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1.
J Environ Manage ; 352: 120051, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38262282

RESUMO

With the rapid growth of the metallurgical industry, there is a significant increase in the production of metallurgical slags. The waste slags pose significant challenges for their disposal because of complex compositions, low utilization rates, and environmental toxicity. One promising approach is to utilize metallurgical slags as catalysts for treatment of refractory organic pollutants in wastewater through advanced oxidation processes (AOPs), achieving the objective of "treating waste with waste". This work provides a literature review of the source, production, and chemical composition of metallurgical slags, including steel slag, copper slag, electrolytic manganese residue, and red mud. It emphasizes the modification methods of metallurgical slags as catalysts and the application in AOPs for degradation of refractory organic pollutants. The reaction conditions, catalytic performance, and degradation mechanisms of organic pollutants using metallurgical slags are summarized. Studies have proved the feasibility of using metallurgical slags as catalysts for removing various pollutants by AOPs. The catalytic performance was significantly influenced by slags-derived catalysts, catalyst modification, and process factors. Future research should focus on addressing the safety and stability of catalysts, developing green and efficient modification methods, enhancing degradation efficiency, and implementing large-scale treatment of real wastewater. This work offers insights into the resource utilization of metallurgical slags and pollutant degradation in wastewater.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Águas Residuárias , Cobre , Substâncias Perigosas , Metalurgia , Oxirredução , Poluentes Químicos da Água/análise
2.
Molecules ; 29(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38338332

RESUMO

In total, three related substances (RS) associated with sotalol hydrochloride (STHCl) were herein identified with a novel gradient high-performance liquid chromatography (HPLC) protocol. Further characterization of these substances was then performed via liquid chromatography-mass spectroscopy (LC-MS/MS) and nuclear magnetic resonance (NMR) approaches. For these analyses, commercial STHCl samples were used for quantitative HPLC studies and the degradation of STHCl under acidic (1M HCl), alkaline (1M NaOH), oxidative (30% H2O2), photolytic (4500 Lx), and thermal stress conditions (100 °C) was assessed. This approach revealed this drug to be resistant to acidic, alkaline, and high-temperature conditions, whereas it was susceptible to light and oxidation as confirmed through long-term experiments. The putative mechanisms governing RS formation were also explored, revealing that RS3 was derived from the manufacturing process, whereas RS2 was generated via oxidation and RS1 was generated in response to light exposure. The cytotoxicity of these RS compounds was then assessed using MTT assays and acute toxicity test. Overall, this study provides details regarding the characterization, isolation, quantification, and toxicological evaluation of STHCl and associated RS compounds together with details regarding the precise, specific, and reliable novel HPLC technique, thus providing the requisite information necessary to ensure STHCl purity and safety.


Assuntos
Sotalol , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Sotalol/farmacologia , Espectrometria de Massas em Tandem/métodos , Peróxido de Hidrogênio , Espectrometria de Massa com Cromatografia Líquida , Estabilidade de Medicamentos , Hidrólise , Oxirredução , Fotólise
3.
Appl Microbiol Biotechnol ; 107(9): 3033-3045, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36995383

RESUMO

Parkinson's disease (PD), a progressive and incurable neurodegenerative disease, has taken a huge economic toll and medical burden on our society. Increasing evidence has shown a strong link between PD and the gut microbiome, but studies on the relationship between the gut microbiome and the severity of PD are limited. In this study, 90 fecal samples were collected from newly diagnosed and untreated patients with PD (n = 47) and matched healthy control subjects (n = 43). The 16S rRNA amplicon and shotgun metagenomic sequencing was performed, aiming to uncover the connection between the gut microbiome and disease severity in PD. The results showed that Desulfovibrio was significantly increased in PD compared to healthy controls and positively correlated with disease severity. The increase in Desulfovibrio was mainly driven by enhanced homogeneous selection and weakened drift. Moreover, through metagenome-assembled genomes (MAGs) analysis, a Desulfovibrio MAG (MAG58) was obtained which was also positively correlated with disease severity. MAG58 possesses a complete assimilatory sulfate reduction pathway and a near-complete dissimilatory sulfate reduction pathway to produce hydrogen sulfide which may influence the development of PD. Based on these results, a potential pathogenic mechanism was presented to illustrate how the increased Desulfovibrio accelerates the development of PD by producing excessive hydrogen sulfide. The present study highlighted the vital role of Desulfovibrio in the development of PD, which may provide a new target for the diagnosis and treatment of PD. KEY POINTS: • The evidence for the link between increased Desulfovibrio and disease severity in PD • A Desulfovibrio MAG was obtained which was correlated with PD • A model was presented to illustrate how increased Desulfovibrio causes PD.


Assuntos
Desulfovibrio , Sulfeto de Hidrogênio , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico , RNA Ribossômico 16S/genética , Gravidade do Paciente , Desulfovibrio/genética , Sulfatos
4.
J Environ Manage ; 344: 118756, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37573697

RESUMO

Microplastics (MPs), as an emerging pollutant, pose a significant threat to humans and ecosystems. However, traditional MPs characterization methods are limited by sample requirements and characterization time. Machine Learning (ML) has emerged as a vital technology for analyzing MPs pollution due to its accuracy, broad application, and powerful feature extraction. Nevertheless, environmental scientists require threshold knowledge before using ML, restricting the ML application in MPs research. Furthermore, imbalanced development of ML in MPs research is a pressing concern. In order to achieve a wide ML application in MPs research, in this review, we comprehensively discussed the size and sources of MPs datasets in relevant literature to help environmental scientists deepen their understanding of the construction of MPs datasets. Commonly used ML algorithms are analyzed from the perspective of interpretability and the need for computer facilities. Additionally, methods for improving and evaluating ML model performance, such as dataset pre-processing, model optimization, and model assessment metrics, are discussed. According to datasets and characterization techniques, MPs identification using ML was divided into three categories in this work: spectral identification, image identification, and spectral imaging identification. Finally, other applications of ML in MPs studies, including toxicity analysis, pollutants adsorption, and microbial colonization, are comprehensively discussed, which reveals the great application potential of ML. Based on the discussion above, this review suggests an algorithm selection strategy to assist researchers in selecting the most suitable ML algorithm in different situations, improving efficiency and decreasing the costs of trial and error. We believe that this work sheds light on the application of ML in MPs study.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Humanos , Microplásticos , Plásticos , Ecossistema , Poluição Ambiental/análise , Poluentes Ambientais/análise , Poluentes Químicos da Água/análise
5.
Mov Disord ; 36(1): 87-95, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33098597

RESUMO

BACKGROUND: Deficits in maintaining and manipulating sequential information online can occur even in patients with mild Parkinson's disease. The subthalamic nucleus may play a modulatory role in the neural system for sequential working memory, which also includes the lateral prefrontal cortex. OBJECTIVES: The objective of this study was to investigate neural markers of sequential working memory deficits in patients with de novo Parkinson's disease. METHODS: A total of 50 patients with de novo Parkinson's disease and 50 healthy controls completed a digit ordering task during functional magnetic resonance imaging scanning. The task separated the maintenance ("pure recall") and manipulation of sequences ("reorder & recall" vs "pure recall"). RESULTS: In healthy controls, individual participants' task accuracy was predicted by the regional activation and functional connectivity of the subthalamic nucleus. Healthy participants who showed lower subthalamic nucleus activation and stronger subthalamic nucleus connectivity with the putamen performed more accurately in maintaining sequences ("pure recall"). Healthy participants who showed greater ordering-related subthalamic nucleus activation change exhibited smaller accuracy costs in manipulating sequences ("reorder & recall" vs "pure recall"). Patients performed less accurately than healthy controls, especially in "reorder & recall" trials, accompanied by an overactivation in the subthalamic nucleus and a loss of synchrony between the subthalamic nucleus and putamen. Individual patients' task accuracy was predicted only by the subthalamic nucleus connectivity. The contribution of the subthalamic nucleus activation or activation change was absent. We observed no change in the lateral prefrontal cortex. CONCLUSIONS: The overactivation and weakened functional connectivity of the subthalamic nucleus are the neural markers of sequential working memory deficits in de novo Parkinson's disease. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Imageamento por Ressonância Magnética , Transtornos da Memória/etiologia , Memória de Curto Prazo , Doença de Parkinson/complicações , Doença de Parkinson/terapia
6.
J Environ Manage ; 299: 113626, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34488105

RESUMO

Polyvinyl chloride (PVC) and polycarbonate (PC) microplastics are major sources of hazardous chlorine and bisphenol A, threatening the ecosystem and environment. Plastic recycling can control the source of microplastics pollution, but the recycling of PVC and PC will be prevented by invalid separation. We established a novel and clean flotation method to separate PVC and PC microplastics by using aluminum coating. Trace amounts of Al(OH)3 can selectively coat the PVC microplastics surface due to its strong affinity for PVC. The contact angle of PVC decreases by 24° due to abundant hydroxyl groups of Al(OH)3 coating, whereas PC remained hydrophobic. Response surface methodology (RSM) combining Box-Behnken design (BBD) is used to optimize modification. A quadratic model is established to predict PC purity, explore the interaction between pH, aluminum chloride concentration, and ultrasonic duration. The recovery and purity of microplastics can exceed 99.65% with parameter optimization. The effects of multi-component, brand, shape, size, and mass ratio of plastics are utilized to evaluate the application potential. The suitable situations and limits of this method are disclosed. The aluminum coating offers significant benefits over other modifications in terms of reaction temperature, treatment time, and pollution prevention. Flotation based on aluminum coating provides a new insight for separating and recycling microplastics.


Assuntos
Cloreto de Polivinila , Eliminação de Resíduos , Alumínio , Ecossistema , Microplásticos , Plásticos , Cimento de Policarboxilato
7.
Environ Sci Technol ; 54(16): 9742-9756, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32659077

RESUMO

Improper disposal of waste plastic has caused much environmental pollution, but plastic recycling can reduce the amount of new and residual waste plastic in the environment through source control. Plastic flotation can separate waste plastics with similar physical and chemical properties, which suggests its promising application in plastic recycling. With the help of the different hydrophilicities waste plastic can be separated by flotation, and hydrophilization can be accomplished by surface modifications. However, no systematic studies addressing these surface reactions have been published yet, and such modifications are a prerequisite for plastic flotation. In this critical review, we not only summarize the various modification mechanisms, including physical regulation, surface oxidation, surface degradation, dechlorination, and coating, but also have reasonably added additional information for some reactions covering surface reconstruction, plastic degradation, polymer stability, wastewater treatment, soil remediation, and chemical recycling of plastic. An entirely novel concept, the "plastic gene", is also proposed to elaborate on some contradictory results. Plastic flotation with clear surface reactions may promote plastic recycling and thereby control waste plastic at the source, save energy, and reduce microplastics. We also predict challenges for clean, efficient, and practical surface modifications and plastic flotation.


Assuntos
Plásticos , Eliminação de Resíduos , Polímeros , Reciclagem , Águas Residuárias
8.
Neurol Sci ; 41(5): 1153-1162, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31897944

RESUMO

BACKGROUND: Obstructive sleep apnea (OSA) is a common sleep disorder in Parkinson's disease (PD). However, the relationship between OSA and PD is still inconsistent. Our study was aimed to evaluate the relationship between PD and OSA. METHODS: Studies on OSA and PD were searched using PubMed, Embase, Web of Science, Cochrane library, and Chinese National Knowledge Infrastructure databases. Review Manager 5.3 software was used to calculate the pooled estimate effect. The inverse variance model was used to pool the mean difference (MD) or hazard ratios (HRs); the Mantel-Haenszel method was used to pool the odds ratio (OR). Heterogeneity among the studies was assessed using I2 statistic and Q test. RESULTS: A total of 12 studies with 93,332 cases were deemed eligible and included in our meta-analysis. Overall, the occurrence of PD was more frequent in patients with OSA (HR 1.59, 95% CI, 1.36-1.85). The subgroup analysis demonstrated the risk similarly by sex. Male and female had HR of incident PD with OSA of 1.56 (95% CI, 1.30-1.87) and 1.60 (95% CI, 1.21-2.11), respectively. The incidence of OSA did not increase in PD patients (OR 0.89, 95% CI, 0.53-1.49). The MD of apnea-hypopnea index (AHI) in PD patients was also not statistically significant (P = 0.5). CONCLUSIONS: The results indicate that OSA is one of independent risk factors of PD. However, OSA does not seem to be abnormally frequent in PD.


Assuntos
Doença de Parkinson/epidemiologia , Apneia Obstrutiva do Sono/epidemiologia , Estudos de Casos e Controles , Humanos , Doença de Parkinson/complicações , Estudos Retrospectivos , Fatores de Risco , Apneia Obstrutiva do Sono/complicações
9.
Zhonghua Yi Xue Za Zhi ; 96(11): 859-62, 2016 Mar 22.
Artigo em Zh | MEDLINE | ID: mdl-27045647

RESUMO

OBJECTIVE: To investigate the clinical characteristics, electrophysiological findings and treatment response of Lewis-Sumner syndrome (LSS). METHODS: Data of nine patients with LSS, who were diagnosed and treated from May 2008 to August 2014 in Department of Neurology, Peking University Third Hospital, were analyzed retrospectively, including clinical features, electrophysiological studies, pathological characteristics, therapy and follow up. RESULTS: The nine cases included seven males and two females, with the average age being 29 years old (18-64 years old). The follow-ups after treatment were between 6 months to 48 months. All 9 cases were asymmetrical onset, and the distal part of limbs was initially affected in 8 cases. Five cases presented with the initial symptom of sensorimotor, 3 cases with purely motor and only 1 case with sensory. The disease developed two forms: multifocal distribution and symmetrical distribution. Electrophysiological studies demonstrated conduction blocks on non-entrapment sites, involving mainly median nerve and ulnar nerve. Sural nerve biopsy presented mild demyelination without inflammatory infiltration. The symptoms of patients had some degrees of improvement after immunotherapy, and the prognosis was favorable. CONCLUSIONS: Lewis-Sumner syndrome presents the initial symptoms of asymmetrical sensorimotor neuropathy mostly affecting the upper extremities. Median nerve and ulnar nerve are the most common involvements. Electrophysiological studies demonstrate motor nerve conduction block. The major finding of pathology is mild demyelinated. The patients have a positive response to immunotherapy.


Assuntos
Doenças Desmielinizantes/fisiopatologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Adolescente , Adulto , Doenças Desmielinizantes/terapia , Fenômenos Eletrofisiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/terapia , Estudos Retrospectivos , Síndrome , Extremidade Superior/fisiopatologia , Adulto Jovem
10.
Zhonghua Nei Ke Za Zhi ; 54(2): 122-4, 2015 Feb.
Artigo em Zh | MEDLINE | ID: mdl-25907842

RESUMO

OBJECTIVE: To investigate effect of genetic variants in angiogenin (ANG) on the susceptibility of familial amyotrophic lateral sclerosis (FALS) in Han Chinese. METHODS: Thirty-one FALS families from 2009 to 2012 were collected and ANG gene was screened in the probands using PCR and direct sequencing. RESULTS: All 31 ALS families were autosomal dominant inheritance. No mutations and single nucleotide polymorphism were detectable in ANG gene in the 31 probands. CONCLUSION: Our study suggests that ANG gene variations may be rare in Chinese Han FALS.


Assuntos
Esclerose Lateral Amiotrófica/etnologia , Esclerose Lateral Amiotrófica/genética , Povo Asiático/genética , Ribonuclease Pancreático/genética , China , Humanos , Mutação , Polimorfismo de Nucleotídeo Único
11.
Zhonghua Nei Ke Za Zhi ; 54(1): 35-9, 2015 Jan.
Artigo em Zh | MEDLINE | ID: mdl-25877144

RESUMO

OBJECTIVE: To characterize the clinical, electrophysiology and neuropathological features of 4 cases with immune-mediated necrotizing myopathy (IMNM). METHODS: We retrospectively analyzed the clinical, electrophysiology, neuropathological characteristics of 4 IMNM patients with muscular and skin biopsy in our department during 4 years (from January 2011 to January 2014). RESULTS: Among these 4 patients, 2 were men and 2 were women (aged 37 to 58 years) with disease duration ranging from 1 month to 60 months. Two patients were with acute onset and 2 with chronic onset. All 4 patients had proximal muscle weakness with three patients with cervical flexor muscle weakness and one with respiratory muscles weakness and noninvasive ventilator assisted respiration. One patient had interstitial lung disease. The anti-signal recognition particle antibodies were strong positive in all 4 patients. Muscle biopsy showed group necrotizing and regenerating fibers in one patient and few scattered necrotizing and regenerating fibers in the other 3 patients. Both muscle fiber hypertrophy and muscle fiber atrophy together with proliferation of connective tissue on endomysium could be viewed in all 4 patients. However, very few inflammatory cells were detectable in patients. One patient was treated with corticosteroids and the other three were treated with combination of corticosteroids and immunosuppressant drugs. CONCLUSIONS: IMNM is characterized by heterogeneity at disease onset, severity and iInvolvement of muscles with, however, similary pathological changes including the presence of numerous necrotic and regenerating fibers with little or none inflammation. Corticosteroid and/or immunosuppressant is effective for patients.


Assuntos
Músculos/imunologia , Doenças Musculares/imunologia , Doenças Musculares/patologia , Biópsia , Feminino , Seguimentos , Humanos , Inflamação , Doenças Pulmonares Intersticiais/complicações , Masculino , Debilidade Muscular/etiologia , Músculos/irrigação sanguínea , Músculos/patologia , Necrose , Estudos Retrospectivos , Pele
12.
Zhonghua Nei Ke Za Zhi ; 53(5): 384-9, 2014 May.
Artigo em Zh | MEDLINE | ID: mdl-25146406

RESUMO

OBJECTIVE: To summarize the clinical features, electrophysiology and neuropathological characteristics of peripheral nerves in patients with vasculitic neuropathy. METHODS: We retrospectively analyzed the clinical, electrophysiology and neuropathological characteristics of 15 patients with vasculitic neuropathy who underwent electrophysiology and sural nerve biopsy in our department from January 2009 to June 2013. RESULTS: There were 8 males and 7 females, aged from 38 to 82 years old, with a peripheral neuropathy course ranged from 0.5 month to 60 months. In the total of 15 patients, 3 patients were diagnosed as nonsystemic vasculitic neuropathy, while the other 12 patients were diagnosed as systemic vasculitis neuropathy (SVN) including 5 cases of primary systemic vasculitis and 7 cases of secondary systemic vasculitis. In patients diagnosed as primary systemic vasculitis, there were 2 cases of Churg-Strass syndrome (CSS) and 3 cases of ANCA associated vasculitis. In patients diagnosed as secondary systemic vasculitis, there were 1 case of systemic lupus erythematosus (SLE), 2 cases of sicca syndrome (SS), 3 cases of rheumatoid arthritis (RA), 1 case of Behcet' s disease associated with thyroid papillary carcinoma, 1 case of hepatitis B and 1 case of RA-associated SS. For the pathological features of vasculitic neuropathy, type 1 lesion was found in 4 patients, type 2 lesion in 2 patients, and type 3 lesion in 9 patients. Axon degeneration was observed in 8 patients, while 7 patients manifested as axon degeneration associated with demyelination and local thickening of the perineurium was found in 2 patients. CONCLUSION: Multiple mononeuropathy and asymmetric polyneuropathy are the common clinical presentations of vasculitic neuropathy. Electrodiagnostic testing almost always reveals the evidence of a predominantly axonal and sensorimotor process with associated demyelination presented in some cases. Sural nerve biopsy shows changes indicative of an axonopathy.


Assuntos
Doenças do Sistema Nervoso Periférico/patologia , Nervo Sural/patologia , Vasculite/patologia , Artrite Reumatoide/complicações , Artrite Reumatoide/patologia , Biópsia , Eletrofisiologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/patologia , Masculino , Condução Nervosa/fisiologia , Polineuropatias/complicações , Polineuropatias/patologia , Estudos Retrospectivos
13.
Zhonghua Yi Xue Za Zhi ; 94(11): 855-8, 2014 Mar 25.
Artigo em Zh | MEDLINE | ID: mdl-24854756

RESUMO

OBJECTIVE: To summarize the clinical features, electrophysiological and neuropathological characteristics of peripheral nerves in patients with primary Sjögren's syndrome (SS). METHODS: We retrospectively analyzed the clinical, electrophysiological and neuropathological characteristics of 5 female SS patients with neuropathy complications undergoing electrophysiology and sural nerve biopsy at our department from January 2011 to June 2013. RESULTS: They had an age range of 20-75 years. The course of peripheral neuropathy ranged 0.5-60 months and the whole course 12-240 months. pSS-associated neuropathy included multiple mononeuropathy (n = 1), symmetrical axonal sensorimotor polyneuropathy (n = 1) and sensory ganglioneuronopathy (n = 3). All biopsies showed varying degrees of myelinated fiber loss. Three biopsies had axonal degeneration associated with demyelination. However, there was no formation of onion bulb regeneration or plexus. Necrotizing vasculitis was diagnosed in 2 cases. CONCLUSION: The manifestations of peripheral nerve n pSS include multiple mononeuropathy, axonal symmetric sensorimotor polyneuropathy and sensory gangioneuronopathy. Sural biopsy shows typical necrotizing vasculitis in some cases and myelinated fiber loss and axonal degeneration in others. The pathogenic mechanisms of neurological involvement in pSS remain unknown. However, vasculitis, ischemic and immunological insults resulting in sensory gangioneuronopathy have been described.


Assuntos
Doenças do Sistema Nervoso Periférico/patologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Síndrome de Sjogren/patologia , Síndrome de Sjogren/fisiopatologia , Adulto , Idoso , Fenômenos Eletrofisiológicos , Feminino , Humanos , Pessoa de Meia-Idade , Nervos Periféricos/patologia , Doenças do Sistema Nervoso Periférico/complicações , Estudos Retrospectivos , Síndrome de Sjogren/complicações , Adulto Jovem
14.
RSC Adv ; 14(5): 3146-3157, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38249666

RESUMO

Monoethanolamines (MEAs) are widely used for CO2 capture, but their regeneration energy consumption is very high. CO2 Phase change absorbents (CPCAs) can be converted into CO2-rich and CO2-lean phases after absorbing CO2, and the regeneration energy consumption can be reduced because only the CO2-rich phase is thermally desorbed. In this paper, a novel CPCA with the composition "MEA/n-butanol/H2O (MNBH)" is proposed. Compared with the reported MEA phase change absorbent, the MNBH absorbent has higher CO2 absorption capacity, smaller absorbent viscosity and CO2-rich phase volume. The MNBH absorbent has the highest CO2 absorption capacity of 2.5227 mol CO2 per mol amine at a mass ratio of 3 : 4 : 3. The CO2 desorption efficiency reaches 89.96% at 120 °C, and the CO2 regeneration energy consumption is 2.6 GJ tCO2-1, which is about 35% lower than that of the 30 wt% MEA absorbent. When the mass ratio of MNBH absorbent was 3 : 6 : 1, the CO2 recycling capacity was 4.1918 mol CO2 L-1, which is 76% higher than that of the conventional 30 wt% MEA absorbent. The phase change absorbent developed in this paper can reduce the desorbent volume by about 50% and has good absorption performance for CO2 in flue gas.

15.
Eur J Med Chem ; 272: 116494, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38749268

RESUMO

Epigenetic alterations promote cancer development by regulating the expression of various oncogenes and anti-oncogenes. Histone methylation modification represents a pivotal area in epigenetic research and numerous publications have demonstrated that aberrant histone methylation is highly correlated with tumorigenesis and development. As a key histone demethylase, lysine-specific demethylase 5B (KDM5B) demethylates lysine 4 of histone 3 (H3K4) and serves as a transcriptional repressor of certain tumor suppressor genes. Meanwhile, KDM5B inhibits STING-induced intrinsic immune response of tumor cells or recruits SETDB1 through non-enzymatic function to silence reverse transcription elements to promote immune escape. The conventional small molecule inhibitors can only inhibit the enzymatic function of KDM5B with no effect on the non-enzymatic function. In the article, we present the development of the first series of KDM5B degraders based on CPI-455 to inhibit the non-enzymatic function. Among them, GT-653 showed optimal KDM5B degradation efficiency in a ubiquitin proteasome-dependent manner. GT-653 efficiently reduced KDM5B protein levels without affecting KDM5B transcription. Interestingly, GT-653 increased H3K4me3 levels and activated the type-I interferon signaling pathway in 22RV1 cells without significant phenotypic response on cell proliferation.


Assuntos
Antineoplásicos , Histona Desmetilases com o Domínio Jumonji , Neoplasias da Próstata , Humanos , Masculino , Histona Desmetilases com o Domínio Jumonji/metabolismo , Histona Desmetilases com o Domínio Jumonji/antagonistas & inibidores , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Regulação para Cima/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Estrutura Molecular , Descoberta de Drogas , Relação Dose-Resposta a Droga , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Proteólise/efeitos dos fármacos , Interferons/metabolismo , Proteínas Nucleares , Proteínas Repressoras
16.
CNS Neurosci Ther ; 30(7): e14851, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38978196

RESUMO

BACKGROUND: Smell loss significantly impacts the quality of life in patients. However, there is limited research on smell loss in individuals with amyotrophic lateral sclerosis (ALS), and the correlation between smell loss and cognitive impairment is unclear. This study aimed to investigate the correlation between smell loss and cognition impairment in ALS patients. METHODS: The study included 216 ALS patients. The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and smell identification test specifically for the Chinese population (CSIT) were administered to evaluate participants' cognitive and olfactory function, respectively. RESULTS: After covarying for age, sex, BMI, education level, degree of hunger, dietary bias, eagerness for food, stress, smoking status, alcohol consumption, and upper respiratory tract infection (URTI) or rhinitis, CSIT scores were significantly correlated with ECAS scores (r = 0.162, p = 0.028), especially the ALS-specific scores (r = 0.158, p = 0.031). Even after excluding patients with URTI or rhinitis, the results were similar. CSIT scores were significantly correlated with ECAS scores (r = 0.224, p = 0.011), especially the ALS-specific scores (r = 0.205, p = 0.019). CONCLUSION: In patients with ALS, smell loss is significantly correlated with cognitive impairment, particularly frontotemporal dysfunction. Cognitive dysfunction may lead to worse olfactory performance in ALS patients.


Assuntos
Esclerose Lateral Amiotrófica , Disfunção Cognitiva , Transtornos do Olfato , Humanos , Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/psicologia , Esclerose Lateral Amiotrófica/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Idoso , Transtornos do Olfato/etiologia , Transtornos do Olfato/epidemiologia , Adulto
17.
Chemosphere ; 312(Pt 1): 137178, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36368541

RESUMO

The COVID-19 epidemic seriously threats the human society and provokes the panic of the public. Personal Protective Equipment (PPE) are widely utilized for frontline health workers to face the ongoing epidemic, especially disposable face masks (DFMs) to prevent airborne transmission of coronavirus. The overproduction and massive utilization of DFMs seriously challenge the management of plastic wastes. A huge amount of DFMs are discharged into environment, potentially induced the generation of microplastics (MPs) owing to physicochemical destruction. The MPs release will pose severe contamination burden on environment and human. In this review, environmental threats of DFMs regarding to DFMs fate in environment and DFMs threats to aquatic and terrestrial species were surveyed. A full summary of recent studies on MPs release from DFMs was provided. The knowledge of extraction and characterizations of MPs, the release behavior, and potential threats of MPs derived from DFMs was discussed. To confront the problem, feasible strategies for control DFMs pollution were analyzed from the perspective of source control and waste management. This review provides a better understanding the threats, fate, and management of DFMs linked to COVID-19 pandemic.


Assuntos
COVID-19 , Máscaras , Humanos , Microplásticos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Plásticos , Pandemias/prevenção & controle
18.
Front Genet ; 14: 1085442, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36923789

RESUMO

Background: Hereditary spastic paraplegia (HSP) constitutes a group of clinically and genetically rare neurodegenerative diseases characterized by progressive corticospinal tract degeneration. The phenotypes and genotypes of HSP are still expanding. In this study, we aimed to analyse the differential diagnosis, clinical features, and genetic distributions of a Chinese HSP patients in a 14-year cohort and to improve our understanding of the disease. Methods: The clinical data of patients with a primary diagnosis of HSP at the initial visit to the Department of the Neurology, Peking University Third Hospital, from 2008 to 2022 were retrospectively collected. Next-generation sequencing gene panels (NGS) combined with a multiplex ligation-amplification assay (MLPA) were conducted. Epidemiological and clinical features and candidate variants in HSP-related genes were analyzed and summarized. Results: 54 cases (probands from 25 different pedigrees and 29 sporadic cases) from 95 patients with a primary diagnosis of HSP were finally confirmed to have a clinical diagnosis of HSP based on clinical criteria, including their clinical findings, family history and long-term follow-up. Earlier disease onset was associated with longer diagnostic delay and longer disease duration and was associated with a lower risk of loss of ability to walk independently. In addition, 20 candidate variants in reported HSP-related genes were identified in these clinically diagnosed HSP patients, including variants in SPAST, ALT1, WASHC5, SPG11, B4GALNT1, and REEP1. The genetic diagnostic rate in these 54 patients was 35.18%. Conclusion: Hereditary spastic paraplegia has high clinical and genetic heterogeneity and is prone to misdiagnosis. Long-term follow-up and genetic testing can partially assist in diagnosing HSP. Our study summarized the clinical features of Chinese HSP patients in a 14-year cohort, expanded the genotype spectrum, and improved our understanding of the disease.

19.
Front Neurol ; 14: 1117243, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36846128

RESUMO

Background: Neuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions and the GGC repeats in the 5'-untranslated region of NOTCH2NLC. The prevalent presence of high-intensity signal along the corticomedullary junction on diffusion-weighted imaging (DWI) helps to recognize this heterogeneous disease despite of highly variable clinical manifestations. However, patients without the typical sign on DWI are often misdiagnosed. Besides, there are no reports of NIID patients presenting with paroxysmal peripheral neuropathy-like onset to date. Case presentation: We present a patient with NIID who suffered recurrent transient numbness in arms for 17 months. Magnetic resonance imaging (MRI) showed diffuse, bilateral white matter lesions without typical subcortical DWI signals. Electrophysiological studies revealed mixed demyelinating and axonal sensorimotor polyneuropathies involving four extremities. After excluding differential diagnosis of peripheral neuropathy through body fluid tests and a sural nerve biopsy, NIID was confirmed by a skin biopsy and the genetic analysis of NOTCH2NLC. Conclusion: This case innovatively demonstrates that NIID could manifest as paroxysmal peripheral neuropathy-like onset, and addresses the electrophysiological characteristics of NIID in depth. We broaden the clinical spectrum of NIID and provide new insights into its differential diagnosis from the perspective of peripheral neuropathy.

20.
Water Res ; 233: 119794, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36868113

RESUMO

Microplastics (MPs) are increasingly released into the environment due to the widespread usage and improper management of plastics. Considerable research efforts have been devoted to the remediation of MPs. Froth flotation has been demonstrated as an effective method to remove MPs in water and sediment. However, there is a lack of knowledge on the regulation of the hydrophobicity/hydrophilicity of MPs surfaces. We found that exposure to the natural environment resulted in the increased hydrophilicity of MPs. The flotation efficiencies of polyvinyl chloride (PVC), polypropylene (PP), polystyrene (PS), and polyethylene glycol terephthalate (PET) MPs decreased to zero after six months of natural incubation in rivers. According to various characterizations, the hydrophilization mechanism is mainly correlated with surface oxidation and the deposition of clay minerals. Inspired by surface wettability conversion, we applied surfactants (collectors) to enhance MPs hydrophobicity and flotation efficiency. Anionic sodium oleate (NaOL) and cationic dodecyl trimethyl ammonium chloride (DTAC) were used to regulate surface hydrophobicity. The effects of collector concentration, pH, conditioning time, and metal ions on MPs flotation were thoroughly elucidated. Characterizations and adsorption experiments were performed to describe the heterogeneous adsorption of surfactants on MPs surfaces. The interaction between surfactants and MPs was explained through density functional theory (DFT) simulations. The dispersion energy between hydrophobic hydrocarbon chains attracts collectors on the MPs surface, and the collector molecules wrap and laminate to MPs surfaces. Flotation using NaOL exhibited a higher removal efficiency, and NaOL was environmentally friendly. Subsequently, we investigated the activation of Ca2+, Fe3+, and Al3+ to further improve the collecting efficiency of NaOL. Under the optimized conditions, MPs in natural rivers could be removed by froth flotation. This study shows the great promise of froth flotation for the application of MPs removal.


Assuntos
Microplásticos , Poluentes Químicos da Água , Plásticos/química , Poliestirenos , Água , Tensoativos
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