Mechanisms of Autoimmune Cell in DA Neuron Apoptosis of Parkinson's Disease: Recent Advancement.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder that manifests as motor and nonmotor symptoms due to the selective loss of midbrain DArgic (DA) neurons. More and more studies have shown that pathological reactions initiated by autoimmune cells play an essential role in the progression of PD. Autoimmune cells exist in the brain parenchyma, cerebrospinal fluid, and meninges; they are considered inducers of neuroinflammation and regulate the immune in the human brain in PD. For example, T cells can recognize α-synuclein presented by antigen-presenting cells to promote neuroinflammation. In addition, B cells will accelerate the apoptosis of DA neurons in the case of PD-related gene mutations. Activation of microglia and damage of DA neurons even form the self-degeneration cycle to deteriorate PD. Numerous autoimmune cells have been considered regulators of apoptosis, α-synuclein misfolding and aggregation, mitochondrial dysfunction, autophagy, and neuroinflammation of DA neurons in PD. The evidence is mounting that autoimmune cells promote DA neuron apoptosis. In this review, we discuss the current knowledge regarding the regulation and function of B cell, T cell, and microglia as well as NK cell in PD pathogenesis, focusing on DA neuron apoptosis to understand the disease better and propose potential target identification for the treatment in the early stages of PD. However, there are still some limitations in our work, for example, the specific mechanism of PD progression caused by autoimmune cells in mitochondrial dysfunction, ferroptosis, and autophagy has not been clarified in detail, which needs to be summarized in further work.

Porous organic polymer overcomes the post-treatment phototoxicity of photodynamic agents and maintains their antitumor efficiency.

Since 1995, photodynamic therapy (PDT) has been utilized as an effective method for cancer treatment. However, the residues of photosensitizers in the normal tissues after PDT can be activated by sunlight to cause severe skin phototoxicity, for which currently there are no clinical solutions. As a result, post-PDT patients need to remain out of sunlight for up to five weeks, which produces great living and mental burdens for patients. Herein, we report that a biocompatible porous organic polymer (POP) with average 3.1 nm porosity is able to suppress the skin phototoxicity of clinically used porphyrin-based photodynamic agents (PDAs), including Photofrin, Talaporfin and Hiporfin, through an adsorption-elimination mechanism. Fluorescence titration and dialysis experiments show that POP can adsorb and retain the PDAs at a micromolar concentration. In vivo experiments demonstrate that POP can significantly suppress the skin phototoxicity caused by all the three PDAs without reducing their PDT efficacy. STATEMENT OF SIGNIFICANCE: Up to now, no efficient clinical treatment for the inhibition of post-PDT phototoxicity of clinically used porphyrin-based PDAs is available. In the manuscript, a water-soluble cationic porous organic polymer has been revealed to include three clinically used PDAs. In vivo experiments show that this inclusion remarkably reduces the content of PDAs in mouse skins, leading to significant alleviation of their post-PDT phototoxicity without no negative effect on their PDT efficacy. Thus, this work provides a strategy for overcoming the drawback of clinically used photodynamic agents.

Supramolecular Crystal Networks Constructed from Cucurbit[8]uril with Two Naphthyl Groups.

Naphthyl groups are widely used as building blocks for the self-assembly of supramolecular crystal networks. Host-guest complexation of cucurbit[8]uril (Q[8]) with two guests NapA and Nap1 in both aqueous solution and solid state has been fully investigated. Experimental data indicated that double guests resided within the cavity of Q[8], generating highly stable homoternary complexes NapA2@Q[8] and Nap12@Q[8]. Meanwhile, the strong hydrogen-bonding and π···π interaction play critical roles in the formation of 1D supramolecular chain, as well as 2D and 3D networks in solid state.

a-PET and Weakened Triplet-Triplet Annihilation Self-Quenching Effects in Benzo-21-Crown-7-Functionalized Diiodo-BODIPY.

Weakening the triplet-triplet annihilation (TTA) self-quenching effect induced by sensitizers remains a tremendous challenge due to the very few investigations carried out on them. Herein, benzo-21-crown-7 (B21C7)-functionalized 2,6-diiodo-1,3,5,7-tetramethyl-8-phenyl-4,4-difluoroboradiazaindacene (DIBDP) was synthesized to investigate the influences of huge bulks and electron-rich cavities of B21C7 moieties on the fluorescence emission and triplet-state lifetimes of DIBDP moieties. Density functional theory (DFT)/time-dependent DFT (TDDFT) computable results preliminarily predicted that B21C7 moieties had influences on the fluorescence emissions of DIBDP moieties but not on their localization of triplet states of B21C7-functionalized DIBDP (B21C7-DIBDP). The UV-vis absorption spectra, fluorescence emission spectra, and cyclic voltammograms verified that there was an electron-transfer process from the B21C7 moiety to the DIBDP moiety in B21C7-DIBDP. However, the calculated results of ΔG CS and E CS values and nanosecond time-resolved transient absorption spectra demonstrated that the electron-transfer process from the B21C7 moiety to the DIBDP moiety in B21C7-DIBDP had direct influences on the fluorescence emission of DIBDP moieties but not on the triplet states of DIBDP moieties. The experimental values of triplet-state lifetimes of B21C7-DIBDP were obviously longer than those of DIBDP at a high concentration (1.0 × 10-5 M); however, the fitted values of intrinsic triplet-state lifetimes of B21C7-DIBDP were slightly greater than those of DIBDP in the same solvent. These results demonstrated that the steric hindrance of B21C7 moieties could weaken the TTA self-quenching effect of DIBDP moieties at a high concentration and the a-PET effect induced a proportion of the produced singlet states of DIBDP moieties and could not emit fluorescence in the form of radiation transition but they could be transformed into triplet states through intersystem crossing (ISC) processes due to the iodine atoms in the DIBDP moiety. The stronger a-PET effects in polar solvents induced smaller fluorescence quantum yields so that more singlet states of DIBDP moieties were transformed into triplet states to weaken the TTA self-quenching effects.

Water-Soluble 3D Covalent Organic Framework that Displays an Enhanced Enrichment Effect of Photosensitizers and Catalysts for the Reduction of Protons to H2.

Covalent organic frameworks (COFs) are emerging porous polymers that have 2D or 3D long-range ordering. Currently available COFs are typically insoluble or decompose upon dissolution, which remarkably restricts their practical implementations. For 3D COFs, the achievement of noninterpenetration, which maximizes their porosity-derived applications, also remains a challenge synthetically. Here, we report the synthesis of the first highly water-soluble 3D COF (sCOF-101) from irreversible polymerization of a preorganized supramolecular organic framework through cucurbit[8]uril (CB[8])-controlled [2 + 2] photodimerization. Synchrotron X-ray scattering and diffraction analyses confirm that sCOF-101 exhibits porosity periodicity, with a channel diameter of 2.3 nm, in both water and the solid state and retains the periodicity under both strongly acidic and basic conditions. As an ordered 3D polymer, sCOF-101 can enrich [Ru(bpy)3]2+ photosensitizers and redox-active polyoxometalates in water, which leads to remarkable increase of their photocatalytic activity for proton reduction to produce H2.

Stimuli-Responsive Supramolecular Assemblies between Twisted Cucurbit[14]uril and Hemicyanine Dyes and Their Analysis Application.

Two supramolecular assemblies between twisted cucurbit[14]uril and hemicyanine dyes have been successfully constructed on the basis of host-guest recognition. These supramolecular assemblies could be reversibly switched under acidic and neutral conditions. Furthermore, they responded to selected chemical stimuli such as methyl violet, thereby exhibiting potential analysis application.

Supramolecular Assembly Mediated by Metal Ions in Aqueous Solution and Its Application in Their Analysis.

A water-soluble fluorescent sensor based on the interaction of twisted cucurbit[14]uril (tQ[14]) and thiazole orange (TO) in aqueous solution was developed. Formation of the tQ[14]/TO complex gives rise to stronger fluorescence in both neutral and acidic aqueous solutions compared with that of free TO. Further experiments on the interaction of the tQ[14]/TO complex with metal ions revealed that, from a series of nineteen selected common metal ions, 1) only Hg2+ can lead to fluorescence enhancement and then quenching of the tQ[14]/TO (2:1) complex in neutral aqueous solution; 2) only Ba2+ can induce fluorescence quenching of the tQ[14]/TO (2:1) complex in aqueous HCl solution (pH 2); furthermore, the tQ[14]/TO/Ba2+ systems exhibit reversible changes in fluorescent intensity on successively adding SO42- and Ba2+ ; and 3) only Ba2+ or Pb2+ can induce fluorescence quenching of the tQ[14]/TO (15:1) complex in aqueous HCl solution (pH 2). Thus, the tQ[14]/TO complex can act as a supramolecular fluorescence-based sensor for the determination of Hg2+ , Ba2+ , and Pb2+ ions.

Host-guest complexation of cucurbit[8]uril with two enantiomers.

Host-guest complexation of cucurbit[8]uril (Q[8]) with two enantiomers, D-3-(2-naphthyl)-alanine (D-NA) and L-3-(2-naphthyl)-alanine (L-NA), has been fully investigated. Experimental data indicate that double guests reside within the cavity of Q[8] in both aqueous solution and solid state, generating highly stable homoternary complexes D-NA2@Q[8] and L-NA2@Q[8].

Binding and Selectivity of Essential Amino Acid Guests to the Inverted Cucurbit[7]uril Host.

Interactions between inverted cucurbit[7]uril (iQ[7]) and essential amino acids have been studied at pH = 7.0 by 1H NMR spectroscopy, electronic absorption spectroscopy, isothermal titration calorimetry, and mass spectrometry. The interactions can be divided into three binding types at pH = 7.0. Experimental results from the present study showed that the host displays a strong binding to the aromatic amino acids, Trp and Phe, and the guests of Lys, Arg, and His lie outside the cavity portal of the host. Meanwhile, the alkyl moieties of the guests Met, Leu, and Ile were accommodated within the cavity of iQ[7], but there was no significant interaction between iQ[7] and Thr or Val. The complexation behavior of iQ[7] with essential amino acids was explored at pH = 3, and the binding of Lys, Arg, and His revealed an unexpected behavior, with their side chains located in the cavity of iQ[7], whereas those of the aromatic Trp and Phe were deeper within the iQ[7] cavity. The alkyl side chains of the guests Met, Leu, Ile, Thr, and Val were also located inside the iQ[7] cavity and formed the host-guest complexes.

Encapsulation of haloalkane 1-(3-chlorophenyl)-4-(3-chloropropyl)-piperazinium in symmetrical α,α',δ,δ'-tetramethyl-cucurbit[6]uril.

Complexation of haloalkane 1-(3-chlorophenyl)-4-(3-chloropropyl)-piperazinium (PZ(+)) dihydrochloride with symmetrical α,α',δ,δ'-tetramethyl-cucurbit[6]uril (TMeQ[6]) has been investigated using NMR spectroscopy, MALDI-TOF mass spectrometry, isothermal titration calorimetry (ITC), and X-ray crystallography. Our data indicate that the chloropropyl group of PZ(+) resides within the cavity of TMeQ[6] in both aqueous solution and the solid state, generating a highly stable inclusion complex PZ(+)@TMeQ[6]. In aqueous solution, the formation of the inclusion complex PZ(+)@TMeQ[6] benefits from the ion-dipole interactions between the guest PZ(+) and the host TMeQ[6]. While in the solid state, hydrogen-bonding interactions also play an important role in stabilizing the inclusion complex PZ(+)@TMeQ[6].

Extended and contorted conformations of alkanediammonium ions in symmetrical α,α',δ,δ'-tetramethylcucurbit[6]uril cavity.

Binding interactions between symmetrical α,α',δ,δ'-tetramethylcucurbit[6]uril (TMeQ[6]) and a series of alkyldiammonium ions in aqueous solution and in the solid state were investigated by (1)H NMR spectroscopy, MALDI-TOF mass spectrometry, X-ray crystallography, and isothermal titration calorimetry (ITC). Their (1)H NMR spectra reveal that the actual binding behaviors vary depending upon the alkyl chain length. Their single-crystal X-ray diffraction analyses indicate the guest 1,2-ethanediammonium is located outside of the TMeQ[6] portal, while the other four alkyldiammonium guests can be accommodated in the TMeQ[6] cavity, forming 1:1 inclusion complexes. Most importantly, the long-chain alkyldiammoniums (1,8-octanediammonium and 1,10-decanediammonium) take a contorted conformation when bound within the TMeQ[6] cavity. Additionally, ITC experiments show that the complexation of the alkyldiammonium guests with TMeQ[6] is mainly enthalpy driven, which benefits from ion-dipole interactions.