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1.
J Am Chem Soc ; 146(19): 13536-13545, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38693624

RESUMO

Herein, we establish a remote hydrosulfonamidation (HSA) of alkenes using palladium catalysis, where N-fluoro-N-(fluoro-sulfonyl)-carbamate with a sulfur(VI) fluoride moiety is demonstrated as a good amidation reagent. The anti-Markovnikov HSA reaction of terminal alkenes and the remote HSA of internal alkenes are achieved to efficiently yield primary N-alkyl-N-(fluorosulfonyl)-carbamates. In addition, this protocol enables the high-value utilization of alkane by combining the dehydrogenation process. The generated N-alkyl products exhibit a unique reactivity of sulfur(VI) fluorides, which can be directly transferred to N-alkyl sulfamides or amines via the sulfur(VI) fluoride exchange reaction, thereby streamlining their synthesis. Moreover, a (pyridyl) benzazole-type ligand proved to be vital for the excellent chemo- and regioselectivities.

2.
Sci Rep ; 14(1): 2392, 2024 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287035

RESUMO

The overall picture of degloving skin and soft tissue injuries (DSTI) remains a blank space in China. Therefore, a retrospective study was designed to summarize the current situation of this injury. Patients diagnosed with DSTI hospitalized between 2013 and 2018 were identified from the Hospital Quality Monitoring System (HQMS) database, of whom demographics, injury characteristics, hospitalization and cost information were analyzed. A total of 62,709 patients were enrolled in this study. Male sex predominated, with a mean age of 43.01 ± 19.70 years. Peasants seemed to be the most vulnerable. East China and Hubei province had the most patients. The most and least frequently injured anatomic site were lower extremity and torso, respectively. Traffic-related accidents and summer accounted for the highest proportion in terms of injury mechanism and season. The operation rate of DSTI roughly showed a growing trend, and the average length of stay was 22.02 ± 29.73 days. At discharge, 0.93% of DSTI patients ended up in death. Medicine accounted mostly for hospitalization cost, while the proportion decreased year by year. More than half DSTI patients paid at their own charge. This study made a relatively detailed description of DSTI patients nationwide, and might provide enlightenments for better prevention and treatment.


Assuntos
Pacientes Internados , Lesões dos Tecidos Moles , Humanos , Masculino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Hospitalização , Pele , Lesões dos Tecidos Moles/epidemiologia , Lesões dos Tecidos Moles/cirurgia
3.
J Am Chem Soc ; 146(5): 3427-3437, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38243892

RESUMO

Despite half a century's advance in the field of transition-metal-catalyzed asymmetric alkene hydrogenation, the enantioselective hydrogenation of purely alkyl-substituted 1,1-dialkylethenes has remained an unmet challenge. Herein, we describe a chiral PCNOx-pincer iridium complex for asymmetric transfer hydrogenation of this alkene class with ethanol, furnishing all-alkyl-substituted tertiary stereocenters. High levels of enantioselectivity can be achieved in the reactions of substrates with secondary/primary and primary/primary alkyl combinations. The catalyst is further applied to the redox isomerization of disubstituted alkenols, producing a tertiary stereocenter remote to the resulting carbonyl group. Mechanistic studies reveal a dihydride species, (PCNOx)Ir(H)2, as the catalytically active intermediate, which can decay to a dimeric species (κ3-PCNOx)IrH(µ-H)2IrH(κ2-PCNOx) via a ligand-remetalation pathway. The catalyst deactivation under the hydrogenation conditions with H2 is much faster than that under the transfer hydrogenation conditions with EtOH, which explains why the (PCNOx)Ir catalyst is effective for the transfer hydrogenation but ineffective for the hydrogenation. The suppression of di-to-trisubstituted alkene isomerization by regioselective 1,2-insertion is partly responsible for the success of this system, underscoring the critical role played by the pincer ligand in enantioselective transfer hydrogenation of 1,1-dialkylethenes. Moreover, computational studies elucidate the significant influence of the London dispersion interaction between the ligand and the substrate on enantioselectivity control, as illustrated by the complete reversal of stereochemistry through cyclohexyl-to-cyclopropyl group substitution in the alkene substrates.

4.
Environ Sci Technol ; 58(2): 1359-1368, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38079615

RESUMO

Lithium holds immense significance in propelling sustainable energy and environmental systems forward. However, existing sensors used for lithium monitoring encounter issues concerning their selectivity and long-term durability. Addressing these challenges is crucial to ensure accurate and reliable lithium measurements during the lithium recovery processes. In response to these concerns, this study proposes a novel approach involving the use of an MXene composite membrane with incorporated poly(sodium 4-styrenesulfonate) (PSS) as an antibiofouling layer on the Li+ ion selective electrode (ISE) sensors. The resulting MXene-PSS Li+ ISE sensor demonstrates exceptional electrochemical performance, showcasing a superior slope (59.42 mV/dec), lower detection limit (10-7.2 M), quicker response time (∼10 s), higher selectivity to Na+ (-2.37) and K+ (-2.54), and reduced impedance (106.9 kΩ) when compared to conventional Li+ ISE sensors. These improvements are attributed to the unique electronic conductivity and layered structure of the MXene-PSS nanosheet coating layer. In addition, the study exhibits the long-term accuracy and durability of the MXene-PSS Li+ ISE sensor by subjecting it to real wastewater testing for 14 days, resulting in sensor reading errors of less than 10% when compared to laboratory validation results. This research highlights the great potential of MXene nanosheet coatings in advancing sensor technology, particularly in challenging applications, such as detecting emerging contaminants and developing implantable biosensors. The findings offer promising prospects for future advancements in sensor technology, particularly in the context of sustainable energy and environmental monitoring.


Assuntos
Eletrodos Seletivos de Íons , Lítio , Nitritos , Elementos de Transição , Impedância Elétrica , Eletrônica
5.
Glob Chang Biol ; 30(1): e17049, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37988188

RESUMO

Nanoparticle pollution has been shown to affect various organisms. However, the effects of nanoparticles on species interactions, and the role of species traits, such as body size, in modulating these effects, are not well-understood. We addressed this issue using competing freshwater phytoplankton species exposed to copper oxide nanoparticles. Increasing nanoparticle concentration resulted in decreased phytoplankton species growth rates and community productivity (both abundance and biomass). Importantly, we consistently found that nanoparticles had greater negative effects on species with smaller cell sizes, such that nanoparticle pollution weakened the competitive dominance of smaller species and promoted species diversity. Moreover, nanoparticles reduced the growth rate differences and competitive ability differences of competing species, while having little effect on species niche differences. Consequently, nanoparticle pollution reduced the selection effect on phytoplankton community abundance, but increased the selection effect on community biomass. Our results suggest cell size as a key functional trait to consider when predicting phytoplankton community structure and ecosystem functioning in the face of increasing nanopollution.


Assuntos
Ecossistema , Fitoplâncton , Biodiversidade , Biomassa , Água Doce
6.
Front Endocrinol (Lausanne) ; 14: 1104202, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36761191

RESUMO

Objectives: National data on the admission rate, distribution, in-hospital mortality, and economic burden of traumatic fractures in China is unclear. We aimed to conduct a cross-sectional population-based study to determine such above data at the national level in China. Methods: A national administrative database was used to review all traumatic fracture hospitalizations in China during 2020, from which a total of 2,025,169 inpatients with traumatic fractures was retrieved. Admission rates and in-hospital mortality rates stratified by age, sex, and region were calculated. The causes of traumatic fracture and economic burden were described. Results: The admission rate of traumatic fractures of all China population in 2020 was 1.437‰. The admission rate increased with age and varied with genders and causes of injuries. Falls are the leading cause of traumatic fracture hospitalization, followed by road traffic injuries. The most common diagnoses were femoral neck fractures, with a number of 138,377. The in-hospital mortality was 1.209‰. Road traffic injuries led to the highest in-hospital mortality. The median length of stay was 10 days, with the median hospitalization cost of ¥20,900 (about $3,056). Conclusion: Traumatic fractures are concerning conditions with a high admission rate and in-hospital mortality in China, which are mainly caused by falls and road traffic injuries. The government should implement more public health policies to enhance the health of the elderly and improve transportation safety to prevent traumatic fractures.


Assuntos
Estresse Financeiro , Fraturas Ósseas , Humanos , Masculino , Feminino , Idoso , Estudos Transversais , Fraturas Ósseas/epidemiologia , Hospitalização , China/epidemiologia
7.
J Clin Transl Hepatol ; 11(2): 416-424, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-36643040

RESUMO

Background and Aims: Patients with biliary atresia (BA) are prone to hepatic decompensation, which might eventually lead to death. This study aimed to identify the possible risk factors affecting in-hospital death in BA patients in China. Methods: We collected data from the Hospital Quality Monitoring System, a national inpatient database. All patients aged up to 2 years old with a diagnosis of BA were included. The subjects were divided to three groups, including Kasai portoenterostomy (KP), liver transplantation (LT), and no surgery. Logistic regression with Firth's method was performed to identify potential influencing variables associated with in-hospital death. Results: During the year 2013 to 2017, there were 14,038 pediatric admissions with a diagnosis of BA. The proportion of in-hospital death in pediatric BA admissions was 1.08%. Compared with patients under six months, there was a higher risk of in-hospital death for children aged six months to 1 year and 1-2 years old. Clinical signs, including cirrhosis, variceal bleeding, and hepatic encephalopathy, were significantly associated with the risk of in-hospital death. In no surgery group, compared to those in Beijing and Shanghai, BA patients admitted in other districts had a lower risk of in-hospital death (OR=0.39, 95% CI: 0.21, 0.70). However, in the LT group, patients admitted in other districts had a higher risk of in-hospital death (OR=9.13, 95% CI: 3.99, 20.87). Conclusions: In-hospital survival remains unsatisfactory for pediatric BA patients with severe complications. Furthermore, more resources and training for BA treatment, especially LT, are essential for districts with poor medical care in the future.

8.
Sci Adv ; 8(38): eabo6586, 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36149964

RESUMO

The dehydrogenation of abundant alkane feedstocks to olefins is one of the mostly intensively investigated reactions in organic catalysis. A long-standing, pervasive challenge in this transformation is the direct dehydrogenation of unactivated 1,1-disubstituted ethane, an aliphatic motif commonly found in organic molecules. Here, we report the design of a diphosphine chloroiridium catalyst for undirected dehydrogenation of this aliphatic class to form valuable 1,1-disubstituted ethylene. Featuring high site selectivity and excellent functional group compatibility, this catalytic system is applicable to late-stage dehydrogenation of complex bioactive molecules. Moreover, the system enables unprecedented dehydrogenation of polypropene with controllable degree of desaturation, dehydrogenating more than 10 in 100 propene units. Further derivatizations of the resulting double bonds afford functionalized polypropenes.

9.
J Cell Mol Med ; 26(10): 2908-2920, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35384279

RESUMO

Spermatogenesis is a cyclical process in which different generations of spermatids undergo a series of developmental steps at a fixed time and finally produce spermatids. Here, we report that overexpression of PD-L1 (B7 homolog1) in the testis causes sperm developmental disorders and infertility in male mice, with severe malformation and sloughing during spermatid development, characterized by disorganized and collapsed seminiferous epithelium structure. PD-L1 needs to be simultaneously expressed on Sertoli cells and spermatogonia to cause spermatogenesis failure. After that, we excluded the influence of factors such as the PD-L1 receptor and humoral regulation, confirming that PD-L1 has an intrinsic function to interact with PD-L1. Studies have shown that PD-L1 not only serves as a ligand but also plays a receptor-like role in signal transduction. PD-L1 interacts with PD-L1 to affect the adhesive function of germ cells, causing malformation and spermatid sloughing. Taken together, these results indicate that PD-L1 can interact with PD-L1 to cause germ cell detachment and male infertility.


Assuntos
Antígeno B7-H1 , Túbulos Seminíferos , Animais , Antígeno B7-H1/genética , Masculino , Camundongos , Células de Sertoli , Espermatogênese/genética , Espermatogônias , Testículo
10.
Mol Neurobiol ; 59(4): 2642-2655, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35142987

RESUMO

Abundant reactive gliosis and neuroinflammation are typical pathogenetic hallmarks of brains in Parkinson's disease (PD) patients, but regulation mechanisms are poorly understood. We are interested in role of programmed death-1 (PD-1) in glial reaction, neuroinflammation and neuronal injury in PD pathogenesis. Using PD mouse model and PD-1 knockout (KO) mice, we designed wild-type-control (WT-CON), WT-1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (WT-MPTP), PD-1-KO-control (KO-CON) and PD-1-KO-MPTP (KO-MPTP), and observed motor dysfunction of animal, morphological distribution of PD-1-positive cells, dopaminergic neuronal injury, glial activation and generation of inflammatory cytokines in midbrains by motor behavior detection, immunohistochemistry and western blot. WT-MPTP mouse model exhibited decrease of PD-1/Iba1-positive microglial cells in the substantia nigra compared with WT-CON mice. By comparison of four groups, PD-1 deficiency showed exacerbation in motor dysfunction of animals, decreased expression of TH protein and TH-positive neuronal protrusions. PD-1 deficiency enhanced microglial activation, production of proinflammatory cytokines like inducible nitric oxide synthase, tumor necrosis factor-α, interleukin-1ß and interleukin-6, and expression and phosphorylation of AKT and ERK1/2 in the substantia nigra of MPTP model. We concluded that PD-1 deficiency could aggravate motor dysfunction of MPTP mouse model by inducing microglial activation and neuroinflammation in midbrains, suggesting that PD-1 signaling abnormality might be possibly involved in PD pathogenesis.


Assuntos
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Doença de Parkinson , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Animais , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/metabolismo , Doenças Neuroinflamatórias , Doença de Parkinson/patologia , Receptor de Morte Celular Programada 1/metabolismo
11.
Environ Sci Technol ; 56(4): 2572-2581, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34968041

RESUMO

Polymeric membrane design is a multidimensional process involving selection of membrane materials and optimization of fabrication conditions from an infinite candidate space. It is impossible to explore the entire space by trial-and-error experimentation. Here, we present a membrane design strategy utilizing machine learning-based Bayesian optimization to precisely identify the optimal combinations of unexplored monomers and their fabrication conditions from an infinite space. We developed ML models to accurately predict water permeability and salt rejection from membrane monomer types (represented by the Morgan fingerprint) and fabrication conditions. We applied Bayesian optimization on the built ML model to inversely identify sets of monomer/fabrication condition combinations with the potential to break the upper bound for water/salt selectivity and permeability. We fabricated eight membranes under the identified combinations and found that they exceeded the present upper bound. Our findings demonstrate that ML-based Bayesian optimization represents a paradigm shift for next-generation separation membrane design.


Assuntos
Aprendizado de Máquina , Membranas Artificiais , Teorema de Bayes , Permeabilidade , Água
12.
J Allergy Clin Immunol Pract ; 9(7): 2645-2655.e14, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33684635

RESUMO

BACKGROUND: Chronic respiratory diseases (CRD) are common among patients with coronavirus disease 2019 (COVID-19). OBJECTIVES: We sought to determine the association between CRD (including disease overlap) and the clinical outcomes of COVID-19. METHODS: Data of diagnoses, comorbidities, medications, laboratory results, and clinical outcomes were extracted from the national COVID-19 reporting system. CRD was diagnosed based on International Classification of Diseases-10 codes. The primary endpoint was the composite outcome of needing invasive ventilation, admission to intensive care unit, or death within 30 days after hospitalization. The secondary endpoint was death within 30 days after hospitalization. RESULTS: We included 39,420 laboratory-confirmed patients from the electronic medical records as of May 6, 2020. Any CRD and CRD overlap was present in 2.8% and 0.2% of patients, respectively. Chronic obstructive pulmonary disease (COPD) was most common (56.6%), followed by bronchiectasis (27.9%) and asthma (21.7%). COPD-bronchiectasis overlap was the most common combination (50.7%), followed by COPD-asthma (36.2%) and asthma-bronchiectasis overlap (15.9%). After adjustment for age, sex, and other systemic comorbidities, patients with COPD (odds ratio [OR]: 1.71, 95% confidence interval [CI]: 1.44-2.03) and asthma (OR: 1.45, 95% CI: 1.05-1.98), but not bronchiectasis, were more likely to reach to the composite endpoint compared with those without at day 30 after hospitalization. Patients with CRD were not associated with a greater likelihood of dying from COVID-19 compared with those without. Patients with CRD overlap did not have a greater risk of reaching the composite endpoint compared with those without. CONCLUSION: CRD was associated with the risk of reaching the composite endpoint, but not death, of COVID-19.


Assuntos
Asma , COVID-19 , Doença Pulmonar Obstrutiva Crônica , Asma/epidemiologia , Comorbidade , Hospitalização , Humanos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2
13.
Environ Geochem Health ; 43(9): 3393-3406, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33555491

RESUMO

Numerous studies had focused on the association between air pollution and health outcomes in recent years. However, little evidence is available on associations between air pollutants and premature rupture of membranes (PROM). Therefore, we performed time-series analysis to evaluate the association between PROM and air pollution. The daily average concentrations of PM2.5, SO2 and NO2 were 54.58 µg/m3, 13.06 µg/m3 and 46.09 µg/m3, respectively, and daily maximum 8-h average O3 concentration was 95.67 µg/m3. The strongest effects of SO2, NO2 and O3 were found in lag4, lag06 and lag09, and an increase of 10 µg/m3 in SO2, NO2 and O3 was corresponding to increase in incidence of PROM of 8.74% (95% CI 2.12-15.79%), 3.09% (95% CI 0.64-5.59%) and 1.68% (95% CI 0.28-3.09%), respectively. There were no significant effects of PM2.5 on PROM. Season-specific analyses found that the effects of PM2.5, SO2 and O3 on PROM were more obvious in cold season, but the statistically significant effect of NO2 was observed in warm season. We also found the modifying effects by maternal age on PROM, and we found that the effects of SO2 and NO2 on PROM were higher among younger mothers (< 35 years) than advanced age mothers (≥ 35 years); however, ≥ 35 years group were more vulnerable to O3 than < 35 years group. This study indicates that air pollution exposure is an important risk factor for PROM and we wish this study could provide evidence to local government to take rigid approaches to control emissions of air pollutants.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China/epidemiologia , Fatores de Risco , Estações do Ano
14.
J Hazard Mater ; 406: 124746, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33341475

RESUMO

Adsorptive membranes offer an effective mode to remove heavy metal ions from contaminated water, due to the synergies made possible by low-cost, high-affinity adsorbents and highly scalable filtration in one system. However, the development of adsorptive membranes is hampered by their instability in the aqueous phase and low binding affinity with a broad spectrum of heavy metals in a reasonable flux. Herein, a regenerated cellulose support membrane is strongly grafted with stable and covalent-bonded polyelectrolyte active layers synthesized by a reactive layer-by-layer (LBL) assembly method. The LBL assembled layers have been successfully tested by scanning electron microscopy, Fourier-transform infrared spectroscopy and X-ray photo-electron spectroscopy. The covalent bonding provides the membrane with long-term stability and a tunable water flux compared to a membrane assembled by electrostatic bonding. The maximum adsorption capacity of the membrane active layers can reach up to 194 mg/g, showing more efficient adsorption at lower heavy metal concentration and higher pH value of feed solution. The membrane can remove multiple ions, such as Cu, Pb, and Cd, by adsorption and is easy to be regenerated and recovered. The strong covalent bonding can extend the membrane lifetime in water purification to remove multiple heavy metals at high efficiency.

15.
Sci Adv ; 6(47)2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33219029

RESUMO

Nature is able to synergistically combine multiple enzymes to conduct well-ordered biosynthetic transformations. Mimicking nature's multicatalysis in vitro may give rise to new chemical transformations via interplay of numerous molecular catalysts in one pot. The direct and selective conversion of abundant n-alkanes to valuable n-alcohols is a reaction with enormous potential applicability but has remained an unreached goal. Here, we show that a quadruple relay catalysis system involving three discrete transition metal catalysts enables selective synthesis of n-alcohols via n-alkane primary C─H bond hydroxymethylation. This one-pot multicatalysis system is composed of Ir-catalyzed alkane dehydrogenation, Rh-catalyzed olefin isomerization and hydroformylation, and Ru-catalyzed aldehyde hydrogenation. This system is further applied to synthesis of α,ω-diols from simple α-olefins through terminal-selective hydroxymethylation of silyl alkanes.

16.
Orphanet J Rare Dis ; 15(1): 154, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32560656

RESUMO

BACKGROUND: Patients with isolated methylmalonic acidemia (MMA) usually experience recurrent episodes of acute metabolic decompensation or metabolic stroke, require frequent hospitalization, and have a relatively high mortality rate. The aim of our study was to assess factors predicting the in-hospital death of pediatric patients with isolated MMA. We performed a retrospective study using data from the Hospital Quality Monitoring System, a national inpatient database in China collected from 2013 to 2017. All patients under 18 years old with a diagnosis of isolated MMA were included. Demographic, hospital-related, and clinical features were collected. Poisson regression was performed to identify potential influencing variables associated with in-hospital death. RESULTS: From 2013 to 2017, among 2317 admissions for pediatric patients diagnosed with isolated MMA, 1.77% had the outcome of death. In the univariate analysis, patients aged under 1 year had a higher risk of death than did those aged 1 year or older (odds ratio [OR] = 2.63, 95% confidence interval [CI]: 1.36-5.07). There was a higher risk of in-hospital death for patients admitted through emergency departments or via referrals than for those admitted through other routes (OR = 3.76, 95% CI: 1.84-7.67). Deaths were higher in hospitals with volumes of less than 50 patients with isolated MMA during the five study years (OR = 2.92, 95% CI: 1.46-5.83). Moreover, the risk of in-hospital death gradually decreased over time (OR = 0.72, 95% CI: 0.57-0.90). In the multivariate analysis, the abovementioned associations with the risk of in-hospital death remained statistically significant. However, no significant associations were observed between specific clinical signs and in-hospital death in either the univariate or the multivariate analysis. CONCLUSIONS: Younger age, admission to hospitals with low patient volumes, and admission through emergency departments or referrals are associated with higher risk of in-hospital death. The co-existence of specific clinical signs appears to have no effect on in-hospital death.


Assuntos
Pacientes Internados , Adolescente , Erros Inatos do Metabolismo dos Aminoácidos , Criança , China , Mortalidade Hospitalar , Humanos , Estudos Retrospectivos
17.
Neuroscience ; 440: 130-145, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32450294

RESUMO

Astrocytes are major glial cells critical in assisting the function of the central nervous system (CNS), but the functional changes and regulation mechanism of reactive astrocytes are still poorly understood in CNS diseases. In this study, mouse primary astrocytes were cultured, and inflammatory insult was performed to observe functional changes in astrocytes and the involvement of Notch-PI3K-AKT signaling activation through immunofluorescence, PCR, Western blot, CCK-8, and inhibition experiments. Notch downstream signal Hes-1 was clearly observed in the astrocytes, and Notch signal inhibitor GSI dose-dependently decreased the cleaved Notch-l level without an influence on cell viability. Inflammatory insult of lipopolysaccharide plus interferon-γ (LPS+IFNγ) induced an increase in pro-inflammatory cytokines, that is, iNOS, IL-1ß, IL-6, and TNF, at the protein and mRNA levels in activated astrocytes, which was reduced or blocked by GSI treatment. The cell viability of the astrocytes did not show significant differences among different groups. While an increase in MyD88, NF-кB, and phosphor-NF-кB was confirmed, upregulation of PI3K, AKT, and phosphor-AKT was observed in the activated astrocytes with LPS+IFNγ insult and was reduced by GSI treatment. Inhibitor experiments showed that inhibition of Notch-PI3K-AKT signaling activation reduced the pro-inflammatory cytokine production triggered by LPS+IFNγ inflammatory insult. This study showed that the reactive astrocytes displayed pro-inflammatory adaptability through Notch-PI3K-AKT signaling activation in response to inflammatory stimulation, suggesting that the Notch-PI3K-AKT pathway in reactive astrocytes may serve as a promising target against CNS inflammatory disorders.


Assuntos
Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Animais , Astrócitos/metabolismo , Células Cultivadas , Sistema Nervoso Central/metabolismo , Citocinas , Lipopolissacarídeos/farmacologia , Camundongos , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
18.
Orphanet J Rare Dis ; 14(1): 292, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842933

RESUMO

BACKGROUND: Methylmalonic acidemia (MMA) and propionic acidemia (PA) are two kinds of diseases caused by inborn errors of metabolism. So far, the epidemiological data on them are limited in China. The aim of our study is to investigate the proportion and characteristics of hospitalized pediatric patients with MMA and PA in China. METHODS: The data in this study were obtained from the Hospital Quality Monitoring System, a national inpatient database in China, with information on the patients hospitalized during the period from 2013 to 2017. We identified the data related to the patients who were under 18 years old and were diagnosed with MMA/PA, and extracted the information on demographic characteristics, hospital location, total cost and other related clinical presentations from the data. RESULTS: Among all hospitalized pediatric patients with liver diseases, there were increasing trends in the proportion of individuals diagnosed with MMA or PA during the period from 2013 (0.76% for MMA; 0.13% for PA) to 2017 (1.61% for MMA; 0.32% for PA). For both MMA and PA, children under 2-year-old accounted for the highest proportion. The median of total cost per hospitalization was relatively high (RMB 7388.53 for MMA; RMB 4999.66 for PA). Moreover, most patients hospitalized in tertiary class A hospitals (MMA: 80.96%, PA: 76.21%); and a majority of pediatric patients admitted in the hospitals in Shanghai and Beijing are from outside districts. Manifestations of nervous system-related symptoms, and metabolic acidosis or anemia in laboratory findings were more common during hospitalization. CONCLUSIONS: The study is the first nationwide one in providing epidemiological and clinical information on hospitalized pediatric patients with MMA/PA. An increasing hospitalization with various presentations and a heavy financial burden were observed. In addition, geographically, the medical resources in China have been unevenly distributed.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Acidemia Propiônica/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/epidemiologia , Pré-Escolar , China/epidemiologia , Bases de Dados Genéticas , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Masculino , Acidemia Propiônica/epidemiologia
19.
PLoS One ; 12(10): e0185249, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28981530

RESUMO

This study proposes a new liver segmentation method based on a sparse a priori statistical shape model (SP-SSM). First, mark points are selected in the liver a priori model and the original image. Then, the a priori shape and its mark points are used to obtain a dictionary for the liver boundary information. Second, the sparse coefficient is calculated based on the correspondence between mark points in the original image and those in the a priori model, and then the sparse statistical model is established by combining the sparse coefficients and the dictionary. Finally, the intensity energy and boundary energy models are built based on the intensity information and the specific boundary information of the original image. Then, the sparse matching constraint model is established based on the sparse coding theory. These models jointly drive the iterative deformation of the sparse statistical model to approximate and accurately extract the liver boundaries. This method can solve the problems of deformation model initialization and a priori method accuracy using the sparse dictionary. The SP-SSM can achieve a mean overlap error of 4.8% and a mean volume difference of 1.8%, whereas the average symmetric surface distance and the root mean square symmetric surface distance can reach 0.8 mm and 1.4 mm, respectively.


Assuntos
Fígado/diagnóstico por imagem , Modelos Anatômicos , Tomografia Computadorizada por Raios X/métodos , Humanos , Fígado/anatomia & histologia
20.
Neural Regen Res ; 10(7): 1147-52, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26330841

RESUMO

MicroRNA-124 (miR-124) is abundantly expressed in neurons in the mammalian central nervous system, and plays critical roles in the regulation of gene expression during embryonic neurogenesis and postnatal neural differentiation. However, the expression profile of miR-124 after spinal cord injury and the underlying regulatory mechanisms are not well understood. In the present study, we examined the expression of miR-124 in mouse brain and spinal cord after spinal cord injury using in situ hybridization. Furthermore, the expression of miR-124 was examined with quantitative RT-PCR at 1, 3 and 7 days after spinal cord injury. The miR-124 expression in neurons at the site of injury was evaluated by in situ hybridization combined with NeuN immunohistochemical staining. The miR-124 was mainly expressed in neurons throughout the brain and spinal cord. The expression of miR-124 in neurons significantly decreased within 7 days after spinal cord injury. Some of the neurons in the peri-lesion area were NeuN(+)/miR-124(-). Moreover, the neurons distal to the peri-lesion site were NeuN(+)/miR-124(+). These findings indicate that miR-124 expression in neurons is reduced after spinal cord injury, and may reflect the severity of spinal cord injury.

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