Mesoscale Acid-Base Complexes Display Size-Associated Photophysical Property and Photochemical Activity.

The properties of single molecules and molecular aggregates can differ dramatically, leading to a long-standing interest in mesoscale aggregation processes. Herein, a series of acid-base molecular complexes is developed by using a tetraphenylethylene-backboned fluorophore, and investigated the photophysical properties and photochemical activities at different aggregation length scales. This fluorophore, with two basic diethylamine groups and two acidic tetrazole groups, exhibits sparse solubility due to multivalent interactions that cause infinite aggregation. The addition of a third acid leads to the formation of fluorophore/acid complexes with good dispersibility and colloidal stability. This assembly process can be controlled by the use of different acids and their stoichiometry, resulting in aggregates ranging in size from a few to hundreds of nanometers. A crystalline structure is obtained to illustrate the complex properties of the acid-base network. Unlike the single molecule, these complexes show a trend of size-related properties for photoluminescence efficiency and photochemical activity. As the amount of acid added increases, the size of the complexes decreases, the aggregation effect of the complexes on fluorescence emission increases, and the rates of the oxidative photocyclization and photodecomposition slow down. This work may help to understand size-controlled molecular materials at the mesoscale for functional design.

The relationship between serum levels of S-100ß and anxiety symptoms in patients with acute stroke.

BACKGROUND: Post-stroke anxiety (PSA) is a common neuropsychiatric affective disorder occurring after a stroke. Animal experiments have indicated that serum S-100ß levels are closely related to anxiety disorder. No clinical study has been done to explore the relationship between serum S-100ß levels and anxiety symptoms in patients with acute stroke. The aim of our study was to investigate the association between serum S-100ß levels and PSA. METHODS: One hundred twenty-six acute stroke patients were recruited and followed up for 1 month. Blood samples were collected within 24 h after admission. The levels of serum S-100ß were measured by enzyme-linked immunosorbent assays. Patients with significant clinical symptoms of anxiety and a Hamilton Anxiety Rating Scale score >7 at 1 month after stroke were diagnosed as PSA. RESULTS: Serum S-100ß levels in the non-PSA group were lower than the PSA group (838.97 (678.20-993.59) ng/L vs. 961.87 (796.09-1479.59) ng/L, Z = -2.661, P = 0.008). In multivariate analyses, we found that decreased risk of PSA was associated with low tertile serum S-100ß levels (≤753.8 ng/L, OR 0.062, 95% CI 0.008-0.475, P = 0.007). CONCLUSIONS: Low serum S-100ß levels at admission may be associated with the decreased risk of PSA.

Unusual Through-Space Interactions between Oxygen Atoms that Mediate Inverse Morphochromism of an AIE Luminogen.

We have studied the photophysics of tetrafurylethene, an aggregation-induced emission luminogen with exceptionally short intramolecular O-O distances of 2.80 Šand a significant red-shifted morphochromism (27 nm) when going from the aggregate to the crystal. The short O-O distances, which are substantially smaller than the sum of the van der Waals radii (3.04 Å), are due to the fact that the oxygen atoms act as an electronic bridge connecting the furan rings on opposite ends of the central double bond, giving rise to a circular delocalization of the π-electron density across the rings. In the excited state the O-O distance is further reduced to 2.70 Å; the increased O-O interaction causes a narrowing of the HOMO-LUMO gap, resulting in the red morphochromism of the emission. Our results show the structural origin of the red-shifted emission lies in close O-O contacts, paving the way for understanding the clusteroluminescence of oxygen-rich non-conjugated systems that emit visible light.

Spiro-Functionalized Diphenylethenes: Suppression of a Reversible Photocyclization Contributes to the Aggregation-Induced Emission Effect.

Many aggregation-induced emission (AIE) materials are featured by the diphenylethene (DPE) moiety which exhibits rich photophysical and photochemical activities. The understanding of these activities behind AIE is essential to guide the design of fluorescent materials with improved performance. Herein by fusing a flexible DPE with a rigid spiro scaffold, we report a class of novel deep-blue material with solid-state fluorescent quantum yield (ΦF) up to 99.8%. Along with the AIE phenomenon, we identified a reversible photocyclization (PC) on DPE with visible chromism, which is, on the contrary, popularized in solutions but blocked by aggregation. We studied the steric and electronic effects of structural perturbation and concluded that the PC is a key process behind the RIMs (restriction of intramolecular motions) mechanism for these materials. Mitigation of the PC leads to enhanced fluorescence in solutions and loss of the AIE characteristics.

Restriction of Access to the Dark State: A New Mechanistic Model for Heteroatom-Containing AIE Systems.

Restriction of intramolecular motion (RIM), as the working mechanism of aggregation-induced emission (AIE), cannot fully explain some heteroatom-containing systems. Now, two excited states are taken into account and a mechanism, restriction of access to dark state (RADS), is specified to elaborate RIM and complete the picture of AIE mechanism. A nitrogen-containing molecule named APA is chosen as a model compound; its weak fluorescence in solution is ascribed to the easy access from the bright (π,π*) state to the close-lying dark (n,π*) state. By either metal complexation or aggregation, the dark state is less accessible due to restriction of the molecular motion leading to the dark state and elevation of the dark state energy, thus the bright state emission is restored. RADS is powerful in elucidating the AIE effect of molecules with excited states favoring non-radiative decay, including overlap-forbidden states such as (n,π*) and CT states, spin-forbidden triplet states, and so on.

Performance of risk prediction models for diabetic foot ulcer: a meta-analysis.

Background: The number of prediction models for diabetic foot ulcer (DFU) risk is increasing, but their methodological quality and clinical applicability are uncertain. We conducted a systematic review to assess their performance. Methods: We searched PubMed, Cochrane Library, and Embase databases up to 10 February 2024 and extracted relevant information from selected prediction models. The Prediction model Risk Of Bias ASsessment Tool (PROBAST) checklist was used to assess bias risk and applicability. All statistical analyses were conducted in Stata 14.0. Results: Initially, 13,562 studies were retrieved, leading to the inclusion of five development and five validation models from eight studies. DFU incidence ranged from 6% to 16.8%, with age and hemoglobin A1C (HbA1c) commonly used as predictive factors. All included studies had a high risk of bias, mainly due to disparities in population characteristics and methodology. In the meta-analysis, we observed area under the curve (AUC) values of 0.78 (95% CI [0.69-0.89]) for development models and 0.84 (95% CI [0.79-0.90]) for validation models. Conclusion: DFU risk prediction models show good overall accuracy, but there is a risk of bias. Adherence to the PROBAST checklist is crucial for improving their clinical applicability.

Renal function affects the safety and efficacy of tirofiban in acute ischemic stroke thrombectomy patients.

BACKGROUND: Acute ischemic stroke poses a significant health threat, and thrombectomy has become a routine treatment. Tirofiban has emerged as a promising adjunct therapy to minimize reocclusion after thrombectomy. We aimed to investigate whether renal function influences the safety and efficacy of tirofiban in patients undergoing endovascular therapy. METHODS: Patients' clinical data collected from the stroke unit were analyzed. The modified Rankin scale score and symptomatic intracranial hemorrhage (sICH) were used as outcome measures. RESULTS: A total of 409 patients (mean age: 66.5 years, 292 males [71.4%]) were included. Tirofiban significantly improved 3-month functional outcomes (adjusted odds ratio [aOR] = 2.408, 95% confidence interval [CI] 1.120-5.175), reduced 3-month mortality (aOR = 0.364, 95% CI 0.155-0.856), and decreased the incidence of sICH (aOR = 0.339, 95% CI 0.149-0.767) in patients with estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m². However, no significant improvement in prognosis was observed with tirofiban in patients with eGFR < 90 mL/min/1.73 m². Interaction analysis suggested a potential influence of renal function on tirofiban efficacy. CONCLUSION: Renal function may impact the efficacy of tirofiban. Administration of tirofiban in direct thrombectomy patients with normal renal function is safe and improves prognosis. However, the prognostic benefits of tirofiban are limited in patients with impaired renal function.

Cooperative assembly of a designer peptide and silk fibroin into hybrid nanofiber gels for neural regeneration after spinal cord injury.

Local reconstruction of a permissive environment with biomaterials is a promising strategy to treat spinal cord injury (SCI). We reported a hybrid hydrogel fabricated from a small functional self-assembling peptide (F-SAP) and large silk fibroin (SF). The diffusion of SF micelles into F-SAP solution was driven by the dynamic synergy between osmotic pressure and F-SAP/SF electrostatic interactions, resulting in the rearrangement of SF micelles and the formation of rod-like filaments with axes nearly perpendicular to F-SAP nanofibers. Spectroscopy analysis, including circular dichroism, Raman and fluorescence, indicated conformation changes of SF from random coil to ß sheet, which contributed to enhanced mechanical properties of the resultant hybrid hydrogel. Furthermore, the F-SAP/SF hybrid hydrogel coupled with controlled release of NT-3 provided a permissive environment for neural regeneration by providing nanofibrous substrates for regenerating axons, inflammatory modulation and remyelination, consequently resulting in improved locomotion and electrophysiological properties. This hydrogel could be used as a long-term stent in vivo for the treatment of SCI.

Regulating the proximity effect of heterocycle-containing AIEgens.

Proximity effect, which refers to the low-lying (n,π*) and (π,π*) states with close energy levels, usually plays a negative role in the luminescent behaviors of heterocyclic luminogens. However, no systematic study attempts to reveal and manipulate proximity effect on luminescent properties. Here, we report a series of methylquinoxaline derivatives with different electron-donating groups, which show different photophysical properties and aggregation-induced emission behaviors. Experimental results and theoretical calculation reveal the gradually changed energy levels and different coupling effects of the closely related (n,π*) and (π,π*) states, which intrinsically regulate proximity effect and aggregation-induced emission behaviors of these luminogens. With the intrinsic nature of heterocycle-containing compounds, they are utilized for sensors and information encryption with dynamic responses to acid/base stimuli. This work reveals both positive and negative impacts of proximity effect in heterocyclic aggregation-induced emission systems and provides a perspective to develop functional and responsive luminogens with aggregation-induced emission properties.

Predictors of functional dependence at one year in acute ischemic stroke with large vessel occlusion.

BACKGROUND: In China, the current status of clinical treatment of eLVO and the factors affecting its long-term prognosis are unclear. OBJECTIVE: This study aims to explore the predictive factors of functional outcomes at one year in patients of acute ischemic stroke with emergent large vessel occlusion (eLVO). METHODS: We retrospectively collected 536 patients who underwent treatments for eLVO. Primary outcomes included one-year functional outcomes and delayed functional independence (DFI). The logistic regression was performed to predict the primary outcome. RESULTS: 431 (85%) survivors participated in the one-year follow-up. In the multivariate logistic analysis adjusted for baseline characteristics, the following factors were found to be significant predictors of functional dependence at one year: old age (aOR = 1.042, 95% CI=1.01-1.076, p = 0.011), low Alberta stroke program early CT score (ASPECTS) (aOR = 0.791, 95% CI=0.671-0.933, p = 0.005), unsuccessful reperfusion (aOR = 0.168, 95% CI=0.048-0.586, p = 0.005), poor medication compliance (aOR = 0.022, 95% CI=0.007-0.072, p < 0.001), and complicated with stroke-associated pneumonia (SAP) (aOR = 2.269, 95% CI=1.103-4.670, p = 0.026). We also found that men (aOR = 3.947, 95% CI=1.15-13.549, p = 0.029) had better medication adherence (aOR = 14.077, 95% CI=1.736-114.157, p = 0.013), and going to rehabilitation centers (aOR = 5.197, 95% CI=1.474-18.327, p = 0.010) were independent predictors of DFI. CONCLUSION: The significant predictors of functional dependence at one year were: old age, low ASPECTS, unsuccessful reperfusion, poor medication adherence, and combination with SAP. Men, good medication adherence, and going to rehabilitation centers contributed to getting delayed functional independence.

High fibrinogen to albumin ratio is associated with hematoma enlargement in spontaneous intracerebral hemorrhage.

BACKGROUND: We investigate whether fibrinogen to albumin ratio could predict hematoma enlargement in patients suffered with spontaneous intracerebral hemorrhage. MATERIALS AND METHODS: A total of 149 patients met the entry criteria and received 1-month follow-up after discharge were divided into tertiles based on fibrinogen to albumin ratio levels (Tertile 1 [<8.06], Tertile 2 [8.06-10.33], Tertile 3 [>10.33]). Univariate analysis and binary logistic regression analysis was performed to explore the relationship between fibrinogen to albumin ratio and hematoma enlargement occurrence. RESULTS: There was a significant difference in fibrinogen to albumin ratio between hematoma enlargement group and non-hematoma enlargement group (10.11 (8.37-11.73) vs 8.81 (7.61-10.39), p = .017). In binary logistic regression analysis, the highest tertile (>10.33) was independently related to hematoma enlargement (OR = 3.152, 95% CI = 1.326-7.493, p = .009). CONCLUSION: Fibrinogen to albumin ratio on admission might be an independent predictor of hematoma enlargement after intracerebral hemorrhage.

Ratiometric Monitoring of Biogenic Amines by a Simple Ammonia-Response Aiegen.

Herein, we developed a paper-based smart sensing chip for the real-time, visual, and non-destructive monitoring of food freshness using a ratiometric aggregation-induced emission (AIE) luminogen (i.e., H+MQ, protonated 4-(triphenylamine)styryl)quinoxalin-2(1H)-one) as pH sensitive indicators. Upon exposure to amine vapors, the deprotonation of H+MQ occurs and triggers its color change from blue to yellow, with the fluorescence redshift from blue to amaranth. Consequently, we successfully achieved the sensitive detection of ammonia vapors by recording the bimodal color and fluorescence changes. Given the high sensitivity of H+MQ to ammonia vapor, a paper-based smart sensor chip was prepared by depositing H+MQ on the commercial qualitative filter paper through a physical deposition strategy. After being placed inside the sealed containers, the developed H+MQ-loaded paper chip was applied to the real-time monitoring of biogenic amine contents according to its color difference and ratio fluorescence change. The detection results were further compared with those obtained by the high-performance liquid chromatography method, which verified the feasibility of the designed paper chip for the food spoilage degree evaluation. Briefly, this work indicates that the designed H+MQ-loaded paper chip could be a promising approach for improving food freshness monitoring.

Mechanistic connotations of restriction of intramolecular motions (RIM).

Restriction of intramolecular motion (RIM) is the widely-accpeted mechanism of aggregation-induced emission (AIE). In this concise and comprehensive perspective, four mechanistic models related to different nonradiative pathways are summarized with examples to disclose the connotation of RIM, and meaningful mechanistic topics for future researches are advised.

Inhibition of 2-aminoethoxydiphenyl borate-induced rat atrial ectopic activity by anti-arrhythmic drugs.

BACKGROUND/AIMS: 2-aminoethoxydiphenyl borate (2-APB) provokes spontaneous mechanical activity in isolated rat left atria. The present study is to characterize 2-APB-induced ectopic activity in rat atria and to investigate the inhibition of 2-APB-induced ectopic activity by anti-arrhythmic drugs. METHODS: 2-APB-induced ectopic activity was measured through an isometric force transducer connected to a multichannel acquisition and analysis system. Intracellular [Ca2+](i) was measured with fluorescence laser scanning confocal microscopy. Voltage-dependent L- type Ca2+ currents were recorded by using patch-clamp technique. RESULTS: 2-APB dose-dependently increased the ectopic activity of left atria at 1, 5, 10, 20, 50 microM. Anti-arrhythmic drugs, quinidine (10 microM), lidocaine (10 microM), verapamil (5 microM), and amiodarone (50 microM, 100 microuM) inhibited 2-APB-induced ectopic activity. 2-APB-induced ectopic activity was inhibited by Ca2+-free bath, Na+/Ca2+ exchanger blockers, 3',4'-dichlorobenzamil hydrochloride (DHC) and Ni2+, not by non-selective cation channel blocker Gd3+. 2-APB also induced ectopic contractions in ventricular tissue straps and the ectopic contractions were inhibited by quinidine, verapamil and DHC. Lidocaine, verapamil and DHC inhibited 2-APB-induced increase of intracellular Ca2+ concentration in cardiomyocytes. Low molecular weight heparin inhibited phenylephrine (PE)-induced but not 2-APB -induced atria ectopic activity, and the pattern of 2-APB-induced ectopic activity was continuous, distinct from the discontinuous activity induced by PE. CONCLUSION: 2-APB-induced atria ectopic activity was inhibited by classic anti-arrhythmic drugs quinidine, lidocaine, verapamil, amiodarone, and Na+/Ca2+ exchanger blockers. It can be used for testing agents able to affect any of Na+, Ca2+ channel, Na+/Ca2+ exchanger without selectivity.

Erratum: An Intelligent AIEgen with Nonmonotonic Multiresponses to Multistimuli.

[This corrects the article DOI: 10.1002/advs.202001845.].

An Intelligent AIEgen with Nonmonotonic Multiresponses to Multistimuli.

Intelligent stimulus-response (S/R) systems are the basis of natural process and machine control, which are intensively explored in biomimetic design and analytical/biological applications. However, nonmonotonic multi-S/R systems are still rarely studied so far. In this work, a rational design strategy is proposed to achieve such a unique S/R system by integrating opposite luminescence behaviors in one molecule. When solvent polarity increases, many heterocyclic or carbonyl-containing compounds often become more emissive due to the suppression of the proximity effect, whereas molecules with donor-acceptor (D-A) structures tend to be less emissive because of the twisted intramolecular charge transfer. Meanwhile, protonation on D/A moieties will weaken/strengthen the D-A interaction to result in blue/redshifted emissions. By combining a protonatable heterocyclic acceptor and a protonatable donor together in one molecule, nonmonotonic brightness responses to polarity stimuli and nonmonotonic color responses to pH stimuli can be achieved. The design strategy is successfully verified by a simple molecule named 4-(dimethylamino)styryl)quinoxalin-2(1H)-one (ASQ). ASQ exhibits nonmonotonic responses to polarity and pH stimuli, and aggregation-induced emission (AIE) with a nonmonotonic AIE curve. Meanwhile, ASQ can be adjusted to emit white light in an acidic environment, and it shows multivalent functionalities including albumin protein sensing, ratiometric pH sensing, and amine gas sensing.

Engineering Microenvironment for Endogenous Neural Regeneration after Spinal Cord Injury by Reassembling Extracellular Matrix.

The formation of a fluid-filled cystic cavity after spinal cord injury (SCI) is a major obstacle for neural regeneration. In this study, the post-SCI cavity was bridged by a functional self-assembling peptide (F-SAP) nanofiber hydrogel coupled with growth factor "cocktail". A sustained release of growth factors was achieved by carefully tailoring the physical hindrances and charge-induced interactions between the growth factors and the peptide nanofibers. Such an engineering microenvironment elicited axon regeneration, as determined by tracing of the descending pathway in the dorsal columns and immunochemical detection of regenerating axons beyond the lesion. Furthermore, the dynamic spatiotemporal activation line of endogenous NSCs (eNSCs) after severe SCI was thoroughly investigated. The results indicated that the growth factor-coupled F-SAP greatly facilitated eNSC proliferation, neuronal differentiation, maturation, myelination, and more importantly, the formation of interconnection with severed descending corticospinal tracts. The robust endogenous neurogenesis essentially led to the recovery of locomotion and electrophysiological properties. In conclusion, the growth factor-coupled F-SAP nanofiber hydrogel elucidated the therapeutic effect of eliciting endogenous neurogenesis by locally reassembling an extracellular matrix.

Aggregate Science: From Structures to Properties.

Molecular science entails the study of structures and properties of materials at the level of single molecules or small interacting complexes of molecules. Moving beyond single molecules and well-defined complexes, aggregates (i.e., irregular clusters of many molecules) serve as a particularly useful form of materials that often display modified or wholly new properties compared to their molecular components. Some unique structures and phenomena such as polymorphic aggregates, aggregation-induced symmetry breaking, and cluster excitons are only identified in aggregates, as a few examples of their exotic features. Here, by virtue of the flourishing research on aggregation-induced emission, the concept of "aggregate science" is put forward to fill the gaps between molecules and aggregates. Structures and properties on the aggregate scale are also systematically summarized. The structure-property relationships established for aggregates are expected to contribute to new materials and technological development. Ultimately, aggregate science may become an interdisciplinary research field and serves as a general platform for academic research.

Advances in injectable self-healing biomedical hydrogels.

In recent years, implantable biomaterials have attracted significant interest owing to their potentials for use in the therapy of physical defects and traumas. Among the implantable biomaterials, hydrogels have received increasing attention for their tunable structures and good rheological behavior. However, the mechanical failures of traditional gel materials during normal operation remain a serious issue. To overcome this problem, hydrogel materials with self-healing and injectable abilities have been developed, with their potential for autonomous self-recovery and minimally invasive implantation. In this paper, the progress of injectable self-healing hydrogels is presented by combining developments in the fundamental knowledge of polymer designs and discussions on the practical biomedical applications of the materials. The mechanisms of different types of self-healing hydrogels are introduced first and their performances are then discussed, followed by a review of the self-healing hydrogels with injectability. The applications of the injectable self-healing hydrogels are discussed in the final section. STATEMENT OF SIGNIFICANCE: This paper provides an overview of the progress of a smart material, injectable self-healing hydrogel, during the past ten years and mainly focuses on its recent development. This paper presents developments in the fundamental knowledge in polymer designs and discussions on the practical biomedical application of the materials, which sheds more light on the advancement of injectable self-healing hydrogels. This paper should be of interest to the readers who are curious about the advances of injectable self-healing hydrogels.

Bionanotube/Poly(3,4-ethylenedioxythiophene) Nanohybrid as an Electrode for the Neural Interface and Dopamine Sensor.

Poly(3,4-ethylene dioxythiophene) (PEDOT) is a promising conductive material widely used for interfacing with tissues in biomedical fields because of its unique properties. However, obtaining high charge injection capability and high stability remains challenging. In this study, pristine carbon nanotubes (CNTs) modified by dopamine (DA) self-polymerization on the surface polydopamine (PDA@CNTs) were utilized as dopants of PEDOT to prepare hybrid films through electrochemical deposition on the indium tin oxide (ITO) electrode. The PDA@CNTs-PEDOT film of the nanotube network topography exhibited excellent stability and strong adhesion to the ITO substrate compared with PEDOT and PEDOT/ p-toulene sulfonate. The PDA@CNTs-PEDOT-coated ITO electrodes demonstrated lower impedance and enhanced charge storage capacity than the bare ITO. When applying exogenous electrical stimulation (ES), robust long neurites sprouted from the dorsal root ganglion (DRG) neurons cultured on the PDA@CNTs-PEDOT film. Moreover, ES promoted Schwann cell migration out from the DRG spheres and enhanced myelination. The PDA@CNTs-PEDOT film served as an excellent electrochemical sensor for the detection of DA in the presence of biomolecule interferences. Results would shed light into the advancement of conducting nanohybrids for applications in the multifunctional bioelectrode in neuroscience.