans [2][4][9][14][19][24][29] Group 2 - The study on ants integrated genomic data from 163 ant species, clarifying their complex phylogenetic relationships and tracing their common ancestor back to approximately 157 million years ago during the Jurassic period [6] - The research on octopuses explored how environmental microbiomes influence their sensory receptors and behavior, providing new evidence for co-evolution between microbes and animals [11] - The investigation into Indigenous Malaysians' skin microbiomes revealed unique microbial communities and insights into chronic fungal infections, potentially informing treatment strategies [16] - The crop breeding study demonstrated that co-delivery of immune receptors can enhance disease resistance across diverse plant species, offering new strategies for sustainable agriculture [21] - The digital reconstruction of mouse embryos at single-cell resolution provided significant insights into early organogenesis and a unique platform for studying development and disease [26] - The research on Denisovans successfully extracted ancient DNA from dental calculus, linking it to a nearly complete skull fossil and enhancing understanding of human evolutionary history in East Asia [30]

Core Viewpoint - The research highlights the discovery of LbuCas13a, a novel CRISPR-Cas protein that can directly target DNA and exhibits strong trans-cleavage activity, leading to the development of a new molecular diagnostic platform called SUREST for high-sensitivity DNA mutation detection [1][3][4]. Group 1: Research Findings - LbuCas13a, derived from Leptotrichia buccalis, can directly target DNA without being restricted by protospacer adjacent motifs (PAM) and shows significant trans-cleavage activity [3]. - The specificity of LbuCas13a for single nucleotides in DNA is enhanced compared to RNA, attributed to the lower affinity of CRISPR RNA (crRNA) for DNA, which increases the energy barrier for crRNA binding [4]. - SUREST, based on LbuCas13a, can detect DNA concentrations as low as 0.3 amol for the CYP2C19 gene, which is crucial for assessing individual drug metabolism capabilities [4][5]. Group 2: Application and Impact - SUREST has been successfully applied in human genotyping scenarios, demonstrating excellent performance across a wide range of mutations and sequence backgrounds [5]. - Overall, SUREST represents a significant advancement in real-time nucleic acid detection technology, making it a valuable tool for pathogen identification and gene mutation analysis in clinical diagnostics [6].

Core Viewpoint - The research published in Nature highlights the design of a new ductile FeNiCoAlTa alloy with unprecedented strength and plasticity, achieved through machine learning techniques, setting a new record for yield strength and tensile ductility in alloys [2][4]. Group 1: Research Findings - The alloy composition is Fe 35 Ni 29 Co 21 Al 12 Ta 3, which demonstrates a remarkable combination of 1.8 GPa yield strength and 25% true uniform elongation [4]. - The study emphasizes the use of machine learning models based on domain knowledge to design multi-principal element alloys, achieving high strength and high ductility [4]. Group 2: Microstructural Innovations - The research team enhanced the alloy's strength by maximizing microstructural heterogeneity, featuring large coherent L1 2 nano-precipitates and incoherent B2 micro-particles [6]. - The B2 micro-particles contribute to a multi-component structure that can accumulate dislocations, thereby maintaining a high strain hardening rate and extending uniform elongation [6].

2025 年 6 月 19 日，浙江大学 林爱福 、 周天华 及 袁瑛 等团队 在 Cell 子刊 Molecular Cell 发表题为 ： Hepatic micropeptide modulates mitochondrial RNA processing machinery in hepatocellular carcinoma 的封面论文 【2】 。 排版丨水成文 人类基因组的复杂性令人叹为观止，但仅约1%的基因编码约两万种蛋白质，而其中被深入研究的仅有几千 种，被认为具有作为药物或检测靶点的更是屈指可数。陆续有研究表明，人类基因组中曾被认为不具备编 码功能的非编码区，同样蕴藏着编码蛋白质的潜力。这些如同"暗物质"般神秘的未被充分研究蛋白质，可 能蕴藏着治疗包括癌症在内多种疾病的关键钥匙，其系统鉴定将为生物学与医学研究带来新思路。 近期，浙江大学 林爱福 与 周天华 团队在人类胃癌等组织样本中鉴定出近万个尚未被充分解析的新型 微肽 ，并借助人工智能 （AI） 技术对其功能进行了系统注释，为肿瘤等恶性疾病的预防和干预提供了新的靶点 和思路。 相 关 论 文 以 ： Comprehensive Disc ...