Surface-Charge-Driven Ferroptosis and Mitochondrial Dysfunction Is Involved in Toxicity Diversity in the Marine Bivalve Exposed to Nanoplastics.

Nanoplastics (NPs) pervade daily life, posing serious threats to marine ecosystems. Despite the crucial role that surface charge plays in NP effects, there is a substantial gap in our understanding of how surface charge influences NP toxicity. Herein, by exposing Ruditapes philippinarum (R. philippinarum) to both positively charged NPs (p-NPs) and negatively charged NPs (n-NPs) at environmentally relevant particle number levels for a duration of 35 days, we unequivocally demonstrate that both types of NPs had discernible impacts on the clams depending on their surface charge. Through transcriptomic and proteomic analyses, we unveiled the primary mechanisms behind p-NP toxicity, which stem from induced mitochondrial dysfunction and ferroptosis. In contrast, n-NPs predominantly stimulated innate immune responses, influencing salivary secretion and modulating the complement and coagulation cascades. Furthermore, in vitro tests on clam immune cells confirmed that internalized p-NPs triggered alterations in mitochondrial morphology, a decrease in membrane potential, and the initiation of ferroptosis. Conversely, n-NPs, to a certain extent, moderated the expression of genes related to immune responses, thus mitigating their adverse effects. Taken together, these findings indicate that the differential surface-charge-driven ferroptosis and mitochondrial dysfunction in clams play a critical role in the toxicity profile of NPs, providing an insightful reference for assessing the ecological toxicity associated with NPs.

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.

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.

Regulating the reaction pathway of nZVI to improve the decontamination performance through magnetic spatial confinement effect.

Nanoscale zero-valent iron (nZVI) shows high effectiveness in the catalyzed removal of contaminants in wastewater treatment. However, the uncontrolled interfacial electron transfer behavior and formation of surface iron oxide (FeOx) layer led to severe electron wasting and occasionally form highly toxic intermediates. Here, we constructed magnetic mesoporous SiO2 shell on surface of nZVI to stimulate a magnetic spatial confinement effect and regulate the electron transfer pattern. Therein, Fe atom facilely spread out from the nZVI core, orderly release electron to surface adsorbed H2O molecule, which is efficiently transformed into active hydrogen (H*). Meanwhile, in-situ Raman revealed that Fe atoms were involved in the formation of penetrable γ-FeOOH rather than FeOx layer, enabling the continuous inward diffusion of H2O and outward diffusion of H* . Employing the catalyzed removal of halogenated phenols as demo reaction, the presence of magnetic mesoporous SiO2 shell utilized the reaction between electrons and H2O to switch the reaction pathway from the reduction/oxidation hybrid process to hydrodehalogantion, and increased the conversion of halogenated phenols-to-phenols by 5.53 times. This study shows the forehand of improving the decontamination performance of nZVI through sophisticated designed surface coating, as well as fine regulating the environmental behavior of magnetic material via micro-magnetic field.

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.

Constructing Prediction Models for Freezing of Gait by Nomogram and Machine Learning: A Longitudinal Study.

Objectives: Although risk factors for freezing of gait (FOG) have been reported, there are still few prediction models based on cohorts that predict FOG. This 1-year longitudinal study was aimed to identify the clinical measurements closely linked with FOG in Chinese patients with Parkinson's disease (PD) and construct prediction models based on those clinical measurements using Cox regression and machine learning. Methods: The study enrolled 967 PD patients without FOG in the Hoehn and Yahr (H&Y) stage 1-3 at baseline. The development of FOG during follow-up was the end-point. Neurologists trained in movement disorders collected information from the patients on a PD medication regimen and their clinical characteristics. The cohort was assessed on the same clinical scales, and the baseline characteristics were recorded and compared. After the patients were divided into the training set and test set by the stratified random sampling method, prediction models were constructed using Cox regression and random forests (RF). Results: At the end of the study, 26.4% (255/967) of the patients suffered from FOG. Patients with FOG had significantly longer disease duration, greater age at baseline and H&Y stage, lower proportion in Tremor Dominant (TD) subtype, a higher proportion in wearing-off, levodopa equivalent daily dosage (LEDD), usage of L-Dopa and catechol-O-methyltransferase (COMT) inhibitors, a higher score in scales of Unified Parkinson's Disease Rate Scale (UPDRS), 39-item Parkinson's Disease Questionnaire (PDQ-39), Non-Motor Symptoms Scale (NMSS), Hamilton Depression Rating Scale (HDRS)-17, Parkinson's Fatigue Scale (PFS), rapid eye movement sleep behavior disorder questionnaire-Hong Kong (RBDQ-HK), Epworth Sleepiness Scale (ESS), and a lower score in scales of Parkinson's Disease Sleep Scale (PDSS) (P < 0.05). The risk factors associated with FOG included PD onset not being under the age of 50 years, a lower degree of tremor symptom, impaired activities of daily living (ADL), UPDRS item 30 posture instability, unexplained weight loss, and a higher degree of fatigue. The concordance index (C-index) was 0.68 for the training set (for internal validation) and 0.71 for the test set (for external validation) of the nomogram prediction model, which showed a good predictive ability for patients in different survival times. The RF model also performed well, the C-index was 0.74 for the test set, and the AUC was 0.74. Conclusions: The study found some new risk factors associated with the FOG including a lower degree of tremor symptom, unexplained weight loss, and a higher degree of fatigue through a longitudinal study, and constructed relatively acceptable prediction models.

Pretreatment of cardiac progenitor cells with bradykinin attenuates H2O2-induced cell apoptosis and improves cardiac function in rats by regulating autophagy.

BACKGROUND: Previous studies have demonstrated that human cardiac c-Kit+ progenitor cells (hCPCs) can effectively improve ischemic heart disease. However, the major challenge in applying hCPCs to clinical therapy is the low survival rate of graft hCPCs in the host heart, which limited the benefit of transplanted hCPCs. Bradykinin (BK) is a principal active agent of the tissue kinin-kallikrein system. Our previous studies have highlighted that BK mediated the growth and migration of CPCs by regulating Ca2+ influx. However, the protective effect of BK on CPCs, improvement in the survival rate of BK-pretreated hCPCs in the infarcted heart, and the related mechanism remain elusive. METHODS: HCPCs were treated with H2O2 to induce cell apoptosis and autophagy, and different concentration of BK was applied to rescue the H2O2-induced injury detected by MTT assay, TUNEL staining, flow cytometry, western blotting, and mitoSOX assays. The role of autophagy in the anti-apoptotic effect of BK was chemically activated or inhibited using the autophagy inducer, rapamycin, or the inhibitor, 3-methyladenine (3-MA). To explore the protective effect of BK on hCPCs, 3-MA or BK-pretreated hCPCs were transplanted into the myocardial infarcted rats. An echocardiogram was used to determine cardiac function, H&E and Masson staining were employed to assess pathological characteristics, HLA gene expression was quantified by qRT-PCR, and immunostaining was applied to examine neovascularization using confocal microscopy. RESULTS: The in vitro results showed that BK suppressed H2O2-induced hCPCs apoptosis and ROS production in a concentration-dependent manner by promoting pAkt and Bcl-2 expression and reducing cleaved caspase 3 and Bax expression. Moreover, BK restrained the H2O2-induced cell autophagy by decreasing LC3II/I, Beclin1, and ATG5 expression and increasing P62 expression. In the in vivo experiment, the transplanted BK- or 3-MA-treated hCPCs were found to be more effectively improved cardiac function by decreasing cardiomyocyte apoptosis, inflammatory infiltration, and myocardial fibrosis, and promoting neovascularization in the infarcted heart, compared to untreated-hCPCs or c-kit- cardiomyocytes (CPC- cells). CONCLUSIONS: Our present study established a new method to rescue transplanted hCPCs in the infarcted cardiac area via regulating cell apoptosis and autophagy of hCPCs by pretreatment with BK, providing a new therapeutic option for heart failure.

[Distribution of Heavy Metals and Their Corresponding Nanoparticles in Different Treatment Unit Processes in the Sewage Treatment Plant].

Total heavy metal concentration, heavy metal nanoparticle concentration, particle size, and the removal effect of different treatment unit processes on heavy metals and heavy metal nanoparticles were analyzed in this study. Inductively coupled plasma mass spectrometry (ICP-MS) and single particle inductively coupled plasma mass spectrometry (SP-ICP-MS) were applied in nine treatment units performing continuous wastewater treatment processes in the Chengdu Shuangliu International Airport sewage treatment plant. Results showed that different treatment unit processes had different effects on the removal of different total heavy metal elements, with the effects on Fe being the most significant; Fe was mainly removed in the secondary sedimentation tank at a rate of 98.53%. The removal effects of different heavy metal nanoparticles varied in different treatment unit processes, with the effects of Ni, Pd, and Fe being the most significant. Heavy metal nanoparticles removal varied by treatment unit processes (aeration grit tank, secondary sedimentation tank, and high-efficiency sedimentation tank). The particle size distribution of heavy metal nanoparticles in different treatment unit processes was 23.28-147.83 nm, and different treatment unit processes did not have a significant impact on the particle size of each heavy metal nanoparticle. In addition, pH exhibited a significant negative correlation with Fe and Fe nanoparticles. Excluding Fe and Fe nanoparticles, other heavy metals and their nanoparticles were not significantly related; thus, different processing unit processes exhibited different removal mechanisms for heavy metals and their corresponding nanoparticles.

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.

Identification of polystyrene nanoplastics using surface enhanced Raman spectroscopy.

There is clear evidence that micro- and nanoplastics are accumulating in the environment, and their increasing concern of potential harm to wildlife has been identified as a major global issue. However, identification of nanoplastics in environmental samples remains a great challenge, and thus highlighting the great need for new approach. Herein, for the first time, we show that surface enhanced Raman spectroscopy (SERS) offered a feasible approach to identify trace polystyrene (PS) nanoplastics, which is the most produced nanoplastics and also widely presented in the natural environment. We found that when PS nanoplastics were surrounded by SERS-active silver nanoparticles (AgNPs), a set of Raman spectra with chemical information could be obtained via SERS mapping. This map showed the potential PS distribution of the nanoplastics on a silicon wafer, allowing a quick and detailed analysis of the nanoplastics. Moreover, the proposed method was able to identify previously undetectable plastic particles as small as ~50 nm spiked in real water, demonstrating the power of SERS to probe nanoplastics. Our work is thus an important step in nanoplastic research, and we believe that this approach can be further developed to study the occurrence, formation, and transports of nanoplastics in the natural environment.

The Roles of Insulin-Like Growth Factor Binding Protein Family in Development and Diseases.

The insulin-like growth factor (IGF) system comprises ligands of IGF-I/II, IGF receptors (IGFR), IGF binding proteins (IGFBPs), and IGFBP hydrolases. The IGF system plays multiple roles during various disease development as IGFs are widely involved in cell proliferation and differentiation through regulating DNA transcription. Meanwhile, IGFBPs, which are mainly synthesized in the liver, can bind to IGFs and perform two different functions: either inhibition of IGFs by forming inactive compounds with IGF or enhancement of the function of IGFs by strengthening the IGF-IGFR interaction. Interestingly, IGFBPs may have wider functions through IGF-independent mechanisms. Studies have shown that IGFBPs play important roles in cardiovascular disease, tumor progression, fetal growth, and neuro-nutrition. In this review, we emphasize that different IGFBP family members have common or unique functions in numerous diseases; moreover, IGFBPs may serve as biomarkers for disease diagnosis and prediction.

Different iron deposition patterns in akinetic/rigid-dominant and tremor-dominant Parkinson's disease.

OBJECTIVE: The loss of dopaminergic cells and excessive iron deposition in some deep brain nuclei are associated with the pathophysiology of PD, and different clinical subtypes may indicate different pathological processes. This study was designed to investigate the relationships between regional iron in the cardinal subcortical nuclei and different clinical subtypes. PATIENTS AND METHODS: Nine Arkinetic/Rigid-dominant Parkinson's disease (PDAR) patients, eight Tremor-dominant (PDTD)patients and 10 matched healthy controls were recruited for this study. The iron content in 8 cardinal subcortical nuclei was measured through SWI sequence scanning (3.0 T), and different patterns of iron deposition were analyzed not only between the PD patients and HC groups but also between the different clinical subtypes. RESULTS: Compared with the healthy controls, the iron content in the substantia nigra pars compacta(SNc), substantia nigra pars reticulata(SNr) from both the severe and milder side in PD groups were significantly increased (P < 0.01 and P < 0.02 for SNc; both P < 0.01 for SNr), and the iron content in the GP of both the severe and milder side of the PDAR patients was significantly increased compared with the PDTD patients (P < 0.01 and P = 0.02, respectively) CONCLUSION: SWI is a very good technique for the in vivo assessment of subcortical nucleus iron content, and abnormal deposition of iron in the SNc and SNr is an obvious characteristic in PD patients. Furthermore, our data indicates that PDAR patients have higher iron content in the GP than PDTD patients and HCs, indicating that abnormal iron deposition in GP is related to the phenotype of Akinetic/Rigid in PD patients.

[A Case of Acute Aortic Dissection Following Intrapartum in a Patient with Marfan ' s Syndrome].

A 33-year-old woman was admitted at 34 +4 weeks after embryo transfer and over 5 d of cutaneous pruritus. Over 2 years ago, the patient had a third-generation test tube baby due to Marfan's syndrome and gave birth to a live baby girl at full term. This time, the glucose tolerance test during the prenatal examination indicated that the patient was with gestational diabetes, and the blood glucose fluctuated within the normal range after the medical nutrition management and exercise control. The heart ultrasound examination during pregnancy showed that the aortic sinus was enlarged to 40 mm, and the left ventricular systolic function was normal. The patient was diagnosed as "intrahepatic cholestasis of pregnancy (mild)". After admission, the gestational age was verified to be 37 +2 weeks according to the time of embryo transfer, and the diagnostic result was modified to be intrahepatic cholestasis of pregnancy (severe). During the test, the patient complainted back pain, which might interpreted as a sign of aortic dissection. Cesarean section was carried out under multidisciplinary cooperation, during which the amount of bleeding was 600 mL, bilateral uterine artery ligation was performed and a live baby boy was delivered. The body mass of the baby was 3 020 g, and the Apgar scores (1-5-10 min after delivery) were 10-10-10. The postoperative CT angiography showed aortic dissection (Type B). It was found in the follow-up that the patient had no discomforts such as chest tightness and shortness of breath, and recovered well after the delivery.

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.

Mutation analysis of CAPN1 in Chinese populations with spastic paraplegia and related neurodegenerative diseases.

BACKGROUND: Mutations in CAPN1 have recently been reported to cause the spastic paraplegia 76 (SPG76) subtype of hereditary spastic paraplegia (HSP). To investigate the role of CAPN1 in spastic paraplegia and other neurodegenerative diseases, including spinocerebellar ataxia (SCA), early-onset Parkinson's disease (EOPD), and amyotrophic lateral sclerosis (ALS) we conducted a mutation analysis of CAPN1 in a cohort of Chinese patients with SPG, SCA, EOPD, and ALS. METHODS: Variants of CAPN1 were detected in the three cohorts by Sanger or whole-exome sequencing, and all exons and exon-intron boundaries of CAPN1 were analysed. RESULTS: A novel CAPN1 splicing variant (NM_001198868: c.338-1G > A) identified in a familial SPG/SCA showed a complex phenotype, including spastic paraplegia, ataxia, and extensor plantar response. This mutation was confirmed by Sanger sequencing and completely co-segregated with the phenotypes. Sequencing of the cDNA from the three affected patients detected a guanine deletion (c.340_340delG) that was predicted to result in an early stop codon after 61 amino acids (p. D114Tfs*62). No CAPN1 pathogenic mutation was found in the EOPD or ALS groups. CONCLUSION: Our data reveal a novel CAPN1 mutation found in patients with SPG/SCA and emphasize the spastic and ataxic phenotypes of SPG76, but CAPN1 may not play a major role in EOPD and ALS.

Cloud-Point Extraction Combined with Thermal Degradation for Nanoplastic Analysis Using Pyrolysis Gas Chromatography-Mass Spectrometry.

The contamination of micro- and nanoplastics in marine systems and freshwater is a global issue. Determination of micro- and nanoplastics in the aqueous environment is of high priority to fully assess the risk that plastic particles will pose. Although microplastics have been detected in a variety of aquatic ecosystems, the analysis of nanoplastics remains an unsolved challenge. Herein, for the first time, a Triton X-45 (TX-45)-based cloud-point extraction (CPE) was proposed to preconcentrate trace nanoplastics in environmental waters. Under the optimum extraction conditions, an enrichment factor of 500 was obtained for two types of nanoplastics with different compositions, polystyrene (PS) and poly(methyl methacrylate) (PMMA), without disturbing their original morphology and sizes. Additionally, following thermal treatment at 190 °C for 3 h, the CPE-obtained extract could be submitted to pyrolysis gas chromatography-mass spectrometry (Py-GC/MS) analysis for mass quantification of nanoplastics. Taking 66.2 nm PS nanoplastics and 86.2 nm PMMA nanoplastics as examples, the proposed method showed excellent reproducibility, and high sensitivity with respective detection limits of 11.5 and 2.5 fM. Feasibility of the proposed approach was verified by application of the optimized procedure to four real water samples. Recoveries of 84.6-96.6% at a spiked level of 88.6 fM for PS nanoplastics and 76.5-96.6% at a spiked level of 50.4 fM for PMMA nanoplastics were obtained. Consequently, this work provides an efficient approach for nanoplastic analysis in environmental waters.

Polyvinylidene Fluoride Micropore Membranes as Solid-Phase Extraction Disk for Preconcentration of Nanoparticulate Silver in Environmental Waters.

Efficient separation and preconcentration of trace nanoparticulate silver (NAg) from large-volume environmental waters is a prerequisite for reliable analysis and therefore understanding the environmental processes of silver nanoparticles (AgNPs). Herein, we report the novel use of polyvinylidene fluoride (PVDF) filter membrane for disk-based solid phase extraction (SPE) of NAg in 1 L of water samples with the disk-based SPE system, which consists of a syringe pump and a syringe filter holder to embed the filter membrane. While the PVDF membrane can selectively adsorb NAg in the presence of Ag+, aqueous solution of 2% (m/v) FL-70 is found to efficiently elute NAg. Analysis of NAg is performed following optimization of filter membrane and elution conditions with an enrichment factor of 1000. Additionally, transmission electron microscopy (TEM), UV-vis spectroscopy, and size-exclusion chromatography coupled with ICP-MS (SEC-ICP-MS) analysis showed that the extraction gives rise to no change in NAg size or shape, making this method attractive for practical applications. Furthermore, feasibility of the protocol is verified by applying it to extract NAg in four real waters with recoveries of 62.2-80.2% at 0.056-0.58 µg/L spiked levels. This work will facilitate robust studies of trace NAg transformation and their hazard assessments in the environment.