The social transmission of empathy relies on observational reinforcement learning.

Theories of moral development propose that empathy is transmitted across individuals. However, the mechanisms through which empathy is socially transmitted remain unclear. Here, we combine computational learning models and functional MRI to investigate whether, and if so, how empathic and non-empathic responses observed in others affect the empathy of female observers. The results of three independent studies showed that watching empathic or non-empathic responses generates a learning signal that respectively increases or decreases empathy ratings of the observer. A fourth study revealed that the learning-related transmission of empathy is stronger when observing human rather than computer demonstrators. Finally, we show that the social transmission of empathy alters empathy-related responses in the anterior insula, i.e., the same region that correlated with empathy baseline ratings, as well as its functional connectivity with the temporoparietal junction. Together, our findings provide a computational and neural mechanism for the social transmission of empathy that accounts for changes in individual empathic responses in empathic and non-empathic social environments.

Proteomics and phosphoproteomics of failing human left ventricle identifies dilated cardiomyopathy-associated phosphorylation of CTNNA3.

The prognosis and treatment outcomes of heart failure (HF) patients rely heavily on disease etiology, yet the majority of underlying signaling mechanisms are complex and not fully elucidated. Phosphorylation is a major point of protein regulation with rapid and profound effects on the function and activity of protein networks. Currently, there is a lack of comprehensive proteomic and phosphoproteomic studies examining cardiac tissue from HF patients with either dilated dilated cardiomyopathy (DCM) or ischemic cardiomyopathy (ICM). Here, we used a combined proteomic and phosphoproteomic approach to identify and quantify more than 5,000 total proteins with greater than 13,000 corresponding phosphorylation sites across explanted left ventricle (LV) tissue samples, including HF patients with DCM vs. nonfailing controls (NFC), and left ventricular infarct vs. noninfarct, and periinfarct vs. noninfarct regions of HF patients with ICM. Each pair-wise comparison revealed unique global proteomic and phosphoproteomic profiles with both shared and etiology-specific perturbations. With this approach, we identified a DCM-associated hyperphosphorylation cluster in the cardiomyocyte intercalated disc (ICD) protein, αT-catenin (CTNNA3). We demonstrate using both ex vivo isolated cardiomyocytes and in vivo using an AAV9-mediated overexpression mouse model, that CTNNA3 phosphorylation at these residues plays a key role in maintaining protein localization at the cardiomyocyte ICD to regulate conductance and cell-cell adhesion. Collectively, this integrative proteomic/phosphoproteomic approach identifies region- and etiology-associated signaling pathways in human HF and describes a role for CTNNA3 phosphorylation in the pathophysiology of DCM.

Identification of congenital aortic valve malformations in juvenile natriuretic peptide receptor 2-deficient mice using high-frequency ultrasound.

Mouse models of congenital aortic valve malformations are useful for studying disease pathobiology, but most models have incomplete penetrance [e.g., ∼2 to 77% prevalence of bicuspid aortic valves (BAVs) across multiple models]. For longitudinal studies of pathologies associated with BAVs and other congenital valve malformations, which manifest over months in mice, it is operationally inefficient, economically burdensome, and ethically challenging to enroll large numbers of mice in studies without first identifying those with valvular abnormalities. To address this need, we established and validated a novel in vivo high-frequency (30 MHz) ultrasound imaging protocol capable of detecting aortic valvular malformations in juvenile mice. Fifty natriuretic peptide receptor 2 heterozygous mice on a low-density lipoprotein receptor-deficient background (Npr2+/-;Ldlr-/-; 32 males and 18 females) were imaged at 4 and 8 wk of age. Fourteen percent of the Npr2+/-;Ldlr-/- mice exhibited features associated with aortic valve malformations, including 1) abnormal transaortic flow patterns on color Doppler (recirculation and regurgitation), 2) peak systolic flow velocities distal to the aortic valves reaching or surpassing ∼1,250 mm/s by pulsed-wave Doppler, and 3) putative fusion of cusps along commissures and abnormal movement elucidated by two-dimensional (2-D) imaging with ultrahigh temporal resolution. Valves with these features were confirmed by ex vivo gross anatomy and histological visualization to have thickened cusps, partial fusions, or Sievers type-0 bicuspid valves. This ultrasound imaging protocol will enable efficient, cost effective, and humane implementation of studies of congenital aortic valvular abnormalities and associated pathologies in a wide range of mouse models.NEW & NOTEWORTHY We developed a high-frequency ultrasound imaging protocol for diagnosing congenital aortic valve structural abnormalities in 4-wk-old mice. Our protocol defines specific criteria to distinguish mice with abnormal aortic valves from those with normal tricuspid valves using color Doppler, pulsed-wave Doppler, and two-dimensional (2-D) imaging with ultrahigh temporal resolution. This approach enables early identification of valvular abnormalities for efficient and ethical experimental design of longitudinal studies of congenital valve diseases and associated pathologies in mice.

Impact of ovary-intact menopause in a mouse model of heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) afflicts over half of all patients with heart failure and is a debilitating and fatal syndrome affecting postmenopausal women more than any other demographic. This bias toward older females calls into question the significance of menopause in the development of HFpEF, but this question has not been probed in detail. In this study, we report the first investigation into the impact of ovary-intact menopause in the context of HFpEF. To replicate the human condition as faithfully as possible, vinylcyclohexene dioxide (VCD) was used to accelerate ovarian failure (AOF) in female mice while leaving the ovaries intact. HFpEF was established with a mouse model that involves two stressors typical in humans: a high-fat diet and hypertension induced from the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME). In young female mice, AOF or HFpEF-associated stressors independently induced abnormal myocardial strain indicative of early subclinical systolic and diastolic cardiac dysfunction. HFpEF but not AOF was associated with elevations in systolic blood pressure. Increased myocyte size and reduced myocardial microvascular density were not observed in any group. Also, a broad panel of measurements that included echocardiography, invasive pressure measurements, histology, and serum hormones revealed no interaction between AOF and HFpEF. Interestingly, AOF did evoke a higher density of infiltrating cardiac immune cells in both healthy and HFpEF mice, suggestive of proinflammatory effects. In contrast to young mice, middle-aged "old" mice did not exhibit cardiac dysfunction from estrogen deprivation alone or from HFpEF-related stressors.NEW & NOTEWORTHY This is the first preclinical study to examine the impact of ovary-intact menopause [accelerated ovarian failure (AOF)] on HFpEF. Echocardiography of young female mice revealed early evidence of diastolic and systolic cardiac dysfunction apparent only on strain imaging in HFpEF only, AOF only, or the combination. Surprisingly, AOF did not exacerbate the HFpEF phenotype. Results in middle-aged "old" females also showed no interaction between HFpEF and AOF and, importantly, no cardiovascular impact from HFpEF or AOF.

Neural representation of perceived race mediates the opposite relationship between subcomponents of self-construals and racial outgroup punishment.

Outgroup aggression characterizes intergroup conflicts in human societies. Previous research on relationships between cultural traits and outgroup aggression behavior showed inconsistent results, leaving open questions regarding whether cultural traits predict individual differences in outgroup aggression and related neural underpinnings. We conducted 2 studies to address this issue by collecting self-construal scores, EEG signals in response to Asian and White faces with painful or neutral expressions, and decisions to apply electric shocks to other-race individuals in a context of interracial conflict. We found that interdependent self-construals were well explained by 2 subcomponents, including esteem for group (EG) and relational interdependence (RI), which are related to focus on group collectives and harmonious relationships, respectively. Moreover, EG was positively associated with the decisions to punish racial outgroup targets, whereas RI was negatively related to the decisions. These opposite relationships were mediated by neural representations of perceived race at 120-160 ms after face onset. Our findings highlight the multifaceted nature of interdependent self-construal and the key role of neural representations of race in mediating the relationships of different subcomponents of cultural traits with racial outgroup punishment decisions in a context of interracial conflict.

Silymarin decreases liver stiffness associated with gut microbiota in patients with metabolic dysfunction-associated steatotic liver disease: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Despite centuries of traditional use of silymarin for hepatoprotection, current randomized controlled trial (RCT) studies on the effectiveness of silymarin in managing metabolic dysfunction-associated steatotic liver disease (MASLD) are limited and inconclusive, particularly when it is administered alone. The low bioavailability of silymarin highlights the possible influence of gut microbiota on the effectiveness of silymarin; however, no human studies have investigated this aspect. OBJECTIVE: To determine the potential efficacy of silymarin in improving MASLD indicators and to investigate the underlying mechanisms related to gut microbiota. METHOD: In this 24-week randomized, double-blind, placebo-controlled trial, 83 patients with MASLD were randomized to either placebo (n = 41) or silymarin (103.2 mg/d, n = 42). At 0, 12, and 24 weeks, liver stiffness and hepatic steatosis were assessed using FibroScan, and blood samples were gathered for biochemical detection, while faecal samples were collected at 0 and 24 weeks for 16S rRNA sequencing. RESULTS: Silymarin supplementation significantly reduced liver stiffness (LSM, -0.21 ± 0.17 vs. 0.41 ± 0.17, P = 0.015) and serum levels of γ-glutamyl transpeptidase (GGT, -8.21 ± 3.01 vs. 1.23 ± 3.16, P = 0.042) and ApoB (-0.02 ± 0.03 vs. 0.07 ± 0.03, P = 0.023) but had no significant effect on the controlled attenuation parameter (CAP), other biochemical indicators (aminotransferases, total bilirubin, glucose and lipid parameters, hsCRP, SOD, and UA), physical measurements (DBP, SBP, BMI, WHR, BF%, and BMR), or APRI and FIB-4 indices. Gut microbiota analysis revealed increased species diversity and enrichment of Oscillospiraceae in the silymarin group. CONCLUSION: These findings suggest that silymarin supplementation could improve liver stiffness in MASLD patients, possibly by modulating the gut microbiota. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2200059043).

Learning from Ingroup Experiences Changes Intergroup Impressions.

Humans form impressions toward individuals of their own social groups (ingroup members) and of different social groups (outgroup members). Outgroup-focused theories predict that intergroup impressions are mainly shaped by experiences with outgroup individuals, while ingroup-focused theories predict that ingroup experiences play a dominant role. Here we test predictions from these two psychological theories by estimating how intergroup impressions are dynamically shaped when people learn from both ingroup and outgroup experiences. While undergoing fMRI, male participants had identical experiences with different ingroup or outgroup members and rated their social closeness and impressions toward the ingroup and the outgroup. Behavioral results showed an initial ingroup bias in impression ratings which was significantly reduced over the course of learning, with larger effects in individuals with stronger ingroup identification. Computational learning models revealed that these changes in intergroup impressions were predicted by the weight given to ingroup prediction errors. Neurally, the individual weight for ingroup prediction errors was related to the coupling between the left inferior parietal lobule and the left anterior insula, which, in turn, predicted learning-related changes in intergroup impressions. Our findings provide computational and neural evidence for ingroup-focused theories, highlighting the importance of ingroup experiences in shaping social impressions in intergroup settings.Significance Statement:Living in multicultural societies, humans interact with individuals of their own social groups (ingroup members) and of different social groups (outgroup members). However, little is known about how people learn from the mixture of ingroup and outgroup interactions, the most natural experiences in current societies. Here, participants had identical, intermixed experiences with different ingroup and outgroup individuals and rated their closeness and impressions toward the ingroup and the outgroup. Combining computational models and fMRI, we find that the weight given to ingroup experiences (ingroup prediction errors) is the main source of intergroup impression change, captured by changes in connectivity between the parietal lobe and insula. These findings highlight the importance of ingroup experiences in shaping intergroup impressions in complex social environments.

Comprehensive ultrasound imaging of right ventricular remodeling under surgically induced pressure overload in mice.

This study reports a new methodology for right heart imaging by ultrasound in mice under right ventricular (RV) pressure overload. Pulmonary artery constriction (PAC) or sham surgeries were performed on C57BL/6 male mice at 8 wk of age. Ultrasound imaging was conducted at 2, 4, and 8 wk postsurgery using both classical and advanced ultrasound imaging modalities including electrocardiogram (ECG)-based kilohertz visualization, anatomical M-mode, and strain imaging. Based on pulsed Doppler, the PAC group demonstrated dramatically enhanced pressure gradient in the main pulmonary artery (MPA) as compared with the sham group. By the application of advanced imaging modalities in novel short-axis views of the ventricles, the PAC group demonstrated increased thickness of RV free wall, enlarged RV chamber, and reduced RV fractional shortening compared with the sham group. The PAC group also showed prolonged RV contraction, asynchronous interplay between RV and left ventricle (LV), and passive leftward motion of the interventricular septum (IVS) at early diastole. Consequently, the PAC group exhibited prolongation of LV isovolumic relaxation time, without change in LV wall thickness or systolic function. Significant correlations were found between the maximal pressure gradient in MPA measured by Doppler and the RV systolic pressure by catheterization, as well as the morphological and functional parameters of RV by ultrasound.NEW & NOTEWORTHY The established protocol overcomes the challenges in right heart imaging in mice, thoroughly elucidating the changes of RV, the dynamics of IVS, and the impact on LV and provides new insights into the pathophysiological mechanism of RV remodeling.

SMC-Derived Hyaluronan Modulates Vascular SMC Phenotype in Murine Atherosclerosis.

[Figure: see text].

Biological characteristics and genomic analysis of a novel Escherichia phage Kayfunavirus CY1.

As the problem of bacterial resistance becomes serious day by day, bacteriophage as a potential antibiotic substitute attracts more and more researchers' interest. In this study, Escherichia phage Kayfunavirus CY1 was isolated from sewage samples of swine farms and identified by biological characteristics and genomic analysis. One-step growth curve showed that the latent period of phage CY1 was about 10 min, the outbreak period was about 40 min and the burst size was 35 PFU/cell. Analysis of the electron microscopy and whole-genome sequence showed that the phage should be classified as a member of the Autographiviridae family, Studiervirinae subfamily. Genomic analysis of phage CY1 (GenBank accession no. OM937123) revealed a genome size of 39,173 bp with an average GC content of 50.51% and 46 coding domain sequences (CDSs). Eight CDSs encoding proteins involved in the replication and regulation of phage DNA, 2 CDSs encoded lysis proteins, 14 CDSs encoded packing and morphogenesis proteins. Genomic and proteomic analysis identified no sequence that encoded for virulence factor, integration-related proteins or antibiotic resistance genes. In summary, morphological and genomics suggest that phage CY1 is more likely a novel Escherichia phage.

Pentacyclic triterpene-amino acid derivatives induced apoptosis and autophagy in tumor cells, affected the JNK and PI3K/AKT/mTOR pathway.

A series of pentacyclic triterpene-amino acid derivatives were synthesized and tested for anti-proliferative activity. The results showed that most of the target compounds had good anti-proliferative activity. 2c did not contain protecting groups and hydrochloride, had excellent cytotoxicity, so it had been selected for further study in the mechanism of action in T24 cells. The data from transcriptome sequencing indicated that 2c was found to be closely related to apoptosis and autophagy. Observation of fluorescence staining and analysis from flow cytometry demonstrated that 2c induced apoptosis and cause cell cycle arrest in S/G2 phase in T24 cells. Molecular mechanism studies exhibited that 2c induced apoptosis in the intrinsic and extrinsic pathways. 2c also induced cellular autophagy in T24 cells. Results from Western Blotting showed that 2c could activate JNK pathway and inhibit PI3K/AKT/mTOR pathway. In conclusion, 2c was deserved further investigation in the field of anti-tumor.

Evaluation of the stiffness of normal cervix and its change with different factors using transvaginal two-dimensional shear wave elastography under strict quality control.

BACKGROUND: The usefulness of transvaginal two-dimensional shear wave elastography (2D SWE) for cervical lesions is still uncertain. This study was to explore the value of transvaginal 2D SWE in the evaluation of the stiffness of normal cervix and its change with different factors under strict quality control (QC). METHODS: Two hundred patients with normal cervix were included in this study and were examined using quantitative 2D SWE to evaluate cervical stiffness and its change with different factors under strict QC. RESULTS: Intra-observer concordance of transvaginal 2D SWE parameters in midsagittal planes were acceptable with intraclass correlation coefficients higher than 0.5. Transvaginal 2D SWE parameters were significantly higher than the corresponding transabdominal parameters. 2D SWE parameters of internal cervical os were significantly higher than the corresponding parameters of external cervical os in a transvaginal midsagittal plane. 2D SWE parameters of external cervical os increased significantly over 50 years old, while these parameters of internal cervical os didn't change significantly with increasing age. 2D SWE parameters of internal cervical os of horizontal position cervix were significantly higher than those of vertical position cervix. SWE parameters of normal cervix did not change according to different menstrual cycles, parities and human papilloma virus test results. CONCLUSIONS: Transvaginal 2D SWE under strict QC could provide quantitative, repeatable and reliable cervical stiffness information. Internal cervical os was stiffer than external cervical os. Menstrual cycles, parities and human papilloma virus test results wouldn't affect cervical stiffness. However, age and cervical positions should be taken into condition while interpreting 2D SWE results of cervical stiffness.

Dynamic assessment of brain perfusion in a middle cerebral artery occlusion rat model by contrast-enhanced ultrasound imaging: a pilot study.

BACKGROUND: The middle cerebral artery occlusion model (MCAo) is a commonly used animal model for cerebral ischemia studies but lacks accessible imaging techniques for the assessment of hemodynamic changes of the model. PURPOSE: The study aims to explore the value of contrast-enhanced ultrasound (CEUS) in evaluating brain perfusion in the early stages after MCAo surgery. MATERIAL AND METHODS: In total, 18 adult male Sprague-Dawley rats were subjected to right MCAo using an intraluminal filament model, and CEUS was performed at the three following timepoints: before (T0), immediately after (T1), and 6 h after permanent MCAo (T2). Twelve rats successfully completed the study, and their brains were removed and stained using 2, 3, 5-triphenyltetrazolium chloride (TTC). CEUS video images were visualized offline, and the time-intensity curves (TICs) were analyzed. Different cerebrovascular patterns and manifestations of the contrast enhancement in rat ischemic hemispheres were observed. Semi-quantitative parameters of TICs in ischemic areas (ROIi) and the surrounding normal- or hypo-perfused areas (ROIn) were calculated and compared between T0, T1, and T2, and also between ROIi and ROIn. RESULTS: A significant correlation was found between the lesion volume (%) determined by TTC and CEUS parameters (r = -0.691, P = 0.013 for peak intensity; r = -0.742, P = 0.006 for area under the curve) at T2. After the same occlusion, there were differences in contrast perfusion in each group. CONCLUSION: This study suggests that CEUS could be an effective imaging tool for studying cerebral ischemia and perfusion in small animals as long as the transcranial acoustic window allows it.

Tip-Induced In-Plane Ferroelectric Superstructure in Zigzag-Wrinkled BaTiO3 Thin Films.

The complex micro-/nanoscale wrinkle morphology primarily fabricated by elastic polymers is usually designed to realize unique functionalities in physiological, biochemical, bioelectric, and optoelectronic systems. In this work, we fabricated inorganic freestanding BaTiO3 ferroelectric thin films with zigzag wrinkle morphology and successfully modulated the ferroelectric domains to form an in-plane (IP) superstructure with periodic surface charge distribution. Our piezoresponse force microscopy (PFM) measurements and phase-field simulation demonstrate that the self-organized strain/stress field in the zigzag-wrinkled BaTiO3 film generates a corresponding pristine domain structure. These domains can be switched by tip-induced strain gradient (flexoelectricity) and naturally form a robust and unique "braided" in-plane domain pattern, which enables us to offer an effective and convenient way to create a microscopic ferroelectric superstructure. The corresponding periodic surface potential distribution provides an extra degree of freedom in addition to the morphology that could regulate cells or polar molecules in physiological and bioelectric applications.

Deficiency in DDR1 Induces Pulmonary Hypertension and Impaired Alveolar Development.

Pulmonary hypertension (PH) is a multifaceted condition characterized by elevated pulmonary arterial pressure, which can result in right ventricular dysfunction and failure. Disorders of lung development can present with secondary PH, which is a leading cause of mortality in infants with bronchopulmonary dysplasia (BPD). DDR1 (discoidin domain receptor 1) is a collagen-binding receptor that regulates tissue fibrosis and inflammation and controls cellular growth and migration. However, the roles of DDR1 in lung development or the pathogenesis of PH are unknown. Studying mice with a DDR1 deletion (Ddr1-/-), we have noted 35% mortality between 1 and 4 months of age, and we demonstrate that DDR1 deficiency results in reduced right ventricular contractility and muscularization of distal pulmonary arteries, consistent with PH. Pathology analysis revealed enlarged alveolar spaces in Ddr1-/- mice by Postnatal Day 7, consistent with impaired alveolar development. Gene expression analysis showed that Ddr1-/- mice have reduced concentrations of alveologenesis factors and epithelial-to-mesenchymal transition markers. Mechanistic studies in vitro confirmed that DDR1 mediated epithelial-to-mesenchymal transition, migration, and growth of alveolar epithelial cells. Taken together, these data suggest that DDR1 plays important roles mediating alveolarization during lung development. Our studies also describe a new model of spontaneous PH and bronchopulmonary dysplasia in mice.

Tripartite motif-containing protein 46 accelerates influenza A H7N9 virus infection by promoting K48-linked ubiquitination of TBK1.

BACKGROUND: Avian influenza A H7N9 emerged in 2013, threatening public health and causing acute respiratory distress syndrome, and even death, in the human population. However, the underlying mechanism by which H7N9 virus causes human infection remains elusive. METHODS: Herein, we infected A549 cells with H7N9 virus for different times and assessed tripartite motif-containing protein 46 (TRIM46) expression. To determine the role of TRIM46 in H7N9 infection, we applied lentivirus-based TRIM46 short hairpin RNA sequences and overexpression plasmids to explore virus replication, and changes in type I interferons and interferon regulatory factor 3 (IRF3) phosphorylation levels in response to silencing and overexpression of TRIM46. Finally, we used Co-immunoprecipitation and ubiquitination assays to examine the mechanism by which TRIM46 mediated the activity of TANK-binding kinase 1 (TBK1). RESULTS: Type I interferons play an important role in defending virus infection. Here, we found that TRIM46 levels were significantly increased during H7N9 virus infection. Furthermore, TRIM46 knockdown inhibited H7N9 virus replication compared to that in the control group, while the production of type I interferons increased. Meanwhile, overexpression of TRIM46 promoted H7N9 virus replication and decrease the production of type I interferons. In addition, the level of phosphorylated IRF3, an important interferon regulatory factor, was increased in TRIM46-silenced cells, but decreased in TRIM46 overexpressing cells. Mechanistically, we observed that TRIM46 could interact with TBK1 to induce its K48-linked ubiquitination, which promoted H7N9 virus infection. CONCLUSION: Our results suggest that TRIM46 negatively regulates the human innate immune response against H7N9 virus infection.

Isolation and characterization of a novel Escherichia coli phage Kayfunavirus ZH4.

Escherichia coli, a gram-negative bacterium, was generally considered conditional pathogenic bacteria and the proportion of bacteria resistant to commonly used specified antibacterial drugs exceeded 50%. Phage therapeutic application has been revitalized since antibiotic resistance in bacteria was increasing. Compared with antibiotics, phage is the virus specific to bacterial hosts. However, further understanding of phage-host interactions is required. In this study, a novel phage specific to a E. coli strain, named as phage Kayfunavirus ZH4, was isolated and characterized. Transmission electron microscopy showed that phage ZH4 belongs to the family Autographiviridae. The whole-genome analysis showed that the length of phage ZH4 genome was 39,496 bp with 49 coding domain sequence (CDS) and no tRNA was detected. Comparative genome and phylogenetic analysis demonstrated that phage ZH4 was highly similar to phages belonging to the genus Kayfunavirus. Moreover, the highest average nucleotide identity (ANI) values of phage ZH4 with all the known phages was 0.86, suggesting that ZH4 was a relatively novel phage. Temperature and pH stability tests showed that phage ZH4 was stable from 4° to 50 °C and pH range from 3 to 11. Host range of phage ZH4 showed that there were only 2 out of 17 strains lysed by phage ZH4. Taken together, phage ZH4 was considered as a novel phage with the potential for applications in the food and pharmaceutical industries.

A validated UPLC-MS/MS method for quantification of glutamine in plasma and pharmacokinetic study of oral glutamine tablets in healthy Beagles.

This study aimed to clarify the laws of glutamine tablets absorption, distribution, and metabolism in Beagles and to provide a basis for formulating dosing regimens. Twelve healthy Beagles were enrolled the absolute bioavailability study with a crossover design . Glutamine tablets (240 mg/kg b.w.) or glutamine sterile solution (60 mg/kg b.w.) were administered. A method for the determination of glutamine in Beagles' plasma by UPLC-MS/MS was established, with high sensitivity, specificity, and simplicity. Based on the study of endogenous glutamine concentration, the mean concentration of the four time points before drug administration was selected as the background concentration of glutamine. Pharmacokinetic parameters were calculated by non-compartment model. The Cmax of glutamine was 136.11 ± 72.51 µg/ml, Tmax was 0.85 ± 0.29 h, and t1/2λz was 0.42 ± 0.27 h after oral administration. The AUC0-t of glutamine was 116.30 ± 75.15 h·µg/ml vs. 44.55 ± 22.48 h·µg/ml following oral and IV administration, respectively, with an absolute bioavailability of 64.74% ± 19.18%. The results showed glutamine was quickly absorbed and eliminated in Beagles with high bioavailability. Therefore, glutamine is suitable to be prepared as oral tablets and recommended to shorten the dosing interval.

[Prenatal screening and diagnosis for a fetus with mosaic sex chromosome abnormality].

OBJECTIVE: To carry out prenatal screening and diagnosis for a woman with advanced maternal age. METHODS: Non-invasive prenatal testing (NIPT) was carried out to determine the risk of fetal chromosome aneuploidy. Aminiocentesis was proceeded for fetal chromosomal karyotyping and copy number variation sequencing (CNV-seq). The fetus was subjected to systematic ultrasound screening in the second trimester. RESULTS: NIPT has indicated there was a loss of fetal sex chromosome. Karotyping of the amniocyte showed a mosaic sex chromosome abnormality 45,X[53]/46,X,+mar[7]. The result of fetal DNA CNV-seq was seq[GRCh37]del(Yq11.1q12) chrY: g.13 104 553-28 819 361del, seq[GRCh37]del(Yp11.32p11.2) chrY: g.10 001-9 873 915del (mosaic ratio: 30%). Ultrasonography discovered that the fetus had renal dysplasia and male external genitalia. The karyotypes of the couple were both normal. CONCLUSION: Multiple genetic tests should be carried out for fetus with a high risk for chromosome aneuploidies signaled by NIPT. It is difficult to predict the post-natal phenotype for fetuses with mosaic sex chromosomal aneuploidies. The couple should be carefully counseled upon genetic counseling.

Myocardial Infarction Induces Cardiac Fibroblast Transformation within Injured and Noninjured Regions of the Mouse Heart.

Heart failure (HF) is associated with pathological remodeling of the myocardium, including the initiation of fibrosis and scar formation by activated cardiac fibroblasts (CFs). Although early CF-dependent scar formation helps prevent cardiac rupture by maintaining the heart's structural integrity, ongoing deposition of the extracellular matrix in the remote and infarct regions can reduce tissue compliance, impair cardiac function, and accelerate progression to HF. In our study, we conducted mass spectrometry (MS) analysis to identify differentially altered proteins and signaling pathways between CFs isolated from 7 day sham and infarcted murine hearts. Surprisingly, CFs from both the remote and infarct regions of injured hearts had a wide number of similarly altered proteins and signaling pathways that were consistent with fibrosis and activation into pathological myofibroblasts. Specifically, proteins enriched in CFs isolated from MI hearts were involved in pathways pertaining to cell-cell and cell-matrix adhesion, chaperone-mediated protein folding, and collagen fibril organization. These results, together with principal component analyses, provided evidence of global CF activation postinjury. Interestingly, however, direct comparisons between CFs from the remote and infarct regions of injured hearts identified 15 differentially expressed proteins between MI remote and MI infarct CFs. Eleven of these proteins (Gpc1, Cthrc1, Vmac, Nexn, Znf185, Sprr1a, Specc1, Emb, Limd2, Pawr, and Mcam) were higher in MI infarct CFs, whereas four proteins (Gstt1, Gstm1, Tceal3, and Inmt) were higher in MI remote CFs. Collectively, our study shows that MI injury induced global changes to the CF proteome, with the magnitude of change reflecting their relative proximity to the site of injury.