搜索结果：Science progress

Exosomes, as key mediators of intercellular communication, carry microRNAs (miRNAs) that play central roles in anticancer drug resistance by regulating the immune status of the tumor microenvironment (TME) and drug-metabolic pathways. In recent years, advances in single vesicle analysis have greatly promoted mechanistic studies on exosomal miRNAs in diffuse large B-cell lymphoma (DLBCL). This article aims to comprehensively review recent advances in the study of exosomal miRNAs in DLBCL. This review explores the value of exosomal miRNAs as tumor biomarkers in diagnosis and prognostic evaluation of DLBCL, and provides an in-depth analysis of molecular networks underlying DLBCL drug resistance mediated through exosomal miRNAs. This study conducted a literature review by searching the PubMed and Web of Science databases to identify the latest research findings regarding the roles of exosomal miRNAs as tumor biomarkers in diagnosis and prognostic evaluation of DLBCL, and the mechanisms by which exosomal miRNAs regulates DLBCL drug resistance. Based on these findings, a narrative review was generated. This article introduces the biogenesis of exosomal miRNA and research progress on exosomal miRNAs as biomarkers in the diagnosis and prognosis of DLBCL. It summarizes the research progress on the mechanisms of exosomal miRNA in regulating therapeutic resistance in DLBCL. And it also discusses the current translational studies using exosomal miRNAs to control drug resistance in DLBCL, and challenges of using extracellular vesicle (EV)-derived miRNAs. These advances will help provide more new strategy for reversing DLBCL drug resistance in the future. Exosomal miRNAs can serve as biomarkers for the diagnosis and prognostic assessment of DLBCL and are associated with DLBCL treatment resistance. Currently, there has been significant progress in research on the mechanisms by which exosomal miRNAs regulate DLBCL resistance, with some mechanisms already validated. It is expected that through more in-depth in vivo and in vitro studies in the future, mature therapeutic targets can be developed.

Ancient DNA (aDNA) research has revolutionised archaeology and forensic science by enabling genomic recovery from highly degraded remains. This review explores the biochemical and environmental factors influencing aDNA preservation, alongside methodological advances that have improved data yield and authenticity. Techniques such as next-generation sequencing (NGS), single-stranded library preparation, and hybridisation capture have transformed the field, allowing recovery from ultrashort fragments and challenging contexts such as warm climates. Authentication strategies-including cytosine deamination profiling, fragment length analysis, and rigorous contamination controls-remain essential to ensure reliability. Applications of aDNA extend beyond ancestry reconstruction and population genetics to include forensic identification, kinship analysis, and pathogen detection. Lessons from forensic genetics, such as stringent validation and contamination mitigation, have informed best practices in archaeological contexts. However, ethical considerations are central to both domains. Issues of Indigenous data sovereignty, consent, repatriation, and culturally sensitive interpretation demand transparent, community-led research frameworks. These principles align with international agreements such as the Nagoya Protocol and emerging guidelines for equitable benefit-sharing. Despite significant progress, challenges persist, including geographic sampling bias, interpretive uncertainty, and the need for interdisciplinary integration. Future directions emphasise long-read sequencing, metagenomic approaches, and artificial intelligence-driven analytics, alongside robust ethical governance. By combining technological innovation with culturally responsible practices, aDNA research continues to advance our understanding of human history while reinforcing the importance of ethical stewardship in forensic and archaeological science.

Although progress towards implementation of international agreements since publication of the UCL-Lancet Commission on Migration and Health in December, 2018, has been slow, global trends in migration and forced displacement have continued to rise. However, the COVID-19 pandemic showed that reaching refugees and migrants with health interventions is feasible with political will. The benefits of refugee-inclusive and migrant-inclusive health-care systems during emergencies (eg, COVID-19 and the war in Ukraine) are apparent, with numerous examples of inclusive policy making being rapidly introduced and innovative models developed to support health-care access, including preventive measures such as vaccination. Lessons from these successes should be learned and incorporated into future policy and practice. However, global political and financial uncertainty and disruption-combined with multiple conflicts and natural disasters-have increased individuals' need to move, which will continue to be exacerbated by the climate crisis. Although new conflicts and exacerbations of existing ones have led to a rise in forced displacement within and across national borders, labour migration has also risen dramatically, with the pandemic highlighting the health and social needs of these groups globally. The need for strong leadership and accountability, engagement of policy makers in the highest-level fora, and improved access to quality health services for refugees and migrants has never been greater. In this Review, nearly 8 years after the UCL-Lancet Commission on Migration and Health was published, we renew our call for action to: (1) improve health-care access and optimise outcomes for refugees and migrants by emphasising health in all migration and forced displacement policies; (2) establish data systems to monitor progress, together with appropriate use of new technologies to improve access, prevent harm, and safeguard privacy; (3) support research on adaptation to and mitigation of the health consequences of climate change on refugees and migrants; and (4) renew focus on the political determinants of health outcomes for people on the move. At this pivotal moment, with geopolitical, sociodemographic, and environmental turmoil, political leaders and societies can shape a better future by leveraging the human capital of migrants and upholding the human rights and dignity of all.

We discuss a recent controversy that occurred in The Cognitive Behavioural Therapist over whether Lilienfeld's critical views on microaggressions theory and research reflect racist beliefs, as alleged by some. This is one of many recent examples of a profoundly antiscientific practice whereby racism allegations chill scientific debate and open inquiry on important research issues. This produces an overtly politicized science that has a corrosive effect on scientific progress and ultimately the useful application of research in clinical practice. The microaggressions controversy provides an especially useful vehicle for challenging this state of affairs given the widespread application of microaggressions theory, including in clinical practice and other applied areas of psychology. Additionally, the arguments made as to why Lilienfeld's critique is racist parallel arguments made by many to claim that other areas of psychological science and practice are also racist. We challenge some of these common arguments and point to a more productive way forward for advancing clinical psychological science and the delivery of effective psychotherapeutic services, especially cognitive behavioral therapy.

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are rare yet life-threatening severe cutaneous adverse drug reactions (SCARs), characterized by high mortality and substantial morbidity risks. Identifying potential high-risk drugs associated with SJS/TEN is crucial for guiding clinical preventive interventions, enabling early detection, and enhancing risk management. With the rapid advancement of data science, adverse drug reaction (ADR) database mining has emerged as a powerful tool for systematically investigating the drug-SJS/TEN association, effectively overcoming the limitations of traditional case reports and small-sample studies regarding data scale and conclusion generalizability. This review summarizes recent advances in identifying potential high-risk drugs for SJS/TEN based on ADR database mining, with all included studies retrieved from peer-reviewed journals and strictly focused on SJS/TEN. We classify and discuss the major potential high-risk drug categories, including antibiotics, antiepileptics, allopurinol, nonsteroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), immune checkpoint inhibitors (ICIs), novel antiandrogens, carbonic anhydrase inhibitors, antivirals, and others. We also summarize their associated genetic susceptibilities, median onset times, and underlying mechanisms. These findings provide valuable references for enhancing medication safety and mitigating severe adverse drug reactions in clinical practice.

Open and reproducible research in materials science relies on the availability of data, code, and established metadata standards. Journal research data policies (RDPs) are a primary mechanism by which these community norms are enforced. We survey RDPs for 171 materials science journals spanning 17 publishers, using an expanded coding framework that captures both data-and-code sharing behavior as well as refereeing standards. We find clear signs of progress in comparison to earlier research on RDPs: nearly all journals provide an RDP, and most mention data availability statements. However, enforceable requirements remain uncommon, public deposition of underlying data is rarely mandatory, and FAIR publication is typically encouraged rather than required. Expectations for research software are substantially less developed than those for data, with limited attention to versioning and persistent identifiers, dependency disclosure, reproducible execution environments, or software quality practices. Aggregating the findings on policy features into an open research data score reveals pronounced heterogeneity across journals. Neither impact factor nor access model reliably predicts policy strength. Double-coding further shows that more complex policies and stricter policies can be more challenging to interpret consistently, and we highlight challenges in consistent RDP encoding across studies. Lastly, we conclude with recommended best practice directions for the future.

Exposure to high altitude can cause acute mountain sickness (AMS) characterized by headache, gastrointestinal symptoms, dizziness and fatigue, which may progress to life-threatening conditions like high-altitude cerebral edema (HACE). Although the pathophysiology and development of AMS have been intensely investigated, the risk factors and underlying mechanisms remain incompletely understood. In addition, objective criteria for the diagnosis of AMS and reliable biomarkers are missing. Here we provide an overview of the molecular and pathophysiological foundations of AMS and review which potential biomarkers have been suggested and in combination with which physiological and psychological correlates of AMS they could improve diagnosis. Moreover, we point out current knowledge gaps and discuss which future research is required to enable AMS diagnosis based on more objective biomedical and psychophysical criteria. Emphasizing the apparent heterogeneity in AMS pathogenesis, we support the classification of different AMS subtypes according to etiological parameters. We propose the hypothesis that both insufficient and excessive hypoxia responses can cause AMS and that the differentiation according to these divergent mechanisms might allow the identification of AMS subtypes that can be characterized better using biomarkers and correlates of AMS.

Indirect transmission of viruses via contaminated surfaces highlights the need for effective antiviral coatings. Recent advances have led to the development of diverse surface engineering strategies, including organic (polymer- and peptide-based) and inorganic (metal-based) coatings. While polymer and peptide-based systems have been extensively explored in the antibacterial field, their application in antiviral coatings remains underexplored despite their demonstrated ability to reduce viral titers. This minireview provides a mechanistically informed overview of polymer- and peptide-based antiviral surface coatings. We summarize recent studies with a focus on coating materials, methods, physicochemical characterization techniques, target viruses, and antiviral performance. In addition, we critically evaluate key limitations in the field, including the lack of standardized testing protocols, restricted diversity of surfaces and viruses, and insufficient assessment of coating durability and cytotoxicity. Finally, we discuss future directions focused on standardized and rationally designed evaluation frameworks to support the practical translation of antiviral coatings.

Protein amyloid fibrils (AFs) have garnered significant attention in the food industry. However, the acid-thermal preparation method has obvious limitations, such as harsh reaction conditions and poor product homogeneity. Therefore, this review aimed to summarize recent research advances in the formation of AFs from various source proteins, with a focus on innovative strategies for optimizing preparation conditions. It also provided an in-depth analysis of the regulatory mechanisms governing the formation of AFs, influenced by environmental factors such as pH, ionic types and strength, heat conditions, and interactions between substances. The kinetic characteristics and morphological evolution of the AFs assembly process were elucidated at the molecular level. The overview of aforementioned formation mechanism lays theoretical foundation for the precise regulation of the functional properties of AFs. Furthermore, thanks to their excellent functional properties, AFs are increasingly applied and play a crucial in fields such as materials science, biomedicine, and food innovation. Therefore, this review presented the latest research trends and application prospects of AFs in these fields. Finally, while comprehensively analyzing the technical advantages, this review also objectively pointed out challenges in recent investigations, including difficulties in large-scale production and insufficient safety assessment, and put suggestions for development suggestions. This review provides valuable theoretical basis and technical reference for the efficient preparation of AFs from edible proteins through modification or environmental regulation strategies. It also holds its significant research value and broad application potential in the development of novel functional materials, personalized food products, and related fields.

With rapid global population growth and worsening sustainable food crises, plant-based dietary patterns are expanding, spurring exploration of high-quality plant proteins. Walnut, a globally cultivated nut, produces defatted walnut meal as a by-product during oil processing, with a high protein content of 50-70%. However, walnut protein's industrial application is in the initial phase due to high glutelin content causing poor solubility/stability and incomplete understanding of functional property regulatory mechanisms. This review integrates recent knowledge on walnut proteins to form a framework covering structural characterization, extraction methods, biological activity and multiple application scenarios. Meanwhile, future research directions for walnut proteins include green/efficient/large-scale production, precise structure-activity characterization of bioactive peptides, and interaction mechanisms in complex food systems. By integrating these research dimensions, this work strengthens the correlation analysis across different research links and clarifies current technical bottlenecks along with future innovation directions. Consequently, it serves as a practical reference for the efficient utilization of walnut protein resources and the development of the plant-based protein industry.

暂无摘要（点击查看详情）

Ventilator-induced lung injury (VILI) causes 40-45% mortality in acute respiratory distress syndrome (ARDS) despite lung-protective ventilation. Current therapies remain empirical, lacking mechanistic understanding of how cells transduce mechanical forces into pathological responses. The mechanosensitive ion channel Piezo1 has emerged as a critical mechanotransducer, yet exhibits a fundamental paradox: endothelial Piezo1 deletion worsens edema while excessive activation disrupts barriers and triggers inflammatory cell death. Conventional "protective versus injurious" frameworks cannot explain these opposing outcomes. We propose the "Context-Dependent Rheostat" model, wherein Piezo1 outcomes depend on mechanical dose, cellular context, and inflammatory milieu. This review synthesizes evidence demonstrating that Piezo1 responses exhibit quantitative inflection points rather than fixed directional effects, with temporal dynamics, cell-type-specific thresholds, and inflammatory priming determining functional transitions. Specifically, endothelial cells preserve barrier integrity within a wider strain tolerance window, whereas epithelial cells exhibit substantially narrower damage thresholds; acute stretch activates protective chromatin remodeling, while sustained ventilation drives ataxia telangiectasia and Rad3-related/checkpoint kinase 1 (ATR/Chk1)-mediated genomic collapse and cellular senescence. Beyond cell-autonomous responses, macrophages emerge as candidate signal-hub cells integrating mechanosensory inputs from endothelial, epithelial, and neutrophil compartments, representing a high-value therapeutic node. This framework fundamentally reframes VILI therapeutics from global Piezo1 modulation toward precision interventions: temporal stage-specific targeting, context-specific threshold resetting, and biomarker-guided stratification. Candidate strategies span nuclear factor erythroid 2-related factor 2 (NRF2) activators for early-phase cytoprotection, Toll-like receptor 4 (TLR4) antagonism, and ATR/Chk1 inhibitors or senolytic combinations for late-phase intervention, guided by circulating DNA-damage marker γH2AX and senescence-associated secretory phenotype markers. We provide a translational roadmap enabling VILI therapy to transition from empirical ventilation adjustment toward mechanistically-guided precision medicine with actionable intervention points.

BackgroundDespite substantial global progress in HIV prevention and treatment, mother-to-child transmission (MTCT) of HIV remains a major public health challenge in sub-Saharan Africa, which accounts for approximately 65% of the world's 39.9 million people living with HIV. Vertical transmission rates vary substantially across regions and over time. We conducted a systematic review and meta-analysis to estimate the overall, temporal, regional, and country level prevalence of HIV MTCT in sub-Saharan Africa.MethodsThis research was conducted between June 2024 and May 2025, in accordance with PRISMA guidelines and a protocol registered in PROSPERO (CRD42025637989). We systematically searched six databases (MEDLINE, Embase, PubMed, ScienceDirect, Web of Science, and the Cochrane Library) for articles published in English or French. We included cross-sectional, cohort, and case-control studies involving HIV-positive pregnant women aged &#x2265;18 years that reported MTCT prevalence. Two reviewers independently screened, extracted data, and assessed study quality (Joanna Briggs Institute and Newcastle-Ottawa Scale). Pooled prevalence and 95% CI were calculated using a random-effects model in STATA 17. Heterogeneity (I2), subgroup analyses (by period, region, country), sensitivity analysis, and funnel plots for publication bias were performed.ResultsFrom 5,848 records, 48 studies (86,376 mothers; 2,875,104 infants) across 15 countries were included. The pooled MTCT prevalence was 7.0% (95% CI 5.2-9.4%; I2 = 99.1%). Temporal trends showed a decline from 26.0% (1993-2000) to 8.0% (2001-2010) and 5.0% (2011-2023). Regionally, West Africa had the highest prevalence (12.1%; 95% CI 6.5-21.6%), Southern Africa had the lowest (4.7%; 95% CI 2.6-8.1%). Approximately 9% of HIV-exposed infants were infected by 24-48 months, 6% were infected by 24 months after enrolment, and 7% tested positive at their first HIV test conducted between 1 and 12 weeks of age.ConclusionAlthough MTCT rates have declined, the current 7.0% remains above the WHO target (<5%) with noted significant regional and national disparities. However, this rate should be interpreted cautiously due to the extremely high heterogeneity (I2 = 99.1%) knowing it's a directional synthesis of available evidence rather than a precise population-level figure.

Structural neuroplasticity supports learning, development, and shapes vulnerability to brain disorders, making it a central priority in neuroscience research. However, progress in humans has remained limited by the inability to probe cellular processes in vivo, leaving mechanistic insight largely dependent on animal models. To address this gap, here we combined the sub-voxel sensitivity of ultra-high-gradient diffusion MRI with the cell-compartment specificity of the Soma and Neurite Density Imaging (SANDI) model to probe structural plasticity directly in the living human brain. By tracking how learning modulates the temporal dynamics of cell bodies and cell processes, we aimed to distinguish plastic from nonplastic biological processes driving changes in microstructure. We found that learning a motor skill triggered two distinct temporal responses: a transient expansion of cell bodies across all brain regions engaged by the task, consistent with a short-lived homeostatic mechanism, and a sustained increase in cell-process density restricted to key motor regions, consistent with structural plasticity. Our approach provides a mechanistic window into human neuroplasticity and marks a significant step toward bridging the gap between animal and human neuroscience.

Scutellaria baicalensis, a perennial herb belonging to the genus Scutellaria (Lamiaceae), has dried roots that are widely used as a traditional Chinese medicinal herb known as "Huangqin". As one of the major chemical constituents of S. baicalensis, its polysaccharides exhibit diverse biological activities, including immunomodulatory effects, regulation of gut microbiota, antioxidant activity, hypoglycemic effects, anti-inflammatory activity, and antimicrobial properties. Modern pharmacological studies have further confirmed the intrinsic relationship between these activities and traditional therapeutic uses at the molecular level, while also revealing their potential applications in functional foods, dietary supplements, and food additives, thereby providing scientific support for the modernization and application of traditional medicine. To systematically summarize the latest research progress on the extraction, isolation, purification, structural characterization, and biological activities of Scutellaria baicalensis polysaccharides (SBP), and to explore their structure-activity relationships and potential research directions, with the aim of supporting their further development and application in the pharmaceutical and functional food industries. Following the PRISMA guidelines, relevant studies were systematically retrieved from PubMed, Web of Science, and CNKI databases, and the latest advances in the extraction, purification, structural characterization, and biological activities of SBP were comprehensively reviewed. Various extraction methods have been established, including hot water extraction, ultrasound-assisted extraction, and microwave-assisted extraction, among which the Sevag method is commonly employed for deproteinization during purification. Structural studies have primarily focused on monosaccharide composition, molecular weight, and glycosidic linkage patterns. Pharmacological studies have demonstrated that these polysaccharides possess multiple biological activities, including immunomodulatory, antioxidant, hypoglycemic, anti-inflammatory, antimicrobial, and gut microbiota-regulating effects. Structure-activity relationship studies indicate that the biological activities of SBP are collectively determined by their multi-level fine structures, including molecular weight, monosaccharide composition, types and patterns of glycosidic linkages, and higher-order spatial conformations, all of which play critical roles in their biological functions. Considerable progress has been achieved in the extraction, purification, structural characterization, and biological evaluation of SBP, demonstrating promising pharmacological potential in immunomodulation, anti-inflammatory activity, and metabolic regulation. However, their higher-order structural characteristics, the structure-activity relationships between specific structural motifs and biological activities, as well as in vivo processes such as bioavailability and metabolic fate, still require further investigation.

Endometriosis is a chronic condition in which tissue similar to the lining of the uterus grows in other parts of the body. It affects roughly 1 in 10 women of reproductive age, often causing severe pelvic pain and infertility. Despite how common it is, patients frequently wait nearly a decade for an accurate diagnosis, and current treatments often rely on trial and error rather than targeted science. This review simplifies the complex biologic "blueprint" of the disease to explain why it behaves the way it does. Recent research shows that endometriosis is more than a one-dimensional hormonal imbalance; it involves several key biologic factors, including genetic drivers, hormonal status, and physical changes such as neuroangiogenesis or fibrosis. Currently, no simple laboratory test or biomarker can predict how the disease will progress, largely because of the heterogeneity and small, retrospective nature of studies. To move toward personalized medicine, larger, more diverse studies that connect each patient's specific genetic profile to their symptoms and disease phenotype are needed. By mapping these molecular details, we can progress toward faster diagnoses, tailored care to each individual's disease burden, and recurrence risk stratification and surgical planning based on molecular characteristics.

Background&#xD;Intervertebral disc (IVD) degeneration is a common chronic disease and may lead to disc herniation. Microdiscectomy removes the herniated tissue, but cannot address altered IVD biomechanics or restore annulus fibrosus (AF) structural integrity. With the development of tissue engineering, AF repair has shown potential in preclinical studies. However, these studies have not been reviewed from a practical experimental perspective, particularly focusing on animal models and evaluation methods. Therefore, this review aims to summarise and compare tissue-engineered AF repair strategies from the past decade and propose guidance for more standardised AF repair assessment.&#xD;Methods&#xD;This scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidance covering studies from 2015 to 2025, a decade marked by rapid advancements in AF repair biomaterials. The search terms used were: ("annulus-fibrosus-repair" OR "intervertebral-disc-repair" OR "annular closure" OR "intervertebral disc regeneration" OR "annulus fibrosus regeneration") AND ("in vitro" OR "in vivo" OR "comput*" OR "animal model" OR "biomechanic*"). Data were collected from Web of Science and PubMed databases.&#xD;Results&#xD;Ninety-nine records were identified from PubMed and 155 from Web of Science in October 2025. After screening, 48 studies were included, demonstrating significant progress in biomaterial-driven AF repair. However, considerable variation was found in animal model selection, defect creation, and evaluation methods, limiting direct comparison across studies. In particular, AF defect sizes were often not consistently scaled to animal disc geometry. Accordingly, this review suggested geometrically scaled defect size ranges for common animal models. In addition, energy dissipation was identified as an important but rarely quantified marker of IVD viscoelastic restoration.&#xD;Conclusion&#xD;This review provides practical guidance on animal model selection, AF defect size, and proposes an evaluation checklist for future AF repair studies. More standardised and physiologically relevant assessment is needed to improve cross-study comparison and support clinical translation.

Increasing evidence suggests that microbiota plays important roles in the pathogenesis and progression of interstitial lung diseases (ILDs). However, the global research landscape and emerging trends in this field remain insufficiently characterized. This study aimed to systematically characterize the research landscape, evolving hotspots, and future trends in the field of host microbiota and ILDs using bibliometric and visualization approaches, and to further explore the progress of related clinical studies. Publications up to November 8, 2025 were retrieved from the Web of Science Core Collection. Concurrently, clinical trials within the same timeframe were extracted from PubMed to assess advancements in the field. Bibliometric and visual analyses were conducted using VOSviewer, CiteSpace, SCImago Graphica, and Microsoft Excel. A total of 295 publications were included, showing a marked increase in research output since 2012. China and the United States were the leading contributors, with the United States demonstrating higher academic impact and stronger international collaboration. Core institutions and authors were mainly concentrated in North America and Europe. Keyword analysis revealed a clear evolution of research focus, shifting from early exposure-related studies and hypersensitivity pneumonitis to lung microbiome dysbiosis, the gut-lung axis, and metagenomic approaches. Recent hotspots emphasize microbiome-based clinical applications, with increasing attention to host-microbiome interactions and immune regulatory mechanisms. Research on microbiota and ILDs has expanded rapidly and shows increasing interdisciplinary integration. Future studies should enhance international collaboration, clarify underlying mechanisms, and promote clinical translation of microbiome-based biomarkers and personalized therapeutic strategies.

Gastrointestinal (GI) cancers are one of the leading causes of cancer death in the world. Since it is often not diagnosed early, it typically becomes resistant to chemotherapy, and genetic alterations in tumors are associated with metabolic remodeling, inflammatory reactions, and immunological evasion. Systemic therapies have improved yet sustained responses in progressive GI disease have not been obtained and require mechanism-directed approaches. Betulinic acid (BA) is an anticancer agent with low normal cell toxicity that exhibits selectivity and is obtained naturally as a pentacyclic triterpenoid. Preclinical results show that BA induces mitochondrial apoptosis, inhibits the PI3K/Akt and NF-&#x3ba;B pathways, inhibits epithelial-mesenchymal transition, and reverses cancer stemness, thereby creating resistance. There are comparative data in favor of pancreatic and colorectal cancers, with strong, validated, and effective data from aggressive disease models; data on gastric cancer accumulate through inflammation and by regulating stemness; esophageal data are preliminary. Nano-delivery is the answer to BA's low solubility and bioavailability, but it still faces challenges related to scale, long-term safety, and regulation. In fact, translational gaps are more about formulation than efficacy, providing a path to optimization, stratification, and clinical progress in GI cancers.