This article investigates the evolutionary history of zoonotic viruses to determine if they must adapt within animal hosts before infecting humans. By analyzing the natural selection patterns of major pathogens like SARS-CoV-2, Ebola, and influenza, researchers found that most viruses do not require significant genetic changes to become capable of human-to-human transmission. Instead, many viruses circulating in the wild are already pre-adapted to jump the species barrier. The study also highlights a unique evolutionary signature for the 1977 H1N1 influenza outbreak, suggesting it was likely the result of laboratory passage rather than natural spillover. These findings provide a phylogenetic framework for distinguishing between natural viral emergence and artificial selection. Ultimately, the research suggests that the selective sieve for most pandemics occurs at the moment of contact rather than through long-term adaptation in a reservoir.

References:

• Havens J L, Pond S L K, Zehr J D, et al. Dynamics of natural selection preceding human viral epidemics and pandemics[J]. bioRxiv, 2025.

This research introduces a novel ferritin aggregation cell engager (FACE) designed to enhance CAR T cell therapy for patients with refractory leukemias. By utilizing the high expression of CD71 receptors on both cancer and therapeutic cells, this platform stabley anchors to CAR T cells to improve their binding strength and sensitivity to low-density antigens. This approach successfully overcomes antigen modulation, a common cause of treatment relapse, without requiring complex genetic re-engineering of the CAR itself. Additionally, the system can be loaded with chemotherapeutic drugs (FACED) to provide a secondary, antigen-independent attack against leukemia cells that have completely lost target expression. Validation across various patient-derived xenograft models demonstrates significantly improved survival rates and a reduced risk of cytokine release syndrome. Ultimately, this universal and flexible engineering strategy offers a promising clinical pathway to treat diverse and aggressive hematological malignancies.

References:

• Li F, Hu Y, Wang Y, et al. Ferritin aggregation cell engager for CAR T avidity engineering against refractory leukemias[J]. Cell, 2026.

The article investigates how β-hydroxybutyrate (BHB), a ketone body produced during a ketogenic diet, enhances the effectiveness of CAR T cell therapy in treating cancer. Through various mouse models and human volunteer data, researchers demonstrated that BHB metabolically reprograms T cells by fueling the TCA cycle and increasing ATP production. This boost in energy leads to superior tumor control, higher rates of cell proliferation, and increased cytokine production compared to standard diets. The study concludes that BHB supplementation is a practical and implementable strategy to improve the potency of adoptive immunotherapies. Furthermore, the findings indicate that these benefits require the continuous presence of BHB in the system rather than just during the initial cell manufacturing phase. Overall, the research highlights a significant link between dietary metabolites and the success of advanced cancer treatments.

References:

• Liu S, Guruprasad P, Ramasubramanian R, et al. β-hydroxybutyrate enhances the metabolic fitness of CAR T cells in cancer[J]. Cell, 2026.

This study presents a comprehensive multi-omic analysis of 110 healthy individuals to map the natural variation of the human immune system and its relationship with the gut microbiome. Researchers identified two primary axes of immunological variability driven by interferon response signatures, which are critical for antiviral defense and therapy outcomes. One specific axis, termed Immune and Microbiome Concomitant Variation (IMCV), reveals that certain immune cell states—such as activated monocytes and memory T cells—are directly coordinated with microbial metabolic pathways and stool metabolites. These coordinated features, including the production of short-chain fatty acids and polyamines, remain remarkably stable within individuals over long periods. The findings suggest that a person's "interferon setpoint" is influenced by their unique microbiome composition, potentially impacting how they respond to vaccinations and cancer immunotherapies. Ultimately, this research provides a foundational resource for understanding how steady-state biological interactions define health and disease susceptibility.

References:

• Babdor J, Patel R K, Davidson B, et al. Immune-microbiome coordination defines interferon setpoints in healthy humans[J]. Cell, 2026.

Researchers have developed "optovolution," a groundbreaking method for the continuous directed evolution of complex, multi-state protein functions using light-responsive selection pressure. By genetically engineering budding yeast to link a protein of interest to essential cell-cycle regulators, the team created a system where cells only proliferate if the protein correctly switches between "on" and "off" states. This approach successfully produced 19 new variants of the LOV transcription factor with enhanced sensitivity and reduced leakiness, while also enabling color-multiplexing via green-light responsiveness. Additionally, the study identifies a genetic deletion that allows the PhyB-PIF system to function without external chemical additives and demonstrates the evolution of a non-light-responsive logic gate. Ultimately, optovolution provides a scalable and precise framework for engineering dynamic biological behaviors that were previously difficult to optimize.

References:

• Gligorovski V, Labagnara M, Scutteri L, et al. Light-directed evolution of dynamic, multi-state, and computational protein functionalities[J]. BioRxiv, 2024: 2024.02. 28.582517.

This research identifies ROCK2 as a critical driver of liver fibrosis, specifically appearing in elevated levels within the vascular endothelial cells and hepatic stellate cells of diseased livers. Scientists developed TDI01, a highly selective and potent inhibitor designed to block this protein’s activity and restore healthy vessel function. The study demonstrates that TDI01 successfully reduces scarring and inflammation in rodent and minipig models of metabolic dysfunction-associated steatohepatitis (MASH). Early human trials confirm the drug is safe and well-tolerated, showing favorable absorption and metabolism in healthy volunteers. Furthermore, an extended clinical study of six patients suggests a promising trend toward reversing liver fibrosis and improving hepatic health. These findings highlight ROCK2 as a viable therapeutic target for treating chronic liver diseases that currently lack effective medical options.

References:

• Hu Y, Yang B, Xiao C, et al. Selective targeting of endothelial and perivascular angiocrine ROCK2 treats liver fibrosis[J]. Cell, 2026.

Researchers have identified α-KG as a key metabolite that naturally combats the pathological vasodilation and erythema associated with rosacea. By activating the OXGR1 receptor in vascular smooth muscle cells, this metabolite triggers a signaling axis that promotes vasoconstriction and reduces skin redness. Detailed cryo-EM imaging revealed a unique bipartite-acid pocket within the receptor, explaining how it recognizes specific acidic molecules like α-KG and itaconate. Using these structural insights, the team developed A-1, a highly selective and potent synthetic agonist that mimics the protective effects of α-KG. In animal models, A-1 demonstrated therapeutic efficacy similar to standard treatments like brimonidine but with a superior safety profile, avoiding common issues like rebound redness. This discovery establishes OXGR1 as a promising therapeutic target for managing chronic vascular skin disorders through metabolic modulation.

References:

• Xiao W, Zhu Y, Tang X, et al. Metabolite-gated vascular contractility switch: OXGR1 activation mechanism enables agonist therapy for rosacea erythema[J]. Cell, 2026.

This research identifies SelO as a conserved mitochondrial enzyme that regulates energy metabolism by hydrolyzing NAD+ into NMN and AMP. Using structural analysis of the bacterial homolog ydiU, scientists discovered that this activity is driven by a unique C-terminal selenocysteine residue and is triggered by increases in mitochondrial pH. The study demonstrates that SelO directly associates with fatty acid oxidation enzymes, effectively acting as a metabolic brake to prevent overactivation. In mice, the absence of this enzyme leads to elevated mitochondrial NAD+ levels and increased lipid utilization, but ultimately results in mitochondrial fragmentation and liver injury. These findings reveal that SelO is a critical protective factor that maintains organelle homeostasis by precisely controlling the spatiotemporal availability of NAD+.

References:

• Jia X, Zhang T, Yang C, et al. NAD+ hydrolysis catalyzed by SelO is required for mitochondrial homeostasis[J]. Cell, 2026.

This research study identifies sildenafil as a potential treatment for Leigh syndrome, a currently untreatable and severe mitochondrial disorder. By screening thousands of existing drugs on patient-derived stem cells, scientists discovered that this PDE5 inhibitor can correct cellular defects, such as abnormal mitochondrial membrane potential and impaired calcium regulation. The drug demonstrated significant efficacy in both human brain organoids and animal models, where it successfully extended lifespan and improved neurological development. Furthermore, off-label clinical use in six patients resulted in enhanced motor function and greater resilience against metabolic crises. These findings suggest that repurposing sildenafil could offer a life-changing therapeutic strategy for individuals suffering from various forms of mitochondrial disease.

References:

• Zink A, Dai D F, Wittich A, et al. Pluripotent stem-cell-based screening uncovers sildenafil as a mitochondrial disease therapy[J]. Cell, 2026.

The paper introduces stVCR, a generative deep-learning framework designed to reconstruct the continuous spatiotemporal dynamics of single cells from discrete snapshots. Because traditional spatial transcriptomics involves destructive sequencing, it typically produces unpaired "pictures" of biological processes rather than a continuous "video." To bridge this gap, stVCR utilizes dynamic optimal transport and rigid-body transformation to align data from different time points into a single coordinate system. This allows researchers to track cell differentiation, migration, and proliferation simultaneously while accounting for changes in cell populations due to division or death. The study validates the model's accuracy and robustness using both simulated datasets and real-world biological applications, such as axolotl brain regeneration and Drosophila embryo development. Ultimately, the framework provides an interpretable method for analyzing how gene expression and physical location interact to drive complex developmental processes.

References:

• Peng Q, Zhou P, Li T. stVCR: spatiotemporal dynamics of single cells[J]. Nature Methods, 2026: 1-12.