IL-6 mediates olfactory dysfunction in a mouse model of allergic rhinitis.

BACKGROUND: Immune-inflammatory response is a key element in the occurrence and development of olfactory dysfunction (OD) in patients with allergic rhinitis (AR). As one of the core factors in immune-inflammatory responses, interleukin (IL)-6 is closely related to the pathogenesis of allergic diseases. It may also play an important role in OD induced by diseases, such as Sjögren's syndrome and coronavirus disease 2019. However, there is no study has reported its role in OD in AR. Thus, this study aimed to investigate the role of IL-6 in AR-related OD, in an attempt to discover a new target for the prevention and treatment of OD in patients with AR. METHODS: Differential expression analysis was performed using the public datasets GSE52804 and GSE140454 for AR, and differentially expressed genes (DEGs) were obtained by obtaining the intersection points between these two datasets. IL-6, a common differential factor, was obtained by intersecting the DEGs with the General Olfactory Sensitivity Database (GOSdb) again. A model of AR mice with OD was developed by sensitizing with ovalbumin (OVA) to verify the reliability of IL-6 as a key factor of OD in AR and explore the potential mechanisms. Furthermore, a supernatant and microglia co-culture model of nasal mucosa epithelial cells stimulated by the allergen house dust mite extract Derp1 was established to identify the cellular and molecular mechanisms of IL-6-mediated OD in AR. RESULTS: The level of IL-6 in the nasal mucosa and olfactory bulb of AR mice with OD significantly increased and showed a positive correlation with the expression of olfactory bulb microglia marker Iba-1 and the severity of OD. In-vitro experiments showed that the level of IL-6 significantly increased in the supernatant after the nasal mucosa epithelial cells were stimulated by Derp1, along with significantly decreased barrier function of the nasal mucosa. The expression levels of neuroinflammatory markers IL-1ß and INOS increased after a conditioned culture of microglia with the supernatant including IL-6. Then knockdown (KD) of IL-6R by small interfering RNA (siRNA), the expression of IL-1ß and INOS significantly diminished. CONCLUSION: IL-6 plays a key role in the occurrence and development of OD in AR, which may be related to its effect on olfactory bulb microglia-mediated neuroinflammation.

Machine learning identifies the risk of complications after laparoscopic radical gastrectomy for gastric cancer.

BACKGROUND: Laparoscopic radical gastrectomy is widely used, and perioperative complications have become a highly concerned issue. AIM: To develop a predictive model for complications in laparoscopic radical gastrectomy for gastric cancer to better predict the likelihood of complications in gastric cancer patients within 30 days after surgery, guide perioperative treatment strategies for gastric cancer patients, and prevent serious complications. METHODS: In total, 998 patients who underwent laparoscopic radical gastrectomy for gastric cancer at 16 Chinese medical centers were included in the training group for the complication model, and 398 patients were included in the validation group. The clinicopathological data and 30-d postoperative complications of gastric cancer patients were collected. Three machine learning methods, lasso regression, random forest, and artificial neural networks, were used to construct postoperative complication prediction models for laparoscopic distal gastrectomy and laparoscopic total gastrectomy, and their prediction efficacy and accuracy were evaluated. RESULTS: The constructed complication model, particularly the random forest model, could better predict serious complications in gastric cancer patients undergoing laparoscopic radical gastrectomy. It exhibited stable performance in external validation and is worthy of further promotion in more centers. CONCLUSION: Using the risk factors identified in multicenter datasets, highly sensitive risk prediction models for complications following laparoscopic radical gastrectomy were established. We hope to facilitate the diagnosis and treatment of preoperative and postoperative decision-making by using these models.

What can molecular assembly learn from catalysed assembly in living organisms?

Molecular assembly is the process of organizing individual molecules into larger structures and complex systems. The self-assembly approach is predominantly utilized in creating artificial molecular assemblies, and was believed to be the primary mode of molecular assembly in living organisms as well. However, it has been shown that the assembly of many biological complexes is "catalysed" by other molecules, rather than relying solely on self-assembly. In this review, we summarize these catalysed-assembly (catassembly) phenomena in living organisms and systematically analyse their mechanisms. We then expand on these phenomena and discuss related concepts, including catalysed-disassembly and catalysed-reassembly. Catassembly proves to be an efficient and highly selective strategy for synergistically controlling and manipulating various noncovalent interactions, especially in hierarchical molecular assemblies. Overreliance on self-assembly may, to some extent, hinder the advancement of artificial molecular assembly with powerful features. Furthermore, inspired by the biological catassembly phenomena, we propose guidelines for designing artificial catassembly systems and developing characterization and theoretical methods, and review pioneering works along this new direction. Overall, this approach may broaden and deepen our understanding of molecular assembly, enabling the construction and control of intelligent assembly systems with advanced functionality.

Autoantibody repertoire profiling in tissue and blood identifies colorectal cancer-specific biomarkers.

Autoantibodies (AAbs) in the blood of colorectal cancer (CRC) patients have been evaluated for tumor detection. However, it remains uncertain whether these AAbs are specific to tumor-associated antigens. In this study, we explored the IgG and IgM autoantibody repertoires in both the in situ tissue microenvironment and peripheral blood as potential tumor-specific biomarkers. We applied high-density protein arrays to profile AAbs in the tumor-infiltrating lymphocyte supernatants and corresponding serum from four patients with CRC, as well as in the serum of three noncancer controls. Our findings revealed that there were more reactive IgM AAbs than IgG in both the cell supernatant and corresponding serum, with a difference of approximately 3-5 times. Immunoglobulin G was predominant in the serum, while IgM was more abundant in the cell supernatant. We identified a range of AAbs present in both the supernatant and the corresponding serum, numbering between 432 and 780, with an average of 53.3% shared. Only 4.7% (n = 23) and 0.2% (n = 2) of reactive antigens for IgG and IgM AAbs, respectively, were specific to CRC. Ultimately, we compiled a list of 19 IgG AAb targets as potential tumor-specific AAb candidates. Autoantibodies against one of the top candidates, p15INK4b-related sequence/regulation of nuclear pre-mRNA domain-containing protein 1A (RPRD1A), were significantly elevated in 53 CRC patients compared to 119 controls (p < 0.0001). The project revealed that tissue-derived IgG AAbs, rather than IgM, are the primary source of tumor-specific AAbs in peripheral blood. It also identified potential tumor-specific AAbs that could be applied for noninvasive screening of CRC.

Distinguishing Protein Chemical Topologies Using Supercharging Ion Mobility Spectrometry-Mass Spectrometry.

A technique combining ion mobility spectrometry-mass spectrometry (IMS-MS) and supercharging electrospray ionization (ESI) has been demonstrated to differentiate protein chemical topology effectively. Incorporating as many charges as possible into proteins via supercharging ESI allows the protein chains to be largely unfolded and stretched, revealing their hidden chemical topology. Different chemical topologies result in differing geometrical sizes of the unfolded proteins due to constraints in torsional rotations in cyclic domains. By introducing new topological indices, such as the chain-length-normalized collision cross-section (CCS) and the maximum charge state (zM ) in the extensively unfolded state, we were able to successfully differentiate various protein chemical topologies, including linear chains, ring-containing topologies (lasso, tadpole, multicyclics, etc.), and mechanically interlocked rings, like catenanes.

Biomacromolecular Characterizations Using State-of-the-Art Quartz Crystal Microbalance with Dissipation.

Biomolecular characterization is essential in fields such as drug discovery, glycomics, and cell biology. This feature article focuses on the experimental use of quartz crystal microbalance with dissipation (QCM-D) as a powerful analytical technique to probe biological events ranging from biomacromolecular interactions and conformational changes of biomacromolecules to surface immobilization of biomacromolecules and cell morphological changes.

Optimizing the detection of emerging infections using mobility-based spatial sampling.

Background: Timely and precise detection of emerging infections is crucial for effective outbreak management and disease control. Human mobility significantly influences infection risks and transmission dynamics, and spatial sampling is a valuable tool for pinpointing potential infections in specific areas. This study explored spatial sampling methods, informed by various mobility patterns, to optimize the allocation of testing resources for detecting emerging infections. Methods: Mobility patterns, derived from clustering point-of-interest data and travel data, were integrated into four spatial sampling approaches to detect emerging infections at the community level. To evaluate the effectiveness of the proposed mobility-based spatial sampling, we conducted analyses using actual and simulated outbreaks under different scenarios of transmissibility, intervention timing, and population density in cities. Results: By leveraging inter-community movement data and initial case locations, the proposed case flow intensity (CFI) and case transmission intensity (CTI)-informed sampling approaches could considerably reduce the number of tests required for both actual and simulated outbreaks. Nonetheless, the prompt use of CFI and CTI within communities is imperative for effective detection, particularly for highly contagious infections in densely populated areas. Conclusions: The mobility-based spatial sampling approach can substantially improve the efficiency of community-level testing for detecting emerging infections. It achieves this by reducing the number of individuals screened while maintaining a high accuracy rate of infection identification. It represents a cost-effective solution to optimize the deployment of testing resources, when necessary, to contain emerging infectious diseases in diverse settings.

The value of serum methylated septin 9 and carcinoembryonic antigen in efficacy evaluation and follow-up monitoring of colorectal cancer.

This study explored the value of the detection of serum methylated septin 9 (mSEPT9) and carcinoembryonic antigen (CEA) in the auxiliary diagnosis, curative effect evaluation, and follow-up monitoring of colorectal cancer (CRC). The diagnosis and treatment data of 208 CRC patients in the First Affiliated Hospital of Xinjiang Medical University (China) were collected from March 2019 to December 2019, and these patients were followed up. The correlation between serum CEA, mSEPT9 levels, and tumor location and size were analyzed. Serum mSEPT9 and CEA were detected before and after surgery and during follow-up after treatment to analyze the value of mSEPT9 in efficacy evaluation and follow-up monitoring. In 87 patients with CRC patients who underwent surgery, the average size of poorly differentiated tumors was the largest (25.01±14.08 cm2), which was significantly different from that of moderately differentiated tumors (P =0.039). There was a statistically significant difference in serum CEA level among different degrees of differentiation (P=0.018). The level of CEA was relatively low when tumors occurred in the transverse and ascending colon. When the level of CEA was high, negative mSEPT9 suggested that the probability of a tumor occurring in the cecum was high; positive mSEPT9 indicated that the tumor was highly likely to occur in the descending or sigmoid colon. Detection before and after surgery revealed that the level of mSEPT9 may be related to the tumor-bearing state of patients. A Follow-up study also showed that the sensitivity and specificity of mSEPT9 for recurrence and metastasis were 83.3% and 97.7%, respectively, and the sensitivity and specificity of CEA were 61.1% and 89.5%, respectively. The combined detection of mSEPT9 and CEA can indicate the location and size of colorectal cancer, while the detection of serum mSEPT9 may have clinical significance in the efficacy evaluation and follow-up monitoring of colorectal cancer. KEY WORDS: Colorectal Cancer, mSEPT9, Recurrence, Metastasis, CEA.

DHCR24 reverses Alzheimer's disease-related pathology and cognitive impairment via increasing hippocampal cholesterol levels in 5xFAD mice.

Accumulating evidences reveal that cellular cholesterol deficiency could trigger the onset of Alzheimer's disease (AD). As a key regulator, 24-dehydrocholesterol reductase (DHCR24) controls cellular cholesterol homeostasis, which was found to be downregulated in AD vulnerable regions and involved in AD-related pathological activities. However, DHCR24 as a potential therapeutic target for AD remains to be identified. In present study, we demonstrated the role of DHCR24 in AD by employing delivery of adeno-associated virus carrying DHCR24 gene into the hippocampus of 5xFAD mice. Here, we found that 5xFAD mice had lower levels of cholesterol and DHCR24 expression, and the cholesterol loss was alleviated by DHCR24 overexpression. Surprisingly, the cognitive impairment of 5xFAD mice was significantly reversed after DHCR24-based gene therapy. Moreover, we revealed that DHCR24 knock-in successfully prevented or reversed AD-related pathology in 5xFAD mice, including amyloid-ß deposition, synaptic injuries, autophagy, reactive astrocytosis, microglial phagocytosis and apoptosis. In conclusion, our results firstly demonstrated that the potential value of DHCR24-mediated regulation of cellular cholesterol level as a promising treatment for AD.

Visualizing the multi-level assembly structures of conjugated molecular systems with chain-length dependent behavior.

It remains challenging to understand the structural evolution of conjugated polymers from single chains to solvated aggregates and film microstructures, although it underpins the performance of optoelectrical devices fabricated via the mainstream solution processing method. With several ensemble visual measurements, here we unravel the morphological evolution process of a model system of isoindigo-based conjugated molecules, including the hidden molecular assembly pathways, the mesoscale network formation, and their unorthodox chain dependence. Short chains show rigid chain conformations forming discrete aggregates in solution, which further grow to form a highly ordered film that exhibits poor electrical performance. In contrast, long chains exhibit flexible chain conformations, creating interlinked aggregates networks in solution, which are directly imprinted into films, forming interconnective solid-state microstructure with excellent electrical performance. Visualizing multi-level assembly structures of conjugated molecules provides a deep understanding of the inheritance of assemblies from solution to solid-state, accelerating the optimization of device fabrication.

A single-domain green fluorescent protein catenane.

Natural proteins exhibit rich structural diversity based on the folds of an invariably linear chain. Macromolecular catenanes that cooperatively fold into a single domain do not belong to the current protein universe, and their design and synthesis open new territories in chemistry. Here, we report the design, synthesis, and properties of a single-domain green fluorescent protein catenane via rewiring the connectivity of GFP's secondary motifs. The synthesis could be achieved in two steps via a pseudorotaxane intermediate or directly via expression in cellulo. Various proteins-of-interest may be inserted at the loop regions to give fusion protein catenanes where the two subunits exhibit enhanced thermal resilience, thermal stability, and mechanical stability due to strong conformational coupling. The strategy can be applied to other proteins with similar fold, giving rise to a family of single-domain fluorescent proteins. The results imply that there may be multiple protein topological variants with desirable functional traits beyond their corresponding linear protein counterparts, which are now made accessible and fully open for exploration.

P2X7 receptor of microglia in olfactory bulb mediates the pathogenesis of olfactory dysfunction in a mouse model of allergic rhinitis.

The pathogenesis of allergic rhinitis (AR)-related olfactory dysfunction (OD) remains unknown. Inhibiting microglial response in olfactory bulb (OB) can ameliorate AR-related OD, but no precise targets have been available. In this study, we established a mouse model of ovalbumin (OVA)-induced AR and combined with the application of P2X7 receptor (P2X7R)-specific antagonists and cell culture in conditioned medium to investigate the role and mechanism of OB microglial P2X7R in AR-related OD. Serum IgE and IL-5 levels determined via ELISA and federated the number of nose-scratching to affirm the success of OVA-induced AR mouse model. Buried food pellet test was used to evaluate the olfactory function of mice. The changes of IBA1, GFAP, P2X7R, IL-1ß, IL-1Ra, and CASPASE 1 were detected by quantitative polymerase chain reaction and western blotting. The levels of adenosine triphosphate (ATP) were determined by the commercialized kit. The morphological changes of microglia were assessed using immunofluorescence staining and Sholl analysis. Findings showed that AR-related OD was associated with OB microglia-mediated imbalance between IL-1ß and IL-1Ra. Treatment with BBG improved the olfactory function in AR mice with restoring the balance between IL-1ß and IL-1Ra. In vitro, the conditioned medium obtained after HNEpC treatment with Der p1 could activate HMC3 to arise inflammatory reaction basing on "ATP-P2X7R-Caspase 1" axis, while inhibition of its P2X7R suppressed the reaction. In brief, microglial P2X7R in OB is a direct effector molecule in AR-related OD and inhibition of it may be a new strategy for the treatment of AR-related OD.

IL-1ß and Allergy: Focusing on Its Role in Allergic Rhinitis.

Allergic rhinitis (AR) is a chronic upper airway immune-inflammation response mediated by immunoglobulin E (IgE) to allergens and can seriously affect the quality of life and work efficiency. Previous studies have shown that interleukin-1ß (IL-1ß) acts as a key cytokine to participate in and promote the occurrence and development of allergic diseases. It has been proposed that IL-1ß may be a potential biomarker of AR. However, its definitive role and potential mechanism in AR have not been fully elucidated, and the clinical sample collection and detection methods were inconsistent among different studies, which have limited the use of IL-1ß as a clinical diagnosis and treatment marker for AR. This article systematically summarizes the research advances in the roles of IL-1ß in allergic diseases, focusing on the changes of IL-1ß in AR and the possible interventions. In addition, based on the findings by our team, we provided new insights into the use of IL-1ß in AR diagnosis and treatment, in an attempt to further promote the clinical application of IL-1ß in AR and other allergic diseases.

Lower Baseline LDL Cholesterol Affects All-cause Mortality in Patients with First Percutaneous Coronary Intervention.

Objective: Foreign studies have reported that coronary artery disease (CAD) patients with high baseline low-density lipoprotein cholesterol (LDL-C) may have a good prognosis, which is called the "cholesterol paradox". This study aimed to examine whether the "cholesterol paradox" also exists in the Chinese population. Methods: A total of 2,056 patients who underwent the first percutaneous coronary intervention (PCI) between 2014 and 2016 were enrolled in this retrospective cohort study and classified into two groups based on baseline LDL-C = 2.6 mmol/L (100 mg/dL). The outcomes of interest included major adverse cardiovascular events (MACE), all-cause mortality, recurrent nonfatal myocardial infarction, unexpected coronary revascularization, or any nonfatal stroke. Results: All-cause mortality occurred in 8 patients (0.7%) from the low-LDL-C group and 12 patients (2.4%) in the high-LDL-C group, with a significant difference between the two groups (adjusted hazard ratio: 4.030, 95% confidence interval: 1.088-14.934; P = 0.037). However, no significant differences existed for the risk of MACE or other secondary endpoints, such as unexpected revascularization, nor any nonfatal stroke in the two groups. Conclusion: In this study, a high baseline LDL-C was not associated with a low risk of clinical outcomes in CAD patients undergoing first PCI, which suggested that the "cholesterol paradox" may be inapplicable to Chinese populations.

Deep brain stimulation improves central nervous system inflammation in Parkinson's disease: Evidence and perspectives.

BACKGROUND: In Parkinson's disease (PD), inflammation may lead to the degeneration of dopaminergic (DAergic) neurons. Previous studies showed that inflammatory mediators mainly contributed to this phenomenon. On the other hand, invasive neuromodulation methods such as deep brain stimulation (DBS) have better therapeutic effects for PD. One possibility is that DBS improves PD by influencing inflammation. Therefore, we further explored the mechanisms underlying inflammatory mediators and DBS in the pathogenesis of PD. METHODS: We measured serum levels of two inflammatory markers, namely RANTES (regulated on activation, normal T cell expressed and secreted) and tumor necrosis factor-alpha (TNF-α), using Luminex assays in 109 preoperative DBS PD patients, 49 postoperative DBS PD patients, and 113 age- and sex-matched controls. The plasma protein data of the different groups were then statistically analyzed. RESULTS: RANTES (p < 0.001) and TNF-α (p = 0.005) levels differed significantly between the three groups. A strong and significant correlation between RANTES levels and Hoehn-Yahr (H-Y) stage was observed in preoperative PD patients (rs  = 0.567, p < 0.001). Significant correlations between RANTES levels and Unified Parkinson's Disease Rating Scale III (UPDRS III) score (rs1  = 0.644, p = 0.033 and rs2  = 0.620, p = 0.042) were observed in matched patients. No correlation was observed for TNF-α levels. CONCLUSION: The results of this study indicate that PD patients have a persistent inflammatory profile, possibly via recruitment of activated monocytes, macrophages, and T lymphocytes to the central nervous system (CNS). DBS was shown to have a significant therapeutic effect on PD, which may arise by improving the inflammatory environment of the central nervous system.

Leveraging Macromolecular Isomerism for Phase Complexity in Janus Nanograins.

It remains intriguing whether macromolecular isomerism, along with competing molecular interactions, could be leveraged to create unconventional phase structures and generate considerable phase complexity in soft matter. Herein, we report the synthesis, assembly, and phase behaviors of a series of precisely defined regioisomeric Janus nanograins with distinct core symmetry. They are named B2DB2 where B stands for iso-butyl-functionalized polyhedral oligomeric silsesquioxanes (POSS) and D stands for dihydroxyl-functionalized POSS. While BPOSS prefers crystallization with a flat interface, DPOSS prefers to phase-separate from BPOSS. In solution, they form 2D crystals owing to strong BPOSS crystallization. In bulk, the subtle competition between crystallization and phase separation is strongly influenced by the core symmetry, leading to distinct phase structures and transition behaviors. The phase complexity was understood based on their symmetry, molecular packing, and free energy profiles. The results demonstrate that regioisomerism could indeed generate profound phase complexity.

Establishment and validation of a plasma oncofetal chondroitin sulfated proteoglycan for pan-cancer detection.

Various biomarkers targeting cell-free DNA (cfDNA) and circulating proteins have been tested for pan-cancer detection. Oncofetal chondroitin sulfate (ofCS), which distinctively modifies proteoglycans (PGs) of most cancer cells and binds specifically to the recombinant Plasmodium falciparum VAR2CSA proteins (rVAR2), is explored for its potential as a plasma biomarker in pan-cancer detection. To quantitate the plasma ofCS/ofCSPGs, we optimized an ELISA using different capture/detection pairs (rVAR2/anti-CD44, -SDC1, and -CSPG4) in a case-control study with six cancer types. We show that the plasma levels of ofCS/ofCSPGs are significantly higher in cancer patients (P values, 1.2 × 10-2 to 4.4 × 10-10). Validation studies are performed with two independent cohorts covering 11 malignant tumors. The individuals in the top decile of ofCS-CD44 have more than 27-fold cancer risk (OR = 27.8, 95%CI = 18.8-41.4, P = 2.72 × 10-62) compared with the lowest 20%. Moreover, the elevated plasma ofCS-CD44 could be detected at the early stage of pan-cancer with strong dose-dependent odds risk prediction.

Orchestrating Chemical and Physical Cross-Linking in Protein Hydrogels to Regulate Embryonic Stem Cell Growth.

Protein hydrogels are ideal candidates for next-generation biomaterials due to their genetically programmable properties. Herein, we report an entirely protein-based hydrogel as an artificial extracellular matrix (ECM) for regulating the embryonic stem cell growth. A synergy between chemical and physical cross-linking was achieved in one step by SpyTag/SpyCatcher reaction and P zipper association at 37 °C. The hydrogels' stress relaxation behaviors can be tuned across a broad spectrum by single-point mutation on a P zipper. It has been found that faster relaxation can promote the growth of HeLa tumor spheroids and embryonic stem cells, and mechanical regulation of embryonic stem cells occurs via retention of the cells at the G1 phase. The results highlight the promise of genetically encoded protein materials as a platform of artificial ECM for understanding and controlling the complex cell-matrix interactions in a 3D cell culture.

Conjugated Polymers in Solution: A Physical Perspective.

Excellent progress has been made in the optoelectronic properties of conjugated polymers by controlling solution-state aggregation. However, due to the wide variety and complex structures of conjugated polymers, it is still challenging to fully understand the complex aggregation process and microstructures both in solution and in the solid state. This Perspective focuses on the chain conformations and the aggregation of conjugated polymers in solution. We discuss the factors in detail which affect solution-state aggregation and microstructures from the perspective of polymer physics in solutions, including chemical structures and environmental conditions. Based on the understanding of multiple interactions of conjugated polymers in solution, strategies to regulate solid-state microstructures and obtain high-performance polymer-based devices from solution-state aggregation are summarized.

ABC-Type, Bola-Form Giant Surfactants: Synthesis and Self-Assembly.

Due to the fast phase separation kinetics and small feature size, the self-assembly of giant molecules has attracted lots of attention. However, there is not much study on multicomponent giant surfactants. In this work, through a modular synthetic strategy, different polyhedral oligomeric silsesquioxane (POSS)-based molecular nanoparticles are installed with diverse functionalities (hydrophobic octavinyl POSS (VPOSS), hydrophilic dihydroxyl-functionalized POSS (DPOSS), and omniphobic perfluoroalkyl-chain-functionalized POSS (FPOSS)) on the ends of one polystyrene (PS) chain to build up a series of triblock bola-form giant surfactants denoted as XPOSS-PSn -FPOSS (X represents V or D). The target molecules are prepared by a combination of atom transfer radical polymerization (ATRP), esterification, as well as Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) and thiol-ene "click" reactions. These macromolecules are thoroughly characterized by combined technologies including nuclear magnetic resonance (NMR), size exclusion chromatography (SEC), and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analyses. It is revealed by small angle X-ray scattering (SAXS) and transmission electron microscopy (TEM) that VPOSS-PSn -FPOSS adopts a two-phase separation scenario where VPOSS and POSS are segregated in one phase. DPOSS-PSn -FPOSS with a third hydrophilic DPOSS shows a three-phase separation scenario, where highly ordered phase structures are difficult to develop owing to the competition of mutual phase separation processes and may be trapped in kinetically metastable states.