In-depth analysis of OTC A208T case induced by OTC gene mutation and research on the prediction and simulation of the impact on protein function.

Background: Ornithine transcarbamylase deficiency (OTCD), a rare hereditary disease caused by gene mutation of ornithine transcarbamylase (OTC), is the most prevalent type among urea cycle disorders. OTCD typically leads to mitochondrial enzyme dysfunction, preventing the synthesis of citrulline from carbamoyl phosphate and ornithine, and is characterized by a remarkable increase in blood ammonia. Specific symptoms may include neurological abnormalities, growth retardation, and other manifestations. Methods: We presented a case of a child diagnosed with OTCD (OMIM: 311250). By using whole-genome sequencing (WGS) for the pedigree and in-depth whole-exome sequencing (WES), we aimed to identify the disease-causing genes. Gene mutation prediction tools were employed to verify the pathogenicity, and the molecular dynamics simulation method was utilized to assess the impact of this mutation on the activity and structural stability of the OTC protein. Results: Whole-exome sequencing detected an OTC variant [NM_000531: c.622 (exon6) G > A, p.A208T]. Through comprehensive analysis with various gene mutation prediction tools and in line with the ACMG guidelines, this mutation site was firmly established as a pathogenic site. Moreover, the molecular dynamics simulation results clearly demonstrated that this mutation would significantly compromise the stability of the OTC protein structure. Conclusion: This study deepens our understanding of the clinical manifestations and characteristics of OTCD, especially the OTC A208T gene mutation site. Given the lack of specific clinical manifestations in OTCD patients, early and accurate diagnosis is crucial for effective treatment and prognosis improvement. To our knowledge, this is the first case of this mutation site reported in China.

A Silver Modified Nanosheet Self-Assembled Hollow Microsphere with Enhanced Conductivity and Permeability.

The utilization of sheet structure composites as a viable conductive filler has been implemented in polymer-based electromagnetic shielding materials. However, the development of an innovative sheet structure to enhance electromagnetic shielding performance remains a significant challenge. Herein, we propose a novel design incorporating silver-modified nanosheet self-assembled hollow spheres to optimize their performance. The unique microporous structure of the hollow composite, combined with the self-assembled surface nanosheets, facilitates multiple reflections of electromagnetic waves, thereby enhancing the dissipation of electromagnetic energy. The contribution of absorbing and reflecting electromagnetic waves in hollow nanostructures could be attributed to both the inner and outer surfaces. When multiple reflection attenuation is implemented, the self-assembled stack structure of nanosheets outside the composite material significantly enhances the occurrence of multiple reflections, thereby effectively improving its shielding performance. The structure also facilitates multiple reflections of incoming electromagnetic waves at the internal and external interfaces of the material, thereby enhancing the shielding efficiency. Simultaneously, the incorporation of silver particles can enhance conductivity and further augment the shielding properties. Finally, the optimized Ag/NiSi-Ni nanocomposites can demonstrate superior initial permeability (2.1 × 10-6 H m-1), saturation magnetization (13.2 emu g-1), and conductivity (1.2 × 10-3 Ω•m). This work could offer insights for structural design of conductive fillers with improved electromagnetic shielding performance.

Human vascularized macrophage-islet organoids to model immune-mediated pancreatic ß cell pyroptosis upon viral infection.

There is a paucity of human models to study immune-mediated host damage. Here, we utilized the GeoMx spatial multi-omics platform to analyze immune cell changes in COVID-19 pancreatic autopsy samples, revealing an accumulation of proinflammatory macrophages. Single-cell RNA sequencing (scRNA-seq) analysis of human islets exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coxsackievirus B4 (CVB4) viruses identified activation of proinflammatory macrophages and ß cell pyroptosis. To distinguish viral versus proinflammatory-macrophage-mediated ß cell pyroptosis, we developed human pluripotent stem cell (hPSC)-derived vascularized macrophage-islet (VMI) organoids. VMI organoids exhibited enhanced marker expression and function in both ß cells and endothelial cells compared with separately cultured cells. Notably, proinflammatory macrophages within VMI organoids induced ß cell pyroptosis. Mechanistic investigations highlighted TNFSF12-TNFRSF12A involvement in proinflammatory-macrophage-mediated ß cell pyroptosis. This study established hPSC-derived VMI organoids as a valuable tool for studying immune-cell-mediated host damage and uncovered the mechanism of ß cell damage during viral exposure.

Engineering TadA ortholog-derived cytosine base editor without motif preference and adenosine activity limitation.

The engineered TadA variants used in cytosine base editors (CBEs) present distinctive advantages, including a smaller size and fewer off-target effects compared to cytosine base editors that rely on natural deaminases. However, the current TadA variants demonstrate a preference for base editing in DNA with specific motif sequences and possess dual deaminase activity, acting on both cytosine and adenosine in adjacent positions, limiting their application scope. To address these issues, we employ TadA orthologs screening and multi sequence alignment (MSA)-guided protein engineering techniques to create a highly effective cytosine base editor (aTdCBE) without motif and adenosine deaminase activity limitations. Notably, the delivery of aTdCBE to a humanized mouse model of Duchenne muscular dystrophy (DMD) mice achieves robust exon 55 skipping and restoration of dystrophin expression. Our advancement in engineering TadA ortholog for cytosine editing enriches the base editing toolkits for gene-editing therapy and other potential applications.

Design, synthesis and antitumor activity of novel 4-oxobutanamide derivatives.

To find highly effective and low-toxicity antitumor drugs to overcome the challenge of cancer, we designed and synthesized a series of novel 4-oxobutanamide derivatives using the principle of molecular hybridization and tested the antiproliferative ability of the title compounds against human cervical carcinoma cells (HeLa), human breast carcinoma cells (MDA-MB-231) and human kidney carcinoma cells (A498). Among them, N1-(4-methoxybenzyl)-N4-(4-methoxyphenyl)-N1-(3,4,5-trimethoxyphenyl) succinimide DN4 (IC50 = 1.94 µM) showed the best proliferation activity on A498, superior to the positive control paclitaxel (IC50 = 8.81 µM) and colchicine (IC50 = 7.17 µM). Compound DN4 not only inhibited the proliferation, adhesion and invasion of A498, but also inhibited angiogenesis and tumor growth in a dose-dependent manner in the xenograft model of A498 cells. In addition, we also predicted the physicochemical properties and toxicity (ADMET) of these derivatives, and the results suggested that these derivatives may have the absorption, distribution, metabolism, excretion, and toxicity properties of drug candidates. Thus, compound DN4 may be a promising drug candidate for the treatment of cancer.

N6-Methyladenosine RNA Modification Regulates Maize Resistance to Maize Chlorotic Mottle Virus Infection.

Maize chlorotic mottle virus (MCMV) is one of the main viruses causing significant losses in maize. N6-methyladenosine (m6A) RNA modification has been proven to play important regulatory roles in plant development and stress response. In this study, we found that MCMV infection significantly up-regulated the m6A level in maize, and methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were performed to investigate the distribution of m6A modified peaks and gene expression patterns in MCMV-infected maize plants. The results showed that 1325 differentially methylated genes (DMGs) and 47 differentially methylated and expressed genes (DMEGs) were identified and analyzed. Moreover, the results of virus-induced gene silencing (VIGS) assays showed that ZmECT18 and ZmGST31 were required for MCMV infection, while silencing of ZmMTC, ZmSCI1 or ZmTIP1 significantly promoted MCMV infection in maize. Our findings provided novel insights into the regulatory roles of m6A modification in maize response to MCMV infection.

Rational Design of Crystalline and Enantiomerically Pure Helicenes with Open-Shell Singlet Ground States.

Helicene diradical derivatives have attracted widespread attentions because of their unique magnetic and chiroptoelectronic properties, however, crystalline and enantiomerically pure forms of helicene diradicals are extremely rare. Herein, we describe the rational design and synthesis of o-quinone functionalized helicene diradicals with crystalline enantiomerical purity. Diradical dianion salt Rac-3K and its enantiomers P/M-3K were obtained by reduction of corresponding precursors Rac-3 and P/M-3 with two equivalent potassium graphite in THF in the presence of (di)benzo-18-crown-6. Neutral dioxoborocyclic helicene diradicals (Rac-3B and P/M-3B) were produced by reactions of Rac-3 or P/M-3 with chlorobis(perfluorophenyl)borane (B(C6F5)2Cl. Crystal structures of compounds Rac-3K, Rac-3B and P/M-3K were obtained by single crystal X-ray diffraction. Their open-shell singlet state ground states were confirmed by electron paramagnetic resonance (EPR) spectroscopy, superconducting quantum interference device (SQUID) measurements and theoretical calculations. Their chiroptical properties were investigated by the electronic circular dichroism (ECD) spectroscopy. This work provides the first examples of enantiopure helicene diradical dianions and boron-containing helicene diradicals.

Preparation and application of a pseudo-templated multi-monomer aflatoxins imprinted polymer.

A functional material was developed with specific recognition properties for aflatoxins for pre-processing enrichment and separation in the detection of aflatoxins in Chinese herbal medicines. In the experiment, ethyl coumarin-3-carboxylate, which has a highly similar structure to the oxonaphthalene o-ketone of aflatoxin, was selected as a pseudo-template, zinc acrylate, neutral red derivative, and methacrylic acid, which have complementary functions, were selected as co-monomers to prepare a pseudo-template multifunctional monomer molecularly imprinted polymer (MIP). The MIP obtained under the optimal preparation conditions has a maximum adsorption capacity of 0.036 mg/mg and an imprinting factor of 3.67. The physical property evaluation of the polymers by Fourier infrared spectrometer, scanning electron microscopy, pore size analyzer, thermogravimetric analyzer, and diffuse reflectance spectroscopy showed that the MIP were successfully prepared and porous spherical-like particles were obtained. The synthesized polymer was used as a solid-phase extraction agent for the separation of aflatoxins from the extract of spina date seed. The linear range of the developed method was 10-1000 ng/mL, the limit of detection was 0.36 ng/mL, the limit of quantification was 1.19 ng/mL, and the recoveries of the extracts at the concentration level of 0.2 µg/mL were in the range 88.0-93.4%, with relative standard deviations (RSDs) of 1.97% (n). The results showed that the preparation of MIPs using ethyl coumarin-3-carboxylate as a template was simple, economical, and convenient. It is expected to become a promising functional material for the enrichment and separation aflatoxins from complex matrices.

Treatment options for tumor progression after initial immunotherapy in advanced non-small cell lung cancer: A real-world study.

OBJECTIVE: Whether to continue administering immunotherapy to patients with advanced non-small cell lung cancer (NSCLC) who have experienced tumor progression remains controversial after immunotherapy. The aims were to explore survival outcomes after further immunotherapy post-progression and to determine the optimal combination therapy in such cases. METHODS: Overall, 507 patients with NSCLC who underwent immunotherapy and experienced tumor progression were retrospectively divided into Immuno-combination and No-immuno groups according to whether additional combination therapy involving immunotherapy was administered post-progression. Progression-free survival (PFS) and overall survival (OS) were evaluated. Subgroup analyses were performed according to the different treatment regimens for patients in the Immuno-combination group. RESULTS: After propensity score matching, there were 150 patients in the No-immuno group and 300 patients in the Immuno combination group. Superior PFS was observed in the Immuno-combination group compared with those in the No-immuno group (6-month PFS: 25.3 % vs. 60.6 %; 12-month PFS: 6.7 % vs. 24.4 %; P < 0.001). Similar intergroup differences were observed for OS (12-month OS: 22.3 % vs. 69.4 %; 18-month OS: 6.4 % vs. 40.4 %; P < 0.001). Superior PFS outcomes were observed in the Immuno+Antiangiogenic group compared with the Immuno+Chemo group (6-month PFS: 51.3 % vs. 71.5 %; 12-month PFS: 23.1 % vs. 25.7 %; P = 0.017). Similar differences in OS were observed between those same subgroups (12-month OS: 62.1 % vs. 77.9 %; 18-month OS: 33.3 % vs. 48.7 %; P = 0.006). CONCLUSION: Patients with NSCLC experiencing tumor progression post-immunotherapy can still benefit from further treatment, with immunotherapy combined with antiangiogenic therapy the most efficacious option.

Air-Processed Efficient Cesium-Based Two-Dimensional Perovskite Solar Cells Based on Asymmetric Chiral Ammonium Salts.

Cesium-based two-dimensional (2D) perovskites with attractive phase and environmental stability have broad application prospects in single-junction and tandem perovskite solar cells (PSCs). However, the severe nonradiative recombination and significant energy losses due to disordered phase orientations and phase distributions greatly hinder the carrier transport performance of cesium-based 2D PSCs and severely limit their photovoltaic performance. Here, we employ an asymmetric chiral spacer cation source, (R)-α-phenylethylamine acrylate (R-α-PEAAA), to prepare high-quality 2D cesium-based films with uniform phase distribution and high out-of-plane orientation by air processing, resulting in efficient carrier transport. More importantly, the asymmetric chiral spacer R-α-PEA has a stronger dipole moment than its isomer (PEA), which can regulate the dielectric properties of cesium-based 2D perovskites and promote charge dissociation. In addition, the chiral R-α-PEA can optimize the morphology and out-of-plane orientation of perovskite films, reduce trap density and nonradiative recombination loss, and optimize energy level alignment, thus enhancing carrier transport. As a result, cesium-based 2D PSCs (R-α-PEA2Cs4Pb5I16, n = 5) achieved a record power conversion efficiency of 19.71% and the unencapsulated device maintained over 90% efficiency after 1500 h of continuous light exposure and ambient storage (35 ± 5% relative humidity). This study provides an idea for the development of chiral 2D perovskite with efficient charge carrier transport toward efficient and stable cesium-based 2D PSCs.

A four-in-one first-in-human study to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and concentration-QTc relationship of HRS-1780, a selective non-steroidal mineralocorticoid receptor antagonist, in healthy men.

BACKGROUND: This first-in-human study evaluated HRS-1780, an oral selective non-steroidal mineralocorticoid receptor antagonist, in healthy men. RESEARCH DESIGN AND METHODS: In single ascending dose (SAD) part, 10 participants for each dose cohort (5, 10, 20, 40, 60, and 80 mg) were randomized (8:2) to HRS-1780 or placebo. In multiple ascending dose part, 12 participants for each dose (10, 20, and 40 mg) were randomized (9:3) to HRS-1780 or placebo once daily for 7 days. The primary endpoint was safety and tolerability. RESULTS: HRS-1780 was well tolerated with all adverse events being mild. In the steady state, the median time to maximum concentration (Tmax) was 0.750 h and mean half-life was 1.76-1.96 h. High-fat/high-calorie meal prolonged Tmax but did not affect exposure. Multiple dosing of HRS-1780 at 40 mg showed a decreasing trend in systolic blood pressure compared with placebo. Changes in plasma aldosterone and norepinephrine with HRS-1780 were higher compared to placebo. Upper bounds of two-sided 90% confidence interval of placebo-adjusted change-from-baseline QTcF were below 10 msec at the maximum concentration in SAD. The trial had limited sample size and short study duration. CONCLUSIONS: HRS-1780 had favorable safety and pharmacokinetic profiles and did not cause clinically meaningful QTcF prolongation. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05638126).

Human Vascularized Macrophage-Islet Organoids to Model Immune-Mediated Pancreatic ß cell Pyroptosis upon Viral Infection.

There is a paucity of human models to study immune-mediated host damage. Here, we utilized the GeoMx spatial multi-omics platform to analyze immune cell changes in COVID-19 pancreatic autopsy samples, revealing an accumulation of proinflammatory macrophages. Single cell RNA-seq analysis of human islets exposed to SARS-CoV-2 or Coxsackievirus B4 (CVB4) viruses identified activation of proinflammatory macrophages and ß cell pyroptosis. To distinguish viral versus proinflammatory macrophage-mediated ß cell pyroptosis, we developed human pluripotent stem cell (hPSC)-derived vascularized macrophage-islet (VMI) organoids. VMI organoids exhibited enhanced marker expression and function in both ß cells and endothelial cells compared to separately cultured cells. Notably, proinflammatory macrophages within VMI organoids induced ß cell pyroptosis. Mechanistic investigations highlighted TNFSF12-TNFRSF12A involvement in proinflammatory macrophage-mediated ß cell pyroptosis. This study established hPSC-derived VMI organoids as a valuable tool for studying immune cell-mediated host damage and uncovered mechanism of ß cell damage during viral exposure.

Stabilizing hexagonally close-packed phase in single-component block copolymers through rational symmetry breaking.

Despite being predicted to be a thermodynamically equilibrium structure, the absence of direct experimental evidence of hexagonally close-packed spherical phase in single-component block copolymers raises uncomfortable concerns regarding the existing fundamental phase principles. This work presents a robust approach to regulate the phase behavior of linear block copolymers by deliberately breaking molecular symmetry, and the hexagonally close-packed lattice is captured in a rigorous single-component system. A collection of discrete A1BA2 triblock copolymers is designed and prepared through an iterative growth method. The precise chemical composition and uniform chain length eliminates inherent size distribution and other molecular defects. Simply by tuning the relative chain length of two end A blocks, a rich array of ordered nanostructures, including Frank-Kasper A15 and σ phases, are fabricated without changing the overall chemistry or composition. More interestingly, hexagonally close-packed spherical phase becomes thermodynamically stable and experimentally accessible attributed to the synergistic contribution of the two end blocks. The shorter A blocks are pulled out from the core domain into the matrix to release packing frustration, while the longer ones stabilize the ordered spherical phase against composition fluctuation that tends to disrupt the lattice. This study adds a missing puzzle piece to the block copolymer phase diagram and provides a robust approach for rational structural engineering.

Severe Hypothermia Induces Ferroptosis in Cerebral Cortical Nerve Cells.

Abnormal shifts in global climate, leading to extreme weather, significantly threaten the safety of individuals involved in outdoor activities. Hypothermia-induced coma or death frequently occurs in clinical and forensic settings. Despite this, the precise mechanism of central nervous system injury due to hypothermia remains unclear, hindering the development of targeted clinical treatments and specific forensic diagnostic indicators. The GEO database was searched to identify datasets related to hypothermia. Post-bioinformatics analyses, DEGs, and ferroptosis-related DEGs (FerrDEGs) were intersected. GSEA was then conducted to elucidate the functions of the Ferr-related genes. Animal experiments conducted in this study demonstrated that hypothermia, compared to the control treatment, can induce significant alterations in iron death-related genes such as PPARG, SCD, ADIPOQ, SAT1, EGR1, and HMOX1 in cerebral cortex nerve cells. These changes lead to iron ion accumulation, lipid peroxidation, and marked expression of iron death-related proteins. The application of the iron death inhibitor Ferrostatin-1 (Fer-1) effectively modulates the expression of these genes, reduces lipid peroxidation, and improves the expression of iron death-related proteins. Severe hypothermia disrupts the metabolism of cerebral cortex nerve cells, causing significant alterations in ferroptosis-related genes. These genetic changes promote ferroptosis through multiple pathways.

Cinquefoil Knot Possessing Dynamic and Tunable Metal Coordination.

While the majority of knots are made from the metal-template approach, the use of entangled, constrained knotted loops to modulate the coordination of the metal ions remains inadequately elucidated. Here, we report on the coordination chemistry of a 140-atom-long cinquefoil knotted strand comprising five tridentate and five bidentate chelating vacancies. The knotted loop is prepared through the self-assembly of asymmetric "3 + 2" dentate ligands with copper(II) ions that favor five-coordination geometry. The formation of the copper(II) pentameric helicate is confirmed by X-ray crystallography, while the corresponding copper(II) knot is characterized by XPS and LR-/HR ESI-MS. Upon removal of the original template, the knotted ligand facilitates zinc(II) ions, which typically form four- or six-coordination geometries, resulting in the formation of an otherwise inaccessible zinc(II) metallic knot with coordinatively unsaturated metal centers. The coordination numbers and geometries of the zinc(II) cations are undoubtedly determined by X-ray crystallography. Despite the kinetically labile nature and high reversibility of the zinc(II) complex preventing the detection of 5-to-6 coordination equilibrium in solution, the effects on metal-ion coordination induced by knotting hold promise for fine-tuning the coordination of metal complexes.

Bio-orthogonal click chemistry strategy for PD-L1-targeted imaging and pyroptosis-mediated chemo-immunotherapy of triple-negative breast cancer.

BACKGROUND: The combination of programmed cell death ligand-1 (PD-L1) immune checkpoint blockade (ICB) and immunogenic cell death (ICD)-inducing chemotherapy has shown promise in cancer immunotherapy. However, triple-negative breast cancer (TNBC) patients undergoing this treatment often face obstacles such as systemic toxicity and low response rates, primarily attributed to the immunosuppressive tumor microenvironment (TME). METHODS AND RESULTS: In this study, PD-L1-targeted theranostic systems were developed utilizing anti-PD-L1 peptide (APP) conjugated with a bio-orthogonal click chemistry group. Initially, TNBC was treated with azide-modified sugar to introduce azide groups onto tumor cell surfaces through metabolic glycoengineering. A PD-L1-targeted probe was developed to evaluate the PD-L1 status of TNBC using magnetic resonance/near-infrared fluorescence imaging. Subsequently, an acidic pH-responsive prodrug was employed to enhance tumor accumulation via bio-orthogonal click chemistry, which enhances PD-L1-targeted ICB, the pH-responsive DOX release and induction of pyroptosis-mediated ICD of TNBC. Combined PD-L1-targeted chemo-immunotherapy effectively reversed the immune-tolerant TME and elicited robust tumor-specific immune responses, resulting in significant inhibition of tumor progression. CONCLUSIONS: Our study has successfully engineered a bio-orthogonal multifunctional theranostic system, which employs bio-orthogonal click chemistry in conjunction with a PD-L1 targeting strategy. This innovative approach has been demonstrated to exhibit significant promise for both the targeted imaging and therapeutic intervention of TNBC.

Natural killer cells promote neutrophil extracellular traps and restrain macular degeneration in mice.

Neovascular age-related macular degeneration (nvAMD) is the leading cause of blindness in the elderly population. Although it is known that nvAMD is associated with focal inflammation, understanding of the precise immune components governing this process remains limited. Here, we identified natural killer (NK) cells as a prominent lymphocyte population infiltrating the perivascular space of choroidal neovascularization (CNV) lesions in patients with nvAMD and in mouse models. Olink proteomic analysis and single-cell RNA sequencing combined with knockout studies demonstrated the involvement of C-C chemokine receptor 5 (CCR5) in NK cell recruitment and extravasation at the CNV sites of mice. Depletion of NK cells or inhibition of activating receptor NK group 2, member D (NKG2D) inhibited the formation of neutrophil extracellular traps, increased vascular leakage, and exacerbated pathological angiogenesis, indicating that NK cells restrain pathogenesis in this mouse model. Age is the strongest risk factor for AMD, and we show that NK cells from aged human donors exhibited a less cytotoxic phenotype. NK cells from old mice exhibited compromised protective effects in the CNV mouse model. In addition, interleukin-2 complex-mediated expansion of NK cells improved CNV formation in mice. Collectively, our study highlights NK cells as a potential therapeutic target for patients with nvAMD.

Large field of view and spatial region of interest transcriptomics in fixed tissue.

Expression profiling in spatially defined regions is crucial for systematically understanding tissue complexity. Here, we report a method of photo-irradiation for in-situ barcoding hybridization and ligation sequencing, named PBHL-seq, which allows targeted expression profiling from the photo-irradiated region of interest in intact fresh frozen and formalin fixation and paraffin embedding (FFPE) tissue samples. PBHL-seq uses photo-caged oligodeoxynucleotides for in situ reverse transcription followed by spatially targeted barcoding of cDNAs to create spatially indexed transcriptomes of photo-illuminated regions. We recover thousands of differentially enriched transcripts from different regions by applying PBHL-seq to OCT-embedded tissue (E14.5 mouse embryo and mouse brain) and FFPE mouse embryo (E15.5). We also apply PBHL-seq to the subcellular microstructures (cytoplasm and nucleus, respectively) and detect thousands of differential expression genes. Thus, PBHL-seq provides an accessible workflow for expression profiles from the region of interest in frozen and FFPE tissue at subcellular resolution with areas expandable to centimeter scale, while preserving the sample intact for downstream analysis to promote the development of transcriptomics.

Photochromism, Thermochromism, and Electrochromism in Solid-State Host-Guest Inclusion Complexes of ß-Cyclodextrin with Dialkylcarboxyl-Substituted Viologens.

Multi-stimuli-responsive chromic materials have immense potential for utilization. Herein, two supramolecular inclusion complexes were prepared by self-assembly of ß-cyclodextrin (ß-CD) with dialkylcarboxyl-substituted viologens, N,N'-di(3-carboxy-propyl)-4,4'-bipyridinium dichloride (CPV·Cl2) and N,N'-di(6-carboxy-hexyl)-4,4'-bipyridinium dibromide (CHV·Br2). The self-assembled inclusion complexes CPV2+@ß-CD and CHV2+@ß-CD2 in the solid-state exhibited naked-eye photochromism, thermochromism, and electrochromism in response to multiple external stimuli including light, temperature, and electric field, respectively. Solid-state UV-vis diffuse reflectance and electron spin resonance (ESR) spectroscopy revealed that the observed photochromism, thermochromism and electrochromism are attributed to the formation of viologen free radicals induced by electron transfer under external stimuli. The excellent stimuli-response chromic properties of the title inclusion complexes support their practical utility in visual display, multiple anticounterfeiting, and multilevel information encryption.