Cyanobacteria are gram-negative prokaryotic microorganisms composed of both broad morphological and phylogenetic diversity inherited from diverse ecosystems like aquatic, terrestrial, or extremophilic environments. In this study, three cyanobacteria strains from the Blue Biotechnology and Ecotoxicology Culture Collection (LEGE-CC) were obtained from different environments in Portugal. Polyphasic analysis was applied for taxonomic identification. The proximate composition analysis indicated the lipid content (6.2% to 9.1% dry weight (DW)), protein content (28.2% to 62.9% DW), and carbohydrate content (19.5% to 46.1% DW). The fatty acid (FA) profiles of the strains revealed the presence of 19 different FAs, with FA 16:0 found in the highest abundance. The lipidomic analysis revealed 230 lipid species, with Laspinema sp. LEGE 06078 displaying the highest diversity (125 lipid species). These included species-specific and common lipids species that denote biochemical uniqueness that are also carriers of omega-3 FA (n-3). Biological assays exhibited strong antioxidant activity against ABTS•+ and DPPH• in Laspinema sp. LEGE 06078, while Sphaerospermopsis sp. LEGE 00249 was renowned for reducing lipids in zebrafish larvae. The findings are of immense significance on the lipidomics diversity of cyanobacteria in terms of nutrition, health, and biotechnology, such as addressing obesity and sustainable resource production.
Culture collections such as the Blue Biotechnology and Ecotoxicology Culture Collection (LEGE-CC) hold approximately 1200 cyanobacterial strains and are critical community resources. However, many isolates in this and other collections have not been described with a polyphasic approach, and this limits further study. Here, we employed a polyphasic methodology that integrates 16S rRNA gene phylogenetic analyses, similarity (p-distance), 16S-23S ITS rRNA region secondary structures, morphological analyses, and habitat assessments to describe four novel cyanobacterial genera from the LEGE-CC, Portugal. Pseudolimnococcus planktonicus gen. et sp. nov. (Chroococcales) is phylogenetically and morphologically related to Limnococcus. The 16S rRNA gene similarity between the types of both genera is only 93.1%. Morphologically, Pseudolimnococcus cells do not reach the original spherical shape before the next division or have aerotopes and firm mucilage, while Limnococcus cells reach the original shape, lack aerotopes, and have diffluent mucilage. Eucapsopsis lusitanus gen. et sp. nov. (Chroococcales) is morphologically similar to Eucapsis but differs from it by having aerotopes and diffluent envelope. Eucapsis lacks aerotopes and has firm mucilaginous envelopes, rarely diffluent. Both genera are phylogenetically very distant from each other and have only 90.68% 16S rRNA gene similarity. Pseudoacaryochloris arrabidensis gen. et sp. nov. (Acaryochloridales) differs from Acaryochloris by the lack of mucilaginous envelope, which is present in Acaryochloris. Both genera are phylogenetically distant and have only 94.1% 16S rRNA gene similarity. Moreover, Acaryochloris is marine (sponge symbiont), while Pseudoacaryochloris is from freshwater. Vasconcelosia minhoensis gen. et sp. nov. (Nodosilineales) is phylogenetically related to Cymatolege but has only 94.3% similarity with this genus. Morphologically both genera are distinct. Vasconcelosia has a Romeria-like structure, while Cymatolege has a Phormidium-like structure. In all cases the 16S-23S ITS rRNA region secondary structures are in agreement with the other analyses. These novel genera expand the diversity of cyanobacteria in culture collections.
The prevention of marine biofouling remains a global challenge due to environmental concerns associated with current biocidal antifouling (AF) agents and increasing regulatory pressure to ban such biocides. Natural products present promising alternatives as effective and eco-friendly AF solutions, with cyanobacteria emerging as a rich source of bioactive compounds due to their remarkable biosynthetic potential. In this study, the AF bio-guided discovery of natural products from the cyanobacterium Leptothoe sp. LEGE 181152 led to the isolation of two nucleosides - adenosine (1) and 2'-deoxyadenosine (2), which were for the first time explored as innovative AF agents. A comprehensive approach was undertaken, including AF efficacy across biological levels, ecotoxicity and ecological risk assessment, and molecular targets elucidation. Compounds 1 and 2 successfully inhibited mussel settlement (EC50 = 6.63; 8.74 µM), without exhibiting lethal effects (LC50 > 200 µM). At these concentrations, both compounds increased the in vitro acetylcholinesterase activity. Functional enrichment analysis revealed effects on proteins associated to ciliary motility and ATP metabolism. Additionally, both compounds inhibited the growth of Navicula sp. ( ̴40 % for 1, and 60 % for 2). In addition to showing no effect on marine biofilm-forming marine bacteria, ecotoxicological assays with nauplii of Artemia salina and Amphibalanus amphitrite revealed no acute toxicity in these species. Furthermore, simulated environmental data indicated a low potential for bioaccumulation and low environmental persistence. Overall, these findings identify adenosine and 2'-deoxyadenosine as novel, low-risk natural AF agents, with real-world applicability as promising candidates for incorporation into marine coatings, thereby contributing to the development of more sustainable solutions for biofouling management.
Recent analyses of genome data indicate that members of the cyanobacterial order Pleurocapsales show tremendous potential for natural product discovery. However, only a few compounds have been reported from this order. Here, we report the isolation of hyellamide (1), a glycosylated N-acyl tyrosine-derived eneamide, from the pleurocapsalean cyanobacterium Hyella patelloides LEGE 07179. The putative biosynthetic gene cluster for 1 was identified in the genome of the producing organism and a biosynthetic proposal is presented. This work sheds light on the chemistry of the Pleurocapsales and expands the chemical repertoire of cyanobacterial natural products to include N-acyl tyrosine-derived molecules.
Genome mining has emerged as an important tool for the discovery of natural products and is particularly effective for the swift identification of ribosomally synthesized and post-translationally modified peptides (RiPPs). Among RiPPs, cyanobactins have gained attention due to their diverse structures and bioactive properties. Here, we explored the Microcoleaceae cyanobacterium LEGE 16532 strain and identified the mon biosynthetic gene cluster (BGC), which was predicted to encode cyanobactin-like molecules. This led to the detection of 11 macrocyclic cyanobactins, the monchicamides, some of which feature mono- or diprenylation. One of the compounds was isolated, monchicamides I (9), and its planar structure was established by LC-HRESIMS/MS data as well as 1D and 2D NMR spectroscopy, confirming forward O-prenylation in Tyr. In addition, the absolute configuration of compound 9 was determined by Marfey's method and chiral-phase HPLC. The structures of the additional cyanobactins were proposed from MS/MS data analysis. The bioactivity profile of the isolated compound was also evaluated, but no cytotoxic, antimicrobial, or antiamoebic activity was observed.
Essential trace metals are vital for cellular processes, such as respiration, DNA replication, and photosynthesis. Cyanobacteria must tightly regulate metal homeostasis to prevent deficiency or toxicity, yet their metallophores remain overlooked. Here, we report lusichelins A-E (1-5), new metallophores isolated from the marine cyanobacterium Lusitaniella coriacea LEGE 07167. Their structures and configurational assignments were determined by using NMR, mass spectrometry, TD-DFT calculations, and retrobiosynthetic insights. Lusichelins feature a unique structural arrangement with thiazoline/thiazole rings connected via a vinyl group, an aliphatic carbon chain, or directly enabling the potential for metal coordination. Genomic analysis identified a hybrid PKS/NRPS biosynthetic gene cluster consistent with the lusichelin structure, bearing traits characteristic of metallophore biosynthesis. Functionally, lusichelins act as metallophores capable of chelating both iron and copper. Lusichelin C (3) consistently bound iron under both metal-rich and metal-limited culture conditions, while copper complexation was only observed under elevated copper levels. At physiologically relevant pH values, no significant metal-binding preference was detected. Moreover, compound production was maximized under metal-rich conditions and in response to copper limitation. Lusichelin B (2) exhibited cytotoxicity against colon carcinoma cells while reversing multidrug resistance via ABCB1 efflux pump modulation. These findings expand our understanding of cyanobacterial metallophores in microbial metal homeostasis and highlight their biological potential.
Cyanobacteria are among the oldest organisms colonizing Earth. Their great biodiversity and ability to biosynthesize secondary metabolites through a variety of routes makes them attractive resources for biotechnological applications and drug discovery. In this pioneer study, four filamentous cyanobacteria (Cephalothrix lacustris LEGE 15493, Leptolyngbya boryana LEGE 15486, Nodosilinea nodulosa LEGE 06104 and Leptothoe sp. LEGE 11479) were explored for their anti-inflammatory potential in cell and cell-free in vitro bioassays, involving different inflammatory mediators and enzymes. Extracts of different polarities were sequentially prepared and chemically characterized for their content of phycobiliproteins (PBPs) and carotenoids. HPLC-PDA analysis of the acetone extracts revealed β-carotene to be the dominant carotenoid (18.4-44.3 mg/g) and zeaxanthin as the dominant xanthophyll (52.7-192.9 mg/g), with Leptothoe sp. LEGE 11479 and Nodosilinea nodulosa LEGE 06104, respectively, being the richest strains. The PBP profile was in accordance with the color presented by the aqueous extracts, with Leptolyngbya boryana LEGE 15486 being the richest in phycocyanin (204.5 μg/mg) and Leptothoe sp. LEGE 11479 the richest in phycoerythrin (78.5 μg/mg). Aqueous extracts were more effective in superoxide anion radical scavenging, while acetone ones were more effective in scavenging nitric oxide radical (●NO) and in inhibiting lipoxygenase. Acetone extracts also reduced ●NO production in lipopolysaccharide-stimulated RAW 264.7 macrophages, with the mechanistic study suggesting a downregulation of the inducible nitric oxide synthase expression. Nodosilinea nodulosa LEGE 06104 and Leptothoe sp. LEGE 11479 acetone extracts presented the lowest IC50 values for the mentioned assays, pointing them out as promising resources for the development of new multi-target anti-inflammatory therapies.
The aim of this study was to document the biodiversity of cyanobacteria genera isolated from intertidal and subtidal zones in Cabo Verde. The identification of the strains was conducted using a polyphasic study, comprising 16S rRNA gene maximum likelihood and Bayesian inference phylogeny, 16S rRNA identity (p-distance), 16S-23S ITS secondary structure, morphological, and habitat analyses. A total of 51 strains were isolated by micromanipulation and by streaking biomass onto Petri dishes with a solid medium. Seventeen strains were identified as belonging to the Salileptolyngbya genus and five to Leptothoe; sixteen strains were distributed across twelve genera. Thirteen strains were grouped into eight distinct clades, but could not be assigned to any cyanobacterial genus, indicating that they could be described as new cyanobacterial genera in the future. The phylogenies also exhibited isolates LEGE 181157, LEGE 181224, and LEGE 181227 clustered with Gibliniella, but in a separate clade from the G. alaskensis type. The 16S rRNA gene identity values among these new isolates and G. alaskensis ranged from 94.4% to 95.5%. The 16S-23S ITS dissimilarity between LEGE 181224 and G. alaskensis was 9.4%. Morphologically, these three LEGE strains differ from G. alaskensis in that they have trichomes that are never coiled and have diffluent mucilaginous envelopes, whereas G. alaskensis has coiled trichomes with firm sheaths. Based on these strains, we describe here a new species of Gibliniella.
This article analyses the Italian Legislative Delegation Bill of 4 September 2025 (DDL 2025), which proposes the recontextualization of healthcare liability through the introduction of Article 590-septies into the Italian Criminal Code (c.p.) and the amendment of Article 590-sexies c.p. and of Articles 5 and 7 of the Gelli-Bianco Act (Law No. 24/2017). The study examines the extent to which the reform, if enacted, would produce a shift of criminal negligence liability from the individual frontline clinician towards the apex management figures of healthcare organizations-at both the corporate and hospital levels-and under what conditions such a shift would be compatible with the constitutional principle of personal criminal responsibility (Art. 27 Const.) and with the evidentiary criteria for criminally relevant omission. Adopting a doctrinal and jurisprudential analysis approach, the study formulates a falsifiable hypothesis, accompanied by four ex post verifiability indicators observable over a five-year time horizon following the possible entry into force of the provision. The analysis demonstrates how the DDL 2025 would recontextualize the notion of culpa-encompassing imperizia (lack of skill), negligenza (negligence), and imprudenza (imprudence), functionally comparable to forms of criminal negligence in common law systems-by linking fault assessment to contextual factors such as organizational deficiencies and resource scarcity. This approach would adopt a deflationary framework, establishing a distinction between avoidable human error and errors caused by systemic dysfunctions and foreshadowing a potential shift of liability towards apex management, who are required to ensure organizational models adequate to patient safety. This orientation, far from constituting a doctrinal novelty, would formalize ex lege a trajectory already established in civil and criminal case law of the Court of Cassation (Cass. No. 6386/2023, "Travaglino"), further intersecting with the administrative liability regime for organizations under Legislative Decree 231/2001. Significant interpretive challenges remain, related to the application of criminal liability criteria to the omissive conduct of healthcare managers, as well as to the contrasting international evidence on the behavioural effectiveness of medical liability reforms. The redefinition of top-management liability would therefore be configured not merely as a tool for the protection of the individual professional but as a derived constitutional guarantee of the right to health and the safety of care, pursued through formalized risk governance, the integration of incident reporting and organizational audit systems, the transition towards Enterprise Risk Management models, and the traceability of apex decision-making processes. Examples drawn from other European jurisdictions illustrate the heterogeneity of legal approaches to medical fault and frame the Italian proposal as a context-specific solution that nonetheless could contribute to the international debate on institutional and organizational accountability for patient safety.
Background/Objective: Root resective procedures are well established tooth-preserving techniques used when pathology is confined to one root of a multirooted tooth or in the furcation area. Although in recent years implant therapy has become a standard approach in many cases, the rising incidence of peri-implantitis has renewed interest in classical conservative treatment alternatives, such as hemisection, root resection and bicuspidization. The aim of this study is to present clinical cases in which hemisection and bicuspidization were performed to maintain compromised molars in function and achieve long-term outcomes. Methods: This retrospective case series study was conducted in a private dental practice and included three patients treated between 2009 and 2017. The presented cases involved molar teeth exhibiting a vertical fracture or extensive subgingival carries in one root while the remaining root(s) demonstrated favourable periodontal, endodontic and restorative prognosis. An interdisciplinary approach was followed in each case, involving comprehensive clinical and radiographic evaluation including cone beam computed tomography when indicated. The clinical treatment included an endodontic approach (primary treatment or retreatment if required) followed by hemisection or bicuspidization and placement of a permanent prosthetic rehabilitation with full-coverage restoration designed to optimize proper load distribution. Clinical and radiographic follow-up examination was done up to six years in case one, after six months in case two and up to six years in case three. Results: The teeth remained in function through their respective follow-up periods. Clinical and radiographic assessments, according to predefined success criteria, demonstrated periodontal stability (probing depth ≤ 4 mm), no evidence of secondary caries or root fracture, absence of clinical symptoms, normal tooth mobility and masticatory function, absence or reduction in periradicular radiolucency, and stable bone levels. Conclusions: Resective techniques require an interdisciplinary approach, namely, careful case selection, lege artis endodontic treatment, precise surgical technique, and appropriate prosthetic rehabilitation, in order to provide predictable and long-term outcomes. Within the limitations of this case series, resective techniques appeared to be a reliable and predictable alternative to extraction and implant placement in carefully selected clinical cases.
Populations of European bison (Bison bonasus), Eurasian beaver (Castor fiber), and Eurasian moose (Alces alces) in Poland are currently experiencing significant growth. These species are subject to strict legal protection or specific regulatory frameworks. The purpose of the study is to analyze Polish legislation concerning the protection of selected species and to identify legislative actions that could ensure healthy, sustainable, and well-managed population levels in Poland. The study also explores carefully regulated forms of sustainable use, including the potential consumption of meat from these species. During this research, the methodology of analysis and scientific interpretation of legal acts was used. Case law and relevant socio-economic and environmental factors were also analyzed and highlighted. The results show that the law currently in force and its interpretation may pose challenges to achieving fully effective conservation outcomes. Wildlife protection requires effective, locally adapted population management. Proposals for legal changes that would support diversified and sustainable management approaches, while maintaining a high level of protection, ensuring environmental stability and sustainability, and ensuring the highest standards of public safety, are presented. De lege ferenda postulates indicate that it is essential to balance the legitimate interests of wildlife conservation, public health, and society.
Cyanobacteria are prolific producers of specialized metabolites of growing interest for blue biotechnology, transversal to various sectors such as cosmetics, foods and pharmaceuticals. In this work, the marine cyanobacterial strain Salileptolyngbya sp. LEGE 181209, from Cabo Verde, was systematically characterized to resolve its taxonomy, pigments profile, and cytotoxicity assessment. A polyphasic workflow combining 16S rRNA gene phylogenies, 16S-23S ITS secondary structures, p-distance, morphology, and scanning electron microscopy (SEM) was used to establish the taxonomic placement of the strain as a new species of the genus. PCR assays targeting the toxin biosynthetic genes mcyA and anaC, and cytotoxicity assays in HaCaT keratinocytes showed low-to-absent cytotoxicity, supporting a safety-forward profile for downstream use. A sequential extraction with solvents of different polarities yielded complementary pigment fractions profiled by HPLC-PDA and spectrophotometry. Total carotenoids reached 72.7 µg mg-1 of dry extract (DE), the profile being dominated by β-carotene and zeaxanthin (≈42 and 8 µg mg-1 of DE, respectively); chlorophyll-a was also very representative, reaching 85.6 µg mg-1 of DE. Phycobiliproteins dominated the polar fraction, with phycocyanin reaching 150 µg mg-1, followed by sugars (19.7 µg of glucose equivalents mg-1) and phenols (8.8 µg of gallic acid equivalents mg-1).
We briefly review the development of fundamental concepts in the current theory and experiments on molecular chirality, including the small effects arising from parity violating weak nuclear interaction. After a short summary of the history of theory and experiments in this field, we discuss the five basic hypotheses on the structure of chiral molecules. One of these introduces parity violation as the dominant effect in isolated molecules. We then provide a brief description of current experiments for measuring the parity violating energy difference ΔpvE between the ground states of enantiomers of chiral molecules by an approach which can also be used for the construction of a molecular quantum switch and for testing other hypotheses of molecular chirality. We finally introduce the long-standing open question of the origin of biomolecular homochirality. We stress the important distinction between hypotheses postulating a selection either by a 'de facto' (chance) or by a 'de lege' mechanism (necessity because of parity violation). This leads to the recent astrophysical detection of chiral molecules in the interstellar medium as a basis for a future possible spectroscopic detection of extra-terrestrial and exoplanetary homochirality as a signature of life.
In 2024, a Bill "On Palliative Care, End-of-Life Decision-Making and Euthanasia" was submitted to the Czech Parliament for consideration. This article evaluates the Bill through doctrinal and ethico-legal analysis and a comparative perspective centred on Belgium, whose model influenced the Czech proposal. The Bill is unusual in combining, within one statute, conventional end-of-life practices - palliative care, withholding or withdrawal of life-sustaining treatment, and palliative sedation - and "assisted death", covering euthanasia and physician-assisted suicide. With regard to conventional practices, the Bill gives legal form to a right to palliative care, introduces "medically inadequate treatment" as the threshold for limiting life-sustaining interventions, and embeds procedural safeguards (information, participation, mediation by an ethics committee, and judicial review) intended to enhance transparency, patient autonomy, and legal certainty for clinicians. With regard to assisted death, the proposal sets out eligibility criteria (adult legal competence, voluntariness, an incurable and irreversible illness, and permanent and unbearable suffering without any prospect of improvement) and a staged procedure: a preliminary request, independent consultation, a qualified written request, final verification immediately before the act, and mandatory ex post review by a commission based on a non-anonymous report. This article shows that the Czech Bill represents a serious and coherent attempt to bring end-of-life regulation in the Czech Republic into conformity with the human-rights standards developed in the case law of the ECtHR. It also advances several de lege ferenda recommendations that seek to synthesise the strengths of the Czech Bill and the Belgian model while avoiding identified shortcomings. These recommendations aim to ensure that any European end-of-life framework remains firmly anchored in human-rights requirements, while also taking into account the practical realities of clinical decision-making and the accumulated legal experience of European states that have already introduced forms of assisted death.
As populations age, more older adults require support with decision-making, often relying on informal caregivers. This multi-methods study explores how informal caregivers in the Netherlands participate in healthcare and financial decision-making for older adults, what factors are associated with their involvement in the decision-making process, and how different legal measures facilitate their participation in decision-making. Drawing on survey data from 815 caregivers and 13 in-depth interviews, the study identifies various types of involvement - from supported to substituted decision-making - with mutual decision-making as a distinct category. Participation is affected by the type, complexity and impact of decisions, the older adult's decision-making abilities, wishes and preferences, and the involvement of others. The need for legal authority varies by relationship and caregiving role. While ex lege measures generally suffice for medical decisions, financial matters often require voluntary measures, which appear inconsistently recognized in practice. When voluntary arrangements are not feasible, adult guardianship measures may offer legal clarity. Although some international rights bodies call for the abolition of substituted decision-making regimes like adult guardianship, this study highlights their practicality in certain contexts. The findings call for legal and policy frameworks that both empower informal caregivers and safeguard the well-being of older adults.
Metastatic tumor cell dissemination is the leading cause of cancer-related deaths. Clustered circulating tumor cells (CTCs) possess higher metastatic potential than single CTCs. Epithelial adherens junction (AJ) proteins typically mediate stable cell-cell interactions; however, these proteins are frequently lost in highly aggressive triple-negative breast cancers (TNBCs), raising the question of how CTCs from such tumors cluster. Here we show that the extracellular matrix (ECM) component hyaluronan (HA) mediates AJ-independent CTC clustering in TNBCs. HA is necessary and sufficient to drive clustering of tumor cells expressing its receptor CD44. Mechanistically, HA initiates contact between neighboring cells through actin-based membrane protrusions. As cells are pulled closer, these initial interactions expand to membrane-membrane contact and are subsequently stabilized by desmosomes. CTC-derived HA also acts as a docking platform to promote heterotypic cluster formation by recruiting non-CTCs, including immune cells. Thus, this ECM-receptor interaction enables CTC clustering and survival under shear stress, enhancing TNBC metastasis.
Antimicrobial resistance (AMR) is escalating worldwide, posing a serious threat to global public health by driving infections that are no longer treatable with conventional antibiotics. CRISPR-Cas technology offers a programmable and highly specific therapeutic alternative by directly targeting the genetic determinants responsible for resistance. Various CRISPR systems can restore antibiotic susceptibility and induce selective bactericidal effects by eliminating resistance genes, disrupting biofilm formation, and inhibiting virulence pathways. Moreover, CRISPR can suppress horizontal gene transfer (HGT) by removing mobile genetic elements such as plasmids, thereby limiting the ecological spread of AMR across humans, animals, and the environment. Advances in delivery platforms-including conjugative plasmids, phagemids, and nanoparticle-based carriers-are expanding the translational potential of CRISPR-based antimicrobial strategies. Concurrent progress in Cas protein engineering, spatiotemporal activity regulation, and AI-driven optimization is expected to overcome current technical barriers. Collectively, these developments position CRISPR-based antimicrobials as next-generation precision therapeutics capable of treating refractory bacterial infections while simultaneously suppressing the dissemination of antibiotic resistance.
The impact of acute cannabis exposure on brain function and cognitive performance varies among individuals. Acute effects of cannabis on behavior may be absent or benign in chronic users, while occasional users experience significant impairment in day-to-day operations. It is hypothesized that repeated cannabis use induces neuroadaptations leading to tolerance and desensitization, although the precise mechanisms underlying these adaptations remain unclear. In this study, we investigated acute and persistent effects of vaporized cannabis on brain dynamics in a placebo-controlled neuroimaging trial involving occasional (n = 23) and chronic (n = 20) cannabis users. Functional resting-state data were collected to assess dynamic functional connectivity changes during intoxication and their association with attentional performance and normative cannabinoid CB1 receptor density. Cannabis intoxication induced significant acute alterations in the dynamics of brain network organization, as shown by a reduced occurrence of a hyperconnected brain state in both user groups. Chronic users also displayed decreased segregation of brain networks independent of treatment condition, suggesting persisting neuroadaptations. Dynamic reconfiguration of hyperconnected brain motifs correlated with attentional performance, which was most impaired in occasional users, indicating tolerance in chronic users. Both the acute and persistent effects of cannabis on dynamic brain state organization were significantly associated with spatial CB1 receptor density. Acute cannabis-induced cognitive impairment is influenced by (persistent) network reconfigurations and CB1 receptor density. These findings emphasize the relevance of neural dynamics and individual neuroadaptations to (prolonged) cannabis use when assessing the behavioral effects of cannabis in therapeutic, legal, and societal settings.
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.
A mesoscale model for chloride diffusion in reinforced concrete was established by considering the blocking effect of reinforcing steel. This model improved the accuracy of chloride concentration prediction and enhanced the reliability of durability-based service-life assessment. First, a series of chloride transport experiments under wetting-drying cycles was carried out on reinforced concrete specimens. These experiments were used to evaluate the effects of exposure condition, rebar blocking, and concrete compressive strength on chloride transport. Then, a mesoscale chloride diffusion model including the rebar-induced blocking effect was developed and validated. Finally, a sensitivity analysis of the key parameters was conducted. The results showed that, compared with concrete without longitudinal reinforcement, wetting-drying cycles had a stronger influence on reinforced concrete with longitudinal bars. The enhancing effect of wetting-drying cycles on chloride ingress was the strongest, followed by compressive strength and then the rebar-induced blocking effect, although the latter was still non-negligible. As the rebar diameter increased, the peak chloride concentration increased, and the chloride concentration around the aggregates also increased more rapidly.