The unfolded protein response (UPR) is a fundamental stress pathway coopted in cancer, and it is thought to drive adaptation, tumor progression, and therapeutic resistance. While the analysis of ‘single-effector’ biomarkers within the tumor microenvironment often fails to capture its spatial, temporal, and cellular complexity, recent advances in high-resolution spatial transcriptomics and single-cell multiomics may enable a shift from static readouts toward more comprehensive multigene UPR signatures. This could help resolve proteostatic heterogeneity at unprecedented resolution. In this review, we provide a pan-cancer perspective on using these quantitative signatures to map proteostatic states. By combining cell biology, mechanobiology, and computational pathology, our proposed translational framework blends morphological hallmarks with multiomic UPR signatures. Although still requiring prospective clinical validation, this approach could improve patient stratification and treatment decisions, advancing the field of precision oncology.

The unfolded protein response (UPR) is a fundamental stress pathway coopted in cancer, and it is thought to drive adaptation, tumor progression, and therapeutic resistance. While the analysis of ‘single-effector’ biomarkers within the tumor microenvironment often fails to capture its spatial, temporal, and cellular complexity, recent advances in high-resolution spatial transcriptomics and single-cell multiomics may enable a shift from static readouts toward more comprehensive multigene UPR signatures. This could help resolve proteostatic heterogeneity at unprecedented resolution. In this review, we provide a pan-cancer perspective on using these quantitative signatures to map proteostatic states. By combining cell biology, mechanobiology, and computational pathology, our proposed translational framework blends morphological hallmarks with multiomic UPR signatures. Although still requiring prospective clinical validation, this approach could improve patient stratification and treatment decisions, advancing the field of precision oncology.

Panvascular intervention can restore lumen patency, exclude structural defects, or replace diseased valves, but procedural success does not reestablish ecological stability within the treated vessel. We propose eco-rebalancing as a tri-ecological framework in which durable device performance depends on coordinated recovery across three domains: the mechanical, cellular, and physicochemical-immune ecologies. Vascular-device suitcordance denotes the spatiotemporal match between a device’s mechanical behavior, biological interface, and material persistence, and the healing trajectory of a specific vascular bed, lesion, and patient; we introduce the Suitcordance Score (Su-Score) as a conceptual metric of that match. This perspective reinterprets restenosis, thrombosis, fibrosis, calcification, and structural degeneration as signatures of incomplete eco-rebalancing, providing a translational basis for device design and patient-device matching.

The Hippo pathway, classically recognized for its roles in cell proliferation, survival, and development, is increasingly recognized as an important regulator of tissue–immune communication. Recent studies suggest that Hippo signaling within epithelial and stromal compartments influences inflammatory, interferon, and fibrotic responses that contribute to autoimmune disease pathogenesis. In this review, we discuss emerging evidence linking Hippo signaling to tissue remodeling, innate immunity, and sex-biased autoimmunity, with particular emphasis on the transcriptional cofactor vestigial-like family member 3. We propose that Hippo-dependent regulation of stromal–immune crosstalk may represent a previously underappreciated mechanism contributing to chronic inflammation and fibrosis, and discuss opportunities for therapeutic intervention.

Panvascular intervention can restore lumen patency, exclude structural defects, or replace diseased valves, but procedural success does not reestablish ecological stability within the treated vessel. We propose eco-rebalancing as a tri-ecological framework in which durable device performance depends on coordinated recovery across three domains: the mechanical, cellular, and physicochemical-immune ecologies. Vascular-device suitcordance denotes the spatiotemporal match between a device’s mechanical behavior, biological interface, and material persistence, and the healing trajectory of a specific vascular bed, lesion, and patient; we introduce the Suitcordance Score (Su-Score) as a conceptual metric of that match. This perspective reinterprets restenosis, thrombosis, fibrosis, calcification, and structural degeneration as signatures of incomplete eco-rebalancing, providing a translational basis for device design and patient-device matching.

The Hippo pathway, classically recognized for its roles in cell proliferation, survival, and development, is increasingly recognized as an important regulator of tissue–immune communication. Recent studies suggest that Hippo signaling within epithelial and stromal compartments influences inflammatory, interferon, and fibrotic responses that contribute to autoimmune disease pathogenesis. In this review, we discuss emerging evidence linking Hippo signaling to tissue remodeling, innate immunity, and sex-biased autoimmunity, with particular emphasis on the transcriptional cofactor vestigial-like family member 3. We propose that Hippo-dependent regulation of stromal–immune crosstalk may represent a previously underappreciated mechanism contributing to chronic inflammation and fibrosis, and discuss opportunities for therapeutic intervention.

Hypoxia is not simply harmful or protective. Recent studies suggest that hypoxia-inducible factor 1-alpha (HIF-1α) acts as a time- and context-sensitive regulator of tissue-state transitions. We propose that transient HIF-1α activity enables regenerative entry, whereas persistent or unresolved signalling promotes maladaptive remodelling, degeneration, and ageing.

Hypoxia is not simply harmful or protective. Recent studies suggest that hypoxia-inducible factor 1-alpha (HIF-1α) acts as a time- and context-sensitive regulator of tissue-state transitions. We propose that transient HIF-1α activity enables regenerative entry, whereas persistent or unresolved signalling promotes maladaptive remodelling, degeneration, and ageing.

Obstructive sleep apnea (OSA) is a prevalent chronic respiratory condition characterized by repetitive upper airway collapse during sleep, leading to transient hypoxemia and arousals from sleep. Multiple risk factors heighten susceptibility to OSA. Intermittent hypoxia caused by OSA can increase the risk of end-organ morbidity. Key mechanisms include mitochondrial dysfunction, excessive production of ROS, and inflammation driven by NF-κB. HIF-1α responses vary by tissue and exposure pattern and may be attenuated during chronic intermittent hypoxia.

Obstructive sleep apnea (OSA) is a prevalent chronic respiratory condition characterized by repetitive upper airway collapse during sleep, leading to transient hypoxemia and arousals from sleep. Multiple risk factors heighten susceptibility to OSA. Intermittent hypoxia caused by OSA can increase the risk of end-organ morbidity. Key mechanisms include mitochondrial dysfunction, excessive production of ROS, and inflammation driven by NF-κB. HIF-1α responses vary by tissue and exposure pattern and may be attenuated during chronic intermittent hypoxia.

Genomics has revolutionised the diagnosis of rare diseases and is now set to transform prevention through integration with newborn screening programmes. This will identify a broader range of severe, treatable diseases while creating the potential for data reuse across the lifetime. However, for effective population-wide implementation, a shift in the healthcare system to support preventive rather than reactive healthcare will need to occur. In addition, potential harms need to be identified and minimised. This review covers key components of this system shift including parental consent and choice, data workflows and reporting, education, and health-economic impact. Utilising digital technology and global collaboration will be integral to successful evidence generation at scale and to the integration of genomics into public health.

Genomics has revolutionised the diagnosis of rare diseases and is now set to transform prevention through integration with newborn screening programmes. This will identify a broader range of severe, treatable diseases while creating the potential for data reuse across the lifetime. However, for effective population-wide implementation, a shift in the healthcare system to support preventive rather than reactive healthcare will need to occur. In addition, potential harms need to be identified and minimised. This review covers key components of this system shift including parental consent and choice, data workflows and reporting, education, and health-economic impact. Utilising digital technology and global collaboration will be integral to successful evidence generation at scale and to the integration of genomics into public health.

Aging is characterized by progressive loss of molecular fidelity that compromises stem-cell function and tissue homeostasis. Aging transcriptomes show widespread disruption of RNA processing, including increased intron retention, cryptic splice-site usage, and altered RNA quality control. These changes arise from somatic mutations as well as accumulated transcriptional, metabolic, and proteostatic stress. Importantly, similar splicing abnormalities are observed in age-associated diseases such as clonal hematopoiesis and neurodegeneration, overlapping with physiological aging states. Here, we synthesize mechanistic, stem-cell, and longevity studies to define declining RNA-processing fidelity as a unifying contributor to aging across systems. We propose the ‘splicing axis of aging’ as a framework linking RNA-processing dysfunction to tissue decline and outline emerging therapeutic strategies to restore spliceosome integrity and RNA homeostasis.

Aging is characterized by progressive loss of molecular fidelity that compromises stem-cell function and tissue homeostasis. Aging transcriptomes show widespread disruption of RNA processing, including increased intron retention, cryptic splice-site usage, and altered RNA quality control. These changes arise from somatic mutations as well as accumulated transcriptional, metabolic, and proteostatic stress. Importantly, similar splicing abnormalities are observed in age-associated diseases such as clonal hematopoiesis and neurodegeneration, overlapping with physiological aging states. Here, we synthesize mechanistic, stem-cell, and longevity studies to define declining RNA-processing fidelity as a unifying contributor to aging across systems. We propose the ‘splicing axis of aging’ as a framework linking RNA-processing dysfunction to tissue decline and outline emerging therapeutic strategies to restore spliceosome integrity and RNA homeostasis.

Despite major advances in cancer genomics and immunotherapy, the field remains limited by experimental models that fail to faithfully recapitulate human tumor initiation, genetic context, and immune-tumor interactions. Traditional animal and immortalized cell models often lack predictive power for therapeutic response and toxicity. Recent advances in human pluripotent stem cell (hPSC) technology have transformed this landscape, enabling the generation of patient-specific cancer models, multicellular organoids and assembloids, and scalable immune effector cells. These platforms now permit mechanistic dissection of tumorigenesis, reconstruction of human tumor microenvironments, and development of off-the-shelf immunotherapies. This review will synthesize these emerging findings, define key technological and biological gaps, and outline future directions for integrating hPSC-based modeling into precision oncology and translational cancer research.

Nuclear receptor agonists face a dilemma: sustained receptor activation improves efficacy but inevitably exacerbates mechanism-based toxicity. Zang et al. challenge this by demonstrating that transient, physiologically synchronized farnesoid X receptor activation maintains efficacy while minimizing adverse effects, introducing temporal control of signaling as a new precision-therapeutic paradigm.

Despite major advances in cancer genomics and immunotherapy, the field remains limited by experimental models that fail to faithfully recapitulate human tumor initiation, genetic context, and immune-tumor interactions. Traditional animal and immortalized cell models often lack predictive power for therapeutic response and toxicity. Recent advances in human pluripotent stem cell (hPSC) technology have transformed this landscape, enabling the generation of patient-specific cancer models, multicellular organoids and assembloids, and scalable immune effector cells. These platforms now permit mechanistic dissection of tumorigenesis, reconstruction of human tumor microenvironments, and development of off-the-shelf immunotherapies. This review will synthesize these emerging findings, define key technological and biological gaps, and outline future directions for integrating hPSC-based modeling into precision oncology and translational cancer research.

Nuclear receptor agonists face a dilemma: sustained receptor activation improves efficacy but inevitably exacerbates mechanism-based toxicity. Zang et al. challenge this by demonstrating that transient, physiologically synchronized farnesoid X receptor activation maintains efficacy while minimizing adverse effects, introducing temporal control of signaling as a new precision-therapeutic paradigm.

Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase, the holoenzyme whose activity maintains telomeres. Beyond this canonical role, emerging evidence indicates that TERT participates in nontelomeric programs with broad relevance to brain health. TERT can function as a transcriptional co-regulator of genes linked to neuronal viability, synaptic plasticity, and neurodegeneration. During aging and in neurodegenerative states, the TERT locus becomes epigenetically repressed, resulting in altered gene expression programs relevant to neuronal resilience. Genetic and pharmacologic restoration of physiological TERT levels reverses multiple aging phenotypes and mitigates molecular and pathological features associated with neurodegenerative disorders, including Alzheimer’s disease. In this opinion article, we synthesize emerging evidence that positions TERT as a central coordinator of brain health and disease.

Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase, the holoenzyme whose activity maintains telomeres. Beyond this canonical role, emerging evidence indicates that TERT participates in nontelomeric programs with broad relevance to brain health. TERT can function as a transcriptional co-regulator of genes linked to neuronal viability, synaptic plasticity, and neurodegeneration. During aging and in neurodegenerative states, the TERT locus becomes epigenetically repressed, resulting in altered gene expression programs relevant to neuronal resilience. Genetic and pharmacologic restoration of physiological TERT levels reverses multiple aging phenotypes and mitigates molecular and pathological features associated with neurodegenerative disorders, including Alzheimer’s disease. In this opinion article, we synthesize emerging evidence that positions TERT as a central coordinator of brain health and disease.

Robinson et al. challenge the reliance on neurosurgery for glioma diagnosis by integrating multi-omic profiling of plasma extracellular vesicles with machine learning. Across independent cohorts, these biomarkers discriminate between glioma and controls and enable longitudinal tracking of tumor burden, establishing a clinically relevant foundation for minimally invasive diagnosis, monitoring, and stratification.

Robinson et al. challenge the reliance on neurosurgery for glioma diagnosis by integrating multi-omic profiling of plasma extracellular vesicles with machine learning. Across independent cohorts, these biomarkers discriminate between glioma and controls and enable longitudinal tracking of tumor burden, establishing a clinically relevant foundation for minimally invasive diagnosis, monitoring, and stratification.

Tumor-associated macrophages (TAMs) critically modulate solid tumor progression and immunotherapy resistance, yet their profound context-dependent heterogeneity defies the traditional M1/M2 dichotomy. In this review, we propose the ‘niche–metabolism axis’ framework, deconstructing the tumor microenvironment into dynamically interacting functional niches (e.g., hypoxic cores and tertiary lymphoid structures). Within these niches, specific physicochemical stresses substantially influence localized TAM metabolic reprogramming. Metabolites such as lactate and lipids act not merely as substrates but as signaling mediators and epigenetic donors, shaping TAM phenotypes. Consequently, TAMs acquire spatial metabolic imprints and evolve into ‘ecosystem engineers’ that actively remodel the immune microenvironment. This framework highlights that therapeutic paradigms should shift from nonselective TAM depletion to niche-specific metabolic–epigenetic reconstruction, providing a precise roadmap for designing next-generation engineered macrophage therapies.

Nonclassical major histocompatibility complex class I (MHC-I) molecules, including human leukocyte antigen E (HLA-E), HLA-F, HLA-G, MHC-I-related protein 1 (MR1), and the CD1 family, constitute a conserved antigen-presenting system that regulates immune surveillance, tissue homeostasis, and tolerance through specialized interactions with innate and unconventional T cells. Although these molecules have long been implicated in cancer, infection, autoimmunity, and transplantation, their distinct immunobiology and therapeutic potential have largely been considered in isolation. Recent advances in structural immunology, single-cell and spatial profiling, engineered immune cell technologies, and early clinical studies have established nonclassical MHC-I pathways as tractable targets for immunotherapy. In this review, we synthesize the biology, disease-associated functions, and therapeutic targeting of these molecules, integrating immune checkpoint blockade, antibody-based therapeutics, and MR1- and CD1-restricted cellular immunotherapies into a unified framework. We further highlight shared immunological principles, emerging clinical translation, and opportunities for universal, off-the-shelf immune interventions.

Tumor-associated macrophages (TAMs) critically modulate solid tumor progression and immunotherapy resistance, yet their profound context-dependent heterogeneity defies the traditional M1/M2 dichotomy. In this review, we propose the ‘niche–metabolism axis’ framework, deconstructing the tumor microenvironment into dynamically interacting functional niches (e.g., hypoxic cores and tertiary lymphoid structures). Within these niches, specific physicochemical stresses substantially influence localized TAM metabolic reprogramming. Metabolites such as lactate and lipids act not merely as substrates but as signaling mediators and epigenetic donors, shaping TAM phenotypes. Consequently, TAMs acquire spatial metabolic imprints and evolve into ‘ecosystem engineers’ that actively remodel the immune microenvironment. This framework highlights that therapeutic paradigms should shift from nonselective TAM depletion to niche-specific metabolic–epigenetic reconstruction, providing a precise roadmap for designing next-generation engineered macrophage therapies.

Nonclassical major histocompatibility complex class I (MHC-I) molecules, including human leukocyte antigen E (HLA-E), HLA-F, HLA-G, MHC-I-related protein 1 (MR1), and the CD1 family, constitute a conserved antigen-presenting system that regulates immune surveillance, tissue homeostasis, and tolerance through specialized interactions with innate and unconventional T cells. Although these molecules have long been implicated in cancer, infection, autoimmunity, and transplantation, their distinct immunobiology and therapeutic potential have largely been considered in isolation. Recent advances in structural immunology, single-cell and spatial profiling, engineered immune cell technologies, and early clinical studies have established nonclassical MHC-I pathways as tractable targets for immunotherapy. In this review, we synthesize the biology, disease-associated functions, and therapeutic targeting of these molecules, integrating immune checkpoint blockade, antibody-based therapeutics, and MR1- and CD1-restricted cellular immunotherapies into a unified framework. We further highlight shared immunological principles, emerging clinical translation, and opportunities for universal, off-the-shelf immune interventions.

Fungal infections cause millions of deaths, yet clinical antifungals span only three drug classes. Koch et al. discover formicitoxins—35 venom peptides from carpenter ants—which are the first from any formicine species. Two outperform voriconazole in vitro and delay infection in vivo. Formicitoxins disrupt fungal membranes independently of existing drug targets.

Skeletal development, maintenance, and repair require precise control of protein production, yet mRNA levels often correlate poorly with protein abundance. Translation is the process through which mRNA is converted into protein, but its role in skeletal biology remains much less understood than that of transcriptional regulation. Recent advances in translatomics have begun to reveal how translational regulation contributes to skeletal development, homeostasis, and repair. Here, we summarize translational control across skeletal lineages, developmental stages, and disease settings. We also discuss emerging approaches for studying mRNA translation and potential therapeutic opportunities that target translational pathways. Understanding how translational regulation shapes skeletal health and disease will open new avenues for precise interventions for skeletal defects.

The unclear regulatory and transport mechanisms of Kirsten rat sarcoma viral oncogene homolog (KRAS) limit a comprehensive understanding of KRAS activity and the development of inhibitors. Wang et al. reported that farnesylation-induced KRAS phase separation drives colon cancer progression and resistance to G12C inhibitors. Statins can block this process, suppress tumor growth, and reverse drug resistance.

Cancer cachexia has long been attributed to circulating factors. Cross et al. now show that, in liver kinase B1 (Lkb1)-mutant lung tumors, local prostaglandin E2 acts on vagal neurons to drive anorexia and wasting, accelerated by fat. Defining metaboception as neural sensing of local signals—a new therapeutic concept.

Fungal infections cause millions of deaths, yet clinical antifungals span only three drug classes. Koch et al. discover formicitoxins—35 venom peptides from carpenter ants—which are the first from any formicine species. Two outperform voriconazole in vitro and delay infection in vivo. Formicitoxins disrupt fungal membranes independently of existing drug targets.

Skeletal development, maintenance, and repair require precise control of protein production, yet mRNA levels often correlate poorly with protein abundance. Translation is the process through which mRNA is converted into protein, but its role in skeletal biology remains much less understood than that of transcriptional regulation. Recent advances in translatomics have begun to reveal how translational regulation contributes to skeletal development, homeostasis, and repair. Here, we summarize translational control across skeletal lineages, developmental stages, and disease settings. We also discuss emerging approaches for studying mRNA translation and potential therapeutic opportunities that target translational pathways. Understanding how translational regulation shapes skeletal health and disease will open new avenues for precise interventions for skeletal defects.

Early lung tumorigenesis depends not only on mutant clones but also on tumor-promoting niches that remain difficult to detect. In Cell, Pandya et al. identify a 14-protein plasma signature that predicts lung cancer years before diagnosis, report interleukin-1β-linked alveolar remodeling, and position tumor promotion as a target for precision prevention.

Interindividual variability in response to cancer therapy is a major challenge in the management of colorectal cancer (CRC). The gut microbiome contributes to differential therapeutic efficacy and toxicity by modifying the pharmacokinetics and pharmacodynamics of anticancer drugs. Furthermore, bacterial products interact with tumor and immune cells, altering therapeutic outcomes. This review focuses on the impact of pharmacomicrobiomics on CRC therapy. We describe how gut microbiota affects drug metabolism on a mechanistic level and outline the interactions of specific microbes and their products with chemo-, targeted, and immunotherapies employed in CRC. Finally, we provide an overview of current strategies, including probiotics, engineered bacteria, and fecal microbiota transplantation, that exploit the gut microbiome to improve therapeutic efficacy and reduce toxicity.

The unclear regulatory and transport mechanisms of Kirsten rat sarcoma viral oncogene homolog (KRAS) limit a comprehensive understanding of KRAS activity and the development of inhibitors. Wang et al. reported that farnesylation-induced KRAS phase separation drives colon cancer progression and resistance to G12C inhibitors. Statins can block this process, suppress tumor growth, and reverse drug resistance.

Cancer cachexia has long been attributed to circulating factors. Cross et al. now show that, in liver kinase B1 (Lkb1)-mutant lung tumors, local prostaglandin E2 acts on vagal neurons to drive anorexia and wasting, accelerated by fat. Defining metaboception as neural sensing of local signals—a new therapeutic concept.

Early lung tumorigenesis depends not only on mutant clones but also on tumor-promoting niches that remain difficult to detect. In Cell, Pandya et al. identify a 14-protein plasma signature that predicts lung cancer years before diagnosis, report interleukin-1β-linked alveolar remodeling, and position tumor promotion as a target for precision prevention.

Interindividual variability in response to cancer therapy is a major challenge in the management of colorectal cancer (CRC). The gut microbiome contributes to differential therapeutic efficacy and toxicity by modifying the pharmacokinetics and pharmacodynamics of anticancer drugs. Furthermore, bacterial products interact with tumor and immune cells, altering therapeutic outcomes. This review focuses on the impact of pharmacomicrobiomics on CRC therapy. We describe how gut microbiota affects drug metabolism on a mechanistic level and outline the interactions of specific microbes and their products with chemo-, targeted, and immunotherapies employed in CRC. Finally, we provide an overview of current strategies, including probiotics, engineered bacteria, and fecal microbiota transplantation, that exploit the gut microbiome to improve therapeutic efficacy and reduce toxicity.

New/suddenly worsened Raynaud’s phenomenon plus:

New/suddenly worsened Raynaud’s phenomenon plus:

Ferroptosis has emerged as a critical contributor to secondary brain injury in cerebrovascular diseases (CVDs). However, the clinical translation of antiferroptotic therapies remains stalled because current strategies often treat CVDs as a uniform entity, neglecting profound pathophysiological heterogeneity. In this review, we propose a pathology-guided framework mapping distinct ferroptotic cascades across CVDs. We delineate how ischemic stroke hinges on endogenous iron retention and the collapse of nuclear factor erythroid 2-related factor 2 antioxidant defenses, whereas hemorrhagic stroke is triggered by acute exogenous heme influx. Furthermore, chronic hypoperfusion in vascular dementia lowers the threshold for oligodendrocyte ferroptosis. By deconstructing these subtype-specific mechanisms—from iron overload modes to lipid vulnerability—we emphasize a paradigm shift for CVD: advancing precision medicine requires mechanism-stratified, context-dependent interventions rather than uniform ferroptosis inhibition.

Ferroptosis has emerged as a critical contributor to secondary brain injury in cerebrovascular diseases (CVDs). However, the clinical translation of antiferroptotic therapies remains stalled because current strategies often treat CVDs as a uniform entity, neglecting profound pathophysiological heterogeneity. In this review, we propose a pathology-guided framework mapping distinct ferroptotic cascades across CVDs. We delineate how ischemic stroke hinges on endogenous iron retention and the collapse of nuclear factor erythroid 2-related factor 2 antioxidant defenses, whereas hemorrhagic stroke is triggered by acute exogenous heme influx. Furthermore, chronic hypoperfusion in vascular dementia lowers the threshold for oligodendrocyte ferroptosis. By deconstructing these subtype-specific mechanisms—from iron overload modes to lipid vulnerability—we emphasize a paradigm shift for CVD: advancing precision medicine requires mechanism-stratified, context-dependent interventions rather than uniform ferroptosis inhibition.

Cartilage is susceptible to degeneration from injury, overuse, or age-related wear. Articular cartilage, the smooth hyaline cartilage covering the ends of bones in synovial joints, has limited intrinsic repair capacity because its avascular, aneural, and alymphatic matrix contains sparse, low-proliferative chondrocytes, allowing matrix damage to persist and drive joint dysfunction and osteoarthritis. Most therapies relieve symptoms without reliably restoring durable cartilage architecture. Recent advances in cell-based therapy, matrix-associated chondrocyte implantation, engineered scaffolds, controlled-release biologics, and quantitative clinical endpoints have shifted the field toward mechanism-based cartilage regeneration. In this feature review, we assess emerging clinical evidence across cell-based strategies, biomaterial- and scaffold-assisted repair, biologics, and combination approaches. We emphasize integrated, multimodal approaches and standardized outcome measures as essential for achieving durable cartilage repair and true disease modification.

Cartilage is susceptible to degeneration from injury, overuse, or age-related wear. Articular cartilage, the smooth hyaline cartilage covering the ends of bones in synovial joints, has limited intrinsic repair capacity because its avascular, aneural, and alymphatic matrix contains sparse, low-proliferative chondrocytes, allowing matrix damage to persist and drive joint dysfunction and osteoarthritis. Most therapies relieve symptoms without reliably restoring durable cartilage architecture. Recent advances in cell-based therapy, matrix-associated chondrocyte implantation, engineered scaffolds, controlled-release biologics, and quantitative clinical endpoints have shifted the field toward mechanism-based cartilage regeneration. In this feature review, we assess emerging clinical evidence across cell-based strategies, biomaterial- and scaffold-assisted repair, biologics, and combination approaches. We emphasize integrated, multimodal approaches and standardized outcome measures as essential for achieving durable cartilage repair and true disease modification.

Rabies is a lethal acute viral encephalitis caused by neurotropic lyssaviruses, particularly Lyssavirus rabies. The current treatment for rabies exposure involves post-exposure prophylaxis (PEP), which includes the administration of the rabies vaccine and rabies immunoglobulins (RIGs). No effective treatments exist to cure symptomatic rabies. Due to the limited availability and high cost of PEP, tens of thousands of deaths still occur worldwide every year. Monoclonal antibodies (mAbs) represent an effective and economical alternative to RIGs. Moreover, recent preclinical studies have provided evidence that monoclonal antibodies can effectively treat symptomatic rabies, overcoming mechanisms of viral immune evasion. In this review, we critically summarize recent studies, focusing on the treatment of rabies exposures using monoclonal antibodies and the potential of monoclonal antibody-based therapies to combat symptomatic rabies.

Horizontal mitochondrial transfer (HMT) outcomes are shaped by donor fitness and transfer context. We propose a post-transfer quality checkpoint that integrates membrane potential, oxidative damage, mitophagy, fusion, and fission to determine the recipient-cell’s response. Depending on donor quality and recipient thresholds, HMT may drive bioenergetic restoration, inflammation, or tumor immune escape. This framework extends route-centered accounts of HMT toward a testable, quality-governed model for therapeutic intervention.

Rabies is a lethal acute viral encephalitis caused by neurotropic lyssaviruses, particularly Lyssavirus rabies. The current treatment for rabies exposure involves post-exposure prophylaxis (PEP), which includes the administration of the rabies vaccine and rabies immunoglobulins (RIGs). No effective treatments exist to cure symptomatic rabies. Due to the limited availability and high cost of PEP, tens of thousands of deaths still occur worldwide every year. Monoclonal antibodies (mAbs) represent an effective and economical alternative to RIGs. Moreover, recent preclinical studies have provided evidence that monoclonal antibodies can effectively treat symptomatic rabies, overcoming mechanisms of viral immune evasion. In this review, we critically summarize recent studies, focusing on the treatment of rabies exposures using monoclonal antibodies and the potential of monoclonal antibody-based therapies to combat symptomatic rabies.

Extracellular vesicles (EVs) are promising liquid biopsy candidates for gastric cancer because they can capture tumor-, immune-, microbial-, and microenvironment-related signals. We argue that the main challenge is no longer simply to find more candidates but to advance EV biomarkers with demonstrated diagnostic, therapeutic-monitoring, or prognostic value toward clinical translation. In this opinion article, we highlight EVs from nonblood biofluids, non-tumor-derived EVs, and underexplored EV cargo types, particularly small noncoding RNA cargoes, as sources of biomarker potential. We further identify insufficient clinical evidence, technical bottlenecks, and incomplete quality-control and regulatory standards as key barriers to their clinical deployment.

Horizontal mitochondrial transfer (HMT) outcomes are shaped by donor fitness and transfer context. We propose a post-transfer quality checkpoint that integrates membrane potential, oxidative damage, mitophagy, fusion, and fission to determine the recipient-cell’s response. Depending on donor quality and recipient thresholds, HMT may drive bioenergetic restoration, inflammation, or tumor immune escape. This framework extends route-centered accounts of HMT toward a testable, quality-governed model for therapeutic intervention.

Extracellular vesicles (EVs) are promising liquid biopsy candidates for gastric cancer because they can capture tumor-, immune-, microbial-, and microenvironment-related signals. We argue that the main challenge is no longer simply to find more candidates but to advance EV biomarkers with demonstrated diagnostic, therapeutic-monitoring, or prognostic value toward clinical translation. In this opinion article, we highlight EVs from nonblood biofluids, non-tumor-derived EVs, and underexplored EV cargo types, particularly small noncoding RNA cargoes, as sources of biomarker potential. We further identify insufficient clinical evidence, technical bottlenecks, and incomplete quality-control and regulatory standards as key barriers to their clinical deployment.