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1.
Carcinogenesis ; 44(1): 93-104, 2023 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-36349938

RESUMEN

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.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Fosforilación/fisiología , Transducción de Señal , Fosfoproteínas Fosfatasas/genética , Adenocarcinoma del Pulmón/genética , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Neoplasias Pulmonares/genética , Línea Celular Tumoral , Proliferación Celular , Proteína Fosfatasa 2C/genética , Proteína Fosfatasa 2C/metabolismo
2.
Small ; 19(1): e2205743, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36372523

RESUMEN

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.


Asunto(s)
Hipoxia , Oxígeno , Humanos , Dominio Catalítico , Cinética , Membrana Celular
3.
Small ; 19(38): e2301261, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37222124

RESUMEN

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.
Artículo en Inglés | MEDLINE | ID: mdl-37201701

RESUMEN

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.


Asunto(s)
Desnitrificación , Aguas Residuales , Oxidación Anaeróbica del Amoníaco , Nitrógeno/metabolismo , Oxidación-Reducción , Reactores Biológicos/microbiología , Aguas del Alcantarillado
5.
BMC Psychiatry ; 23(1): 887, 2023 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-38017507

RESUMEN

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.


Asunto(s)
Neoplasias de la Mama , Trastornos del Sueño-Vigilia , Humanos , Femenino , Calidad del Sueño , Neoplasias de la Mama/complicaciones , Miedo , Comorbilidad , Trastornos del Sueño-Vigilia/complicaciones , Trastornos del Sueño-Vigilia/epidemiología , Ansiedad/complicaciones , Depresión
6.
Cell Biochem Funct ; 41(8): 1106-1114, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38041420

RESUMEN

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.


Asunto(s)
ARN Ribosómico , Ribosomas , ARN Ribosómico/genética , ARN Ribosómico/metabolismo , Ribosomas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Metilación
7.
Phytopathology ; 112(6): 1264-1272, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34982575

RESUMEN

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.


Asunto(s)
Fungicidas Industriales , Solanum lycopersicum , Acetilación , Antifúngicos/metabolismo , Botrytis/genética , Frutas/microbiología , Fungicidas Industriales/metabolismo , Fungicidas Industriales/farmacología , Histonas/genética , Histonas/metabolismo , Inmunidad , Solanum lycopersicum/genética , Solanum lycopersicum/microbiología , Enfermedades de las Plantas/microbiología , Transcripción Genética , Ácido Valproico/metabolismo , Ácido Valproico/farmacología
8.
BMC Public Health ; 21(1): 1977, 2021 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-34727917

RESUMEN

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.


Asunto(s)
Accidentes de Tránsito , Saneamiento , China/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad
9.
J Sci Food Agric ; 101(13): 5314-5324, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34032287

RESUMEN

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.


Asunto(s)
Glycine max/metabolismo , Isoflavonas/metabolismo , Sustancias Protectoras/metabolismo , Neoplasias Gástricas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Isoflavonas/análisis , Masculino , Persona de Mediana Edad , Sustancias Protectoras/análisis , Factores de Riesgo , Semillas/química , Semillas/metabolismo , Alimentos de Soja/análisis , Glycine max/química , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/prevención & control , Adulto Joven
10.
J Exp Bot ; 71(14): 4083-4092, 2020 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-32280991

RESUMEN

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.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Proteínas de Arabidopsis/genética , ARN Helicasas DEAD-box/genética , Células Germinativas de las Plantas , Mutación , Óvulo Vegetal/genética
11.
BMC Public Health ; 20(1): 1164, 2020 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-32711503

RESUMEN

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.


Asunto(s)
Infecciones por Coronavirus/epidemiología , Epidemias , Conocimientos, Actitudes y Práctica en Salud , Neumonía Viral/epidemiología , Viaje/estadística & datos numéricos , Adulto , COVID-19 , China/epidemiología , Infecciones por Coronavirus/prevención & control , Estudios Transversales , Femenino , Gobierno , Humanos , Masculino , Persona de Mediana Edad , Pandemias/prevención & control , Neumonía Viral/prevención & control , Cuarentena/psicología , Medición de Riesgo , Adulto Joven
12.
BMC Health Serv Res ; 20(1): 936, 2020 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-33046067

RESUMEN

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.


Asunto(s)
Hospitales Generales/organización & administración , Política Organizacional , Violencia Laboral/prevención & control , Adulto , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Personal de Hospital/psicología , Personal de Hospital/estadística & datos numéricos , Encuestas y Cuestionarios , Centros de Atención Terciaria/organización & administración , Violencia Laboral/estadística & datos numéricos
13.
J Enzyme Inhib Med Chem ; 34(1): 250-263, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30734612

RESUMEN

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.


Asunto(s)
Descubrimiento de Drogas , Inhibidores Enzimáticos/farmacología , Indolamina-Pirrol 2,3,-Dioxigenasa/antagonistas & inhibidores , Piridinas/farmacología , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Humanos , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Simulación del Acoplamiento Molecular , Estructura Molecular , Piridinas/síntesis química , Piridinas/química , Relación Estructura-Actividad
14.
J Integr Plant Biol ; 60(4): 266-269, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29193792

RESUMEN

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.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/embriología , Arabidopsis/metabolismo , Proteínas Ribosómicas/metabolismo , Semillas/embriología , Semillas/metabolismo , Arabidopsis/genética , Ácidos Indolacéticos/metabolismo , Plantas Modificadas Genéticamente
15.
Wei Sheng Wu Xue Bao ; 57(1): 54-65, 2017 Jan 04.
Artículo en Zh | MEDLINE | ID: mdl-29746760

RESUMEN

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.


Asunto(s)
Amidohidrolasas/genética , Bacillus subtilis/genética , Proteínas Bacterianas/genética , Glicina/análogos & derivados , Amidohidrolasas/metabolismo , Bacillus subtilis/metabolismo , Proteínas Bacterianas/metabolismo , Geobacillus stearothermophilus/enzimología , Glicina/biosíntesis , Ingeniería Metabólica , Plásmidos/genética , Plásmidos/metabolismo , Rhodobacteraceae/enzimología
16.
J Control Release ; 372: 778-794, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38936744

RESUMEN

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.


Asunto(s)
Alopecia Areata , Portadores de Fármacos , Folículo Piloso , Lípidos , Piperidinas , Pirimidinas , Absorción Cutánea , Animales , Alopecia Areata/tratamiento farmacológico , Folículo Piloso/metabolismo , Folículo Piloso/efectos de los fármacos , Piperidinas/administración & dosificación , Piperidinas/farmacocinética , Piperidinas/farmacología , Piperidinas/uso terapéutico , Pirimidinas/administración & dosificación , Pirimidinas/farmacocinética , Pirimidinas/farmacología , Pirimidinas/uso terapéutico , Porcinos , Lípidos/química , Lípidos/administración & dosificación , Portadores de Fármacos/química , Ratones Endogámicos C3H , Nanopartículas/administración & dosificación , Ratones , Nanoestructuras/administración & dosificación , Femenino , Liposomas
17.
NanoImpact ; 35: 100515, 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38857755

RESUMEN

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.

18.
Emotion ; 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38512195

RESUMEN

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).

19.
Heliyon ; 10(11): e31250, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38828344

RESUMEN

This study aimed to ascertain the delayed effects of various exposure temperatures on infectious diarrhea. We performed a Bayesian random-effects network meta-analysis to calculate relative risks (RR) with 95 % confidence intervals (95 % CI). The heterogeneity was analyzed by subgroup analysis. There were 25 cross-sectional studies totaling 6858735 patients included in this analysis, with 12 articles each investigating the effects of both hyperthermia and hypothermia. Results revealed that both high temperature (RRsingle = 1.22, 95%CI:1.04-1.44, RRcum = 2.96, 95%CI:1.60-5.48, P < 0.05) and low temperature (RRsingle = 1.17, 95%CI:1.02-1.37, RRcum = 2.19, 95%CI:1.33-3.64, P < 0.05) significantly increased the risk of infectious diarrhea, while high temperature caused greater. As-sociations with strengthening in bacillary dysentery were found for high temperatures (RRcum = 2.03, 95%CI:1.41-3.01, P < 0.05; RRsingle = 1.17, 95%CI:0.90-1.62, P > 0.05), while the statistical significance of low temperatures in lowering bacterial dysentery had vanished. This investigation examined that high temperature and low temperature were the conditions that posed the greatest risk for infectious diarrhea. This research offers fresh perspectives on preventing infectious diarrhea and will hopefully enlighten future studies on the impact of temperature management on infectious diarrhea.

20.
J Colloid Interface Sci ; 658: 772-782, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38154240

RESUMEN

Aerogels with 3D porous structures have been attracting increasing attention among functional materials due to their advantages of being lightweight and high specific surface area. Precise control of the porous structure of aerogel is essential to improve its performance. In this work, polylactic acid (PLA) aerogels with distinctly different microstructures were fabricated by precisely controlling the phase separation behavior of the ternary solution system. Rheological and theoretical analyses have revealed that the interactions between polymer molecules, solvents and non-solvents play a crucial role in determining the nucleation and growth of poor olymer and rich polymer phases. By adjusting the non-solvent type and the solution composition, aerogels with spider network structure, bead-like connected microsphere structure, and cluster petal structure were obtained. Ideal spinodal phase separation conditions were obtained to produce aerogels with a homogeneous fiber network structure. The optimum PLA aerogel achieved an extremely porosity of 96 % and a high specific surface area of 114 m2/g, which rendered it with excellent triboelectric generation performance. Thus, this work provides fundamental insights into the precise regulation of the phase separation behavior and the structure of the aerogel, which can help boost the performance and expand the applications of PLA aerogels.

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