Pharmacological PINK1 activation ameliorates Pathology in Parkinson's Disease models.

PINK1 loss-of-function mutations and exposure to mitochondrial toxins are causative for Parkinson's disease (PD) and Parkinsonism, respectively. We demonstrate that pathological α-synuclein deposition, the hallmark pathology of idiopathic PD, induces mitochondrial dysfunction, and impairs mitophagy as evidenced by the accumulation of the PINK1 substrate pS65-Ubiquitin (pUb). We discovered MTK458, a brain penetrant small molecule that binds to PINK1 and stabilizes its active complex, resulting in increased rates of mitophagy. Treatment with MTK458 mediates clearance of accumulated pUb and α-synuclein pathology in α-synuclein pathology models in vitro and in vivo. Our findings from preclinical PD models suggest that pharmacological activation of PINK1 warrants further clinical evaluation as a therapeutic strategy for disease modification in PD.

Complete genome sequence of Candidatus Phytoplasma australasiaticum WF_GM2021, a plant pathogen associated with soybean witches' broom disease in Taiwan.

The complete genome sequence of Candidatus Phytoplasma australasiaticum strain WF_GM2021, which consists of one 633,005-bp circular chromosome, is presented in this work. This uncultivated plant-pathogenic bacterium is associated with soybean (Glycine max) witches' broom disease in Wufeng District, Taichung City, Taiwan.

Pharmacological PINK1 activation ameliorates Pathology in Parkinson's Disease models.

PINK1 loss-of-function mutations and exposure to mitochondrial toxins are causative for Parkinson's disease (PD) and Parkinsonism, respectively. We demonstrate that pathological α-synuclein deposition, the hallmark pathology of idiopathic PD, induces mitochondrial dysfunction and impairs mitophagy, driving accumulation of the PINK1 substrate pS65-Ubiquitin (pUb) in primary neurons and in vivo. We synthesized MTK458, a brain penetrant small molecule that binds to PINK1 and stabilizes an active heterocomplex, thereby increasing mitophagy. MTK458 mediates clearance of α-synuclein pathology in PFF seeding models in vitro and in vivo and reduces pUb. We developed an ultrasensitive assay to quantify pUb levels in plasma and observed an increase in pUb in PD subjects that correlates with disease progression, paralleling our observations in PD models. Our combined findings from preclinical PD models and patient biofluids suggest that pharmacological activation of PINK1 is worthy of further study as a therapeutic strategy for disease modification in PD. Highlights: Discovery of a plasma Parkinson's Disease biomarker candidate, pS65-Ubiquitin (pUb)Plasma pUb levels correlate with disease status and progression in PD patients.Identification of a potent, brain penetrant PINK1 activator, MTK458MTK458 selectively activates PINK1 by stimulating dimerization and stabilization of the PINK1/TOM complexMTK458 drives clearance of α-synuclein pathology and normalizes pUb in in vivo Parkinson's models.

One-step metallization of weft-knitted fabrics for wearable biaxial strain sensors.

One-step direct patterning of high definition conductive tracks in textiles is realized through laser direct writing in combination with a silver organometallic ink developed in-house. Photoreduction, nano-crystallization, and sintering are accomplished in one pass under the irradiation of a CW green laser light (λ = 532 nm) at moderate intensities (I ≥ 95 mW/mm2). By tailoring the surface tension and viscosity of the ink, high-definition conductive tracks are formed in weft-knitted polyester-Spandex composite fabrics, well-following the laser's profile with negligible coffee stain effect. Length resistance as low as 4 Ω/cm is measured and anisotropy of the gauge factor as high as 25 is achieved. The metallized fabric exhibits reversible and hysteresis-free electromechanical responses subject to high strains. Durability assessment qualifies that the as-metallized strain sensors are able to sustain their performance for over 5000 stretch/release cycles, demonstrating its potential applications in biaxial strain sensing and interactive smart textiles.

Examining factors associated with postintervention recidivism in DUI repeat offenders after alcohol treatment: One-year follow-up study.

Taiwan has deemed driving under the influence of alcohol (DUI) to be criminal, and offenders are subjected to fines and jail penalties without being offered alcohol-related treatment, although alcohol use problems are prevalent in this population. We followed the recidivism records of DUI repeat offenders for one year after they had received a newly established legal-medical joint intervention program for alcohol treatment and examined factors related to postintervention recidivism. In this study, 231 DUI repeat offenders with alcohol use problems screened out by the Alcohol Use Disorder Identification Test were referred from the prosecutors' office to one psychiatric hospital for SBIRT-based alcohol treatment. We divided the participants into two groups based on the official recidivism records within the year following the end of treatment. The study used a Cox proportional hazards model to examine the hazard ratio of the baseline clinical characteristics and intervention duration for post-treatment recidivism. The study used generalized estimation equation models to examine changes in psychological symptoms and drinking behaviors over time. We found that participants who recidivated in the next year after intervention did not differ from those without recidivism records in all measurements except for the length of duration they stayed in treatment. Survival analysis determined that participants who had received the intervention for >4 months showed significantly lower rates of one-year postintervention recidivism rates The study participants showed improved psychological symptoms and drinking behaviors during the follow-up period. In conclusion, adequate duration of alcohol treatment is a significant factor associated with a lower risk of postintervention recidivism. The results provide some insight into the design of a collaborative program between legal and medical systems to reduce DUI recidivism and improve mental health of DUI repeat offenders.

Identification of 16SrII-V Phytoplasma Associated with Mungbean Phyllody Disease in Taiwan.

Mungbean (Vigna radiata (L.) R. Wilczek), an important legume crop in Asia, is primarily cultivated in the central-southern region of western Taiwan. In 2020, mungbean exhibiting typical phytoplasma-induced disease symptoms such as witches' broom, phyllody, virescence, and proliferation was observed in Yunlin County, Taiwan. Moreover, the seed harvested from diseased plants displayed premature germination. Transmission electron microscopy examination of leaf veins prepared from symptomatic mungbean demonstrated that the occlusion of sieve tubes resulted from the accumulation of phytoplasma-like bodies in sieve elements along with filament-like structures in sieve pores. The association of phytoplasma in symptomatic mungbean was confirmed by PCR analyses of the 16S ribosomal RNA (rRNA) and immunodominant membrane protein genes. Further analyses of the 16S rRNA-based phylogenetic tree and the iPhyClassifier-based virtual restriction fragment length polymorphism study demonstrated that the phytoplasma-associated mungbean phyllody disease identified in this study belongs to the 16SrII-V subgroup. BLAST analysis and the phylogenetic analysis indicated that the SAP11-like protein identified in mungbean phyllody disease is identical to peanut witches' broom phytoplasma SAP11, which explains the witches' broom phenotype observed in symptomatic mungbean. The results described in this report confirm that the 16SrII-V phytoplasma, a widely distributed phytoplasma associated with peanut witches' broom disease in Taiwan, has also infected mungbean. This is not only the first instance of mungbean phyllody disease found in Taiwan but also the first instance of mungbean phyllody disease caused by 16SrII-V subgroup phytoplasma.

Tau Reduction Prevents Key Features of Autism in Mouse Models.

Autism is characterized by repetitive behaviors, impaired social interactions, and communication deficits. It is a prevalent neurodevelopmental disorder, and available treatments offer little benefit. Here, we show that genetically reducing the protein tau prevents behavioral signs of autism in two mouse models simulating distinct causes of this condition. Similar to a proportion of people with autism, both models have epilepsy, abnormally enlarged brains, and overactivation of the phosphatidylinositol 3-kinase (PI3K)/Akt (protein kinase B)/ mammalian target of rapamycin (mTOR) signaling pathway. All of these abnormalities were prevented or markedly diminished by partial or complete genetic removal of tau. We identify disinhibition of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a negative PI3K regulator that tau controls, as a plausible mechanism and demonstrate that tau interacts with PTEN via tau's proline-rich domain. Our findings suggest an enabling role of tau in the pathogenesis of autism and identify tau reduction as a potential therapeutic strategy for some of the disorders that cause this condition.

Plasmonically Enhanced Enantioselective Nanocolorimetry.

We report on the generation of a super- and homochiral field where linearly polarized incident light is twisted by plasmonic dimeric nanostructure within the gap. The asymmetry in exciting a molecule's chiral polarizability is enhanced, resulting in discriminatory nanocolorimetry. A chromaticity shift is used to discriminate the handedness of chiral molecules which is sensitive, faster, and self-referenced, and requires only a single scan as compared to existing methods.

Nano-colorimetrically determined refractive index variation with ultra-high chromatic resolution.

We develop a front-to-end solution where the shift of chromaticity from scattering of plasmonic nanoparticles is used as the reporter for nano-environmental refractive index variation. By co-projecting possible power combinations of RGB LEDs and digitized color grid density of CCD with various luminance onto the CIE 1931 chromaticity diagram, optimum condition for nanoenvironment sensing can be achieved. The highest resolution for local refractive index change is 0.0021 per distinguishable color, which is higher than that of a typical handheld spectrometer by 4.8 times. This result shows great potential in simplifying nano-environment sensing instruments and is particularly useful for multi-point dynamical process.

[Photolysis Mechanism of p-Nitrophenol by Nitrocellulose Membrane in Aqueous Solution].

To investigate the potential application of nitrocellulose membrane (NCM) in water treatment, this study examined the photolysis of p-nitrophenol, with NCM as the source of reactive oxygen species. Effects of solution pH, light conditions, and water dissolved substances on p-nitrophenol photolysis were investigated, and possible mechanisms were discussed. The results demonstrated that the quantum yield for hydroxyl radicals from the NCM was 1.30×10-4, which is approximately 1.86 times higher than that from TiO2. The photolysis rate of p-nitrophenol in the presence of NCM was 0.0055 min-1, which is much higher than that in pure water (9.52×10-4 min-1). This promotion was mainly caused by photo-induced generation of ·OH on NCM surface under light, in which UVA plays an important role in photolysis. The photolysis rate of p-nitrophenol increased with the increase of light intensity and membrane area. Acidic solution (pH=2.0) was preferred for the degradation of p-nitrophenol, with a photolysis rate of 0.0165 min-1; the corresponding degradation of p-nitrophenol exceeded 90% in 120 min. The effects of dissolved substances on photolysis were significantly different. NO3- promoted photolysis by generation of ·OH, and dissolved organic matter decreased photolysis through light attenuation. The intermediate products of gas chromatography-mass spectrometry analysis mainly included phenol, hydroquinone, malonic acid, and oxalic acid, and the possible photolysis pathway was given accordingly.

Neuronal levels and sequence of tau modulate the power of brain rhythms.

Neural network dysfunction may contribute to functional decline and disease progression in neurodegenerative disorders. Diverse lines of evidence suggest that neuronal accumulation of tau promotes network dysfunction and cognitive decline. The A152T-variant of human tau (hTau-A152T) increases the risk of Alzheimer's disease (AD) and several other tauopathies. When overexpressed in neurons of transgenic mice, it causes age-dependent neuronal loss and cognitive decline, as well as non-convulsive epileptic activity, which is also seen in patients with AD. Using intracranial EEG recordings with electrodes implanted over the parietal cortex, we demonstrate that hTau-A152T increases the power of brain oscillations in the 0.5-6 Hz range more than wildtype human tau in transgenic lines with comparable levels of human tau protein in brain, and that genetic ablation of endogenous tau in Mapt-/- mice decreases the power of these oscillations as compared to wildtype controls. Suppression of hTau-A152T production in doxycycline-regulatable transgenic mice reversed their abnormal network activity. Treatment of hTau-A152T mice with the antiepileptic drug levetiracetam also rapidly and persistently reversed their brain dysrhythmia and network hypersynchrony. These findings suggest that both the level and the sequence of tau modulate the power of specific brain oscillations. The potential of EEG spectral changes as a biomarker deserves to be explored in clinical trials of tau-lowering therapeutics. Our results also suggest that levetiracetam treatment is able to counteract tau-dependent neural network dysfunction. Tau reduction and levetiracetam treatment may be of benefit in AD and other conditions associated with brain dysrhythmias and network hypersynchrony.

Probing the DOM-mediated photodegradation of methylmercury by using organic ligands with different molecular structures as the DOM model.

Photodegradation is the main depletion pathway for methylmercury (MeHg) in surface water. The formation of MeHg-dissolved organic matter (DOM) complexes has been found to be a key step in MeHg photodegradation. However, the major functional groups involved in the DOM-mediated process have yet to be clearly resolved. In this work, we systematically investigated the effects of DOM molecular structures on MeHg photodegradation by using a variety of organic ligands with different functional groups (e.g., thiosalicylate, thiophenol, and thioaniline). The results showed that thiol and phenyl groups may be the major functional groups governing DOM-mediated MeHg photodegradation, with photodegradation rates also dependent on the type (carboxyl, hydroxyl, and amino group) and position (ortho-, meta-, and para-) of other chemical substituents. The addition of "non-photochemically active" thiol ligands (e.g., mercaptoethanol and dithiothreitol) and high concentrations of Cl- can significantly inhibit the o-thiosalicylate-induced MeHg photodegradation, indicating that complexation of MeHg with these ligands is necessary for MeHg photodegradation. Sparging with O2 had a negligible effect on MeHg photodegradation, while sparging with N2 significantly enhanced MeHg photodegradation. This finding suggests that MeHg photodegradation may be a reductive process, which was further supported by identification of the degradation products of MeHg. A possible protonolysis mechanism of MeHg photodegradation in the presence of o-thiosalicylate was then proposed based on the findings of this study.

Facile Photoinduced Generation of Hydroxyl Radical on a Nitrocellulose Membrane Surface and its Application in the Degradation of Organic Pollutants.

A simple, clean, and efficient method has been developed for generating hydroxyl radicals on a nitrocellulose membrane (NCM) under light of wavelengths greater than 280 nm. Hydroxyl radicals formed on the NCM surface, diffusing into the bulk solution under irradiation. Radical generation was shown to be dependent on the nature of the NCM and light, and independent of the properties of the bulk solution. The quantum yield for hydroxyl radicals from the NCM was 1.72×10-4 , which is approximately 2.46 times that from TiO2 . This hydroxyl radical generation method was preliminarily applied in the photodegradation of organic pollutants, in which electrostatic interactions between the pollutant molecules and the NCM surface were found to play a key role. Further applications of this hydroxyl radical generation method should be assessed.

Efficient decolorization of typical azo dyes using low-frequency ultrasound in presence of carbonate and hydrogen peroxide.

The aims of this study as to evaluate and understand the decolorization of azo dyes using carbonate and hydrogen peroxide under low-frequency ultrasonic irradiation. Under optimal conditions, the decolorization ratio of acid orange 8 (AO 8), a typical azo dye, was > 90% after 2 h of irradiation. The decolorization rate of AO 8 was 0.023 min-1 under ultrasonic irradiation, which was about two times that without ultrasound. Different from the results of other published studies, OH played a minor role, while CO3- played the most important role in AO 8 ultrasonic decolorization in the presence of CO32- and H2O2, with a contribution of 56.52%, followed by CO42- (32.61%) and 1O2 (10.87%). Another difference is that CO3- formed through the cleavage of peroxymonocarbonate or peroxydicarbonate under ultrasonic irradiation rather than through reaction between hydroxyl radical and carbonate. Investigations for different azo dyes revealed that the decolorization rate decreased in the order AO 8 ≈ orange II > acid red 9 > acid yellow 11, probably because of molecular differences among the azo dyes.

Unraveling current hysteresis effects in regular-type C60-CH3NH3PbI3 heterojunction solar cells.

Comprehensive studies were carried out to understand the origin of the current hysteresis effects in highly efficient C60-CH3NH3PbI3(MAPbI3) heterojunction solar cells, using atomic-force microscopy, transmittance spectra, photoluminescence spectra, X-ray diffraction patterns and a femtosecond time-resolved pump-probe technique. The power conversion efficiency (PCE) of C60-MAPbI3 solar cells can be increased to 18.23% by eliminating the point (lattice) defects in the MAPbI3 thin film which is fabricated by using the one-step spin-coating method with toluene washing treatment. The experimental results show that the point defects and surface defects of the MAPbI3 thin films can be minimized by varying the dropping time of the washing solvent. The point defects (surface defects) can be reduced with an (a) increase (decrease) in the dropping time, resulting in an optimized dropping time for obtaining the defect-minimized MAPbI3 thin film deposited on top of the C60 thin film. Consequently, the formation of the defect-minimized MAPbI3 thin film allows for high-efficiency MAPbI3 solar cells.

Catalytic role of iron in the formation of silver nanoparticles in photo-irradiated Ag+-dissolved organic matter solution.

Photo-reduction of Ag+ to silver nanoparticle (AgNPs) by dissolved organic matter (DOM) is a possible source of naturally occurring AgNPs. However, how this photo-reduction process is influenced by ubiquitous metal ions is still not well understood. In addition, in previous studies, the formation of AgNPs in DOM solution was usually monitored by UV-Vis spectroscopy, and there is still lack of quantitative analysis for the formed AgNPs. In the present study, the role of Fe2+/Fe3+ at environmental concentration level on this photochemical process was investigated, and the enhanced formation of AgNPs by Fe2+/Fe3+ was probed and quantified by using UV-Vis spectroscopy, transmission electron microscopy, and liquid chromatography-inductively coupled plasma mass spectrometry. It was demonstrated that while Fe3+ can oxidize AgNPs to release Ag+, Fe2+ can reduce Ag+ into AgNPs. However, the DOM-induced reduction of Fe3+ makes iron an effective electron shuttle between DOM and Ag+, and both Fe2+ and Fe3+ enhanced AgNP formation. The impacts of environmentally relevant factors, including DOM concentration and solution pH, on this process were studied comprehensively, which showed that the catalytic role of iron was more significant at higher DOM concentration and lower pH. This iron-enhanced formation of AgNPs in photo-irradiated Ag+-DOM solution have great environmental implications on the formation of natural AgNPs and the transformation of engineered AgNPs in acidic surface water with high iron content.

An Effective Method to Detect Volatile Intermediates Generated in the Bioconversion of Coal to Methane by Gas Chromatography-Mass Spectrometry after In-Situ Extraction Using Headspace Solid-Phase Micro-Extraction under Strict Anaerobic Conditions.

Bioconversion of coal to methane has gained increased attention in recent decades because of its economic and environmental advantages. However, the mechanism of this process is difficult to study in depth, partly because of difficulties associated with the analysis of intermediates generated in coal bioconversion. In this investigation, we report on an effective method to analyze volatile intermediates generated in the bioconversion of coal under strict anaerobic conditions. We conduct in-situ extraction of intermediates using headspace solid-phase micro-extraction followed by detection by gas chromatography-mass spectrometry. Bioconversion simulation equipment was modified and combined with a solid-phase micro-extraction device. In-situ extraction could be achieved by using the combined units, to avoid a breakdown in anaerobic conditions and to maintain the experiment continuity. More than 30 intermediates were identified qualitatively in the conversion process, and the variation in trends of some typical intermediates has been discussed. Volatile organic acids (C2-C7) were chosen for a quantitative study of the intermediates because of their importance during coal bioconversion to methane. Fiber coating, extraction time, and solution acidity were optimized in the solid-phase micro-extraction procedure. The pressure was enhanced during the bioconversion process to investigate the influence of headspace pressure on analyte extraction. The detection limits of the method ranged from 0.0006 to 0.02 mmol/L for the volatile organic acids and the relative standard deviations were between 4.6% and 11.5%. The volatile organic acids (C2-C7) generated in the bioconversion process were 0.01-1.15 mmol/L with a recovery range from 80% to 105%. The developed method is useful for further in-depth research on the bioconversion of coal to methane.

Degradation of 2,4,6-Trichlorophenol Using Hydrogen Peroxide Catalyzed by Nanoscale Zero-Valent Iron Supported on Ion Exchange Resin.

Nanoscale zero-valent iron (NZVI) supported on ion exchange resin was prepared and characterized by scanning electron microscope and energy dispersive spectroscopy, with a simple model developed for describing the catalyst. The degradation of 2,4,6-trichlorophenol (2,4,6-TCP) by hydrogen peroxide using NZVI supported on ion exchange resin as the catalyst, was studied. The results showed that 2,4,6-TCP with a concentration of 1 mmol L(-1) could be well degraded into low molecule weight organic acids in two hours. The optimized condition was as follows: pH, 3.0; temperature, 35 degrees C; catalyst dosage, 1.5 g; and hydrogen peroxide, 0.16 mmol L(-1). The catalyst has good reusability, with no catalytic efficiency decreasing even after ten times recycles. A possible mechanism of 2,4,6-TCP degradation was proposed, based on the products indentified by GC-MS after derived using trimethylsulfonium hydroxide.

Fuzzy logic feedback control for fed-batch enzymatic hydrolysis of lignocellulosic biomass.

A fuzzy logic feedback control system was developed for process monitoring and feeding control in fed-batch enzymatic hydrolysis of a lignocellulosic biomass, dilute acid-pretreated corn stover. Digested glucose from hydrolysis reaction was assigned as input while doser feeding time and speed of pretreated biomass were responses from fuzzy logic control system. Membership functions for these three variables and rule-base were created based on batch hydrolysis data. The system response was first tested in LabVIEW environment then the performance was evaluated through real-time hydrolysis reaction. The feeding operations were determined timely by fuzzy logic control system and efficient responses were shown to plateau phases during hydrolysis. Feeding of proper amount of cellulose and maintaining solids content was well balanced. Fuzzy logic proved to be a robust and effective online feeding control tool for fed-batch enzymatic hydrolysis.