搜索结果：Advanced biology

Management of prostate cancer has improved over the past two decades, driven by innovations in detection of metastatic disease, biomarker characterization, and treatment. This review summarizes the latest progress in managing advanced states of this disease, spanning high risk biochemical recurrence, metastatic hormone sensitive prostate cancer (mHSPC), and metastatic castration resistant prostate cancer (mCRPC). Improved outcomes for patients have been seen with earlier use of androgen receptor pathway inhibitors in the setting of high risk biochemical recurrence and mHSPC. Meanwhile, individuals with mCRPC now represent a more diverse population, differentiated by both their previous treatments and other biological features. Advanced imaging and genomic biomarkers improve patient selection and permit more personalized therapy. Landmark clinical trials and meta-analyses have established and/or refined the role of chemotherapy, poly-ADP ribose polymerase (PARP) inhibitors, and 177Lu-PSMA-617 in this disease space. Finally, as patients with prostate cancer are living longer, the review focuses on understanding and managing potential adverse events, including cardiac and hematologic toxicity and bone health.

Burn wounds often cause severe complications such as infection and delayed healing. Advanced scaffolds mimicking the extracellular matrix can promote tissue regeneration and reduce infection risk. In this work, an interpenetrating polymer network (IPN) hydrogel was engineered by crosslinking polyacrylamide within a hyaluronic-acid/methyl-cellulose matrix using extrusion-based 3D printing. Antibacterial functionality was achieved by incorporating amoxicillin (AMX) at different loadings. The ink's rheology confirmed strong shear-thinning behavior, suitable for layer-by-layer deposition. AMX addition slightly increased viscosity but maintained printability. Printed scaffolds were characterized for microstructure, thermal stability, chemistry, swelling, and degradation. They exhibited rapid water absorption and controlled mass loss over time. Antibacterial tests showed strong inhibition against both Escherichia coli and Staphylococcus aureus for all AMX-loaded scaffolds, whereas the drug-free control displayed only minor activity, likely from HA. Cytocompatibility studies confirmed high fibroblast and keratinocyte viability, with the 0.5 wt% AMX scaffold achieving the best overall performance. These results indicate that HA/MC/AAm IPN hydrogels, particularly those with 0.5 wt% AMX, offer a promising 3D-printed platform combining structural integrity, sustained antibiotic release, and cell support, making them suitable candidates for burn wound management.

Chronic pancreatitis (CP) is associated with sarcopenia and functional decline, yet the underlying mechanisms remain underexplored. Neuromuscular junction (NMJ) degradation and neurotrophic imbalance may play key roles, but relevant studies remain scarce. We recruited 74 healthy controls, 65 patients with early CP, and 57 patients with advanced CP for evaluation of sarcopenia, including handgrip strength (HGS), muscle mass, and gait speed. Physical performance was measured using the Short Physical Performance Battery (SPPB). Plasma C-terminal agrin fragment-22 (CAF22; a marker of NMJ degradation), brain-derived neurotrophic factor (BDNF), and markers of inflammation, oxidative stress, and nutritional status were measured. Sarcopenia prevalence and functional impairment increased significantly with CP severity. Plasma CAF22 showed a stepwise increase from controls to early and advanced CP, with increases of 10.2% and 24.3%, respectively. BDNF declined by 12.4% in advanced CP, while the total protein and albumin were lowest in advanced CP. CAF22 displayed robust associations with HGS, gait speed, and SPPB across all groups, with the largest effect sizes in advanced CP. BDNF exhibited positive associations with muscle function, while inflammatory, oxidative, and nutritional biomarkers exhibited weaker and stage-dependent relationships. These associations appeared to strengthen with worsening CP, suggesting that neuromuscular, inflammatory, and metabolic stressors may become more closely linked to functional decline in advanced disease. CP is associated with progressive sarcopenia along with NMJ degeneration, neurotrophic imbalance, inflammation, oxidative stress, and nutritional decline. These findings highlight the potential value of CAF22 and BDNF as biomarkers of functional impairment.

Bone healing, remodeling, and pathology are strongly regulated by mechanical stimulation. However, conventional two-dimensional (2D) in vitro culture systems fail to reproduce the complex mechanical and biological microenvironment of human bone, limiting their translational relevance. In recent years, bone-on-chip (BoC) platforms, as part of the broader organ-on-chip (OoC) technology, have emerged as advanced microfluidic systems that enable the study of bone biology under dynamic and highly controlled conditions that more closely mimic in vivo physiology. This systematic review aimed to gather the available in vitro evidence on mechanically stimulated BoC models, with a particular focus on osteogenic differentiation outcomes and the technical characteristics underlying these platforms. Following a comprehensive literature search and structured data extraction, biological parameters (cell types, culture conditions, scaffolds), chip design and fabrication strategies, mechanical loading modalities, and assessment assays were systematically analyzed. Across the included studies, fluid shear stress was the most frequently applied mechanical stimulus and was generally associated with enhanced osteogenic differentiation compared with static cultures, although substantial heterogeneity was observed in loading protocols and outcome measures. Overall, this review provides a consolidated technical and biological overview of mechanically stimulated BoC systems and highlights key methodological considerations for future platform development. By integrating microengineering approaches with bone and stem cell biology, BoC models hold significant potential for advancing bone tissue engineering, mechanobiology research, and translational applications, including dentistry-related bone regeneration and biomaterial testing.

Metastatic castration-resistant prostate cancer (CRPC) remains a clinical challenge, and epithelial-mesenchymal transition (EMT) contributes to metastatic progression and reduced response to therapy. However, the upstream epigenetic mechanisms that sustain EMT programs in advanced prostate cancer (PCa) are not fully defined. We identify the histone H3 lysine 9 (H3K9) methyltransferase SET domain bifurcated 1 (SETDB1) as a key regulator of EMT and metastasis through direct repression of RhoB, the small GTPase. SETDB1 is genomically amplified and transcriptionally upregulated in metastatic CRPC, and SETDB1 depletion reduces cell migration, invasion, and metastatic dissemination. Integrated chromatin profiling and transcriptomic analyses demonstrate that SETDB1 occupies the RhoB promoter and mediates its transcriptional silencing through H3K9 methylation. Restoration of RhoB reverses EMT gene expression and suppresses invasive behavior, whereas RhoB knockdown rescues the effects of SETDB1 depletion, establishing RhoB as a critical downstream effector of SETDB1 function. Androgen signaling inhibitor-resistant PCa models exhibit RhoB loss and EMT activation, linking this axis to therapy-resistant phenotypes. Finally, antisense oligonucleotide-mediated SETDB1 silencing restores RhoB expression and suppresses EMT and invasion in CRPC cell models. Together, these findings define a SETDB1-RhoB epigenetic pathway that promotes EMT and metastatic progression in PCa and may be therapeutically targeted in advanced disease. Prostate cancer is a leading cause of cancer-related death in men. Although many patients initially respond to hormone therapies that block androgen receptor signaling, advanced prostate cancer often becomes resistant to treatment and spreads to other organs. One process that helps cancer spread is called epithelial–mesenchymal transition (EMT), in which tumor cells become more mobile and invasive. In this study, we investigated how the protein SETDB1 contributes to prostate cancer progression. We found that SETDB1 suppresses the tumor suppressor gene RHOB, which normally helps prevent EMT and cancer cell migration. Using genomic, molecular, and animal models, we showed that increased SETDB1 activity promotes EMT, invasion, and metastasis in prostate cancer. Importantly, restoring RhoB reversed many of these aggressive features. These findings identify the SETDB1–RhoB pathway as a potential therapeutic target for advanced prostate cancer.

Male lactotroph pituitary neuroendocrine tumors (PitNETs) are often considered more aggressive than those in women, but surgically treated cohorts are highly selected and may reflect differences in presentation and indication for surgery. We examined whether advanced clinical presentation in surgically treated lactotroph PitNETs is accompanied by distinct pathologic features. We reviewed 43 patients who underwent surgery for lactotroph PitNETs between 2018 and 2023 at a high-volume referral center. Cases were classified by surgical indication as preference for surgery/intolerance to dopamine agonists (P/I, n=26), resistance with hormonal symptoms (R/H, n=10), and resistance with mass effect (R/M, n=7). Clinical, radiologic, and pathologic parameters, including Ki-67, cytokeratin (CAM5.2), estrogen receptor, somatostatin receptor 2/5, and O6-methylguanine-DNA methyltransferase, were compared. Postoperative endocrinological remission was assessed at the last follow-up (median: 34 mo). All tumors were prolactin-immunoreactive, confirming lactotroph differentiation. Patients in the R/M group were older (median: 56 y), predominantly male (71.4%), and had larger tumors (median: 26 mm) with more frequent cavernous sinus invasion (Knosp grade 4, 85.7%) than those in the other groups. Long-term endocrinological remission differed significantly by indication (P/I, 88.5%; R/H, 80.0%; and R/M, 0%). In contrast, Ki-67 labeling index did not differ significantly across groups (P/I, 1.3%; R/H, 1.5%; and R/M, 2.6%; P=0.598), and no clear between-group differences were identified in CAM5.2 pattern, estrogen receptor, somatostatin receptor 2/5, or O6-methylguanine-DNA methyltransferase status. These findings suggest that the clinically most advanced surgical cases are not matched by distinct pathologic differences in the markers assessed and that the apparent aggressiveness of male-predominant mass-effect cases should not be interpreted solely as reflecting intrinsically aggressive tumor biology.

The MYC pathway is highly activated in gastric cancer (GC), but the MYC oncogene's structural biology makes direct pharmacological inhibition very difficult. We hypothesized that BRD4, as a major co-activator of MYC, maintains MYC-dependent survival circuits, thus making BRD4 a key therapeutic vulnerability in late GC. We carried out a comprehensive transcriptomic analysis by utilizing large-scale data sets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), then these computational forecasts were later verified in strict clinical cohorts via molecular and histological methods. Functional verification was done through genetic and pharmacological interference by means of CRISPR-Cas9 gene deletion and PROTAC-induced protein breakdown with ARV771, ultimately, the therapeutic efficacy and systemic safety of these interventions were assessed in vivo with mouse xenograft models. Our analyses revealed that the expression of BRD4 was significantly increased in GC tissues and there was a strong connection between this increase and the MYC hyperactivation, advanced TNM staging, and shortened patient survival. Our knockout (KO) experiments found that the viability of tumor cells depended greatly on the BRD4 - MYC - BCL2 signaling pathway because when BRD4 was depleted, the expression of BCL2, a crucial anti-apoptotic protein, decreased substantially. When pharmacological intervention was applied using ARV771, these cancer-related characteristics were effectively reversed, resulting in the suppression of tumor proliferation, the decrease of BCL2 levels, and significant inhibition of the growth of xenograft tumors in vivo without observable toxicity. Our findings suggest that BRD4 acts a chief epigenetic controller which promotes the progress of GC by intensifying MYC-dependent survival and ARV771 blocks this survival advantage, thus presenting a highly compelling rationale for integrating BRD4 degraders into modern targeted regimens.

Axillary management after neoadjuvant chemotherapy (NAC) in node-positive breast cancer remains controversial. This study assessed the association between total lymph node count, in the context of metastatic lymph node count and lymph node ratio (LNR), and recurrence after NAC in a cohort of young women with node-positive breast cancer. Retrospective data were analyzed from 274 women aged &#x2264;&#xa0;45 years diagnosed with clinical T1-3, N1-3, M0 invasive breast cancer between January 2010 and December 2023 who received NAC before undergoing surgery at our institution. Primary outcomes were recurrence and overall survival. Total lymph node counts across three LNR tiers were compared between women with at least one metastatic node out of at least three retrieved nodes who did and did not develop recurrence. Patients who developed a recurrence presented with more advanced clinical T (p&#xa0;<&#xa0;0.001) and N (p&#xa0;=&#xa0;0.01) staging and had greater residual burden of disease in both the breast (p&#xa0;<&#xa0;0.001) and the lymph nodes (p&#xa0;<&#xa0;0.001) than did patients with no recurrence. There was no significant correlation between total number of lymph nodes excised and recurrence in women with at least one metastatic node out of at least three examined nodes in any of the low (p&#xa0;=&#xa0;0.39), intermediate (p&#xa0;=&#xa0;0.47), or high (p&#xa0;=&#xa0;0.67) LNR tiers. Tumor biology, chemoresistance, and residual tumor burden after NAC may influence oncologic outcomes more than the number of nodes removed or the extent of nodal surgery. Prospective, large-scale, long-term studies are needed to rigorously address this question, particularly in this young, high-risk population.

Pharmaceutical bioanalysis plays a central role in drug development, therapeutic drug monitoring, pharmacokinetics, metabolomics, and clinical diagnostics; however, the increasing complexity of biological and pharmaceutical matrices has created major analytical challenges related to matrix effects and analyte instability. Endogenous compounds such as phospholipids, proteins, salts, metabolites, and formulation excipients can interfere with chromatographic separation and electrospray ionization, leading to ion suppression or enhancement, signal fluctuations, reduced sensitivity, and compromised quantitative accuracy. In addition, hydrolysis, oxidation, photodegradation, enzymatic degradation, and adsorption processes can significantly affect analyte stability during sample collection, storage, preparation, and LC-MS analysis. This review critically evaluates the mechanistic basis of matrix effects and analytical instability in pharmaceutical bioanalysis and highlights recent advances in intelligent analytical technologies designed to improve analytical robustness, reproducibility, and sustainability. Advanced sample preparation strategies, including selective SPE, phospholipid-removal systems, MIP, and microextraction technologies, together with modern LC-MS platforms such as UHPLC-MS/MS and HRMS, have significantly enhanced trace-level pharmaceutical analysis in complex matrices. Furthermore, artificial intelligence-assisted workflows, microfluidics, biosensors, and omics-based analytical systems are transforming pharmaceutical bioanalysis toward automated and smart analytical ecosystems. Future pharmaceutical bioanalysis is expected to integrate intelligent, sustainable, and highly automated analytical systems that combine AI-driven analytics, advanced LC-MS technologies, green and white analytical chemistry principles, and harmonized regulatory frameworks to improve clinical applicability, analytical reliability, and environmental sustainability.

Male breast cancer (MBC) is a rare but increasingly recognized malignancy that remains underrepresented in research, policy, and clinical practice. Persistent misconceptions that breast cancer is exclusively female disease contribute to delayed presentation, advanced-stage diagnosis, and poorer outcomes in men. This article examines global disparities affecting awareness, diagnosis, treatment, research inclusion, and psychosocial care, and proposes strategic actions to advance equitable and inclusive oncology. This article is based on a targeted review of peer-reviewed studies, epidemiologic analyses, clinical reports, and guideline documents addressing the epidemiology, biology, diagnosis, management, genetics, and psychosocial impact of MBC. Literature was identified through structured searches of academic databases including PubMed and scholarly and authoritative institutional sources. Findings were synthesized thematically to identify gaps, systemic barriers, and priority interventions. MBC accounts for approximately 0.5%-1% of all breast cancer cases globally, with evidence suggesting rising incidence and late-stage detection. Limited public and professional awareness contributes to diagnostic delays, while absence of routine screening and male-specific protocols further complicates early identification. Clinical management is commonly extrapolated from female breast cancer trials despite biological and hormonal differences that may influence treatment response and toxicity. Men also experience psychosocial burdens, including stigma, isolation, threats to identity, and lack of tailored support services. Pathogenic variants such as BRCA1/2, CHEK2, PALB2 are relatively prevalent among affected men, yet genetic counseling and cascade testing remain underutilized. Together, these factors create a persistent "silent burden" and contribute to suboptimal outcomes. Addressing inequities in MBC requires coordinated global action, including sex-disaggregated data systems, inclusive clinical research, male-specific diagnostic and treatment guidance, targeted awareness initiatives, and integrated psychosocial and genetic services. Recognizing MBC within national and global cancer agendas is essential to improving early detection, optimizing treatment outcomes, and ensuring equitable, evidence-based care for all individuals affected by breast cancer.

Single-molecule techniques have transformed molecular biology by enabling direct observation of individual biomolecular events in real time. While single-molecule localization methods have advanced spatial resolution, they lack the temporal resolution needed to capture dynamic interactions. Single-molecule fluorescence resonance energy transfer (smFRET) addresses this gap by revealing transient molecular states often hidden in ensemble measurements. However, extracting reliable kinetic parameters from smFRET data is hindered by noise artifacts, photophysical effects, and the analytical complexity of stochastic state transitions. To address these limitations, Single-Molecule Interaction Simulation (SMIS) provides a robust framework that enables kinetic analysis by simulating molecular transitions and generating interpretable dwell-time distributions. Unlike traditional approaches requiring complex differential equations, SMIS simplifies kinetic modeling and directly addresses challenges in reproducibility. This chapter outlines a comprehensive protocol for implementing SMIS, from defining kinetic schemes to extracting kinetic rate constants by comparing simulation outcomes against experimental data. By integrating SMIS into the analysis workflow, researchers can extract accurate kinetic insights from smFRET experiments, extending their applicability and enhancing the interpretability of single-molecule studies.

Neurological diseases (NDs) continue to be a leading cause of disability and mortality worldwide, largely due to delayed diagnosis and limited access to rapid assessment. Blood-based biomarkers (BBMs) provide minimally invasive, objective, and early molecular indicators of pathological changes in the brain. By combining sensitive signal transduction, simplified sample processing, and rapid readout, point-of-care testing (POCT) technologies offer transformative opportunities to translate BBM discoveries into real-time and decentralized neurological diagnostics. This review systematically categorizes the most widely studied and translationally valuable neurological BBMs and discusses their biological features and clinical relevance, with emphasis on their kinetics, diagnostic specificity, and analytical requirements. We further discuss emerging sensing strategies enabling sensitive and rapid BBM detection, focusing on signal amplification performance, multiplex detection capabilities, and readout time of electrochemical biosensors and optical biosensors, as well as their combination with paper-based devices, microfluidics, smartphones, and artificial intelligence. Importantly, we discuss the rational matching of different sensing modalities with the physicochemical characteristics of specific biomarkers. Moreover, we examine clinical needs and commercially available POCT strategies for NDs, highlighting two disease-oriented scenarios: rapid diagnosis for acute neurological injuries and self-screening and longitudinal monitoring for chronic neurodegenerative disorders. Finally, we provide a dedicated section on the key translation challenges facing neurological BBM-based POCT devices. Together, by integrating biomarker biology, advanced sensing technologies, and disease-specific clinical needs, this review proposes a biomarker- and disease-oriented framework for neurological POCT development. This framework aims to accelerate the development of clinically actionable diagnostic tools that support timely screening, early diagnosis, risk stratification, and longitudinal monitoring across the continuum of neurological care.

Paediatric high-grade gliomas (pHGGs) are aggressive childhood brain tumours with five-year survival rates below 20%. They are distinct from adult high-grade gliomas (aHGGs), driven by histone mutations, disrupted developmental programs, and an immunologically restrained tumour microenvironment (TME). While chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of haematological malignancies, its application to pHGGs faces significant challenges for clinical translation. This review aims to provide a comprehensive overview of pHGG biology, CAR-T cell therapy principles, and current preclinical models, highlighting translational gaps and strategies to bridge them. We first examined the molecular and cellular landscape of pHGGs, emphasizing the unique features that shape responsiveness to antigen-directed therapies, detailing the mechanisms of CAR-T therapy, successes in haematological malignancies, and specific challenges in central nervous system (CNS) tumours. Next, we critically discussed the preclinical platforms, ranging from traditional 2D cultures to advanced patient-derived 3D systems and in vivo mouse models. While these systems provide mechanistic insights and enable assessment of CAR-T efficacy, none fully replicate the paediatric TME or developmental context, contributing to the recurrent gap between preclinical efficacy and clinical outcomes. This review highlights current knowledge, translational limitations, and future strategies to enhance CAR-T research in paediatric neuro-oncology.

The origin of life signifies one of science's most profound mysteries, demanding integrative comprehension from chemistry, biology, and physics. In this review we examine the coupled roles of chemical evolution, biological evolution, gravity and light in shaping the earliest stages of life. We discuss how conditions established by the Big Bang, stellar nucleosynthesis and early planetary environments provided the energetic conditions necessary for the emergence of prebiotic chemistry. Going beyond the geocentric perspective, we explore extraterrestrial chemistry and analyze how gravitational fields and electromagnetic radiation jointly influence molecular stability, reaction kinetics, diffusion and spatial confinement. A central hypothesis advanced here is that planetary gravity constitutes a critical, but underappreciated physical selector in prebiotic evolution. Excessively strong gravity may suppress molecular mobility and dynamic self-organization whereas very weak gravity may prevent the retention, concentration, and stabilization of reactive intermediates. Earth's gravitational acceleration (&#x223c;9.81 m s&#x207b;&#xb2;) may therefore represent a "sweet spot" regime that optimally balances stability and dynamism. Using illustrative examples from prebiotic reaction networks, vesicle self-organization, osmolarity-driven processes, and early peptide-based catalysis, we discuss how gravity could have shaped the emergence of sustained metabolic networks, molecular surrogates, and protocellular systems. We further extend this framework to later evolutionary transitions, including the role of cytoskeletal elements in overcoming gravitational constraints during the colonization of land. Together, this interdisciplinary synopsis provides evidence for gravity's role as a continuous physical selector acting from chemical evolution to biological complexity, with implications for planetary habitability and the potential uniqueness of life on Earth.

The application of computational anthropomorphic phantoms has become imperative in the field of radiation dosimetry because they facilitate anatomically faithful simulations of energy deposition within the human body. Their development reflects significant advances in computational modeling, with a transition from early stylized geometries to voxel-based, mesh-based, and Non-Uniform Rational B-Splines (NURBS) representations. The recent introduction of ICRP mesh-type reference computational phantoms (MRCPs), including advanced maternal and fetal models, has significantly improved the representation of anatomical heterogeneity. When coupled with Monte Carlo simulation codes (e.g., EGSnrc, MCNP, Geant4, PENELOPE, GATE, and TOPAS), these phantoms offer robust frameworks for calculating radiation transport. Additionally, a transition is underway in the dosimetric paradigm, marked by a shift from macroscopic organ assessments that utilize Condensed History algorithms to subcellular microdosimetry that relies on event-by-event Track Structure codes. Consequently, recent advances have extended their applications in a range of disciplines, including radiotherapy, nuclear medicine, and diagnostic imaging. These advances have also been used in vivo monitoring calibration and modeling of complex radiobiological effects at the DNA level via platforms like TOPAS-nBio. Artificial intelligence and digital-twin approaches are increasingly being explored as tools to support individualized dosimetry and adaptive treatment planning. This review delineates historical developments, methodological breakthroughs, and emerging trends in this field, highlighting the emergence of a new research frontier at the intersection of physics, biology, and computer science for personalized radiation dosimetry.

Ovarian cancer (OC) is a highly heterogeneous and lethal gynecological malignancy. Precision oncology has shifted the management paradigm to comprehensive molecular profiling. Genomic-based diagnostics are now a clinical necessity for accurate prognostic stratification and the rational selection of targeted therapeutics, such as PARP and immune checkpoint inhibitors. This review evaluates current literature regarding the distinct genomic landscapes defining OC histotypes to underlined the role of molecular profiling in the diagnostic field of OC. We discuss the practical implementation, technical aspect, and clinical validity of the main molecular diagnostic platforms, focusing on tissue-based Comprehensive Genomic Profiling (CGP) and Homologous Recombination Deficiency (HRD). Furthermore, we explore emerging translational data on liquid biopsy (LBx) applications. While current tissue-based methodologies provide critical baseline data, the OC diagnostic paradigm must pivot from static testing to proactive and longitudinal tracking. Integrating advanced LBx approaches enables a real-time monitoring of dynamic parameters as minimal residual disease (MRD) and acquired resistance. Integrating these dynamic blood-based assays with multi-omic profiling and artificial intelligence (AI)-driven tools allows a full understanding of the complex tumor behavior.

Pulmonary edema, a life-threatening condition in acute lung injury/acute respiratory distress syndrome (ALI/ARDS), is driven by dysregulated inflammation, barrier disruption, and alveolar fluid accumulation. Effective therapies that simultaneously target these multiple pathological processes with high lung specificity are urgently needed. We engineered carrier-free, self-assembled nanoparticles from the natural products magnolol (Mag) and atractylenolide I (ATI) at an optimal 4:1 molar ratio. The Mag-ATI nanoparticles (MA NPs) exhibited an average hydrodynamic diameter of approximately 220.2&#xa0;nm, excellent colloidal stability, and a pH-responsive release profile favorable for the acidic pulmonary microenvironment. The drug loading was 81.7&#x2009;&#xb1;&#x2009;0.356% for Mag and 18.2&#x2009;&#xb1;&#x2009;0.129% for ATI, encapsulation efficiency exceeded 97% for both. In a murine lipopolysaccharide (LPS)-induced ALI model, MA NPs potently ameliorated pulmonary edema, outperforming individual drugs or their physical mixture. Biodistribution studies confirmed the MA NPs' efficient lung accumulation, with a fluorescence intensity 3.6-5.9 times higher than in other organs, and specific targeting to alveolar epithelial cells. Mechanistically, Mag inhibited TRPV4-mediated Ca2+ influx, thereby suppressing the downstream cAMP/AQP5 axis to limit water permeability and restore alveolar fluid balance. Mag and ATI attenuated inflammatory signaling via the protein kinase B (AKT)/nuclear factor kappa B (NF&#x2011;&#x3ba;B) pathway. Furthermore, Mag and ATI preserved epithelial barrier integrity by stabilizing tight junction proteins. These multi-modal mechanisms were systematically validated both in vitro and in vivo. Importantly, MA NPs demonstrated a favorable safety profile with no significant systemic toxicity. This study presents a novel, carrier-free nanotherapeutic platform that integrates the efficacy-enhancing rationale of traditional herbal medicine with advanced nanoassembly. By enabling coordinated modulation of inflammation, barrier function, and fluid homeostasis, MA NPs offer a potent, targeted, and translational strategy for the treatment of ALI/ARDS.

Hepatology is experiencing major shifts in disease etiologies and raising demand for multidisciplinary care. However, a globally harmonized framework defining core training content remains lacking. We aimed to develop a globally informed expert consensus framework for the content of core hepatology training, in order to provide a structured foundation for curriculum development. A two-round modified Delphi using the RAND/UCLA Appropriateness Method (RAM) was conducted. A comprehensive list of curriculum items was developed from international training standards, refined by a steering committee, and rated by a stratified international panel. Consensus was determined using medians and a disagreement index (DI), which classified curriculum items as essential, desirable, or optional. 456 experts completed Round 1, of whom 78.7% also completed Round 2. Consensus was strongest for foundational knowledge and core diagnostic skills, including interpretation of abnormal liver function and liver screening test results, and non-invasive fibrosis assessment (both DI=0). Management of major liver diseases was consistently prioritized as essential. Procedures with the highest endorsement for independent performance were paracentesis, transient elastography, variceal screening, and endoscopic variceal therapy. Consensus was limited for conventional ultrasonography and advanced interventions, reflecting regional variability in resources and scope of practice. Most experts (79.1%) supported formal training in research methodology, and the median recommended fellowship length was 24 months. Subgroup differences were mainly observed in selected resource-dependent or highly specialized items. This global consensus offers a priority-stratified outline of core hepatology training content providing a practical foundation for curriculum development and staged implementation across diverse health systems. Our study provides a consensus-based, priority-stratified framework for core hepatology training content that may inform curriculum development and local adaptation, given the growing global burden of liver disease and the heterogeneity of training standards. This framework may support curriculum mapping and local adaptation for trainees, program directors, professional societies, and policymakers, including in settings where structured hepatology training pathways are still evolving. In practical terms, these findings may assist educators and institutions in reviewing and refining national curricula and training structures. However, specific implementation decisions, including accreditation requirements and procedural training standards, will need to be adapted to local regulatory and resource contexts. Recognizing that these recommendations are based on expert consensus rather than outcome data and may be variably implementable in resource-limited settings, the next steps are pilot implementation in diverse settings, evaluation of trainee and patient outcomes, and iterative revision, supported by coordinated efforts from societies, governments, and training institutions.

Bone regeneration presents a significant clinical challenge due to the complex interplay between biological processes and the local mechanical environment. While polymeric scaffolds are widely utilized for their tunable physicochemical properties, traditional designs often fail to replicate the dynamic mechanical cues required for optimal tissue remodeling. This review critically examines the mechanobiological design of bioinspired polymeric scaffolds. We first categorize native bone mechanics and the role of mechanical stimuli-such as stiffness, fluid shear, and stability-in regulating the fracture healing cascade. We then bridge these biological principles with advanced fabrication strategies, analyzing how natural, synthetic, and composite polymers can be engineered to mimic the hierarchical stiffness and bioactivity of native bone. Furthermore, we discuss the role of computational modeling (e.g., Finite Element Analysis) in predicting scaffold performance and highlight emerging technologies, including 4D printing and piezoelectric scaffolds, which offer time-dependent and mechano-electrical adaptability. Finally, we address current barriers to clinical translation and propose future directions for mechanically adaptive systems that actively guide regeneration.