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1.
World J Pediatr ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35006581

RESUMO

BACKGROUND: Combining local anesthetics with dexmedetomidine (DEX) for nerve blocks has been tested and confirmed as an alternative technique to strengthen analgesia in adults, but the evidence supported this proposal in pediatrics was not convincing enough. Thus, we intend to conduct a meta-analysis to make an appraisal of the effects of DEX as a local anesthetic adjuvant on peripheral nerve blocks in children. METHODS: The analysis has been registered on https://www.crd.york.ac.uk/prospero/ with the registration number CRD42021254029 on June 10th, 2021. PubMed, Ovid MEDLINE, Embase and Cochrane central register were searched for the randomized controlled trials (RCTs) that are relevant to child/pain/DEX or block up to April 30, 2021. RESULTS: Eight RCTs were included for data analysis. The pooled results showed a significantly reduced number of patients who required postoperative analgesics within DEX groups [odds ratio = 0.1, 95% confidence interval (CI) 0.03-0.32, P < 0.001]. And DEX significantly prolonged the duration of analgesia of local anesthetics in the meantime [standardized mean difference (SMD) = 4.93, 95% CI 3.02-6.83, P < 0.001]. Nevertheless, adding DEX as an adjunct to local anesthetics would significantly decrease heart rate (SMD = - 0.95, 95% CI - 1.45 to - 0.45, P < 0.001) and increase sedation score (SMD = 1.6, 95% CI 0.53-2.66, P = 0.003) simultaneously. CONCLUSIONS: Adding DEX as an adjunct to peripheral nerve blocks can prolong analgesia until postoperative 8 hours in pediatric patients. However, the benefits should be weighed against the increasing risk of bradycardia and sedation in critical children.

2.
Cell Mol Life Sci ; 79(1): 64, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013841

RESUMO

Nicotinic acetylcholine receptors (nAChRs) are widespread throughout the central nervous system. Signaling through nAChRs contributes to numerous higher-order functions, including memory and cognition, as well as abnormalities such as nicotine addiction and neurodegenerative disorders. Although recent studies indicate that the PDZ-containing proteins comprising PSD-95 family co-localize with nicotinic acetylcholine receptors and mediate downstream signaling in the neurons, the mechanisms by which α7nAChRs are regulated remain unclear. Here, we show that the PDZ-LIM domain family protein PDLIM5 binds to α7nAChRs and plays a role in nicotine-induced α7nAChRs upregulation and surface expression. We find that chronic exposure to 1 µM nicotine upregulated α7, ß2-contained nAChRs and PDLIM5 in cultured hippocampal neurons, and the upregulation of α7nAChRs and PDLIM5 is increased more on the cell membrane than the cytoplasm. Interestingly, in primary hippocampal neurons, α7nAChRs and ß2nAChRs display distinct patterns of expression, with α7nAChRs colocalized more with PDLIM5. Furthermore, PDLIM5 interacts with α7nAChRs, but not ß2nAChRs in native brain neurons. Knocking down of PDLIM5 in SH-SY5Y abolishes nicotine-induced upregulation of α7nAChRs. In primary hippocampal neurons, using shRNA against PDLIM5 decreased both surface clustering of α7nAChRs and α7nAChRs-mediated currents. Proteomics analysis and isothermal titration calorimetry (ITC) results show that PDLIM5 interacts with α7nAChRs through the PDZ domain, and the interaction between PDLIM5 and α7nAChRs can be promoted by nicotine. Collectively, our data suggest a novel cellular role of PDLIM5 in the regulation of α7nAChRs, which may be relevant to plastic changes in the nervous system.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34982379

RESUMO

The progress of agricultural green technology is an important means and fundamental way to achieve high-quality development of agriculture. The current study takes the panel data of 31 provinces in China from 1998 to 2018 and uses the Epsilon Based Measure-Global Malmquist-Luenberger (EBM-GML) model to measure China's agricultural green technological progress (AGTP) and discusses its dynamic evolution characteristics in the spatiotemporal dimensions. Finally, we analyze the spatial spillover effects of AGTP by the spatial Dubin model. The results show that China's AGTP showed a trend of first rising and then falling, and the average value is 1.0525. AGTP has obvious regional unbalanced development, and the regional differences are expanding. It shows that AGTP between adjacent areas is closely linked. The Moran's I index shows that AGTP has a significant positive spatial correlation. The local Moran's I index shows that AGTP is concentrated in Northwest, Northeast, and North China, and green technological is degraded in East and South China. From the spatial spillover effects of AGTP, the level of agricultural economic development, real GDP per capita, and urbanization have significantly promoted AGTP in the local and neighboring areas, while the agricultural internal structure and the level of labor inhibit AGTP in the local and neighboring areas. In addition, the administrative environmental policy (ENVP) and the economic environmental policy (ECOP) have negative impacts in neighboring areas, while the policy has negative spillover effects and positive spillover effects in the local area, respectively. Therefore, we should adhere to the concept of green development, pay attention to the regional exchange of green technology, concentrate policies on low-low concentration areas, and increase the follow-up tracking and supervision mechanism of the policy design and implementation process.

4.
Acta Physiol (Oxf) ; : e13778, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34989474

RESUMO

AIMS: Acute kidney injury (AKI), a major health burden, lacks effective therapy. Anti-inflammatory actions of a disintegrin and metalloproteinase with a thrombospondin type 1 motif member 13 (ADAMTS13) may provide a new treatment option for AKI. Along with inflammation, oxidative stress is critical for AKI development, yet the impact of ADAMTS13 on oxidative stress in AKI remains to be fully elucidated. METHODS: We assess recombinant human ADAMTS13 (rhADAMTS13) actions on oxidative stress in a murine ischemia/reperfusion (IR) model. Antioxidant stress-enzyme activities, renal morphology, kidney function markers and vascular function of isolated afferent arterioles are quantified. RESULTS: rhADAMTS13 provided after IR, reduces blood urea nitrogen (BUN) by 33% and serum creatinine (Scr) by 73% in 24 hours post-IR. rhADAMTS13 reduces BUN (40.03±20.34mmol/L vs 72.35±18.74mmol/L, P < 0.01), Scr (75.67±51.19µmol/L vs 176.17±55.38µmol/L, P < 0.01) and proteinuria by 41% in 48 hours post-IR as well. Moreover, rhADAMTS13 administration decreases malondialdehyde (MDA) and increases the activity of antioxidant stress enzymes, and attenuates reactive oxygen species production. rhADAMTS13 also upregulates nuclear factor-erythroid-2-related factor 2/heme oxygenase-1, enhances antioxidant enzymes activity, and alleviates endothelial dysfunction. Finally, treatment with rhADAMTS13 mitigates severe functional and morphological injury present in IR mice. Extracellular signal-regulated kinase (ERK) phosphorylation is limited by rhADAMTS13 and PPARγ expression is partly restored in ischemic kidneys. Co-administration of von Willebrand factor (VWF) impairs rhADAMTS13's antioxidant capacity and its protective role in IR. CONCLUSION: rhADAMTS13 alleviates renal IR injury through antioxidant effects by cleaving VWF.

5.
Anal Chim Acta ; 1189: 339208, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34815044

RESUMO

The electrochemical method for highly sensitive determination of arsenic(III) in real water samples with noble-metal-free nanomaterials is still a difficult but significant task. Here, an electrochemical sensor driven by noble-metal-free layered porous Fe3O4/Co3S4 nanosheets was successfully employed for As(III) analysis, which was prepared via a facile two-step method involves a hydrothermal treatment and a subsequent sulfurization process. As expected, the electrochemical detection of As(III) in 0.1 M HAc-NaAc (pH 6.0) by square wave anodic stripping voltammetry (SWASV) with a considerable sensitivity of 4.359 µA/µg·L-1 was obtained, which is better than the commonly used noble metals modified electrodes. Experimental and characterization results elucidate the enhancement of As(III) electrochemical performance could be attributed to its nano-porous structure, the presence of oxygen vacancies and strong synergetic coupling effects between Fe3O4 and Co3S4 species. Besides, the Fe3O4/Co3S4 modified screen printed carbon electrode (Fe3O4/Co3S4-SPCE) shows remarkable stability and repeatability, valuable anti-interference ability and could be used for detection in real water samples. Consequently, the results confirm that as-prepared porous Fe3O4/Co3S4 nanosheets is identified as a promising modifier to detect As(III) in real sample analysis.


Assuntos
Técnicas Eletroquímicas , Oxigênio , Carbono , Eletrodos , Ouro
6.
J Am Chem Soc ; 144(1): 547-555, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-34932339

RESUMO

Controlled construction of bimetallic nanostructures with a well-defined heterophase is of great significance for developing highly efficient nanocatalysts and investigating the structure-dependent catalytic performance. Here, a wet-chemical synthesis method is used to prepare Au@Pd core-shell nanorods with a unique fcc-2H-fcc heterophase (fcc: face-centered cubic; 2H: hexagonal close-packed with a stacking sequence of "AB"). The obtained fcc-2H-fcc heterophase Au@Pd core-shell nanorods exhibit superior electrocatalytic ethanol oxidation performance with a mass activity as high as 6.82 A mgPd-1, which is 2.44, 6.96, and 6.43 times those of 2H-Pd nanoparticles, fcc-Pd nanoparticles, and commercial Pd/C, respectively. The operando infrared reflection absorption spectroscopy reveals a C2 pathway with fast reaction kinetics for the ethanol oxidation on the prepared heterophase Au@Pd nanorods. Our experimental results together with density functional theory calculations indicate that the enhanced performance of heterophase Au@Pd nanorods can be attributed to the unconventional 2H phase, the 2H/fcc phase boundary, and the lattice expansion of the Pd shell. Moreover, the heterophase Au@Pd nanorods can also serve as an efficient catalyst for the electrochemical oxidation of methanol, ethylene glycol, and glycerol. Our work in the area of phase engineering of nanomaterials (PENs) opens the way for developing high-performance electrocatalysts toward future practical applications.

7.
Front Cell Dev Biol ; 9: 769193, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34901015

RESUMO

Embryonic development and stem cell differentiation are orchestrated by changes in sequential binding of regulatory transcriptional factors to their motifs. These processes are invariably accompanied by the alternations in chromatin accessibility, conformation, and histone modification. Odontoblast lineage originates from cranial neural crest cells and is crucial in dentinogenesis. Our previous work revealed several transcription factors (TFs) that promote odontoblast differentiation. However, it remains elusive as to whether chromatin accessibility affects odontoblast terminal differentiation. Herein, integration of single-cell RNA-seq and bulk RNA-seq revealed that in vitro odontoblast differentiation using dental papilla cells at E18.5 was comparable to the crown odontoblast differentiation trajectory of OC (osteocalcin)-positive odontogenic lineage. Before in vitro odontoblast differentiation, ATAC-seq and H3K27Ac CUT and Tag experiments demonstrated high accessibility of chromatin regions adjacent to genes associated with odontogenic potential. However, following odontoblastic induction, regions near mineralization-related genes became accessible. Integration of RNA-seq and ATAC-seq results further revealed that the expression levels of these genes were correlated with the accessibility of nearby chromatin. Time-course ATAC-seq experiments further demonstrated that odontoblast terminal differentiation was correlated with the occupation of the basic region/leucine zipper motif (bZIP) TF family, whereby we validated the positive role of ATF5 in vitro. Collectively, this study reports a global mapping of open chromatin regulatory elements during dentinogenesis and illustrates how these regions are regulated via dynamic binding of different TF families, resulting in odontoblast terminal differentiation. The findings also shed light on understanding the genetic regulation of dentin regeneration using dental mesenchymal stem cells.

8.
Int J Oral Sci ; 13(1): 44, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34911932

RESUMO

Human dental pulp stem cells (hDPSCs) are easily obtained multipotent cells, however, their potential value in regenerative medicine is hindered by the phenotypic and functional changes after conventional monolayer expansion. Here, we employed single-cell RNA sequencing (scRNA-seq) to comprehensively study the transcriptional difference between the freshly isolated and monolayer cultured DPSCs. The cell cluster analysis based on our scRNA-seq data showed that monolayer culture resulted in a significant cellular composition switch compared to the freshly isolated DPSCs. However, one subpopulation, characterized as MCAM(+)JAG(+)PDGFRA(-), maintained the most transcriptional characteristics compared to their freshly isolated counterparts. Notably, immunofluorescent staining revealed that the MCAM(+)JAG(+)PDGFRA(-) hDPSCs uniquely located in the perivascular region of human dental pulp tissue. Flow-cytometry analysis confirmed that their proportion remained relatively stable (~2%) regardless of physiological senescence or dental caries. Consistent with the annotation of scRNA-seq data, MCAM(+)JAG(+)PDGFRA(-) hDPSCs showed higher proliferation capacity and enhanced in vitro multilineage differentiation potentials (osteogenic, chondrogenic and adipogenic) compared with their counterparts PDGFRA(+) subpopulation. Furthermore, the MCAM(+)JAG(+)PDGFRA(-) hDPSCs showed enhanced bone tissue formation and adipose tissue formation after 4-week subcutaneous implantation in nude mice. Taken together, our study for the first time revealed the cellular composition switch of monolayer cultured hDPSCs compared to the freshly isolated hDPSCs. After in vitro expansion, the MCAM(+)JAG(+)PDGFRA(-) subpopulation resembled the most transcriptional characteristics of fresh hDPSCs which may be beneficial for further tissue regeneration applications.


Assuntos
Cárie Dentária , Animais , Diferenciação Celular , Polpa Dentária , Humanos , Camundongos , Camundongos Nus , Células-Tronco
9.
Kidney Int ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34843754

RESUMO

An increase of glomerular filtration rate (GFR) is a common observation in early diabetes and is considered a key risk factor for subsequent kidney injury. However, the mechanisms underlying diabetic hyperfiltration have not been fully clarified. Here, we tested the hypothesis that macula densa neuronal nitric oxide synthase (NOS1) is upregulated via sodium glucose cotransporter type 1 (SGLT1) in diabetes, which then inhibits tubuloglomerular feedback (TGF) promoting glomerular hyperfiltration. Therefore, we examined changes in cortical NOS1 expression and phosphorylation, nitric oxide production in the macula densa, TGF response, and GFR during the early stage of insulin-deficient (Akita) diabetes in wild-type and macula densa-specific NOS1 knockout mice. A set of sophisticated techniques including microperfusion of juxtaglomerular apparatus in vitro, micropuncture of kidney tubules in vivo, and clearance kinetics of plasma fluorescent-sinistrin were employed. Complementary studies tested the role of SGLT1 in SGLT1 knockout mice and explored NOS1 expression and phosphorylation in kidney biopsies of cadaveric donors. Diabetic mice had upregulated macula densa NOS1, inhibited TGF and elevated GFR. Macula densa-selective NOS1 knockout attenuated the diabetes-induced TGF inhibition and GFR elevation. Additionally, deletion of SGLT1 prevented the upregulation of macula densa NOS1 and attenuated inhibition of TGF in diabetic mice. Furthermore, the expression and phosphorylation levels of NOS1 were increased in cadaveric kidneys of diabetics and positively correlated with blood glucose as well as estimated GFR in the donors. Thus, our findings demonstrate that the macula densa SGLT1-NOS1-TGF pathway plays a crucial role in the control of GFR in diabetes.

10.
Neuroendocrinology ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34847556

RESUMO

Background Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder characterized by high androgen levels. The aim of this study was to evaluate the effects of hyperandrogenism on the hypothalamus, and subsequently on the food intake and obesity in females. Methods A dihydroxy testosterone (DHT)-induced rat model was established to recapitulate the hyperandrogenism features of PCOS patients. Body weight and food intake of the rats were recorded. The food intake of DHT-induced rats was restricted by pair feeding to exclude possible effects of weight gain on the hypothalamus. The expression levels of relevant proteins and mRNAs in the hypothalamus, primary hypothalamic neurons exposed to DHT were analyzed by Western blotting and RT-PCR respectively. The leptin levels in serum and cerebrospinal fluid (CSF) were measured, and leptin was injected via the intracerebroventricular (ICV) route to test the leptin sensitivity of hypothalamus. Results The excessive pre-puberty androgen levels in the DHT-induced rats markedly elevated food intake prior to weight gain. Consistent with this, the expression of NPY and Agouti-related peptide (Agrp) mRNAs were up-regulated, which occurred prior to obesity and even with restricted food intake. In addition, the hypothalamic sensitivity to insulin and leptin was also impaired in the DHT-induced rats before obesity and with restricted food intake. DHT significantly reduced the leptin levels in the CSF, and ICV injection of leptin inhibited the DHT-induced increase in food intake. Conclusions Androgen excess increased food intake in rats and promoted obesity by down-regulating insulin and leptin signaling in the hypothalamus, most likely by suppressing leptin levels in the CSF.

11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(12): 1180-1184, 2021 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-34839502

RESUMO

OBJECTIVE: Patients with 22q11.2 microduplications have highly variable clinical phenotypes. The clinical manifestations and prognosis of 19 fetuses carrying 22q11.2 microduplications were analyzed. METHODS: The fetuses were analyzed by single nucleotide polymorphism array (SNP array), which was followed by parental validation. Pregnancy outcome and clinical features of the newborns were analyzed in order to delineate genotype-phenotype correlation. RESULTS: Two fetuses were identified by karyotyping analysis of amniotic fluid samples. SNP array revealed that all have carried a 468.8 kb~3.4 Mb duplication in 22q11.2 region. Two couples have refused parental verification. Seven cases were inherited from the mother, 6 were from the father, and 4 cases were de novo in origin. Three couples opted termination of the pregnancy. One fetus perished at birth. Five newborns showed delayed growth, the remaining 10 were normal. CONCLUSION: The prenatal phenotype of fetuses carrying 22q11.2 microduplications are nonspecific, and the phenotypes of survivors may become more diverse along with increased age. Professional evaluation and long-term follow-up should be recommended.


Assuntos
Aconselhamento Genético , Diagnóstico Pré-Natal , Feminino , Feto , Humanos , Recém-Nascido , Cariotipagem , Fenótipo , Gravidez
12.
Dis Markers ; 2021: 1405045, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790276

RESUMO

Background: Growing studies have demonstrated that long noncoding RNAs (lncRNAs) play important roles in tumor progression. In this study, we aimed to explore the potential roles of lncRNA LINC00958 (LINC00958) and its biological functions in epithelial ovarian cancer (EOC). Methods: The expression of LINC00958 in 11 cases of EOC and adjacent nontumor specimens and five cell lines was detected by qRT-PCR. CCK-8, colony formation, and flow cytometry assays were conducted to study the cell viabilities of EOC cells. Wound scratch and transwell analyses were carried out for the examination of cell invasion and migration of EOC cells. The targeting associations between LINC00958 and STAT1 were demonstrated by ChIP analyses combined with luciferase reporter assays. The related proteins of Wnt/ß-catenin signaling were determined using RT-PCR. Results: Higher levels of LINC00958 were observed in EOC tissues and cell lines. Our data also revealed that high LINC00958 expression was partly induced by STAT1. Functionally, knockdown of LINC00958 suppressed the proliferation, migration, and invasion of EOC cells. Mechanistic investigation showed that the inhibitory effect of LINC00958 knockdown on EOC cells was mediated by the Wnt/ß-catenin signaling. Conclusion: Our findings suggested that STAT1-induced overexpression of LINC00958 promoted EOC progression by modulating Wnt/ß-catenin signaling.

13.
Front Public Health ; 9: 686705, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790640

RESUMO

The COVID-19 outbreak caused by the Severe Acute Respiratory Syndrome CoronaVirus type 2 (SARS-CoV-2) has spread across the world. However, our understanding of the public responses, in particular in adopting protective behaviors, has been limited. The current study aimed to determine the level of protective behaviors adopted by the residents in China and its association with their cultural attributes. A national cross-sectional online survey was conducted in mainland China from 4th to 13th August 2020. Protective behaviors were assessed as a summed score (ranging from 0 to 40) measured by ten items. The self-report tendency of study participants toward the four cultural attributes (individualism, egalitarianism, fatalism, hierarchy) was rated on a seven-point Likert scale. A total of 17651 respondents returned a valid questionnaire, representing 47.9% of those who accessed the online survey. Most (89.8%) respondents aged between 18 and 45 years in the age range of and 47.7% were male. High levels of protective behaviors (34.04 ± 5.78) were reported. The respondents had high scores in the cultural attributes of hierarchy (Median = 5) and egalitarianism (Median = 5), compared with low scores in individualism (Median = 1) and fatalism (Median = 1). High levels of protective behaviors were associated a higher tendency toward egalitarianism (AOR = 2.90, 95% CI 2.67-3.15) and hierarchy (AOR = 1.66, 95% CI 1.53-1.81) and a low tendency toward fatalism (AOR = 1.79, 95% CI 1.63-1.97) and individualism (AOR = 2.62, 95% CI 2.41-2.85). The cultural attributes explained 17.3% of the variations in the protective behavioral scores. In conclusion, the adoption of protective behaviors is associated a risk culture characterized by high levels of hierarchy and egalitarianism and low levels of individualism and fatalism. Government actions and communication strategies need to adapt to the cultural characteristics of their target audience.


Assuntos
COVID-19 , Adolescente , Adulto , China/epidemiologia , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Inquéritos e Questionários , Adulto Jovem
14.
Ann Palliat Med ; 10(10): 10584-10590, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34763505

RESUMO

BACKGROUND: A meta-analysis was conducted to examine the correlation between Helicobacter pylori infection and chronic urticaria. METHODS: We searched Chinese and English databases, including CNKI, Wanfang, and Weipu, using search terms such as Helicobacter pylori infection, and chronic urticaria for articles published from the establishment of the databases to February 2021 examining the correlation between Helicobacter pylori infection and chronic urticaria. The retrieved articles contained data on Helicobacter pylori infection rates in chronic urticaria cases in different regions of the north and south in China. The retrieved articles underwent strict screenings according to inclusion and exclusion criteria. Revman5.3 software was used to perform a meta-analysis on the data of the included articles. RESULTS: A total of 39 documents were retrieved following the searches. According to the inclusion and exclusion criteria, a total of 6 articles on 6 studies, comprising a total of 1,320 patients, were finally included in the meta-analysis. The results showed that the heterogeneity was high (I2=58%). A random-effects model was performed. An analysis of the correlation between Helicobacter pylori infection and chronic urticaria revealed significant differences between the study group and the control group [odds ratio (OR) =3.00; 95% confidence interval (CI): 1.98-4.55; P<0.00001]. The infection rate of Helicobacter pylori among chronic urticaria cases in the northern population was 16.1% (95% CI: 15.6-16.6%); of these patients 12.2% were male and 21.4% were female. The infection rate of Helicobacter pylori among chronic urticaria cases in the southern population was 18.0% (95% CI: 17.5-18.5%); of these patients, 12.3% were male and 23.1% were female. There was no significant difference in the prevalence between the male population, the female population, and the general population in the north and the south (P>0.05). DISCUSSION: Helicobacter pylori infection is correlated with the occurrence of chronic urticaria. There is no significant difference in the infection rate of Helicobacter pylori in chronic urticaria cases in different regions of the north and south. This study had some limitations. First, the number of patients included in each study was low, which may affect the accuracy of the results. Second, the detection methods were not uniform; thus, further research is required to support the conclusions drawn.


Assuntos
Urticária Crônica , Infecções por Helicobacter , Helicobacter pylori , Urticária , Doença Crônica , Feminino , Humanos , Masculino
15.
J Phys Chem Lett ; 12(45): 11182-11190, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34761944

RESUMO

Quantum defects have been shown to play an essential role in nonradiative recombination in metal halide perovskites (MHPs). Nonetheless, the processes of charge transfer assisted by defects are still ambiguous. Herein, we theoretically study the nonradiative multiphonon processes among different types of quantum defects in MHPs using Markvart's model for the induced mechanisms of electron-electron and electron-phonon interactions. We find that the charge carrier can transfer between the neighboring levels of the same type of shallow defects by multiphonon processes, but it will be distinctly suppressed with an increase in the defect depth. For the nonradiation multiphonon transitions between donor- and acceptor-like defects, the processes are very fast and not sensitive to the defect depth, which provides a possible explanation for the phenomenon of blinking of photoluminescence spectra. We also discuss the temperature dependence of these multiphonon processes and find that their variational trends depend on the comparison of the Huang-Rhys factor with the emitted phonon number. These theoretical results not only fill some of the gaps in defect-assisted nonradiative processes in the perovskite materials but also provide deeper physical insights into producing higher-performance perovskite-based devices.

16.
Kaohsiung J Med Sci ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34783160

RESUMO

Melanoma is a skin cancer characterized by early metastasis and high mortality. Radiotherapy is a common treatment for melanoma in patients. Long noncoding RNAs play pivotal roles in regulating the radiosensitivity of many tumors, including melanomas. In this study, the role of LINC01224 in the radiosensitivity of melanoma cells was explored. The expression of LINC01224 in melanoma was examined by reverse transcription-quantitative polymerase chain reaction, and the results showed that LINC01224 was upregulated in melanoma tissues and cells. The effects of LINC01224 on cell proliferation and apoptosis in melanoma were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT), colony formation, and flow cytometry assays. The effects of LINC01224 on the radiosensitivity of melanoma were analyzed by colony formation assay. The results implied that LINC01224 knockdown inhibited cell viability and proliferation but enhanced cell apoptosis and radiosensitivity. Luciferase reporter and RNA pull-down assays were performed to evaluate the relationships between LINC01224 and miR-193a-5p or miR-193a-5p and nuclear receptor subfamily 1 group D member 2 (NR1D2). We found that LINC01224 binds to miR-193a-5p, which directly targets NR1D2. In addition, we discovered that LINC01224 upregulated NR1D2 expression by sponging miR-193a-5p in melanoma cells. Overall, the data collected in this study suggest that LINC01224 exerts oncogenic effects in melanoma via the miR-193a-5p/NR1D2 axis.

17.
Cell Mol Life Sci ; 78(23): 7831-7849, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34724098

RESUMO

Randall's plaques (RP) are well established as precursor lesions of idiopathic calcium oxalate (CaOx) stones, and the process of biomineralization driven by osteogenic-like cells has been highlighted in RP formation, but the mechanism is poorly understood. Given the inhibitory role of α-Klotho (KL), an aging suppressor protein with high expression in kidneys, in ectopic calcification and the close association between KL gene polymorphisms and urolithiasis susceptibility, we determined the potential role of KL in RP formation. This study found that both soluble KL (s-KL) and transmembrane KL (m-KL) were downregulated, and that s-KL but not m-KL was inversely correlated with upregulation of osteogenic markers in RP tissues. Additionally, s-KL expression was markedly suppressed in human renal interstitial fibroblasts (hRIFs) and slightly suppressed in HK-2 cells after osteogenic induction, intriguingly, which was echoed to the greater osteogenic capability of hRIFs than HK-2 cells. Further investigations showed the inhibitory effect of s-KL on hRIF osteogenic differentiation in vitro and in vivo. Moreover, coculture with recombinant human KL (r-KL) or HK-2 cells suppressed osteogenic differentiation of hRIFs, and this effect was abolished by coculture with KL-silenced HK-2 cells or the ß-catenin agonist SKL2001. Mechanistically, s-KL inactivated the Wnt-ß-catenin pathway by directly binding to Wnt2 and upregulating SFRP1. Further investigations identified activation of the Wnt-ß-catenin pathway and downregulation of SFRP1 and DKK1 in RP tissues. In summary, this study identified s-KL deficiency as a pathological feature of RP and revealed that s-KL released from HK-2 cells inhibited osteogenic differentiation of hRIFs by inactivating the Wnt-ß-catenin pathway, not only providing in-depth insight into the role of s-KL in renal interstitial biomineralization but also shedding new light on the interaction of renal tubular epithelial cells with interstitial cells to clarify RP formation.

19.
Cancer Manag Res ; 13: 8241-8255, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34754244

RESUMO

Purpose: To evaluate the dynamics of early serum tumour markers (STMs) and the neutrophil-to-lymphocyte ratio (NLR) to predict clinical efficacy and prognosis of advanced non-small-cell lung cancer (NSCLC) patients who received programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors. Patients and Methods: We retrospectively reviewed patients with advanced NSCLC treated with PD-1/PD-L1 inhibitors between September 2017 and August 2020. NLR and STMs were routinely measured between immunotherapy initiation and the first radiological evaluation. A combination score based on the leading STM and NLR and their dynamic changes was established. The effects of leading STM change, NLR change, and the combination score on the objective response rate (ORR), durable clinical benefit (DCB), progression-free survival (PFS), and overall survival (OS) were analysed. The accuracy of the combination score was evaluated by receiver operating characteristic (ROC) curve and the area under the curve (AUC). Results: Overall, 124 patients were included in this retrospective cohort study. The ORR was 22.8%, DCB was 54.5%, and the median OS and PFS were 21.6 and 14.9 months, respectively. Patients with low combination scores had a significantly improved ORR and DCB compared with those with intermediate or high scores (P = 0.002 for ORR, P < 0.0001 for DCB). In a multivariate model, the combination score was an independent indicator of PFS (P < 0.0001) and OS (P < 0.0001). The AUC demonstrated that the combination score (AUC = 0.706) has greater predictive power than either the posttreatment NLR (AUC = 0.668) or the leading STM change (AUC = 0.648) alone. Conclusion: An easy, cost-effective, and novel combination score based on the dynamics of an early STM and the NLR can accurately predict the clinical efficacy of PD-1/PD-L1 inhibitors and prognosis in advanced NSCLC patients.

20.
J Mol Model ; 27(12): 343, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34739562

RESUMO

In order to clarify the solvent effect on the thermal decomposition of explosive, the N-NO2 trigger-bond strengths and ring strains of RDX (cyclotrimethylenetrinitramine) in its H-bonded complexes with solvent molecules (i.e., tetrahydrofuran, acetone, toluene, and benzene), and the activation energies of the intermolecular hydrogen exchanges between the solvent molecules and C3H8O2N4 or CH4O2N2, as the model molecule of RDX, were investigated by the BHandHLYP, B3LYP, MP2(full), and M06-2X methods with the 6-311 + + G(2df,2p) basis set, accompanied by a comparison with the calculations by the integral equation formalism polarized continuum model. The solvent effects ignore the ring strain while strengthening the N-NO2 bond, leading to a possible decreased sensitivity, as is opposite to the experimental results. However, the activation energies are in the order of C3H8O2N4/CH4O2N2∙∙∙acetone < C3H8O2N4/CH4O2N2∙∙∙THF < C3H8O2N4/CH4O2N2∙∙∙toluene < C3H8O2N4/CH4O2N2∙∙∙benzene < C3H8O2N4/CH4O2N2, suggesting that the order of the critical explosion temperatures might be RDX∙∙∙acetone < RDX∙∙∙THF < RDX∙∙∙toluene < RDX∙∙∙benzene < RDX, as is roughly consistent with the experimental results. Therefore, the intermolecular hydrogen exchange with the HONO elimination is a possible mechanism of the solvent effect on the initial thermal decomposition of RDX. The solvent effect on the sensitivity is analyzed by the surface electrostatic potentials.

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