Predicting short-term outcomes in atrial-fibrillation-related stroke using machine learning.

Background: Prognostic prediction and the identification of prognostic factors are critical during the early period of atrial-fibrillation (AF)-related strokes as AF is associated with poor outcomes in stroke patients. Methods: Two independent datasets, namely, the Korean Atrial Fibrillation Evaluation Registry in Ischemic Stroke Patients (K-ATTENTION) and the Korea University Stroke Registry (KUSR), were used for internal and external validation, respectively. These datasets include common variables such as demographic, laboratory, and imaging findings during early hospitalization. Outcomes were unfavorable functional status with modified Rankin scores of 3 or higher and mortality at 3 months. We developed two machine learning models, namely, a tree-based model and a multi-layer perceptron (MLP), along with a baseline logistic regression model. The area under the receiver operating characteristic curve (AUROC) was used as the outcome metric. The Shapley additive explanation (SHAP) method was used to evaluate the contributions of variables. Results: Machine learning models outperformed logistic regression in predicting both outcomes. For 3-month unfavorable outcomes, MLP exhibited significantly higher AUROC values of 0.890 and 0.859 in internal and external validation sets, respectively, than those of logistic regression. For 3-month mortality, both machine learning models exhibited significantly higher AUROC values than the logistic regression for internal validation but not for external validation. The most significant predictor for both outcomes was the initial National Institute of Health and Stroke Scale. Conclusion: The explainable machine learning model can reliably predict short-term outcomes and identify high-risk patients with AF-related strokes.

Incidence and Distribution of the Pathogens Causing GI Infections at a University Hospital of Korea.

BACKGROUND: Gastrointestinal (GI) infections, caused by various pathogens such as bacteria, viruses, protozoa, and parasites, are the second most common infectious diseases. Molecular diagnostics that can simultaneously detect these pathogens are commonly used in syndromic approaches. The authors aimed to identify the causative pathogens of GI infections to provide clinically useful information. METHODS: This retrospective study used molecular diagnostic methods to determine the incidence and distribution of GI pathogens according to gender, age, and season and analyze their coinfection from August 2020 to December 2022. RESULTS: The overall incidence of at least one GI pathogen was 40.1% (991/2, 471). The positivity rates for bacteria and viruses were 33.1% (817/2, 471) and 9.2% (227/2,471), respectively; the positivity rate for bacteria was significantly higher than that for viruses (p < 0.001). The incidence of GI pathogens according to age group was highest in group 3 (59.9%), followed by group 4 (57.0%). The most common bacterial pathogen associated with GI infections was C. difficile, followed by diarrheagenic E. coli, Campylobacter spp., and Salmonella spp. Enteropathogenic E. coli accounted for a large percentage of diarrheagenic E. coli (63.6%, 157/247). Among the viral pathogens, norovirus GI/GII was the most commonly detected virus, followed by adenovirus F40/41 and rotavirus A. For bacterial- or viral-positive cases, the distribution of GI pathogens according to age group showed the highest proportion of C. difficile in all groups, except for group 2. In group 2, rotavirus A accounted for the highest percentage (61.1%, 22/36). The incidence of GI pathogens was the highest in summer (36.1%), followed by autumn (32.7%), and winter (18.0%). The co-infection rate with two or more pathogens was 16.9% (167/991). The rates of co-infection with two or more bacteria, bacteria and viruses, and two viruses were 58.1%, 31.7%, and 10.2%, re-spectively. CONCLUSIONS: Information on the incidence and distribution of GI pathogens might be clinically useful; however, unlike the distribution of other infectious pathogens, it is necessary to consider that microorganisms identified through molecular diagnostics can be detected even in healthy people without clinical symptoms.

Antiplatelet regimens after ischemic stroke or transient ischemic attack: a systematic review and updated network meta-analysis.

Background: It is still uncertain which antiplatelet regimen had the greatest net clinical benefit in patients who have suffered a transient ischemic attack or non-cardioembolic ischemic stroke, and it is necessary to choose the optimal regimen according to the clinical situation. Methods: We utilized 3 databases of Medline, Embase, and the Cochrane Central Register of Controlled Trials to find randomized controlled trials that met our criteria, and performed network meta-analyses in recurrent stroke, composite outcomes, major bleeding events, recurrent ischemic stroke, and all bleeding events. Three-dimensional clustered rank plots were used to obtain the net clinical benefit. Subgroup analyses were performed according to the symptom-onset-to-treatment time (<72 and >72 h), stroke subtypes (large artery atherosclerosis and small vessel occlusion), and dual antiplatelet agent treatment duration. Results: A total of 69 trials were enrolled. Cilostazol was associated with a lower risk of recurrent stroke, major bleeding events, composite outcomes, recurrent ischemic stroke, and all bleeding events compared to low to medium dose aspirin. The three-dimensional rank plot showed that cilostazol had the highest net clinical benefit. The combination of aspirin plus clopidogrel had greater efficacy in the <72 h after stroke onset and large artery atherosclerosis subgroups, and when it was restricted to1 month of use major bleeding risk was not higher than aspirin. The combination of aspirin plus dipyridamole had greater efficacy and safety comparable to aspirin in terms of small vessel occlusion. Conclusions: The efficacy and safety profiles among antiplatelet regimens may differ according to clinical situation, although cilostazol, aspirin plus clopidogrel, and aspirin plus dipyridamole may be considered as preferable options.

Strong Bathochromic Shift of Conjugated Polymer Nanowires Assembled with a Liquid Crystalline Alkyl Benzoic Acid via a Film Dispersion Process.

We present aqueous dispersions of conjugated polymer nanowires (CPNWs) with improved light absorption properties aimed at aqueous-based applications. We assembled films of a donor-acceptor-type conjugated polymer and liquid crystalline 4-n-octylbenzoic acid by removing a cosolvent of their mixture solutions, followed by annealing of the films, and then formed aqueous-dispersed CPNWs with an aspect ratio >1000 by dispersing the films under ultrasonication at a basic pH. X-ray and spectroscopy studies showed that the polymer and liquid crystal molecules form independent domains in film assemblies and highly organized layer structures in CPNWs. Our ordered molecular assemblies in films and aqueous dispersions of CPNWs open up a new route to fabricate nanowires of low-band-gap linear conjugated polymers with the absorption maximum at 794 nm remarkably red-shifted from 666 nm of CPNWs prepared by an emulsion process. Our results suggest the presence of semicrystalline polymorphs ß1 and ß2 phases in CPNWs due to long-range π-π stacking of conjugated backbones in compactly organized lamellar structures. The resulting delocalization with a reduced energy bang gap should be beneficial for enhancing charge transfer and energy-conversion efficiencies in aqueous-based applications such as photocatalysis.

Antiplatelet regimens for Asian patients with ischemic stroke or transient ischemic attack: a systematic review and network meta-analysis.

BACKGROUND: The optimal antiplatelet treatment for the secondary prevention of non-cardioembolic stroke or transient ischemic attack (TIA) remains uncertain in Asians. METHODS: We searched for eligible randomized control trials in Medline, Embase, and the Cochrane Library. A Bayesian network meta-analysis (NMA) was performed to assess the efficacy and safety of antiplatelet regimens with placebo as the control. Each therapy was compared using relative risk ratios (RR) and 95% credible intervals (CrI), and ranked according to the value of the surface under the cumulative ranking curve. RESULTS: A total of 84,103 patients from 32 studies were included: patients in used aspirin (n=26,834); cilostazol (n=3,303); clopidogrel (n=12,406); prasugrel (n=1,885); sarpogrelate (n=752); ticagrelor (n=1,933); ticlopidine (n=1,644); triflusal (n=391); aspirin plus cilostazol (n=1,120), aspirin plus clopidogrel (n=4,623); aspirin plus dipyridamole (n=10,853); aspirin plus ticagrelor (n=5,859); aspirin plus ticlopidine (n=132). Patients who used aspirin plus clopidogrel and cilostazol had a lower risk of recurrent stroke than those who used placebo. Patients administered with aspirin plus ticagrelor, aspirin plus clopidogrel, and cilostazol had a lower risk of composite vascular events than those administered placebo. Patients administered aspirin plus ticagrelor had a higher risk of major bleeding than those administered placebo. Clustered three-dimensional rank plots of recurrent stroke, major bleeding, and composite vascular events demonstrated that cilostazol had higher values of the surface under the cumulative ranking curve than other treatments. CONCLUSIONS: Of the antiplatelet regimens, cilostazol showed the best net clinical benefits than other antiplatelet regimens in Asians with non-cardioembolic stroke or TIA.

Lifetime and diffusion distance of singlet oxygen in air under everyday atmospheric conditions.

Singlet oxygen is a toxic chemical but powerful oxidant, exploited in many chemical and biological applications. However, the lifetime of singlet oxygen in air under atmospheric conditions is yet to be known. This has limited safe usage of singlet oxygen in air, despite being a strong antimicrobial agent with the unique property of relaxing to breathable oxygen after serving its purpose. Here, we solve this long-standing problem by combining experimental and theoretical research efforts; we generate singlet oxygen using a photosensitizer at a local source and monitor the time-dependent extent of singlet oxygen reaction with probe molecules at a detector, precisely controlling the detector distance from the source. To explain our experimental results, we employ a theoretical model that fully accounts for singlet oxygen diffusion, radiative and nonradiative relaxations, and the bimolecular reaction with probe molecules at the detector. For all cases investigated, our model, with only two adjustable parameters, provides an excellent quantitative explanation of the experiment. From this analysis, we extract the lifetime of singlet oxygen in the air to be 2.80 s at 23 °C under 1 atm, during which time singlet oxygen diffuses about 0.992 cm. The correctness of this estimation is confirmed by a simple mean-first-passage time analysis of the maximum distance singlet oxygen can reach from the source. We also confirm the sterilization effects of singlet oxygen for distances up to 0.6-0.8 cm, depending on the bacteria strain in question, between the bacteria and the singlet oxygen source.

Associations between Living Alone and Smoking and Alcohol Consumption in Korean Adults.

BACKGROUND: Recently, single-person households have increased in Korea and this trend may have potential public health implications and affect various health behaviors. This study investigated the associations between living alone and health behaviors such as smoking and alcohol consumption among Korean adults. METHODS: We used data from the 6th Korea National Health and Nutrition Examination Survey between 2013 and 2015 and a total of 17,088 adults were included. We performed a multivariable logistic regression analysis and calculated odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Single-person households accounted for about 10% of the total participants. The proportions of currently smoking and heavy alcohol consumption were higher among individuals living alone than those living together among younger women and middle-aged and elderly men and women. In the multivariable logistic regression analysis, living alone was associated with increased odds of currently smoking compared to living together among middle-aged men and women (OR, 7.37; 95% CI, 2.33-23.32 in men and OR, 2.36; 95% CI, 1.04-5.36 in women) after adjusting for confounding variables. CONCLUSION: From this nationwide, population-based study, we found that living alone is associated with increased odds of currently smoking, especially in middle-aged people. Public health concerns may be warranted for middle-aged single-person households to reduce health risks related to smoking.

Variabilities in Weight and Waist Circumference and Risk of Myocardial Infarction, Stroke, and Mortality: A Nationwide Cohort Study.

BACKGROUND: Evidence regarding the association between variabilities in obesity measures and health outcomes is limited. We aimed to examine the association between variabilities in obesity measures and cardiovascular outcomes and all-cause mortality. METHODS: We identified 4,244,460 individuals who underwent health examination conducted by the Korean National Health Insurance Service during 2012, with ≥3 anthropometric measurements between 2009 and 2012. Variabilities in body weight (BW) and waist circumference (WC) were assessed using four indices including variability independent of the mean (VIM). We performed multivariable Cox proportional hazards regression analyses. RESULTS: During follow-up of 4.4 years, 16,095, 18,957, and 30,200 cases of myocardial infarction (MI), stroke, and all-cause mortality were recorded. Compared to individuals with the lowest quartiles, incrementally higher risks of study outcomes and those of stroke and all-cause mortality were observed among individuals in higher quartiles of VIM for BW and VIM for WC, respectively. The multivariable adjusted hazard ratios and 95% confidence intervals comparing the highest versus lowest quartile groups of VIM for BW were 1.17 (1.12 to 1.22) for MI, 1.20 (1.16 to 1.25) for stroke, and 1.66 (1.60 to 1.71) for all-cause mortality; 1.07 (1.03 to 1.12) for stroke and 1.29 (1.25 to 1.33) for all-cause mortality regarding VIM for WC. These associations were similar with respect to the other indices for variability. CONCLUSION: This study revealed positive associations between variabilities in BW and WC and cardiovascular outcomes and allcause mortality. Our findings suggest that variabilities in obesity measures are associated with adverse health outcomes in the general population.

Smart Hybrid Nanocomposite for Photodynamic Inactivation of Cancer Cells with Selectivity.

Photodynamic therapy has been efficiently applied for cancer therapy. Here, we have fabricated the folic acid (FA)- and pheophorbide A (PA)-conjugated FA/PA@Fe3O4 nanoparticle (smart hybrid nanocomposite, SHN) to enhance the photodynamic inactivation (PDI) of specific cancer cells. SHN coated with the PDI agent is designed to have selectivity for the folate receptor (FR) expressed on cancer cells. Structural characteristics and morphology of the fabricated MNPs were studied with X-ray diffraction and scanning electron microscopy. The photophysical properties of SHN were investigated with absorption, emission spectroscopies, and Fourier transform infrared spectroscopy. In addition, the magnetic property of Fe3O4 nanoparticle (MNP) can be utilized for the collection of SHNs by an external magnetic field. The photofunctionality was given by the photosensitizer, PA, which generates reactive oxygen species by irradiation of visible light. Generation of singlet oxygen was directly evaluated with time-resolved phosphorescence spectroscopy. Biocompatibility and cellular interaction of SHN were also analyzed by using various cancer cells, such as KB, HeLa, and MCF-7 cells which express different levels of FR on the surface. Cellular adsorption and the PDI effect of SHN on the various cancer cells in vitro were correlated well with the surface expression levels of FR, suggesting potential applicability of SHN on specific targeting and PDI of FR-positive cancers.

Obesity, abdominal obesity and subsequent risk of kidney cancer: a cohort study of 23.3 million East Asians.

BACKGROUND: Limited evidence exists regarding associations between obesity and kidney cancer among Asians. We examined the associations between obesity measures and risk of kidney cancer. METHODS: We included 23,313,046 adults who underwent health examinations provided by the Korean National Health Insurance Service 2009-2012 and performed multivariable Cox proportional hazards regression analyses. RESULTS: During 5.4 years of follow-up, 18,036 cases of kidney cancer were recorded, and cumulative incidence was 0.12%. General and abdominal obesity were associated with 1.32-fold increased risk of kidney cancer compared with groups without either obesity status. Underweight individuals showed decreased adjusted hazard ratio (HR) for kidney cancer (0.76, 95% confidence interval: 0.68-0.85) compared to those with normal body mass index (BMI), while the HRs increased among individuals with BMI 23-24.9 kg/m2 (1.23, 1.18-1.28), 25-29.9 kg/m2 (1.41, 1.36-1.46) and ≥30 kg/m2 (1.77, 1.65-1.90) (P for trend < 0.001). HRs of kidney cancer increased with increasing waist circumference (WC) (P for trend < 0.001). Compared to non-obese condition, the coexistence of general and abdominal obesity increased the HR (1.45, 1.40-1.50). CONCLUSIONS: This study demonstrated positive associations of BMI and WC with kidney cancer risk. General and abdominal obesity may be risk factors of kidney cancer.

Chronic renal dysfunction, proteinuria, and risk of Parkinson's disease in the elderly.

BACKGROUND: The roles of chronic kidney disease and proteinuria in the development of Parkinson's disease have not been widely studied. The objective of this study was to examine the associations of chronic renal dysfunction and proteinuria with the risk of PD in older adults using cohort data of the whole South Korean population. METHODS: We included 3,580,435 individuals aged ≥65 years who had undergone health checkups provided by the National Health Insurance Service of South Korea between 2009 and 2012 and were followed until 2015. Multivariable Cox proportional hazards regression models were performed. RESULTS: During a mean follow-up of 5.2 ± 1.3 years, 30,813 individuals (0.86% of the total population) developed PD. Lower estimated glomerular filtration rate and a higher degree of proteinuria on a dipstick test were associated with higher incidence probability of PD (log-rank P < 0.001). In Cox regression models, chronic renal dysfunction graded by estimated glomerular filtration rate (mL/min/1.73 m2 ) was associated with increased risk of PD after adjusting for potential confounding variables; hazard ratio (95% confidence interval) was 1.13 (1.10-1.17) for estimated glomerular filtration rate 60-90, 1.36 (1.31-1.42) for estimated glomerular filtration rate 30-60, and 1.47 (1.32-1.63) for estimated glomerular filtration rate <30 (P for trend <0.001). Proteinuria ≥1+ was also associated with increased risk of PD development (hazard ratio, 1.12; 95% confidence interval, 1.06-1.18). Coexistence of chronic kidney disease and proteinuria showed an increased hazard ratio of 1.33 (95% confidence interval, 1.23-1.45) for PD occurrence. CONCLUSIONS: Our findings suggest that chronic renal dysfunction and dipstick-positive proteinuria may be independent risk factors for the development of PD in older adults. © 2019 International Parkinson and Movement Disorder Society.

Selective C-C bond formation from rhodium-catalyzed C-H activation reaction of 2-arylpyridines with 3-aryl-2H-azirines.

A novel method for the synthesis of acylmethyl-substituted 2-arylpyridine derivatives using 3-aryl-2H-azirines was developed by exploring a prototype reaction using DFT-calculations and carrying out targeted experiments guided by the calculated mechanism. 2H-Azirine was initially hypothesized to ring-open at the metal center to furnish familiar metal nitrene complexes that may undergo C-N coupling. Computational studies quickly revealed and prototype experimental work confirmed that neither the formation of the expected metal nitrene complexes nor the C-N coupling were viable. Instead, azirine ring-opening followed by C-C coupling was found to be much more favorable to give imines that readily underwent hydrolysis in aqueous conditions to form acylmethyl-substituted products. This new method was highly versatile and selective toward a wide range of substrates with high functional group tolerance. The utility of the new method is demonstrated by a convenient one-pot synthesis of biologically relevant heterocycles such as pyridoisoindole and pyridoisoqunolinone.

Study of Singlet Oxygen Dynamics on Silicon Polymer Matrix.

We report a detailed analysis of singlet oxygen generated from the photofunctional polymer film (PFPF) matrix which is the silicone polymer film (PDMS) embedded with a photosensitizer. Activation and deactivation dynamics of singlet oxygen generated from PFPFs were investigated with time-resolved phosphorescence spectroscopy. The singlet oxygen generated from PFPFs was dissipated into three different regions of the polymer matrix; the inside (component A), the surface (component B), and the outside (component C). According to the deactivation dynamics of singlet oxygen in the polymer matrix, the components B and C are expected to be more important for various applications.

Target-oriented photofunctional nanoparticles (TOPFNs) for selective photodynamic inactivation of Methicillin-resistant Staphylococcus aureus (MRSA).

To inactivate methicillin-resistant Staphylococcus aureus (MRSA) with minimum damage to host cells and tissue, target-oriented photofunctional nanoparticles (TOPFNs) were fabricated and characterized. MRSA is a predominant infective pathogen even in hospital and non-hospital environments due to its ability to develop high levels of resistance to several classes of antibiotics through various pathways. To solve this major problem, photodynamic inactivation (PDI) method applies to treat antibiotic-resistant bacteria. PDI involves the photosensitizer (PS) and light with a specific wavelength to be able to apply for a non-invasive therapeutic procedure to treat pathogenic bacteria by inducing apoptosis or necrosis of microorganisms. However, most current PDI researches have suffered from the instability of PDI agents in the biological environment due to the lack of selectivity and low solubility of PDI agents, which leads to the low PDI efficiency. In this study, the TOPFNs were fabricated by an esterification reaction to introduce hematoporphyrin (HP) and MRSA antibody to the surface of Fe3O4 nanoparticles. The TOPFNs were designed as dispersible PDI agent in biological condition, which was effectively used for selectively capturing and killing of MRSA. The capture efficiency TOPFNs was compared with PFNs as a negative control. The results showed that the capture efficiency of TOPFNs and PFNs was 95.55% and 6.43% in MRSA and L-929 cell mixed condition, respectively. And TOPFNs have a selective killing ability for MRSA with minimum damage to L-929 cells. Furthermore, PDI effect of TOPFNs was evaluated on the mice in vivo condition in order to check the possibility of practical medical application.

Effectiveness of Intraluminal Air Decompression on Postcolonoscopic Pain According to Reinsertion Site.

BACKGROUND: Colonoscopy is a very effective and essential examination to diagnose colorectal cancer; however, many patients experience discomfort due to post-examination abdominal pain, which reduces colonoscopy compliance. This study was conducted to determine methods for reducing post-colonoscopic abdominal pain. METHODS: We conducted a randomized controlled study of 405 male and female adults who visited Hana General Hospital in Cheongju. We surveyed general characteristics, history of colonoscopy, and other related factors, then categorized examinees into 5 groups (0-5) according to the site of scope reinsertion. Pain was measured using a numeric rating scale (NRS). RESULTS: The mean age of examinees in this study was 47.8 years, and 210 participants had prior experience of colonoscopy. No significant difference was observed between variables, with the exception of reinsertion duration (P=0.005). Pain scores were different between performing physicians (P=0.006), and were higher when the subjective level of procedure difficulty was low (P=0.026) in univariate analysis. Pain scores decreased as the reinsertion site became closer to the proximal colon (P<0.001), but there was no significant difference between groups 3 and 4. The results of multiple logistic regression analysis, including univariate analysis, showed that group 1 had 0.48 times, group 2 had 0.38 times, group 3 had 0.09 times, and group 4 had 0.03 times odds ratio (moderate-to-severe pain, NRS ≥4) than control group 0. CONCLUSION: Air decompression by scope reinsertion is an effective way to reduce abdominal pain after colonoscopy. Removing air when the reinserted scope approaches the hepatic flexure seems to be the most effective method to reduce post-colonoscopic pain.

Discovery of boronic acid-based fluorescent probes targeting amyloid-beta plaques in Alzheimer's disease.

A boronic acid-based fluorescent probe was developed for diagnosis of amyloid-ß (Aß) plaques from Alzheimer's disease (AD). Probe 4c, which included boronic acid as a functional group, exhibited a significant increase (64.37-fold, FAß/F0) in fluorescence intensity as a response to Aß aggregates, with a blue shift (105nm) in the maximum emission wavelength. We found that boronic acid as a functional group improved the binding affinity (KD value=0.79±0.05µM for 4c) for Aß aggregates and confirmed that 4c selectively stained Aß plaques in brain sections from APP/PS1 mice. Ex vivo fluorescence imaging using mice (normal and APP/PS1) also revealed that 4c was able to penetrate the blood-brain barrier (BBB) and to stain Aß plaques in the brain. From these results, we believe that 4c will be useful as a fluorescent probe in preclinical research related to AD. Furthermore, we believe that our results with boronic acid also provide valuable information for the development of a probe for Aß plaques.

Development of fluorescent probes that bind and stain amyloid plaques in Alzheimer's disease.

ß-amyloid (Aß) plaques in the brain are composed of Aß40 and Aß42 peptides, and are the defining pathological feature of Alzheimer's disease (AD). Fluorescent probes that can detect Aß plaques have gained increasing interest as potential tools for in vitro and in vivo monitoring of the progression of AD. In this study, chalcone-mimic fluorescent probe 5 was designed and prepared. Probe 5 exhibited an approximately 50-fold increase in emission intensity after mixing with Aß42 aggregates, a high affinity for Aß42 aggregates (K D = 1.59 µM), and reasonable lipophilicity (log P value = 2.55). Probe 5 also exhibited specific staining of Aß plaques in the transgenic mice (APP/PS1) brain sections. Ex vivo fluorescence imaging of the brain from normal and TG mice revealed that probe 5 was able to penetrate the BBB and stain the Aß plaques. These results suggest that chalcone-mimic probe 5 possessed the requirements of a fluorescent probe for Aß plaques and may be useful in AD research.

Production of rubusoside from stevioside by using a thermostable lactase from Thermus thermophilus and solubility enhancement of liquiritin and teniposide.

Solubility is an important factor for achieving the desired plasma level of drug for pharmacological response. About 40% of drugs are not soluble in water in practice and therefore are slowly absorbed, which results in insufficient and uneven bioavailability and GI toxicity. Rubusoside (Ru) is a sweetener component in herbal tea and was discovered to enhance the solubility of a number of pharmaceutically and medicinally important compounds, including anticancer compounds. In this study, thirty-one hydrolyzing enzymes were screened for the conversion of stevioside (Ste) to Ru. Recombinant lactase from Thermus thermophiles which was expressed in Escherichia coli converted stevioside to rubusoside as a main product. Immobilized lactase was prepared and used for the production of rubusoside; twelve reaction cycles were repeated with 95.4% of Ste hydrolysis and 49 g L(-1) of Ru was produced. The optimum rubusoside synthesis yield was 86% at 200 g L(-1), 1200 U lactase. The purified 10% rubusoside solution showed increased water solubility of liquiritin from 0.98 mg mL(-1) to 4.70±0.12 mg mL(-1) and 0 mg mL(-1) to 3.42±0.11 mg mL(-1) in the case of teniposide.