Cytoskeletal and inter-cellular junction remodelling in endometrial organoids under oxygen-glucose deprivation: a new potential pathological mechanism for thin endometria.

STUDY QUESTION: What is the pathological mechanism involved in a thin endometrium, particularly under ischaemic conditions? SUMMARY ANSWER: Endometrial dysfunction in patients with thin endometrium primarily results from remodelling in cytoskeletons and cellular junctions of endometrial epithelial cells under ischemic conditions. WHAT IS KNOWN ALREADY: A healthy endometrium is essential for successful embryo implantation and subsequent pregnancy; ischemic conditions in a thin endometrium compromise fertility outcomes. STUDY DESIGN, SIZE, DURATION: We recruited 10 patients with thin endometrium and 15 patients with healthy endometrium. Doppler ultrasound and immunohistochemical results confirmed the presence of insufficient endometrial blood perfusion in patients with thin endometrium. Organoids were constructed using healthy endometrial tissue and cultured under oxygen-glucose deprivation (OGD) conditions for 24 h. The morphological, transcriptomic, protein expression, and signaling pathway changes in the OGD organoids were observed. These findings were validated in both thin endometrial tissue and healthy endometrial tissue samples. PARTICIPANTS/MATERIALS, SETTING, METHODS: Endometrial thickness and blood flow were measured during the late follicular phase using transvaginal Doppler ultrasound. Endometrial tissue was obtained via hysteroscopy. Fresh endometrial tissues were used for the generation and culture of human endometrial organoids. Organoids were cultured in an appropriate medium and subjected to OGD to simulate ischemic conditions. Apoptosis and cell death were assessed using Annexin-V/propidium iodide staining. Immunofluorescence analysis, RNA sequencing, western blotting, simple westerns, immunohistochemistry, and electron microscopy were conducted to evaluate cellular and molecular changes. MAIN RESULTS AND THE ROLE OF CHANCE: Patients with thin endometrium showed significantly reduced endometrial thickness and altered blood flow patterns compared to those with healthy endometrium. Immunohistochemical staining revealed fewer CD34-positive blood vessels and glands in the thin endometrium group. Organoids cultured under OGD conditions exhibited significant morphological changes, increased apoptosis, and cell death. RNA-seq identified differentially expressed genes related to cytoskeletal remodeling and stress responses. OGD induced a strong cytoskeletal reorganization, mediated by the RhoA/ROCK signaling pathway. Additionally, electron microscopy indicated compromised epithelial integrity and abnormal cell junctions in thin endometrial tissues. Upregulation of hypoxia markers (HIF-1α and HIF-2α) and activation of the RhoA/ROCK pathway were also observed in thin endometrial tissues, suggesting ischemia and hypoxia as underlying mechanisms. LARGE SCALE DATA: none. LIMITATIONS AND REASONS FOR CAUTION: The study was conducted in an in vitro model, which may not fully replicate the complexity of in vivo conditions. WIDER IMPLICATIONS OF THE FINDINGS: This research provides a new three-dimensional in vitro model of thin endometrium, as well as novel insights into the pathophysiological mechanisms of endometrial ischaemia in thin endometrium, offering potential avenues for identifying therapeutic targets for treating fertility issues related to thin endometrium. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Natural Science Foundation of China (81925013); National Key Research and Development Project of China (2022YFC2702500, 2021YFC2700303, 2021YFC2700601); the Capital Health Research and Development Project (SF2022-1-4092); the National Natural Science Foundation of China (82288102, 81925013, 82225019, 82192873); Special Project on Capital Clinical Diagnosis and Treatment Technology Research and Transformation Application (Z211100002921054); the Frontiers Medical Center, Tianfu Jincheng Laboratory Foundation(TFJC2023010001). The authors declare that no competing interests exist.

Gender differences in adolescent food preferences and their association with parent food preferences: data from the China Health and Nutrition Survey (CHNS).

PURPOSE: Food preference is an important factor that affects one's eating behavior and dietary intake. Parent food preferences and food choices may influence children food preferences. This study is aimed to describe gender differences and time trends of Chinese adolescent food preferences and to explore the association between adolescent and their parent food preferences. METHODS: The data were drawn from four waves of the China Health and Nutrition Survey (CHNS) conducted between 2006 and 2015. Participants were asked to indicate their degree of preferences for five food categories (fast food, salty snack food, fruits, vegetables, and soft/sugary drinks) using a 5-point Likert scale (from "dislike very much" to "like very much"). Logistic regression was performed to determine the association of food preferences between adolescents and their parents. RESULTS: Adolescent preferences for unhealthy foods were significantly higher than those of adults. Adolescent food preferences for fruits and vegetables decreased slightly over nine years, and there were gender differences in healthy food preferences (girls > boys, P < 0.05). Regardless of boys or girls, adolescent food preferences for healthy foods (fruits and vegetables) were significantly associated with both their fathers (OR: 3.64-4.58 for boys and 2.71-4.39 for girls) and mothers (OR: 2.13-4.11 for boys and 3.07-5.66 for girls) food preferences. For fast food and salty snack food preferences, boys appeared to be influenced greater by their fathers than girls, while girls appeared to be influenced greater by their mothers than boys. CONCLUSIONS: The present study reveals a high degree of unhealthy food preferences among Chinese adolescents and a gender-specific association of fast food and salty snack preference between Chinese adolescents and their parents. Our results may be useful for interventions to reduce adolescent unhealthy food preferences and intakes.

Green Synthesis and Antifungal Activities of Novel N-Aryl Carbamate Derivatives.

Carbamate is a key structural motif in the development of fungicidal compounds, which is still promising and robust in the discovery of green pesticides. Herein, we report the synthesis and evaluation of the fungicidal activity of 35 carbamate derivatives, among which 19 compounds were synthesized in our previous report. These derivatives were synthesized from aromatic amides in a single step, which was a green oxidation process for Hofmann rearrangement using oxone, KCl and NaOH. Their chemical structures were characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry. Their antifungal activity was tested against seven plant fungal pathogens. Many of the compounds exhibited good antifungal activity in vitro (inhibitory rate > 60% at 50 µg/mL). Compound 1ag exhibited excellent broad-spectrum antifungal activities with inhibition rates close to or higher than 70% at 50 µg/mL. Notably, compound 1af demonstrated the most potent inhibition against F. graminearum, with an EC50 value of 12.50 µg/mL, while compound 1z was the most promising candidate fungicide against F. oxysporum (EC50 = 16.65 µg/mL). The structure-activity relationships are also discussed in this paper. These results suggest that the N-aryl carbamate derivatives secured by our green protocol warrant further investigation as potential lead compounds for novel antifungal agents.

Phosphorus doped and defect modified graphitic carbon nitride for boosting photocatalytic hydrogen production.

The enhancement of photogenerated carrier separation efficiency is a significant factor in the improvement of photocatalyst performance in photocatalytic hydrogen evolution. Heteroatom doping and defect construction have been considered valid methods to boost the photocatalytic activity of graphitic carbon nitride. Herein, we report graphitic carbon nitride modified with P doping and N defects (PCNx), and the effects of doping and defects were investigated in photocatalytic H2 evolution. Its hydrogen evolution rate can reach up to about 59.1 µmol h-1, which is more than 123.1 times higher than pristine graphitic carbon nitride under visible light irradiation. Importantly, the apparent quantum efficiency reaches 8.73% at 420 nm. The excellent performance of the PCNx photocatalyst was attributed to the following aspects: (I) the large BET surface area of PCNx affords more active sites for H2 production and (II) the introduction of P and N defects can accelerate the charge carrier separation and transfer efficiency, leading to more efficient photocatalytic hydrogen production. The photocatalyst showed obviously enhanced activities.

Surface Coordination of Pd/ZnIn2S4 toward Enhanced Photocatalytic Activity for Pyridine Denitrification.

New surface coordination photocatalytic systems that are inspired by natural photosynthesis have significant potential to boost fuel denitrification. Despite this, the direct synthesis of efficient surface coordination photocatalysts remains a major challenge. Herein, it is verified that a coordination photocatalyst can be constructed by coupling Pd and CTAB-modified ZnIn2S4 semiconductors. The optimized Pd/ZnIn2S4 showed a superior degradation rate of 81% for fuel denitrification within 240 min, which was 2.25 times higher than that of ZnIn2S4. From the in situ FTIR and XPS spectra of 1% Pd/ZnIn2S4 before and after pyridine adsorption, we find that pyridine can be selectively adsorbed and form Zn⋅⋅⋅C-N or In⋅⋅⋅C-N on the surface of Pd/ZnIn2S4. Meanwhile, the superior electrical conductivity of Pd can be combined with ZnIn2S4 to promote photocatalytic denitrification. This work also explains the surface/interface coordination effect of metal/nanosheets at the molecular level, playing an important role in photocatalytic fuel denitrification.

Maternal feeding practices and toddlers' fruit and vegetable consumption: results from the DIT-Coombe Hospital birth cohort in Ireland.

BACKGROUND: Health benefits of fruit and vegetable have been well recognized. However, insufficient consumption of fruit and vegetable is prevalent among toddlers, and has become a global public health issue. Maternal feeding practices are potential factors influencing toddlers' dietary intake, including fruit and vegetable intake. This study was conducted to explore the influence of maternal feeding practices on toddlers' fruit and vegetable consumption in Ireland. METHODS: A follow-up to the DIT-Coombe Hospital birth cohort was conducted. Mothers in the original cohort were invited to participate in the present follow-up study by phone. A questionnaire assessing maternal feeding behavior and the child's 3-day food diary was sent to mothers who agreed to take part in the present study by post, together with a self-addressed stamped envelope. RESULTS: There were 193 mother-children pairs included in the analysis, and the mean age of children was 2.4 (SD 0.7) years old. Toddlers' mean daily intakes of vegetable and fruit were 67.57 (SD 45.95) g and 213.35 (SD 170.78) g, respectively. Logistic regression analyses showed that maternal practice of breastfeeding for more than 4 weeks was positively associated with fruit (OR = 2.93, 95% CI: 1.29-6.64) and vegetable (OR = 1.95, 95% CI: 1.00-3.81) intake or the contribution of fruit (OR = 2.62, 95% CI: 1.19-5.80) and vegetable (OR = 2.02, 95% CI: 1.02-3.99) to the total diet. Letting the child eat with other family members was associated with high vegetable intake (OR = 5.45, 95%CI: 1.69-17.61) and high contribution of vegetable to total diet (OR = 3.78, 95% CI: 1.04-13.82). Not being too worried about the child's refusal to eat was positively associated with toddlers' vegetable intake (OR = 2.10, 95%CI: 1.09-4.05). CONCLUSIONS: To increase children's fruit and vegetable intake, and develop good eating habits, parents should eat with their toddlers, be patient and not put much pressure on their children in the context of meal feeding.

Low-dose aspirin for primary prevention of adverse pregnancy outcomes in twin pregnancies: an observational cohort study based on propensity score matching.

BACKGROUND: Since the effectiveness of low-dose aspirin (LDA) in twin pregnancies is uncertain, we aimed to preliminarily assess whether LDA is beneficial in preventing preeclampsia in twin pregnancies. METHODS: This study is an observational study in two hospitals in China. Among 932 women, 277 in the First Affiliated Hospital of Chongqing Medical University were routinely treated with aspirin (100 mg daily) from 12 to 16 weeks to 35 weeks of gestational age, while 655 in Chongqing Health Center for Women and Children were not taking aspirin during pregnancy. We followed each subject and the individual details were recorded. RESULTS: LDA significantly reduced the risk of preeclampsia (RR 0.48; 95% CI 0.24-0.95) and preterm birth 34 weeks (RR 0.50; 95% CI 0.29-0.86) and showed possible benefits to lower the rate of SGA babies (RR 0.74; 95% CI 0.55-1.00). Moreover, the risk of postpartum hemorrhage was not increased by LDA (RR 0.89; 95% CI 0.35-2.26). CONCLUSIONS: Treatment with low-dose aspirin in twin pregnancies could offer some protection against adverse pregnancy outcomes in the absence of significantly increased risk of postpartum hemorrhage. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR); ChiCTR-OOC-16008203 , Retrospectively registered date: April 1st, 2016.

Real-world in-hospital outcomes and potential predictors of heart failure in primigravid women with heart disease in Southwestern China.

BACKGROUND: Little is known about the status of maternal, obstetric, and neonatal complications and the potential predictors of developing heart failure (HF) in mothers with underlying heart disease (HD) in Southwestern China. METHODS: The eligible records from the YiduCloud database from December 1, 2010 to December 31, 2019 were screened. The maternal clinical characteristics and the in-hospital outcomes were collected and compared in primigravid women with and without HD. The HD subtypes analyzed included valvular HD (VHD), cardiomyopathy, adult congenital HD (ACHD), pulmonary hypertension (PH), and other cardiac conditions. RESULTS: Among 45,067 primigravid women, 508 (1.1%) had HD, in which 207 (41%) had ACHD, 66 (13%) had VHD, 84 (17%) had cardiomyopathy, 7 (1%) had PH, and 144 (28%) had other cardiac diseases. The maternal cardiac events and the neonatal complications occurred in 28% and 23.3%, respectively, of women with HD and were predominant in the PH group. In multivariable regression, HF was associated with the New York Heart Association (NYHA) class ≥3 (OR = 15.9, 95% confidence interval [CI] = 2.5-99.7; P = 0.003), heart rate ≥ 100 bpm (OR = 3.8, 95% CI = 1.1-13.5; P = 0.036), ejection fraction ≤60% (OR = 6.4, 95% CI = 2.0-21.0; P = 0.002) and left ventricular end-diastolic diameter ≥ 50 mm (OR = 3.4, 95% CI = 1.1-11.2; P = 0.041) at the beginning of pregnancy. CONCLUSIONS: Maternal and neonatal complications are higher in primigravid women with HD particularly in the PH group compared with primigravid women without HD. Women with HD should be guided on the potential predictors for HF and closely monitored during pregnancy to reduce maternal and neonatal complications.

Maternal Utero-Placental Perfusion Discordance in Monochorionic-Diamniotic Twin Pregnancies with Selective Growth Restriction Assessed by Three-Dimensional Power Doppler Ultrasound.

BACKGROUND The aim of this study was to assess the correlation between selective growth restriction (sGR) and co-twin utero-placental perfusion discordance by using three-dimensional power Doppler (3DPD). MATERIAL AND METHODS We prospectively recruited 60 sGR and 64 normal monochorionic-diamniotic (MCDA) twin pregnancies. Vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were assessed by 3DPD, while umbilical artery pulsatility index (UA-PI), middle cerebral artery peak systolic velocity (MCA-PSV), pulsatility index (MCA-PI), and cerebroplacental ratio (CPR) were assessed by conventional Doppler imaging. RESULTS In sGR co-twins, the VI, FI, VFI, MCA-PI, and CPR were significantly lower, while the UA-PI and MCA-PSV were significantly greater, in the smaller fetuses compared with the larger fetuses; significant differences were also observed in the VI, FI, VFI, CPR, and UA-PI in normal co-twins. Compared with the appropriately grown twins, the discordances of the VI, FI, VFI, UA-PI, MCA-PI, and CPR were increased in the sGR cohort. The discordances of the VI, FI, VFI, UA-PI, MCA-PI, and CPR were associated with birthweight discordance, and the FI discordance and CPR discordance were independently associated with sGR. The combination of the FI and CPR discordance showed a higher predictive accuracy for sGR, with an area under the ROC curve of 0.813, and a sensitivity and specificity of 68.33% and 85.94%, respectively. CONCLUSIONS MCDA twin pregnancies with birthweight discordance presented utero-placental perfusion deterioration assessed by 3DPD prior to sGR diagnosis. Co-twin utero-placental perfusion discordance was significantly correlated with growth discordance, and this correlation was more predictive of sGR when 3DPD was combined with conventional Doppler imaging.

Double- versus single-balloon catheters for labour induction and cervical ripening: a meta-analysis.

BACKGROUND: The induction of labour is an increasingly common procedure in the obstetrics field. Various methods have been used to induce labour, among which balloon catheters play an important role. Whether the specifically designed double-balloon catheter is better than the single-balloon device in terms of efficacy, efficiency, safety and patient satisfaction remains controversial. Identifying even small differences between these two devices could be useful to guide clinical practices, to further explore their mechanisms, and to promote a better understanding of the optimal methods for inducing labour. METHODS: Using the population, intervention, comparison, outcomes and study designs (PICOS) principle, we searched the PubMed, EMBASE, OVID, SCI, CENTRAL, ClinicalTrial.gov , and CDSR databases to identify relevant randomised controlled trials (RCTs) from inception through February 14, 2018. The primary outcome was the caesarean delivery rate, and the secondary outcomes focused on efficacy, efficiency, safety, and patient satisfaction. The relative risks or mean differences, including their 95% confidence intervals, were calculated using fixed-effects or random-effects models. All statistical analyses were completed with RevMan version 5.3. RESULTS: From a total of 1326 articles, 7 RCTs involving 1159 women were included. There were no significant differences in primary outcomes (RR, 0.88 [0.65, 1.2]; p-value, 0.43) or secondary outcomes identified between single- and double-balloon catheters. However, heterogeneity existed for some aspects. CONCLUSION: Both kinds of balloon catheter have similar levels of efficacy, efficiency, safety and patient satisfaction; however, the single-balloon method is considered to be more cost-effective.

Gestational Diabetes Mellitus Changes the Metabolomes of Human Colostrum, Transition Milk and Mature Milk.

BACKGROUND Gestational diabetes mellitus (GDM) is a pregnancy complication that is diagnosed by the novel onset of abnormal glucose intolerance. Our study aimed to investigate the changes in human breast milk metabolome over the first month of lactation and how GDM affects milk metabolome. MATERIAL AND METHODS Colostrum, transition milk, and mature milk samples from women with normal uncomplicated pregnancies (n=94) and women with GDM-complicated pregnancies (n=90) were subjected to metabolomic profiling by the use of gas chromatography-mass spectrometry (GC-MS). RESULTS For the uncomplicated pregnancies, there were 59 metabolites that significantly differed among colostrum, transition milk, and mature milk samples, while 58 metabolites differed in colostrum, transition milk, and mature milk samples from the GDM pregnancies. There were 28 metabolites that were found to be significantly different between women with normal pregnancies and women with GDM pregnancies among colostrum, transition milk, and mature milk samples. CONCLUSIONS The metabolic profile of human milk is dynamic throughout the first months of lactation. High levels of amino acids in colostrum and high levels of saturated fatty acids and unsaturated fatty acids in mature milk, which may be critical for neonatal development in the first month of life, were features of both normal and GDM pregnancies.

Orientation Histogram-Based Center-Surround Interaction: An Integration Approach for Contour Detection.

Contour is a critical feature for image description and object recognition in many computer vision tasks. However, detection of object contour remains a challenging problem because of disturbances from texture edges. This letter proposes a scheme to handle texture edges by implementing contour integration. The proposed scheme integrates structural segments into contours while inhibiting texture edges with the help of the orientation histogram-based center-surround interaction model. In the model, local edges within surroundings exert a modulatory effect on central contour cues based on the co-occurrence statistics of local edges described by the divergence of orientation histograms in the local region. We evaluate the proposed scheme on two well-known challenging boundary detection data sets (RuG and BSDS500). The experiments demonstrate that our scheme achieves a high [Formula: see text]-measure of up to 0.74. Results show that our scheme achieves integrating accurate contour while eliminating most of texture edges, a novel approach to long-range feature analysis.

Gamma-glutamylcyclotransferase promotes the growth of human glioma cells by activating Notch-Akt signaling.

Glioma as an aggressive type tumor is rapidly growing and has become one of the leading cause of cancer-related death worldwide. γ-Glutamylcyclotransferase (GGCT) has been shown as a diagnostic marker in various cancers. To reveal whether there is a correlation between GGCT and human glioma, GGCT expression in human glioma tissues and cell lines was first determined. We found that GGCT expression was up-regulated in human glioma tissues and cell lines. Further, we demonstrate that GGCT knockdown inhibits glioma cell T98G and U251 proliferation and colony formation, whereas GGCT overexpression leads to oppose effects. GGCT overexpression promotes the expression of Notch receptors and activates Akt signaling in glioma cells, and Notch-Akt signaling is activated in glioma tissues with high expression of GGCT. Finally, we show that inhibition of Notch-Akt signaling with Notch inhibitor MK-0752 blocks the effects of GGCT on glioma proliferation and colony formation. In conclusion, GGCT plays a critical role in glioma cell proliferation and may be a potential cancer therapeutic target.

Family treatment courts and the COVID-19 pandemic: Barriers and facilitators to program implementation, client engagement, and recovery.

INTRODUCTION: Family Treatment Courts (FTCs) serve child welfare-involved parents with substance use issues who are working toward recovery and reunification with their children. Research has linked FTCs to successful outcomes such as treatment access and completion and family reunification, but there has been less attention to factors that hinder and facilitate program implementation and client engagement. Moreover, little is known about how the shift to virtual services during the COVID-19 pandemic impacted FTC programs and the families they serve. METHODS: This study examined interview data gathered from staff in six FTCs located in different regions of the country to investigate the impact of the pandemic on programs and the clients they serve. Interviews conducted with clients from one FTC in the Midwest reinforce the data. RESULTS: FTC programs and professionals adjusted to the pandemic by attempting to replicate face-to-face services in an online environment. Virtual services were vital for sustaining FTCs and mitigating barriers to client engagement during the pandemic. At the same time, FTCs were compelled to navigate new barriers to online program implementation as well as acute challenges that clients faced such as greater isolation and reduced treatment access. CONCLUSIONS: We discuss implications from these findings with an eye toward maximizing FTC implementation and impact through the intentional use of both in-person programming and online technology after the pandemic.

GLUT3 transcriptional activation by ZEB1 fuels the Warburg effect and promotes ovarian cancer progression.

Ovarian cancer (OvCa) is characterized by early metastasis and high mortality rates, underscoring the need for deeper understanding of these aspects. This study explores the role of glucose transporter 3 (GLUT3) driven by zinc finger E-box-binding homeobox 1 (ZEB1) in OvCa progression and metastasis. Specifically, this study explored whether ZEB1 promotes glycolysis and assessed the potential involvement of GLUT3 in this process in OvCa cells. Our findings revealed that ZEB1 and GLUT3 were excessively expressed and closely correlated in OvCa. Mechanistically, ZEB1 activates the transcription of GLUT3 by binding to its promoter region. Increased expression of GLUT3 driven by ZEB1 dramatically enhances glycolysis, and thus fuels Warburg Effect to promote OvCa progression and metastasis. Consistently, elevated ZEB1 and GLUT3 expression in clinical OvCa is correlated with poor prognosis, reinforcing the profound contribution of ZEB1-GLUT3 axis to OvCa. These results suggest that activation of GLUT3 expression by ZEB1 is crucial for the proliferation and metastasis of OvCa via fueling glycolysis, shedding new light on OvCa treatment.

Selenium Status Associates with Thyroid Hormone and Thyroid Dysfunction in Older Chinese Adults.

Selenium (Se) is physiologically essential for thyroid function. However, epidemiological studies on the association between Se status and thyroid function are limited and the results are inconsistent. Therefore, we explored this association in an elderly Chinese population sample. Participants in the cross-sectional study were people aged 65 years or older who provided fingernail and whole blood samples. Hyperthyroidism and hypothyroidism were defined by serum thyroid hormones concentrations, including thyroid stimulating hormone (TSH), total triiodothyronine (TT3), total thyroxine (TT4), free thyroxine (FT3), and free thyrotropin (FT4). Significant positive association was observed between whole blood and fingernail Se concentrations (r = 0.672, P < 0.001). Compared with the lowest Se quartile (Q1), the other fingernail Se quartile groups had lower TSH, higher FT3 and FT4 levels, and Q2 had higher TT3 levels after adjusting for covariates; the other whole blood Se quartile groups had lower TSH levels, Q2 had higher FT3, FT4 and TT3 levels, Q3 had higher FT3 levels, and Q4 had higher FT4 levels after adjusting for covariates. Compared with Q1, the adjusted odds ratios (OR) and 95% confidence intervals (95%CIs) of hypothyroidism for Q4 of whole blood Se was 0.141 (0.029,0.675), and the adjusted OR (95%CIs) of hyperthyroidism for Q2 and Q3 of fingernail Se were 4.121 (1.233,13.733) and 3.614 (1.095,11.926). Higher Se levels were significantly associated with lower TSH levels and higher levels of TT3, FT3 and FT4. Meanwhile, higher Se levels were associated with lower risk of hypothyroidism and higher risk of hyperthyroidism.

The proto-oncogene tyrosine kinase c-SRC facilitates glioblastoma progression by remodeling fatty acid synthesis.

Increased fatty acid synthesis benefits glioblastoma malignancy. However, the coordinated regulation of cytosolic acetyl-CoA production, the exclusive substrate for fatty acid synthesis, remains unclear. Here, we show that proto-oncogene tyrosine kinase c-SRC is activated in glioblastoma and remodels cytosolic acetyl-CoA production for fatty acid synthesis. Firstly, acetate is an important substrate for fatty acid synthesis in glioblastoma. c-SRC phosphorylates acetyl-CoA synthetase ACSS2 at Tyr530 and Tyr562 to stimulate the conversion of acetate to acetyl-CoA in cytosol. Secondly, c-SRC inhibits citrate-derived acetyl-CoA synthesis by phosphorylating ATP-citrate lyase ACLY at Tyr682. ACLY phosphorylation shunts citrate to IDH1-catalyzed NADPH production to provide reducing equivalent for fatty acid synthesis. The c-SRC-unresponsive double-mutation of ACSS2 and ACLY significantly reduces fatty acid synthesis and hampers glioblastoma progression. In conclusion, this remodeling fulfills the dual needs of glioblastoma cells for both acetyl-CoA and NADPH in fatty acid synthesis and provides evidence for glioma treatment by c-SRC inhibition.

Vertical distribution of total mercury and methylmercury in sediment of the Fugong mangrove area at Jiulong River Estuary, Fujian, China.

The concentrations and vertical distributions of total mercury (Hg) and methylmercury (methyl Hg) in the sediment of the Fugong mangrove area, located at the Jiulong River Estuary, Fujian, China, were investigated. The concentrations of total mercury were between 0.12-0.17 and 0.11-40.14 microg/g, while concentrations of methylmercury were between 0.15-1.8 and 0.081-0.58 ng/g (as mercury), in the dry and rainy seasons, respectively. The total mercury concentration was not correlated with the sampling depth. As the depth increased, methylmercury concentrations first increased to their maximum level at a depth of 10-25 cm, and then decreased; this was similar to the vertical distribution characteristics of methylmercury/total mercury ratios. The mangrove ecosystem was considered as a source of methylmercury for adjacent areas, due to the higher average methylmercury concentration in the mangrove sediment than other sediments nearby. Statistically significant logarithmic correlations, conic correlations, and negative correlations were observed for methylmercury and sulfide concentration, sediment organic matter, and sediment pH, respectively.

Dual Distillation Discriminator Networks for Domain Adaptive Few-Shot Learning.

Domain Adaptive Few-Shot Learning (DA-FSL) aims at accomplishing few-shot classification tasks on a novel domain with the aid of a large number of source-style samples and several target-style samples. It is essential for DA-FSL to transfer task knowledge from the source domain to the target domain and overcome the asymmetry amount of labeled data in both domains. To this end, we propose Dual Distillation Discriminator Networks (D3Net) from the perspective of the lack of labeled target domain style samples in DA-FSL. Specifically, we employ the idea of distillation discrimination to avoid the over-fitting caused by the unequal number of samples in the target and source domains, which trains the student discriminator by the soft labels from the teacher discriminator. Meanwhile, we design the task propagation stage and the mixed domain stage respectively from the level of feature space and instances to generate more target-style samples, which apply the task distributions and the sample diversity of the source domain to enhance the target domain. Our D3Net realizes the distribution alignment between the source domain and the target domain and constraints the FSL task distribution by prototype distributions on the mixed domain. Extensive experiments on three DA-FSL benchmark datasets, i.e., mini-ImageNet, tiered-ImageNet, and DomainNet, demonstrate that our D3Net achieves competitive performance.

Impact of a family treatment court on child permanency and safety.

BACKGROUND: Family Treatment Courts have been linked to promising effects on key child welfare outcomes, though few rigorous program evaluations have been conducted. OBJECTIVE: This study employs a robust quasi-experimental design to evaluate effects associated with Family Treatment Court participation on child permanency and safety. PARTICIPANTS AND SETTING: The sample included 648 eligible adults who were referred to a Family Treatment Court in a Midwest metropolitan area, including 266 program participants and 382 non-participants. METHODS: Propensity score weighting was applied to match program and comparison groups on demographic and case characteristics. Child welfare records yielded safety and permanency outcomes. Participants and non-participants were compared following an intent-to-treat principle, with logistic regressions used to test the odds of reunification and maltreatment recurrence, and Kaplan-Meier analyses used to explore time to reunification and permanency. Moderation tests were performed to analyze differences in program impact across racial/ethnic groups and substance use types. RESULTS: Compared to non-participants, program participants were 81 % more likely to reunify. Group differences in time to reunification and permanency were mixed, and there was no evidence of program impact on maltreatment recurrence. Substance use type and race/ethnicity did not moderate associations between program participation and study outcomes. CONCLUSIONS: Mounting evidence suggests that Family Treatment Courts are more effective than usual services in promoting family reunification, though it is unclear if these interventions hasten reunification or increase safety post-reunification. Rigorous evaluations are needed to explore moderating and mediating processes and identify implementation drivers and local conditions that contribute to heterogeneous results.