搜索结果：Tissue barriers

Infertility affects millions of women worldwide, and despite current treatment options, definitive therapies remain limited. Emerging regenerative medicine strategies, particularly stem cell therapy and three-dimensional (3D) bioprinting, offer significant potential to repair and regenerate female reproductive tissues. In this scoping review, 199 studies, including in vitro experiments, animal models, and early-stage clinical investigations, were analyzed to evaluate scientific advancements and translational potential in female reproductive tissue engineering. The focus was on stem cell sources, the development of bioinks, and the applications of 3D bioprinting to reconstruct the endometrium, ovary, cervix, and vagina. Stem cells derived from bone marrow, adipose tissue, and menstrual blood improved ovarian function and endometrial regeneration, with several animal studies reporting successful pregnancies. Concurrently, 3D bioprinting technologies enabled the creation of cell-laden scaffolds with promising potential for tissue reconstruction. Remaining challenges include the development of biocompatible bioinks, formation of functional vascular networks, and accurate recreation of extracellular matrix microenvironments. Most current approaches remain at the preclinical stage; however, the growing body of experimental evidence and early clinical investigations indicate promising translational potential and gradual progress toward future clinical application in female reproductive medicine. Although most advances remain at the preclinical stage, the integration of stem cell therapy and 3D bioprinting demonstrates increasing translational readiness and a clear pathway toward future clinical applications. This review highlights the current progress, existing barriers, and essential research directions for advancing regenerative strategies in female reproductive health.

Background Telemedicine can be used to improve healthcare access. However, it is used less frequently in Japan, particularly in the rural areas. Rural healthcare systems in Japan are unique in that medical services are delivered through a collaboration between core hospitals and rural clinics. Rural clinics provide primary care, whereas core hospitals are expected to provide support through telemedicine-based inter-professional communication. This study qualitatively investigated the major barriers and facilitators of telemedicine adoption in rural settings, particularly from the perspective of core hospitals that support rural clinics. Methods One-on-one semi-structured interviews were conducted at nine core hospitals that used or were ready to use telemedicine systems. The interviews investigated barriers to and facilitators of telemedicine adoption. Results Three barriers and 10 facilitators were identified regarding the telemedicine adoption. These barriers included: 1) budgetary, 2) human resources, and 3) operational issues. Facilitators were conceptually grouped into three domains: 1) institutional and policy-level support (incentives, establishment of operational rules and guidelines, consultation services by local governments, use of consultants, and preparation of trouble response teams), 2) professional and workforce development (human resource education), and 3) community and cultural acceptance (user-friendly systems, collaboration across communities, overcoming field-level apprehension, and resident comprehension). Conclusions While barriers largely reflected structural constraints, facilitators were identified across the institutional, professional, and community levels. Among these, the development of user-friendly systems emerged as a potentially important facilitator in the context of telemedicine adoption in rural Japan. These findings may provide useful insights for promoting telemedicine adoption in core hospitals supporting rural healthcare in Japan.

The Antimicrobial Resistance Laboratory Network (AR Lab Network) was developed by the Centers for Disease Control and Prevention (CDC) to detect and prevent antimicrobial-resistant threats. However, low submission rates of antimicrobial-resistant isolates limit the AR Lab Network's ability to address antimicrobial resistance (AMR). This study expands on a study conducted in Texas Public Health Region 8 (PHR8). The aim of this study was to investigate submission barriers for antimicrobial-resistant isolates in Texas acute care hospitals (ACH) and critical access hospitals (CAH). A survey was designed and emailed to laboratory professionals to identify barriers to antimicrobial-resistant isolate submission. Responses were analyzed using two-sided Fisher's exact tests to identify associations between responses and respondent characteristics. Of the Texas laboratory personnel invited to participate, 123 responses from 211 hospitals were received, for a response rate of 58.29%. Lack of awareness of the AR Lab Network was the most frequently cited submission barrier (50.48% of respondents). Other submission barriers included submission to another laboratory (49.53%), lack of staff time (42.86%), lack of training or certified personnel (41.9%), and a submission process that was too time-consuming (40%). As in the Texas PHR8 study, it was found that, regardless of the respondent's role, time in that role, or the type of hospital in which they worked, the most common barrier to antimicrobial-resistant isolate submission was lack of awareness of the AR Lab Network. In the future, the identified barriers will be addressed by implementing educational outreach programs about the AR Lab Network for Texas hospitals and healthcare facilities.

Adoptive cell therapy (ACT) for solid tumours frequently fails because the tumour microenvironment (TME) imposes multiple, overlapping barriers, including stromal exclusion, suppressive myeloid networks, inhibitory cytokines and metabolites, and antigen heterogeneity. Collectively, these factors markedly restrict the infiltration, persistence, and cytotoxic function of effector lymphocytes. In this Review, we synthesise recent primary studies, consensus guidance, and clinical-trial evidence on engineered-cell therapies, including chimeric antigen receptor (CAR) T cells, T-cell receptor-engineered T cells (TCR-T cells), CAR-NK cells, CAR-macrophages (CAR-M), and emerging in vivo CAR-engineering strategies, together with extracellular-vesicle (EV)-based therapeutics. We then map each platform to mechanism-linked resistance nodes within the TME. For engineered cells, key design levers include context-restricted recognition to reduce on-target/off-tumour toxicity, resistance to dominant suppressive pathways such as TGF-β and adenosine signalling, improved trafficking and tissue penetration, and controllability through transient programming or pharmacological switches. For EVs, the main translational advantages include tissue penetration, modular surface engineering, cargo loading, and their acellular nature, which avoids risks related to in vivo cellular expansion but introduces distinct challenges such as rapid clearance, immunogenicity, batch heterogeneity, and uncertain potency assays. Early clinical data using KRAS G12D-targeting engineered exosomes in metastatic pancreatic cancer support the feasibility of this approach and suggest that EVs may also remodel the immune microenvironment, providing a rationale for combination strategies. We propose a barrier-matched framework in which engineered cells and extracellular vesicles are assigned as functionally orthogonal but complementary modules: engineered cells provide adaptive cytotoxicity, whereas EVs enable microenvironmental reconditioning. This framework may help guide rational combination strategies designed to systematically dismantle resistance in solid tumours.

Tracheal damage arising from inflammation, trauma, congenital anomalies, or tumors can lead to life-threatening complications, yet current treatments, including surgical reconstruction, stenting, laser therapies, autografts, and allografts, remain inadequate, especially for long-segment defects. As a result, tracheal tissue engineering has emerged as a promising alternative, aiming to create functional biomimetic constructs that reduce dependence on complex surgeries, long-term stenting, and immunosuppression. Advances in additive manufacturing and 3D bioprinting have accelerated progress toward engineered tracheal substitutes; however, a fully functional, clinically viable 3D-bioprinted human tracheal graft has yet to be realized. This review assesses current bioengineering strategies, with a particular emphasis on the interplay between cell sources, scaffold materials, and fabrication methods, specifically focusing on 3D bioprinted tracheal constructs. Across existing studies, the most promising direction lies in multi-material, multicellular, spatially patterned bioprinting approaches that can better recapitulate the trachea's complex biomechanics and heterogeneous tissue composition. Finally, we summarize regulatory considerations and outline key scientific and translational barriers, emphasizing that overcoming challenges in vascularization, innervation, and long-term functional integration will be essential to achieving a physiologically aligned, clinically deployable tracheal substitute.

The persistent shortage of donor organs has renewed interest in porcine xenotransplantation as a scalable alternative to human allotransplantation. Advances in genome engineering and immunomodulation have accelerated the field from experimental proof-of-concept toward early clinical translation. This review summarizes recent progress in donor pig genetic modification, targeted immunosuppressive strategies, surgical implementation, and rejection surveillance. Multigene-edited pigs lacking major carbohydrate xenoantigens and expressing human complement, coagulation, and cytoprotective regulators have substantially reduced hyperacute and acute vascular rejection. In parallel, costimulation blockade targeting the CD40/CD154 pathway has enabled prolonged graft survival in non-human primates and supported the first pig-to-human heart and kidney transplants. Improvements in organ preservation, recipient selection, and molecular monitoring, including circulating graft-derived DNA and multi-omic profiling, have further strengthened translational readiness. Complementary porcine models, including pig-to-pig transplantation and vascularized composite tissue transplantation, provide valuable platforms for studying tolerance induction, surgical refinement, and long-term graft biology. Human-to-pig chimerism has also been explored as a potential strategy to promote immune tolerance and improve graft compatibility. Despite these advances, major barriers remain, including delayed antibody-mediated rejection, coagulation dysregulation, innate immune activation, infectious safety, and regulatory challenges. Porcine xenotransplantation has now entered an early clinical era, with durable immune control and long-term safety representing the next decisive milestones.

Flavonoids represent one of the most pharmacologically diverse classes of natural polyphenols, demonstrating broad therapeutic potential in oncology, neurodegeneration, cardiovascular, and metabolic disorders. However, their clinical utility has been limited by intrinsic physicochemical deficiencies, including low aqueous solubility, chemical instability, and extensive first-pass metabolism. Traditional formulation strategies have proven inadequate at overcoming these barriers. Nano-enabled delivery platforms circumvent these limitations through rational nanocarrier design, effectively enhancing dissolution kinetics, protecting labile compounds from degradation, and modulating tissue distribution. This comprehensive review critically examines the current landscape of flavonoid-loaded nanoformulations on the recent advancements (2020-2025), with a particular emphasis on cutaneous delivery (topical/transdermal), elucidating formulation-driven mechanisms of bioavailability enhancement. Furthermore, it critically highlights the growing significance of co-delivery approaches of flavonoids with other therapeutic agents or with each other within advanced nanoplatforms in improving therapeutic benefits or diminishing the drug's adverse effects. Nano-engineered delivery platforms effectively neutralize the bioavailability constraints of flavonoids, unlocking their full pharmacological potential and elevating clinical therapeutic efficacy.

To study a fertility-sparing, minimally invasive surgical approach to numerous bilateral ovarian dermoid cysts, emphasizing techniques that preserve ovarian tissue and minimize electrosurgical injury. Surgical video demonstration. Academic tertiary referral center. A 25-year-old nulligravid woman presented with pelvic pain. Pelvic ultrasound demonstrated multiple, bilateral heterogeneous cystic ovarian masses. Magnetic resonance imaging was obtained for surgical planning. The patient included in this video gave consent for publication of the video and posting of the video online including social media, the journal website, scientific literature websites (such as PubMed, ScienceDirect, Scopus, etc.) and other applicable sites. Institutional Review Board (IRB) approval was not required for this case report per institutional policy; patient consent was obtained as noted above. Preoperative anti-Müllerian hormone (AMH) was discussed but not obtained prior to surgery; given the bilateral and numerous dermoid burden, the patient is planning oocyte cryopreservation, at which time ovarian reserve will be assessed. Robot-assisted bilateral ovarian cystectomy. The robotic platform was selected to leverage tremor filtration and articulated instrumentation for delicate dissection in a case with multiple large teratomas; the techniques described remain applicable to conventional laparoscopy. N/A RESULTS: This video outlines key surgical steps including strategic robotic port placement for optimal access and identification of the cyst-ovarian interface. Vasoconstrictive infiltration with dilute vasopressin (20 units in 400 mL normal saline) was performed to facilitate hydro-dissection of tissue planes and reduce intra-operative bleeding. Blunt dissection was used to develop the correct plane-primarily using cold scissors-with brief, targeted monopolar cut current reserved for vascular tissue to minimize lateral thermal spread. With traction-countertraction techniques facilitated enucleation followed by prompt containment and irrigation in event of spillage. Meticulous hemostasis was achieved using short, targeted applications of monopolar energy with a fine instrument tip to minimize hematoma or fluid collection that could obscure postoperative imaging. The ovarian cortex was then re-approximated with selective suturing. All cysts were successfully excised. The procedure was completed without complication. Pathology confirmed bilateral mature cystic teratomas. The postoperative course was uncomplicated, postoperative imaging demonstrated normal ovarian morphology, adhesion barriers were not used as the peritoneum remained intact with no exposed raw ovarian surfaces, and the patient was counseled regarding an approximate 5% recurrence risk. Extensive bilateral dermoid disease does not preclude minimally invasive, fertility-sparing surgery. Even in cases of large and numerous cysts, careful adherence to tissue-preserving principles allows restoration of functional ovarian anatomy. Key strategies include use of vasoconstrictive agents to reduce bleeding and facilitate tissue-plane dissection, prioritizing blunt and hydro-dissection, selective suturing for hemostasis, and rapid management of spillage. This approach offers a reproducible framework for reproductive surgeons managing complex bilateral ovarian pathology in patients desiring future fertility.

Plastic and reconstructive surgery (PRS) aims to restore form and function, thereby improving patients' quality of life. In recent years, nanotechnology has emerged as a promising field, offering innovative solutions in tissue engineering, wound healing, implant design, and aesthetic applications. This scoping review evaluates recent advancements, clinical applications, and limitations of nanotechnology-based approaches in plastic surgery. A structured literature search was conducted in PubMed using combinations of keywords including "nanotechnology", "nanoparticles", "plastic surgery", "reconstructive surgery", "wound healing", "tissue engineering", and "aesthetic medicine", combined using Boolean operators (AND/OR). Example search string: ("nanotechnology" OR "nanoparticles" OR "nanomedicine") AND ("plastic surgery" OR "reconstructive surgery" OR "wound healing" OR "tissue engineering" OR "aesthetic medicine"). Inclusion criteria included English-language articles published within the past five years focusing on nanotechnology applications in PRS. Reviews, preclinical studies, and clinical studies were included. Editorials, conference abstracts, and studies not directly relevant were excluded. Key data were extracted, including nanomaterial types, methods of application, and reported therapeutic outcomes, and findings were synthesized through thematic analysis. This review identified diverse nanotechnology applications, including nanoskin development, nanoparticle-mediated drug delivery, nanoscaffolds for tissue regeneration, and improved biomaterials for reconstructive procedures such as breast reconstruction. Notable innovations included enhanced wound healing outcomes using clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)-based approaches, burn treatment using tilapia skin xenografts, and chitosan-based nanoparticles demonstrating antimicrobial activity and drug delivery potential. Despite promising preclinical and early clinical results, widespread clinical translation remains limited. Key barriers include insufficient long-term safety and toxicity data, challenges in large-scale production, and regulatory constraints. Nanotechnology in Plastic and Reconstructive Surgery. Created in BioRender. Yong, C.L. (2026) https://BioRender.com/l1pmh1n.

Background Helicopter Emergency Medical Services (HEMS) play an important role in geographically challenging regions such as Nepal, where mountainous terrain, limited road infrastructure, and remote settlements can delay access to advanced medical care. However, mission cancellations remain a significant operational challenge and may reduce system efficiency and timely patient transfer. Objective The study aimed to analyse the reasons for HEMS mission cancellations at a tertiary care centre in Nepal and identify the financial, operational, environmental, and patient-related factors influencing HEMS utilisation. Methods A retrospective observational study was conducted using HEMS coordination data from Mediciti Hospital, Kathmandu, Nepal, between February 2023 and July 2024. All cancelled HEMS missions during the study period were included. Cancellation reasons were categorised using data from the hospital's call register book and analysed descriptively using frequencies and percentages. Results During the 18-month study period, 407 HEMS calls were recorded. Of these, 249 missions (61.1%) were completed, and 158 missions (38.8%) were cancelled. Financial constraints were the most common reason for cancellation (54 missions, 34.18%), followed by miscellaneous operational causes (18 missions, 11.39%), helicopter unavailability (17 missions, 10.76%), and visual flight rules (VFR) limitations (16 missions, 10.13%). Weather-related factors accounted for 12 cancellations (7.59%), while night operation limitations contributed to 13 cancellations (8.23%). Patient-related factors, including preference for another medical centre, non-transferable clinical status, and self-transport, accounted for a smaller proportion of cancellations overall. Conclusion Financial and operational limitations were the leading causes of HEMS mission cancellations in this single-centre Nepalese study. Improving financial protection mechanisms, increasing helicopter availability, and expanding night-flight and all-weather operational capability may improve the efficiency and reliability of HEMS delivery in resource-limited mountainous settings. Further multicentre prospective studies are required to better inform sustainable HEMS development in Nepal.

Imaging Mass Cytometry (IMC) enables highly multiplexed, spatially resolved single-cell proteomics, providing simultaneous measurement of dozens of protein markers while preserving tissue architecture. Despite its analytical power, IMC data analysis remains fragmented across multiple software environments, requiring researchers to combine independent tools for visualization, preprocessing, segmentation, feature extraction, phenotyping, batch correction, and spatial analysis. This fragmentation increases technical barriers, complicates reproducibility, and limits accessibility for non-computational users. We developed OpenIMC, an open-source platform that integrates the major stages of IMC analysis within a unified graphical and command-line framework. OpenIMC supports image visualization, quality control, preprocessing, segmentation, feature extraction, dimensionality reduction, batch effect correction, clustering, phenotyping, and spatial analysis while maintaining interoperability with established community tools. The platform incorporates automated provenance tracking, records analytical parameters and software versions, and enables export and sharing of complete analytical sessions. Benchmarking demonstrated deterministic behavior across repeated runs, complete concordance between graphical and command-line workflows, and strong agreement with established IMC analysis pipelines. OpenIMC additionally provides support for high-resolution IMC workflows, including signal attenuation modeling and image deconvolution. We apply OpenIMC to two datasets of circulating cells and breast tissue to demonstrate the platform's ability to support integrated single-cell and spatial proteomics analysis. OpenIMC reduces the complexity of IMC data analysis by providing a unified, reproducible, and extensible framework for common IMC workflows. By combining interactive visualization with scalable computational analysis, OpenIMC lowers technical barriers and facilitates reproducible single-cell and spatial proteomics research.

Antimicrobial resistance (AMR) represents a critical and escalating threat to global health, driven not only by microbial evolution but also by fundamental limitations in the pharmacokinetic and spatial delivery of antimicrobial agents in vivo. Conventional antibiotics exhibit non-specific systemic distribution, frequently fail to achieve sustained therapeutic concentrations at infection sites, and expose both pathogenic and commensal microbiota to sub-inhibitory levels that accelerate resistance selection. In contrast, infected tissues exhibit distinct and dynamic microenvironmental features-including acidic pH, elevated reactive oxygen species, pathogen-associated enzymatic activity, hypoxia, and localized inflammatory signaling-that are largely absent in healthy tissues and provide exploitable triggers for targeted therapy. Stimuli-responsive nanocarriers are engineered to sense and respond to these pathological cues, enabling spatiotemporally controlled and infection-specific drug release while minimizing systemic exposure. In this review, we systematically analyze the mechanistic foundations of pH-, enzyme-, redox-, and multi-stimuli-responsive nanocarriers, with particular emphasis on how trigger-induced physicochemical transformations govern drug retention, activation, penetration, and release within drug-resistant infection niches. We further examine how these platforms address key resistance-associated barriers, including impaired tissue penetration, biofilm-associated tolerance, intracellular pathogen persistence, efflux-mediated drug extrusion, and enzymatic antibiotic degradation. Importantly, we provide a critical comparison between passive nanocarriers, stimuli-responsive systems, and free antibiotics, highlighting the conditions under which infection-synchronized delivery enhances antimicrobial efficacy, reduces off-target toxicity, and mitigates resistance-selective pressure. We also evaluate current translational challenges, including microenvironmental heterogeneity, trigger variability, long-term safety, scalable manufacturing, and regulatory complexity. Collectively, stimuli-responsive nanocarriers represent a paradigm shift from passive systemic exposure toward context-aware, site-selective antimicrobial intervention, offering a promising strategy to overcome persistent limitations in anti-infective therapy and address AMR beyond the pace of conventional antibiotic discovery.

Diabetic wound healing poses a major clinical challenge. One of the promising therapy, the flap transplantation surgery exhibited unsatisfactorily low flap survival due to the intertwined pathological barriers: impaired angiogenesis, excessive oxidative stress, and persistent inflammation, leading to poor tissue repair. While the therapeutic platforms based on extracellular vesicles (EVs) emerges as a promising treatment, its efficacy is often limited by the inadequate yield and rapid in vivo clearance. To address this challenge, this study developed a strategy centered on preconditioning human umbilical vein endothelial cells (HUVECs) with high glucose (HG) stress to produce HG-preconditioned extracellular vesicles (hEVs), which significantly improve production, enrich regenerative cargoes (e.g., HIF-1α, VEGF), and enhance homologous cellular internalization. The hEVs derived from HUVECs were encapsulated by microfluidically fabricated gelatin methacryloyl (GelMA) microgels to create GelMA@hEVs. The biodegradable and biocompatible GelMA microgels enabled a sustained hEVs release profile. Therefore, GelMA@hEVs exhibited significant efficacy improvement in promoting endothelial cell proliferation, migration, and tube formation critical for vascularization, mitigating reactive oxygen species, and modulating macrophage polarization toward a pro-reparative phenotype. Mechanistically, these therapeutic effects relied on activating the HIF-1α/VEGF pathway, a core axis for angiogenesis dysregulated in diabetes. In diabetic ischaemic flap models, GelMA@hEVs significantly improved flap survival, restored vascular perfusion, and facilitated tissue regeneration without systemic toxicity. Altogether, this work provides a generalizable strategy for diabetic ischaemic flap repair by combining engineered EVs as bioactive cargo with a microgel scaffold for sustained delivery, offering a promising in situ tissue engineering solution.

Adhesions are a common complication following surgery, and they can cause significant morbidity. However, adhesions are not easily diagnosed with imaging, and often only become apparent when they cause intestinal obstruction symptoms. The pathophysiology of adhesion formation is complex, thus despite advances in surgical techniques and postoperative care, adhesions remain a persistent problem in clinical practice. Despite evidence for efficacy of some strategies in reducing adhesion formation question remain regarding the indications and impact on clinically relevant outcomes. The paper, supported by the World Society of Emergency Surgery (WSES), aims to provide a thorough examination of the pathophysiological mechanisms underlying adhesion formation and assess the efficacy of existing preventive strategies to guide future research and clinical practice in the management of adhesions. Study design and Framework This position paper was developed in accordance with the World Society of Emergency Surgery (WSES) methodology for consensus-based guidelines. The objective was to synthesize current evidence on adhesion pathophysiology and translate it into a clinically applicable "Narrative". Expert Panel Selection and Composition: The expert panel was composed of international specialists in general, trauma, and emergency surgery. Experts were selected based on their clinical leadership and academic contributions to the fields of peritoneal surgery and postoperative complication management. The panel included senior representatives from major surgical departments in Singapore (Sengkang and Singapore General Hospital), The Netherlands (Radboud University), and Italy (University of Bologna and Bufalini Hospital). Literature Search and Evidence Synthesis: A comprehensive search was conducted across major medical databases (e.g., PubMed, Scopus, Cochrane Library) to identify literature concerning the pathophysiology and prevention of adhesions. The search strategy employed Medical Subject Headings (MeSH) descriptors and keywords including: "peritoneal adhesions," "postoperative adhesions," "adhesion prevention," "adhesion barriers," "carboxymethylcellulose," "hyaluronic acid," "icodextrin," "oxidized regenerated cellulose," "polyethylene glycol," "adhesive small bowel obstruction," "adhesiolysis". No language restrictions were applied to the search strategy. A total of 56 studies were selected, including systematic reviews, meta-analyses, randomized clinical trials (RCTs), and retrospective cohort studies. The panel focused on clinically relevant outcomes, specifically looking for evidence that connected interventions to reduced rates of adhesive small bowel obstruction (ASBO) and reoperation. Studies were screened based on their ability to address three specific pillars: surgical approach (MIS vs. Open), technical manoeuvres (haemostasis and tissue handling), and the use of mechanical or chemical adjuncts. Consensus Achievement and Formulation: The recommendations were developed through a structured, iterative revision process: Literature Synthesis: Lead authors performed the primary review and drafted the pathophysiological and preventative sections. Internal Peer Review: The manuscript underwent rigorous revision by the international expert panel to reach a consensus on the position statements. Final Validation: All authors reviewed and approved the final manuscript and the resulting "Bundle" recommendations to ensure they were supported by the cited data. A total of 56 studies (systematic review and meta-analysis, randomized clinical trial, retrospective comparative cohort studies, case series) have been included in this paper to be discussed. Surgical techniques, as well as chemical and mechanical barriers were discussed in depth in this paper to come up with the recommendation. The WSES expert panel suggests the following bundle to reduce postoperative peritoneal adhesions: Bundle 1: Whenever possible, opt for minimally invasive surgery (MIS) or laparoscopic procedures. Bundle 2: Good surgical techniques. Bundle 3: Utilise barriers.

LIM homeobox 2 (LHX2) is a LIM-homeodomain (HD) transcription factor that participates in regulating vertebrate development, tissue homeostasis, and injury repair. This review systematically synthesizes the pleiotropic functions of LHX2 across multiple organ systems. During development, LHX2 directs regional specification and cell fate determination in the cerebral cortex, hippocampus, and retina, while regulating limb bud patterning and the development of the visual, olfactory, reproductive, and hematopoietic systems. During homeostasis, LHX2 acts as a key negative regulator to maintain the quiescent state of hepatic stellate cells (HSCs), osteoclast precursors, astrocytes, and hair follicle stem cells, thereby preserving tissue integrity. Following injury, LHX2 switches to a pro-regenerative mode, promoting re-epithelialization, axon regeneration, and hematopoietic niche remodeling. Dysregulation of LHX2 is causally linked to neurodevelopmental disorders, ocular malformations, liver fibrosis, osteoporosis, and various cancers. Emerging evidence also implicates LHX2 in metabolic-epigenetic circuits, the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) and Wingless/Int-1 (Wnt)/β-catenin axes, as well as microRNA (miRNA) regulation. We also discuss therapeutic strategies targeting LHX2, including molecular engineering to overcome species barriers, and outline key knowledge gaps. A comprehensive understanding of LHX2-regulated networks holds promise for advancing regenerative medicine and enabling precision interventions in developmental disorders.

Rare diseases, affecting approximately 8% of the global population, remain among the most underserved areas in modern medicine due to their low prevalence, complex genetic origins, and limited commercial incentives for drug development. Rare neurological disorders, in particular, pose formidable challenges owing to their progressive nature and the difficulty of delivering thera-peutics across the blood-brain barrier. This review explores the emerging role of nanomedicine in transforming rare disease management through precision-targeted drug delivery, enhanced bioavail-ability, and the ability to bypass biological barriers. Nanoparticles (NPs)-including PEGylated NPs, lipid-based NPs, polymeric NPs, and hybrid formulations-are being engineered to deliver therapeu-tic agents for gene therapy, enzyme replacement, and RNA interference. These platforms have shown promise in treating conditions such as Krabbe disease, Niemann-Pick type C1, spinocerebel-lar ataxia type 1, and prion diseases. Additionally, nanotherapeutics are being investigated for pulmonary and congenital lung disorders, including cystic fibrosis and idiopathic pulmonary fibro-sis, with improved tissue penetration and reduced systemic toxicity. The review also highlights the potential of AI-integrated diagnostics and personalized nanomedicine to address disease heterogene-ity and improve patient outcomes. Despite these advances, significant barriers remain, including regulatory complexity, high development costs, and limited clinical models. The manuscript calls for collaborative innovation across academia, industry, and regulatory bodies to accelerate clinical translation and ensure equitable access. By bridging molecular innovation with patient-centric care, nanotherapeutics offer a paradigm shift in the diagnosis and treatment of rare diseases, potentially redefining therapeutic landscapes and improving the quality of life for affected individuals.

This article describes how techniques such as advanced imaging, nucleic acid evaluation, integrated approaches, and data collection systems can facilitate the examination of a stillbirth or newborn, particularly when an autopsy is not possible. The traditional autopsy remains the gold standard for investigating stillbirth and neonatal death. However, declining rates due to parental refusal, financial constraints, and cultural barriers highlight the need to widely adopt modern alternatives. This review examines emerging ancillary and advanced diagnostic techniques necessary to maximize diagnostic yield and ensure equitable access to comprehensive postmortem evaluations. Since imaging alone often misses critical microscopic pathologies, hybrid methods like Minimally Invasive Autopsy with Laparoscopically Assisted Sampling (MinImAL) are essential. MinImAL combines Postmortem Magnetic Resonance Imaging (PMMR) with image-guided tissue sampling to acquire specimens for histological and microbiological analysis. Complementary molecular techniques aid in identifying underlying genetic causes and informing recurrence risk. The success of these tests relies on optimized tissue selection. Systemic improvements include adopting standardized protocols, establishing Stillbirth Centers of Excellence, and using Artificial Intelligence (AI) for risk prediction. Importantly, integrating these advanced, less invasive methods is vital for addressing financial and racial health disparities, especially given the lack of Medicaid coverage for autopsy, thereby ensuring all bereaved families receive accurate and necessary diagnostic information.

The remarkable success of mRNA-lipid nanoparticles (LNP) vaccines during the SARS-CoV-2 pandemic have highlighted the critical role of this cutting-edge technology as a cornerstone for contemporary vaccine innovation. Efforts to enhance mRNA-LNP vaccine efficacy have driven specific interest in optimizing nanoparticle design to improve immune cell transfection. Nevertheless, the precise mechanisms driving immune responses, including cell identity and their activation states within immune and local tissues, remain unclear and system-dependent. Muscle tissue is an ideal site for mRNA vaccine administration due to its ribosome abundance, ensuring efficient translation of the delivered mRNA into the encoded protein. Additionally, the localized nature of muscle injections ensures controlled biodistribution and minimizes systemic side effects, making it a safe and effective route for generating robust immune responses. In line with these observations, we developed a lipid-polymer hybrid nanosystem that effectively complexes mRNA, demonstrating high efficiency in transfecting muscle cells and tissue. Importantly, this delivery resulted in a robust adaptive immune response, characterized by both potent humoral and cellular immunity, highlighting the effectiveness of this nanosystem for mRNA-based vaccination. Overall, these findings highlight the need to consider the role of muscle cells as potential antigen-producing reservoirs in immune modulation when designing mRNA vaccines.

The clinical translation of personalized cancer vaccines is currently impeded by the dual challenges of rapid antigen manufacturing and inefficient delivery to lymphoid tissues. In this study, we present a biohybrid nanovaccine platform that bridges synthetic biology and acoustic engineering to enable a noninvasive airway-to-lymph-node vaccination strategy. Leveraging an engineered nonpathogenic Escherichia coli TOP10 strain as living antigen factories, we construct ultrasound-responsive, manganese-chelated bacterial membrane nanovesicles that encapsulate biosynthesized tumor antigens. Following nebulized inhalation, low-intensity ultrasound triggers the acoustic droplet vaporization of these nanovesicles. This process induces cavitation-enhanced lymphatic trafficking, which actively overcomes pulmonary physiological barriers to promote deep tissue penetration and efficient antigen drainage to pulmonary lymph nodes. The spatiotemporally controlled co-delivery of antigenic proteins, innate bacterial adjuvants, and Mn2+ orchestrates a potent immune cascade, driving robust dendritic cell maturation and antigen cross-presentation. Consequently, this 'inhale-and-act' strategy elicits strong systemic antitumor immunity for next-generation personalized immunotherapy.