Aging is a complex biological process, which is affected by several factors, lifestyle, diet, genetic or epigenetic factors, environmental stress, and metabolisms. Among others, several reports observed increased glycolysis in senescent cells (SnCs) and individual aging, whose causal effects or biological mechanisms have been unclear. Recently, we identified PGAM1-Chk1 binding as a booster for glycolytic metabolism and cell viability in SnCs. Secretary phenotype of inflammatory factors, known as SASP (senescence associated secretary phenotype), is one of prominent properties in SnCs, which accelerates chronic inflammation and aging-relevant dysfunctions in tissues. Inhibition of PGAM1-Chk1 binding removes SnCs and suppresses SASP, alleviating organ damages and pulmonary fibrosis in vivo. Thus, PGAM1-Chk1 interaction; represents a novel target for senolysis to preserve resilience in aging.

Understanding how molecular mechanisms occur and shape brain function and dysfunction remains a central challenge in neuroscience. Although bulk omics methods have contributed significantly to the field, they fail to address the cellular and spatial heterogeneity of the brain. Single-cell and spatial multi-omics approaches emerged to address these limitations by enabling integrated, high-resolution profiling of molecular layers while preserving cellular and tissue context. However, despite their impact on basic neuroscience, the clinical translation of these methods remains limited by cost, technical complexity, and analytical challenges. In this review, we summarize recent advances in single-cell and spatial multi-omics applied to brain research, critically evaluating their technological capabilities, translational potential, and current limitations. We further highlight emerging directions, including spatiotemporal integration, morphomics, improved reproducibility, and the expansion of multi-omics research to biologically and environmentally diverse populations.

Smart electrochromic devices based on reversible electrodeposition/dissolution have attracted increasing attention owing to their large optical modulation, simplified device configuration, and potential multifunctionality. Different from conventional electrochromic systems relying on ion insertion/extraction in pre-deposited films, these devices offer dynamic optical regulation through reversible electrochemical deposition and dissolution at the electrode/electrolyte interface. In this review, recent progress in reversible electrodeposition-based electrochromic devices is summarized with emphasis on three representative families: reversible metal, iodine, and MnO₂ electrodeposition. For metal-based devices, deposition morphology, alloy composition, electrolyte regulation, and electrode surface modification are key factors determining optical contrast, color tunability, and cycling stability. For iodine systems, the suppression of the polyiodide shuttle and dead iodine formation is central to achieving stable neutral-color modulation. For MnO₂ systems, reversible Mn²⁺/MnO₂ conversion enables wide UV–visible modulation and multicolor states, while dead manganese residues and non-uniform deposition remain major challenges. Finally, the common design principles and system-specific trade-offs are compared and discussed, followed by an outlook on practical reliability, large-area fabrication, adaptive thermal regulation, and multifunctional integration. This review aims at inspiring future endeavors towards implementation of reversible (non-)metal electrodeposition-based smart electrochromic devices.

Once dismissed as mere cellular waste, extracellular vesicles (EVs) have undergone a conceptual redefinition, emerging as programmable therapeutic scaffolds with broad biomedical applications. Modern EVs design has progressed past the conventional framework of localized cargo delivery to isolated recipient cells; instead, the focus has shifted toward systemic, multi-cellular niche remodeling aimed at restoring tissue-level homeostasis. This review provides a comprehensive analysis of the engineering strategies to overcome the biological bottlenecks of naive EVs, specifically rapid systemic clearance and inefficient cytosolic delivery. We detail current strategies for active loading and for bypassing endolysosomal entrapment to facilitate in-situ translation of therapeutic mRNA. Furthermore, we discuss how the synergy between engineered EVs and responsive biomaterial scaffolds provides the spatiotemporal control necessary for localized reprogramming of diseased microenvironments. Finally, by examining application paradigms across oncology, regenerative medicine, and neurodegeneration alongside existing regulatory classification frameworks, this review provides a roadmap for transitioning intelligent vesicle platforms from benchtop discovery to clinical-grade compliance.

Ultraviolet germicidal irradiation (UVGI) is widely applied in heating, ventilation, and air-conditioning systems to reduce airborne pathogen transmission, yet its effectiveness depends on airflow-driven changes in lamp thermal condition and particle residence time. This study experimentally characterises the coupled thermal and optical performance of 95 W and 60 W low-pressure mercury UV-C lamps and uses the measured irradiance fields for comparative germicidal assessment. Air velocities of 1.1-2.5 m/s and ambient temperatures of 14-22 °C were varied to quantify their effects on lamp-surface temperature and 254 nm output. The 95 W lamp maintained near-maximum output over a broader operating range, whereas the 60 W lamp was more sensitive to convective cooling. Reynolds and Rayleigh numbers ranged from approximately to and to, respectively, while the convection-to-radiation heat-loss ratio increased with airflow velocity. Mean modelled UV dose increased with lamp count and decreased with airflow velocity. At 1.1 m/s, six-lamp arrays delivered mean modelled doses of approximately 191 J/m² for the 95 W lamps and 146 J/m² for the 60 W lamps. Published UV susceptibility constants produced calculated reductions exceeding 6 log for susceptible viral and bacterial species, whereas the calculated reductions for Aspergillus spores ranged from below 0.05 to approximately 0.4 log. These microbial reductions were calculated from the measured irradiance fields and published susceptibility constants and were not experimentally validated using bioaerosols. The results provide a measurement-informed basis for comparing lamp power, airflow condition, and lamp arrangement in in-duct UVGI systems.

Photothermal phase change materials (PCMs) are emerging as one kind of multifunctional wearable energy materials that integrate latent-heat storage with solar-to-thermal conversion, electrothermal heating, radiative regulation, and intelligent sensing. Unlike conventional PCMs, wearable photothermal PCMs should simultaneously satisfy thermal performance, flexibility, breathability, leakage resistance, cycling stability, and skin compatibility. We summarize recent progress in photothermal PCMs for wearable thermal management and intelligent healthcare, focusing on material systems, energy-conversion mechanisms, and application scenarios. Shape-stabilized solid-liquid composites, intrinsically flexible solid-solid/polymeric PCMs, photothermal-filler-enhanced composites, and PC-Azo molecular solar thermal systems are discussed. Their applications in personal thermal management, solar-thermal/optically switched heat release, wearable thermotherapy, intelligent healthcare, wearable electronics, and self-powered systems are highlighted. Finally, key challenges and future opportunities are proposed, including human-centered evaluation standards, multimodal thermal regulation, epidermal phase-change hydrogels, phase-change solar thermal textiles, and AI-guided material design.

Cellular senescence is a stress-induced cell-cycle arrest program accompanied by the senescence-associated secretory phenotype (SASP). While senescent cells are typically eliminated through immune surveillance under normal physiological conditions, they tend to accumulate progressively during aging and in chronic diseases. This review summarizes current evidence suggesting that such persistence is attributable not only to immune system decline but also to active, cell-intrinsic mechanisms of immune evasion. We discuss how senescent cells escape clearance by weakening immune recognition, suppressing phagocytic removal, resisting apoptosis, remodeling the inflammatory and structural microenvironment through SASP, and activating inhibitory checkpoint pathways in aged tissues. Furthermore, we investigate the contribution of these mechanisms to representative age-related diseases across multiple organs. Finally, we highlight emerging therapeutic strategies aimed at targeting the immune evasion of senescent cells, including checkpoint modulation, CAR-based cell therapies, vaccination approaches and other immune-bypass strategies. Collectively, these insights underscore immune evasion as a critical determinant of senescent cell persistence and a promising target for interventions in aging and age-related diseases.

The autonomic nervous system (ANS) regulates myeloid cell biology across lymphoid and non-lymphoid tissues. Sympathetic, parasympathetic, and enteric circuits shape the myeloid cell development, positioning or activation, and antigen presentation through norepinephrine, acetylcholine, dopamine and neuropeptides. In primary lymphoid organs, autonomic signals regulate myeloid progenitors and thymic macrophages, shaping the output and functional competence of innate immune compartments. In secondary lymphoid organs, most extensively characterized in the spleen, neural efferent pathways control macrophages, dendritic cells, monocytes and neutrophils, influencing phagocytosis, cytokine production and lymphocyte priming. Distinct neuro-myeloid interactions occur in the gut, where the enteric nervous system is a mandatory relay for parasympathetic signals to intestinal myeloid cells, and in the tumor microenvironment, where sympathetic and dopaminergic signals regulate tumor-associated myeloid subsets in tumor type-specific ways. The functional output of ANS-myeloid communication is guided by tissue context, myeloid cell identity, receptor type, and signal dynamics. The systemic characterization of these neuroimmune variables will be critical to design therapeutic strategies targeting the ANS-myeloid axis in infection, inflammation, autoimmunity and cancer.

Hydrodynamic electron transport, in which electrical transport in solids resembles fluid hydrodynamics when momentum-conserving electron-electron scattering dominates, has attracted much attention over the past decade. However, its thermal aspects have received considerably less attention. In this paper, we systematically simulate electron transport in a graphene Corbino disk by solving the steady-state Boltzmann transport equation with a dual relaxation-time Callaway model, in which momentum-conserving and momentum-relaxing scatterings are explicitly distinguished. By varying the magnetic field strength and scattering rates, we compare the charge and heat flux responses across the diffusive-to-hydrodynamic crossover under both electric field and temperature-gradient driving. We show that magnetic-field-induced deflection of both fluxes is strongly enhanced in the hydrodynamic regime but nearly suppressed in the diffusive regime. Under electric-field driving, a pronounced temperature rise is observed in the hydrodynamic regime du to reduced dissipation, while the diffusive regime remains nearly isothermal. Under temperature-gradient driving, the deflection exhibits the opposite chirality to that in the electric-field case. These findings establish that thermal transport can provide a sensitive and independent diagnostic of electro hydrodynamics, and identify the magnetic field as an effective discriminator between collective and dissipative conduction.

Owing to their stable axial chirality, atropisomeric biaryl compounds have found widespread applications in medicinal chemistry, natural product chemistry, and agricultural chemistry. Up to now, two principal strategies have been established for the synthesis of axially chiral biaryls: the enantioselective construction of the aryl-aryl axis via asymmetric coupling reactions, and the stereoselective modification of a pre-existing axis, which includes asymmetric construction of one aromatic ring, desymmetrization of prochiral substrates, and dynamic kinetic resolution (DKR) of biaryl skeletons. Among these strategies, enantioselective C−H functionalization avoids the use of pre-functionalized substrates and installs sterically demanding groups that enhance rotational barriers, thereby serving as an ideal DKR tool for the construction of atropisomeric biaryls directly from biaryl substrates with low rotational barriers. In this review, based on the nature of the directing groups, we summarize three distinct strategies for enantioselective C−H functionalization of biaryls with free axial rotation: directing group (DG)-mediated, transient DG-enabled, and DG-free approaches. The mechanisms and substrate scopes of selected representative reactions are also briefly discussed.

Aims: Cervical cancer is the second most common cancer globally in women of reproductive age. Current immunotherapies offer only moderate improvement in overall survival for metastatic or refractory disease, highlighting the need for more effective, patient-directed immunotherapies.

Methods: A unified pipelinereprocessed all The Cancer Genome Atlas (TCGA) and genotype tissue expression (GTEx) samples from raw reads using identical alignment and quantification parameters to screen a curated set of 259 high-confidence surface protein genes. This analysis provided the foundation for selecting differentially overexpressed cell surface receptors as potential antibody-drug conjugate (ADCs) targets . Recombinant single chain variable fragment (scFv)-O6-alkylguanine-DNA alkyltransferase (SNAP) fusion proteins were expressed, purified and characterised using immunoblotting. The dose-dependent and selective cytotoxicity of an auristatin F-conjugated (scFv)-SNAP fusion protein was verified in vitro.

Results: Bioinformatic screening revealed 30 potential targets overexpressed in cervical carcinoma (Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (CESC)) vs. healthy tissues. Tissue-of-origin analysis (endocervix vs. ectocervix) further refined priorities. These results, together with supporting evidence from the literature, justified drug production.. The (scFv)-SNAP fusion proteins exhibited strong surface binding across cervical cancer cell lines and, when conjugated to auristatin F, showed dose-dependent cytotoxicity at nanomolar concentrations, confirming the differences observed in transcriptomic analyses of endo- vs. ectocervix profiling.

Conclusion: Bioinformatics and in vitro validation synergize powerfully from initial screening through subtype refinement to iterative target confirmation, enabling a precision medicine approach for cervical cancer-specific immunotherapies. The (scFv)-SNAP-auristatin F (ADC) conjugates reproduced this refinement, showing highly promising potential.

The rapid development of the low-altitude economy has positioned vertiports as critical heavy-asset hubs in urban logistics networks, where siting decisions affect both delivery access and facility utilization. Existing maximum-coverage models do not explicitly represent station throughput or allocated order volumes. This study therefore retains the original three-stage framework-demand assessment, hierarchical facility polygon intersection point set (HFPIPS) candidate generation, and capacitated location-allocation, while correcting the demand surface to use area-weighted land-use shares and clarifying that the utilization floor is an application-specific minimum-throughput rule rather than a new algebraic form. In Nanjing, 8,811 demand grids and 10,283 planning candidates produce 2,678,898 radius-feasible pairs, reduced to 374,873 pairs by demand-adaptive pruning. Under a 300 s single-thread budget, the high-coverage capacitated facility location problem (CFLP) returns a verified feasible incumbent of 195 stations delivering 156,300 orders/day (78.13%), with 66.79% average utilization, 22.50% minimum utilization, and 0.953 km average delivery distance. At the same 195-site budget, a deterministic maximal covering location problem (MCLP)-greedy baseline achieves 97.05% nominal geometric coverage but only 63.87% capacity-feasible delivery. Removing the utilization floor delivers only 29 additional orders while opening four extra sites and permitting utilization as low as 1.58%. Land-use coefficient contrast tests change delivery by less than 0.27 percentage points and preserve the selected station set. The results support capacity-aware planning, while building-level engineering data, heterogeneous fleets, temporal demand, and unresolved solver gaps remain limitations.

DNA integrity and stability are intricately linked to DNA damage repair (DDR) pathways, which have long been well characterized through a biochemical perspective. However, the physical properties of the nucleus in which DNA damage occurs have been long overlooked, leaving the relationship between nuclear mechanics and DDR poorly defined. In this review, we describe the core mechanical components, including the lamina, chromatin, and linker of nucleoskeleton and cytoskeleton (LINC) complex, which collectively determine nuclear stiffness, tension, and structural integrity. We further define the regulatory role of nuclear mechanics in DDR, with particular emphasis on DNA double-strand break (DSB) repair. Aberrant nuclear stiffening, tension, and envelope rupture may cause persistent DNA repair failure and genomic instability. Nuclear mechanics are aberrantly altered in cancers, therefore manipulating nuclear mechanics may counteract therapeutic drug resistance via regulating DDR efficiency in cancer cells. Throughout, we conclude that nuclear mechanics acts as a physical rheostat for DDR. Manipulating nuclear stiffness, tension, or envelope integrity susceptibility offers a new therapeutic axis for sensitizing tumors to DNA-damaging agents.

Seawater electrolysis is a promising route for sustainable hydrogen production, yet its practical deployment is severely restricted by the chloride-rich electrolyte environment, which imposes more stringent demands on anodic oxygen evolution reaction (OER) catalysts than conventional purified water electrolysis. Chloride ions not only trigger competing chlorine-related reactions but also accelerate catalyst corrosion, surface reconstruction, active-site degradation, and interfacial reaction complexity, making the rational design of active and durable chloride-resistant catalysts a central challenge in this field. In this context, synchrotron radiation (SR)-based spectroscopies have emerged as indispensable tools for bridging catalyst design and mechanistic understanding under operating conditions. In particular, X-ray absorption spectroscopy (XAS) enables direct probing of the oxidation state, electronic structure, and local coordination environment of catalytic centers, providing atomic-scale insights into chloride-induced structural evolution, active-site reconstruction, and stability regulation. SR-based infrared spectroscopy (SR-IR) offers molecular-level information on adsorbed intermediates, surface functional groups, and interfacial water structure, thereby revealing how chloride perturbs reaction pathways and interfacial chemistry during seawater electrolysis with large-scale applications in the future. This review first summarizes the fundamental challenges of seawater electrolysis, with emphasis on the critical role of chloride in governing catalyst selectivity and durability; it then introduces the basic principles and unique advantages of XAS and IR, highlighting their irreplaceable value in studying working electrocatalytic systems; subsequently, recent progress in applying these techniques to chloride-resistant catalyst design and reaction mechanism studies is discussed; finally, future opportunities are outlined, which are expected to substantially deepen the understanding of chloride-related processes and guide the rational development of efficient, robust, and low-cost catalysts for seawater electrolysis.

Reactive oxygen species (ROS) are typically elevated at inflammatory sites due to the influx of large numbers of neutrophils and other myeloid cells that produce high levels of oxygen free radicals as microbicidal agents. Reactive oxygen intermediates are also generated as a byproduct of cellular metabolism, due to mitochondrial damage, exposure to toxins or radiation, and are also frequently increased during inflammatory reactions. However, although oxidative stress is often implicated as an initiator or amplifier of inflammation, particularly in the context of cancer, how reactive oxygen modulates inflammatory signalling remains poorly understood. Here we discuss the diversity of pathways and molecules implicated in promoting or suppressing inflammation in response to ROS. As we shall see, reactive oxygen has been reported to influence inflammatory outputs through direct effects on phosphatases that regulate nuclear factor kappa B (NF-κB) activation, through activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) or hypoxia-inducible factor (HIF)-1 transcription factors that can directly or indirectly promote inflammatory gene expression, by provoking DNA damage leading to activation of the cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS)/stimulator of interferon genes (STING) pathway, or through promoting assembly of inflammasomes. Thus, there are a multitude of routes by which ROS can influence inflammatory responses. How reactive oxygen promotes inflammation in specific contexts is likely to be influenced by several factors, including the source of ROS, whether intracellular or extracellular, the responding cell type, as well as the extent of deviation from normal homeostatic setpoints. Understanding how reactive oxygen shapes inflammation has important implications for therapeutic intervention in multiple disease states.

Aims: Spatially resolved omics technologies enable investigation of cellular interactions within their local microenvironments (neighbourhoods) directly in situ. Although several computational methods have been developed for neighbourhood analysis, significant limitations remain in how neighbourhoods are defined and interrogated. Here, we present Kandinsky, a toolkit that provides a flexible and versatile framework for defining and analysing cell neighbourhoods.

Methods: We developed Kandinsky to improve flexibility in neighbourhood analysis and maximise compatibility with a wide range of spatial omics data. We therefore implemented multiple approaches for identifying cell- or spot-based neighbourhoods that serve as input for four analytical modules: differential gene or protein expression analysis, neighbourhood clustering, co-localisation/dispersion, and spatial hot and cold areas. In addition to its core functionality, Kandinsky enables the execution of external tools within the same analytical framework.

Results: We applied Kandinsky to real and simulated spatial datasets to benchmark its performance against existing methods and demonstrate its ability to uncover biologically meaningful spatial interactions. Kandinsky achieved competitive performance in terms of accuracy, memory usage, and runtime. In real datasets, it suggested transcriptional changes associated with acinar-to-beta cell reprogramming in the healthy pancreas; recapitulated stromal, immune, and tumour-associated clusters in pancreatic cancer; revealed the spatial co-localisation of myoepithelial cells with specific breast cancer subpopulations; and confirmed the association between regions of high CD74 expression and immune cell infiltration.

Conclusion: Kandinsky is a flexible and versatile toolkit for neighbourhood analysis that facilitates the exploration and interpretation of complex spatial omics data.

Photodynamic therapy (PDT) induces immunogenic cell death (ICD) through reactive oxygen species (ROS) generation, bridging localized tumor ablation with systemic antitumor immunity. However, the tumor microenvironment (TME) erects three barriers that intercept the PDT-immune cascade at distinct levels. The biochemical barrier, defined by chronic hypoxia and elevated antioxidant defenses, restricts ROS accumulation below the ICD threshold. The physical barrier, constructed by a dense extracellular matrix and activated cancer-associated fibroblasts, confines photosensitizers to the tumor periphery and excludes effector immune cells. The immunosuppressive barrier, mediated by tumor-associated macrophages, regulatory T cells, and myeloid-derived suppressor cells, neutralizes immune activation signals even after successful ICD induction. These barriers are deeply coupled: breaching any single layer yields limited benefit when the others remain intact. This review examines how barrier-oriented PDT-immunotherapy strategies, particularly nanoplatform-enabled approaches, can relieve these three barriers and restore the PDT-immune cascade.

Ferroptosis is an iron-dependent form of programmed cell death defined by the lethal accumulation of lipid peroxides. Accumulating evidence indicates that ferroptosis plays a critical role in a wide range of pathological processes, including tumor progression, ischemia-reperfusion injury, and neurodegenerative diseases. The key determinants of cellular susceptibility to ferroptosis are the homeostasis of iron and lipid metabolism, whose maintenance relies heavily on the precise regulation of inter-organelle communication networks. In this review, we focus on the spatial biology of ferroptosis regulation. From three core dimensions, iron homeostasis modulation, lipid metabolism remodeling, and redox balance maintenance, we systematically dissect the mechanisms by which signal crosstalk and functional coordination among multiple organelles (lysosomes, endoplasmic reticulum, mitochondria, plasma membrane, nucleus, lipid droplets, Golgi apparatus, and peroxisome) govern ferroptosis initiation, signal amplification, and cellular defense responses. Comprehensive elucidation of this multi-organellar coordinated regulatory network will not only advance our fundamental understanding of ferroptosis execution but also provide a holistic perspective for the development of organelle-targeted therapeutic strategies against human diseases.

P2-type layered manganese-based oxides are promising cathode materials for sodium-ion batteries (SIBs) but suffer from structural instability and irreversible phase transitions. This study demonstrates that iron doping in P2-Na_2/3Li_1/6Fe_1/6Mn_2/3O₂ (NLFM) effectively reconfigures the structural and redox chemistry. Structural and electrochemical analyses reveal that Fe³⁺ incorporation expands the Na⁺ interlayer spacing, enhances reversible cationic (Fe³⁺/Fe⁴⁺) and anionic redox activity, and promotes a dominant surface-controlled charge storage mechanism. Consequently, the NLFM cathode delivers a high initial capacity of 225 mAh·g^-1 at 0.1 C, an impressive initial Coulombic efficiency of 110.21%, and superior cycling stability (73.6% capacity retention after 100 cycles at 1 C). Furthermore, Fe doping effectively mitigates the Jahn-Teller distortion and the reversible P2 to O2 phase transition at high voltages. This work highlights the multi-functional role of iron doping in stabilizing the structure and optimizing the redox chemistry of P2-type cathodes, providing an effective strategy for developing high-energy and durable SIBs cathodes.

Ferroptosis is a form of regulated cell death driven by iron-dependent lipid peroxidation, and is therefore intrinsically coupled to cellular redox metabolism. Progression of ferroptosis is regulated by an integrated network of metabolic signaling pathways that involve inter-organellar communication. In this Review, we synthesize recent progress in the field that has advanced our understanding of the metabolic determinants of ferroptosis. We discuss key metabolites which participate in the execution and prevention of ferroptosis, describe major signaling axes that impinge on regulating these metabolic activities to determine cellular ferroptosis sensitivity, and highlight how compartmentalized metabolism within and across distinct intracellular organelles collectively shape ferroptosis progression. Together, this Review aims to provide a framework that unifies metabolic state, signaling plasticity and organellar cooperation as a mechanistic basis of ferroptosis, underscoring its implications in the pathogenesis of various diseases including cancer.

Quantum theory departs from classical physics in its treatment of correlations, most prominently through the phenomena of contextuality and nonlocality. Once regarded primarily as foundational curiosities, these effects are now understood as key operational resources for quantum computation, communication, and simulation. Although traditionally investigated in distinct settings, recent theoretical and experimental advances have revealed deep conceptual, mathematical, and operational connections between them. This review presents a unified perspective on these developments based on sheaf-theoretic and graph-theoretic frameworks, which provide theory-independent characterizations of statistical correlations. These approaches clarify the structural relationship between contextuality and nonlocality, facilitate the formulation of experimentally testable inequalities, and guide implementations in realistic physical platforms, with particular emphasis on photonic experiments using structured light and orbital-angular-momentum encoding for high-dimensional quantum states. By bridging abstract theoretical structures and concrete experimental realizations, this review sheds light on the nonclassical foundations of quantum correlations and their emerging role in quantum technologies.

Myeloid cells are central components of innate immunity and are highly responsive to environmental and lifestyle-associated cues. Among them, neutrophils are the most abundant circulating leukocytes in humans and have rapid turnover, traditionally leading to the view that they act mainly as short-lived effector cells. However, emerging evidence indicates that neutrophil function can be durably reshaped through upstream reprogramming of hematopoietic stem and progenitor cells and the bone marrow niche, resulting in trained-immunity-like changes in newly generated neutrophils. In this review, we discuss how lifestyle-associated factors shape neutrophil-associated immunity within the broader context of myeloid immune regulation, with a particular focus on long-term neutrophil functional reprogramming. We summarize current evidence that lifestyle and metabolic factors shape neutrophil production, mobilization, tissue recruitment, and effector programs. We further highlight that lifestyle induced neutrophil reprogramming is context dependent and may be either adaptive or maladaptive. Finally, we propose future directions for translating lifestyle-based immune modulation into strategies that limit chronic inflammation while preserving antimicrobial defense.

Alzheimer’s disease (AD) and related dementias are closely associated with alterations in microglial states. These microglial changes occur in response to amyloid-β (Aβ) accumulation and aberrant tau phosphorylation and can either protect against or exacerbate AD progression, depending on factors such as disease stage, genetic background, and environmental influences. This review focuses on recent advances in understanding the protective functions and features of microglia during the early stages of AD, while highlighting the outstanding questions regarding how these protective states deteriorate and become dysfunctional as the disease progresses. Interestingly, epidemiological studies have suggested an inverse relationship between AD and cancer incidence, and in this context, we provide a comparative analysis of microglial phenotypes in AD and cancer to speculate on how insights from anti-tumor microglia may inspire new strategies for reprogramming microglia to combat AD and related dementias.

Ferroptosis is a form of programmed cell death driven by iron-dependent lipid peroxidation. Inducing ferroptosis in tumor cells has emerged as a crucial strategy for cancer treatment and overcoming therapeutic resistance. Ferroptosis suppressor protein 1 (FSP1), identified in recent years, is a key ferroptosis-inhibitory factor that operates independently of glutathione peroxidase 4 (GPX4). FSP1 is highly expressed in multiple malignant tumors, and its expression levels are tightly associated with unfavorable patient prognosis, treatment resistance, and tumor progression. Specific stresses within the tumor microenvironment, including hypoxia, metabolic stress, and the development of drug resistance, can drive a shift in ferroptosis resistance mechanisms from GPX4-dependent to FSP1-dependent pathways. Such plasticity renders FSP1 a druggable target in specific cancer genotypes or at particular stages of tumor progression. Indeed, genetic or pharmacological inhibition of FSP1 has yielded potent antitumor effects across diverse preclinical models. This review systematically summarizes the structural characteristics of FSP1, the molecular mechanisms through which it suppresses ferroptosis, the multilayered regulatory networks controlling its activity, and its roles in different malignancies. We deeply analyze the plasticity of FSP1 dependency in tumor cells in vivo and comprehensively review the latest preclinical progress on small-molecule FSP1 inhibitors and related combinatorial therapeutic strategies. This review aims to establish a theoretical framework to support the clinical translation of FSP1-targeted antitumor strategies.