A Self-Healing Conductive Elastomer Based on a Polymerizable Deep Eutectic Solvent.

Conductive elastomers are extensively used in electronics; however, they are prone to mechanical damage, have shortened service life, and cause environmental pollution and resource waste under the influence of external factors. Therefore, conductive elastomers with rapid self-healing properties are crucial for solving these problems. To that end, a conductive elastomer based on a polymerizable deep eutectic solvent as the matrix is developed in this study. The contents of certain small molecules and conductive particles are adjusted to yield a conductive elastomer with excellent comprehensive performance. The elastomer exhibited noteworthy fracture strength (15.7 MPa), ultrahigh fracture elongation (2400%), excellent light transmittance (95.6%), and remarkable self-healing characteristics, with complete electrical healing achieved within 0.6 s, ≈63% strain, and ≈64% stress recovered within 1 min, and healing efficiency close to 99% realized within 24 h. By leveraging these properties, the elastomer is used to construct a sensor that exhibited a gauge factor of ≈0.574 in the strain range 0-2400% and excellent stability. Moreover, the CCK-8 toxicity test and fluorescence staining experiment have demonstrated that conductive elastomers have excellent cell compatibility and also have excellent potential in the field of biomedicine. In particular, the sensor is effectively applied in human motion detection, health monitoring.

Role of diet in the risks of esophageal adenocarcinoma and squamous cell carcinoma: an updated umbrella review.

PURPOSE: This updated umbrella review aimed to evaluate the evidence regarding the associations between dietary factors and the risks of esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched to identify relevant studies. The quality of the included meta-analyses was evaluated using A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2). For each association, the number of cases, random effects pooled effect size, 95% confidence intervals (CIs), heterogeneity, 95% prediction interval (PrI), small-study effect, and excess significance bias were recalculated to determine the evidence level. RESULTS: We identified 33 meta-analyses describing 58 dietary factors associated with ESCC and 29 meta-analyses describing 38 dietary factors associated with EAC. There was convincing evidence regarding the association of 2 dietary factors (areca nut and high alcohol) with the risk of ESCC. There was highly suggestive evidence regarding the association of only 1 dietary factor (healthy pattern) with the risk of ESCC. There was suggestive evidence regarding the association of 11 dietary factors with the risk of ESCC, including fruit, citrus fruit, vegetables, pickled vegetables, maté tea, moderate alcohol, hot beverages and foods, hot tea, salt, folate, and vitamin B6. There was convincing evidence regarding the association of one dietary factor (vitamin B6) with the risk of EAC. There was suggestive evidence regarding the association of 4 dietary factors with the risk of EAC, including processed meat, dietary fibre, carbohydrate, and vitamin B12. The convincing evidence regarding the associations between dietary factors and the risks of ESCC and EAC remained robust in sensitivity analyses. CONCLUSIONS: This umbrella review highlighted convincing evidence regarding the associations of areca nut and high alcohol with a higher risk of ESCC. Additionally, an association between vitamin B6 and a decreased risk of EAC was observed. Further research is needed to examine the dietary factors with weak evidence regarding their associations with ESCC and EAC.

Photoheterotroph improved the growth and nutrient levels of Chlorella vulgaris and the related molecular mechanism.

Microalgae are rich in fatty acids, proteins, and other nutrients, which have gained the general attention of researchers all over the world. For the development of Chlorella vulgaris in food and feed industry, this study was conducted to investigate the differences in C. vulgaris' growth and nutritional components under different culture conditions (autotrophic, heterotrophic, photoheterotrophic) and the internal factors through cell counting in combination with transcriptome and nutrient analyses. The results showed that, under the photoheterotrophic condition, Chlorella's growth and the contents of lipid and protein were significantly higher than that under the heterotrophic condition, and the moisture content was lower than that under the heterotrophic condition. The saturated fatty acid content under the photoheterotrophic condition was the lowest, while the polyunsaturated fatty acid content was significantly higher than those under the other two conditions. There were 46,583 differentially expressed genes (DEGs), including 33,039 up-regulated DEGs (70.93%) and 13,544 down-regulated DEGs (29.07%), under the photoheterotrophic condition in comparison with the autotrophic condition. The fold change between the two conditions of samples of up-regulated genes was higher than that of the down-regulated genes. The KEGG enrichment showed that the up-regulated DEGs in the photoheterotrophic condition were significantly enriched in 5 pathways, including protein processing in endoplasmic reticulum pathway, photosynthesis pathway, photosynthesis-antenna protein pathway, endocytosis pathway, and phosphonate and phosphinate metabolism pathway. DEGs related to fatty acid metabolic pathways were significantly enriched in the fatty acid biosynthesis pathway and the biosynthesis of unsaturated fatty acid pathway. The qPCR analysis showed that the expression pattern of the selected genes was consistent with that of transcriptome analysis. The results of this study lay a theoretical foundation for the large-scale production of Chlorella and its application in food, feed, and biodiesel. KEY POINTS: • Nutrient levels under photoheterotrophic condition were higher than other conditions. • Six important pathways were discovered that affect changes in nutritional composition. • Explored genes encode important enzymes in the differential metabolic pathways.

Glucocorticoid use and varying doses on the long-term outcomes of offspring born to patients with systemic lupus erythematosus.

This study aims to assess the impact of non-fluorinated glucocorticoid use and varying doses on the long-term physical, neurological, and social-emotional development outcomes of offspring born to patients with systemic lupus erythematosus (SLE). The goal is to provide guidance on the appropriate dosage of glucocorticoids during pregnancy in SLE patients. We conducted a follow-up study on the offspring of SLE patients who had pregnancies and were admitted to our obstetrics department between January 1, 2016, and September 30, 2021. Patients who received immunosuppressants and dexamethasone were excluded from the study. The SLE patients were categorized into three groups based on their glucocorticoid use during pregnancy: hormone-free group, ≤ 10 mg/day group, and > 10 mg/day group (equivalent to prednisone). Most patients in the three groups were used hydroxychloroquine during pregnancy. We assessed the physical development status, including weight, height (length), and other relevant factors in three groups. Additionally, we utilized the Age and Stages Questionnaires, Third Edition (ASQ-3) to evaluate the development of communication, gross motor, fine motor, problem-solving, and personal-social. The social-emotional development status was assessed using the Age and Stages Questionnaires: Social-Emotional (ASQ: SE). We standardized the weight, height (length), body mass index, and ASQ-3 domain scores of children of different ages and genders into Z-scores for comparison. The results of this study demonstrated no statistically significant differences in the long-term physical development, neurological development, and social-emotional development outcomes of the offspring of SLE patients in three groups. However, while not reaching statistical significance, it was found that the offspring of the > 10 mg/day group had lower height (length) Z-scores and communication Z-scores compared to the other groups.   Conclusion: The use of non-fluorinated glucocorticoids during pregnancy and varying doses did not have a significant impact on the long-term physical, neurological, and social-emotional development outcomes of offspring born to SLE patients. However, the offspring of SLE patients treated with glucocorticoids > 10 mg/day during pregnancy may be necessary to strengthen the monitoring of height (length) and communication skills in the long term. What is Known: • Fetal exposure to glucocorticoids can have implications for the development of multiple systems and may persist after birth, potentially increasing the risk of neurological abnormalities and other diseases. • There is limited research on the long-term development of offspring born to SLE patients, especially the patients treated with glucocorticoids. What is New: • The use of non-fluorinated glucocorticoids during pregnancy and varying doses did not have a significant impact on the long-term outcomes of offspring born to SLE patients. • The offspring of SLE patients treated with glucocorticoids >10 mg/day during pregnancy may be necessary to strengthen the monitoring of height (length) and communication skills in the long term.

[Association between self-control and co-occurrence of depressive symptoms and overweight or obesity during adolescence and early adulthood: A ten-year prospective cohort study based on national surveys].

OBJECTIVE: To explore the association between self-control and the co-occurrence of depressive symptoms and overweight or obesity from adolescence to early adulthood in the Chinese population, and to provide a scientific basis for personalized interventions targeting individuals with different risks in the future. METHODS: From a prospective cohort study that lasted for 10 years: The China family panel studies (CFPS), a total of 608 children and adolescents meeting the following inclusion and exclusion criteria were included as study subjects: (1) Aged 10 to 19 years, at normal weight according to Chinese standards, and without depressive symptom in 2010; (2) Had self-control scores, and with at least two measurements of depressive symptoms and body mass index (BMI) between 2010 and 2020; (3) The only one or the youngest child and adolescent from each family. The co-occurrence of depressive symptoms and overweight or obesity was defined in three ways: Both of the average level of standardized scores of depressive symptoms and BMI Z-scores across multiple measurements over time were at a high level, or both of the trajectories of depressive symptoms and BMI over time based on the latent classification trajectory model (LCTM) belonging to the "risk-type", or individuals had depressive symptoms and overweight/obesity at the last follow-up survey. The multinomial Logistic regression model was used to examine the association between standardized scores of self-control and the co-occurrence of depressive symptoms and overweight or obesity. RESULTS: The score of self-control was associated with the co-occurrence of depressive symptoms and overweight or obesity when using healthy individuals as the reference group after adjusting for age (years), gender (male/female), area (urban/rural), weekly physical activity duration (high/low), parental education level (college or above/high school or below), parental weight status (overweight or obese or not), and parental depressive symptoms (with depressive symptoms or not), regardless of the definition of the risk population. Specifically, the risk of co-occurrence of depressive symptoms and overweight or obesity was reduced by 33% (95%CI: 14% to 48%, based on the average level across multiple measurements over time) to 78% (95%CI: 6% to 95%, based on the joint trajectories of depressive symptoms and BMI over time) per 1-standard deviation (1-SD) increase in self-control score. In addition, the risk of depressive-symptom-dominant and overweight-or-obesity-dominant was reduced by 25% (95%CI: 4% to 42%, only based on the average level across multiple measurements over time) and 21% (95%CI: 1% to 37%, only based on the joint trajectories of depressive symptoms and BMI over time) per 1-SD increase in self-control score, respectively. The results from sensitivity analysis that defined individuals' weight status according to World Health Organization (WHO) standards were consistent with our main findings. CONCLUSION: Individuals with higher self-control scores from adolescence to early adulthood have a lower risk of co-occurrence of depressive symptoms and overweight or obesity, suggesting that personalized interventions for co-occurrence of depressive symptoms and overweight or obesity can be carried out based on self-control scores in the future.

All-in-One: Plasmonic Janus Heterostructures for Efficient Cooperative Photoredox Catalysis.

Janus heterostructures consisting of multiple jointed components with distinct properties have gained growing interest in the photoredox catalytic field. Herein, we have developed a facile low-temperature method to gain anisotropic one-dimensional Au-tipped CdS (Au-CdS) nanorods (NRs), followed by assembling Ru molecular co-catalyst (RuN5) onto the surface of the NRs. The CdS NRs decorated with plasmonic Au nanoparticles (NPs) and RuN5 complex harness the virtues of metal-semiconductor and inorganic-organic interface, giving directional charge transfer channels, spatially separated reaction sites, and enhanced local electric field distribution. As a result, the Au-CdS-RuN5 can act as an efficient dual-function photocatalyst for simultaneous H2 evolution and valorization of biomass-derived alcohols. Benefiting from the interfacial charge decoupling and selective chemical bond activation, the optimal all-in-one Au-CdS-RuN5 heterostructure shows greatly enhanced photoactivity and selectivity as compared to bare CdS NRs, along with a remarkable apparent quantum yield of 40.2% at 400 nm. The structural evolution and working mechanism of the heterostructures are systematically analyzed based on experimental and computational results.

Plant-based dietary patterns and risk of esophageal cancer: A prospective cohort study spanning 17 years.

Objective: Plant-based diets have multiple health benefits for cancers; however, little is known about the association between plant-based dietary patterns and esophageal cancer (EC).This study presents an investigation of the prospective associations among three predefined indices of plant-based dietary patterns and the risk of EC. Methods: We performed endoscopic screening for 15,709 participants aged 40-69 years from two high-risk areas of China from January 2005 to December 2009 and followed the cohort until December 31, 2022. The overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI), were calculated using survey responses to assess dietary patterns. We applied Cox proportional hazard regression to estimate the multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) of EC across 3 plant-based diet indices and further stratified the analysis by subgroups. Results: The final study sample included 15,184 participants in the cohort. During a follow-up of 219,365 person-years, 176 patients with EC were identified. When the highest quartile was compared with the lowest quartile, the pooled multivariable-adjusted HR of EC was 0.50 (95% CI, 0.32-0.77) for hPDI. In addition, the HR per 10-point increase in the hPDI score was 0.42 (95% CI, 0.27-0.66) for ECs. Conversely, uPDI was positively associated with the risk of EC, and the HR was 1.80 (95% CI, 1.16-2.82). The HR per 10-point increase in the uPDI score was 1.90 (95% CI, 1.26-2.88) for ECs. The associations between these scores and the risk of EC were consistent in most subgroups. These results remained robust in sensitivity analyses. Conclusions: A healthy plant-based dietary pattern was associated with a reduced risk of EC. Emphasizing the healthiness and quality of plant-based diets may be important for preventing the development of EC.

[Research progress on the manifestations and prognosis of neonatal lupus erythematosus in various systems]. / æ–°ç”Ÿå„¿çº¢æ–‘ç‹¼ç–®å„ç³»ç»Ÿè¡¨çŽ°åŠé¢„åŽç ”ç©¶è¿›å±•.

Neonatal lupus erythematosus (NLE) is caused by the transmission of maternal anti-Ro/SSA antibodies, anti-La/SSB antibodies, and other autoantibodies to the fetus through the placenta. Usually, with the disappearance of autoantibodies in the children's body, abnormal changes in the mucocutaneous, blood system, and digestive system can spontaneously subside, but the damage to various systems caused by autoantibodies may persist for a long time. This article provides a comprehensive review of the manifestations and prognosis of NLE in various systems, including mucocutaneous, blood system, circulatory system, nervous system, digestive system, respiratory system, aiming to provide reference for clinical work.

[Factors influencing the occurrence of small for gestational age at different degrees]. / ä¸åŒç¨‹åº¦å°äºŽèƒŽé¾„å„¿å‘ç”Ÿçš„å½±å“å› ç´ åˆ†æž.

OBJECTIVES: To investigate the factors influencing the occurrence of small for gestational age (SGA) at different degrees and provide a basis for early identification of severe SGA cases. METHODS: Neonatal and maternal prenatal information were retrospectively collected from January 2018 to December 2022 at Peking University People's Hospital. The neonates were divided into three groups: severe SGA group (birth weight below the 3rd percentile for gestational age and sex), mild SGA group (birth weight ≥3rd percentile and <10th percentile), and non-SGA group (birth weight ≥10th percentile). An ordered multinomial logistic regression model was used to analyze the factors influencing the occurrence of SGA at different degrees. RESULTS: A total of 14 821 neonates were included, including 258 cases (1.74%) in the severe SGA group, 902 cases (6.09%) in the mild SGA group, and 13 661 cases (92.17%) in the non-SGA group. The proportions of preterm births and stillbirths were higher in the severe SGA group compared to the mild SGA and non-SGA groups (P<0.0125). The proportion of neonatal asphyxia was higher in both the severe SGA and mild SGA groups compared to the non-SGA group (P<0.0125). Ordered multinomial logistic regression analysis showed that maternal pre-pregnancy underweight (OR=1.838), maternal pre-pregnancy obesity (OR=3.024), in vitro fertilization-embryo transfer (OR=2.649), preeclampsia (OR=1.743), connective tissue disease during pregnancy (OR=1.795), nuchal cord (OR=1.213), oligohydramnios (OR=1.848), and intrauterine growth restriction (OR=27.691) were all associated with a higher risk of severe SGA (P<0.05). Maternal parity as a multipara (OR=0.457) was associated with a lower likelihood of severe SGA (P<0.05). CONCLUSIONS: Maternal pre-pregnancy underweight, maternal pre-pregnancy obesity, in vitro fertilization-embryo transfer, preeclampsia, connective tissue disease during pregnancy, oligohydramnios, nuchal cord, and intrauterine growth restriction are closely related to the occurrence of more severe SGA. Maternal parity as a multipara acts as a protective factor against the occurrence of severe SGA.

The Plasma Concentration of Ticagrelor and Aspirin as a Predictor of Bleeding Complications in Chinese Acute Coronary Syndrome Patients With Dual Antiplatelet Therapy: A Prospective Observational Study.

PURPOSE: This study evaluated the association among the plasma concentration of ticagrelor, ARC124910XX, aspirin, and salicylic acid with the risk of recent bleeding in patients with the acute coronary syndrome. To this end, we developed an accurate model to predict bleeding. METHODS: A total of 84 patients included in this study cohort between May 2021 and November 2021. The risk factors were identified by univariate and multivariate analyses, and statistically significant risk factors identified in the multivariate analysis were included in the nomogram. We used the calibration curve and the receiver operating characteristic curve to verify the accuracy of the prediction model. RESULTS: Multivariable logistic analysis showed that ticagrelor concentration (odds ratio [OR]: 2.47, 95% confidence interval [CI], 1.51-4.75, P = 0.002), ST-segment elevation acute myocardial infarction (OR: 32.2, 95% CI, 2.37-780, P = 0.016), and lipid-lowering drugs (OR: 11.52, 95% CI, 1.91-110, P = 0.015) were positively correlated with bleeding. However, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (OR: 0.04, 95% CI, 0.004-0.213, P < 0.001) was negatively correlated with bleeding. The receiver operating characteristic curve analysis showed that ticagrelor concentration and these factors together predict the occurrence of bleeding (area under receiver operating characteristic curve = 0.945, 95% CI, 0.896-0.994) and that ticagrelor concentration >694.90 ng/mL is the threshold of bleeding concentration (area under receiver operating characteristic curve = 0.696, 95% CI, 0.558-0.834). CONCLUSION: In patients with acute coronary syndrome treated with dual antiplatelet therapy, ticagrelor concentration >694.90 ng/mL was an independent risk factor for bleeding (OR: 2.47, 95% CI, 1.51-4.75, P = 0.002), but ARC124910XX and salicylic acid concentration did not affect bleeding risk ( P > 0.05).

Assessing the role of intrinsic disorder in RNA-binding protein function: hnRNP K as a case study.

RNA-binding proteins (RBPs) typically bind to RNA in a sequence-specific manner, resulting in post-transcriptional gene regulation. While the various classes of RNA-binding domains are largely structured, flexible linkers are frequently observed between them. Emerging evidence suggests that these unstructured regions may help spatially position the RNA-binding domains allowing for RNA binding and/or may contribute directly to RNA association via certain sequence motifs contained within them. The importance of these unstructured regions is widely appreciated; however, understanding their contribution to RNA binding, protein stability, and function has been difficult to ascertain. Thus, it is crucial to have a set of rapid and economical assays that do not require specialized instrumentation to study their impact on RBP function. Herein, we discuss the use of plate-based and cell-based thermal shift assays to study the impact of the intrinsically disordered region on the function of a highly conserved RBP, hnRNP K.

Mechanistic Understanding and Reactivity Analyses for the Photochemistry of Disubstituted Tetrazoles.

The photolysis of tetrazoles has undergone extensive research. However, there are still some problems to be solved in terms of mechanistic understanding and reactivity analyses, which leaves room for theoretical calculations. Herein, multiconfiguration perturbation theory at the CASPT2//CASSCF level was employed to account for electron correction effects involved in the photolysis of four disubstituted tetrazoles. Based on calculations of vertical excitation properties and evaluations of intersystem crossing (ISC) efficiencies in the Frank-Condon region, the combination of space and electronic effects is found in maximum-absorption excitation. Two types of ISC (1ππ* → 3nπ*, 1ππ* → 3ππ*) are determined in disubstituted tetrazoles, and the obtained rates follow the El-Sayed rule. Through mapping three representative types of minimum energy profiles for the photolysis of 1,5-, and 2,5-disubstituted tetrazoles, a conclusion can be drawn that the photolysis of tetrazoles exhibits reactivity characteristic of bond-breaking selectivity. Kinetic evaluations show that the photogeneration of singlet imidoylnitrene operates predominately over that in the triplet state, which can be confirmed by a double-well model in the triplet potential energy surface of 1,5-disubstituted tetrazole. Similar mechanistic explorations and reactivity analyses were also applied to the photolysis of 2,5-disubstituted tetrazole to unveil fragmentation patterns of nitrile imine generation. All computational efforts allow us to better understand the photoreactions of disubstituted tetrazoles and to provide useful strategies for regulating their unique reactivity.

Quality marker prediction in Trillium tschonoskii based on UHPLC-MS chemical characterisation and network pharmacology.

INTRODUCTION: As a folk herbal medicine, Trillium tschonoskii has been used for thousands of years. However, due to the complexity of the chemical constituents of this herb, few investigations have acquired a comprehensive understanding of its quality markers. OBJECTIVE: This study was conducted to characterise the chemical composition of T. tschonoskii and identify its potential quality markers. MATERIAL AND METHODS: A systematic analytical method based on ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS) was used to characterise the constituents of T. tschonoskii. Multivariate statistical analysis was performed to investigate the chemical differences between different tissues, as well as the relationship between chemical compositions and habitats. The potential quality markers were predicted via network pharmacology and molecular docking, then confirmed by cellular assays. RESULTS: A total of 77 compounds were co-isolated and identified, and among them, 26 were discovered from the genus Trillium for the first time. Ten batches of roots/rhizomes were explicitly clustered into five groups according to the climate types of the habitats, and the clusters of the fruits and roots/rhizomes from the same plants were independent due to the significant difference in chemical composition. Diosgenin had a good docking affinity with the relevant targets within the IL-17 pathway and cytokine pathway and could significantly inhibit TNF-α expression in hypoxic brain microvascular endothelial cells (BMECs). CONCLUSION: This is the first study to establish the chemical composition profile of T. tschonoskii by UHPLC-MS systematically, and diosgenin was confirmed to be a potential quality marker of T. tschonoskii for the treatment of headaches.

Research on Rotating Machinery Fault Diagnosis Based on an Improved Eulerian Video Motion Magnification.

Rotating machinery condition monitoring and fault diagnosis are important bases for maintenance decisions, as the vibrations generated during operation are usually imperceptible to the naked eye. Eulerian video motion magnification (EVMM) can reveal subtle changes and has been widely used in various fields such as medicine, structural analysis, and fault diagnosis, etc. However, the method has a bound relationship among three parameters: spatial wavelength, amplification factor, and displacement function, so it is necessary to adjust the parameters manually in practical applications. In this paper, on the basis of the original method, an automatic solution of spatial cutoff wavelength based on brightness is proposed. First, an input video is decomposed into image sequences, their RGB color spaces are transformed into HSV color spaces, and the Value channel image representing brightness is selected to automatically calculate the spatial cutoff frequency, and then the spatial cutoff wavelength is determined, and the motion magnification video in the specified frequency band is obtained by substituting it into the original method. Then, a publicly available video is taken as an example for simulation analysis. By comparing the time-brightness curves of the three videos (original video, motion magnification video obtained by the original method and the improved method), it is apparent that the proposed method exhibits the most significant brightness variation. Finally, taking an overhung rotor-bearing test device as the object, five conditions are set, respectively: normal, rotor unbalance, loosened anchor bolt of the bearing seat, compound fault, rotor misalignment. The proposed method is adopted to magnify the motion of the characteristic frequency bands including 1X frequency and 2X frequency. The results show that no obvious displacement is found in normal working conditions, and that the rotor unbalance fault has an overall axial shaking, the bearing seat at the loose place has an obvious vertical displacement, while the compound fault combines the both fault characteristics, and the rotor misalignment fault has an obvious axial displacement of the free-end bearing seat. The method proposed in this paper can automatically obtain the space cutoff wavelength, which solves the problem of defects arising from manually adjusting the parameters in the original method, and provides a new method for rotating machinery fault diagnosis and other fields of application.

[Research progress on long-term developmental outcomes of offspring of pregnant women with systemic lupus erythematosus]. / å¦Šå¨ åˆå¹¶ç³»ç»Ÿæ€§çº¢æ–‘ç‹¼ç–®æ‚£è€ å­ä»£è¿œæœŸå‘è‚²ç»“å±€çš„ç ”ç©¶è¿›å±•.

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease that affects multiple organs and systems. It is more common in women of childbearing age. Compared with the general population, pregnant women with SLE are at a significantly increased risk of adverse perinatal outcomes such as preterm birth and intrauterine growth restriction. In addition, the offspring of SLE patients may also be adversely affected by in utero exposure to maternal autoantibodies, cytokines, and drugs. This article summarizes the long-term developmental outcomes of offspring of pregnant women with SLE in terms of the blood system, circulatory system, nervous system, and immune system.

Low-dose telomerase is required for the expansion and migration of placental mesenchymal stem cells.

Telomerase is activated in pluripotent stem cells and the majority of tumors and is postulated to be necessary for the acquisition of self-renewal and long-term proliferation. Placental mesenchymal stem cells (PMSCs) are very promising in regenerative medicine owing to their great capacity for self-renewal and differentiation potential. Although telomerase activity in the placenta is naturally low, it remains unclear whether telomerase activity is required for the properties of PMSCs. We herein isolated and identified a PMSC line carrying compound heterozygote variations in hTERT (DC-PMSCs) that lost telomerase activity, showed a typical surface phenotype of MSCs, and was able to differentiate into multiple cell lineages. DC-PMSCs showed accelerated telomere erosion, advanced senescence, and diminished migratory and invasive capabilities. RNA-seq identified 361 differentially expressed genes between DC-PMSCs and control groups, most of which were enriched in extracellular matrix, ECM, and related pathways. Knockdown of telomerase subunit genes in PMSCs confirmed the phenotype and attenuated the expression of extracellular matrix components and matrix metalloproteases. Our results suggest that low telomerase activity is not essential for the properties of MSCs, but that it is required for community maintenance and for the migration of PMSCs.

AXL/MERTK inhibitor ONO-7475 potently synergizes with venetoclax and overcomes venetoclax resistance to kill FLT3-ITD acute myeloid leukemia.

FMS-like Tyrosine Kinase 3 (FLT3) mutation is associated with poor survival in acute myeloid leukemia (AML). The specific Anexelekto/MER Tyrosine Kinase (AXL) inhibitor, ONO-7475, kills FLT3-mutant AML cells with targets including Extracellular- signal Regulated Kinase (ERK) and Myeloid Cell Leukemia 1 (MCL1). ERK and MCL1 are known resistance factors for Venetoclax (ABT-199), a popular drug for AML therapy, prompting the investigation of the efficacy of ONO-7475 in combination with ABT-199 in vitro and in vivo. ONO-7475 synergizes with ABT-199 to potently kill FLT3-mutant acute myeloid leukemia cell lines and primary cells. ONO-7475 is effective against ABT-199-resistant cells including cells that overexpress MCL1. Proteomic analyses revealed that ABT-199-resistant cells expressed elevated levels of pro-growth and anti-apoptotic proteins compared to parental cells, and that ONO-7475 reduced the expression of these proteins in both the parental and ABT-199-resistant cells. ONO-7475 treatment significantly extended survival as a single in vivo agent using acute myeloid leukemia cell lines and PDX models. Compared to ONO-7474 monotherapy, the combination of ONO-7475/ABT-199 was even more potent in reducing leukemic burden and prolonging the survival of mice in both model systems. These results suggest that the ONO-7475/ABT-199 combination may be effective for AML therapy.

Correlation between apelin and VEGF levels in retinopathy of prematurity: a matched case-control study.

BACKGROUND: Although several clinical studies have analysed the relationship between the levels of vascular endothelial growth factor (VEGF) and apelin-13 in venous blood and retinopathy of prematurity (ROP), no definitive conclusions have been reached. This study aimed to investigate the relationship between apelin-13 levels and VEGF levels and ROP. METHODS: Differences in plasma apelin-13 and VEGF levels were analysed in two groups of infants born with birth weight < 1500 g and gestational age < 32 weeks at Peking University People' s Hospital. One group comprised infants diagnosed with ROP and the other group was a control group comprising infants without ROP. RESULTS: Apelin-13 levels were significantly lower in the ROP group than in the control group, while VEGF levels showed the opposite result (both P < 0.001). Infants with severe ROP had lower apelin-13 levels and higher VEGF levels than with mild ROP (both P < 0.05).The receiver operating characteristic curve for apelin-13 level as the indicator of ROP showed that a cut-off value of 119.6 pg/mL yielded a sensitivity of 84.8% and a specificity of 63.6%, while for VEGF level, the cut-off value of 84.3 pg/mL exhibited a sensitivity of 84.8% and a specificity of 66.7%. CONCLUSIONS: Plasma apelin-13 and VEGF levels at 4-6 weeks of age may play a role in assisting the diagnosis of ROP.

Plasma Level of Apelin as a Promising Factor for Retinopathy of Prematurity.

INTRODUCTION: To investigate the relevance of plasma levels of apelin and other risk factors in infants with retinopathy of prematurity (ROP). METHODS: This was a single-center cross-sectional study. Fifty preterm infants with ROP and 50 preterm infants without ROP were enrolled. The analysis included evaluation of gestational age, birth weight, and measurement of plasma concentrations of apelin, vascular endothelial growth factor (VEGF), erythropoietin (EPO), and insulin-like growth factor (IGF-1) using enzyme-linked immunosorbent assay. RESULTS: The mean BW and GA of babies with ROP were considerably lower than those without ROP (P < 0.001, P = 0.003, respectively). Plasma levels of VEGF, EPO, and IGF-1 were all lower in babies with ROP (all P < 0.001), while plasma apelin levels were greater (P < 0.001). We compared the sensitivity and selected the best cut-offs while keeping the specificity constant (80.0%). Among all the criteria, plasma apelin levels had the best sensitivity (72%), with a 21.08 pg/mL cut-off. Multivariable logistic regression analyses showed that the plasma level of apelin was the only parameter associated with ROP (P = 0.02, OR = 16, CI = 95%: 1.54-166.53). The AUC of the multivariable regression model that comprised GA, BW alone was 0.67, while the model that included apelin was 0.90. CONCLUSIONS: Plasma apelin level demonstrated good sensitivity and specificity with regard to the association of ROP, the inclusion of apelin may be a promising factor to include in screening criteria.

Does self-reported symptom questionnaire play a role in nonadherence to colonoscopy for risk-increased population in the Tianjin colorectal cancer screening programme?

BACKGROUND: A colorectal cancer screening programme (CCSP) was implemented from 2012 to 2017 in Tianjin, China. Residents with a positive faecal immunochemical test (FIT) or positive self-reported symptom questionnaire (SRSQ) were recommended to undergo colonoscopy. The objective was to investigate the potential factors associated with nonadherence to colonoscopy among a risk-increased population. METHODS: Data were obtained from the CCSP database, and 199,522 residents with positive FIT or positive SRSQ during two screening rounds (2012-2017) were included in the analysis. Logistic regression analysis was performed to assess the association between nonadherence to colonoscopy and potential predictors. RESULTS: A total of 152,870 (76.6%) individuals did not undergo colonoscopy after positive FIT or positive SRSQ. Residents with positive SRSQ but without positive FIT were more likely not to undergo colonoscopy (negative FIT: OR, 2.35; 95% CI, 2.29-2.41, no FIT: OR, 1.27; 95% CI, 1.24-1.31). Patients without a cancer history were less likely to undergo colonoscopy even if they received risk-increased reports based on the SRSQ. CONCLUSION: In the CCSP, seventy-seven percent of the risk-increased population did not undergo colonoscopy. FIT should be recommended since positive FIT results are related to improved adherence to colonoscopy. Residents with negative FIT but positive SRSQ should be informed of the potential cancer risk to ensure adherence to colonoscopy.