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1.
Sci Total Environ ; 934: 173368, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38777064

RESUMO

Perfluorooctanoic acid (PFOA) is a persistent compound, raising considerable global apprehension due to its resistance to breakdown and detrimental impacts on human health and aquatic environments. Pressure-driven membrane technologies treating PFAS-contaminated water are expensive and prone to fouling. This study presented a parametric investigation of the effectiveness of cellulose triacetate membrane in the forward osmosis (FO) membrane for removing PFOA from an aqueous solution. The study examined the influence of membrane orientation modes, feed pH, draw solution composition and concentration, and PFOA concentration on the performance of FO. The experimental results demonstrated that PFOA rejection was 99 % with MgCl2 and slightly >98 % with NaCl draw solutions due to the mechanism of PFOA binding to the membrane surface through Mg2+ ions. This finding highlights the crucial role of the draw solution's composition in PFOA treatment. Laboratory results revealed that membrane rejection of PFOA was 99 % at neutral and acidic pH levels but decreased to 95 % in an alkaline solution at pH 9. The decrease in membrane rejection is attributed to the dissociation of the membrane's functional groups, consequently causing pore swelling. The results were confirmed by calculating the average pore radius of the CTA membrane, which increased from 27.94 nm at pH 5 to 30.70 nm at pH 9. Also, variations in the PFOA concentration from 5 to 100 mg/L did not significantly impact the membrane rejection, indicating the process's capability to handle a wide range of PFOA concentrations. When seawater was the draw solution, the FO membrane rejected 99 % of PFOA concentrations ranging from 5 mg/L to 100 mg/L. The CTA FO treating PFOA-contaminated wastewater from soil remediation achieved a 90 % recovery rate and water flux recovery of 96.5 % after cleaning with DI water at 40 °C, followed by osmotic backwash. The results suggest the potential of using abundant and cost-effective natural solutions in the FO process, all without evident membrane fouling.

2.
Sci Total Environ ; 930: 172516, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38636874

RESUMO

The electrokinetic process has been proposed for in-situ soil remediation to minimize excavation work and exposure to hazardous materials. The precipitation of heavy metals in alkaline pH near the cathode is still challenging. Reactive filter media and enhancement agents have been used in electrokinetics to enhance the removal of heavy metals. This study investigated coupling industrial iron slag waste and iron slag-activated carbon reactive filter media with electrokinetic for a single and mixture of heavy metals treatment. Instead of using acid enhancement agents, the anolyte solution was recycled to neutralize the alkaline front at the cathode, reducing the operation cost and chemical use. Experiments were conducted for 2 and 3 weeks at 20 mA electric current. Copper removal increased from 3.11 % to 23 % when iron slag reactive filter media was coupled with electrokinetic. Copper removal increased to 70.14 % in the electrokinetic experiment with iron slag-activated carbon reactive filter media. The copper removal increased to 89.21 % when the anolyte solution was recycled to the cathode compartment. Copper removal reached 93.45 % when the reactive filter media-electrokinetic process with anolyte recirculation was extended to 3 weeks. The reactive filter media- an electrokinetic process with anolyte recycling was evaluated for removing copper, nickel, and zinc mixture, and results revealed 81.1 % copper removal, 89.04 % nickel removal, and 92.31 % zinc removal in a 3-week experiment. The greater nickel and zinc removal is attributed to their higher solubility than copper. The results demonstrated the cost-effectiveness and efficiency of the electrokinetic with iron slag-activated carbon reactive filter media with anolyte recirculation for soil remediation from heavy metals.

3.
Environ Pollut ; 346: 123637, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38408507

RESUMO

Widespread contamination by heavy metals (HMs) and dyes poses a major health risk to people and ecosystems requiring effective treatment. In this work, rice husk (RH) and shrimp shells were extracted to obtain amorphous silica and chitosan, respectively, which were utilized to produce nano-chitosan-coated silica (NCCS). To ensure the stability of the nanoparticles, silica was freeze-dried after being coated with nano-chitosan. Functional groups (-NH2, -OH, P]O) from chitosan nanoparticles (CNPs) were introduced to the surface of silica during this process. Dyes such as brilliant green (BG), methylene blue (MB) and reactive brown (RB) as well as HMs (Cr6+, Pb2+, Cd2+, Ni2+) were removed by adsorbents. CNPs showed the highest adsorption capacity for RB (59.52 mg/g) among dyes and Cr6+ (42.55 mg/g) among HMs. CNPs showed the highest adsorption capacity for HMs among different adsorbents. Although NCCS and CNPs showed similar adsorption capabilities for HMs and dyes, NCCS showed the best stability. The adsorption performance decreased as RB > Cr6+ > MB > BG > Pb2+ > Cd2+ > Ni2+. The adsorption reactions followed both pseudo-first-order and second-order kinetics, and was spontaneous from thermodynamic analysis. In summary, the waste-derived adsorbents demonstrated excellent potential for removing HMs and dyes from water, while supporting effective management solid waste.


Assuntos
Quitosana , Metais Pesados , Oryza , Poluentes Químicos da Água , Humanos , Cádmio , Corantes , Água , Ecossistema , Chumbo , Dióxido de Silício , Adsorção , Cinética , Concentração de Íons de Hidrogênio
5.
Nanomaterials (Basel) ; 14(2)2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38251100

RESUMO

Pharmaceuticals are widely used and often discharged without metabolism into the aquatic systems. The photocatalytic degradation of pharmaceutical compounds propranolol, mebeverine, and carbamazepine was studied using different titanium dioxide nanostructures suspended in water under UV and UV-visible irradiation. Among three different photocatalysts, the degradation was most effective by using Degussa P25 TiO2, followed by Hombikat UV100 and Aldrich TiO2. The photocatalytic performance was dependent on photocatalyst dosage, with an optimum concentration of 150 mg L-1. The natural aquatic colloids were shown to enhance the extent of photocatalysis, and the effect was correlated with their aromatic carbon content. In addition, the photocatalysis of pharmaceuticals was enhanced by the presence of nitrate, but inhibited by the presence of 2-propanol, indicating the importance of hydroxyl radicals. Under optimum conditions, the pharmaceuticals were rapidly degraded, with a half-life of 1.9 min, 2.1 min, and 3.2 min for propranolol, mebeverine, and carbamazepine, respectively. In treating sewage effluent samples, the photocatalytic rate constants for propranolol (0.28 min-1), mebeverine (0.21 min-1), and carbamazepine (0.15 min-1) were similar to those in water samples, demonstrating the potential of photocatalysis as a clean technology for the effective removal of pharmaceuticals from sewage effluent.

6.
Mar Environ Res ; 194: 106343, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38215624

RESUMO

The increasing prevalence of microplastic pollution in aquatic environments has raised concerns about its impact on marine life. Among the different types of microplastics, polystyrene microplastics (PSMPs) are one of the most commonly detected in aquatic systems. Chaetoceros neogracile (diatom) is an essential part of the marine food web and plays a critical role in nutrient cycling. This study aimed to monitor the ecotoxicological impact of PSMPs on diatoms and observe enzymatic interactions through molecular docking simulations. Results showed that diatom growth decreased with increasing concentrations and exposure time to PSMPs, and the lowest photosynthetic efficiency (Fv/Fm) value was observed after 72 and 96 h of exposure to 200 mg L-1 of PSMPs. High concentrations of PSMPs led to a decrease in chlorophyll a content (up to 64.4%) and protein content (up to 35.5%). Molecular docking simulations revealed potential interactions between PSMPs and the extrinsic protein in photosystem II protein of diatoms, suggesting a strong affinity between the two. These findings indicate a detrimental effect of PSMPs on the growth and photosynthetic efficiency of diatoms and highlight the need for further research on the impact of microplastics on marine microbial processes.


Assuntos
Diatomáceas , Poluentes Químicos da Água , Microplásticos/toxicidade , Poliestirenos/toxicidade , Plásticos/toxicidade , Clorofila A , Simulação de Acoplamento Molecular , Poluentes Químicos da Água/metabolismo
7.
J Hazard Mater ; 465: 133419, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38183942

RESUMO

The reclamation and reuse of electrolytic manganese residue (EMR) as a bulk hazard solid waste are limited by its residual ammonia nitrogen (NH4+-N) and manganese (Mn2+). This work adopts a co-processing strategy comprising air-jet milling (AJM) and horizontal-shaking leaching (HSL) for refining and leaching disposal of NH4+-N and Mn2+ in EMR. Results indicate that the co-use of AJM and HSL could significantly enhance the leaching of NH4+-N and Mn2+ in EMR. Under optimal milling conditions (50 Hz frequency, 10 min milling time, 12 h oscillation time, 400 rpm rate, 30 â„ƒ temperature, and solid-to-liquid ratio of 1:30), NH4+-N and Mn2+ leaching efficiencies were optimized to 96.73% and 97.35%, respectively, while the fineness of EMR was refined to 1.78 µm. The leaching efficiencies of NH4+-N and Mn2+ were 58.83% and 46.96% higher than those attained without AJM processing. The AJM used strong airflow to give necessary kinetic energy to EMR particles, which then collided and sifted to become refined particles. The AJM disposal converted kinetic energy into heat energy upon particle collisions, causing EMR phase transformation, and particularly hydrated sulfate dehydration. The work provides a fire-new and high-efficiency method for significantly and simply leaching NH4+-N and Mn2+ from EMR.

8.
Environ Pollut ; 341: 122889, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37972679

RESUMO

Emerging contaminants (ECs) are increasingly recognized as threats to human health and ecosystems. This review evaluates advanced analytical methods, particularly mass spectrometry, for detecting ECs and understanding their toxicity, transformation pathways, and environmental distribution. Our findings underscore the reliability of current techniques and the potential of upcoming methods. The adverse effects of ECs on aquatic life necessitate both in vitro and in vivo toxicity assessments. Evaluating the distribution and degradation of ECs reveals that they undergo physical, chemical, and biological transformations. Remediation strategies such as advanced oxidation, adsorption, and membrane bioreactors effectively treat EC-contaminated waters, with combinations of these techniques showing the highest efficacy. To minimize the impact of ECs, a proactive approach involving monitoring, regulations, and public education is vital. Future research should prioritize the refining of detection methods and formulation of robust policies for EC management.


Assuntos
Ecossistema , Poluentes Químicos da Água , Humanos , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Reprodutibilidade dos Testes , Poluição da Água
9.
Sci Total Environ ; 912: 169224, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38101639

RESUMO

Water pollution by pathogenic bacteria and organic dyes poses potential health hazards for human and aquatic life. This study aims to explore the potential of bioactive compounds extracted from two microalgae species (Spirogyra and Ocillatoria) for water pollution control. The optimization of the extraction process for bioactive compounds resulted in the highest yield at 25 min for Spirogyra and 30 min for Ocillatotia species. Further, the extracted bioactive compounds were analyzed using Fourier transform infrared spectroscopy (FTIR) and gas chromatography-mass spectroscopy (GC-MS). The bioactive compounds exhibited significant antibacterial activity against gram-positive and gram-negative bacteria. Notably, Spirogyra species exhibited a higher zone of inhibition (19.5-20.7 mm) than Ocillatoria species (17.0-18.0 mm) against both gram-positive and gram-negative bacterial strains. Furthermore, the photocatalytic potential of these bioactive compounds was examined by assessing the photodegradation of methylene blue (MB) and crystal violet (CV) dyes under different light sources. The findings revealed that Spirogyra species exhibited better photocatalytic activity than Ocillatoria species for MB and CV. For MB, 89.75 %, 77.82 % and 63.54 % were photodegraded when exposed to UV light, sunlight and visible light using Spirogyra extract, compared to 84.90 %, 74.70 % and 58.30 % by Ocillatoria extract. Regarding CV, Spirogyra extract achieved photodegradation efficiency of 88.94 %, 76.59 % and 64.50 % under UV light, sunlight and visible light, higher than 83.60 %, 73.60 % and 57.70 % by Ocillatoria extract. Both Spirogyra and Ocillatoria species demonstrated the best performance for dye photodegradation under UV irradiation, demonstrating great potential for nature-based water treatment.


Assuntos
Microalgas , Spirogyra , Humanos , Antibacterianos/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Azul de Metileno/química , Corantes , Catálise
10.
J Hazard Mater ; 464: 132894, 2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-37952337

RESUMO

Antibiotics are extensively used for health protection and food production, causing antibiotic pollution in the aquatic environment. This study aims to determine the bioavailability and bioaccumulation of typical antibiotics sulfamethoxazole (SMX) and roxithromycin (RTM) in zebrafish under environmentally realistic conditions. Four different microcosms, i.e. water, water-sediment, water-zebrafish, and water-sediment-zebrafish were constructed, with three replicates in parallel. The concentrations of SMX and RTM in water, sediment and zebrafish were extracted and analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to assess their kinetic behavior and bioavailability. In the water-sediment system, the dissolved concentration of both SMX and RTM decreased with time following the first-order kinetic while their adsorption by sediment increased with time. In the water-zebrafish system, SMX and RTM bioaccumulation was increasing with time following the pseudo second-order kinetics. RTM bioaccumulation in zebrafish (up to 16.4 ng/g) was an order of magnitude higher than SMX (up to 5.2 ng/g), likely due to RTM being more hydrophobic than SMX. In addition, the bioaccumulation factor (BAF) value of SMX in zebrafish was greater than its sediment partition coefficient, while the opposite trend was observed for RTM, demonstrating the importance of antibiotics properties in affecting their bioavailability. Furthermore, increasing dissolved organic carbon concentration in water reduced SMX bioaccumulation, but increased RTM bioaccumulation at the same time. The findings are important in future studies of environmental fate and bioavailability of toxic chemicals with different pollution sources and physicochemical properties.


Assuntos
Roxitromicina , Sulfametoxazol , Animais , Sulfametoxazol/análise , Peixe-Zebra , Água/química , Adsorção , Bioacumulação , Espectrometria de Massas em Tandem , Sedimentos Geológicos/química , Antibacterianos/análise
11.
Sci Total Environ ; 912: 169319, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38110094

RESUMO

The swift growth of cities worldwide poses significant challenges in ensuring a sufficient water, energy, and food supply. The Nexus has innovated valuable systems to address these challenges. However, a crucial issue is the potential for pollution resulting from these systems, which directly and indirectly impacts public health and the overall quality of urban living. This study comprehensively reviews the interconnected challenges of the water-energy-food (WEF) nexus and various forms of pollution in cities. The primary focus of this review article is to showcase the findings of WEF nexus studies regarding various pollutions across different geographical regions and spatial scales. It aims to examine the problems resulting from these pollutions, specifically their effects on human health and urban life. It also delves into the sources of pollution as identified in these studies. Furthermore, the article will highlight the proposed solutions from the research aimed at effectively mitigating pollution in each sector studied. This article is a systematic review which analyses research sources from the Scopus database. It extensively reviewed 2463 peer-reviewed published articles and focused explicitly on articles related to the WEF nexus that discussed pollution. Our study emphasizes, firstly, raising awareness about the crucial link between the WEF nexus, pollution, urban environments, and human health among policymakers and key stakeholders, including urban planners, industry partners and municipalities. This is to promote the development of policies that encourage sustainable practices and key stakeholders. Secondly, it evaluates WEF nexus and pollution research methods and findings, aiding in identifying research gaps technological innovation and potential, as well as enhancing decision-making. Lastly, it outlines future research challenges, providing a roadmap for researchers and policymakers to advance understanding in this domain and identify opportunities for resource efficiency and collaboration between different sectors.

12.
J Hazard Mater ; 460: 132360, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37657326

RESUMO

The efficacy of the Standalone Electrokinetic (EK) process in soil PFAS removal is negligible, primarily due to the intersecting mechanisms of electromigration and electroosmosis transportation. Consequently, the redistribution of PFAS across the soil matrix occurs, hampering effective remediation efforts. Permeable reactive barrier (PRB) has been used to capture contaminants and extract them at the end of the EK process. This study conducted laboratory-scale tests to evaluate the feasibility of the iron slag PRB enhanced-EK process in conjunction with Sodium Cholate (NaC) biosurfactant as a cost-effective and sustainable method for removing PFOA from the soil. A 2 cm iron slag-based PRB with a pH of 9.5, obtained from the steel-making industry, was strategically embedded in the middle of the EK reactors to capture PFOA within the soil. The main component of the slag, iron oxide, exhibited significant adsorption capacity for PFOA contamination. The laboratory-scale tests were conducted over two weeks, revealing a PFOA removal rate of more than 79% in the slag/activated carbon PRB-EK test with NaC enhancement and 70% PFOA removal in the slag/activated carbon PRB-EK without NaC. By extending the duration of the slag/AC PRB-EK test with NaC enhancement to three weeks, the PFOA removal rate increased to 94.09%, with the slag/AC PRB capturing over 87% of the initial PFOA concentration of 10 mg/L. The specific energy required for soil decontamination by the EK process was determined to be 0.15 kWh/kg. The outcomes of this study confirm the feasibility of utilizing iron slag waste in the EK process to capture PFOA contaminants, offering a sustainable approach to soil decontamination. Combining iron slag PRB and NaC biosurfactant provides a cost-effective and environmentally friendly method for efficient PFOA removal from soil.

13.
J Neurosci ; 43(35): 6197-6211, 2023 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-37536983

RESUMO

Alzheimer's disease (AD) increases the risk for seizures and sleep disorders. We show here that germline deletion of ß-site amyloid precursor protein (APP) cleaving enzyme-1 (BACE1) in neurons, but not in astrocytes, increased epileptiform activity. However, Bace1 deletion at adult ages did not alter the normal EEG waveform, indicating less concern for BACE1 inhibition in patients. Moreover, we showed that deletion of Bace1 in the adult was able to reverse epileptiform activity in 5xFAD mice. Intriguingly, treating 5xFAD and APPNL-G-F/NL-G-F (APP KI) mice of either sex with one BACE1 inhibitor Lanabecestat (AZD3293) dramatically increased epileptiform spiking, likely resulting from an off-target effect. We also monitored sleep-wake pathologies in these mice and showed increased wakefulness, decreased non-rapid eye movement sleep, and rapid eye movement sleep in both 5xFAD and APP KI mice; BACE1 inhibition in the adult 5xFAD mice reversed plaque load and sleep disturbances, but this was not seen in APP KI mice. Further studies with and without BACE1 inhibitor treatment showed different levels of plaque-associated microgliosis and activated microglial proteins in 5xFAD mice compared with APP KI mice. Together, BACE1 inhibition should be developed to avoid off-target effect for achieving benefits in reducing epileptic activity and sleep disturbance in Alzheimer's patients.SIGNIFICANCE STATEMENT BACE1 is widely recognized as a therapeutic target for treating Alzheimer's disease patients. However, BACE1 inhibitors failed in clinical trials because of inability to show cognitive improvement in patients. Here we show that BACE1 inhibition actually reduces sleep disturbances and epileptic seizures; both are seen in AD patients. We further showed that one of clinically tested BACE1 inhibitors does have off-target effects, and development of safer BACE1 inhibitors will be beneficial to AD patients. Results from this study will provide useful guidance for additional drug development.


Assuntos
Doença de Alzheimer , Transtornos do Sono-Vigília , Camundongos , Animais , Doença de Alzheimer/complicações , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Camundongos Transgênicos , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/genética , Ácido Aspártico Endopeptidases/metabolismo , Placa Amiloide , Convulsões , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/genética , Sono , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Modelos Animais de Doenças
14.
Environ Sci Pollut Res Int ; 30(42): 95810-95827, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37558920

RESUMO

The adsorption process of inorganic arsenic (As) plays an important role in its mobility, bioavailability, and toxicity in the river environment. In this work, the adsorption of dissolved arsenite (As(III)) and arsenate (As(V)) by microplastics (MPs) pellets (polystyrene (PS) and low-density polyethylene (LDPE)), river sediment, and their mixture were investigated to assess the adsorption affinities and mechanism. The adsorption kinetics showed slow and mild rising zones from the natural behavior of the chemical adsorption. The results indicated that both MP characteristics and water properties played a significant role in the adsorption behavior of inorganic As species. The As adsorption equilibrium was modeled well by both Langmuir and Freundlich isotherms and partly fitted with the Sips model suggesting that both mono-layer and multi-layer adsorption occurred during adsorption The spontaneous adsorption process for both As(III) and As(V) was evidenced by the adsorption thermodynamics. The maximum adsorption capacities of As(III) and As(V) reached 143.3 mg/kg and 109.8 mg/kg on PS in deionized water, which were higher than those on sediment-PS mixture (119.3 mg/kg, 99.2 mg/kg), which were all lower than on sediment alone (263.3 mg/kg, 398.7 mg/kg). The Fourier transform infrared spectroscopy analysis identified that As(III) and As(V) interaction with sediment surface functional groups was the main adsorption mechanism from surface complexation and coordination. Two functional groups of polystyrene (-NH2, -OH) were mainly involved in the adsorption of inorganic As species on PS, while -COO- and -OH functional groups contributed to the adsorption mechanism of inorganic As species on LDPE. The findings provide valuable insight on the adsorption behavior and mechanisms of As(III) and As(V) in river systems in the presence of MPs particles. Both PS and LDPE were shown to be less effective than river sediment in the adsorption of As species from water, which provides a different perspective in understanding the scale of MPs impact in pollutant transport in the aquatic environment.


Assuntos
Arsênio , Arsenicais , Poluentes Químicos da Água , Poliestirenos/análise , Arsênio/análise , Polietileno , Plásticos/química , Rios , Adsorção , Poluentes Químicos da Água/análise , Microplásticos/química , Água/análise
15.
Sci Total Environ ; 894: 165049, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37355110

RESUMO

This work presents an innovative approach to developing a low-carbon and hazard-free cementitious material (EGC) by activating ground granulated blast-furnace slag (GGBS) with electrolytic manganese residue (EMR), which has an excellent heavy metal solidified capacity. Herein, the multi-step leaching was creatively conducted to investigate the solidified morphology of heavy metals in hazardous EMR. CO2 emission per unit strength factor was calculated to quantitatively analyze the low-carbon degree. The results show that the added hazardous EMR rich in sulfate and the dilution effect caused by the decrease in GGBS lessen the final setting time and fluidity. Low-temperature calcination (200 °C) alters the dissolution rate of ettringite and AFm-like phases by changing the sulfate crystal. Excessive acidic EMR consumes more calcium hydroxide and lowers the pH of the EGC system, resulting in weakened GGBS activity. The formation of jouravskite, thaumasite, and henritermierite are AFm-like hydrated lamellated structures, which provides evidence for the immobilization of Mn2+ in EMR. Vast Mn2+ are embedded in the main interlayer of [Ca2Al(OH)6]+ by substituting Al to form AFm-like phase. The lowest 60d unit compressive strength carbon emission of the EGC system containing 20 % calcinated EMR is 0.78 kg∙MPa-1∙m-3, meaning the substitution barrier is better addressed by adding calcined EMR. This work provides an innovative solution for high value-added and hazard-free utilization for EMR and carbon reduction in the cement industry.

16.
Front Neurol ; 14: 1135472, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37360342

RESUMO

Objective: Delirium is associated with worse outcomes in patients with stroke and neurocritical illness, but delirium detection in these patients can be challenging with existing screening tools. To address this gap, we aimed to develop and evaluate machine learning models that detect episodes of post-stroke delirium based on data from wearable activity monitors in conjunction with stroke-related clinical features. Design: Prospective observational cohort study. Setting: Neurocritical Care and Stroke Units at an academic medical center. Patients: We recruited 39 patients with moderate-to-severe acute intracerebral hemorrhage (ICH) and hemiparesis over a 1-year period [mean (SD) age 71.3 (12.20), 54% male, median (IQR) initial NIH Stroke Scale 14.5 (6), median (IQR) ICH score 2 (1)]. Measurements and main results: Each patient received daily assessments for delirium by an attending neurologist, while activity data were recorded throughout each patient's hospitalization using wrist-worn actigraph devices (on both paretic and non-paretic arms). We compared the predictive accuracy of Random Forest, SVM and XGBoost machine learning methods in classifying daily delirium status using clinical information alone and combined with actigraph data. Among our study cohort, 85% of patients (n = 33) had at least one delirium episode, while 71% of monitoring days (n = 209) were rated as days with delirium. Clinical information alone had a low accuracy in detecting delirium on a day-to-day basis [accuracy mean (SD) 62% (18%), F1 score mean (SD) 50% (17%)]. Prediction performance improved significantly (p < 0.001) with the addition of actigraph data [accuracy mean (SD) 74% (10%), F1 score 65% (10%)]. Among actigraphy features, night-time actigraph data were especially relevant for classification accuracy. Conclusions: We found that actigraphy in conjunction with machine learning models improves clinical detection of delirium in patients with stroke, thus paving the way to make actigraph-assisted predictions clinically actionable.

17.
Sci Rep ; 13(1): 8011, 2023 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-37198258

RESUMO

Adoptive immune therapies based on the transfer of antigen-specific T cells have been used successfully to treat various cancers and viral infections, but improved techniques are needed to identify optimally protective human T cell receptors (TCRs). Here we present a high-throughput approach to the identification of natively paired human TCRα and TCRß (TCRα:ß) genes encoding heterodimeric TCRs that recognize specific peptide antigens bound to major histocompatibility complex molecules (pMHCs). We first captured and cloned TCRα:ß genes from individual cells, ensuring fidelity using a suppression PCR. We then screened TCRα:ß libraries expressed in an immortalized cell line using peptide-pulsed antigen-presenting cells and sequenced activated clones to identify the cognate TCRs. Our results validated an experimental pipeline that allows large-scale repertoire datasets to be annotated with functional specificity information, facilitating the discovery of therapeutically relevant TCRs.


Assuntos
Receptores de Antígenos de Linfócitos T , Linfócitos T , Humanos , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Clonagem Molecular , Antígenos , Peptídeos/genética
18.
Hum Mol Genet ; 32(16): 2587-2599, 2023 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-37228035

RESUMO

Reticulon (RTN) proteins are a family of proteins biochemically identified for shaping tubular endoplasmic reticulum, a subcellular structure important for vesicular transport and cell-to-cell communication. In our recent study of mice with knockout of both reticulon 1 (Rtn1) and Rtn3, we discovered that Rtn1-/-;Rtn3-/- (brief as R1R3dKO) mice exhibited neonatal lethality, despite the fact that mice deficient in either RTN1 or RTN3 alone exhibit no discernible phenotypes. This has been the first case to find early lethality in animals with deletion of partial members of RTN proteins. The complete penetrance for neonatal lethality can be attributed to multiple defects including the impaired neuromuscular junction found in the diaphragm. We also observed significantly impaired axonal growth in a regional-specific manner, detected by immunohistochemical staining with antibodies to neurofilament light chain and neurofilament medium chain. Ultrastructural examination by electron microscopy revealed a significant reduction in synaptic active zone length in the hippocampus. Mechanistic exploration by unbiased proteomic assays revealed reduction of proteins such as FMR1, Staufen2, Cyfip1, Cullin-4B and PDE2a, which are known components in the fragile X mental retardation pathway. Together, our results reveal that RTN1 and RTN3 are required to orchestrate neurofilament organization and intact synaptic structure of the central nervous system.


Assuntos
Axônios , Citoesqueleto , Hipocampo , Proteínas do Tecido Nervoso , Animais , Camundongos , Genes Letais , Camundongos Knockout , Axônios/metabolismo , Axônios/patologia , Citoesqueleto/metabolismo , Citoesqueleto/patologia , Proteínas do Tecido Nervoso/metabolismo , Retículo Endoplasmático/metabolismo , Sinapses , Hipocampo/metabolismo , Hipocampo/patologia
19.
Mar Pollut Bull ; 192: 115071, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37236097

RESUMO

Phthalic acid esters (PAEs) are known as the most widely used plasticizer as well as one of the ubiquitously distributed emerging pollutants. Biodegradation and bioremediation via application of PAEs-degrading microbes is promising. In this study, a novel marine microbe, Gordonia hongkongensis RL-LY01, was isolated from mangrove sediment showing high di-(2-ethylhexyl) phthalate (DEHP) degradation capacity. Strain RL-LY01 could degrade a wide range of PAEs and the degradation kinetics of DEHP followed the first-order decay model. Meanwhile, good environmental adaptability, preference to alkaline conditions and good tolerance to salinity and metal ions was shown. Further, metabolic pathway of DEHP in strain RL-LY01 was proposed, with di-ethyl phthalate, phthalic acid, benzoic acid and catechol as intermediates. Additionally, one known mono-alkyl phthalate hydrolase gene (mehpH) was identified. Finally, the excellent performance during bioremediation of artificial DEHP-contaminated saline soil and sediment indicated strain RL-LY01 employs great application potential for the bioremediation of PAE-contaminated environments.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , Biodegradação Ambiental , Solo , Ésteres , Dibutilftalato
20.
Mol Neurodegener ; 18(1): 31, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-37143090

RESUMO

BACKGROUND: Abnormal accumulation of amyloid beta peptide (Aß) in the brain induces a cascade of pathological changes in Alzheimer's disease (AD), and inhibiting BACE1, which is required for Aß generation, is therefore being explored for the treatment of AD by reducing Aß accumulation. As Bace1 knockout mice exhibit increased number of reactive astrocytes and AD brains have reactive astrocytes that surround amyloid plaques, we investigated the role of BACE1 in astrocytes and determined whether BACE1 regulates astrocytic functions. METHODS: We conducted unbiased single cell RNA-seq (scRNA-seq) using purified astrocytes from Bace1 KO mice and wild type control littermates. Similar scRNA-seq was also conducted using AD mice with conditional deletion of Bace1 in the adult stage (5xFAD;Bace1fl/fl;UBC-creER compared to 5xFAD;Bace1fl/fl controls). We compared the transcriptomes of astrocyte and reactive astrocyte clusters and identified several differentially expressed genes, which were further validated using Bace1 KO astrocyte cultures. Mice with astrocyte-specific Bace1 knockout in 5xFAD background were used to compare amyloid deposition. Mechanistic studies using cultured astrocytes were used to identify BACE1 substrates for changes in gene expression and signaling activity. RESULTS: Among altered genes, Clusterin (Clu) and Cxcl14 were significantly upregulated and validated by measuring protein levels. Moreover, BACE1 deficiency enhanced both astrocytic Aß uptake and degradation, and this effect was significantly attenuated by siRNA knockdown of Clu. Mechanistic study suggests that BACE1 deficiency abolishes cleavage of astrocytic insulin receptors (IR), and this may enhance expression of Clu and Cxcl14. Acutely isolated astrocytes from astrocyte-specific knockout of Bace1 mice (Bace1 fl/fl;Gfap-cre) show similar increases in CLU and IR. Furthermore, astrocyte-specific knockout of Bace1 in a 5xFAD background resulted in a significant attenuation in cortical Aß plaque load through enhanced clearance. CONCLUSION: Together, our study suggests that BACE1 in astrocytes regulates expression of Clu and Cxcl14, likely via the control of insulin receptor pathway, and inhibition of astrocytic BACE1 is a potential alternative strategy for enhancing Aß clearance.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Animais , Camundongos , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Astrócitos/metabolismo , Clusterina/metabolismo , Camundongos Knockout , Camundongos Transgênicos
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