Medium-chain chlorinated paraffins (MCCPs) induce renal cell aging and ferroptosis.

PURPOSE: Medium-chained chlorinated paraffins (MCCPs) are a class of chlorinated derivatives of straight-chain n-alkanes with complex compositions, which are widely used in industry. The chlorinated paraffins (CPs) are divided into short chain chlorinated paraffins (SCCPs), medium chain chlorinated paraffins (MCCPs) and long chain chlorinated paraffins (LCCPs). SCCPs have been banned due to their severe bioaccumulation and biotoxicity. Therefore, MCCPs are used as a substitute for SCCPs. However, the toxicological data of MCCPs are still very limited. For this, we systematically investigated the toxicological impact of MCCPs on a renal cell model in the current study. Our work provides basic research data for analyzing the toxicological effects of MCCPs, suggesting that MCCPs should be restricted in their usage. METHOD: A series of biochemical experiments was performed, including Western blot, indirect immunofluorescence assay, and ELISA was performed to analyze the toxicological effects of MCCPs. RESULTS: Two renal cell lines were used as a model for assessing the toxicological effects of MCCPs. Cell proliferation assays showed that MCCPs could inhibit the proliferation of kidney cells in a dose-dependent manner. Further studies showed that MCCPs induced ferroptosis in kidney cells by evaluating a series of ferroptosis marker molecules. Additionally, MCCPs induced inflammatory response and premature senescence in HEK293 and NRK-52E cells. Molecular mechanism experiments showed that ferroptosis induced by MCCPs emerged as a significant contributor to premature aging of kidney cells. CONCLUSION: The current study provides basic research data to analyze the toxicological effects of MCCPs and their toxicity mechanisms. It also provides a theoretical basis for the assessment of the potential ecological risk of MCCPs, as well as basic experimental data for the rational and standardized use of MCCPs.

The association of hypophysitis with immune checkpoint inhibitors use: Gaining insight through the FDA pharmacovigilance database.

The use of immune checkpoint inhibitor (ICI) marked a revolutionary change in cancer treatment and opened new avenues for cancer therapy, but ICI can also trigger immune-related adverse events (irAEs). Here, we investigated the publicly available US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to gain insight into the possible association between immune checkpoint inhibitors and hypophysitis. Data on adverse events (AEs) due to hypophysitisfor nivolumab, pembrolizumab, ipilimumab, and atezolizumab were collected from the US FDA Adverse Event Reporting System from the first quarter of 2004 to the second quarter of 2021, and the signals for hypophysitis associated with the four drugs were examined using the reporting odds ratio (ROR) method. The number of reported hypophysitis events ≥ 3 and the lower limit of the 95% confidence interval (CI) of the ROR > 1 were considered positive for hypophysitis signals. A total of 1252 AE reports of hypophysitis associated with nivolumab, pembrolizumab, ipilimumab, and atezolizumab were collected, including 419, 149, 643, and 41 cases, respectively. The RORs of hypophysitis were 289.58 (95% CI 258.49-324.40), 171.74 (95% CI 144.91-203.54), 2248.57 (95% CI 2025.31-2496.45), and 97.29 (95% CI 71.28-132.79), respectively. All four drugs were statistically correlated with the target AE, with the correlation being, in descending order, ipilimumab, nivolumab, pembrolizumab, and atezolizumab. Nivolumab, pembrolizumab, ipilimumab, and atezolizumab have all been associated with hypophysitis, which can negatively impact quality of life, and early recognition and management of immune checkpoint inhibitor-related hypophysitis is critical.

Self-Powered Colorful Dynamic Electrowetting Display Systems Based on Triboelectricity.

Electrowetting displays (EWDs) based on microfluidics are highly sought after in the fields of electronic devices, smart homes, and information communication. However, the power supply of the EWD systems for visually engaging multi-color displays remains a big challenge. Herein, self-powered colorful dynamic display systems are developed by integrating the triboelectric nanogenerator (TENG) with the EWD device. The TENG is designed with a nanotube-patterned surface and can generate open-circuit voltages ranging from 30 to 295 V by controlling the contact area. The wetting property of the micro-droplet exhibits a response to the applied voltage, enabling the triboelectricity-triggered electrowetting-on-dielectric. Driven by the voltage of 160 V, the monochromatic EWD exhibits bright color switching from magenta to transparent with a pixel aperture ratio of 78%, and the recovery process can be rapidly completed. Furthermore, the self-powered colorful dynamic EWD system can be achieved. By selectively applying the voltage to the pixels in the three monochromatic layers that constitute the colorful EWD, the wetting properties of the fluids can be controlled, allowing for colorful dynamic display. This work contributes to the advancement of color display technology for portable and wearable electronic ink displays, indoor and outdoor sports equipment, and information communication.

Clinical Manifestations, Genetic Variants and Therapeutic Evaluation in Sporadic Chinese Patients with Idiopathic Hypogonadotropic Hypogonadism.

Purpose: Genetic factors account for a large proportion of idiopathic hypogonadotropic hypogonadism (IHH) etiologies, although not necessarily a complete genetic basis. This study aimed to characterize the clinical presentations, genetic variants, and therapeutic outcomes of patients with sporadic IHH, which may be helpful for genetic counseling and treatment decisions. Patients and Methods: Eleven Chinese patients with IHH were retrospectively analyzed. Rare genetic variants were evaluated using whole-exome sequencing and bioinformatics analysis and were further classified according to the ACMG-AMP guidelines. The therapeutic responses of patients were further evaluated. Results: Six heterozygous variants of SOX10, WDR11, PROKR2, CHD7 and FGF17 were detected in five Kallmann syndrome (KS) patients, whereas two heterozygous variants of CHD7 and PROKR2 were detected in two normosmic IHH (nIHH) patients. Among these variants, a novel likely pathogenic variant in the SOX10 (c.429-1G>C) was considered to cause the KS phenotype in patient 02, and two potential variants of uncertain significance (VUS) in CHD7 (c.3344G>A and c.7391A>G) possibly contributed to the KS phenotype in patient 05 and the nIHH phenotype in patient 07, which need to be confirmed by further evidence. Additionally, long-term testosterone or estradiol replacement treatment effectively improved the development of sexual characteristics in patients with IHH. Conclusion: Next-generation sequencing is a powerful tool for identifying the molecular etiology and early diagnosis of IHH. Efficient therapeutic outcomes strongly indicate a need for timely treatment.

Accurate and Wide-Voltage-Range Modeling of Electrowetting with a Lattice Boltzmann Approach.

The lattice Boltzmann method (LBM) has been widely used in multi-phase fluid mechanics and is known to be more computationally efficient than the traditional method of numerically solving Navier-Stokes and Cahn-Hilliard equations. Electrowetting is an important component of interfacial sciences, in which the liquid-liquid and solid-liquid interfaces are tuned by electrostatics. Modeling electrowetting using the LBM can be categorized into surface and bulk methods. By modifying the surface tension scalar, the surface method easily reproduces the fundamental Young-Lippmann (YL) equation at low voltages but fails to capture contact angle saturation at high voltages. With fully coupled hydrodynamics and electrostatics in the form of spatially dependent matrices, the bulk method can successfully show contact angle saturation, but it is often unable to reproduce the YL equation due to its intrinsic inaccuracies. The inaccuracies are mainly due to the fact that while the hydrodynamics are all described by continuous physical quantities in the framework of diffusive interfaces, the interfacial electrostatics are governed by discontinuous electric fields caused by sheet charge density. In this paper, we show that accurately modeling electrowetting using the LBM is non-trivial. Additional modeling work, especially the treatment of interfacial electric fields, is needed to recover the fundamental YL equation at low voltages and predict contact angle saturation at high voltages, with a systematic model validation over key parameters and applications.

Astragaloside IV improves renal function and alleviates renal damage and inflammation in rats with chronic glomerulonephritis.

From Astragalus membranaceus (Fisch.) Bge.var. mongholicus (Bge.) Hsiao, astragaloside IV (AS-IV), a saponin can be purified and is considered traditional Chinese medicine. The purpose of this study was to evaluate the AS-IV-mediated mechanism on chronic glomerulonephritis (CGN). A cationic bovine serum albumin-induced CGN rat model was established and 10, 15, or 20 mg/kg of AS-IV was administered to measure renal function and inflammatory infiltration. Influences of AS-IV on proliferation, cell cycle, and inflammation of LPS-induced rat mesangial cells (RMCs) were determined. The results demonstrated that AS-IV alleviated renal dysfunction, renal lesions, and inflammation in CGN rats. AS-IV prolonged the G0-G1 phase, shortened the S phase, and inhibited cell proliferation and inflammation in RMCs. AS-IV can promote miR-181d-5p expression to inhibit CSF1. miR-181d-5p promotion or CSF1 suppression could further enhance the therapeutic role of AS-IV in CGN rats, while miR-181d-5p silencing or CSF1 overexpression abolished the effect of AS-IV. In conclusion, AS-IV by mediating the miR-181d-5p/CSF1 axis protects against CGN.

Achieving Solution-Processed Non-Doped Single-Emitting-Layer White Organic Light-Emitting Diodes through Adjusting Pyrene-Based Polyaromatic Hydrocarbon.

Single-emitting-layer white organic light-emitting diodes (SEL-WOLEDs) have developed rapidly in recent years due to the outstanding advantages of high efficiency, simple device structure, low cost, less phase separation, and stable emission color. Nevertheless, the relatively complicated host-dopant system is usually essential for most previous SEL-WOLEDs and the development of simple non-doped SEL-WOLEDs lags behind. Hence the straightforward synthesis of single-white-emitting molecules for non-doped SEL-WOLEDs still remains a great challengeable task. In this article, we designed and synthesized two new pyrene-based polyaromatic hydrocarbons (PAHs) and used them as emitting layer materials in the OLED devices. When the molecules change from the mono-fused one to bis-fused one, the emitting light changes from greenish to white color. Further study indicated that the bis-fused molecule PyD with more twisted and extended backbone packed in neat Cmca space group in single-crystal system compared with P21 /n for PyS, which may be favorable to form excimers in the solid state and broaden the emission spectrum in the OLEDs. As a result, a solution-processed non-doped single-white-emitting-molecule SEL-WOLED with high performance (e. g., a high color rendering index of 66) is reported. The findings will be beneficial not only to further development of simple WOLEDs, but also to other related organic optoelectronic technology.

Effects of an afternoon nap on sustained attention and working memory: The role of physiological arousal and sleep variables.

Taking a short midday nap has been associated with higher alertness and better cognitive task performance. Yet, the mechanisms associated with nap-dependent performance enhancement are unclear. The current study was conducted to explore the impact of physiological arousal during cognitive task and sleep architecture during a pre-task nap on post-nap behavioral outcomes. A within-subjects design (N = 18) was employed, in which participants either took a nap or remained awake for 40 min during the post-lunch period. The psychomotor vigilance test (PVT) and n-back task were administered to assess sustained attention and working memory, respectively, with each task including one block of easy trials and one block of difficult trials. Results showed that a short midday nap improved sustained attention but not working memory. In addition, a midday nap induced lower physiological arousal during the performance on both cognitive tasks, with relatively higher delta and lower beta activity. The relative power of theta and alpha were positively correlated with performance on the easy PVT, whereas the alpha power was negatively correlated with performance on the difficult PVT, and the theta power was negatively correlated with reaction speed in the n-back task regardless of the task difficulty. Meanwhile, the shorter total sleep time and longer time of wake after sleep onset were associated with the faster overall reaction speed in PVT easy trials. These findings suggested that both changes in physiological arousal and sleep variables might account for changes in task performance after a short midday nap.

Molecular diagnosis for growth hormone deficiency in Chinese children and adolescents and evaluation of impact of rare genetic variants on treatment efficacy of growth hormone.

BACKGROUND: Growth hormone is an effective therapy for growth hormone deficiency (GHD) but with a rather variable individual sensitivity. It is unclear whether rare genetic variants may contribute to the differential GH responsiveness. METHODS: The present study aims to investigate the molecular etiology of GHD in Chinese children and adolescents and evaluate the impact of rare variants on therapeutic efficacies of GH. RESULTS: Twenty-one rare heterozygous variant were classified as promising uncertain significance (n = 14), pathogenic (n = 5) or likely pathogenic (n = 2) for 21 of the 93 GHD patients. After GHD patients harboring these rare variants were excluded, inter-individual variability in the response to GH therapy obviously reduced and the negative correlation between initiation age of treatment and height SDS change became stronger in the group without rare variants. Among rare variants, 7 (likely) pathogenic variants (7.5%, 7/93) involved a total of 6 genes not only associated with GH secretion (PROKR2, LZTR1), but also growth plate chondrocyte signaling (ACAN, FBN1, COL9A1) or genetic syndromes (PTPN11). CONCLUSIONS: Rare genetic variants are an important factor contributing to differential GH responsiveness and genetic testing should be factored into accurate diagnosis and treatment decision making in the future. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR1900026510.

Human pharmacokinetics prediction with an in vitro-in vivo correction factor approach and in vitro drug-drug interaction profile of bictegravir, a potent integrase-strand transfer inhibitor component in approved biktarvy® for the treatment of HIV-1 infection.

Bictegravir (BIC) is a potent small-molecule integrase strand-transfer inhibitor (INSTI) and a component of Biktarvy®, a single-tablet combination regimen that is currently approved for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. The in vitro properties, pharmacokinetics (PK), and drug-drug interaction (DDI) profile of BIC were characterised in vitro and in vivo.BIC is a weakly acidic, ionisable, lipophilic, highly plasma protein-bound BCS class 2 molecule, which makes it difficult to predict human PK using standard methods. Its systemic plasma clearance is low, and the volume of distribution is approximately the volume of extracellular water in nonclinical species. BIC metabolism is predominantly mediated by cytochrome P450 enzyme (CYP) 3A and UDP-glucuronosyltransferase 1A1. BIC shows a low potential to perpetrate clinically meaningful DDIs via known drug metabolising enzymes or transporters.The human PK of BIC was predicted using a combination of bioavailability and volume of distribution scaled from nonclinical species and a modified in vitro-in vivo correlation (IVIVC) correction for clearance. Phase 1 studies in healthy subjects largely bore out the prediction and supported the methods used. The approach presented herein could be useful for other drug molecules where standard projections are not sufficiently accurate. .

Intelligent Algorithm-Based Analysis on Ultrasound Image Characteristics of Patients with Lower Extremity Arteriosclerosis Occlusion and Its Correlation with Diabetic Mellitus Foot.

Objective: The study focused on the correlation between lower extremity arteriosclerosis and diabetic mellitus (DM) foot, and it was explored by virtue of ultrasound images processed by an intelligent algorithm. Methods: A total of 60 DM foot patients admitted to our hospital in the past three years were selected and divided into two groups according to their condition. Patients with DM foot alone were in group B (30 cases), and patients with DM foot combined with lower extremity arteriosclerosis occlusion were in group C (30 cases). 30 healthy people were in group A as a control. Color Doppler ultrasound was used to examine the arteries of the lower extremities of all subjects. It the intramedia thickness (IMT) from the femoral artery to the dorsal foot artery was recorded, whether there was plaque in the artery or knowing the size of the plaque, its echo, and distribution, and whether the artery had stenosis. Next, the stenosis percentage was calculated. Additionally, the general information of patients was analyzed. At the same time, an intelligent algorithm was used to process ultrasound images, and its effects on image quality were evaluated. Results: Doppler ultrasound images processed by Artificial Bee Colony (ABC) had less noise and better quality, and key information about the lesion was clearly displayed. There was no statistical difference between the general data of the three groups of patients; group B and group C had higher IMT value, plaque incidence, arterial stenosis incidence, and degree of stenosis versus group A, and there were statistically significant differences between groups B and C. In particular, the incidence of femoral artery stenosis and the degree of stenosis were significantly higher in group C than in group B. The rate of stenosis above grade I in group C was as high as 71%, while that in group B was only 19%; in Group C, the incidence of stenosis above grade II was 30%, and that in group B was 13.1%. Compared with group A, group B and group C had decreased peak arterial blood velocity (PSV), resistance index (RI), and pulse index (PI), and there were statistically significant differences between groups B and C. Conclusion: DM foot is a risk factor for arteriosclerosis occlusion; color Doppler ultrasound demonstrates good diagnostic effects on arteriosclerosis occlusion; the algorithm proposed in this study can improve the quality of Doppler ultrasound images and has a high application value.

Effect of comprehensive nursing intervention on serum inflammatory factors and quality of life in patients with pelvic inflammatory disease.

OBJECTIVE: To explore the improvement of quality of life of patients with pelvic inflammatory disease by comprehensive nursing intervention. METHODS: Altogether 118 patients with pelvic inflammatory disease admitted to our hospital from February 2018 to December 2019 were obtained and grouped into the control group (CG) and the experimental group (EG). The CG was given routine nursing and the EG was given comprehensive nursing intervention. The clinical efficacy, changes of serum inflammatory factors, negative emotion scores, treatment compliance and quality of life of the two groups were compared. The satisfaction of nursing care of patients in two groups was counted. RESULTS: The total effective rate of treatment in the EG was evidently higher than that in the CG. Before nursing, there was no significant difference in serum inflammatory factors, SDS and SAS scores and quality of life scores between the two groups (P<0.05). After nursing intervention, the levels of serum inflammatory factors, SDS and SAS scores and quality of life scores in the EG were evidently better than those in the CG, and their satisfaction with nursing was evidently higher than that in the CG (all P< 0.05). CONCLUSION: Comprehensive nursing intervention can effectively improve the quality of life of patients with pelvic inflammatory disease, and as such it is worth popularizing.

Bubble Manipulation Driven by Alternating Current Electrowetting: Oscillation Modes and Surface Detachment.

In this paper, a millimeter-sized bubble in water pending on a substrate is manipulated by applying an alternating current (AC) electric field, known as electrowetting on dielectric. In this setup, standing waves on the bubble surface are observed. The amplitude of these waves varies with frequency, and three resonance peaks (21, 76, and 134 Hz) can be identified. By incorporating the nonlinear friction force for the contact line to an existing surface mode model, a significant improvement to explain the spectrum of the oscillations is obtained, predicting three peak positions, widths, and heights with good accuracy. We also show that bubble detachment correlates with the low-frequency resonance peak. It is found experimentally that if close enough to this peak, then bubbles at sufficiently high voltages are observed to detach from the substrate. This suggests that inertial effects can effectively promote bubble detachment. To confirm this hypothesis, the bubble dynamics is simulated with COMSOL using the full Navier-Stokes equation with a two-phase field and electrostatic stresses. It was found that the bubble experimental detachment process is quite well-reproduced in the simulation, confirming the role of fluid inertia for the detachment process. Given the nice correspondence between the experimental state diagrams and the theoretical modeling, this work contributes to identify a window for precise and reliable bubble manipulation by means of AC electrowetting.

A Retrospective Analysis of Patients with Short Stature in Eastern China between 2013 and 2019.

OBJECTIVE: To identify the aetiology of growth and development diseases and assess the long-term effectiveness of recombinant human growth hormone (rhGH) therapy in a real-life clinical setting and provide better guidance in clinical strategy and decision making. METHODS: This retrospective study included 1145 children and adolescents with short stature admitted to the Department of Endocrinology, Affiliated Hospital of Jining Medical University, from January 2013 to December 2019, of whom 484 received rhGH treatment. The related anthropometrics and laboratory examinations were assessed in all participants. RESULTS: A total of 1145 children and adolescents with short stature aged 10.5 ± 3.3 years, including 740 boys and 405 girls, were analysed in this study. The number of children and adolescents with short stature gradually increased per year from 2013 to 2019. The mean pretreatment height standard deviation score (SDS) and insulin-like growth factor-1 SDS were -2.93 ± 1.05 and -1.01 (-1.83--0.16), respectively. The majority of the children (658, 57.47%) were prepubescent. In total, 484 subjects aged 10.6 ± 3.2 years received rhGH and were followed up, and among them, 292 children were treated for more than one year. As the treatment time increased, the children's height SDS gradually increased, and most of them attained a height SDS within the normal range. The mean height SDS in children who were treated for more than one year was -3.0 ± 1.0 at baseline and gradually increased to -0.8 ± 0.3 by year 6. The results were consistent across subgroups of different aetiologies of short stature. CONCLUSIONS: Increasing attention has been given to the height of children during the period of 2013-2019 in eastern China. The present findings indicate that children with short stature need to be referred to a specialist centre to diagnose the cause of growth failure and that short children receiving rhGH therapy show a significant increase in height over time.

Association between insulin-like growth factor-1 and systolic blood pressure in children and adolescents with short stature.

The relationship between insulin-like growth factor-1 (IGF-1) and systolic blood pressure (SBP) is controversial in adults and children. The purpose of this study was to investigate the relationship between the IGF-1 standard deviation score (IGF-1 SDS) and SBP in children with short stature. A cross-sectional analysis including 1315 children with short stature was conducted from March 2013 to October 2020. We estimated IGF-1, blood pressure and other laboratory tests, and anthropometric indicators were also evaluated. Subgroup analyses of the pubertal stage, sex, growth hormone levels, thyroid hormone levels, fasting blood glucose levels, and triglyceride levels were performed. A positive association between the IGF-1 SDS and SBP was observed by univariate analysis (p < .001). We further found a nonlinear association between the IGF-1 SDS and SBP. The inflection point for the curve was found at an IGF-1 SDS level of -2.91. In multivariate piecewise linear regression, there was a positive association between the IGF-1 SDS and SBP when the IGF-1 SDS was greater than -2.91 (ß 1.56, 95% CI: 0.91, 2.22; p < .001). However, we did not observe a significant relationship between the IGF-1 SDS and SBP when the IGF-1 SDS level was less than -2.91 (ß -0.95, 95% CI -3.17, 1.28; p = .379). This association was consistent across subgroup analyses. The present study demonstrated that there is a nonlinear relationship between the IGF-1 SDS and SBP in children with short stature. Increased serum IGF-1 levels were associated with elevated SBP when the IGF-1 levels reached the inflection point.

Association Between Hemoglobin and Growth Hormone Peak in Chinese Children and Adolescents with Short Stature: A Cross-Sectional Study.

OBJECTIVE: This research aimed to investigate the relationship between hemoglobin (Hb) and growth hormone (GH) peak in children and adolescents with short stature. DESIGN: This cross-sectional study included a total of 787 children and adolescents with short stature. Anthropometric and biochemical indicators were measured at baseline. All patients underwent GH provocation tests with L-dopa and insulin to assess GH peak levels. RESULTS: The univariate analysis results showed that Hb was positively associated with GH peak (ß 0.07, P=0.001). Furthermore, a non-linear relationship was detected between Hb and GH peaks through smooth curve fitting, and the inflection point was 123 g/L after multivariate piecewise linear regression analysis. GH peak increased with Hb elevation when the Hb level was greater than 123 g/L (ß 0.08, 95% CI 0.01, 0.14; P=0.0207). CONCLUSION: In children and adolescents with short stature, we found GH peak was positively associated with the Hb level when the Hb level reached the inflection point.

Association between Insulin-Like Growth Factor-1 and Relative Skeletal Maturation: A Retrospective Cohort Study of Short Children and Adolescents.

OBJECTIVE: Delays in skeletal maturity are related to bone mass and fracture risk in children, but the factors that determine it are unknown. We aimed to identify the association between insulin-like growth factor-1 (IGF-1) and skeletal maturation before and after growth hormone (GH) treatment. METHODS: In this retrospective cohort study, we observed 783 short children and adolescents, 229 of whom received GH therapy. Skeletal maturation was assessed based on the difference between bone age (BA) and chronological age (CA) (noted as BA-CA). Anthropometric data and laboratory values were measured, and BA was evaluated using the Greulich and Pyle method. RESULTS: The delayed BA group was defined as BA-CA < -2 SD (n = 457), and the occurrence rate of BA delay was 58.37%. A nonlinear relationship was observed between the IGF-1 standard deviation score (IGF-1 SDS) and BA-CA before and after GH therapy. Before GH therapy, there was a significant positive association between the IGF-1 SDS and BA-CA when the IGF-1 level was greater than -2 SDS (ß 0.17, 95% CI 0.08, 027; P < 0.001). However, we did not observe a significant relationship between the IGF-1 SDS and BA-CA when the IGF-1 level was lower than -2 SDS (ß 0.07, 95% CI -0.12, 0.26; P = 0.454). After GH therapy, there was a significant positive association between the IGF-1 SDS and BA-CA when the IGF-1 level was lower than 2 SDS (ß 0.20, 95% CI 0.12, 028; P < 0.001). However, we did not observe a significant relationship between the IGF-1 SDS and BA-CA when the IGF-1 level was greater than 2 SDS (ß -0.03, 95% CI -0.33, 0.27; P = 0.866). CONCLUSION: BA is more delayed in short children and adolescents. There is a nonlinear relationship between IGF-1 and BA maturation in short children before and after GH treatment. These findings suggest that a low level of IGF-1 may contribute to BA delay in short children and adolescents.

Boosting Upconversion Photoluminescence and Multielectrical Properties via Er-Doping-Modulated Vacancy Control in Ba0.85Ca0.15Ti0.9Zr0.1O3.

The lead-free 0.5(Ba0.7Ca0.3)TiO3-0.5Ba(Ti0.8Zr0.2)O3 (BCTZ) ceramics with Er doping have shown good upconversion photoluminescence (PL) and desirable optical temperature sensing properties. To bridge a relationship between the structure/intrinsic defects and properties of rare-earth-doped ferroelectrics, we designed and fabricated a series of BCTZ ceramics doped with 1 mol % Er3+ by combining the first-principles calculations and experimental measurements. Theoretically, we discovered that Er can occupy both A sites (i.e., replacing Ba or Ca) and B sites (i.e., replacing Ti or Zr) in the BCTZ lattice and highlighted that the Er-doping-induced vacancy concentration decreases for both the oxygen vacancies (V o) and cation vacancies (V c). Experimentally, the enhanced PL performance and the dielectric, ferroelectric, and piezoelectric properties of the Er-doped BCTZ ceramics have been observed. Finally, the physical origin of Er-induced property enhancement in BCTZ has been elaborated according to the charge density and chemical bonding analysis. These results open up a path to investigate the effects of site substitution and vacancies on optoelectronic properties of multifunctional rare-earth-doped ferroelectrics.

Electric field-responsive photoluminescence color switching and reversible properties via Tb/Eu co-doped ergodic relaxor ferroelectrics.

A facile strategy of color switching has been developed through reversibly multicolored photoluminescence modulation in dual rare-earth element modified 0.94Bi0.5Na0.5TiO3-0.06BaTiO3 (BNT6BT-Tb/Eu-x) relaxor ferroelectrics via the application of in situ electric fields. By virtue of the chemical and charge disorder induced by the trivalent rare earth ions, more dynamic and weakly correlated polar nanoregions are formed, which facilitate a reversible transition between the randomly oriented polar nanoregions and unstable ordered ferroelectric domains under an electric field. The electroceramics thus become more ergodic, exhibiting giant and reversible electric field-induced strain as well as structural symmetry changes around the luminescent centers and the BNT6BT-Tb/Eu-0.04 sample reveals the highest ergodicity degree. Accordingly, the overall emission color can be modulated reversibly between orange and green by purely physical stimuli (an electric field). The design of the color modulation elucidated in this work should inspire similar research expanded to other soft ferroelectrics for optical tuning and displays at ambient temperature. This should also be helpful for the realization of regulating the physical coupling (photoluminescence color switching-ergodic relaxor ferroelectrics) in multifunctional inorganic materials.

Inhibition of Acetyl-CoA Carboxylase by Phosphorylation or the Inhibitor ND-654 Suppresses Lipogenesis and Hepatocellular Carcinoma.

The incidence of hepatocellular carcinoma (HCC) is rapidly increasing due to the prevalence of obesity and non-alcoholic fatty liver disease, but the molecular triggers that initiate disease development are not fully understood. We demonstrate that mice with targeted loss-of-function point mutations within the AMP-activated protein kinase (AMPK) phosphorylation sites on acetyl-CoA carboxylase 1 (ACC1 Ser79Ala) and ACC2 (ACC2 Ser212Ala) have increased liver de novo lipogenesis (DNL) and liver lesions. The same mutation in ACC1 also increases DNL and proliferation in human liver cancer cells. Consistent with these findings, a novel, liver-specific ACC inhibitor (ND-654) that mimics the effects of ACC phosphorylation inhibits hepatic DNL and the development of HCC, improving survival of tumor-bearing rats when used alone and in combination with the multi-kinase inhibitor sorafenib. These studies highlight the importance of DNL and dysregulation of AMPK-mediated ACC phosphorylation in accelerating HCC and the potential of ACC inhibitors for treatment.