Ligand-based virtual-screening identified a novel CFTR ligand which improves the defective cell surface expression of misfolded ABC transporters.

Cystic fibrosis (CF) is a monogenetic disease caused by the mutation of CFTR, a cAMP-regulated Cl- channel expressing at the apical plasma membrane (PM) of epithelia. ∆F508-CFTR, the most common mutant in CF, fails to reach the PM due to its misfolding and premature degradation at the endoplasmic reticulum (ER). Recently, CFTR modulators have been developed to correct CFTR abnormalities, with some being used as therapeutic agents for CF treatment. One notable example is Trikafta, a triple combination of CFTR modulators (TEZ/ELX/IVA), which significantly enhances the functionality of ΔF508-CFTR on the PM. However, there's room for improvement in its therapeutic effectiveness since TEZ/ELX/IVA doesn't fully stabilize ΔF508-CFTR on the PM. To discover new CFTR modulators, we conducted a virtual screening of approximately 4.3 million compounds based on the chemical structures of existing CFTR modulators. This effort led us to identify a novel CFTR ligand named FR3. Unlike clinically available CFTR modulators, FR3 appears to operate through a distinct mechanism of action. FR3 enhances the functional expression of ΔF508-CFTR on the apical PM in airway epithelial cell lines by stabilizing NBD1. Notably, FR3 counteracted the degradation of mature ΔF508-CFTR, which still occurs despite the presence of TEZ/ELX/IVA. Furthermore, FR3 corrected the defective PM expression of a misfolded ABCB1 mutant. Therefore, FR3 may be a potential lead compound for addressing diseases resulting from the misfolding of ABC transporters.

Identification of α-Tocopherol succinate as an RFFL-substrate interaction inhibitor inducing peripheral CFTR stabilization and apoptosis.

The E3 ubiquitin ligase RFFL is an apoptotic inhibitor highly expressed in cancers and its knockdown suppresses cancer cell growth and sensitizes to chemotherapy. RFFL also participates in peripheral protein quality control which removes the functional cell surface ΔF508-CFTR channel and reduces the efficacy of pharmaceutical therapy for cystic fibrosis (CF). Although RFFL inhibitors have therapeutic potential for both cancer and CF, they remain undiscovered. Here, a chemical array screening has identified α-tocopherol succinate (αTOS) as an RFFL ligand. NMR analysis revealed that αTOS directly binds to RFFL's substrate-binding region without affecting the E3 enzymatic activity. Consequently, αTOS inhibits the RFFL-substrate interaction, ΔF508-CFTR ubiquitination and elimination from the plasma membrane of epithelial cells, resulting in the increased functional CFTR channel. Among the α-tocopherol (αTOL) analogs we tested, only αTOS inhibited the RFFL-substrate interaction and increased the cell surface ΔF508-CFTR, depending on RFFL expression. Similarly, the unique proapoptotic effect of αTOS was dependent on RFFL expression. Thus, unlike other αTOL analogs, αTOS acts as an RFFL protein-protein interaction inhibitor which may explain its unique biological properties among αTOL analogs. Moreover, αTOS may act as a CFTR stabilizer, a novel class of drugs that extend cell surface ΔF508-CFTR lifetime.

The multiple ubiquitination mechanisms in CFTR peripheral quality control.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated anion channel, which is expressed on the apical plasma membrane (PM) of epithelial cells. Mutations in the CFTR gene cause cystic fibrosis (CF), one of the most common genetic diseases among Caucasians. Most CF-associated mutations result in misfolded CFTR proteins that are degraded by the endoplasmic reticulum quality control (ERQC) mechanism. However, the mutant CFTR reaching the PM through therapeutic agents is still ubiquitinated and degraded by the peripheral protein quality control (PeriQC) mechanism, resulting in reduced therapeutic efficacy. Moreover, certain CFTR mutants that can reach the PM under physiological conditions are degraded by PeriQC. Thus, it may be beneficial to counteract the selective ubiquitination in PeriQC to enhance therapeutic outcomes for CF. Recently, the molecular mechanisms of CFTR PeriQC have been revealed, and several ubiquitination mechanisms, including both chaperone-dependent and -independent pathways, have been identified. In this review, we will discuss the latest findings related to CFTR PeriQC and propose potential novel therapeutic strategies for CF.

The Ubiquitin Ligase RNF34 Participates in the Peripheral Quality Control of CFTR (RNF34 Role in CFTR PeriQC).

The peripheral protein quality control (periQC) system eliminates the conformationally defective cystic fibrosis transmembrane conductance regulator (CFTR), including ∆F508-CFTR, from the plasma membrane (PM) and limits the efficacy of pharmacological therapy for cystic fibrosis (CF). The ubiquitin (Ub) ligase RFFL is responsible for the chaperone-independent ubiquitination and lysosomal degradation of CFTR in the periQC. Here, we report that the Ub ligase RNF34 participates in the CFTR periQC in parallel to RFFL. An in vitro study reveals that RNF34 directly recognizes the CFTR NBD1 and selectively promotes the ubiquitination of unfolded proteins. RNF34 was localized in the cytoplasm and endosomes, where RFFL was equally colocalized. RNF34 ablation increased the PM density as well as the mature form of ∆F508-CFTR rescued at low temperatures. RFFL ablation, with the exception of RNF34 ablation, increased the functional PM expression of ∆F508-CFTR upon a triple combination of CFTR modulators (Trikafta) treatment by inhibiting the K63-linked polyubiquitination. Interestingly, simultaneous ablation of RNF34 and RFFL dramatically increased the functional PM ∆F508-CFTR by inhibiting the ubiquitination in the post-Golgi compartments. The CFTR-NLuc assay demonstrates that simultaneous ablation of RNF34 and RFFL dramatically inhibits the degradation of mature ∆F508-CFTR after Trikafta treatment. Therefore, these results suggest that RNF34 plays a crucial role in the CFTR periQC, especially when there is insufficient RFFL. We propose that simultaneous inhibition of RFFL and RNF34 may improve the efficacy of CFTR modulators.

Preliminary study of the role of general hospital psychiatric ward for patients with dementia in Japan.

A psychiatric ward in a general hospital might be suitable for people with dementia because of the comprehensive medical care available. The aim was to investigate the characteristics of 86 patients with dementia admitted to psychiatric ward in a general hospital. About 40% of the patients were admitted due to a diagnosis of dementia and the need for treatment of a physical disease. The expected roles of psychiatric ward in a general hospital for patients with dementia include the acute care of physical and psychological problems and a differential diagnosis.

Appropriate height of dental chairs for effective administration of chest compressions by female dentists.

Objectives: The aim of this study was to determine the appropriate height of a dental chair for the administration of effective chest compressions by female dentists. Materials and methods: We asked 19 female dentists to perform metronome-guided chest compressions at a rate of 100 compressions per minute for 2 min on the floor and on a dental chair. We set the height of the dental chair to 76, 73, 70, 67, and 64 cm. We measured the compression depth and proportion of compressions performed at an adequate depth. We then compared the quality of chest compressions between the tall and short (relative to the average body height) groups of participants. We also asked the participants to specify their preferred compression height or condition for chest compression administration. Results: The participants recorded their maximum chest compression depth (35.0 ± 8.8 mm) at a height of 67 cm. There was no significant difference in chest compression depth between the tall and short groups, irrespective of the compression height. The maximum depth of chest compressions was achieved at a height of 67 cm (from the floor to the compression surface) in both groups, with no significant difference. The participants most frequently identified 67 cm as the most suitable height for the administration of chest compressions. Conclusion: For female dentists, a height of 67 cm is considered suitable for the administration of chest compressions in the standing position, regardless of physique.

Rapid Deterioration of Basic Life Support Skills in Dentists With Basic Life Support Healthcare Provider.

The aim of this study was to investigate the correlation between basic life support skills in dentists who had completed the American Heart Association's Basic Life Support (BLS) Healthcare Provider qualification and time since course completion. Thirty-six dentists who had completed the 2005 BLS Healthcare Provider course participated in the study. We asked participants to perform 2 cycles of cardiopulmonary resuscitation on a mannequin and evaluated basic life support skills. Dentists who had previously completed the BLS Healthcare Provider course displayed both prolonged reaction times, and the quality of their basic life support skills deteriorated rapidly. There were no correlations between basic life support skills and time since course completion. Our results suggest that basic life support skills deteriorate rapidly for dentists who have completed the BLS Healthcare Provider. Newer guidelines stressing chest compressions over ventilation may help improve performance over time, allowing better cardiopulmonary resuscitation in dental office emergencies. Moreover, it may be effective to provide a more specialized version of the life support course to train the dentists, stressing issues that may be more likely to occur in the dental office.

Transient cardiac arrest in a child with Down syndrome during anesthesia induction with sevoflurane: a case report.

BACKGROUND: This report describes a case of transient cardiac arrest in a child with Down syndrome. The cardiac arrest occurred during induction of anesthesia with sevoflurane. To the best of our knowledge, this is the first such report. CASE PRESENTATION: A 14-year-old boy was scheduled to undergo dental treatment under general anesthesia because of his mental disorder. He had congenital atrial and ventricular septal defects and patent ductus arteriosus, which had been repaired previously. Therefore, we anticipated no problems with his cardiovascular system during the perioperative period. Because the sedation administered before the insertion of an intravenous catheter and arterial line was insufficient to induce an anesthetic effect, general anesthesia was induced by using a mixture of sevoflurane (5 %) with oxygen in nitrous oxide. A few minutes after the induction of anesthesia, the patient unexpectedly experienced bradycardia (heart rate <30 beats/min), and his electrocardiography findings indicated asystole. After a few minutes of cardiopulmonary resuscitation, the patient's heart rate returned to normal. CONCLUSIONS: We postulated that the asystole was triggered by a dysfunction in the autonomic cardiac regulation and sympathetic activation, which often occurs in patients with Down syndrome, and due to the use of high concentrations of sevoflurane. In future cases of pediatric patients with Down syndrome, with or without heart disease, the concentration of sevoflurane administered during surgery should be increased gradually. Moreover, an intravenous catheter should be promptly inserted to administer anticholinergic drugs as quickly as possible in order to prevent transient cardiac arrest.

Greater than the Sum of Its Parts: δ can be Constructed from Item Level Data.

"δ", a latent variable constructed from cognitive performance and functional status measures, can accurately diagnose dementia. The minimal assessment needed is unknown. We have constructed a δ homolog, "dTEXAS", from Telephone Executive Assessment Scale (TEXAS) items, and validated it in a convenience sample of Japanese persons (n = 176). dTEXAS scores correlated strongly with both Instrumental Activities of Daily Living (IADL) (r = -0.86, p <  0.001) and Clinical Dementia Rating Scale (CDR) (r = 0.71, p <  0.001). Constructed independently of their diagnoses, dTEXAS scores accurately distinguished dementia versus controls (area under the receiver operating curve [(AUC; ROC) = 0.92], dementia versus mild cognitive impairment (MCI) (AUC = 0.80) and controls versus MCI (AUC = 0.74). These AUCs are higher than those of multiple observed executive measures, as reported recently by Matsuoka et al., 2014. A dTEXAS score of -0.58 best discriminated between dementia versus controls with 90.1% sensitivity and 80.0% specificity.

δ Scores are Exportable Across Cultural and Linguistic Boundaries.

The latent variable "δ", can accurately diagnose dementia. Its generalizability across populations is unknown. We constructed a δ homolog ("dT2J") in data collected by the Texas Alzheimer's Research and Care Consortium (TARCC). From this, we calculated a composite d-score "d". We then tested d's generalizability across random subsets of TARCC participants and to a convenience sample of elderly Japanese persons with normal cognition (NC), mild cognitive impairment (MCI), and dementia (AD) (n = 176). dT2J was indicated by Instrumental Activities of Daily Living and psychometric measures. Embedded in this battery were the Mini-Mental Status Examination (MMSE) and an executive clock-drawing task (CLOX). Only MMSE and CLOX were available in both TARCC and the Japanese cohort. Therefore, a second composite variable, "T2J", was constructed solely from the factor loadings of CLOX and MMSE on d. The diagnostic accuracy of T2J was estimated in the validation sample, the remainder of the TARCC cohort, and in the Japanese sample. The areas under the receiver operating curve (AUC; ROC) for T2J were compared in each sample, and against d in TARCC. The AUCs for T2J were statistically indiscriminable within TARCC, and in Japanese persons. In Japanese persons, AUCs for T2J were 0.97 for the discrimination between AD versus NC, 0.86 for AD versus MCI, and 0.79 for NC versus MCI. The AUCs for T2J in Japanese persons were higher than any individual psychometric measure in that sample. Valid d-score composites can be abstracted from a subset of δ's indicators. Moreover, those composites are exportable across cultural and linguistic boundaries.

Stellate Ganglion Block, Compared With Xenon Light Irradiation, Is a More Effective Treatment of Neurosensory Deficits Resulting From Orthognathic Surgery, as Measured by Current Perception Threshold.

PURPOSE: The aim of this study was to evaluate the relative effectiveness of stellate ganglion blockade (SGB) versus xenon light irradiation (XLI) for the treatment of neurosensory deficits resulting from orthognathic surgery as determined by a comparison of prospective measurements of electrical current perception thresholds (CPTs) and ranged CPTs (R-CPTs). MATERIALS AND METHODS: CPT and R-CPT in the mental foramen area were measured during electrical stimulation at 98 different sites on the body in patients who had undergone orthognathic surgery. After surgery, patients were assigned to the SGB group or the XLI group. CPT and R-CPT of the 2 groups were measured at stimulation frequencies of 2,000, 250, and 5 Hz before surgery, 1 week after surgery, and after 10 treatment sessions. Furthermore, the influence of surgical factors, such as genioplasty and a surgically exposed inferior alveolar nerve (IAN), was examined in the 2 groups. RESULTS: Patients' CPT and R-CPT values indicated a considerable amount of sensory disturbance in most cases after surgery. The change in magnitude of all CPT and R-CPT values for the SGB group decreased considerably compared with that for the XLI group after treatment. There was no correlation between CPT or R-CPT values and surgical factors (eg, genioplasty and exposure of the IAN). CONCLUSION: SGB of the IAN could be an effective method for treating neurosensory deficits after orthognathic surgery on the IAN.

Greater than the sum of its parts: δ Improves upon a battery's diagnostic performance.

OBJECTIVE: "δ", a latent variable constructed from batteries that contain both cognitive and functional status measures, can accurately diagnose dementia relative to expert clinicians. The minimal assessment needed is unknown. METHODS: We validated 2 δ homologs in a convenience sample of elderly Japanese persons with normal cognition (NC), mild cognitive impairment (MCI), and dementia (n = 176). The latent δ homolog "d" (for dementia) was constructed from Instrumental Activities of Daily Living (IADL) and Japanese translations of the Executive Clock-Drawing Task (CLOX), Frontal Assessment Battery (FAB), and Executive Interview (EXIT25). The latent delta homolog "d3" was constructed from a restricted set of d's factor loadings. RESULTS: d and d3 were highly intercorrelated (r = .97) and strongly related to both IADL and dementia severity, as rated blindly by the Clinical Dementia Rating Scale (CDR). d was more strongly related to IADL and CDR than any of its indicators. In multivariate regression, d explained more variance in CDR scores than all of its indicators combined. d's areas under the receiver operating characteristic curve (AUC) were 0.95 for the discrimination between Alzheimer's disease (AD) vs. NC, 0.84 for AD vs. MCI and 0.81 for NC vs. MCI. d3's AUC's were statistically indiscriminable. These AUC's are higher than any of d's indicators, as reported recently by Matsuoka et al. (2014), as well as the Mini-Mental State Examination (MMSE), which had been made available by Matsuoka et al. to the CDR raters. CONCLUSIONS: Latent variables can improve upon a battery's diagnostic performance and offer the potential for accurate dementia case-finding after a minimal bedside assessment.

Japanese versions of the executive interview (J-EXIT25) and the executive clock drawing task (J-CLOX) for older people.

BACKGROUND: The aim of the study was to develop the Japanese versions of Executive Interview (J-EXIT25) and Executive Clock Drawing Task (J-CLOX) and to evaluate the aspects of executive function that these two tests will be examining. METHODS: The concurrent validity and reliability of J-EXIT25 and J-CLOX were first examined in all participants (n = 201). Next, the relationship between the two tests was examined using receiver operating characteristic (ROC), correlation, and regression analyses in healthy participants (n = 45) and participants with mild cognitive impairment (n = 36) and dementia (n = 95). RESULTS: Satisfactory concurrent validity and reliability of J-EXIT25 and J-CLOX were shown. ROC analysis indicated that J-EXIT25 and J-CLOX1 were superior to the Frontal Assessment Battery, but inferior to the Mini-Mental State Examination (MMSE), in discriminating between non-dementia and dementia. J-EXIT25, J-CLOX1, and J-CLOX2 scores were significantly correlated with age, scores on the MMSE, Instrumental Activities of Daily Living (IADL) and Physical Self-Maintenance Scale (PSMS), and care level. In stepwise regression analyses of IADL scores, MMSE and J-EXIT25 were significantly independent predictors in men, and MMSE, age, and J-CLOX1 were significantly independent predictors in women. J-EXIT25, MMSE, and J-CLOX1 were significantly independent predictors in stepwise regression analysis of PSMS scores, and J-EXIT25 was the only significantly independent predictor in stepwise regression analysis of care level. CONCLUSIONS: J-EXIT25 and J-CLOX are valid and reliable instruments for assessment of executive function in older people. The present results suggest that these tests have common and distinct psychometric properties in the assessment of executive function.

White-matter hyperintensities predict delirium after cardiac surgery.

OBJECTIVES: Postoperative delirium is a common psychiatric disorder among patients who undergo cardiac surgery. Although several studies have investigated risk factors for delirium after cardiac surgery, the association between delirium and cerebral white-matter hyperintensities (WMH) on magnetic resonance (MR) imaging has not been previously studied. The aim of this study was to identify general risk factors for delirium, as well as to examine the specific relationship between WMH and delirium. DESIGN: Retrospective chart review. SETTING: University hospital. PARTICIPANTS: A total of 130 patients who underwent cardiac surgery. MEASUREMENTS: Variables recorded included patient demographics, comorbidities, mental health, laboratory data, surgical information, and cerebrovascular disease. The presence of WMH was assessed using MR images. Two groups of patients were compared (patients with and without delirium) using both univariate and multiple logistic analyses. RESULTS: Delirium occurred in 18 patients (13.8%) and patients with delirium were significantly older than patients who did not develop delirium. The prevalence of severe WMH (Fazekas score = 3) was significantly higher in patients with delirium. Three independent predictors of delirium were identified: abnormal creatinine (odds ratio [OR]: 4.5; 95% confidence interval [CI]: 1.4-13.9), severe WMH (OR: 3.9; 95% CI: 1.2-12.5), and duration of surgery (OR: 1.4; 95% CI: 1.0-1.8). CONCLUSIONS: The results of this study suggest that white-matter abnormality is one of the most important risk factors for development of delirium after cardiac surgery. These factors can be used for prediction and prevention of delirium following cardiac surgery.

Neural correlates of the components of the clock drawing test.

BACKGROUND: The aim of this study was to identify the neural correlates of each component of the clock drawing test (CDT) in drug-naïve patients with Alzheimer's disease (AD) using single photon emission computed tomography. METHODS: The participants were 95 drug-naïve patients with AD. The Rouleau CDT was used to score the clock drawings. The score for the Rouleau CDT (R total) is separated into three components: the scores for the clock face (R1), the numbers (R2), and the hands (R3). A multiple regression analysis was performed to examine the relationship of each score (i.e. R total, R1, R2, and R3) with regional cerebral blood flow (rCBF). Age, gender, and education were included as covariates. The statistical threshold was set to a family-wise error (FWE)-corrected p value of 0.05 at the voxel level. RESULTS: The R total score was positively correlated with rCBF in the bilateral parietal and posterior temporal lobes and the right middle frontal gyrus. R1 was not significantly positively correlated with rCBF, R2 was significantly positively correlated with rCBF in the right posterior temporal lobe and the left posterior middle temporal lobe, and R3 was significantly positively correlated with rCBF in the bilateral parietal lobes, the right posterior temporal lobe, the right middle frontal gyrus, and the right occipital lobe. CONCLUSIONS: Various brain regions were associated with each component of the CDT. These results suggest that an assessment of these components is useful for the detection of localization of brain damage.

Treatment in a ward for elderly patients with dementia in Japan.

BACKGROUND: Japan has become the world's most aged country. The percentage of elderly people in Japan is estimated to reach 25.2% in 2013, and the number of patients with dementia is estimated to reach 2.5 million in 2015. In addition to its deterioration of physical function and activities of daily living (ADL), behavioral and psychological symptoms of dementia (BPSD) often become major clinical problems, greatly annoying patients and their caregivers. In Japan, we utilize wards for elderly patients with dementia (WEDs) for BPSD treatment. However, there are few studies investigating the effectiveness of treatment in a WED. In such treatment, physical complications are a challenge physicians must overcome while treating BPSD and safely returning patients home or to the institutions in which they live. Therefore, we investigated the effectiveness of treatment in a WED, focusing on physical complications. METHODS: The subjects were 88 patients who were admitted to and discharged from a WED. Severity of dementia, basic ADL, and BPSD were investigated using the Clinical Dementia Rating, Physical Self-Maintenance Scale (PSMS), and Neuropsychiatric Inventory. Differences in characteristics between patients discharged from the WED because of physical complications and all other patients were also examined. RESULTS: We found significant improvements in the PSMS score and decreases in delusions and sleep disturbances in all patients. Patients discharged from the WED because of physical complications had significantly greater severity of dementia at discharge compared to all other patients. CONCLUSION: Treatment in a WED seems to be effective for BPSD and ADL, but care should be taken regarding physical complications, especially in patients with advanced dementia.

Effect of toki-shakuyaku-san on regional cerebral blood flow in patients with mild cognitive impairment and Alzheimer's disease.

The aim of this study was to examine the effect of toki-shakuyaku-san (TSS) on mild cognitive impairment (MCI) and Alzheimer's disease (AD) using single-photon emission computed tomography (SPECT). All subjects were administered TSS (7.5 g/day) for eight weeks. SPECT and evaluations using the Mini Mental State Examination (MMSE), Neuropsychiatric Inventory, and Physical Self-Maintenance Scale were performed before and after treatment with TSS. Three patients with MCI and five patients with AD completed the study. No adverse events occurred during the study period. After treatment with TSS, regional cerebral blood flow (rCBF) in the posterior cingulate was significantly higher than that before treatment. No brain region showed a significant decrease in rCBF. TSS treatment also tended to improve the score for orientation to place on the MMSE. These results suggest that TSS could be useful for treatment of MCI and AD.

The success rate of nasotracheal intubation using lightwand does not depend on the laryngoscopic view.

PURPOSE: The purpose of this study was to evaluate the usefulness of Trachlight (TL) for nasotracheal intubation and to determine the relationship between the grade of laryngeal view and the subsequent ease of nasotracheal intubation using TL. METHODS: Patients requiring nasotracheal intubation were enrolled in this study. Laryngoscopy was performed in all patients under topical anesthesia, with 8% lidocaine spray applied to the supraglottic region and the vocal cords. Glottic visualization during laryngoscopy was assessed using the Cormack and Lehane classification. Patients were allocated to four groups according to this classification. If the TL intubation was unsuccessful after three attempts, intubation was carried out using direct laryngoscopy. Intubation difficulty was assessed by the original 6-point scale and the total intubation time was also recorded. RESULTS: Trachlight intubation was successful in 89.1% of the 110 patients enrolled in the study. There was no observed correlation between the original 6-point scale and glottic visualization. The total intubation time and the ratio of "unsuccessful" cases were not significantly different among the four groups. CONCLUSION: No relationship was found between the ease of nasotracheal intubation using TL and glottic visualization.

A novel use of TiO2 fiber for photocatalytic ozonation of 2,4-dichlorophenoxyacetic acid in aqueous solution.

More efficient oxidation methods are needed to degrade especially newly emerging recalcitrant organic contaminants at low concentrations in the water environment. Reduced photonic efficiency of immobilized TiO2 is a major challenge in TiO2-assisted advanced oxidation processes (AOP). Mineralization of 2,4-dichllorophenoxyacetic acid (2,4-D) in low aqueous solution by O3/UV/TiO2 using the world's first high-strength TiO2 fiber was investigated and compared with O3, UV/TiO2, and O3/TiO2 in laboratory batch experiments. The 2,4-D degradation and total organic carbon (TOC) removal followed pseudo first-order reaction kinetic, while their rates in O3/UV/TiO2 were respectively about 1.5 and 2.4 times larger than the summation of the values in 03 and UV/TiO2. The O3/UV/TiO2 was characterized by few aromatics with very low abundance, fast disappearance of aliphatics and more than 95% dechlorination. The discrepancies in organic carbon mass balance among the intermediates and 2,4-D were attributed mainly to few apparently major unidentified intermediates. The significantly enhanced 2,4-D mineralization in O3/UV/TiO2 was attributed to increased ozone dissolution followed by its decomposition, and reduced electron-hole recombination in presence of dissolved ozone resulting in a large number of hydroxyl radical (*OH) generation from more than one parallel path. The removal efficiencies of the systems can further be enhanced by optimizing design parameters, and O3/UV/TiO2 with the TiO2 fiber is promising to mineralize recalcitrant organic contaminants in water at low concentrations.