Photolysis of dinotefuran and nitenpyram in water and ice phase: Influence mechanism of temperature over photolysis.

Neonicotinoids are widely used pesticides around the world, but the photolysis of neonicotinoids in cold agricultural region are still in blank. This paper aimed to study the influence of cold temperature over photolysis of neonicotinoids. To this end, the photolysis rates and photoproducts of dinotefuran and nitenpyram in water, ice and freeze-thawing condition were determined. Coupled with quantum chemistry calculation, the influence mechanisms of temperature and medium were investigated. The results showed the photolysis rates of neonicotinoids in water condition slightly declined with the lowered temperature due to the photolysis reactions were endothermic reactions. However, the photolysis rates increased by 89.8 %, 59.2 %, 49.4 % and 9.5 % for dinotefuran and nitenpyram in ice and thawing condition, respectively. This phenomenon was posed by the concentration-enhancing effect and change of photo-chemical properties of neonicotinoids in ice condition, which included lowered bond cleavage energy, lowered first excited singlet state energy and expanded light absorption range. The photolysis pathways of the two neonicotinoids did not change in different medium, but the concentration of carboxyl products was relatively higher than that of water condition due to the more amounts of reactive oxygen species in ice medium, which might increase the secondary pollution risk after ice-off in spring due to the higher ecotoxicity to nontarget organism of these photoproducts. The influence of cold temperature and medium change should be considered for the environmental fate and risk assessment of neonicotinoids in cold agricultural region.

The effect of balint practice on reducing stress, anxiety and depression levels of psychiatric nurses and improving empathy level.

OBJECTIVE: To explore the effect of Balint Group in improving stress, negative mood and empathy of psychiatric nurses. METHOD: In March 2022-March 2023, 150 psychiatric nurses from four hospitals in Lanzhou were selected for the study, randomly grouped into experimental group and control groups (75 per group), the experimental group participated the Balint Group activities biweekly, the control group only attended mental health knowledge lectures. Job stress, negative emotion and empathy of the two groups before and after the intervention were evaluated and compared by using job stressor Scale, coping style Assessment Scale, self-assessment scale for depression, self-assessment Scale for anxiety and Jefferson Empathy Scale. RESULTS: After intervention, the job stressor scale and coping style evaluation of nurses in the two groups were significantly decreased, and the experimental group was lower than the control group (P < 0.05). The depression and anxiety of nurses in the two groups were significantly improved, and the experimental group was better than the control group (P < 0.05). The differences in the total score and dimensions of Jefferson Empathy scale in the experimental group after intervention were higher than those in the control group (P < 0.05). CONCLUSION: Balint group activities can effectively relieve the stress, depression and anxiety of psychiatric nurses, and improve the ability of empathy at work.

Efficacy evaluation of albumin-bound paclitaxel combined with carboplatin as neoadjuvant chemotherapy for primary epithelial ovarian cancer.

OBJECTIVE: This study aimed to compare the efficacy of albumin-bound paclitaxel combined with carboplatin (Nab-TC) with that of traditional solvent-based paclitaxel combined with carboplatin (TC) as neoadjuvant chemotherapy (NAC) regimens for primary epithelial ovarian cancer. METHODS: Eighty patients with advanced primary epithelial ovarian cancer admitted for treatment at the Harbin Medical University Cancer Hospital from January 2015 to January 2020 were retrospectively selected. All patients underwent surgery after 1-4 courses of NAC with Nab-TC or TC regimen. Among the patients included for study, 40 patients in each group. RESULTS: The ORR in Nab-TC group was better compared to TC group (45% vs 40%), but the difference was not significant (P = 0.651). While the reduction rate of CA-125 value in the Nab-TC group was significantly better (P < 0.05). The postoperative complication rate such as postoperative blood transfusion (5% vs 35%) and postoperative infusion of human albumin (25% vs 55%) were significantly lower relative to the TC group. The median progression-free survival of the Nab-TC group was significantly longer relative to the TC group (20 months vs 13 months, P = 0.012), and the patient's quality of life was also better in the Nab-TC group (P < 0.05). Our study demonstrated that Nab-TC regimen and R0 represented the independent prognostic factors. CONCLUSION: The efficacy of the Nab-TC regimen as NAC for advanced primary epithelial ovarian cancer was non-inferior to that of the TC regimen along with a lower incidence of adverse reactions, a longer PFS and a higher quality of life, supporting its therapeutic value in the clinic.

Diminution of context association memory structure in subjects with subjective cognitive decline.

Alzheimer's disease (AD) progresses insidiously from the preclinical stage to dementia. While people with subjective cognitive decline (SCD) have normal cognitive performance, some may be in the preclinical stage of AD. Neurofibrillary tangles appear first in the transentorhinal cortex, followed by the entorhinal cortex in the clinically silent stage of AD. We expected the earliest changes in subjects with SCD to occur in medial temporal subfields other than the hippocampal proper. These selective structural changes would affect specific memory subcomponents. We used the Family Picture subtest of the Wechsler Memory Scale-III, which was modified to separately compute character, activity, and location subscores for episodic memory subcomponents. We recruited 43 subjects with SCD, 44 subjects with amnesic mild cognitive impairment, and 34 normal controls. MRI was used to assess cortical thickness, subcortical gray matter volume, and fractional anisotropy. The results demonstrated that SCD subjects showed significant cortical atrophy in their bilateral parahippocampus and perirhinal and the left entorhinal cortices but not in their hippocampal regions. SCD subjects also exhibited significantly decreased mean fractional anisotropy in their bilateral uncinate fasciculi. The diminution of cortical thickness over the mesial temporal subfields corresponded to brain areas with early tangle deposition, and early degradation of the uncinate fasciculus was in accordance with the retrogenesis hypothesis. The parahippocampus and perirhinal cortex contribute mainly to context association memory while the entorhinal cortex, along with the uncinate fasciculus, contributes to content-related contextual memory. We proposed that context association and related memory structures are vulnerable in the SCD stage.

Efficacy of non-invasive brain stimulation combined with antidepressant medications for depression: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Antidepressants, noninvasive brain stimulation (NIBS), and their combination are commonly used in routine clinical practice. Nevertheless, there is a continuous dispute regarding whether the effectiveness of NIBS in combination with antidepressants exceeds that of antidepressants alone. This meta-analysis aimed to evaluate the existing evidence and draw a definitive conclusion on this issue. METHODS: We conducted a comprehensive search of five databases: Embase, PubMed, Web of Science, SinoMed, and the Cochrane Database of Randomized Controlled Trials. The search was conducted until October 6, 2023. The primary outcomes were the pre- and post-intervention depression and anxiety scores. Secondary outcomes included dropout rates, response rates, and certain levels of neurotransmitters [ 5-hydroxytryptamine (5-HT), dopamine (DA), and gamma-aminobutyric acid (GABA)] at the end of the intervention. Subgroup, meta-regression, and sensitivity analyses were performed to explore the sources of heterogeneity. The data were analysed using R 4.2.2. RESULTS: We included 18 RCTs [1357 participants; 11 studies used repetitive transcranial magnetic stimulation (rTMS) and 7 studies used transcranial direct current stimulation (tDCS)]. The follow-up duration varied from two weeks to three months. Overall, whether in combination with rTMS or tDCS, antidepressants proved more effective in alleviating depressive symptoms compared to when used as monotherapy. However, this advantage was not evident during the follow-up period. (p > 0.05). And the combination's efficacy in improving anxiety was found to be lacking. Post-treatment serum levels of 5-HT, DA, and GABA were higher in the rTMS group were higher than antidepressant medication group (p < 0.05). Furthermore, subgroup analysis results indicated that only the rTMS + antidepressant medication treatment significantly improved remission and remission rates. The meta-regression results showed that the type of antidepressant and the sex of the participants had a significant association with the depression score. CONCLUSION: Combination treatment with NIBS was significantly more effective in improving depression symptoms than medication alone. rTMS combined with antidepressants appears to be more effective in improving response and remission rates. However, efficacy may be influenced by the type of medicine used in combination, and long-term efficacy data is lacking. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023388259.

Photolysis mechanism of eleven insecticides under simulated sunlight irradiation: Kinetics, pathway and QSAR.

Insecticides are widely used in crop protection against insects and frequently detected in aquatic environment. Photolysis kinetics are directly related with exposure assessment and risk assessment. However, the photolysis mechanism of neonicotinoid insecticides with different structures has not been studied and compared systematically in the literature. In this paper, the photolysis rate constants in water were determined for eleven insecticides under irradiation of simulated sunlight. At the same time, the photolysis mechanism and effect of dissolved organic matter (DOM) on their photolysis were studied. The results showed that photolysis rates of eleven insecticides vary in a large range. The photolysis rates of nitro-substituted neonicotinoids and butenolide insecticide are much faster than that of cyanoimino-substituted neonicotinoids and sulfoximine insecticide. The ROS scavenging activity assays reveal that direct photolysis dominates the degradation of seven insecticides and, on the other hand, self-sensitized photolysis dominates four insecticides. The shading-effect from DOM can reduce the direct photolysis rates, on the other hand, ROSs generated by triplet-state DOM (3DOM*) can also accelerate photolysis of insecticides. According to the photolytic products identified from HPLC-MS, these eleven insecticides have different photolysis pathways. Six insecticides are degraded from the removal of nitro group from their parent compounds and four insecticides are degraded through ·OH reaction or singlet oxygen (1O2) reaction. QSAR (quantitative structure-activity relationship) analysis showed that photolysis rate was directly related to the energy gap between the highest occupied molecular orbital to the lowest unfilled molecular orbital (Egap = ELUMO-EHOMO) and dipole moment (δ). These two descriptors reflect the chemical stability and reactivity of insecticides. The pathways developed from identified products and the molecular descriptors of QSAR models can well verify the photolysis mechanisms of eleven insecticides.

Photolysis and photo-enhanced toxicity of three novel designed neonicotinoids: Impact of novel modifying groups.

Three novel neonicotinoids (cycloxaprid, flupyradifurone and sulfoxaflor) were designed to reduce the biotoxicity for non-target organisms. These neonicotinoids were photolyzed under light radiation, but it was unclear for the photo-enhanced toxicity and influences of the novel modifying group of the three neonicotinoids. The photolysis and photo-enhanced toxicity experiments were performed for the three neonicotinoids, coupled with quantum chemistry calculation, the mechanisms of photolysis, photo-enhanced toxicity and the influences of novel modifying groups were analyzed. The results showed the photolysis pathways were enriched as compared with previous neonicotinoids due to the composition of modifying groups, singlet oxygen and hydroxyl participated the photolysis of cycloxaprid and flupyradifurone. All tested neonicotinoids exhibited photo-enhanced toxicity to Vibrio fischeri. Due to the difference of photolysis mechanism and toxicity to V. fischeri, the photo-enhanced toxicity curves showed diverse variation when histidine, tert-butanol or dissolved organic matters was in presence of the test solutions. The impact of novel modifying groups over photolysis and photo-enhanced toxicity were analyzed based on the comparison with previous neonicotinoids, theoretically predicted UV-Vis spectra and photo-physical/chemical property descriptors. The data showed the composition of novel modifying group increased the light absorption and photo-chemical activities for the three neonicotinoids.

Relationship between photolysis mechanism and photo-enhanced toxicity to Vibrio Fischeri for neonicotinoids with cyano-amidine and nitroguanidine structures.

Neonicotinoids are widely used pesticides that contaminate aquatic environments. Although these chemicals can be photolyzed under sunlight radiation, it is unclear for the relationship between photolysis mechanism and toxicity change in aquatic organisms. This study aims to determine the photo-enhanced toxicity of four neonicotinoids with different main structures (acetamiprid, and thiacloprid for cyano-amidine structure, imidacloprid and imidaclothiz for nitroguanidine). To Achieve the goal, photolysis kinetics, effect of dissolved organic matter (DOM) and reactive oxygen species (ROSs) scavengers on photolysis rates, photoproducts, and photo-enhanced toxicity to Vibrio fischeri were investigated for four neonicotinoids. The results showed direct photolysis plays a key role in the photo-degradation of imidacloprid and imidaclothiz (photolysis rate constants are 7.85 × 10-3 and 6.48 × 10-3 min-1, respectively), while the photosensitization process of acetamiprid and thiacloprid was dominated by ·OH reactions and transformation (photolysis rate constants are 1.16 × 10-4 and 1.21 × 10-4 min-1, respectively). All four neonicotinoid insecticides exerted photo-enhanced toxicity to Vibrio fischeri, indicating photolytic product(s) posed greater toxicity than their parent compounds. The addition of DOM and ROS scavengers influenced photo-chemical transformation rates of parent compounds and their intermediates, leading to diverse effects on photolysis rates and photo-enhanced toxicity for the four insecticides as a result of different photo-chemical transformation processes. Based upon the detection of chemical structures of intermediates and Gaussian calculations, we observed different photo-enhanced toxicity mechanisms for the four neonicotinoid insecticides. Molecular docking was used to analyze the toxicity mechanism of parent compounds and photolytic products. A theoretical model was subsequently employed to describe the variability of toxicity response to each of the four neonicotinoids.

Photochemical behavior and photo-induced toxicity of chiral pesticides and their chiral monomers in aqueous environment.

The photochemical behaviors of chiral pollutants in aqueous solutions are rarely studied using chiral monomers, which may hamper their precise risk assessment and lead to suspicious conclusions. In this study, we systematically investigated the phototransformation behavior and toxicity evolution of two widely used chiral pesticides (triadimefon (TF) and triadimenol (TN)) at enantiomer and diastereomer levels, and proposed a calculation method of total photolysis rate constants of chiral mixture. Results show that TF and TN could be photodegraded faster in pure water than in natural waters, and the observed photolysis rate constants (kobs) of TN with two chiral centers exhibit enantioselectivity, i.e., kobs(TN-RS) = kobs(TN-SR) > kobs(TN-RR) = kobs(TN-SS). The photolysis of TF and TN mainly occurs through their excited singlet and triplet states, respectively. Their photodegradation pathways mainly include dechlorination and elimination of triazole ring. TF could also undergo ether bond cleavage. It is also found that, both TF and TN exhibit photo-induced toxicity to V. fischeri, due to the generation of more toxic products than parent compounds. Furthermore, TN exhibits enantioselective photo-induced toxicity after 240-min irradiation, which could be ascribed to the formation of chiral products. These results could benefit the understanding of enantioselective environmental behavior of chiral pollutants.

Fractional-Order Boosted Jellyfish Search Optimizer with Gaussian Mutation for Income Forecast of Rural Resident.

The disposable income of residents can reflect the living standard of people in the area. For government departments, it is necessary to master the trend of rural resident income to formulate corresponding policies benefiting farmers. Thus, this paper proposes a grey model with an improved jellyfish search optimizer to predict the rural resident income in Shaanxi Province. Firstly, by applying fractional-order modified strategy and Gaussian mutation mechanism to the original algorithm, the proposed algorithm shows better performance in solving accuracy, stability, and convergence acceleration when compared with different classical methods on cec2017 and cec2019 test functions. Then, based on the fractional time-delayed grey model, a discrete fractional time-delayed grey model with triangular residual correction (TDFTDGM) is proposed by replacing the derivative with a first-order difference and introducing the triangular residual correction functions. Finally, the improved jellyfish search optimizer is used to explore the optimal order of the TDFTDGM model. The all-around performance of the forecast model is incomparable to additional grey models compared on four measure criteria, which means it is a practical approach for long-term prediction with small samples. Moreover, the forecast data of rural resident income in Shaanxi Province from 2021 to 2025 are given for reference.

Study on Bond-Slip Behavior between Seawater Sea-Sand Concrete and Carbon Fiber-Reinforced Polymer (CFRP) Bars with Different Surface Shapes.

The application of CFRP bar and seawater sea-sand concrete (SSSC) in construction can overcome the shortcomings in conventional reinforced concrete, such as corrosion induced by carbonation and chloride ingress. In this study, the bond-slip behavior between an SSSC cube and CFRP bar has been investigated, and different CFRP bar surface shapes have been considered. A total of 27 specimens (9 groups) were fabricated for a pull-out test, where three types of CFRP bar with different surface shapes were used: smooth regular bars, double-wrapped bars and ribbed bars. Bond strength, bond-slip curve, and failure mode have been presented and discussed. FE models have been constructed and validated by experimental results. The effect of concrete compressive strength and relative area of ribs on bond strength has been studied through numerical simulations. It is found that the bond strength increased with concrete compressive strength, and the ribbed bar had significantly higher bond strength than the smooth regular bar. Pull-out failure was observed when the cover-depth-to-bar-diameter ratio was no less than 4 and, otherwise, splitting failure occurred. In addition, a simple formula has been proposed to approximately evaluate the bond strength between an SSSC cube and CFRP bar and validated by experimental results, and analytical expressions for different bond-slip curves have also been developed.

Comparative analysis on the photolysis kinetics of four neonicotinoid pesticides and their photo-induced toxicity to Vibrio Fischeri: Pathway and toxic mechanism.

Neonicotinoids are widely used pesticides all over the world and pose severe water pollution. Although they can be degraded via absorbing sunlight, few attentions have been paid to the environmental risks of their photolysis products. In this paper, the photo-toxicity was investigated for four neonicotinoids (dinotefuran, nitenpyram, thiamethoxam and clothianidin) based on a series of experiments (i.e., photolysis kinetics, radical scavenging, bioluminescent inhibition test to Vibrio Fischeri and intermediate identification) and in-silico calculation of photolysis pathway. The results show that direct photolysis dominates the photolysis of the four neonicotinoids under simulated sunlight radiation. The bioluminescent inhibition kinetics shows that all four neonicotinoids have photo-induced toxicity to V. fischeri, but with different light-induced responses. Scavenging radicals (·OH and 1O2) will decrease the photo-induced toxicity of all the four neonicotinoids, indicating radicals play important roles to the photo-chemical reactions of intermediates. Dissolved organic matters exhibit slightly shading effect to the photolysis rates of four parent compounds. However, the ROSs generated by DOM can accelerate the photo-chemical reactions of intermediates, leading to different photo-induced toxicity in present of DOM. According to the detected intermediates and Gaussian calculations, there are different photolysis pathways and mechanisms for the four neonicotinoids. The calculation for photo-sensitization reactions with 3O2 indicates that both energy transfer reactions and electron transfer reactions can be produced under simulated sunlight radiation, which further consolidate that reactive oxygen species are involved in the photolysis process. A theoretical model has been developed to explain the toxicity variations of four neonicotinoids in different aqueous conditions.

Experimental Study of Fatigue and Fracture Behavior of Carbon Fiber-Reinforced Polymer (CFRP) Straps.

The hanger is one of the important components for through and half-through arch bridges. Conventional steel hangers are vulnerable to corrosion due to corrosive environments. Therefore, a new type of bridge hangers consisting of Carbon Fiber-Reinforced Polymer (CFRP) straps was developed recently. The CFRP straps are self-anchored, which is formed by layers-winding, and they have great advantages in corrosive environments such as high resistance to corrosion. In this study, the fatigue and fracture behavior of CFRP straps has been experimentally investigated. Firstly, the tensile testing of four CFRP strap specimens was conducted to investigate the static fracture behavior of CFRP straps, and three stages were observed, including delamination, cracking, and brittle rupture. Then, a fatigue test of thirty-nine specimens (four groups) was carried out to study the fatigue behavior of CFRP straps, where two types of pins, titanium alloy pin and CFRP pin, and two loading frequencies, 10 Hz and 15 Hz, were used. The number of cycles to failure, displacement, fatigue failure strain, outside surface temperature at the vertex of specimen, and scanning electron microscope (SEM) photographs were recorded and analyzed to investigate the fatigue behavior of CFRP straps. The experiment results show that the temperature development at the vertex of the CFRP strap varies obviously if different pins are used due to the different friction coefficients. In addition, the fatigue life of CFRP straps decreases significantly with the increase in loading rate for the titanium pin, while it only reduces slightly with the increase in loading rate for the CFRP pin.

Machine Learning-Based Classification of Subjective Cognitive Decline, Mild Cognitive Impairment, and Alzheimer's Dementia Using Neuroimage and Plasma Biomarkers.

Alzheimer's disease (AD) progresses relentlessly from the preclinical to the dementia stage. The process begins decades before the diagnosis of dementia. Therefore, it is crucial to detect early manifestations to prevent cognitive decline. Recent advances in artificial intelligence help tackle the complex high-dimensional data encountered in clinical decision-making. In total, we recruited 206 subjects, including 69 cognitively unimpaired, 40 subjective cognitive decline (SCD), 34 mild cognitive impairment (MCI), and 63 AD dementia (ADD). We included 3 demographic, 1 clinical, 18 brain-image, and 3 plasma biomarker (Aß1-42, Aß1-40, and tau protein) features. We employed the linear discriminant analysis method for feature extraction to make data more distinguishable after dimension reduction. The sequential forward selection method was used for feature selection to identify the 12 best features for machine learning classifiers. We used both random forest and support vector machine as classifiers. The area under the receiver operative curve (AUROC) was close to 0.9 between diseased (combining ADD and MCI) and the controls. AUROC was higher than 0.85 between SCD and controls, 0.90 between MCI and SCD, and above 0.85 between ADD and MCI. We can differentiate between adjacent phases of the AD spectrum with blood biomarkers and brain MR images with the help of machine learning algorithms.

Bio-uptake, tissue distribution and metabolism of a neonicotinoid insecticide clothianidin in zebrafish.

Neonicotinoids have been often detected in aquatic environment with high concentrations; however, little is known about their risk and fate to/in fish. This study systematically investigated the bio-uptake, tissue distribution and metabolism of neonicotinoids in zebrafish, taking clothianidin (CLO) as an example. The results revealed the uptake and elimination kinetics of CLO in whole fish and different tissues was very similar, and its bioconcentration factor (<1) indicates the low bioaccumulation potential in zebrafish. The highest accumulative tissues for CLO were found to be intestine and liver. Eight biotransformation products were identified in intestine and liver, and the metabolic pathways were found to be N-demethylation and nitro-reduction. The metabolic kinetics of two products (desmethyl clothianidin and clothianidin urea) revealed the metabolism of CLO mainly occurred in liver and intestine. This suggested that the hepatobiliary system played an important role in the metabolism and elimination of CLO. This study provides a comprehensive evaluation of the toxicokinetics of CLO in zebrafish, and these results can contribute to its ecological risk assessment.

Prognostic Features of Sporadic Creutzfeldt-Jakob Disease: An Analysis of Taiwan's Nationwide Surveillance.

OBJECTIVES: To study the prognostic features of Creutzfeldt-Jakob disease (CJD) and shed light on its future therapy. DESIGN: Retrospective cohort study of a longitudinal national cohort of the Taiwan Centers for Disease Control. SETTING AND PARTICIPANTS: All patients with suspected CJD are reported to the CJD surveillance unit of the Taiwan Centers for Disease Control. An expert committee discussed the reported cases and designated a consensus-based diagnosis. From 1996 to 2020, a total of 809 cases were referred to the CJD surveillance unit for confirmation; of these, 441 cases (women, n = 230) were determined to be sporadic CJD. METHODS: We investigated the clinical manifestations and laboratory findings for 400 patients diagnosed with definite or probable sporadic CJD. We used Kaplan-Meier analyses and Cox proportional hazards model to identify prognostic factors. RESULTS: The mean age of onset was 67 ± 9.9 years. The mean survival duration was 13.3 ± 14.2 (median 10) months. The leading clinical symptoms were myoclonus (73%) and akinetic mutism (54%). For PRNP polymorphism, 99% of patients (195/197) showed a methionine homozygous genotype at codon 129 (M129M). The sensitivity of periodic sharp wave complexes (PSWCs) on electroencephalograms (EEGs) was 59.7%. The sensitivity of cerebrospinal fluid 14-3-3 protein and total tau protein (>1200 pg/mL) were 69.7% and 75.6%, respectively. Younger patients lived longer than those aged ≥65 years [hazard ratio (HR) 0.466, P < .001]. Women had a better survival probability in the first 3 years than their male counterparts (HR 0.712, P = .005). PSWCs had a persistent negative effect on survival (HR 0.788, P < .05). Although uncommon, epileptic seizures were the only clinical prognostic factor for survival time (HR 0.768, P < .05). PSWCs can be used as an EEG biomarker for prognosis. Epileptic seizures, though not common, are the only clinical prognostic factor for a short survival. CONCLUSIONS AND IMPLICATIONS: We found that a lower age of onset and female gender favor the survival of patients with sCJD. PSWCs are EEG biomarkers unfavorable for survival, and so are epileptic seizures.

Pharmacological treatment for Alzheimer's disease: current approaches and future strategies.

More than a decade after the first approval of the use of acetylcholine esterase inhibitor on patients with Alzheimer's disease, we still not have a single treatment or combination therapy that can effectively stop or reverse the relentless progression of such neurodegenerative disease. Recently therapeutics targeting amyloid hypothesis have undergone scrutiny by many clinical trials. These include gamma secretase inhibitor for reducing beta amyloid formation, agents for preventing aggregation of amyloid oligomers, and immunotherapy for enhancing clearance of amyloid and plaque. Therapies targeting hyperphosphorylated tau is another promising mechanism to be tackled with. Other agents enforcing mitochondria functions, enhancing serotonin receptors, modulating advanced glycation end products, and neurotrophic factors, as well as other therapies are also emerging. We review current treatments and therapeutic strategies already undergone different stage of clinical trails in this report. We propose that therapeutics of various combination composed of symptomatic treatments and disease modifying therapies will become standard regimens of AD treatment with much better efficacy than current approaches.

QSAR modeling for the ozonation of diverse organic compounds in water.

The ozonation-based advanced oxidation process is a promising treatment technology for wastewater with micropollutants. The second-order reaction rate constant (kO3) of ozone (O3) with organic compounds is an important index for estimating removal efficiency of organic pollutants in engineered treatment; however, the experimental kO3 values are currently only available for hundreds of chemicals. In this study, two quantitative-structure activity relationship (QSAR) models were developed to predict kO3 of various organic chemicals with multiple linear regression (MLR) and support vector machine (SVM) methods. The built QSAR models cover a large dataset (136 chemicals) and more structurally diverse chemicals as compared to the existing models. The MLR model possesses satisfactory goodness-of-fit (R2tr = 0.734), robustness (Q2LOO = 0.700, Q2BOOT = 0.772) and predictive ability (R2ext = 0.797, Q2ext = 0.794), and the SVM model also has good fitness (R2tr = 0.862) and predictability (R2ext = 0.782, Q2ext = 0.775). The applicability domain of the models has been extended and includes chemicals (especially some emerging pollutants) that are rarely covered in many previous models. The underlying molecular structural factors influencing ozonation are revealed. The energy of the highest occupied molecular orbital (EHOMO) and the phenol/enol/carboxyl OH group (O-057) are the two most important molecular structural factors governing the reactivity of organic compounds with ozone. The developed models can serve as a prescreening tool for the removal prediction of organic pollutants by ozone.

Photolysis and photo-induced toxicity of pyraclostrobin to Vibrio fischeri: Pathway and toxic mechanism.

Pyraclostrobin is a fungicide used widely across the world. However, its photolysis pathway and toxic mechanism is unclear. In this study, photolysis and photo-induced toxicity of pyraclostrobin to Vibrio fischeri were determined. The results showed that direct photolysis dominated the degradation of pyraclostrobin. Gas Chromatography-Mass spectrometry and quantum chemical calculation revealed that the pyraclostrobin was firstly photo-degraded into Methyl N-phenyl-carbamate and 1-(4-chlorophenyl)-3-hydroxy-1H-pyrzole, synthetic intermediates of pyraclostrobin, then into aniline, benzoquinone and acids. Toxicity assay showed that bioluminescent inhibition rate to V. fischeri fluctuated with radiation/illumination time and the toxicity curve can be classified into three phases (Phase I: 0-10 min, incline; Phase II: 10-60 min, decline; Phase III: 60-120 min, incline). The up-and-down curve indicates the change of parent compound during the photolysis. Simulation of molecular docking showed that the CDOCKER interaction energy of pyraclostrobin (-44.71) lower than other intermediate products (>-30.00), indicating that the parent compound is more toxic than its intermediates. An increased toxicity observed in the toxicity curve was attributed to the generation of benzoquinone with log1/EC50 of 6.73, which can greatly change structure of target luciferase in Vibrio fischeri. In addition, the addition of radical scavengers can inhibit the bioluminescence of the tested solutions, indicating the involvement of radicals in the transformation of intermediates. This paper reveals that one of photochemical transformation products of pyraclostrobin can cause more toxic than its parent compound to bacteria. Environmental risk assessment should consider not only the parent compound, but also its metabolites.

Incidence of and Mortality Due to Human Prion Diseases in Taiwan: A Prospective 20-Year Nationwide Surveillance Study from 1998 to 2017.

INTRODUCTION: Epidemiologic studies of Creutzfeldt-Jakob disease (CJD) have been undertaken worldwide since the new variant CJD outbreak in 1996 in the United Kingdom. A nationwide report system, the Creutzfeldt-Jakob Disease Surveillance Unit (CJDSU), directed by the Centers for Disease Control of Taiwan, was established in 1997 to identify human prion diseases. METHODS: From 1998 to 2017, 647 cases were referred to the committee for confirmation. The report to CJDSU included a structured questionnaire recording the clinical, demographic data, and potential iatrogenic exposure, and the results of the clinical and laboratory examination, including tests of blood and cerebrospinal fluid, electroencephalography, and brain magnetic resonance imaging. RESULTS: In total, 356 cases (women, n=178) were ascertained to be human prion diseases, and 97.4% (n=347) were sporadic CJD, including three definite, 314 probable, and 30 possible cases; one probable variant CJD and 8 cases of the genetic form human prion diseases. The age- and gender-specific average annual incidence were also significantly higher in the second decade (0.95/1,000,000) than in the first decade (0.63/1,000,000), with an incidence rate ratio of 1.51. The incidences increased with increasing age, reaching a peak at the age of 70-79 years. The 10-year survival curve for sCJD patients showed that the 1-, 5-, and 10-year cumulative survival rate were 52%, 5%, and 1%, respectively. PRNP polymorphisms in 170 patients showed that 98.8% were M129M and 97.6% E219E. DISCUSSION: The significant increase in incidence after 2008 suggests the increase in the awareness of this rare disease among physicians. The longer disease duration in patients with sCJD in Taiwan than in other countries indicates that the comprehensive support of the health care system, as well as the end-of-life care culture in Taiwan, may prolong survival time in patients with such a progressive and fatal disease.