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1.
Org Biomol Chem ; 22(20): 4047-4051, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38712523

RESUMO

Herein, electroreductive umpolung benzylic deuteration of p-QMs using cheap and easily accessible D2O as a deuterium source is reported. Various value-added benzylic deuterated diarylmethanes can be synthesized without the requirement of noble metal catalysts, redox reagents, and strong bases. The establishment of this protocol will provide an alternative strategy for acquiring benzylic deuterated diarylmethanes.

2.
Ecotoxicol Environ Saf ; 278: 116415, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38703406

RESUMO

The combined pollution of microplastics (MPs) and sulfamethoxazole (SMZ) often occurs in aquatic ecosystems, posing a serious threat to animal and human health. However, little is known about the liver damage caused by the single or co-exposure of MPs and SMZ, and its specific mechanisms are still poorly understood. In this study, we investigated the effects of co-exposure to 20 µm or 80 nm MPs and SMZ in both larval and adult zebrafish models. Firstly, we observed a significant decrease in the number of hepatocytes and the liver damage in larval zebrafish worsened following co-exposure to SMZ and MPs. Additionally, the number of macrophages and neutrophils decreased, while the expression of inflammatory cytokines and antioxidant enzyme activities increased after co-exposure in larval zebrafish. Transcriptome analysis revealed significant changes in gene expression in the co-exposed groups, particularly in processes related to oxidation-reduction, inflammatory response, and the MAPK signaling pathway in the liver of adult zebrafish. Co-exposure of SMZ and MPs also promoted hepatocyte apoptosis and inhibited proliferation levels, which was associated with the translocation of Nrf2 from the cytoplasm to the nucleus and an increase in protein levels of Nrf2 and NF-kB p65 in the adult zebrafish. Furthermore, our pharmacological experiments demonstrated that inhibiting ROS and blocking the MAPK signaling pathway partially rescued the liver injury induced by co-exposure both in larval and adult zebrafish. In conclusion, our findings suggest that co-exposure to SMZ and MPs induces hepatic dysfunction through the ROS-mediated MAPK signaling pathway in zebrafish. This information provides novel insights into the potential environmental risk of MPs and hazardous pollutants co-existence in aquatic ecosystems.


Assuntos
Microplásticos , Espécies Reativas de Oxigênio , Sulfametoxazol , Poluentes Químicos da Água , Peixe-Zebra , Animais , Sulfametoxazol/toxicidade , Microplásticos/toxicidade , Poluentes Químicos da Água/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fígado/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Larva/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos
3.
Environ Pollut ; 351: 124101, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38710361

RESUMO

Both nanoplastics (NPs) and 3-tert-butyl-4-hydroxyanisole (3-BHA) are environmental contaminants that can bio-accumulate through the food chain. However, the combined effects of which on mammalian female reproductive system remain unclear. Here, the female ICR-CD1 mice were used to evaluate the damage effects of ovaries and uterus after NPs and 3-BHA co-treatment for 35 days. Firstly, co-exposure significantly reduced the body weight and organ index of ovaries and uterus in mice. Secondly, combined effects of NPs and 3-BHA exacerbated the histopathological abnormalities to the ovaries and uterus and decreased female sex hormones such as FSH and LH while increased antioxidant activities including CAT and GSH-Px. Moreover, the apoptotic genes, inflammatory cytokines and the key reproductive development genes such as FSTL1 were significantly up-regulated under co-exposure conditions. Thirdly, through transcriptional and bioinformatics analysis, immunofluorescence and western blotting assays, together with molecular docking simulation, we determined that co-exposure up-regulated the FSTL1, TGF-ß and p-Smad1/5/9 but down-regulated the expression of BMP4. Finally, the pharmacological rescue experiments further demonstrated that co-exposure of NPs and 3-BHA mainly exacerbated the female reproductive toxicity through FSTL1-mediated BMP4/TGF-ß/SMAD signaling pathway. Taken together, our studies provided the theoretical basis of new environmental pollutants on the reproductive health in female mammals.


Assuntos
Camundongos Endogâmicos ICR , Ovário , Poliestirenos , Útero , Animais , Feminino , Camundongos , Útero/efeitos dos fármacos , Útero/metabolismo , Ovário/efeitos dos fármacos , Ovário/metabolismo , Poliestirenos/toxicidade , Reprodução/efeitos dos fármacos , Microplásticos/toxicidade , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 4/metabolismo , Nanopartículas/toxicidade , Simulação de Acoplamento Molecular , Poluentes Ambientais/toxicidade , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/genética
4.
Biomaterials ; 309: 122608, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38744189

RESUMO

Necroptotic immunogenic cell death (ICD) can activate the human immune system to treat the metastasis and recurrence of triple-negative breast cancer (TNBC). However, developing the necroptotic inducer and precisely delivering it to the tumor site is the key issue. Herein, we reported that the combination of shikonin (SHK) and chitosan silver nanoparticles (Chi-Ag NPs) effectively induced ICD by triggering necroptosis in 4T1 cells. Moreover, to address the lack of selectivity of drugs for in vivo application, we developed an MUC1 aptamer-targeted nanocomplex (MUC1@Chi-Ag@CPB@SHK, abbreviated as MUC1@ACS) for co-delivering SHK and Chi-Ag NPs. The accumulation of MUC1@ACS NPs at the tumor site showed a 6.02-fold increase compared to the free drug. Subsequently, upon reaching the tumor site, the acid-responsive release of SHK and Chi-Ag NPs from MUC1@ACS NPs cooperatively induced necroptosis in tumor cells by upregulating the expression of RIPK3, p-RIPK3, and tetrameric MLKL, thereby effectively triggering ICD. The sequential maturation of dendritic cells (DCs) subsequently enhanced the infiltration of CD8+ and CD4+ T cells in tumors, while inhibiting regulatory T cells (Treg cells), resulting in the effective treatment of primary and distal tumor growth and the inhibition of TNBC metastasis. This work highlights the importance of nanoparticles in mediating drug interactions during necroptotic ICD.


Assuntos
Quitosana , Nanopartículas Metálicas , Naftoquinonas , Necroptose , Proteína Serina-Treonina Quinases de Interação com Receptores , Prata , Neoplasias de Mama Triplo Negativas , Naftoquinonas/farmacologia , Naftoquinonas/química , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Quitosana/química , Prata/química , Prata/farmacologia , Animais , Nanopartículas Metálicas/química , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Linhagem Celular Tumoral , Feminino , Necroptose/efeitos dos fármacos , Humanos , Camundongos , Morte Celular Imunogênica/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Mucina-1/metabolismo , Sinergismo Farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química
5.
Org Lett ; 26(21): 4427-4432, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38757832

RESUMO

2,3-Diaryl propanoic acids are important structures as a result of their widespread presence in numerous bioactive compounds. However, the limitations of existing synthetic techniques include the requirement for costly catalysts and limited substrates. Here, we developed a novel electroreductive arylcarboxylation of alkenes with CO2 based on a radical-polar crossover pathway assisted by easily accessible dimethyl terephthalate as a reductive mediator. This method will provide an efficient strategy for the synthesis of 2,3-diarylpropanoic acids.

6.
Sci Rep ; 14(1): 5351, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438512

RESUMO

This study aims at suggesting an end-to-end algorithm based on a U-net-optimized generative adversarial network to predict anterior neck lower jaw angles (ANLJA), which are employed to define fetal head posture (FHP) during nuchal translucency (NT) measurement. We prospectively collected 720 FHP images (half hyperextension and half normal posture) and regarded manual measurement as the gold standard. Seventy percent of the FHP images (half hyperextension and half normal posture) were used to fit models, and the rest to evaluate them in the hyperextension group, normal posture group (NPG), and total group. The root mean square error, explained variation, and mean absolute percentage error (MAPE) were utilized for the validity assessment; the two-sample t test, Mann-Whitney U test, Wilcoxon signed-rank test, Bland-Altman plot, and intraclass correlation coefficient (ICC) for the reliability evaluation. Our suggested algorithm outperformed all the competitors in all groups and indices regarding validity, except for the MAPE, where the Inception-v3 surpassed ours in the NPG. The two-sample t test and Mann-Whitney U test indicated no significant difference between the suggested method and the gold standard in group-level comparison. The Wilcoxon signed-rank test revealed significant differences between our new approach and the gold standard in personal-level comparison. All points in Bland-Altman plots fell between the upper and lower limits of agreement. The inter-ICCs of ultrasonographers, our proposed algorithm, and its opponents were graded good reliability, good or moderate reliability, and moderate or poor reliability, respectively. Our proposed approach surpasses the competition and is as reliable as manual measurement.


Assuntos
Mandíbula , Medição da Translucência Nucal , Humanos , Feminino , Gravidez , Reprodutibilidade dos Testes , Mandíbula/diagnóstico por imagem , Feto/diagnóstico por imagem , Cuidado Pré-Natal
7.
J Integr Plant Biol ; 66(4): 709-730, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38483018

RESUMO

Hybrid rice (Oryza sativa) generally outperforms its inbred parents in yield and stress tolerance, a phenomenon termed heterosis, but the underlying mechanism is not completely understood. Here, we combined transcriptome, proteome, physiological, and heterosis analyses to examine the salt response of super hybrid rice Chaoyou1000 (CY1000). In addition to surpassing the mean values for its two parents (mid-parent heterosis), CY1000 exhibited a higher reactive oxygen species scavenging ability than both its parents (over-parent heterosis or heterobeltiosis). Nonadditive expression and allele-specific gene expression assays showed that the glutathione S-transferase gene OsGSTU26 and the amino acid transporter gene OsAAT30 may have major roles in heterosis for salt tolerance, acting in an overdominant fashion in CY1000. Furthermore, we identified OsWRKY72 as a common transcription factor that binds and regulates OsGSTU26 and OsAAT30. The salt-sensitive phenotypes were associated with the OsWRKY72paternal genotype or the OsAAT30maternal genotype in core rice germplasm varieties. OsWRKY72paternal specifically repressed the expression of OsGSTU26 under salt stress, leading to salinity sensitivity, while OsWRKY72maternal specifically repressed OsAAT30, resulting in salinity tolerance. These results suggest that the OsWRKY72-OsAAT30/OsGSTU26 module may play an important role in heterosis for salt tolerance in an overdominant fashion in CY1000 hybrid rice, providing valuable clues to elucidate the mechanism of heterosis for salinity tolerance in hybrid rice.


Assuntos
Vigor Híbrido , Oryza , Vigor Híbrido/genética , Espécies Reativas de Oxigênio/metabolismo , Oryza/genética , Oryza/metabolismo , Tolerância ao Sal/genética , Fenótipo
8.
Bioorg Chem ; 143: 107084, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38176376

RESUMO

In the chemical investigation of Inula japonica, a total of 29 sesquiterpenoids (1-29) were obtained, including pseudoguaine-, xanthane-, eudesmane-, and 1,10-secoeudesmane-type compounds, as well as their dimers. Among them, six new dimeric sesquiterpenoids, bisinulains A-F (1-5, 7), characterized by a [4 + 2] biogenetic pathway between different sesquiterpenoid monomers were identified. Additionally, three new monomers named inulaterins A-C (13, 18 and 21) were discovered. The structures of these compounds were determined through analysis of spectroscopic data, X-ray crystallographic data, and ECD experiments. To assess their potential anti-inflammatory activities, the sesquiterpenoid dimers were tested for their ability to inhibit NO production in LPS-stimulated RAW 264.7 cells. Furthermore, the compounds that exhibited anti-inflammatory effects underwent evaluation for their anti-fibrotic potential using a TGF-ß-induced epithelial-mesenchymal transition model in A549 cells. As a result, bisinulain B (2) was screened out to significantly inhibit the production of cytokines involved in pulmonary fibrosis such as NO, α-SMA, collagen I and fibronectin.


Assuntos
Inula , Sesquiterpenos , Animais , Camundongos , Humanos , Inula/química , Estrutura Molecular , Células RAW 264.7 , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Células A549 , Sesquiterpenos/farmacologia , Sesquiterpenos/química
9.
J Matern Fetal Neonatal Med ; 36(2): 2285239, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38010356

RESUMO

Objective: To evaluate the changes in cardiac morphology of fetuses with congenital heart disease (CHD) using the fetal heart quantitative technique (fetalHQ).Methods: A total of 20 normal pregnant women (control group) and 20 pregnant women suspected of fetal CHD (case group) were included in this study. The dynamic images of the four-chamber view of the fetal heart were recorded and analyzed using fetalHQ. The global sphericity index (GSI) and 24-segment SI of the two groups were compared. The differences in the left and right ventricular 24-segment SI for each group were investigated.Results: There was no statistically significant difference in the GSI between the two groups (p > 0.05). The difference in the SI values of left ventricular segments 1-2 between the case group and control group was statistically significant (all p < 0.05), while the intergroup difference in SI of left ventricular segments 3-24 was not significant (all p > 0.05). The SI of the 24 segments of the right ventricle showed no significant intergroup difference (all p > 0.05). The difference in the left and right ventricular 24-segment SI in the case group did not reach statistical significance (all p > 0.05). In the control group, the SI values between the left and right ventricles were significantly different in segments 18-24 (all p < 0.05), and no significant difference was found in segments 1-17 (all p > 0.05). There was a statistically significant intergroup difference in the percentage of unusual left ventricular SI, determined based on Z-score (p < 0.05), and the percentage of outliers for the right ventricle between the two groups showed no significant difference (p > 0.05).Conclusion: The fetalHQ is regarded as a straightforward and reliable approach for assessing the cardiac GSI and 24-segment SI of left and right ventricles in fetuses diagnosed with CHD. While CHD may not significantly impact the overall shape of the fetal heart or the geometric shape of the right ventricle, in this study, a notable increase in SI values for the left ventricular 1-2 segments was observed, indicating a more flattened ventricular chamber. Additionally, the morphological distinctions between the left and right ventricles in fetuses with CHD are no longer discernible.


Assuntos
Doenças Fetais , Cardiopatias Congênitas , Feminino , Humanos , Gravidez , Ultrassonografia Pré-Natal/métodos , Coração Fetal/diagnóstico por imagem , Cardiopatias Congênitas/diagnóstico , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/anormalidades
10.
Rice (N Y) ; 16(1): 44, 2023 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-37804355

RESUMO

BACKGROUND: The Glucan synthase-like (GSL) genes are indispensable for some important highly-specialized developmental and cellular processes involving callose synthesis and deposition in plants. At present, the best-characterized reproductive functions of GSL genes are those for pollen formation and ovary expansion, but their role in seed initiation remains unknown. RESULTS: We identified a rice seed mutant, watery seed 1-1 (ws1-1), which contained a mutation in the OsGSL2 gene. The mutant produced seeds lacking embryo and endosperm but filled with transparent and sucrose-rich liquid. In a ws1-1 spikelet, the ovule development was normal, but the microsporogenesis and male gametophyte development were compromised, resulting in the reduction of fertile pollen. After fertilization, while the seed coat normally developed, the embryo failed to differentiate normally. In addition, the divided endosperm-free nuclei did not migrate to the periphery of the embryo sac but aggregated so that their proliferation and cellularization were arrested. Moreover, the degeneration of nucellus cells was delayed in ws1-1. OsGSL2 is highly expressed in reproductive organs and developing seeds. Disrupting OsGSL2 reduced callose deposition on the outer walls of the microspores and impaired the formation of the annular callose sheath in developing caryopsis, leading to pollen defect and seed abortion. CONCLUSIONS: Our findings revealed that OsGSL2 is essential for rice fertility and is required for embryo differentiation and endosperm-free nucleus positioning, indicating a distinct role of OsGSL2, a callose synthase gene, in seed initiation, which provides new insight into the regulation of seed development in cereals.

11.
BMC Pregnancy Childbirth ; 23(1): 723, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37821915

RESUMO

BACKGROUND: Whether intrauterine transmission of COVID-19 occurs remains uncertain, and it remains unclear whether the disease affects fetuses. We present a case of intrauterine transmission of SARS-CoV-2 infection and the prenatal ultrasonographic findings of the fetus in a pregnant woman with mild COVID-19. CASE PRESENTATION: A 30-year-old woman was admitted to our hospital for ultrasound examination in January 2023 at 26+ 3 weeks' gestation. Twenty-one days prior, her COVID-19 nucleic acid test was positive, and she had mild symptoms, including fever (38.3 °C), headache, chills, ankle pain and cough. After receiving symptomatic treatment, she fully recovered. Prenatal ultrasound revealed that the placenta was diffusely distributed with punctate echogenic foci, hepatomegaly, and the volume of bilateral lungs decreased significantly, with enhanced echo. In addition, we found that the surface of the fetal brain demonstrated widened gyri with a flattened surface. The prenatal MRI confirmed these fetal abnormalities. Amniotic fluid was tested for SARS-CoV-2, and the sample tested was positive for the virus. After careful consideration, the pregnant woman decided to terminate the pregnancy. CONCLUSION: The intrauterine transmission of COVID-19 is certain. Moreover, the intrauterine transmission of COVID-19 may cause abnormalities in various organs of the fetus.


Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , Feminino , Gravidez , Humanos , Adulto , SARS-CoV-2 , Gestantes , Complicações Infecciosas na Gravidez/diagnóstico , Feto , Placenta/diagnóstico por imagem , Líquido Amniótico , Transmissão Vertical de Doenças Infecciosas , Ultrassonografia Pré-Natal
14.
Sci Adv ; 9(26): eade0387, 2023 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-37390202

RESUMO

P23, historically known as a heat shock protein 90 (HSP90) co-chaperone, exerts some of its critical functions in an HSP90-independent manner, particularly when it translocates into the nucleus. The molecular nature underlying how this HSP90-independent p23 function is achieved remains as a biological mystery. Here, we found that p23 is a previously unidentified transcription factor of COX-2, and its nuclear localization predicts the poor clinical outcomes. Intratumor succinate promotes p23 succinylation at K7, K33, and K79, which drives its nuclear translocation for COX-2 transcription and consequently fascinates tumor growth. We then identified M16 as a potent p23 succinylation inhibitor from 1.6 million compounds through a combined virtual and biological screening. M16 inhibited p23 succinylation and nuclear translocation, attenuated COX-2 transcription in a p23-dependent manner, and markedly suppressed tumor growth. Therefore, our study defines p23 as a succinate-activated transcription factor in tumor progression and provides a rationale for inhibiting p23 succinylation as an anticancer chemotherapy.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Ácido Succínico , Fatores de Transcrição/genética , Ciclo-Oxigenase 2/genética , Piridinolcarbamato , Carcinogênese/genética , Transformação Celular Neoplásica , Succinatos , Adenocarcinoma de Pulmão/genética , Chaperonas Moleculares/genética , Proteínas de Choque Térmico HSP90/genética , Neoplasias Pulmonares/genética
15.
Plant Physiol ; 191(3): 1684-1701, 2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-36517254

RESUMO

Crop reproductive development is vulnerable to heat stress, and the genetic modulation of thermotolerance during the reproductive phase, especially the early stage, remains poorly understood. We isolated a Poaceae-specific FAR-RED ELONGATED HYPOCOTYLS3 (FHY3)/FAR-RED IMPAIRED RESPONSE1 (FAR1)family transcription factor, Thermo-sensitive Spikelet Defects 1 (TSD1), derived from transposase in rice (Oryza sativa) TSD1 was highly expressed in spikelets, induced by heat, and specifically enhanced the thermotolerance of spikelet morphogenesis. Disrupting TSD1 did not affect vegetative growth but markedly retarded spikelet initiation and development, as well as caused varying degrees of spikelet degeneration, depending on the temperature. Most tsd1 spikelets were normal at low temperature but gradually degenerated as temperature increased, and all disappeared at high temperature, leading to naked branches. TSD1 directly promoted the transcription of YABBY1 and YABBY3 and could physically interact with YABBY1 and three TOB proteins, YABBY5, YABBY4, and YABBY3. These YABBY proteins can form either homodimers or heterodimers and play an important role in spikelet morphogenesis, similar to TSD1. Notably, the knockout mutant yab5-ko and double mutant tsd1 yab5-ko resembled tsd1 in spikelet appearance and response to temperature, indicating that these genes likely participate in spikelet development through the cooperative TSD1-YABBY module. These findings reveal a distinctive function of FHY3/FAR1 family genes and a unique TSD1-YABBY complex to acclimate spikelet development to high temperature in rice, providing insight into the regulating pathway of enhancing thermotolerance in plant reproductive development.


Assuntos
Oryza , Temperatura , Temperatura Alta , Temperatura Baixa , Reprodução , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
16.
Sci Rep ; 12(1): 15034, 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36057697

RESUMO

Understanding the shear strength degradation mechanism of a rock mass joint surface under cyclic shear load and determining a corresponding analytical model is an important foundation for accurately evaluating the safety of rock mass engineering under seismic loads. It is worth noting that, to date, there has been a dearth of studies on the strength characteristics of joint surfaces that consider the number of loading cycles, normal load, and initial undulant angle of the structural plane. In this study, focused on the behaviour of sandstone, the particle flow code (PFC) modelling framework was used to simulate a joint surface cyclic shear test considering first- and second-order undulations. Based on the experimental results, the comprehensive effects of the number of cyclic shear cycles, the normal stress, first- and second-order undulation and the dilatancy angle on shear stress during cyclic shear were analysed. Formulas for the joint surface shear basic friction angle and dilatancy angle under cyclic shear were proposed, and a method for calculating the joint surface peak shear strength under cyclic shear considering the deterioration of the dilatancy angle and basic friction angle was established. The peak shear strength of a sample after five cycles of shearing was calculated using the proposed formula and compared with the results of numerical simulations, the Barton method, and the Homand method. The results showed that the calculated values have good consistency with the results of the numerical simulations, demonstrating the effectiveness and accuracy of the proposed formula. However, under a low normal stress, there could be errors in estimating the cyclic shear strength of the joint surface.

17.
Front Pharmacol ; 13: 978587, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091773

RESUMO

Background: Neuroinflammation plays a crucial role in the pathogenesis and progression of various neurodegenerative diseases, including Alzheimer's disease. The Ginkgo biloba leaf extract (GBE) has been widely used to treat cerebral and peripheral blood circulation disorders. However, its potential targets and underlying mechanisms regarding neuroinflammation have not yet been characterized. Aims: The purpose of this study was to investigate and validate the anti-neuroinflammatory properties of GBE against lipopolysaccharide (LPS)-mediated inflammation and to determine the underlying molecular mechanisms. Methods: The effect of GBE on LPS-induced release of inflammatory cytokines was examined using ELISA and western blot assay. The effects of GBE on NF-κB binding activity and translocation were determined via luciferase, streptavidin-agarose pulldown, and immunofluorescence assays. The potential targets of GBE were screened from the GEO and microRNA databases and further identified via qPCR, luciferase, gene mutation, and western blot assays. Results: GBE significantly inhibited LPS-induced pro-inflammatory responses in BV-2 and U87 cells, with no obvious cytotoxicity. GBE significantly induced miR-146b-5p expression, which negatively regulated TRAF6 expression by targeting its 3'-UTR. Thus, due to TRAF6 suppression, GBE decreases the transcriptional activity of NF-κB and the expression of pro-inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and cyclooxygenase (COX)-2, and finally reverses LPS-induced neuroinflammation. Conclusion: Our study revealed the anti-neuroinflammatory mechanism of GBE through the miR-146b-5p/TRAF6 axis and provided a theoretical basis for its rational clinical application.

18.
Sci Rep ; 12(1): 13637, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35948621

RESUMO

Accurately determining the shear strength of structural planes is crucial for evaluating the stability of rock masses. The shear test using the sawtooth structural plane usually captures the main influencing factors of its shear characteristics. In this study, the two-dimensional particle flow code (PFC2D) numerical simulation method was used to conduct shear tests on the sawtooth structural planes of rock masses with undulant angles of 10°, 20°, and 30°, respectively. With the increase in normal stress and the undulant angle, the shear failure of the structural planes was found to no longer be pure slip failure or shear failure but accompanied by a compression-induced fracture phenomenon. Based on the analysis of the shear test results, a peak shear strength model considering different undulant angles and normal stresses was proposed, and the hyperbolic function post-peak shear strength model was improved. The peak shear strength obtained from the physical direct shear tests was compared with those calculated using the proposed model, Parton model, and Shen model. The calculation error under low and high normal stress of the proposed method was found to be within an acceptable range. Additionally, when calculating the peak shear strength of a structural plane under high normal stress, applying the calculation method proposed in this study is a better option than applying the other models. Furthermore, although the variation trend of the post-peak shear strength was similar to that of the experimental results, the values obtained using the hyperbolic variation model were too large. The variation trend of the post-peak shear strength obtained using the improved function was essentially consistent with the experimental results, and the calculated values were close to the experimental results. The systematic research on the shear strength calculation model of rock mass structural planes contributes to the theoretical research of rock mass mechanics, and this study can act as a guide for landslide prediction and control projects.

19.
Eur J Pediatr ; 181(10): 3645-3654, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35978254

RESUMO

To establish the cross-sectional reference values of cerebral ventricular size for the Chinese newborns by the most correlated explanatory variables. The anterior horn width (AHW), thalamo-occipital distance (TOD), and ventricular index (VI) were collected prospectively from 1- to 7-day neonates without potential neurological problems. All neonates were delivered or treated at the Hunan Provincial Maternal and Child Health Care Hospital or Second Xiangya Hospital of Central South University between February and August 2021. The most correlated explanatory variables were identified with the max-min normalization and multiple regression. The reference values were then established based on the above variables. Additionally, intraclass correlation coefficients (ICC) were applied to evaluate the reliability of the overall data collection process. This prospective study consisted of 1848 neonates. The AHW was most highly correlated with GA; the TOD and VI were most strongly correlated with birth weight. All the foregoing correlations were positive ones. Heteroscedasticity and influential points existed in both TOD and VI. The ICCAHW was the largest to a specific rater or between raters, the ICCTOD the second largest, and the ICCVI the smallest. CONCLUSIONS: We recommend using the GA-based AHW reference values and birth weight-based TOD and VI ones. We also present a comparison of GA-based upper limits from all available reference intervals. Moreover, we determine that measurement errors are the primary cause of influential points and heteroscedasticity in TOD and VI studies and infer that the studies of TOD and VI are vulnerable to them. WHAT IS KNOWN: • Reference values of infantile cerebral ventricles are vital in diagnosing and treating cerebral ventricular dilatation. • Precursors established gestational age-based reference values subjectively. WHAT IS NEW: • We set cross-sectional reference values based on the most correlated variables for Chinese neonates and compared all available gestational age-based upper limits. • Influential points and heteroscedasticity mainly caused by measurement errors are common in TOD and VI studies.


Assuntos
Ventrículos Cerebrais , Peso ao Nascer , Criança , China , Estudos Transversais , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Gravidez , Estudos Prospectivos , Valores de Referência , Reprodutibilidade dos Testes
20.
Sci Rep ; 12(1): 9406, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35672364

RESUMO

When a rock mass shears along a joint surface, the shear resistance is affected by joint surface undulations and friction between the contact regions. During an earthquake, the seismic load causes dynamic deterioration of the joint surface mechanical properties, mostly reflected as follows. (1) The peak shear strength of the joint surface decreases with an increase in the shear rate. (2) Under a seismic load cyclic shear, the undulant angle αk decreases. (3) Under a dynamic load, the friction coefficient of the joint surface is reduced. By studying the cyclic shear test of the joint surface, the strength deterioration effect of the joint surface under cyclic shearing is first analysed, and the equations of the dilatation angle and the basic friction angle of the joint surface under the cyclic shearing load are proposed. Then, starting with the effect of cyclic shear deterioration on the joint surface in the rock mass and the reduction in the dynamic friction coefficient between sliding rock blocks caused by relative velocity, an equation for calculating the shear strength of a rock mass joint surface under cyclic shear loading is recommended. Through two case calculations, the shear strength obtained using the proposed method is compared with the experimental results. The results show that the model proposed in this study is in good agreement with the experimental results and can also be used to calculate the structural surface shear strength of the asperity-rich sample. However, when the calculation equation is used to estimate the cyclic shear strength of the joint surface where the sum of the initial undulation angle and the basic friction angle is greater than 70°, there may be some errors in the calculation results.

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