Direct oral anticoagulants for oral anticoagulants-naïve Asian patients with atrial fibrillation and end-stage renal disease undergoing dialysis.

In Asian patients with atrial fibrillation (AF) and end-stage renal disease (ESRD) undergoing dialysis, the use of direct oral anticoagulants (DOACs) remains debatable. From the national health insurance claims data in South Korea, we included 425 new users of OAC among patients with non-valvular AF and ESRD undergoing dialysis between 2013 and 2020. Patients were categorized into DOAC (n = 106) and warfarin group (n = 319). Clinical outcomes, including ischemic stroke, myocardial infarction (MI), intracranial hemorrhage (ICH), and gastrointestinal (GI) bleeding, were compared between the two groups using inverse probability of treatment weighting (IPTW) analysis. During the median follow-up of 3.2 years, the incidence of ischemic stroke was significantly reduced in the DOAC compared to the warfarin group [Hazard ratio (HR) 0.07; P = 0.001]. However, the incidence of MI (HR 1.32; P = 0.41) and GI bleeding (HR 1.78; P = 0.06) were not significantly different between the two groups. No ICH events occurred in the DOAC group, although the incidence rate did not differ significantly between the two groups (P = 0.17). In Asian patients with AF and ESRD undergoing dialysis, DOACs may be associated with a reduced risk of ischemic stroke compared with warfarin. The MI, ICH, and GI bleeding rates may be comparable between DOACs and warfarin.

Long-Term Enhancement of Botulinum Toxin Injections for Post-Stroke Spasticity by Use of Stretching Exercises-A Randomized Controlled Trial.

Botulinum toxin A (BONT/A) injections play a central role in the treatment of upper limb spasticity in stroke patients. We proposed structured stretching exercises to enhance the effect of post-stroke spasticity relief of the upper limbs following BONT/A injections. A total of 43 patients who had a stroke with grade 2 spasticity or higher on the Modified Ashworth Scale (MAS) in their upper-limb muscles were randomly assigned to the intervention (n = 21) or control group (n = 22). The former received structured stretching exercises after their BONT/A injections for 20 min, 5 days per week, for 6 months at a hospital, while the others conducted self-stretching exercises at home. The outcome measures were assessed before the intervention (T0) and after three (T1) and six months (T2). Significantly greater improvements in the MAS scores of the elbows, wrists, and fingers were found in the intervention group's patients at T1 and T2. The behavioral outcome measures, including shoulder pain, activities of daily living, and quality of life, and our electrophysiological studies also showed a significantly higher enhancement in this patient group. In conclusion, the structured stretching exercises plus BONT/A injections for six months showed a superior effect in relieving post-stroke upper-limb spasticity compared to self-stretching exercises.

Scalable electron tomography for connectomics.

We demonstrate limited-tilt, serial section electron tomography (ET), which can non-destructively map brain circuits over large 3D volumes and reveal high-resolution, supramolecular details within subvolumes of interest. We show accelerated ET imaging of thick sections (>500 nm) with the capacity to resolve key features of neuronal circuits including chemical synapses, endocytic structures, and gap junctions. Furthermore, we systematically assessed how imaging parameters affect image quality and speed to enable connectomic-scale projects.

The Development of an Artificial Intelligence Video Analysis-Based Web Application to Diagnose Oropharyngeal Dysphagia: A Pilot Study.

The gold standard test for diagnosing dysphagia is the videofluoroscopic swallowing study (VFSS). However, the accuracy of this test varies depending on the specialist's skill level. We proposed a VFSS-based artificial intelligence (AI) web application to diagnose dysphagia. Video from the VFSS consists of multiframe data that contain approximately 300 images. To label the data, the server separated them into frames during the upload and stored them as a video for analysis. Then, the separated data were loaded into a labeling tool to perform the labeling. The labeled file was downloaded, and an AI model was developed by training with You Only Look Once (YOLOv7). Using a utility called SplitFolders, the entire dataset was divided according to a ratio of training (70%), test (10%), and validation (20%). When a VFSS video file was uploaded to an application equipped with the developed AI model, it was automatically classified and labeled as oral, pharyngeal, or esophageal. The dysphagia of a person was categorized as either penetration or aspiration, and the final analyzed result was displayed to the viewer. The following labeling datasets were created for the AI learning: oral (n = 2355), pharyngeal (n = 2338), esophageal (n = 1480), penetration (n = 1856), and aspiration (n = 1320); the learning results of the YOLO model, which analyzed dysphagia using the dataset, were predicted with accuracies of 0.90, 0.82, 0.79, 0.92, and 0.96, respectively. This is expected to help clinicians more efficiently suggest the proper dietary options for patients with oropharyngeal dysphagia.

Therapeutic Efficacy of Ultrasound-Guided Selective Nerve Block on Chronic Cervical Radiculopathy.

Background and Objectives: Cervical radiculopathy (CR) manifests as pain and sensorimotor disturbances in the upper extremities, often resulting from nerve root compression due to intervertebral disc herniation, degenerative changes, or trauma. While conservative treatments are initially preferred, persistent or severe cases may require surgical intervention. Ultrasound-guided selective nerve root block (SNRB) has emerged as a promising intervention for alleviating symptoms and potentially obviating the need for surgery. This study evaluates the therapeutic efficacy of ultrasound-guided SNRB in managing chronic CR, aiming to determine its potential in symptom relief and delaying or avoiding surgical procedures. Materials and Methods: A retrospective analysis was conducted on 720 outpatients treated for CR between October 2019 and March 2022. After excluding patients with traumatic CR, previous surgeries, malignancies, progressive neurological symptoms requiring immediate surgery, or inadequate conservative treatment, 92 patients who had experienced cervical radicular pain for more than three months and had failed to improve after more than six weeks of conservative treatment with VAS scores ≥ 5 were included. The patients underwent single or multiple ultrasound-guided SNRB procedures, involving the injection of dexamethasone and lidocaine under real-time ultrasound guidance. Symptom severity was assessed at the baseline, and at 4, 8, and 12 weeks post-procedure using the Visual Analog Scale (VAS). The data collected included age, sex, presence of neck and/or radicular pain, physical examination findings, recurrence of symptoms, improvement in symptoms, and whether surgical intervention was ultimately required. Statistical analyses were performed to identify the factors associated with symptom improvement or recurrence. Results: Significant symptom improvement was observed in 69 (75.0%) participants post-SNRB, with 55 (79.7%) showing improvement at 4 weeks, 11 (15.9%) at 8 weeks, and 3 (4.4%) at 12 weeks. Symptom recurrence, defined by an increase in VAS score accompanied by a pain flare lasting at least 24 h after a pain-free interval of at least one month, was noted in 48 (52.2%) patients. The presence of combined neck and radicular pain was a significant predictor of recurrence (p = 0.008). No significant associations were found between symptom relief and factors such as age, gender, initial pain severity, or MRI findings. Conclusions: Ultrasound-guided SNRB effectively manages chronic CR, providing substantial symptom relief and potentially reducing the need for surgical intervention. This technique offers a promising conservative treatment option, especially given its real-time visualization advantages and minimal radiation exposure.

Unilateral retrobulbar haemorrhage in a cat secondary to suspected anticoagulant rodenticide intoxication.

A 6-month-old intact female mixed-breed kitten presented with severe exophthalmos of the left eye. Periocular lesions, including subconjunctival haemorrhage, third eyelid protrusion, and left eyelid oedema, were detected in the absence of globe retropulsion. The left intraocular pressure was increased, and ocular ultrasonography revealed ipsilateral retrobulbar fluid. Coagulation panels were markedly prolonged and severe anaemia was detected. Ultrasound-guided retrobulbar centesis performed to decrease intraocular pressure yielded blood. Based on the history and clinical findings, anticoagulant rodenticide intoxication was suspected. Treatment included partial tarsorrhaphy and the administration of topical antibiotics, artificial tears, and vitamin K1. Fresh whole blood and fresh frozen plasma were transfused for supportive therapy. Coagulation parameters improved after 7 days of hospitalisation. The periocular lesions resolved within 14 days, despite persistent optic nerve damage and blindness. This case report raises the possibility that anticoagulant rodenticide toxicity may result in retrobulbar haemorrhage in the absence of other typical cavitary bleeding. Although uncommon, anticoagulant rodenticide toxicity should be considered in cats with retrobulbar haemorrhage.

Laminin as a Key Extracellular Matrix for Proliferation, Differentiation, and Maturation of Porcine Muscle Stem Cell Cultivation.

Extracellular matrix (ECM) proteins play a crucial role in culturing muscle stem cells (MuSCs). However, there is a lack of extensive research on how each of these proteins influences proliferation and differentiation of MuSCs from livestock animals. Therefore, we investigated the effects of various ECM coatings-collagen, fibronectin, gelatin, and laminin-on the proliferation, differentiation, and maturation of porcine MuSCs. Porcine MuSCs, isolated from 14-day-old Berkshire piglets, were cultured on ECM-coated plates, undergoing three days of proliferation followed by three days of differentiation. MuSCs on laminin showed higher proliferation rate than others (p<0.05). There was no significant difference in the mRNA expression levels of PAX7, MYF5, and MYOD among MuSCs on laminin, collagen, and fibronectin (p>0.05). During the differentiation period, MuSCs cultured on laminin exhibited a significantly higher differentiation rate, resulting in thicker myotubes compared to those on other ECMs (p<0.05). Also, MuSCs on laminin showed higher expression of mRNA related with maturated muscle fiber such as MYH1 and MYH4 corresponding to muscle fiber type IIx and muscle fiber type IIb, respectively, compared with MuSCs on other ECM coatings (p<0.05). In summary, our comparison of ECMs revealed that laminin significantly enhances MuSC proliferation and differentiation, outperforming other ECMs. Specifically, muscle fibers cultured on laminin exhibited a more mature phenotype. These findings underscore laminin's potential to advance in vitro muscle research and cultured meat production, highlighting its role in supporting rapid cell proliferation, higher differentiation rates, and the development of mature muscle fibers.

Restoration Temperature Control through Glass Transition Temperature Modulation of Shape Memory Polymer for Thermally Switchable Adhesive.

Shape memory polymers (SMPs) undergo changes between arbitrary shapes and programmed shapes upon exposure to specific stimulus, allowing them to restore their original shape. All kinds of external stimuli have a threshold to change the shape of the SMP. Especially, for the thermal type SMP, the critical temperature for shape restoration is typically near the glass transition temperature (Tg). In this study, the controllability of the restoration temperature is analyzed by adjusting the Tg of the polymer using Norland Optical Adhesive 63, which can be cured with UV irradiation. By varying the ambient temperature from 20 to 120 °C during UV exposure, Tg changes ranging from 35.84 to 50.50 °C are obtained, with corresponding changes in restoration temperature. As a practical application, a thermal-activated SMP dry adhesive is developed with programmable Tg and switchable adhesion. The fabricated SMP dry adhesive exhibited strong adhesion to substrates with various surface roughness. Additionally, the shape memory effect allowed for easy detachment through shape recovery, and different adhesive performances at different temperatures are achieved by programming various Tg values. Moreover, the simple manufacturing process of the SMP dry adhesive is confirmed to be suitable for continuous fabrication processes based on roll-to-roll methods.

Toe Grip Strength Is Associated with Improving Gait Function in Patients with Subacute Stroke.

Toe grip strength has recently been suggested to play an essential role in maintaining balance and postural stability for ambulatory function in older populations. This study aimed to investigate its association with improving gait function three months after onset in patients with subacute stroke. This longitudinal cohort study included 98 first-ever stroke patients (67 ± 9 years, 56% female) within one month from the onset who could not ambulate independently. Functional outcome indicators, including toe grip strength, hand grip strength, knee extensor strength, Fugl-Meyer Assessment of Lower Extremity (FMA_LE), and the Postural Assessment Scale for Stroke (PASS), were assessed before and three months after the intervention. We analyzed the correlation between participants' gait function using a 10-meter walk test time and various functional indicators. Then, multiple linear regression analysis was used to investigate whether toe grip strength was related to the improvement of gait function. Correlation analysis revealed a significant positive correlation between the 10MWT time and toe grip strength ratio (affected/unaffected side), with a moderate effect size (r = -0.61, p <0.001). Multiple regression analysis with covariates showed a significant relationship between 10MWT time and toe grip strength ratio (ß = -0.113, p < 0.001), FMA_LE (ß = -1.315, p = 0.004), PASS (ß = -3.275, p <0.001), and age (ß = -0.159, p = 0.004). In conclusion, toe grip strength was an essential factor associated with ambulatory function improvement in subacute stroke patients three months after onset. Additional toe grip muscle strengthening rehabilitation treatment can be expected to help improve the ambulatory function of subacute stroke patients in the future.

A 42-year-old patient with renal cell carcinoma presenting as low back pain: A case report.

RATIONALE: Renal cell carcinoma (RCC) is the most common renal neoplasm, accounting for 2.4% of all cancers in Korea. Although the usual clinical manifestations of RCC include flank pain, hematuria, and palpable mass, RCC is generally characterized by a lack of early warning signs and is mostly discovered incidentally in advanced stage. This case report describes a 42-year-old Korean man diagnosed with giant RCC who presented with simple back pain. PATIENT CONCERNS: The clinical manifestation of a 42-year-old Korean man was chronic back pain. DIAGNOSES: Contrast-enhanced computed tomography showed a 19.1-cm sized heterogeneous enhancing mass on the right kidney and tumor thrombosis extending into inferior vena cava. INTERVENTION: Due to the large size of the tumor and extensive tumor thrombosis, the multidisciplinary team decided to administer neoadjuvant chemotherapy and an anticoagulant. Following 12 cycles of treatment with nivolumab and cabozantinib, he underwent a right radical nephrectomy with an adrenalectomy and tumor thrombectomy. OUTCOMES: Treatment was successful and posttreatment he started a cancer rehabilitation program. He was followed-up as an outpatient and no longer complains of back pain. LESSONS: RCC can manifest clinically as back pain, with diagnosis being difficult without appropriate imaging modalities. RCC should be included in the differential diagnosis of patients with low back pain, even at a young age.

Artificial intelligence predicts undiagnosed atrial fibrillation in patients with embolic stroke of undetermined source using sinus rhythm electrocardiograms.

BACKGROUND: Artificial intelligence (AI)-enabled sinus rhythm (SR) electrocardiogram (ECG) interpretation can aid in identifying undiagnosed paroxysmal atrial fibrillation (AF) in patients with embolic stroke of undetermined source (ESUS). OBJECTIVE: The purpose of this study was to assess the efficacy of an AI model in identifying AF based on SR ECGs in patients with ESUS. METHODS: A transformer-based vision AI model was developed using 737,815 SR ECGs from patients with and without AF to detect current paroxysmal AF or predict the future development of AF within a 2-year period. Probability of AF was calculated from baseline SR ECGs using this algorithm. Its diagnostic performance was further tested in a cohort of 352 ESUS patients from 4 tertiary hospitals, all of whom were monitored using an insertable cardiac monitor (ICM) for AF surveillance. RESULTS: Over 25.1-month follow-up, AF episodes lasting ≥1 hour were identified in 58 patients (14.4%) using ICMs. In the receiver operating curve (ROC) analysis, the area under the curve for the AI algorithm to identify AF ≥1 hour was 0.806, which improved to 0.880 after integrating the clinical parameters into the model. The AI algorithm exhibited greater accuracy in identifying longer AF episodes (ROC for AF ≥12 hours: 0.837, for AF ≥24 hours: 0.879) and a temporal trend indicating that the AI-based AF risk score increased as the ECG recording approached the AF onset (P for trend <.0001). CONCLUSIONS: Our AI model demonstrated excellent diagnostic performance in predicting AF in patients with ESUS, potentially enhancing patient prognosis through timely intervention and secondary prevention of ischemic stroke in ESUS cohorts.

Risk of Subsequent Primary Cancers in Thyroid Cancer Survivors according to the Dose of Levothyroxine: A Nationwide Cohort Study.

BACKGRUOUND: Current research has not investigated the effect of thyroid-stimulating hormone suppression therapy with levothyroxine on the risk for developing subsequent primary cancers (SPCs). This study aimed to investigate the association between levothyroxine dosage and the risk for SPCs in thyroid cancer patients. METHODS: We conducted a nationwide population-based retrospective cohort study form Korean National Health Insurance database. This cohort included 342,920 thyroid cancer patients between 2004 and 2018. Patients were divided into the non-levothyroxine and the levothyroxine groups, the latter consisting of four dosage subgroups according to quartiles. Cox proportional hazard models were performed to evaluate the risk for SPCs by adjusting for variables including cumulative doses of radioactive iodine (RAI) therapy. RESULTS: A total of 17,410 SPC cases were observed over a median 7.3 years of follow-up. The high-dose levothyroxine subgroups (Q3 and Q4) had a higher risk for SPC (adjusted hazard ratio [HR], 1.14 and 1.27; 95% confidence interval [CI], 1.05-1.24 and 1.17- 1.37; respectively) compared to the non-levothyroxine group. In particular, the adjusted HR of stomach (1.31), colorectal (1.60), liver and biliary tract (1.95), and pancreatic (2.48) cancers were increased in the Q4 subgroup. We consistently observed a positive association between high levothyroxine dosage per body weight and risk of SPCs, even after adjusting for various confounding variables. Moreover, similar results were identified in the stratified analyses according to thyroidectomy type and RAI therapy, as well as in a subgroup analysis of patients with good adherence. CONCLUSION: High-dose levothyroxine use was associated with increased risk of SPCs among thyroid cancer patients regardless of RAI therapy.

Metabolomic changes in culture media with varying passage numbers of pig muscle stem cell culture for cultured meat production.

Selecting the primary cells in an optimal state for cultured meat production is a crucial challenge in commercializing cultured meat. We investigated the metabolomic changes in culture media according to passage numbers for indirectly assessing the state of primary cells. Pig skeletal muscle stem cells (PSCs) harvested from the biceps femoris muscles of 7-d-old crossbred pigs (Landrace × Yorkshire × Duroc, LYD) were used for cell characterization. Fresh media (FM) and spent media (SM) of PSCs during passages 1 to 3 in vitro culture were prepared for metabolomics analysis. SM was collected on the third day of proliferation for each passage of PSCs. Cell characterization analysis revealed that the proliferation rate was highest at passage 2; however, a significant loss of expression of myogenic marker genes was observed at passage 3. Based on metabolomic profiles of culture media, FM and SM groups (SM1, SM2, and SM3) were clearly separated by partial least squares-discriminant analysis. A total of seven differentially abundant metabolites (DAMs) were identified from FM and SM for each passage, based on the following criteria: P < 0.05, fold change > 1.5 or < 0.66, and a variable importance in projection score > 1.5. All seven DAMs and their interconnected metabolites might be primarily used as substrates for energy production and most of them were relatively abundant in SM3. Among the seven DAMs, the three potential biomarkers (γ-glutamyl-L-leucine, cytosine, and ketoleucine), which showed significant changes exclusively in SM3, each had an area under the curve value of 1. Therefore, monitoring the levels of these key metabolites in culture media could serve as a quality control measure for cultured meat production by enabling the indirect detection of suboptimal PSCs based on their proliferation ability.

Unravelling the main mechanism responsible for nocturnal CO2 uptake by dryland soils.

Soil respiration, or CO2 efflux from soil, is a crucial component of the terrestrial carbon cycle in climate models. Contrastingly, many dryland soils absorb atmospheric CO2 at night, but the exact mechanisms driving this uptake are actively debated. Here we used a mechanistic model with heuristic approaches to unravel the underlying processes of the observed patterns of soil-atmosphere CO2 fluxes. We show that the temperature drop during nighttime is the main driver of CO2 uptake by increasing CO2 solubility and local water pH of a thin water film on soil particle surfaces, providing favourable conditions for carbonate precipitation. Our data demonstrate that the nocturnal inorganic carbon absorption is a common soil process, but often offset by biological CO2 production. The uptake rates can be impacted by different successional stages of biocrusts that consume or produce CO2 and modify the pH of the soil water film, which can be maintained by non-rainfall water inputs, such as pore space condensation. Annual estimates of nocturnal carbon uptake, based on in situ continuous measurements at the soil level in drylands are still very scarce, but fluxes of up to several tens of g C m-2 y-1 have been reported, potentially accounting for a considerable fraction of the global residual terrestrial carbon sink.

2D MOFs and Zeolites for Composite Membrane and Gas Separation Applications: A Brief Review.

Commercial membranes have predominantly been fabricated from polymers due to their economic viability and processability. This choice offers significant advantages in energy efficiency, cost-effectiveness, and operational simplicity compared to conventional separation techniques like distillation. However, polymeric membranes inherently exhibit a trade-off between their permeability and selectivity, which is summarized in the Robeson upper bound. To potentially surpass these limitations, mixed-matrix membranes (MMMs) can be an alternative solution, which can be constructed by combining polymers with inorganic additives such as metal-organic frameworks (MOFs) and zeolites. Incorporating high-aspect-ratio fillers like MOF nanosheets and zeolite nanosheets is of significant importance. This incorporation not only enhances the efficiency of separation processes but also reinforces the mechanical robustness of the membranes. We outline synthesis techniques for producing two-dimensional (2D) crystals (including nanocrystals with high aspect ratio) and provide examples of their integration into membranes to customize separation performances. Moreover, we propose a potential trajectory for research in the area of high-aspect-ratio materials-based MMMs, supported by a mathematical-model-based performance prediction.

A framework for inferring and analyzing pharmacotherapy treatment patterns.

BACKGROUND: To discover pharmacotherapy prescription patterns and their statistical associations with outcomes through a clinical pathway inference framework applied to real-world data. METHODS: We apply machine learning steps in our framework using a 2006 to 2020 cohort of veterans with major depressive disorder (MDD). Outpatient antidepressant pharmacy fills, dispensed inpatient antidepressant medications, emergency department visits, self-harm, and all-cause mortality data were extracted from the Department of Veterans Affairs Corporate Data Warehouse. RESULTS: Our MDD cohort consisted of 252,179 individuals. During the study period there were 98,417 emergency department visits, 1,016 cases of self-harm, and 1,507 deaths from all causes. The top ten prescription patterns accounted for 69.3% of the data for individuals starting antidepressants at the fluoxetine equivalent of 20-39 mg. Additionally, we found associations between outcomes and dosage change. CONCLUSIONS: For 252,179 Veterans who served in Iraq and Afghanistan with subsequent MDD noted in their electronic medical records, we documented and described the major pharmacotherapy prescription patterns implemented by Veterans Health Administration providers. Ten patterns accounted for almost 70% of the data. Associations between antidepressant usage and outcomes in observational data may be confounded. The low numbers of adverse events, especially those associated with all-cause mortality, make our calculations imprecise. Furthermore, our outcomes are also indications for both disease and treatment. Despite these limitations, we demonstrate the usefulness of our framework in providing operational insight into clinical practice, and our results underscore the need for increased monitoring during critical points of treatment.

Synaptic wiring motifs in posterior parietal cortex support decision-making.

The posterior parietal cortex exhibits choice-selective activity during perceptual decision-making tasks1-10. However, it is not known how this selective activity arises from the underlying synaptic connectivity. Here we combined virtual-reality behaviour, two-photon calcium imaging, high-throughput electron microscopy and circuit modelling to analyse how synaptic connectivity between neurons in the posterior parietal cortex relates to their selective activity. We found that excitatory pyramidal neurons preferentially target inhibitory interneurons with the same selectivity. In turn, inhibitory interneurons preferentially target pyramidal neurons with opposite selectivity, forming an opponent inhibition motif. This motif was present even between neurons with activity peaks in different task epochs. We developed neural-circuit models of the computations performed by these motifs, and found that opponent inhibition between neural populations with opposite selectivity amplifies selective inputs, thereby improving the encoding of trial-type information. The models also predict that opponent inhibition between neurons with activity peaks in different task epochs contributes to creating choice-specific sequential activity. These results provide evidence for how synaptic connectivity in cortical circuits supports a learned decision-making task.

Highly Stretchable Thermoplastic Polyurethane Separators for Li-Ion Batteries Based on Non-Solvent-Induced Phase Separation Method.

The growing interest in wearable and portable devices has stimulated the need for flexible and stretchable lithium-ion batteries (LiBs). A crucial component in these batteries is the separator, which provides a pathway for Li-ion transfer and prevents electrode contact. In a flexible and stretchable LiB, the separator must exhibit stretchability and elasticity akin to its existing counterparts. Here, we developed a non-modified thermoplastic polyurethane (TPU) separator using the non-solvent induced phase separation (NIPS) technique. We compared their performance with commercially available polypropylene (PP) separators. Our results demonstrate that TPU separators exhibit superior elasticity based on repeated stretch/release tests with excellent thermal stability and electrolyte wettability. Furthermore, our findings confirm that TPU separators, even after being repeatedly stretched and released, can function effectively without severe damage in a fabricated coin cell LiB with high oxidative stability, as evidenced by linear sweep voltammetry, like commercially available separators.

Isomerism of Cyclodextrin Tetramer Induced by Alkali Halide Cluster Ions Observed by Ion Mobility Spectrometry-Mass Spectrometry.

Cyclodextrins (CDs) exhibit versatile self-assembly properties due to their hydrophilic and hydrophobic components, with applications such as drug delivery and selective binding. While research on CD self-assembly is extensive, limited studies have explored their aggregation behavior, particularly in interactions with small ionic guests. The present work investigates the structure of ß-CD tetramers aggregated with alkali metal chloride clusters using ion mobility spectrometry-mass spectrometry (IMS-MS). The results revealed that diverse structures emerge in the tetramer depending on the alkali metal cluster size. Notably, the doubly charged tetramer exhibits distinct aggregation trends with specific numbers of MCl clusters for Na+ and K+ ions. After initially adopting a bucket-wheel structure with two internal cations, the structure transforms into a new isomer with a tetrahedral configuration upon cluster addition. The formation of the new isomer structure is closely linked to filling the cavity volume with MCl clusters and ionic interactions, which possibly compensate for the weakened hydrogen bonds between CDs. Theoretical calculations further support the structures, showing well-matched collision cross-section (CCS) values compared with the experimental CCS values. This study highlights the role of alkali metal chloride clusters as potential templates, leading to the formation of novel CD assemblies.