The clinical application of chemodynamic therapyis impeded by the insufficient intracellular H 2 O 2 level in tumor tissues.H erein, we developed as upramolecular nanoparticle via asimple one-step supramolecular polymerization-induced self-assembly process using platinum (IV) complex-modified b-cyclodextrin-ferrocene conjugates as supramolecular monomers.T he supramolecular nanoparticles could dissociate rapidly upon exposure to endogenous H 2 O 2 in the tumor and release hydroxyl radicals as well as platinum (IV) prodrugs in situ, which is reduced into cisplatin to significantly promote the generation of H 2 O 2 in the tumor tissue.Thus,the supramolecular nanomedicine overcomes the limitation of conventional chemodynamic therapyvia the self-augmented cascade radical generation and drug release.I na ddition, dissociated supramolecular nanoparticles could be readily excreted from the body via renal clearance to effectively avoid systemic toxicity and ensure long term biocompatibility of the nanomedicine. This work may provide new insights on the design and development of novel supramolecular nanoassemblies for cascade chemo/chemodynamic therapy.

BackgroundOsteosarcoma is the most common primary sarcoma of the bone. Lung osteosarcoma metastases at diagnosis have a significantly poor prognosis, even when surgery plus chemotherapy are performed. Our goal was to analyze clinical and sarcoma characteristics that could help identify factors related to an increased rate of lung metastasis and to identify different modes of treatment and its correlation with survival.Materials and MethodsThe Surveillance, Epidemiology, and End Results (SEER) database was used to identify all osteosarcoma patients diagnosed from 2010 to 2015. Patient characteristics such as age, sex, ethnicity, marital status, tumor location, histologic grade, surgery, chemotherapy, radiation therapy, SEER cause-specific death classification, survival, and lung metastasis were collected. These factors were analyzed using Univariate and multivariate regression models in survival analyses.ResultsA total of 1057 osteosarcoma patients diagnosed from 2010 to 2015 were included, of which 176 were patients with lung metastasis. Substantial disparities in the rate of lung metastasis existed when osteosarcoma patients were stratified according to tumor location (P = 0.0002) and tumor size (P < .001). Using a Multivariate Cox regression model, being older than 30 years (vs. younger than 30, HR = 2.171, 95% CI = 1.623–2.905, P < .0001), having a tumor >5–10 cm (vs. <5 cm, HR = 2.046, 95% CI = 1.153–3.632, P = 0.0014) and >10 cm (vs. <5 cm, HR = 3.610, 95% CI = 2.066–6.310, P < .0001) were related to an increased HR for all-cause death. The HR decreased in patients with surgery (vs. no surgery, HR = 0.189, 95% CI = 0.138–0.260, P < 0.0001) and osteosarcoma. As for osteosarcoma patients with lung metastases, Multivariate Cox regressions revealed that an increased HR was associated with being older than 30 years (vs. younger than 30 years, HR = 2.142, 95% CI = 1.273–3.605, P = .0041) and married (vs. no marriage, HR = 2.418, 95% CI = 1.400–4.176, P= .0015), while a decreased HR was related to having had surgery (vs. no surgery, HR = 0.282, 95% CI = 0.171–0.464, P < .0001) and chemotherapy (vs. no chemotherapy, HR = 0.107, 95% CI = 0.050–0.229, P < .0001).ConclusionsAdvanced age (older than 30 years) and large tumors were related to a higher risk of lung metastases in osteosarcoma patients. Therefore, patients who were diagnosed at advanced age or had large tumors should receive comprehensive chest CT scans. Surgery and chemotherapy can significantly improve the survival of metastatic patients, while radiotherapy did not improve survival in these patients.

Myotonia congenita is a non-dystrophic muscle disorder affecting the excitability of the skeletal muscle membrane. It can be inherited either as an autosomal dominant (Thomsen's myotonia) or an autosomal recessive (Becker's myotonia) trait. Both types are characterised by myotonia (muscle stiffness) and muscular hypertrophy, and are caused by mutations in the muscle chloride channel gene, CLCN1. At least 50 different CLCN1 mutations have been described worldwide, but in many studies only about half of the patients showed mutations in CLCN1. Limitations in the mutation detection methods and genetic heterogeneity might be explanations. In the current study, we sequenced the entire CLCN1 gene in 15 Northern Norwegian and three Northern Swedish MC families. Our data show a high prevalence of myotonia congenita in Northern Norway similar to Northern Finland, but with a much higher degree of mutation heterogeneity. In total, eight different mutations and three polymorphisms (T87T, D718D, and P727L) were detected. Three mutations (F287S, A331T, and 2284+5C4T) were novel while the others (IVS1+3A4T, 979G4A, F413C, A531V, and R894X) have been reported previously. The mutations F413C, A531V, and R894X predominated in our patient material. Compound heterozygosity for A531V/R894X was the predominant genotype. In two probands, three mutations cosegregated with myotonia. No CLCN1 mutations were identified in two families. Our data support the presence of genetic heterogeneity and additional modifying factors in myotonia congenita. European Journal of Human Genetics (2001) 9, 903 ± 909.

Supramolecular polymers (SPs) have attracted broad interest because of their intriguing features and functions. Host–guest interactions often impart tunable physicochemical properties, reversible hierarchical organization, and stimuli‐responsiveness to SPs for diverse biomedical applications. Characterized by strong but dynamic interactions with guest molecules, cucurbit[n]uril (CB[n]) has shown great potential as an important building block of various functional polymers for biomedical applications. In this Minireview, we summarize the most recent examples regarding the design, fabrication, and biomedical applications of CB[n]‐based supramolecular polymers (CSPs), which are categorized as noncovalent and covalent CSPs according to the interactions between the CB[n] and polymer backbones. The design principles of CSPs and their unique advantages for biomedical applications, as well as the developmental trends and future perspectives of this cross‐disciplinary area are also discussed.

Pre-eclampsia is associated with increased levels of cholesterol and uric acid and an inflamed placenta expressing danger-sensing pattern recognition receptors (PRRs). Crystalline cholesterol and uric acid activate the PRR Nod-like receptor protein (NLRP)3 inflammasome to release interleukin (IL)-1β and result in vigorous inflammation. We aimed to characterize crystal-induced NLRP3 activation in placental inflammation and examine its role in pre-eclampsia. We confirmed that serum total cholesterol and uric acid were elevated in pre-eclamptic compared to healthy pregnancies and correlated positively to high sensitivity C-reactive protein (hsCRP) and the pre-eclampsia marker soluble fms-like tyrosine kinase-1 (sFlt-1). The NLRP3 inflammasome pathway components (NLRP3, caspase-1, IL-1β) and priming factors [complement component 5a (C5a) and terminal complement complex (TCC)] were co-expressed by the syncytiotrophoblast layer which covers the placental surface and interacts with maternal blood. The expression of IL-1β and TCC was increased significantly and C5a-positive regions in the syncytiotrophoblast layer appeared more frequent in pre-eclamptic compared to normal pregnancies. In-vitro activation of placental explants and trophoblasts confirmed NLRP3 inflammasome pathway functionality by complement-primed crystal-induced release of IL-1β. This study confirms crystal-induced NLRP3 inflammasome activation located at the syncytiotrophoblast layer as a mechanism of placental inflammation and suggests contribution of enhanced NLRP3 activation to the harmful placental inflammation in pre-eclampsia.

In the recent decade, macrocycle-surfaced polymer nanocapsules have been developed and studied as potential drug carriers. In particular, a unique group of these nanocapsules were constructed from a covalently self-assembled polymer network based on several classic macrocycles including cucurbituril, pillararene, and calixarene. The unique structure of these nanocapsules consists of a liquid or solid core and a shell laced with macrocycles in which the macrocycles not only act as the shell matrix of the nanocapsules but also allow further facile, modular functionalization via host−guest interactions with guesttagged molecules. More interestingly, when a responsive cross-linker was introduced between the macrocycles, the payload inside the nanocapsules could be selectively released in the presence of typical hallmarks of certain diseases, which is of great interest for biomedical applications. In this Topical Review, macrocycle-surfaced polymer nanocapsules derived from covalently self-assembled polymer networks are introduced systemically with a focus on the molecular design and biomedical applications.

Mitochondrial fission is often associated with the development of oxidative stress related diseases, as the fragmentation of mitochondria undermines their membranes, advances production of reactive oxygen species, and promotes apoptosis. Therefore, induction of mitochondrial aggregation and fusion could potentially reverse such medical conditions. Herein, a supramolecular strategy to induce mitochondrial aggregation and fusion is developed for the first time. A polyethylene glycol (PEG) system that was dually tagged with triphenylphosphonium (TPP) and adamantane (ADA), namely TPP-PEG-ADA, was designed to target mitochondria and functionalize their surfaces with ADA. Thereafter, the addition of cucurbit[7]­uril (CB[7]) grafted hyaluronic acid (HA) induced supramolecular aggregation and fusion of mitochondria, via strong host–guest interactions between the CB[7] moiety of CB[7]-HA and ADA residing on the surface of mitochondria. As a proof-of-principle, chemically stressed SH-SY5Y cells and zebrafish neurons were effectively protected via this supramolecular mitochondrial fusion strategy in vitro and in vivo, respectively. This study may open up new venues in not only fundamentally controlling mitochondrial dynamics but also addressing the medical needs to treat diseases associated with mitochondrial fission and fragmentation.

Herein, a biocompatible 2D metal-organic frameworks (Cu-TCPP(Fe)) based on TCPP(M) (TCPP = tetrakis (4-carboxyphenyl) porphyrin, M = Fe) and copper ion were synthesized as a novel drug carrier. Sequentially, the cisplatin was loaded on the merge of carboxyl-rich Cu-TCPP(Fe) through forming favorable carboxyl-drug interactions. The prepared Pt/Cu-TCPP(Fe) showed highly enhanced cytotoxicity than that of free cisplatin in human pulmonary carcinoma A549 cells, whereas inverse inhibitory effects were observed in human normal BEAS-2B cells. Further, the mechanism of action about the desirable results was also elaborated. Our study highlighted the potential synergies between the nanocarrier and the anticancer drugs.