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1.
Plant Physiol ; 191(3): 1684-1701, 2023 03 17.
Article in English | MEDLINE | ID: mdl-36517254

ABSTRACT

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.


Subject(s)
Oryza , Temperature , Hot Temperature , Cold Temperature , Reproduction , Plant Proteins/genetics , Plant Proteins/metabolism
2.
Org Biomol Chem ; 22(20): 4047-4051, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38712523

ABSTRACT

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.

3.
Bioorg Chem ; 143: 107084, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38176376

ABSTRACT

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.


Subject(s)
Inula , Sesquiterpenes , Animals , Mice , Humans , Inula/chemistry , Molecular Structure , RAW 264.7 Cells , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , A549 Cells , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistry
4.
Ecotoxicol Environ Saf ; 278: 116415, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38703406

ABSTRACT

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.


Subject(s)
Microplastics , Reactive Oxygen Species , Sulfamethoxazole , Water Pollutants, Chemical , Zebrafish , Animals , Sulfamethoxazole/toxicity , Microplastics/toxicity , Water Pollutants, Chemical/toxicity , Reactive Oxygen Species/metabolism , MAP Kinase Signaling System/drug effects , Liver/drug effects , Chemical and Drug Induced Liver Injury/pathology , Larva/drug effects , Apoptosis/drug effects , Hepatocytes/drug effects
5.
J Integr Plant Biol ; 66(4): 709-730, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38483018

ABSTRACT

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.


Subject(s)
Hybrid Vigor , Oryza , Hybrid Vigor/genetics , Reactive Oxygen Species/metabolism , Oryza/genetics , Oryza/metabolism , Salt Tolerance/genetics , Phenotype
6.
BMC Pregnancy Childbirth ; 23(1): 723, 2023 Oct 11.
Article in English | MEDLINE | ID: mdl-37821915

ABSTRACT

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.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Female , Pregnancy , Humans , Adult , SARS-CoV-2 , Pregnant Women , Pregnancy Complications, Infectious/diagnosis , Fetus , Placenta/diagnostic imaging , Amniotic Fluid , Infectious Disease Transmission, Vertical , Ultrasonography, Prenatal
7.
Eur J Pediatr ; 181(10): 3645-3654, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35978254

ABSTRACT

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.


Subject(s)
Cerebral Ventricles , Birth Weight , Child , China , Cross-Sectional Studies , Female , Gestational Age , Humans , Infant, Newborn , Pregnancy , Prospective Studies , Reference Values , Reproducibility of Results
8.
Angew Chem Int Ed Engl ; 58(29): 9959-9963, 2019 07 15.
Article in English | MEDLINE | ID: mdl-31099941

ABSTRACT

The rapid development of fluorescent probes for monitoring target enzymes is still a great challenge owing to the lack of efficient ways to optimize a specific fluorophore. Herein, a practical two-dimensional strategy was designed for the development of an isoform-specific probe for CYP3A4, a key cytochrome P450 isoform responsible for the oxidation of most clinical drugs. In first dimension of the design strategy, a potential two-photon fluorescent substrate (NN) for CYP3A4 was effectively selected using ensemble-based virtual screening. In the second dimension, various substituent groups were introduced into NN to optimize the isoform-selectivity and reactivity. Finally, with ideal selectivity and sensitivity, NEN was successfully applied to the real-time detection of CYP3A4 in living cells and zebrafish. These findings suggested that our strategy is practical for developing an isoform-specific probe for a target enzyme.


Subject(s)
Cytochrome P-450 CYP3A/metabolism , Fluorescent Dyes/therapeutic use , Fluorescent Dyes/pharmacology , Humans
9.
Anal Chem ; 90(6): 3965-3973, 2018 03 20.
Article in English | MEDLINE | ID: mdl-29493228

ABSTRACT

Visualization of endogenous disease-associated enzymes is of great clinical significance, as it could allow earlier clinical diagnosis and timely intervention. Herein, we first synthesized and characterized an enzyme-activatable near-infrared fluorescent probe, GP-DM, for determining the activity of dipeptidyl peptidase IV (DPP IV), which is associated with various pathological processes, especially in diabetes and malignant tumors. GP-DM emitted significant turn-on NIR fluorescent signals simultaneously in response to DPP IV, making it favorable for accurately and dynamically monitoring DPP IV activity in vitro and in vivo. GP-DM exhibited excellent specificity and sensitivity in DPP IV imaging, as indicated by its higher catalytic activity than other human serine hydrolases and by its strong anti-interference ability to a complex biological matrix, which was fully characterized in a series of phenotyping reactions and inhibition assays. Encouraged by the advantages mentioned above, we successfully used GP-DM to evaluate endogenous DPP IV activity in various biological samples (plasma and tissue preparations) and living tumor cells and performed real-time in vivo bioimaging of DPP IV in zebrafish and tumor-bearing nude mice. All of the results reflected and highlighted the potential application value of GP-DM in the early detection of pathologies, individual tailoring of drug therapy, and image-guided tumor resection. Furthermore, our results revealed that DPP IV, a key target enzyme, is closely associated with the migration and proliferation of cancer cells and regulating the biological activity of DPP IV may be a useful approach for cancer therapy.


Subject(s)
Dipeptidyl Peptidase 4/analysis , Fluorescent Dyes/chemistry , Optical Imaging/methods , Animals , Dipeptidyl Peptidase 4/blood , Dipeptidyl Peptidase 4/metabolism , Enzyme Assays/methods , Hep G2 Cells , Humans , Infrared Rays , Mice , Microscopy, Confocal/methods , Neoplasms/diagnostic imaging , Neoplasms/enzymology , Zebrafish
10.
Bioorg Chem ; 81: 93-97, 2018 12.
Article in English | MEDLINE | ID: mdl-30118990

ABSTRACT

Euphoroids A-C (1-3), three new ent-abietane-type diterpenoids, together with ten known analogues (4-13) were obtained from the roots of Euphorbia ebracteolata. The structures of these compounds were determined by extensive spectroscopic data analysis, including UV, HRESIMS, 1D-, and 2D-NMR data. The inhibitory effects of compounds 1-13 on human cancer cells were determined using the MTT assay. The results revealed that new compounds 2 and 3 showed moderate cytotoxic activities against human cancer cell lines. Especially, compound 3 displayed selective cytotoxic effect agains cancer cell lines.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Diterpenes/pharmacology , Euphorbia/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Proliferation/drug effects , Diterpenes/chemistry , Diterpenes/isolation & purification , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Plant Roots/chemistry , Structure-Activity Relationship , Tumor Cells, Cultured
11.
J Pineal Res ; 62(4)2017 May.
Article in English | MEDLINE | ID: mdl-28099762

ABSTRACT

Melatonin is present in virtually all organisms from bacteria to mammals, and it exhibits a broad spectrum of biological functions, including synchronization of circadian rhythms and oncostatic activity. Several functions of melatonin are mediated by its membrane receptors, but others are receptor-independent. For the latter, melatonin is required to penetrate membrane and enters intracellular compartments. However, the mechanism by which melatonin enters cells remains debatable. In this study, it was identified that melatonin and its sulfation metabolites were the substrates of oligopeptide transporter (PEPT) 1/2 and organic anion transporter (OAT) 3, respectively. The docking analysis showed that the binding of melatonin to PEPT1/2 was attributed to their low binding energy and suitable binding conformation in which melatonin was embedded in the active site of PEPT1/2 and fitted well with the cavity in three-dimensional space. PEPT1/2 transporters play a pivotal role in melatonin uptake in cells. Melatonin's membrane transportation via PEPT1/2 renders its oncostatic effect in malignant cells. For the first time, PEPT1/2 were identified to localize in the mitochondrial membrane of human cancer cell lines of PC3 and U118. PEPT1/2 facilitated the transportation of melatonin into mitochondria. Melatonin accumulation in mitochondria induced apoptosis of PC3 and U118 cells. Thus, PEPT1/2 can potentially be used as a cancer cell-targeted melatonin delivery system to improve the therapeutic effects of melatonin in cancer treatment.


Subject(s)
Melatonin/metabolism , Mitochondria/metabolism , Symporters/metabolism , Blotting, Western , Caco-2 Cells , Cell Line , Chromatography, Liquid , Flow Cytometry , HeLa Cells , Humans , Membrane Potential, Mitochondrial/genetics , Membrane Potential, Mitochondrial/physiology , Peptide Transporter 1 , Reactive Oxygen Species/metabolism , Symporters/genetics , Tandem Mass Spectrometry
12.
Zhonghua Yu Fang Yi Xue Za Zhi ; 49(10): 860-5, 2015 Oct.
Article in Zh | MEDLINE | ID: mdl-26813716

ABSTRACT

OBJECTIVE: To analyze pupils' neglect status aged 6-11 years in China's rural. METHODS: According to the principle of multi-stage stratified cluster sampling, to extract 7,943 pupils aged 6-11 years for the survey from 56 primary schools in 28 counties in nine provinces, from December 2012 to March 2013. Proceed questionnaire survey by the scale from "Neglect Evaluation Norms for pupils aged 6-8 years in Rural Areas of China" and "Neglect Evaluation Norms for pupils aged 9-11 years in Rural Areas of China". And analyze neglect rates and neglect degrees of the different grades, gender, family types and different levels of neglect. RESULTS: The total neglect rate of China's rural pupils aged 6-8 and 9-11 years was 40.2% (1,258/3,130) and 42.5% (1,498/3,526) respectively, which differences had no statistical significant (χ2=3.59, P=0.058); the total neglect degree was 46.04±8.87 and 44.78±10.43 respectively, which differences had statistical significant (t=5.01, P<0.001); the differences of neglect rates and neglect degrees between male (41.4% (657/1,587) and 46.28±8.76) and female (39.0% (601/1,543) and 45.78±8.97) of aged 6-8 were all no statistical significant (χ2=1.87, P=0.171; t=1.49, P=0.136); the neglect rates and neglect degrees of male (46.3% (816/1,763) and 45.53±10.11) were higher than female (38.7% (682/1,763) and 44.06±10.69) in the group of aged 9-11, which differences were all statistical significant (χ2=20.84, t=3.97, P<0.001); the male neglect rate in the group of aged 6-8 in social neglect (11.7% (198/1,691)) and the neglect degree in educational neglect (48.09±9.70) were higher than female (9.4% (155/1,648) and 47.37±9.89), which differences were all statistical significance (χ2=14.55, P<0.001, t=2.22, P=0.026), the male neglect rate in the group of aged 9-11 in physical neglect (20.4% (398/1,954)) was higher than female (16.7% (326/1 957)), which differences had statistical significance (χ2=8.92, P=0.003). CONCLUSION: The neglect status of Chinese pupils aged 6-11 years in rural was serious, and we should find out risk factors and provide efficient prevention measures.


Subject(s)
Child Abuse , Rural Population , Child , China , Female , Humans , Male , Physical Examination , Pupil , Risk Factors , Schools , Surveys and Questionnaires
13.
Zhonghua Yu Fang Yi Xue Za Zhi ; 48(6): 476-83, 2014 Jun.
Article in Zh | MEDLINE | ID: mdl-25219436

ABSTRACT

OBJECTIVE: To develop a standard Neglect Evaluation Scale which is suitable for rural primary school students in China. METHODS: According to the principle of multi-stage stratified cluster sampling, a field investigation was conducted among primary school students in 28 counties from 7 provinces and 2 municipalities. The questionnaires were self-designed, and determined by multiple rounds of pilots and revisions. Among 5 862 students, 2 792 (6-8 years' old) and 3 070 (9-11 years' old) were investigated by using two kinds of Neglect Evaluation questionnaires, respectively. After project analysis, factor analysis, reliability and validity analysis, the reliability and stability of the scale were tested. Then percentile method was used to determine the evaluation standard to develop and finalize the formal scale. RESULTS: The numbers of the remaining items for 6-8 year-old group and 9-11 year-old group is 69 and 58, respectively, both of which contain six levels of neglect, including body, emotion, health care, education, security, and society. 4 times of factor analysis were conducted in both of the two groups. The factor loadings in these two groups were 0.290-0.700 and 0.276-0.729 respectively. Reliability test results showed that the two kinds of scales' Cronbach alpha coefficient were 0.924 and 0.929 respectively, split-half reliability were 0.891 and 0.904 respectively, the retest reliability were 0.559 and 0.892 respectively, the differences were statistically significant (P < 0.05). The retest reliability among 6-8 year-old group in medical neglect level had no statistical significance, but was close to the cut-off point (P = 0.054). The test results of external validity indicated that both of the two scales could reflect the neglect status of the subjects (P < 0.05), but the subjective and objective evaluation towards neglect were not consistent. The cut-off points for judging whether the children were neglected or not among 6-8 year-old and 9-11 year-old groups were 159 and 137 respectively; and the adjusted values were 160 and 135 respectively. CONCLUSION: The two norm scales developed by this study showed good discriminability, reliability, validity, and stability. The norms developed on the basis of the scales was suitable for the situation of rural students in primary schools in China.


Subject(s)
Child Abuse , Rural Population , Students , Surveys and Questionnaires , Child , China , Factor Analysis, Statistical , Humans , Reproducibility of Results , Schools
15.
Org Lett ; 26(21): 4427-4432, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38757832

ABSTRACT

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.

16.
Sci Rep ; 14(1): 5351, 2024 03 04.
Article in English | MEDLINE | ID: mdl-38438512

ABSTRACT

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.


Subject(s)
Mandible , Nuchal Translucency Measurement , Humans , Female , Pregnancy , Reproducibility of Results , Mandible/diagnostic imaging , Fetus/diagnostic imaging , Prenatal Care
17.
Environ Pollut ; 351: 124101, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38710361

ABSTRACT

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.


Subject(s)
Mice, Inbred ICR , Ovary , Polystyrenes , Uterus , Animals , Female , Mice , Uterus/drug effects , Uterus/metabolism , Ovary/drug effects , Ovary/metabolism , Polystyrenes/toxicity , Reproduction/drug effects , Microplastics/toxicity , Bone Morphogenetic Protein 4/genetics , Bone Morphogenetic Protein 4/metabolism , Nanoparticles/toxicity , Molecular Docking Simulation , Environmental Pollutants/toxicity , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta/genetics
18.
Biomaterials ; 309: 122608, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38744189

ABSTRACT

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.


Subject(s)
Chitosan , Metal Nanoparticles , Naphthoquinones , Necroptosis , Receptor-Interacting Protein Serine-Threonine Kinases , Silver , Triple Negative Breast Neoplasms , Naphthoquinones/pharmacology , Naphthoquinones/chemistry , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/drug therapy , Chitosan/chemistry , Silver/chemistry , Silver/pharmacology , Animals , Metal Nanoparticles/chemistry , Receptor-Interacting Protein Serine-Threonine Kinases/metabolism , Cell Line, Tumor , Female , Necroptosis/drug effects , Humans , Mice , Immunogenic Cell Death/drug effects , Mice, Inbred BALB C , Mucin-1/metabolism , Drug Synergism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/chemistry
19.
J Headache Pain ; 14: 85, 2013 Oct 17.
Article in English | MEDLINE | ID: mdl-24134520

ABSTRACT

BACKGROUND: Advanced neuroimaging approaches have been employed to prove that migraine was a central nervous system disorder. This study aims to examine resting-state abnormalities in migraine without aura (MWoA) patients stratified by disease duration, and to explore the neuroimaging markers for reflecting the disease duration. METHODS: 40 eligible MWoA patients and 20 matched healthy volunteers were included in the study. Regional homogeneity (ReHo) analysis was used to identify the local features of spontaneous brain activity in MWoA patients stratified by disease duration, and analysis was performed to investigate the correlation of overlapped brain dysfunction in MWoA patients with different disease duration (long-term and short-term) and course of disease. RESULTS: Compared with healthy controls, MWoA patients with long-term disease duration showed comprehensive neuronal dysfunction than patients with short-term disease duration. In addition, increased average ReHo values in the thalamus, brain stem, and temporal pole showed significantly positive correlations with the disease duration. On the contrary, ReHo values were negatively correlated with the duration of disease in the anterior cingulate cortex, insula, posterior cingulate cortex and superior occipital gyrus. CONCLUSIONS: Our findings of progressive brain damage in relation to increasing disease duration suggest that migraine without aura is a progressive central nervous disease, and the length of the disease duration was one of the key reasons to cause brain dysfunction in MwoA patients. The repeated migraine attacks over time result in resting-state abnormalities of selective brain regions belonging to the pain processing and cognition. We predict that these brain regions are sensitive neuroimaging markers for reflecting the disease duration of migraine patients without aura.


Subject(s)
Brain/pathology , Migraine without Aura/pathology , Adult , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male
20.
Zhonghua Yu Fang Yi Xue Za Zhi ; 47(2): 129-34, 2013 Feb.
Article in Zh | MEDLINE | ID: mdl-23719103

ABSTRACT

OBJECTIVE: To develop the national neglect norms for urban primary school students in China. METHODS: According to multi-stage stratified cluster sampling principle, 24 cities of 13 provinces (municipalities) in China were selected during December 1 to 31, 2008. A total of 1491 students in grade 1 - 3 and 2236 students in grade 4 - 6 were selected. Questionnaire was designed by authors and the final norms were determined through several statistical analysis methods, such as item analysis method, factor analysis method, reliability analysis method. The reliability analysis and validity analysis were used to test the stability and reliability of the norms. The evaluation criteria of the scale was determined by the percentile method, then the initial development of the norm was completed. RESULTS: The two questionnaires of grade 1 - 3 and grade 4 - 6 students consisted of 55 and 57 items, respectively, whose item loadings were ranged from 0.301 to 0.687 and 0.321 to 0.730, which met the statistical requirements. For grade 1 - 3 students, the scale's total Cronbach α coefficients was 0.914, the total split-half reliability coefficients was 0.896, the Cronbach α coefficients of four level was above 0.737 except medical and social neglect, split-half reliability was ranged from 0.461 to 0.757; for grade 4-6 students, the scale's total Cronbach α coefficients was 0.916, split-half reliability was 0.883, except social neglect, the Cronbach α coefficients of other level was ranged 0.457 to 0.856, split-half reliability was ranged from 0.500 to 0.798. The total neglect cut-off score of the two scales grade 1-3 and 4-6 were 125 and 155, respectively. CONCLUSION: The structure of two norms was reasonable. The scales have good stability and reliability.


Subject(s)
Child Abuse/prevention & control , Students , Surveys and Questionnaires , Child , Child Abuse/statistics & numerical data , China/epidemiology , Female , Humans , Male , Reproducibility of Results , Schools
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