NEDD4L is a promoter for angiogenesis and cell proliferation in human umbilical vein endothelial cells.

Dysregulated angiogenesis leads to neovascularization, which can promote or exacerbate various diseases. Previous studies have proved that NEDD4L plays an important role in hypertension and atherosclerosis. Hence, we hypothesized that NEDD4L may be a critical regulator of endothelial cell (EC) function. This study aimed to define the role of NEDD4L in regulating EC angiogenesis and elucidate their underlying mechanisms. Loss- and gain-of-function of NEDD4L detected the angiogenesis and mobility role in human umbilical vein endothelial cells (HUVECs) using Matrigel tube formation assay, cell proliferation and migration. Pharmacological pathway inhibitors and western blot were used to determine the underlying mechanism of NEDD4L-regulated endothelial functions. Knockdown of NEDD4L suppressed tube formation, cell proliferation and cell migration in HUVECs, whereas NEDD4L overexpression promoted these functions. Moreover, NEDD4L-regulated angiogenesis and cell progression are associated with the phosphorylation of Akt, Erk1/2 and eNOS and the expression of VEGFR2 and cyclin D1 and D3. Mechanically, further evidence was confirmed by using Akt blocker MK-2206, Erk1/2 blocker U0126 and eNOS blocker L-NAME. Overexpression NEDD4L-promoted angiogenesis, cell migration and cell proliferation were restrained by these inhibitors. In addition, overexpression NEDD4L-promoted cell cycle-related proteins cyclin D1 and D3 were also suppressed by Akt blocker MK-2206, Erk1/2 blocker U0126 and eNOS blocker L-NAME. Our results demonstrated a novel finding that NEDD4L promotes angiogenesis and cell progression by regulating the Akt/Erk/eNOS pathways.

GGC expansions in NOTCH2NLC contribute to Parkinson disease and dopaminergic neuron degeneration.

BACKGROUND AND PURPOSE: The role of GGC repeat expansions within NOTCH2NLC in Parkinson's disease (PD) and the substantia nigra (SN) dopaminergic neuron remains unclear. Here, we profile the NOTCH2NLC GGC repeat expansions in a large cohort of patients with PD. We also investigate the role of GGC repeat expansions within NOTCH2NLC in the dopaminergic neurodegeneration of SN. METHODS: A total of 2,522 patients diagnosed with PD and 1,085 health controls were analyzed for the repeat expansions of NOTCH2NLC by repeat-primed PCR and GC-rich PCR assay. Furthermore, the effects of GGC repeat expansions in NOTCH2NLC on dopaminergic neurons were investigated by using recombinant adeno-associated virus (AAV)-mediated overexpression of NOTCH2NLC with 98 GGC repeats in the SN of mice by stereotactic injection. RESULTS: Four PD pedigrees (4/333, 1.2%) and three sporadic PD patients (3/2189, 0.14%) were identified with pathogenic GGC repeat expansions (larger than 60 GGC repeats) in the NOTCH2NLC gene, while eight PD patients and one healthy control were identified with intermediate GGC repeat expansions ranging from 41 to 60 repeats. No significant difference was observed in the distribution of intermediate NOTCH2NLC GGC repeat expansions between PD cases and controls (Fisher's exact test p-value = 0.29). Skin biopsy showed P62-positive intranuclear NOTCH2NLC-polyGlycine (polyG) inclusions in the skin nerve fibers of patient. Expanded GGC repeats in NOTCH2NLC produced widespread intranuclear and perinuclear polyG inclusions, which led to a severe loss of dopaminergic neurons in the SN. Consistently, polyG inclusions were presented in the SN of EIIa-NOTCH2NLC-(GGC)98 transgenic mice and also led to dopaminergic neuron loss in the SN. CONCLUSIONS: Overall, our findings provide strong evidence that GGC repeat expansions within NOTCH2NLC contribute to the pathogenesis of PD and cause degeneration of nigral dopaminergic neurons.

Multitask Deep Learning Enabling a Synergy for Cadmium and Methane Mitigation with Biochar Amendments in Paddy Soils.

Biochar has demonstrated significant promise in addressing heavy metal contamination and methane (CH4) emissions in paddy soils; however, achieving a synergy between these two goals is challenging due to various variables, including the characteristics of biochar and soil properties that influence biochar's performance. Here, we successfully developed an interpretable multitask deep learning (MTDL) model by employing a tensor tracking paradigm to facilitate parameter sharing between two separate data sets, enabling a synergy between Cd and CH4 mitigation with biochar amendments. The characteristics of biochar contribute similar weightings of 67.9% and 62.5% to Cd and CH4 mitigation, respectively, but their relative importance in determining biochar's performance varies significantly. Notably, this MTDL model excels in custom-tailoring biochar to synergistically mitigate Cd and CH4 in paddy soils across a wide geographic range, surpassing traditional machine learning models. Our findings deepen our understanding of the interactive effects of Cd and CH4 mitigation with biochar amendments in paddy soils, and they also potentially extend the application of artificial intelligence in sustainable environmental remediation, especially when dealing with multiple objectives.

Research Progress of Natural Product Photosensitizers in Photodynamic Therapy.

Photodynamic therapy is a noninvasive cancer treatment that utilizes photosensitizers to generate reactive oxygen species upon light exposure, leading to tumor cell apoptosis. Although photosensitizers have shown efficacy in clinical practice, they are associated with certain disadvantages, such as a certain degree of toxicity and limited availability. Recent studies have shown that natural product photosensitizers offer promising options due to their low toxicity and potential therapeutic effects. In this review, we provide a summary and evaluation of the current clinical photosensitizers that are commonly used and delve into the anticancer potential of natural product photosensitizers like psoralens, quinonoids, chlorophyll derivatives, curcumin, chrysophanol, doxorubicin, tetracyclines, Leguminosae extracts, and Lonicera japonica extract. The emphasis is on their phototoxicity, pharmacological benefits, and effectiveness against different types of diseases. Novel and more effective natural product photosensitizers for future clinical application are yet to be explored in further research. In conclusion, natural product photosensitizers have potential in photodynamic therapy and represent a promising area of research for cancer treatment.

Indium Cyanamide for Industrial-Grade CO2 Electroreduction to Formic Acid.

Developing industrial-grade electroreduction of CO2 to produce formate (HCOO-)/formic acid (HCOOH) depends on highly active electrocatalysts. However, structural changes due to the inevitable self-reduction of catalysts result in severe long-term stability issues at industrial-grade current density. Herein, linear cyanamide anion ([NCN]2-)-constructed indium cyanamide nanoparticles (InNCN) were investigated for CO2 reduction to HCOO- with a Faradaic efficiency of up to 96% under a partial current density (jformate) of 250 mA cm-2. Bulk electrolysis at a jformate of 400 mA cm-2 requires only -0.72 VRHE applied potential with iR correction. It also achieves continuous production of pure HCOOH at ∼125 mA cm-2 for 160 h. The excellent activity and stability of InNCN are attributed to its unique structural features, including strongly σ-donating [NCN]2- ligands, the potential structural transformation of [N═C═N]2- and [N≡C-N]2-, and the open framework structure. This study affirms metal cyanamides as promising novel materials for electrocatalytic CO2 reduction, broadening the variety of CO2 reduction catalysts and the understanding of structure-activity relationships.

Size-Dependent Uptake and Depuration of Nanoplastics in Tilapia (Oreochromis niloticus) and Distinct Intestinal Impacts.

Nanoplastics (NPs, <1 µm) are of great concern worldwide because of their high potential risk toward organisms in aquatic systems, while very little work has been focused on their tissue-specific toxicokinetics due to the limitations of NP quantification for such a purpose. In this study, NPs with two different sizes (86 and 185 nm) were doped with palladium (Pd) to accurately determine the uptake and depuration kinetics in various tissues (intestine, stomach, liver, gill, and muscle) of tilapia (Oreochromis niloticus) in water, and subsequently, the corresponding toxic effects in the intestine were explored. Our results revealed uptake and depuration constants of 2.70-378 L kg-1 day-1 and 0.138-0.407 day-1 for NPs in tilapia for the first time, and the NPs in tissues were found to be highly dependent on the particle size. The intestine exhibited the greatest relative accumulation of both sizes of NPs; the smaller NPs caused more severe damage than the larger NPs to the intestinal mucosal layer, while the larger NPs induced a greater impact on microbiota composition. The findings of this work explicitly indicate the size-dependent toxicokinetics and intestinal toxicity pathways of NPs, providing new insights into the ecological effects of NPs on aquatic organisms.

Nanoplastic Exposure at Environmental Concentrations Disrupts Hepatic Lipid Metabolism through Oxidative Stress Induction and Endoplasmic Reticulum Homeostasis Perturbation.

In this study, we investigated the mechanism underlying the perturbation of hepatic lipid metabolism in response to micro/nanoplastic (MP/NP) exposure at environmentally relevant concentrations. Polystyrene (PS) MPs/NPs with different sizes (0.1, 0.5, and 5.0 µm) were studied for their effects on the homeostasis and function of Nile tilapia (Oreochromis niloticus) liver. Results showed that PS MPs/NPs were readily internalized and accumulated in various internal organs/tissues, especially in fish liver and muscle. Smaller-sized NPs caused more severe toxicity than larger MPs, including hepatic steatosis, inflammatory response, and disturbed liver function. Mechanistically, PS NPs with a particle size of 100 nm perturbed protein homeostasis in the endoplasmic reticulum (ER) by inhibiting the expression of chaperone proteins and genes involved in ER-associated degradation. This led to the activation of the PERK-eIF2α pathway, which caused dysfunction of hepatic lipid metabolism. Induction of oxidative stress and activation of the Nrf2/Keap1 pathway were also involved in the PS NP-induced hepatic lipid accumulation. These findings highlight the potential adverse effects of environmental MPs/NPs on aquatic organisms, raising concerns about their ecotoxicity and food safety.

Cu-doped mesoporous SnO2 nanoparticles with rich grain boundaries and oxygen vacancies for photocatalytic CO2-to-CO conversion.

Photocatalytic conversion of carbon dioxide into fuels provides an effective approach to realize carbon resource utilization. However, the photocatalytic efficiency is still relatively low due to the recombination of photogenerated charges. Herein, we have designed Cu-doped SnO2 nanoparticles (Cu-SnO2) using a glucose-involved hydrothermal crystallization method for the photocatalytic reduction of CO2. The rich oxygen vacancies facilitated the separation and transfer of photogenerated charges, and the confined effect of the typical mesoporous structure promoted the adsorption of CO2, especially a high density of grain boundaries (GBs) and the doping of atomic Cu would introduce new active sites to activate CO2 molecules. This elaborately designed catalyst exhibited super and stable photocatalytic conversion activity of CO2-into-CO, with a CO optimal yield of 107 µmol g-1 in 4 h, which was 2.75 times that over pure SnO2. In situ Raman results indicated that the CO2 reduction reaction followed a *COOH pathway on Cu-SnO2. This work provides implications for the construction of a catalyst with rich defects in the field of energy and environmental catalysis.

The Chinese Parkinson's Disease Registry (CPDR): Study Design and Baseline Patient Characteristics.

BACKGROUND: There is a lack of large multicenter Parkinson's disease (PD) cohort studies and limited data on the natural history of PD in China. OBJECTIVES: The objective of this study was to launch the Chinese Parkinson's Disease Registry (CPDR) and to report its protocol, cross-sectional baseline data, and prospects for a comprehensive observational, longitudinal, multicenter study. METHODS: The CPDR recruited PD patients from 19 clinical sites across China between January 2018 and December 2020. Clinical data were collected prospectively using at least 17 core assessment scales. Patients were followed up for clinical outcomes through face-to-face interviews biennially. RESULTS: We launched the CPDR in China based on the Parkinson's Disease & Movement Disorders Multicenter Database and Collaborative Network (PD-MDCNC). A total of 3148 PD patients were enrolled comprising 1623 men (51.6%) and 1525 women (48.4%). The proportions of early-onset PD (EOPD, age at onset ≤50 years) and late-onset PD (LOPD) were 897 (28.5%) and 2251 (71.5%), respectively. Stratification by age at onset showed that EOPD manifested milder motor and nonmotor phenotypes and was related to increased probability of dyskinesia. Comparison across genders suggested a slightly older average age at PD onset, milder motor symptoms, and a higher rate of developing levodopa-induced dyskinesias in women. CONCLUSIONS: The CPDR is one of the largest multicenter, observational, longitudinal, and natural history studies of PD in China. It offers an opportunity to expand the understanding of clinical features, genetic, imaging, and biological markers of PD progression. © 2022 International Parkinson and Movement Disorder Society.

Heart-targeting exosomes from human cardiosphere-derived cells improve the therapeutic effect on cardiac hypertrophy.

Exosomes of human cardiosphere-derived cells (CDCs) are very promising for treating cardiovascular disorders. However, the current challenge is inconvenient delivery methods of exosomes for clinical application. The present study aims to explore the potential to enhance the therapeutic effect of exosome (EXO) from human CDCs to myocardial hypertrophy. A heart homing peptide (HHP) was displayed on the surface of exosomes derived from CDCs that were forced to express the HHP fused on the N-terminus of the lysosomal-associated membrane protein 2b (LAMP2b). The cardiomyocyte-targeting capability of exosomes were analyzed and their therapeutic effects were evaluated in a mouse model of myocardial hypertrophy induced by transverse aorta constriction (TAC). The molecular mechanisms of the therapeutic effects were dissected in angiotensin II-induced neonatal rat cardiomyocyte (NRCMs) hypertrophy model using a combination of biochemistry, immunohistochemistry and molecular biology techniques. We found that HHP-exosomes (HHP-EXO) accumulated more in mouse hearts after intravenous delivery and in cultured NRCMs than control exosomes (CON-EXO). Cardiac function of TAC mice was significantly improved with intravenous HHP-EXO administration. Left ventricular hypertrophy was reduced more by HHP-EXO than CON-EXO via inhibition of ß-MHC, BNP, GP130, p-STAT3, p-ERK1/2, and p-AKT. Similar results were obtained in angiotensin II-induced hypertrophy of NRCMs, in which the beneficial effects of HHP-EXO were abolished by miRNA-148a inhibition. Our results indicate that HHP-EXO preferentially target the heart and improve the therapeutic effect of CDCs-exosomes on cardiac hypertrophy. The beneficial therapeutic effect is most likely attributed to miRNA-148a-mediated suppression of GP130, which in turn inhibits STAT3/ERK1/2/AKT signaling pathway, leading to improved cardiac function and remodeling.

Concanavalin A promotes angiogenesis and proliferation in endothelial cells through the Akt/ERK/Cyclin D1 axis.

CONTEXT: Concanavalin A (Con A) exhibited multiple roles in cancer cells. However, the role of Con A in endothelial cells was not reported. OBJECTIVE: Our present study investigated the potential angiogenic role of Con A in endothelial cells and ischaemic hind-limb mice. MATERIALS AND METHODS: Human umbilical vein endothelial cells and Ea.hy926 cells were employed to determine the effect of Con A (0.3, 1, and 3 µg/mL) or vehicle on angiogenesis and cell proliferation with tube formation, ELISA, flow cytometry, EdU, and western blot. Hind-limb ischaemic mice were conducted to determine the pro-angiogenic effect of Con A (10 mg/kg) for 7 days. RESULTS: Con A promoted tube formation to about three-fold higher than the control group and increased the secretion of VEGFa, PDGFaa, and bFGF in the medium. The cell viability was promoted to 1.3-fold by Con A 3 µg/mL, and cell cycle progression of G0G1 phase was decreased from 77% in the vehicle group to 70% in Con A 3 µg/mL, G2M was promoted from 15 to 19%, and S-phase was from 7 to 10%. Con A significantly stimulated phosphorylation of Akt and ERK1/2 and expression of cyclin D1 and decreased the expression of p27. These effects of Con A were antagonised by the PI3K inhibitor LY294002 (10 µM) and MEK pathway antagonist PD98059 (10 µM). Moreover, Con A (10 mg/kg) exhibited a repair effect in ischaemic hind-limb mice. DISCUSSION AND CONCLUSIONS: This study will provide a new option for treating ischaemic disease by local injection with Con A.

Functional mapping of language-related areas from natural, narrative speech during awake craniotomy surgery.

Accurate localization of brain regions responsible for language and cognitive functions in epilepsy patients is important. Electrocorticography (ECoG)-based real-time functional mapping (RTFM) has been shown to be a safer alternative to electrical cortical stimulation mapping (ESM), which is currently the clinical/gold standard. Conventional methods for analyzing RTFM data mostly account for the ECoG signal in certain frequency bands, especially high gamma. Compared to ESM, they have limited accuracy when assessing channel responses. In the present study, we developed a novel RTFM method based on tensor component analysis (TCA) to address the limitations of current estimation methods. Our approach analyzes the whole frequency spectrum of the ECoG signal during natural continuous speech. We construct third-order tensors that contain multichannel time-frequency information and use TCA to extract low-dimensional temporal, spectral and spatial modes. Temporal modulation scores (correlation values) are then calculated between the time series of voice envelope features and TCA-estimated temporal courses, and significant temporal modulation determines which components' channel weightings are displayed to the neurosurgeon as a guide for follow-up ESM. In our experiments, data from thirteen patients with refractory epilepsy were recorded during preoperative evaluation for their epileptogenic zones (EZs), which were located adjacent to the eloquent cortex. Our results showed higher detection accuracy of our proposed method in a narrative speech task, suggesting that our method complements ESM and is an improvement over the prior RTFM method. To our knowledge, this is the first TCA-based method to pinpoint language-specific brain regions during continuous speech that uses whole-band ECoG.

Protein Corona-Mediated Extraction for Quantitative Analysis of Nanoplastics in Environmental Waters by Pyrolysis Gas Chromatography/Mass Spectrometry.

There is a growing concern about the effects of nanoplastics on biological safety and human health because of their global ubiquity in the environment. Methodologies for quantitative analysis of nanoplastics are important for the critical evaluation of their possible risks. Herein, a sensitive yet simple and environmentally friendly extraction approach mediated by protein corona is developed and coupled to pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) for nanoplastic determination in environmental waters. The developed methodology involved the formation of protein corona by addition of bovine serum albumin (BSA) to samples and protein precipitation via salting out. Then, the resulting extract was directly introduced to Py-GC/MS for nanoplastic mass quantification. Taking 50 nm polystyrene (PS) particles as a model, the highest extraction efficiency for nanoplastics was achieved under the extraction conditions of BSA concentration of 20 mg/L, equilibration time of 5 min, pH 3.0, 10% (w/v) NaCl, incubation temperature of 80 °C, and incubation period of 15 min. The extraction was confirmed to be mediated by the protein corona by transmission electron microscopy (TEM) analysis of the extracted nanoplastics. In total, 1.92 and 2.82 µg/L PS nanoplastics were detected in river water and the influent of wastewater treatment plant (WWTP), respectively. Furthermore, the feasibility of the present methodology was demonstrated by applying to extract PS and poly(methyl methacrylate) (PMMA) nanoplastics from real waters with recoveries of 72.1-98.9% at 14.2-50.4 µg/L spiked levels. Consequently, our method has provided new insights and possibilities for the investigation of nanoplastic pollution and its risk assessment in the environment.

Sequential Isolation of Microplastics and Nanoplastics in Environmental Waters by Membrane Filtration, Followed by Cloud-Point Extraction.

Respective detection of microplastics (MPs) and nanoplastics (NPs) is of great importance for their different environmental behaviors and toxicities. Using spherical polystyrene (PS) and poly(methyl methacrylate) (PMMA) plastics as models, the efficiency for sequential isolation of MPs and NPs by membrane filtration and cloud-point extraction was evaluated. After filtering through a glass membrane (1 µm pore size), over 90.7% of MPs were trapped on the membrane, whereas above 93.0% of NPs remained in the filtrate. The collected MPs together with the glass membrane were frozen in liquid nitrogen, ground, and suspended in water (1 mL) and subjected to pyrolysis-gas chromatography-mass spectrometry (Py-GC/MS) determination. The NPs in the filtrate were concentrated by cloud-point extraction, heated at 190 °C to degrade the extractant, and then determined by Py-GC/MS. For MPs and NPs spiked in pure water, the method detection limits are in the range of 0.05-1.9 µg/L. The proposed method is applied to analyze four real water samples, with the detection of 1.6-7.6 µg/L PS MPs and 0.6 µg/L PMMA MPs in three samples, and spiked recoveries of 75.0-102% for MPs and 67.8-87.2% for NPs. Our method offers a novel sample pretreatment approach for the respective determination of MPs and NPs.

Quantitative Analysis of Polystyrene and Poly(methyl methacrylate) Nanoplastics in Tissues of Aquatic Animals.

Micro- and nanoplastics unavoidably enter into organisms and humans as a result of widespread exposures through drinking waters, foods, and even inhalation. However, owing to the limited availability of quantitative analytical methods, the effect of nanoplastics inside animal bodies is poorly understood. Herein, we report a sensitive and robust method to determine the chemical composition, mass concentration, and size distribution of nanoplastics in biological matrices. This breakthrough is based on a novel procedure including alkaline digestion and protein precipitation to extract nanoplastics from tissues of aquatic animals, followed by quantitative analysis with pyrolysis gas chromatography-mass spectrometry. The optimized procedure exhibited good reproducibility and high sensitivity with the respective detection limits of 0.03 µg/g for polystyrene (PS) nanoplastics and 0.09 µg/g poly(methyl methacrylate) (PMMA) nanoplastics. This method also preserved the original morphology and size of nanoplastics. Furthermore, to demonstrate the feasibility of the proposed method, 14 species of aquatic animals were collected, and PS nanoplastics in a concentration range of 0.093-0.785 µg/g were detected in three of these animals. Recovery rates of 73.0-89.1% were further obtained for PS and PMMA nanospheres when they were spiked into the tissues of Zebra snail and Corbicula fluminea at levels of 1.84-2.12 µg/g. Consequently, this method provides a powerful tool for tracking nanoplastics in animals.

Reduction of Ionic Silver by Sulfur Dioxide as a Source of Silver Nanoparticles in the Environment.

The natural formation of silver nanoparticles (AgNPs) via biotic and abiotic pathways in water and soil media contributes to the biogeochemical cycle of silver metal in the environment. However, the formation of AgNPs in the atmosphere has not been reported. Here, we describe a previously unreported source of AgNPs via the reduction of Ag(I) by SO2 in the atmosphere, especially in moist environments, using multipronged advanced analytical and surface techniques. The rapid reduction of Ag(I) in the atmospheric aqueous phase was mainly caused by the sulfite ions formed from the dissolution of SO2 in water, which contributed to the formation of AgNPs and was consistent with the Finke-Watzky model with a major contribution of the reduction-nucleation process. Sunlight irradiation excited SO2 to form triplet SO2, which reacted with water to form H2SO3 and greatly enhanced Ag(I) reduction and AgNP formation. Different pH values affected the speciation of Ag(I) and S(IV), which were jointly involved in the reduction of Ag(I). The formation of AgNPs was also observed in the atmospheric gas phase via direct reduction of Ag(I) by SO2(gas), which occurred even in 50 ppbv SO2(gas). The natural occurrence of AgNPs in the atmosphere may also be involved in silver corrosion, AgNP transformation and regeneration, detoxification of gaseous pollutants, and the sulfur cycle in the environment.

The role of genetics in Parkinson's disease: a large cohort study in Chinese mainland population.

This study aimed to determine the mutational spectrum of familial Parkinson's disease and sporadic early-onset Parkinson's disease (sEOPD) in a mainland Chinese population and the clinical features of mutation carriers. We performed multiplex ligation-dependent probe amplification assays and whole-exome sequencing for 1676 unrelated patients with Parkinson's disease in a mainland Chinese population, including 192 probands from families with autosomal-recessive Parkinson's disease, 242 probands from families with autosomal-dominant Parkinson's disease, and 1242 sEOPD patients (age at onset ≤ 50). According to standards and guidelines from the American College of Medical Genetics and Genomics, pathogenic/likely pathogenic variants in 23 known Parkinson's disease-associated genes occurred more frequently in the autosomal-recessive Parkinson's disease cohort (65 of 192, 33.85%) than in the autosomal-dominant Parkinson's disease cohort (10 of 242, 4.13%) and the sEOPD cohort (57 of 1242, 4.59%), which leads to an overall molecular diagnostic yield of 7.88% (132 of 1676). We found that PRKN was the most frequently mutated gene (n = 83, 4.95%) and present the first evidence of an SNCA duplication and LRRK2 p.N1437D variant in mainland China. In addition, several novel pathogenic/likely pathogenic variants including LRRK2 (p.V1447M and p.Y1645S), ATP13A2 (p.R735X and p.A819D), FBXO7 (p.G67E), LRP10 (c.322dupC/p.G109Rfs*51) and TMEM230 (c.429delT/p.P144Qfs*2) were identified in our cohort. Furthermore, the age at onset of the 132 probands with genetic diagnoses (median, 31.5 years) was about 14.5 years earlier than that of patients without molecular diagnoses (i.e. non-carriers, median 46.0 years). Specifically, the age at onset of Parkinson's disease patients with pathogenic/likely pathogenic variants in ATP13A2, PLA2G6, PRKN, or PINK1 was significantly lower than that of non-carriers, while the age at onset of carriers with other gene pathogenic/likely pathogenic variants was similar to that of non-carriers. The clinical spectrum of Parkinson's disease-associated gene carriers in this mainland Chinese population was similar to that of other populations. We also detected 61 probands with GBA possibly pathogenic variants (3.64%) and 59 probands with GBA p.L444P (3.52%). These results shed insight into the genetic spectrum and clinical manifestations of Parkinson's disease in mainland China and expand the existing repertoire of pathogenic or likely pathogenic variants involved in known Parkinson's disease-associated genes. Our data highlight the importance of genetic testing in Parkinson's disease patients with age at onset < 40 years, especially in those from families with a recessive inheritance pattern, who may benefit from early diagnosis and treatment.

Clinical application of intraoperative trial-free online-based language mapping for patients with refractory epilepsy.

OBJECTIVE: The objective of the study was to develop and clinically test a trial-free online-based language mapping method for localizing the eloquent cortex easily in epilepsy operation. METHODS: Nine patients with refractory epilepsy were included in this study according to the results of preoperative evaluation for their epileptogenic zones (EZs) located adjacent to the eloquent cortex. When patients were awakened up from general anesthesia during operation, the trial-free online-based language-mapping paradigm was performed. All positive points marked on the cortex in each test were labeled and superimposed together as the result of functional mapping for each patient. The eloquent cortex was mapped according to the results obtained both from the intraoperative trial-free task localization method and the traditional electrical cortical stimulation (ECS). RESULTS: All patients completed this paradigms twice within 10 min. Based on the results of mapping, the EZs were tried to fully resected on the premise of preserving the mapped eloquent cortex as much as possible. The postoperative follow-up showed the outcome of Engel I in six patients and Engel II in three patients, whereas only two patients had aphemia after surgery and recovered within one week and three months, respectively. SIGNIFICANCE: The intraoperative trial-free online-based language mapping method was primarily identified to be safe and effective. This novel method seems to be promising and worthy of improvement.

Speciation Analysis of Ag2S and ZnS Nanoparticles at the ng/L Level in Environmental Waters by Cloud Point Extraction Coupled with LC-ICPMS.

Toxicity and transport of metal-based nanoparticles (M-NPs) in environmental waters strongly depend on their speciation. A detailed understanding of the composition and speciation of M-NPs is necessary in order to move this field forward. Unfortunately, there is a shortage of analytical methods for metal-sulfide nanoparticles (MS-NPs) in the environment. In this work, a cloud point extraction (CPE) method combined with liquid chromatography hyphenated to inductively coupled plasma mass spectrometry (LC-ICPMS) is developed for sensitive determination of Ag2S- and ZnS-NPs. Under the condition of 0.15% (w/v) of Triton X-114 (TX-114), pH 5, 20 mM NaNO3, incubation temperature of 45 °C, and time of 15 min, MS-NPs and non-MS-NPs were extracted into the surfactant-rich phase. With the sequent addition of 10 mM bis(p-sulfonatophenyl)phenylphosphane dehydrate dipotassium (BSPP) aqueous solution (100 µL) into the CPE-obtained extract, the non-MS-NPs were selectively dissociated into their ionic counterparts while maintaining the original size and shape of Ag2S- and ZnS-NPs. Interestingly, the micelle-mediated behavior suddenly disappeared with the addition of BSPP. Thus, the extract can be injected to LC-ICPMS for speciation analysis of trace Ag2S- and ZnS-NPs. This method exhibited excellent reproducibility (relative standard deviations < 4.9%), high sensitivity with the respective detection limits of 8 ng/L for Ag2S-NPs and 15 ng/L for ZnS-NPs, enabling recoveries of 81.3-96.6% for Ag2S-NPs and 83.9-93.5% for ZnS-NPs when they were spiked into three environmental water samples. Due to its potential applicability to low concentrations of Ag2S- and ZnS-NPs, this method is particularly convenient for monitoring the transformations of AgNPs and ZnO-NPs in the environment.

Release of ZrO2 nanoparticles from ZrO2/Polymer nanocomposite in wastewater treatment processes.

The widespread use of nano-enabled water treatment composites (NWTCs) can result in the release of nanoparticles (NPs) into environmental waters. Studying the release of NPs from NWTCs is of great significance for evaluating the material stability, and environment and biological safety. This work evaluated the amount and species of Zr released from a NWTC, a ZrO2/polymer composite (HZO@D201), during the treatment of electroplating wastewater. About 5 g of the HZO@D201 particles, consisting of porous spheres (0.8 mm in diameter) loaded with ZrO2 NPs, were packed into a glass column (130 mm in length and 20 mm in diameter) and treated with wastewater at a flow rate of 25 mL/hr. The release of Zr occurred mainly in the initial stages of water treatment, decreased with the increase of treatment volume, and approached an equilibrium value of approximately 3.79 µg/L at the treatment volume of about 800 bed volumes. The total amount of Zr released in the effluent was in the range of 2.62-140 µg/L, which was mainly present in the form of ZrO2 NPs. The amounts of Zr released under acidic and alkaline conditions were markedly higher than that under neutral conditions, while the presence of humic acid significantly inhibited the release of Zr. Our study implied that the NWTCs could be a source of engineered NPs in environmental waters, and should be considered in evaluating the safety of ZrO2/polymer composites in water treatment.