The airway neuro-immune axis as a therapeutic target in allergic airway diseases.

Recent evidence has increasingly underscored the importance of the neuro-immune axis in mediating allergic airway diseases, such as allergic asthma and allergic rhinitis. The intimate spatial relationship between neurons and immune cells suggests that their interactions play a pivotal role in regulating allergic airway inflammation. Upon direct activation by allergens, neurons and immune cells engage in interactions, during which neurotransmitters and neuropeptides released by neurons modulate immune cell activity. Meanwhile, immune cells release inflammatory mediators such as histamine and cytokines, stimulating neurons and amplifying neuropeptide production, thereby exacerbating allergic inflammation. The dynamic interplay between the nervous and immune systems suggests that targeting the neuro-immune axis in the airway could represent a novel approach to treating allergic airway diseases. This review summarized recent evidence on the nervous system's regulatory mechanisms in immune responses and identified potential therapeutic targets along the peripheral nerve-immune axis for allergic asthma and allergic rhinitis. The findings will provide novel perspectives on the management of allergic airway diseases in the future.

Chirality Induction and Memory of Pillar[4]arene[1]quinone Derivatives in Visible-Light Range.

Pillar[4]arene[1]quinone derivatives (PQXs) were synthesized by the oxidation of pillar[5]arenes, which exhibited notable charge transfer (CT) transitions at approximately 485 nm. Successful chiral resolution of two pairs of enantiomeric conformers was achieved. Despite reduced binding affinity, PQXs demonstrated slower racemization kinetics. Visible-light chiroptical induction with a significant dissymmetry factor was attained by complexing PQXs with a chiral guest. The induced enantiomeric excess could be maintained through competitive binding with an achiral guest, offering a promising strategy for chiral sensing and memory.

Expanding the Anti-Stokes Shift of TTA-UC to 1.04 eV by Chemical Tuning of BODIPY-Based Organic Photosensitizers.

A series of BODIPY-derivatives B-1 ∼ B-5 were synthesized as metal-free photosensitizers in triplet-triplet annihilation (TTA) upconversion (UC) with the purpose of finely tuning the excited state properties to reduce the energy loss during intersystem crossing (ISC), and hence to expand the anti-Stokes shift of TTA-UC. It was revealed that B-5 showed a ΔEST of as small as 0.28 eV, thus, providing a large anti-Stokes shift of 1.04 eV in TTA-UC with organic sensitizers. A deep red-blue upconversion emission with UC quantum yields of up to 10.7% (out of a 50% maximum) was observed.

Chiroptical regulation of macrocyclic arenes with flipping-induced inversion of planar chirality.

Studies on various macrocyclic arenes have received increasing attention due to their straightforward syntheses, convenient derivatization, and unique complexation properties. Represented by pillar[n]arenes, several distinctive macrocyclic arenes have recently emerged with the following characteristics: they possess a pair of enantiomeric planar chiral conformations, and interconversion between these enantiomeric conformations can be achieved through the flipping of ring units. Complexation of a chiral guest with these macrocyclic arenes will lead to a shift of the equilibrium between the Rp and Sp conformers, leading to intriguing possibilities for chiral induction and sensing. By the introduction of bulky substituents on the rims, employing rotaxanation or pseudocatenation, planar chirality could be locked, enabling the enantiomeric separation of the chiral structures. The induced or separated chiral conformers/compounds exhibit significant chiroptical properties. These macrocyclic arenes, with flipping-induced inversion of planar chirality, demonstrated intriguing chiral induction dynamics and kinetics. In this featured review, we systematically summarize the progress in chiroptical induction/regulation of these macrocyclic arenes, particularly in the fields of chiral sensing, molecular machines, molecular recognition, and assembly.

Asymmetric Photoreactions in Supramolecular Assemblies.

ConspectusStereochemical control of excited-state asymmetric photoreactions has been one of the most challenging topics of modern photochemistry. The short-lived character of electronically excited photosubstrates and their low activation energy barriers to form both enantiomers are the major obstacles to achieving significant enantioselectivity in excited-state asymmetric photochemistry. Recent research demonstrated that the supramolecular strategy is promising to control the stereochemical outcome of asymmetric photoreaction through relatively strong and long-lasting noncovalent interaction at both ground and excited states. In this methodology, chiral hosts/assemblies provide the chiral environment for photochemically transferring chirality to the complexed photosubstrate in both the ground and the excited states by virtue of relatively strong supramolecular interactions, such as hydrogen bonding, van der Waals, π-π, electrostatic, and hydrophobic interactions. The orientation and conformation of the photosubstrate can be critically manipulated by the supramolecular complexation to ensure the subsequent effective stereoselective photochemical conversion.This Account describes our recent advance in asymmetric photoreactions in supramolecular assemblies. Several chiral photoreactions, including photoisomerization of cycloolefins and photocyclodimerization of anthracene and naphthalene derivatives, have been mediated by various supramolecular hosts, such as cyclodextrin (CD), cucurbituril, pillararene, and chiral polymer. The following advantages of supramolecular asymmetric photochemistry were evidenced: (1) The improvement of stereoselectivity can be enabled by the careful design and fabrication of chiral host molecules. (2) Supramolecular complexation could effectively regulate the orientation and conformation of photosubstrates, thus resulting in novel reaction pathways which create unusual photoproducts that are not achievable through traditional reaction conditions. (3) Asymmetric photoreactions in supramolecular systems showed strong correlations with the external environmental variants, such as temperature, solvent, irradiation wavelength, and pressure, which therefore provide a powerful tool for the regulation of stereoselectivities of excited-state photoreactions. (4) Utilizing supramolecular complexation can dramatically speed up photoreactions, a combination of appropriate photosensitizers/photocatalysts being able to drive catalyzed chiral photoreactions effectively. (5) Photoisomerization in chiral supramolecular systems has been applied to chiroptical molecular devices, which exhibited multiple stimulus-response functions and advanced switching performances. We believe that these concepts, methods, and principles derived therefrom are instructive in designing chiral supramolecular hosts, elucidating the stereodifferentiation mechanisms in the ground and excited states, and analyzing and improving the stereochemical outcomes of a diverse range of supramolecular chiral photoreactions.

"First Come, First Served" and Threshold Effects in a Central-to-Planar-to-Helical Hierarchical Chiral Induction.

Perylene diimide tethered pillar[5]arene derivatives form aggregates in non-polar organic solvents, and the complexation of cationic amino acid ethyl ester (cAA-OEt) with the aggregates induce a central-to-planar-to-helical chirality transfer, leading to intensive circular dichroism (CD) signals having dissymmetric factors (gabs ) of up to 3.67×10-2 . The hierarchical chiral induction exhibited an intriguing threshold dose effect, namely, the chiral induction does not occur in the low concentration range of cAA-OEt but is triggered when cAA-OEt exceeds a threshold concentration. The inhibited interconversion between the Rp and Sp conformers of pillar[5]arene, which is further restricted in the aggregation, plays a crucial role in the threshold effect. When adding enantiopure cAA-OEt first to the threshold concentration and then adding an equal amount of the antipodal cAA-OEt to give cAA-OEt in racemic form, CD spectra having the same sign as the CD induced by first adding pure cAA-OEt were induced, thus showing an unprecedented "first come, first served" effect.

Chiroptical induction with prism[5]arene alkoxy-homologs.

The complexation of prism[5]arenes with amino acid derivatives showed association constants of up to 107 M-1, significant CD with gabs of up to 0.8 × 10-2 and CPL with glum of 2 × 10-3. The absolute configuration-CD signal correlation was established. The CD spectra varied significantly with the substituents on the prism[5]arenes.

Bibliometric analysis of the global research development of bone metastases in prostate cancer: A 22-year study.

Background: Prostate cancer (PCa) is the second most diagnosed cancer in men. Most PCa-related deaths result from metastatic disease. Metastases occur most often in the bones (90%). However, the current treatments for bone metastases in PCa are not very effective. Here we present an overview of the current research situation of bone metastases in PCa, focusing on hotspots and trends. Methods: We searched the Web of Science Core Collection database for publications related to bone metastases in PCa published between 1999 and 2021. We used VOSviewer, CiteSpace, and a bibliometric online platform to perform a bibliometric analysis of countries, institutions, authors, journals, references, and keywords. Results: A total of 4,832 related articles were included in the present study. The USA published the most articles in the field, followed by China and England. The University of Texas MD Anderson Cancer Center is the leading institution in the research field of bone metastases in PCa. Saad F, from Canada, has made great achievements in this area by publishing 91 related articles. Prostate is the journal which published most related articles, and Mundy GR, 2002, Nat Rev Cancer, is the most cited article in this field. Furthermore, the analysis of author keywords can be divided into five clusters: (1) diagnosis of PCa, (2) mechanism of bone metastasis, (3) drug treatments of bone metastases, (4) radiotherapy of bone metastases, and (5) treatments and prognosis of PCa. Conclusions: mCRPC has been the hottest topic in PCa in recent years. CT is the most common diagnostic method for bone metastases. Enzalutamide and radium-223, as important treatments for bone metastases in PCa, bring about widespread attention. Furthermore, the researchers focus on the tumor microenvironment and biomarkers to explore the mechanism and the therapeutic targets of bone metastases in PCa.

Triplet-triplet annihilation upconversion in LAPONITE®/PVP nanocomposites: absolute quantum yields of up to 23.8% in the solid state and application to anti-counterfeiting.

The low quantum efficiency in the solid phase and the highly efficient quenching by oxygen are two major weaknesses limiting the practical applications of triplet-triplet annihilation (TTA) upconversion (UC). Herein, we report an organic-inorganic hybrid nanocomposites fabricated by self-assembly of LAPONITE® clay and poly(N-vinyl-2-pyrrolidone) (PVP), which serves as excellent matrix for solid-state TTA-UC even in air. In the hybrid hydrogel doped by TTA-UC components, the anionic acceptors are arranged in an ordered manner at the nano-disk edge through electrostatic attraction, which avoids haphazard accumulation of the acceptors and allows for highly efficient inter-acceptor triplet energy migration. Moreover, the entangled PVP could not only protect the triplet excitons from oxygen quenching but even proactively eliminate oxygen by photoirradiation. Significantly, the dried gel prepared by completely removing water from the hydrogel gave absolute UC quantum efficiencies of up to 23.8% (out of a 50% maximum), which is the highest TTA-UC efficiency obtained in the solid state. The dried gels are readily made into powder by grinding with maintained UC emissions, making them convenient for application to information encryption and anti-counterfeiting security by virtue of the high UC quantum efficiency and insensitivity to oxygen.

Synthesis of cyclodextrin derivatives for enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylate.

Photochemical methods are increasingly being used in organic synthesis. They are especially useful for preparing many compounds that are not readily accessible through thermal or enzymatic reactions. The supramolecular strategy has proved highly promising in recent years for manipulating the stereochemical outcome of chiral photoreactions through relatively strong and long-lasting noncovalent interactions in both ground and excited states. Among the numerous chiral photochemical reactions, photocyclodimerization of 2-anthracenecarboxylate (AC) is the most comprehensively studied supramolecular chiral photoreaction and has essentially become a benchmark reaction for evaluating supramolecular photochirogenesis. Cyclodextrin (CD) derivatives were the earliest and are the most widely applied chiral host for mediating photoreactions. Herein, we use CD-mediated photocyclodimerization of AC as an example to introduce the operation process of supramolecular chiral photoreactions. The protocol includes the following contents: (i) the preparation, purification and characterization of ß-CD derivatives; (ii) methods for investigating the host-guest inclusion behavior between AC and ß-CD derivatives; (iii) the photochemical reaction operation flow under different solvent and temperature conditions; (iv) chiral high-performance liquid chromatography (HPLC) analyses of the product distribution and enantioselectivity. The protocol is introduced by using representative examples of the synthesis of ß-CD derivatives and the manipulation of environmental factors that give excellent regio- and enantioselectivities in the photocyclodimerization of AC. The synthesis and purification of ß-CD derivatives require 3-5 d of work. The photoirradiation of AC with ß-CD derivatives can be done within 1 h. The product analysis requires 5 h.

BODIPY-conjugated bis-terpyridine Ru(II) complexes showing ultra-long luminescence lifetimes and applications to triplet-triplet annihilation upconversion.

The poor excited-state properties of bis-terpyridine Ru(II) complexes have significantly limited the applications of these complexes as sensitizers in photocatalysis and triplet-triplet annihilation upconversion. In the present work, two novel ruthenium bis-terpyridine complexes (Ru-1 and Ru-2) conjugated with visible-light-harvesting bodipy chromophores were synthesized. These complexes showed strong absorption of visible light, the bodipy-localized intraligand triplet state (3IL) was efficiently populated, and the phosphorescence of bodipy at room temperature in both complexes was observed. The luminescence lifetimes of these complexes were significantly prolonged, with that of the heteroleptic complex Ru-2 prolonged to 37.9 µs and that of the homoleptic bis-terpyridine complex Ru-1 unprecedentedly prolonged to 356 µs, which was hundreds of times longer than the current longest emissive state achieved in ruthenium terpyridine complexes. The ultra-long triplet lifetimes and strong visible-light absorbing ability made them new candidates of triplet sensitizers, and were first applied to TTA-UC for terpyridine Ru(II) complexes with a Ru-1/Py system showing a ΦUC of 2.93% in dilute solutions at concentrations as low as 1.0 µM.

Host-Guest Complexation-Induced Aggregation Based on Pyrene-Modified Cyclodextrins for Improved Electronic Circular Dichroism and Circularly Polarized Luminescence.

Several γ-cyclodextrin (CD) derivatives mono- or di-substituted by pyrenes at the primary rim of the CD were demonstrated to aggregate into nano-strips in aqueous solutions, with the pyrene moieties interpenetrating into γ-CD cavities. The hydrophobic complexation-induced aggregation provides a rigid chiral environment for the pyrenes and leads to significant electronic circular dichroism (ECD) and circularly polarized luminescence (CPL) activities, giving unprecedently high gabs and glum values up to 4.3×10-2 and 5.3×10-2 , respectively. The aggregates lead to excimer emission with high quantum yields and show BCPL and BiCPL up to 338. 6 M-1 cm-1 and 169.3 M-1 cm-1 , respectively.

γ-Cyclodextrin-based [2]rotaxane stoppered with gold(I)-ethynyl complexation: phosphorescent sensing for nitroaromatics.

A [2]rotaxane is assembled by γ-cyclodextrin (γ-CD) with threaded 1,4-diethynylbiphenyl and bulky Au(I)-phosphine stoppers. The phosphorescence of the [2]rotaxane has been observed in aerated aqueous solution and found to be quenched by nitroaromatics due to γ-CD-based co-binding, providing a sensitive approach towards explosive-sensing.

Catalytic Chiral Photochemistry Sensitized by Chiral Hosts-Grafted Upconverted Nanoparticles.

Singlet chiral photocatalysis is highly challenging. Herein, we report fluorescence resonance energy transfer (FRET)-based chiral photocatalysis with γ-cyclodextrin (CD)-grafted lanthanide-doped upconverted nanoparticles (UCNP). The CD-modified UCNP strongly emits in the UV wavelength region upon excitation with a 980 nm laser, which selectively sensitizes the photosubstrates complexed by CD on the surface of UCNP through FRET. Therefore, enantiodifferentiating photocyclodimerization of anthracene or naphthalene derivatives sensitized by the CD-modified UCNP gives photoproducts in good enantioselectivity even in the presence of a catalytic amount of CD-modified UCNP. Moreover, the photocatalysts are readily separated and could be reused for at least six cycles without decreasing the enantioselectivity.

The More the Slower: Self-Inhibition in Supramolecular Chirality Induction, Memory, Erasure, and Reversion.

Self-inhibition has been observed widely in hierarchical biochemical processes but has yet to be demonstrated in pure molecular physical rather than chemical or biological processes. Herein, we report an unprecedented example of self-inhibition during the supramolecular chirality induction, memory, erasure, and inversion processes of pillar[5]arene (P[5]) derivatives. The addition of chiral alanine ethyl ester to bulky substituent-modified P[5]s led to time-dependent chirality induction due to the shift in the equilibrium of the SP and RP conformers P[5]. Intriguingly, more chiral inducers led to more intensive final chiroptical properties but lower chiral induction rates. Thus, the chiral inducer plays the role of both activator and inhibitor. Such self-inhibition essentially arises from kinetics manipulation of three tandem equilibria. Moreover, the chiroptical properties could be memorized by replacing the chiral inducer with an achiral competitive binder, and the chiroptical signal could be erased and reversed by an antipodal chiral inducer, which also showed the self-inhibition property.

Neuroimaging Study Investigating the Supraspinal Control of Lower Urinary Tract Function in Man With Orthotopic Ileal Neobladder.

Introduction: Recent studies employing functional imaging methodology have revealed reference brain regions of urinary tract function, namely, the midbrain periaqueductal gray matter, thalamus, and cingulate and prefrontal cortices. The orthotopic ileal neobladder is a desirable method for urinary diversion after radical cystectomy, but its supraspinal control remains unknown. We aimed to evaluate brain activity while maintaining urinary urgency and voluntary urinary control in male subjects with ileal orthotopic neobladders by performing functional MRI (fMRI) during a block design experiment. Materials and Methods: Patients were recruited at the Sun Yat-sen Memorial Hospital of the Sun Yat-sen University from October 2017 to May 2019. Two tasks were performed during fMRI scanning: (1) repeated infusion and withdrawal of sterile saline solution into and out of the neobladder to simulate urgency; and (2) repeated contraction of the pelvic floor muscle with a full neobladder to induce inhibition of micturition since the subjects were asked not to urinate. The obtained data were visualized and statistically analyzed. Results: Sixteen subjects were recruited in the study, and data were obtained from 10 subjects: mean age 60.1 years, average postoperative time 20.2 months, and daytime continence rate 100%. The parahippocampus, frontal lobe, vermis, and anterior cingulate cortex were activated with large bladder volumes, and the thalamus and caudate nucleus were deactivated during voluntary urinary control. Conclusion: A complex supraspinal program is involved during ileal orthotopic neobladder control, which is significantly different from that with normal bladders, in which the original intestine visceral volume sensation is preserved.

GADD45B Is a Potential Diagnostic and Therapeutic Target Gene in Chemotherapy-Resistant Prostate Cancer.

BACKGROUND: Chemoresistance is the major cause of death in advanced prostate cancer (PCa), especially in metastatic PCa (mPCa). However, the molecular mechanisms underlying the chemoresistance of PCa remain unclear. Understanding the reason behind the drug resistance would be helpful in developing new treatment approaches. METHODS: The Cancer Genome Atlas, Gene Expression Omnibus datasets, and clinical samples were used to examine the correlation between growth arrest and DNA damage-inducible 45 beta (GADD45B) with clinical characteristics and prognosis. Lentiviral transfection was used to construct GADD45B overexpression cell lines. Hypoxic incubator, low serum medium, or docetaxel was used to build environmental stress model or chemotherapy cell model. The MTS assay and colony formation assay were used to test cell viability. Apoptosis and cell cycle were detected by flow cytometry. The RNA and protein levels of related biomarkers were tested by Western blotting and quantitative polymerase chain reaction. Bioinformatics analysis after RNA sequencing was performed to identify the possible mechanism of how GADD45B regulates chemotherapy resistance. RESULTS: GADD45B was related to distant metastasis but not to Gleason score, prostate-specific antigen level, T stage, or lymph node metastasis and indicated a good prognosis. The level of GADD45B increased significantly in PCa cells that faced environmental stress. It was found that a high level of GADD45B significantly enhanced the chemosensitivity. Furthermore, high GADD45B promoted cell apoptosis via mitogen-activated protein kinase (MAPK) pathway. CONCLUSION: GADD45B promoted chemosensitivity of prostate cancer through MAPK pathway. GADD45B could serve as a diagnostic biomarker and therapeutic target for mPCa or chemotherapy-resistant patients.

Supramolecular Enantiodifferentiating Photocyclodimerization of 2-Anthracenecarboxylic Acid Mediated by Bridged ß-Cyclodextrins: Critical Effects of the Host Structure, pH and Co-Solvents.

Several sulfoxide- and sulfone-bridged ß-cyclodextrin (CD) dimers were synthesized for mediating the enantiodifferentiating [4+4] photocyclodimerization of 2-anthracenecarboxylic acid (AC). The complexation behavior of these chiral hosts with AC was investigated by UV-vis, circular dichroism, fluorescence, and NMR spectroscopies and certified the formation of 1 : 1 and 1 : 2 host-guest complexes. The product distribution and enantioselectivity of the photoreaction turned out to be a critical function of the chemical structure of bridged CDs. Comparing to the sulfur-bridged 2AX -3GX ß-CD dimer 7, the conversion of the photolyzes with sulfoxide-bridged was significantly improved, and the ee of cyclodimer 2 was remarkably increased from -82.8% with 7 to -96.7% with the sulfoxide-bridged 2AX -3GX ß-CD dimer 8. The relative yields and ee values of the slipped cyclodimers 5 and 6 were greatly enhanced in the presence of 6 M CsCl. The reaction selectivity is susceptible to the pH variation of the aqueous buffer solution, demonstrating that the supramolecular photochirogenesis is controlled by multidimensional factors, including the chemical structure of the chiral host, solvent, and pH conditions.

Age-related macular degeneration and premorbid allergic diseases: a population-based case-control study.

Evidence indicates that age-related macular degeneration (AMD) is associated with the prior presence of allergic diseases; however, large-scale studies in the literature are limited. A case-control study was conducted to describe the relationship between premorbid allergic diseases and AMD using Taiwan's National Health Insurance database. Eligibility criteria for inclusion of new adult AMD cases from 2000 to 2013 were set up. We defined the year of diagnosis as the index year. Age-, gender-, index year- matched controls who were drawn from the same database. The case control ratio was 1:4. For all participants, all premorbid conditions staring 1996 to index year were documented. Binary logistic regression was used to describe factors related to AMD occurrence. The AMD group consisted of 10,911 patients, and the comparison group consisted of 43,644 individuals. Patients with AMD showed significant associations with premorbid allergic diseases (aOR 1.54, 95% CI 1.47-1.61), specifically with allergic conjunctivitis (aOR 2.07, 95% CI 1.94-2.20), allergic rhinitis (aOR 1.32, 95% CI 1.25-1.39), asthma (aOR 0.99, 95% CI 0.93-1.06), and atopic dermatitis (aOR 1.04, 95% CI 0.94-1.17). Further analyses indicated that patients with more concurrent allergic diseases have higher associations with AMD than those with fewer concurrent diseases. Patients with more annual medical visits for their allergic diseases also showed higher associations with AMD than those with fewer visits. AMD is significantly associated with premorbid allergic diseases. The underlying mechanisms must be further investigated.

Design and Synthesis of Fluorescent 1,3-Diaryl-ß-carbolines and 1,3-Diaryl-3,4-dihydro-ß-carbolines.

The 1,3-diaryl-ß-carboline derivatives, including 3,4-dihydro variants, were synthesized via a multiple-step approach. These compounds possess rigid and twisted configurations, which are expected to exhibit unique optical properties. The absorption and fluorescence properties of the newly synthesized compounds were investigated. These synthetic 1,3-diaryl-ß-carbolines displayed strong emission in the range of 387-409 nm and exhibited absolute photoluminescence quantum yields of up to 74%. Density functional theory calculations were performed to better elucidate the geometric, electronic, and optical properties of these novel 1,3-diaryl-ß-carbolines.