Advancing bladder cancer management: development of a prognostic model and personalized therapy.

Background: Bladder cancer (BLCA) was recognized as a significant public health challenge due to its high incidence and mortality rates. The influence of molecular subtypes on treatment outcomes was well-acknowledged, necessitating further exploration of their characterization and application. This study was aimed at enhancing the understanding of BLCA by mapping its molecular heterogeneity and developing a robust prognostic model using single-cell and bulk RNA sequencing data. Additionally, immunological characteristics and personalized treatment strategies were investigated through the risk score. Methods: Single-cell RNA sequencing (scRNA-seq) data from GSE135337 and bulk RNA-seq data from several sources, including GSE13507, GSE31684, GSE32894, GSE69795, and TCGA-BLCA, were utilized. Molecular subtypes, particularly the basal-squamous (Ba/Sq) subtype associated with poor prognosis, were identified. A prognostic model was constructed using LASSO and Cox regression analyses focused on genes linked with the Ba/Sq subtype. this model was validated across internal and external datasets to ensure predictive accuracy. High- and low-risk groups based on the risk score derived from TCGA-BLCA data were analyzed to examine their immune-related molecular profiles and treatment responses. Results: Six molecular subtypes were identified, with the Ba/Sq subtype being consistently associated with poor prognosis. The prognostic model, based on basal-squamous subtype-related genes (BSSRGs), was shown to have strong predictive performance across diverse clinical settings with AUC values at 1, 3, and 5 years indicating robust predictability in training, testing, and entire datasets. Analysis of the different risk groups revealed distinct immune infiltration and microenvironments. Generally higher tumor mutation burden (TMB) scores and lower tumor immune dysfunction and exclusion (TIDE) scores were exhibited by the low-risk group, suggesting varied potentials for systemic drug response between the groups. Finally, significant differences in potential systemic drug response rates were also observed between risk groups. Conclusions: The study introduced and validated a new prognostic model for BLCA based on BSSRGs, which was proven effective in prognosis prediction. The potential for personalized therapy, optimized by patient stratification and immune profiling, was highlighted by our risk score, aiming to improve treatment efficacy. This approach was promised to offer significant advancements in managing BLCA, tailoring treatments based on detailed molecular and immunological insights.

Supramolecular Biopharmaceutical Carriers Based on Host-Guest Interactions.

Traditional drugs have the disadvantages of poor permeability and low solubility, which makes the utilization of pesticides lower and brings many side effects. With the continuous development of supramolecular chemistry in recent years, it has also played an irreplaceable role in the field of pharmaceutical science. Supramolecular macrocycles, such as crown ethers, cyclodextrins, calixarenes, pillararenes and cucurbiturils, are potentially good candidates for drug carriers due to their biocompatibility, hydrophobic cavity and ease of derivatization. The encapsulation of drugs based on host-guest interaction has the advantage of being adjustable and reversible as well as improving the low availability of drugs. Here, the recent advances in methods and strategies for drug encapsulation and release based on supramolecular macrocycles with host-guest interactions have been systematically summarized, laying a bright foundation for the development of novel nanopesticide preparations in the future and pointing out future directions of novel biopesticide research.

Controlled release of drug molecules by pillararene-modified nanosystems.

Stimuli-responsive nanosystems have attracted the interest of researchers due to their intelligent function of controlled release regulated by a variety of external stimuli and have been applied in biomedical fields. Pillar[n]arenes with the advantages of a rigid structure, electron holes and easy functionalization are considered as excellent candidates for the construction of host-guest nanosystems. In recent years, many pillararene modified nanosystems have been reported in response to different stimuli. In this feature article, we summarize the advance of stimuli-responsive pillararene modified nanosystems for controlled release of drugs from the perspectives of decomposition release and gated release, focusing on the control principles of these nanosystems. We expect that this review can enlighten and guide investigators in the field of stimuli-responsive controlled release.

Enantioselective Dynamic Self-Assembly of Histidine Droplets on Pillar[5]arene-Modified Interfaces.

The self-assembly of macroscopic droplets on interfaces has attracted much attention and shown promising potential in the field of materials as a sensing or delivery system. Herein, we reported a new strategy to construct a d-tartaric acid-functionalized pillar[5]arene (d-TP5) interface for macroscopic differentiation of histidine enantiomers. At the molecular level, it has been proved that d-TP5 has the ability to distinguish between l-Histidine and d-Histidine ( KL/ KD = 4.6). Furthermore, a functional d-TP5 surface was constructed by a click reaction and characterized by contact angle measurements and attenuated total reflection-Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy analyses. The d-TP5 surface exhibited the selective dynamic adhesion of l-His droplets on the tilted interface. It means that a d-TP5 surface can distinguish histidine enantiomers at a macrolevel. The amount of d/l-His absorbed by a d-TP5 surface and the morphology of His particles formed by removing the solvent have been investigated to prove that the self-assembly of His occurs on the d-TP5 surface. The possible mechanism has been discussed from host-guest interaction and chiral recognition. The proposed chiral material displays rapidly remarkable selectivity and is convenient to be utilized, which should be suitable for comprehending chiral recognition processing and applied to chiral recognition detection of histidine in a living body.

Bioinspired γ-Cyclodextrin Pseudorotaxane Assembly Nanochannel for Selective Amino Acid Transport.

Amino acid metabolic abnormalities will cause serious diseases, which arise from the different biological effect of enantiomers. Therefore, it is necessary to design and construct an artificial chiral amino acid gated transport system, which can effectively recognize and selectively transport chiral amino acids. Herein, based on the host-guest interaction, a switchable chiral discrimination system for amino acid enantiomers is reported, and the biomimetic nanochannel was functionalized with N-(1-naphthyl) ethylenediamine (NEDA), which acts as the guest and γ-CD was used as the host. The artificial nanochannel performs highly chiral selective gating for l-phenylalanine and well regulates the process of amino acid transportation. Moreover, the channel can easily actualize the reversible switching under the influence of a pH change; thus, our biomimetic nanochannel with a host-guest assembly can be widely used in chiral detection and drug delivery.

A biomimetic chiral-driven ionic gate constructed by pillar[6]arene-based host-guest systems.

Inspired by glucose-sensitive ion channels, herein we describe a biomimetic glucose-enantiomer-driven ion gate via the introduction of the chiral pillar[6]arene-based host-guest systems into the artificial nanochannels. The chiral nanochannels show a high chiral-driven ionic gate for glucose enantiomers and can be switched "off" by D-glucose and be switched "on" by L-glucose. Remarkably, the chiral nanochannel also exhibited a good reversibility toward glucose enantiomers. Further research indicates that the switching behaviors differed due to the differences in binding strength between chiral pillar[6]arene and glucose enantiomers, which can lead to the different surface charge within nanochannel. Given these promising results, the studies of chiral-driven ion gates may not only give interesting insight for the research of biological and pathological processes caused by glucose-sensitive ion channels, but also help to understand the origin of the high stereoselectivity in life systems.

Alanine-Based Chiral Metallogels via Supramolecular Coordination Complex Platforms: Metallogelation Induced Chirality Transfer.

Chiral self-assemblies constantly attract great interest because of their potential to provide insight into biological systems and materials science. Herein we report on the efficient preparation of alanine-based chiral metallacycles, rhomboids 1D and 1L and hexagons 2D and 2L using a Pt(II) ← pyridyl directional bonding approach. The metallacycles are subsequently assembled into nanospheres at low concentration, that generate chiral metallogels at high concentration driven by hydrogen bonding, hydrophobic and π-π interactions. The gels consist of microscopic chiral nanofibers with well-defined helicity, as confirmed by circular dichroism (CD) and scanning (SEM) and transmission electron (TEM) microscopies. Given these results, we expect this technique will not only unlock interesting new approaches to understand homochirality in nature but also allow the design of versatile soft materials containing chiral supramolecular cores.

A light-regulated host-guest-based nanochannel system inspired by channelrhodopsins protein.

The light-controlled gating of ion transport across membranes is central to nature (e.g., in protein channels). Herein, inspired by channelrhodopsins, we introduce a facile non-covalent approach towards light-responsive biomimetic channelrhodopsin nanochannels using host-guest interactions between a negative pillararene host and a positive azobenzene guest. By switching between threading and dethreading states with alternating visible and UV light irradiation, the functional channels can be flexible to regulate the inner surface charge of the channels, which in turn was exploited to achieve different forms of ion transport, for instance, cation-selective transport and anion-selective transport. Additionally, the pillararene-azobenzene-based nanochannel system could be used to construct a light-activated valve for molecular transport. Given these promising results, we suggest that this system could not only provide a better understanding of some biological processes, but also be applied for drug delivery and various biotechnological applications.Light-controlled gating of ion transport across membranes occurs in nature via channelrhodopsin nanochannels. Here, the authors show facile non-covalent approach towards light-responsive biomimetic nanochannels using host-guest interactions between a negative pillararene host and a positive azobenzene guest.

Chiral Responsive Liquid Quantum Dots.

How to convert the weak chiral-interaction into the macroscopic properties of materials remains a huge challenge. Here, this study develops highly fluorescent, selectively chiral-responsive liquid quantum dots (liquid QDs) based on the hydrophobic interaction between the chiral chains and the oleic acid-stabilized QDs, which have been designated as (S)-1810-QDs. The fluorescence spectrum and liquidity of thermal control demonstrate the fluorescence properties and the fluidic behavior of (S)-1810-QDs in the solvent-free state. Especially, (S)-1810-QDs exhibit a highly chiral-selective response toward (1R, 2S)-2-amino-1,2-diphenyl ethanol. It is anticipated that this study will facilitate the construction of smart chiral fluidic sensors. More importantly, (S)-1810-QDs can become an attractive material for chiral separation.

Chiral Selective Transport of Proteins by Cysteine-Enantiomer-Modified Nanopores.

Chirality is an intriguing and intrinsic feature of life and is highly associated with many significant biological processes. However, whether it influences the translocation behavior of proteins remains unclear. Herein, based on biomimetic strategies, we made chiral nanopores modified with cysteine enantiomers, and studied the chirality gating effects on protein transport. The results show that protein is preferentially transported through nanopores modified with l-cysteine because of chiral interaction, indicating chirality strongly influences protein transport process. This study presents a new method for better understanding the role of chirality in selective protein transport processes and provides a convenient approach for studying protein chiral separation and targeted treatments.

Temperature-Sensitive Artificial Channels through Pillar[5]arene-based Host-Guest Interactions.

In living systems, temperature-sensitive ion channels play a vital role in numerous cellular processes and can be controlled by biological ion channels in response to specific temperature stimuli. Facile pillar[5]arene-based host-guest interactions are introduced into a nanochannel pattern for constructing a temperature-sensitive artificial channel. Ion transport was switched from cations to anions by controlling the extent of the host bound to the guest with temperature stimuli. This efect is mainly due to the changing of the inner surface charge and wettability of the nanochannel during the process. This study paves a new way for better understanding the mechanism of temperature-sensitive properties and shows great promise for biomedical research.

Single Nanochannel Platform for Detecting Chiral Drugs.

Chiral drugs play an essential role in medical and biochemical systems, and thus enantioselective analysis of chiral molecules has become a central focus in chemical, biological, medical, and pharmaceutical research. The design of chiral drug-detecting systems is a long-term and challenging task. Here we report the use of a modification-free nanochannel method for enantioselective recognition of S-naproxen from R-naproxen using N-acetyl-l-cysteine-capped gold nanoparticles as a chiral selector. The chiral discrimination is based on a drug-induced nanoparticle diastereoselective aggregation mechanism that blocks ion transport through the nanochannel. We demonstrated that high S-Npx selectivity in both water and biological samples can be achieved. This simple method has potential applications as a general platform for the detection of chiral molecules.

Correction: The macroscopic wettable surface: fabricated by calix[4]arene-based host-guest interaction and chiral discrimination of glucose.

Correction for 'The macroscopic wettable surface: fabricated by calix[4]arene-based host-guest interaction and chiral discrimination of glucose' by Yue Sun et al., Chem. Commun., 2016, 52, 14416-14418.

The macroscopic wettable surface: fabricated by calix[4]arene-based host-guest interaction and chiral discrimination of glucose.

Herein, we reported a new strategy based on self-assembly chemistry for chiral discrimination of glucose on a new S-mandelic acid-appended calix[4]arene (S-MC4) modified nanostructure, which exhibits macroscopic chiral preference for d-glucose via contact angle measurements (CA). The proposed macroscopic chiral device displays rapidly remarkable specificity and is convenient to use, which should be suitable for diagnostic purposes, nanomedical applications, etc.

Selective molecular recognition on calixarene-functionalized 3D surfaces.

Host-guest recognition plays an important role in biological analysis and biosensing. Accordingly, great efforts have been devoted to the development of sensors using versatile 3D surface materials. These functionalized nanomaterials possess the advantages of high selectivity and visual signals, enabling the selective detection of ions, amino acids, proteins, and other biological molecules. Therefore, in this feature article, we present some significant and representative examples of molecular recognition on calixarene functionalized 3D surface nanomaterials. By virtue of host-guest interactions, the functional interfaces displaying high selectivity and featuring a reversible switch response towards the environmental stimuli with various signal output (electrochemical and optical signals) are herein introduced. Furthermore, various 3D surface materials with unique signal amplification in molecular recognition are presented, including quantum dots (QDs), metal nanoparticles (NPs), nanotubes, and mesoporous silica. These excellent properties enable calixarene-functionalized 3D materials to become an outstanding platform for molecular recognition, offering convenient approaches for sensing and separation.

Macroscopic Responsive Liquid Quantum Dots Constructed via Pillar[5]arene-Based Host-Guest Interactions.

Liquid quantum dots (QDs) have been used as a fluorescent films sensor. Constructing a macroscopic, responsive, liquid QD system for lysine (Lys) is a challenging task. To achieve a selective macroscopic response towards Lys, herein we present a new strategy for integrating host-guest chemistry into a liquid QD system. Water-soluble pillar[5]arene WP5 was designed and synthesized as a host. WP5 was introduced onto the surface of PEG1810-modified QDs by host-guest interactions to obtain liquid WP5-1810-QDs. The interaction between WP5 and Lys is stronger than that between WP5 and PEG-1810, causing WP5 to be released from the 1810-QDs surface in the presence of Lys, resulting in macroscopic fluorescence quenching. This smart material shows promise in amino acid sensing and separation.

Dynamic Self-Assembly Adhesion of a Paraquat Droplet on a Pillar[5]arene Surface.

The adhesion of herbicide droplets on leaf surfaces plays an important role in the herbicide's adsorption by crops. How to control the adhesive binding which occurs through dynamic self-assembly between the macroscopic droplet and the surface is a challenging task. We introduce a host onto surfaces that controls the binding of guests in the paraquat droplets. The pillar[5]arene-functional surface showed the selective binding of paraquat droplets via the host-guest interaction. The work is promising for improving the efficiency of herbicides.

The synthesis of pillar[5]arene functionalized graphene as a fluorescent probe for paraquat in living cells and mice.

As complex organisms vary in vivo, it remains a challenging task to get fluorescence 'turn on' imaging for special targets. To address this task, we have adopted a new strategy of inducing pillararene based host-guest interactions onto biocompatible graphene. By means of fluorescence competition displacement, hydrazino-pillar[5]arene modified graphene has been synthesized and provided as a 'turn on' probe for paraquat through monitoring of the fluorescence signal both in living cells and mice.

Macroscopic switches constructed through host-guest chemistry.

Molecular switch systems, having been extensively studied in the solution phase, have the ability to perform with good controllability and rapid-responsiveness, making them ideally suited for the design of molecular devices for drug delivery, and information or sensing functions. Inspired by a wide range of objects with visual changes, like Mimosa pudica towards external stimuli, in order to understand molecular switches well, they must be interfaced with the macroscopic world so that they can be directly realized by visual detectable changes even observed by the naked eye. This can be critical for fabricating intelligent microfluidics and laboratory-on-chip devices, that may have wide applications in the fields of biology and materials science. But to realize this objective, especially for fabricating macroscopic surface switches, unveiling host-guest weak interactions to achieve visual phenomena is still the greatest thrill. Thankfully, surface contact angles provide us with a wonderful method to further investigate the microscopic origin of the macroscopic changes. Therefore, interfacial modification becomes a paramount process. Macrocyclic compounds, encompassing an innovative concept to deal with reversible noncovalent interactions between macrocyclic hosts and suitable guests, are good candidates for surface functionalization. In this feature article, we discuss recent developments in macroscopic contact angle switches formed by different macrocyclic hosts and highlight the properties of these new functional surfaces and their potential applications.

Temperature-Responsive Switch Constructed from an Anthracene-Functionalized Pillar[5]arene-Based Host-Guest System.

A monofunctionalized anthracene pillar[5]arene (MAP5) was designed and synthesized by a click reaction. MAP5 was bound to an ionic liquid through host-guest interactions to modify a gold interface. The bonding and release of MAP5 was readily and reversibly controlled by temperature regulation. The developed temperature-responsive switch at an interface can be used in memory storage, drug delivery, and sensing.