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1.
Carcinogenesis ; 44(1): 93-104, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-36349938

RESUMO

The p38 MAP kinase (MAPK) signaling pathway is a key signal transduction cascade that cancer cells employ to sense and adapt to a plethora of environmental stimuli and has attracted much attention as a promising target for cancer therapy. Although the kinases that phosphorylate p38 have been extensively studied, the negative regulation of p38 phosphorylation remains to be elucidated. Here, we found that PPM1G was highly expressed in lung adenocarcinoma (LUAD) compared to normal tissues, and higher levels of PPM1G were observed in adverse staged LUAD. Furthermore, the higher levels of PPM1G were highly correlated with poor prognosis, according to the Cancer Genome Atlas cohort. Most importantly, we identified phospho-MEK6 as a direct substrate of PPM1G. PPM1G, a metal-dependent protein phosphatase family phosphatase, could reduce p38 phosphorylation via MEK6 dephosphorylation and contribute to the proliferation, invasion and metastasis of LUAD. Our study highlighted the essential role of PPM1G in LUAD and shed new light on unveiling the regulation of p38 activity via direct dephosphorylation of MEK6 in malignant transformation. Together, this study provides new insight into the complexity of regulating the versatile p38 signaling and suggests new directions in intervening in p38 MAPK signaling.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Fosforilação/fisiologia , Transdução de Sinais , Fosfoproteínas Fosfatases/genética , Adenocarcinoma de Pulmão/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Neoplasias Pulmonares/genética , Linhagem Celular Tumoral , Proliferação de Células , Proteína Fosfatase 2C/genética , Proteína Fosfatase 2C/metabolismo
2.
Small ; 19(1): e2205743, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36372523

RESUMO

Single-atom catalysts (SACs) are of tremendous current research due to maximized use of metal atoms and enhanced activity and selectivity for a great variety of chemical reactions. Hierarchically structured SACs have been explored to further increase the number and accessibility of active sites to realize the full potentials of SACs. However, though plausible-sounding, these supposed advantages of hierarchically structured SACs are largely untested. The assumed enhancing effects on the formation of intermediates on and the overall reaction kinetics remain largely unknown. Herein is reported a Fe-SAC with a hierarchical hollow structure (Fe/HH) that showed excellent activity in oxygen reduction reaction and proton exchange membrane fuel cell. Comparative experimental and computational studies with respect to Fe/SS-the counterpart of Fe/HH with a compact primary structure-reveal a significantly increased number of active sites and their utilization in Fe/HH as reflected by the facilitated formation of the rate-determining-step intermediate Fe-OOH*. This work thus establishes unambiguously the connection between the increased utilization of active sites and the enhanced kinetics of the electrocatalytic reduction of oxygen.


Assuntos
Hipóxia , Oxigênio , Humanos , Domínio Catalítico , Cinética , Membrana Celular
3.
Small ; 19(38): e2301261, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37222124

RESUMO

Perovskite oxides stand out as emerging oxygen evolution reaction (OER) catalysts on account of their effective electrocatalytic performance and low costs. Nevertheless, perovskite oxides suffer from severe bubble overpotential and inhibited electrochemical performance in large current densities due to their small specific surface areas and structural compactness. Herein, the study highlights the electrospun nickel-substituted La0.5 Sr0.5 FeO3-δ (LSF) porous perovskite nanofibers, that is, La0.5 Sr0.5 Fe1-x Nix O3-δ (denoted as ES-LSFN-x, x = 0, 0.1, 0.3, and 0.5), as high-performance OER electrocatalysts. The most effective La0.5 Sr0.5 Fe0.5 Ni0.5 O3-δ (ES-LSFN-0.5) nanofibers suggest a larger specific surface area, higher porosity, and faster mass transfer than the counterpart sample prepared by conventional sol-gel method (SG-LSFN-0.5), showing notably increased geometric and intrinsic activities. The bubble visualization results demonstrate that the enriched and nano-sized porosity of ES-LSFN-0.5 enables reinforced aerophobicity and rapid detachment of oxygen bubbles, thereby reducing the bubble overpotential and enhancing the electrochemical performance. As a result, the ES-LSFN-0.5-based anion exchange membrane water electrolysis delivers a superior stability of 100 h while the SG-LSFN-0.5 counterpart degrades rapidly within 20 h under a current density of 100 mA cm-2 . The results highlight the advantage of porous electrocatalysts in optimizing the performance of large current density water electrolysis devices by reducing the bubble overpotential.

4.
Environ Res ; 231(Pt 2): 116192, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37201701

RESUMO

The response characteristic and performance stabilization of anammox process under the stress of the potential organic pollutants support the application of ammonia-nitrogen wastewater treatment. In the present study, nitrogen removal performance was significantly suppressed with the addition of 4-chlorophenol. The activity of anammox process was inhibited by 14.23% (0.1 mg/L), 20.54% (1 mg/L) and 78.15% (10 mg/L), respectively. Metagenomic analysis revealed a significant decrease in the abundance of KEGG pathways associated with carbohydrate and amino acid metabolism with increasing 4-chlorophenol concentration. Metabolic pathway profiles suggest that putrescine is down-regulated at high 4-chlorophenol stress due to inhibition of nitrogen metabolism processes, while it is up-regulated to reduce oxidative damage. In addition, the presence of 4-chlorophenol induced an enhancement of EPS and bacterial debris decomposition, and a partial conversion of 4-chlorophenol to p-nitrophenol. This study unravels the mechanism of effect on anammox consortia in response to 4-CP, which could provide supplementary to facilitate its full-scale application.


Assuntos
Desnitrificação , Águas Residuárias , Oxidação Anaeróbia da Amônia , Nitrogênio/metabolismo , Oxirredução , Reatores Biológicos/microbiologia , Esgotos
5.
BMC Psychiatry ; 23(1): 887, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-38017507

RESUMO

BACKGROUND: There is a complex relationship between social anxiety and sleep quality. However, network analysis studies of associations between social anxiety and sleep quality are lacking, particularly among patients with breast cancer. The current study aimed to extend this research to a sample of patients with breast cancer and to examine symptom-level associations between social anxiety and sleep quality using network analysis. METHODS: Network analysis was conducted to explore their associations and identify bridge items of social anxiety and sleep quality. RESULTS: The network structure revealed 9 important edges between social anxiety and sleep quality. "Subjective sleep quality" had the highest EI value in the network. "Working difficulty under watching" and "Sleep disorders" had the highest BEI values in their own communities. CONCLUSION: There are complex pathological correlation pathways between social anxiety and sleep quality in breast cancer patients. "Subjective sleep quality", "Working difficulty under watching" and "Sleep disorders" have the potential to be intervention targets for sleep disorder-social anxiety comorbidity. Medical staff can take corresponding interventions according to the the centrality indices and bridge centrality indicators identified in this study, which is likely to effectively reduce the comorbidity of sleep disorders and social anxiety.


Assuntos
Neoplasias da Mama , Transtornos do Sono-Vigília , Humanos , Feminino , Qualidade do Sono , Neoplasias da Mama/complicações , Medo , Comorbidade , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/epidemiologia , Ansiedade/complicações , Depressão
6.
Cell Biochem Funct ; 41(8): 1106-1114, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38041420

RESUMO

The N-methyladenosine (m6A) modification of ribosomal RNA (rRNA) plays critical roles in regulating the function of ribosomes, the essential molecular machines that translate genetic information from mRNA into proteins. Specifically, m6A modification affects ribosome biogenesis, stability, and function by regulating the processing and maturation of rRNA, the assembly and composition of ribosomes, and the accuracy and efficiency of translation. Furthermore, m6A modification allows for dynamic regulation of translation in response to environmental and cellular signals. Therefore, a deeper understanding of the mechanisms and functions of m6A modification in rRNA will advance our knowledge of ribosome-mediated gene expression and facilitate the development of new therapeutic strategies for ribosome-related diseases.


Assuntos
RNA Ribossômico , Ribossomos , RNA Ribossômico/genética , RNA Ribossômico/metabolismo , Ribossomos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Metilação
7.
Phytopathology ; 112(6): 1264-1272, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34982575

RESUMO

Botrytis cinerea causes gray mold resulting in enormous financial loss. Fungicide resistance of B. cinerea has become a serious issue in food safety and agricultural environmental protection. Sodium valproate (SV) has been used in clinical trials; thus, it is an excellent candidate for fungicide development, considering its safety. However, the antifungal activity remains unclear. SV was effective against B. cinerea by enhancing acetylation of histone H3, including H3K9ac, H3K14ac, and H3K56ac. A transcriptomics analysis revealed that the expression of 1,557 genes changed significantly in response to SV. A pathway enrichment analysis identified 16 significant GO terms, in which molecular functions were mainly involved. In addition, the expression levels of 13 genes involved in B. cinerea virulence and five genes involved in tomato immune response were altered by the SV treatment. These results indicate that SV inhibits B. cinerea by enhancing acetylation of histone H3 and modifying gene transcription. Thus, SV is an effective, safe, potential antifungal agent for control of both pre- and postharvest losses caused by B. cinerea.


Assuntos
Fungicidas Industriais , Solanum lycopersicum , Acetilação , Antifúngicos/metabolismo , Botrytis/genética , Frutas/microbiologia , Fungicidas Industriais/metabolismo , Fungicidas Industriais/farmacologia , Histonas/genética , Histonas/metabolismo , Imunidade , Solanum lycopersicum/genética , Solanum lycopersicum/microbiologia , Doenças das Plantas/microbiologia , Transcrição Gênica , Ácido Valproico/metabolismo , Ácido Valproico/farmacologia
8.
BMC Public Health ; 21(1): 1977, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34727917

RESUMO

BACKGROUND: With increasing urbanization in developing countries, sanitation workers are frequently involved in road traffic collisions. Our purpose was to study specific collisions involving sanitation workers and provide decision-making suggestions and reference measures for the sanitation industry and urban managers to reduce the occurrence of collisions. METHODS: We obtained online news data about sanitation worker road traffic collisions in China between 2013 and 2017 and analyzed occurrence time and location, victim characteristics, and causes of collisions. RESULTS: In China, between 2013 and 2017, 511 road traffic collisions were reported, with the fewest in February and July. Most occurred around 5:00 a.m. in Eastern regions and in urban areas. Victims were mainly over 50 years old, with more females than males. Collisions usually resulted in death at the scene. The ambiguity of laws, the exploitation of workers through industry outsourcing, and the difficulty of processing claims may be the main factors preventing victims from obtaining legal compensation. CONCLUSIONS: The most common cause of collisions was drivers' speeding, but workers also regularly risk death by crossing the road in pursuit of their duties. The absence of legal controls for environmental protection, the excessive pursuit of efficiency in urban governance, and the lack of basic education of sanitation workers are underlying causes of collisions. Raising awareness about sanitation worker road traffic collisions will help protect the work safety rights of this vulnerable group.


Assuntos
Acidentes de Trânsito , Saneamento , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
J Sci Food Agric ; 101(13): 5314-5324, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34032287

RESUMO

Soy contains many bioactive phytochemicals, such as isoflavones, which have the effect of preventing many cancers. Some studies have shown the beneficial effect of soy-based food and isoflavone intake on gastric cancer (GC), while others claimed no effect. Therefore, whether the beneficial effect of soy-based food is related to its fermentation or whether its protective effect comes from isoflavones still remains inconclusive. Our aim was to investigate the relationship between total soybean, fermented soybean, non-fermented soybean and isoflavone intake, and the risk of GC. Ten cohort studies and 21 case-control studies involving 916 354 participants were included. The association between soy-based food and isoflavone intake and the risk of GC was calculated with the pooled relative risks (RRs) for the highest versus lowest intake categories. The results showed that isoflavone intake might be a protective factor to GC, but the result was not statistically significant (RR = 0.92; 95% CI: 0.79-1.07). However, total soybean intake could significantly decrease the risk of GC by 36% (RR = 0.64; 95% CI: 0.51-0.80), which might be credited to non-fermented soybean products (RR = 0.79; 95% CI: 0.71-0.87). In contrast, high intake of fermented soybean products could increase the risk of GC (RR = 1.19; 95% CI: 1.02-1.38). High intake of total soybean and non-fermented soybean products could reduce the risk of GC, and high intake of fermented soybean products could increase the risk, which indicated that the beneficial effect of soy-based food might be related to its non-fermentation. However, high intake of isoflavones may not be associated with the incidence of GC. © 2021 Society of Chemical Industry.


Assuntos
Glycine max/metabolismo , Isoflavonas/metabolismo , Substâncias Protetoras/metabolismo , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Isoflavonas/análise , Masculino , Pessoa de Meia-Idade , Substâncias Protetoras/análise , Fatores de Risco , Sementes/química , Sementes/metabolismo , Alimentos de Soja/análise , Glycine max/química , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/prevenção & controle , Adulto Jovem
10.
J Exp Bot ; 71(14): 4083-4092, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32280991

RESUMO

The maturation of male and female gametophytes together with its impact on plant sexual reproduction has not received much attention, and the molecular mechanisms underlying the process are largely unknown. Here, we show that Arabidopsis DEAD-box RNA helicase 29 (RH29) is critical for the functional maturation of both male and female gametophytes. Homozygous rh29 mutants could not be obtained, and heterozygous mutant plants were semi-sterile. Progression of the cell cycle in rh29 female gametophytes was delayed. Delayed pollination experiments showed that rh29 female gametophytes underwent cell-fate specification but were unable to develop into functional gametophytes. Functional specification but not morphogenesis was also disrupted in rh29 male gametophytes, causing defective pollen tube growth in the pistil. RH29 was highly and specifically expressed in gametophytic cells. RH29 shares high amino acid sequence identity with yeast Dbp10p, which partially rescues the aborted-ovules phenotype of rh29/RH29 plants. RH29 is essential for the synthesis of REGULATORY PARTICLE TRIPLE A ATPase 5a (RPT5a), a subunit of the regulatory particle of the 26S proteasome. Our results suggest that gametophyte functional maturation is a necessary process for successful fertilization and that RH29 is essential for the functional maturation of both male and female gametophytes.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Proteínas de Arabidopsis/genética , RNA Helicases DEAD-box/genética , Células Germinativas Vegetais , Mutação , Óvulo Vegetal/genética
11.
BMC Public Health ; 20(1): 1164, 2020 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-32711503

RESUMO

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) that first occurred in Wuhan, China, is currently spreading throughout China. The majority of infected patients either traveled to Wuhan or came into contact with an infected person from Wuhan. Investigating members of the public with a travel history to Wuhan became the primary focus of the Chinese government's epidemic prevention and control measures, but several instances of withheld histories were uncovered as localized clusters of infections broke out. This study investigated the public's willingness and beliefs associated with reporting travel history to high-risk epidemic regions, to provide effective suggestions and measures for encouraging travel reporting. METHODS: A cross-sectional study was conducted online between February 12 and 19, 2020. Descriptive analysis, chi-squared test, and Fisher's exact test were used to identify socio-demographic factors and beliefs associated with reporting, as well as their impact on the willingness to report on travel history to high-risk epidemic regions. RESULTS: Of the 1344 respondents, 91 (6.77%) expressed an inclination to deliberately withhold travel history. Those who understood the benefits of reporting and the legal consequences for deliberately withholding information, showed greater willingness to report their history (P < 0.05); conversely, those who believed reporting would stigmatize them and feared being quarantined after reporting showed less willingness to report (P < 0.05). CONCLUSIONS: As any incident of withheld history can have unpredictable outcomes, the proportion of people who deliberately withhold information deserves attention. Appropriate public risk communication and public advocacy strategies should be implemented to strengthen the understanding that reporting on travel history facilitates infection screening and prompt treatment, and to decrease the fear of potentially becoming quarantined after reporting. Additionally, social support and policies should be established, and measures should be taken to alleviate stigmatization and discrimination against potential patients and reporters of travel history. Reinforcing the legal accountability of withholding travel history and strengthening systematic community monitoring are the measures that China is currently taking to encourage reporting on travel history to high-risk epidemic regions. These non-pharmaceutical interventions are relevant for countries that are currently facing the spread of the epidemic and those at risk of its potential spread.


Assuntos
Infecções por Coronavirus/epidemiologia , Epidemias , Conhecimentos, Atitudes e Prática em Saúde , Pneumonia Viral/epidemiologia , Viagem/estatística & dados numéricos , Adulto , COVID-19 , China/epidemiologia , Infecções por Coronavirus/prevenção & controle , Estudos Transversais , Feminino , Governo , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Quarentena/psicologia , Medição de Risco , Adulto Jovem
12.
BMC Health Serv Res ; 20(1): 936, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046067

RESUMO

BACKGROUND: To evaluate the impact of a restricted access policy on workplace violence in a healthcare setting. METHODS: We surveyed healthcare workers before and after the implementation of a restricted-access policy at a tertiary hospital in north-eastern China. Data were collected in April 2017 and January 2019. Fisher's exact test were used to compare the difference in workplace violence prevalence between responses to two surveys. Survey 1 (S1) collected data from 345 healthcare professionals who had worked in the inpatient ward for at least 12 months. Survey 2 (S2) included 338 healthcare workers from the same ward who had been employed for more than two years. The effective response rates for the two studies was 79.31 and 83.25%, respectively. All 18 female security guards were included in the investigation in S2. RESULTS: The prevalence of psychological violence was 62.03% in S1 and 34.62% in S2, the difference in prevalence showing statistical significance (P = 0.000), while the prevalence of physical violence was 3.77 and 4.73% respectively, showing no statistical significance (P = 0.573). The change in the rate of injury caused by physical violence was also statistically significant at 76.92 and 31.25% (P = 0.025), respectively. Security guards were at high risk of workplace violence under the policy. Most healthcare professionals thought this policy ameliorated treatment order, the sense of security, anxiety about workplace violence, and so forth, but one-third of the respondents thought that it caused patient dissatisfaction. CONCLUSION: While the restricted access policy may be effective for healthcare professionals in avoiding or dealing with violence, such policy could contribute to new problems regarding the safety of security guards and the potential dissatisfaction of patients. The policy should be further developed to alleviate this phenomenon.


Assuntos
Hospitais Gerais/organização & administração , Política Organizacional , Violência no Trabalho/prevenção & controle , Adulto , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recursos Humanos em Hospital/psicologia , Recursos Humanos em Hospital/estatística & dados numéricos , Inquéritos e Questionários , Centros de Atenção Terciária/organização & administração , Violência no Trabalho/estatística & dados numéricos
13.
J Enzyme Inhib Med Chem ; 34(1): 250-263, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30734612

RESUMO

With the aim of discovering novel IDO1 inhibitors, a combined similarity search and molecular docking approach was employed to the discovery of 32 hit compounds. Testing the screened hit compounds has led to several novel submicromolar inhibitors. Especially for compounds LVS-019 with cyanopyridine scaffold, showed good IDO1 inhibitory activity. To discover more compounds with similar structures to LVS-019, a shape-based model was then generated on the basis of it and the second-round virtual screening was carried out leading to 23 derivatives. Molecular docking studies suggested a possible binding mode of LVS-019, which provides a good starting point for the development of cyanopyridine scaffold compounds as potent IDO1 inhibitor. To improve potency of these hits, we further designed and synthesised another 14 derivatives of LVS-019. Among these compounds, LBJ-10 showed improved potency compared to the hits and displayed comparable potency to the control GDC-0919 analogue. LBJ-10 can serve as ideal leads for further modifications as IDO1 inhibitors for cancer treatment.


Assuntos
Descoberta de Drogas , Inibidores Enzimáticos/farmacologia , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Piridinas/farmacologia , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Simulação de Acoplamento Molecular , Estrutura Molecular , Piridinas/síntese química , Piridinas/química , Relação Estrutura-Atividade
14.
J Integr Plant Biol ; 60(4): 266-269, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29193792

RESUMO

During embryogenesis, plants are thought to use a mechanism that allows the suspensor to maintain its identity. Here, we reported that RPL18aB is involved in this mechanism in Arabidopsis thaliana. The suspensor cells proliferated in rpl18aB and formed a multicellular structure rather than undergo programmed cell death, as in wild type. Suspensors of rpl18aB expressed the embryo proper marker, DRN::GFP, but not the suspensor marker, WOX8::GFP. In addition, auxin accumulated throughout the suspensors of rpl18aB proembryos. Suspensor-specific expression of RPL18aB could rescue the cell proliferation defects in rpl18aB suspensors. These findings supported a role for RPL18aB in maintaining suspensor identity.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/embriologia , Arabidopsis/metabolismo , Proteínas Ribossômicas/metabolismo , Sementes/embriologia , Sementes/metabolismo , Arabidopsis/genética , Ácidos Indolacéticos/metabolismo , Plantas Geneticamente Modificadas
15.
Wei Sheng Wu Xue Bao ; 57(1): 54-65, 2017 Jan 04.
Artigo em Zh | MEDLINE | ID: mdl-29746760

RESUMO

Objective: We aimed at co-expressing heterologous D-hydantoinase and N-carbamoylase in Bacillus subtilis, and evaluating the feasibility of producing D-p-hydroxyphenylglycine by the recombinant B. subtilis whole-cell catalysis. Methods: The Paco expression cassette was combined with the coding sequence of hyd or sd1 gene as an artificial gene to express D-hydantoinase. The PAE expression cassette was combined with the coding sequence of adc gene as an artificial gene to express N-carbamoylase. The D-hydantoinase and N-carbamoylase co-expression plasmids pHCS(sd1+adc) and pHCY(hyd+adc) were constructed, using plasmid pHP13 as carrier; the co-expression plasmids pUCS(sd1+adc) was constructed, using plasmid pUB110 as carrier. The additional copy of acoR and sigL gene was integrated at chromosome. The skf and sdp gene were knocked out in B. subtilis. All recombinant strains bearing co-expression plasmid were characterized by analyzing whole-cell catalysis activity. Results: In the recombinant strains with plasmid pHCY and with pHCS, the whole-cell catalytic activity reached 0.21 U/mL and 0.31 U/mL, respectively. After the over-expression of acoR, sigL, and high-copy-number pUCS, the whole-cell catalytic activity reached 1.0 U/mL. Conclusion: Overexpression of acoR, sigL and the deletion of skf, sdp genes had significant effects on the catalysis activity of recombinant whole-cell.


Assuntos
Amidoidrolases/genética , Bacillus subtilis/genética , Proteínas de Bactérias/genética , Glicina/análogos & derivados , Amidoidrolases/metabolismo , Bacillus subtilis/metabolismo , Proteínas de Bactérias/metabolismo , Geobacillus stearothermophilus/enzimologia , Glicina/biossíntese , Engenharia Metabólica , Plasmídeos/genética , Plasmídeos/metabolismo , Rhodobacteraceae/enzimologia
16.
J Control Release ; 372: 778-794, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38936744

RESUMO

Alopecia areata affects over 140 million people worldwide and causes severe psychological distress. The Janus kinase (JAK) inhibitor, tofacitinib, shows significant potential in therapeutic applications for treating alopecia areata; however, the systemic adverse effects of oral administration and low absorption rate at the target site limit its application. Hence, to address this issue, we designed topical formulations of tofacitinib-loaded cationic lipid nanoparticles (TFB-cNLPs) with particle sizes of approximately 200 nm. TFB-cNLPs promoted percutaneous absorption and hair follicle targeting in an ex vivo pig ear model. TFB-cNLP decreased IFN-γ-induced alopecia areata symptoms in an in vitro follicle model by blocking the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. It also reduced the number of CD8+NKG2D+T cells in a C3H mouse model of alopecia areata in vivo, thereby inhibiting the progression of alopecia areata and reversing hair loss. These findings suggest that TFB-cNLP enhanced hair follicle targeting and has the potential for topical treatment or prevention of alopecia areata.


Assuntos
Alopecia em Áreas , Portadores de Fármacos , Folículo Piloso , Lipídeos , Piperidinas , Pirimidinas , Absorção Cutânea , Animais , Alopecia em Áreas/tratamento farmacológico , Folículo Piloso/metabolismo , Folículo Piloso/efeitos dos fármacos , Piperidinas/administração & dosagem , Piperidinas/farmacocinética , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Pirimidinas/administração & dosagem , Pirimidinas/farmacocinética , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Suínos , Lipídeos/química , Lipídeos/administração & dosagem , Portadores de Fármacos/química , Camundongos Endogâmicos C3H , Nanopartículas/administração & dosagem , Camundongos , Nanoestruturas/administração & dosagem , Feminino , Lipossomos
17.
Materials (Basel) ; 17(15)2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39124346

RESUMO

Concrete structures frequently manifest diverse defects throughout their manufacturing and usage processes due to factors such as design, construction, environmental conditions and distress mechanisms. In this paper, a multilevel convolutional neural network (CNN) combined with array ultrasonic testing (AUT) is proposed for identifying the locations of hole defects in concrete structures. By refining the detection area layer by layer, AUT is used to collect ultrasonic signals containing hole defect information, and the original echo signal is input to CNN for the classification of hole locations. The advantage of the proposed method is that the corresponding defect location information can be obtained directly from the input ultrasonic signal without manual discrimination. It effectively addresses the issue of traditional methods being insufficiently accurate when dealing with complex structures or hidden defects. The analysis process is as follows. First, COMSOL-Multiphysics finite element software is utilized to simulate the AUT detection process and generate a large amount of ultrasonic echo data. Next, the extracted signal data are trained and learned using the proposed multilevel CNN approach to achieve progressive localization of internal structural defects. Afterwards, a comparative analysis is conducted between the proposed multilevel CNN method and traditional CNN approaches. The results show that the defect localization accuracy of the proposed multilevel CNN approach improved from 85.38% to 95.27% compared to traditional CNN methods. Furthermore, the computation time required for this process is reduced, indicating that the method not only achieves higher recognition precision but also operates with greater efficiency. Finally, a simple experimental verification is conducted; the results show that this method has strong robustness in recognizing noisy ultrasonic signals, provides effective solutions, and can be used as a reference for future defect detection.

18.
NanoImpact ; 35: 100515, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38857755

RESUMO

This study explored the response of superoxide dismutase (SOD) under superparamagnetic iron oxide nanoparticles (SPIONs)-induced oxidative stress using combined cellular and molecular methods. Results found that SPIONs induced the inhibition of catalase activity, the U-inverted change of SOD activity and the accumulation of reactive oxygen species (ROS), leading to oxidative damage and cytotoxicity. The change of intracellular SOD activity was resulted from the increase of molecular activity induced by directly interacting with SPIONs and ROS-inhibition of activity. The increase of molecular activity could be attributed to the structural and conformational changes of SOD, which were caused by the direct interaction of SOD with SPIONs. The SOD-SPIONs interaction and its interacting mechanism were explored by multi-spectroscopy, isothermal titration calorimetry and zeta potential assays. SOD binds to SPIONs majorly via hydrophobic forces with the involvement of electrostatic forces. SPIONs approximately adsorb 11 units of SOD molecule with the binding affinity of 2.99 × 106 M-1. The binding sites on SOD were located around Tyr residues, whose hydrophilicity increased upon interacting with SPIONs. The binding to SPIONs loosened the peptide chains, changed the secondary structure and reduced the aggregation state of SOD.

19.
Emotion ; 24(6): 1417-1427, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38512195

RESUMO

Previous research has shown mixed results regarding the relationship between social class and children's prosocial behavior. The current study aims to further our understanding of these findings by exploring the relationship between social class and children's prosocial behavior in a moral context. Study 1 (N = 833) found that when a target child pursued a morally negative goal and subsequently experienced misfortune, children from higher social class, compared to those from lower social class, experienced greater schadenfreude and exhibited less prosocial behavior. The relation between social class and prosocial behavior was mediated by schadenfreude. Study 2 (N = 389) investigated whether the greater schadenfreude experienced by children from higher social class was due to a weaker empathic response to misfortune or a stronger sense of deservingness. The results revealed a sequential mediation effect of social class on prosocial behavior through deservingness and schadenfreude. These findings provide insight into the impact of social class on the development of children's moral judgment, emotions, and behavior. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Comportamento Infantil , Empatia , Princípios Morais , Comportamento Social , Classe Social , Humanos , Masculino , Feminino , Criança , Empatia/fisiologia , Emoções
20.
Eur J Gastroenterol Hepatol ; 36(7): 916-923, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38829944

RESUMO

Infections significantly increase mortality in acute liver failure (ALF) patients, and there are no risk prediction models for early diagnosis and treatment of infections in ALF patients. This study aims to develop a risk prediction model for bacterial infections in ALF patients to guide rational antibiotic therapy. The data of ALF patients admitted to the Second Hospital of Hebei Medical University in China from January 2017 to January 2022 were retrospectively analyzed for training and internal validation. Patients were selected according to the updated 2011 American Association for the Study of Liver Diseases position paper on ALF. Serological indicators and model scores were collected within 24 h of admission. New models were developed using the multivariate logistic regression analysis. An optimal model was selected by receiver operating characteristic (ROC) analysis, Hosmer-Lemeshow test, the calibration curve, the Brier score, the bootstrap resampling, and the decision curve analysis. A nomogram was plotted to visualize the results. A total of 125 ALF patients were evaluated and 79 were included in the training set. The neutrophil-to-lymphocyte ratio and sequential organ failure assessment (SOFA) were integrated into the new model as independent predictive factors. The new SOFA-based model outperformed other models with an area under the ROC curve of 0.799 [95% confidence interval (CI): 0.652-0.926], the superior calibration and predictive performance in internal validation. High-risk individuals with a nomogram score ≥26 are recommended for antibiotic therapy. The new SOFA-based model demonstrates high accuracy and clinical utility in guiding antibiotic therapy in ALF patients.


Assuntos
Antibacterianos , Infecções Bacterianas , Falência Hepática Aguda , Nomogramas , Escores de Disfunção Orgânica , Curva ROC , Humanos , Feminino , Masculino , Falência Hepática Aguda/diagnóstico , Pessoa de Meia-Idade , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/tratamento farmacológico , Medição de Risco , Estudos Retrospectivos , Adulto , Antibacterianos/uso terapêutico , Fatores de Risco , China/epidemiologia , Valor Preditivo dos Testes , Neutrófilos , Reprodutibilidade dos Testes , Contagem de Linfócitos
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