Sleep quality during pregnancy and fetal growth: A prospective cohort study.

The aim of this study is to investigate the association between sleep quality during pregnancy and fetal growth. Pregnant women and their fetuses at 16-20 gestational weeks in Nantong Maternal and Child Health Hospital were recruited. Women were classified as having "good sleep quality" (Pittsburgh Sleep Quality Index score ≤ 5) and "poor sleep quality" (Pittsburgh Sleep Quality Index score > 5) according to the Pittsburgh Sleep Quality Index scores. The fetal growth was evaluated by three ultrasonographic examinations, birth weight and birth length. We used general linear model and multiple linear regression models to estimate the associations. A total of 386 pairs of mother and infant were included in the data analysis. After adjusting for gestational weight gain, anxiety and depression, fetuses in the good sleep quality group had greater abdominal circumference (p = 0.039 for 28-31+6 weeks gestation, p = 0.012 for 37-40+6 weeks gestation) and femur length (p = 0.014 for 28-31+6 weeks gestation, p = 0.041for 37-40+6 weeks gestation) at 28-31+6 weeks gestation and 37-40+6 weeks gestation, and increased femur length (p = 0.007) at 28-31+6 weeks gestation. Birth weights (p = 0.018) were positively associated with sleep quality. Poor sleep quality was associated with poor intrauterine physical development, decreased abdominal circumference and femur length, and lower birth weight after adjusting for confounding factors. Attention to the fetal growth of pregnant women with poor sleep quality has the potential to decrease the risk of adverse fetal outcomes.

Plasma Cell-Free DNA Is a Potential Biomarker for Diagnosis of Calcific Aortic Valve Disease.

INTRODUCTION: Calcific aortic valve disease (CAVD) is the third most common cardiovascular disease in aging populations. Despite a growing number of biomarkers having been shown to be associated with CAVD, a marker suitable for routine testing in clinical practice is still needed. Plasma cell-free DNA (cfDNA) has been suggested as a biomarker for diagnosis and prognosis in multiple diseases. In this study, we aimed to test whether cfDNA could be used as a biomarker for the diagnosis of CAVD. METHODS: Serum samples were collected from 137 diagnosed CAVD patients and 180 normal controls. The amount of cfDNA was quantified by amplifying a short fragment (ALU 115) and a long fragment (ALU 247) using quantitative real-time PCR. The cfDNA integrity (cfDI) was calculated as the ratio of ALU247 to ALU115. The association between CAVD and cfDI was evaluated using regression analysis. RESULTS: CAVD patients had increased ALU 115 fragments (median, 185.14 (416.42) versus 302.83 (665.41), p < 0.05) but a decreased value of cfDI (mean, 0.50 ± 0.25 vs. 0.41 ± 0.26, p < 0.01) in their serum when compared to controls. This difference was more dramatic in non-rheumatic CAVD patients (p < 0.001) versus rheumatic CAVD patients (no significant difference). Similarly, CAVD patients with bicuspid aortic valve (BAV) (p < 0.01) showed a greater difference than non-BAV CAVD patients (p < 0.05). Linear regression and logistic regression showed that cfDI was independently and significantly associated with the presence of CAVD (95% CI, 0.096 to 0.773, p < 0.05). The ROC assay revealed that cfDI combined with clinical characteristics had a better diagnostic value than cfDI alone (AUC = 0.6191, p < 0.001). CONCLUSION: cfDI may be a potential biomarker for diagnosis of CAVD.

Antinuclear antibody (ANA) status predicts immune-related adverse events in liver cancer patients undergoing anti-PD-1 therapy.

Immune-related adverse events (irAEs) clinically resemble autoimmune diseases, indicating autoantibodies could be potential biomarkers for the prediction of irAEs. This study aimed to assess the predictive value of peripheral blood antinuclear antibody (ANA) status for irAEs, considering the time and severity of irAEs, as well as treatment outcome in liver cancer patients administered anti-PD-1 therapy. Ninety-three patients with advanced primary liver cancer administered anti-PD-1 treatment were analyzed retrospectively. They were divided into the ANA positive (ANA+, titer ≥ 1:100) and negative (ANA-, titer < 1:100) groups. Development of irAEs, progression-free survival (PFS), and overall survival (OS) were assessed. Compared with ANA- patients, ANA+ cases were more prone to develop irAEs (43.3% vs. 19.2%, P = 0.031). With the increase of ANA titers, the frequency of irAEs increased. The time interval between anti-PD-1 therapy and the onset of irAEs was significantly shorter in ANA+ patients compared with the ANA- group (median, 1.7 months vs. 5.0 months, P = 0.022). Moreover, the time between anti-PD-1 therapy and irAE occurrence decreased with increasing ANA titer. In addition, PFS and OS were decreased in ANA+ patients compared with the ANA- group (median PFS, 2.8 months vs. 4.2 months, P = 0.043; median OS, 21.1 months vs. not reached, P = 0.041). IrAEs occur at higher frequency in ANA+ liver cancer patients undergoing anti-PD-1 therapy. ANA titer could help predict irAE development and treatment outcome in these patients.

Umbilical artery cord blood glucose predicted hypoglycemia in gestational diabetes mellitus and other at-risk newborns.

BACKGROUND: To explore the value of umbilical artery cord blood glucose (UACBG) in predicting hypoglycemia in gestational diabetes mellitus (GDM) and other at-risk newborns, and to provide a cut-off UACBG value for predicting hypoglycemia occurrence. METHODS: In this prospective study, we enrolled at-risk infants delivered vaginally, including neonates born to mothers with GDM, premature, macrosomic, and low birth weight. We separated the infants into GDM group and other at-risk group. All subjects underwent UACBG measurement during delivery. Neonatal peripheral blood glucose measurement was performed at 0.5 and 2 h after birth. The predictive performance of UACBG for neonatal hypoglycemia was assessed using receiver operating characteristic curve (ROC), area under curve (AUC), sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV). RESULTS: 916 newborns were included, with 538 in GDM group and 378 in other at-risk group. 85 neonates were diagnosed hypoglycemia within 2 h after birth, including 36 belonging to GDM group and 49 to other at-risk group. For hypoglycemia prediction within 2 h, the best cut-off of UACBG was 4.150 mmol/L, yielding an AUC of 0.688 (95% CI 0.625-0.751) and a NPV of 0.933. In detail, the AUC was 0.680 in GDM group (95% CI 0.589-0.771), with the optimal cut-off of 4.150 mmol/L and a NPV of 0.950. In other at-risk group, the AUC was 0.678(95% CI 0.586-0.771), the best threshold was 3.950 mmol/L and the NPV was 0.908. No significant differences were observed between GDM group and other at-risk group in AUC at 0.5 h, 2 h and within 2 h. CONCLUSIONS: UACBG has a high NPV for predicting neonatal hypoglycemia within 2 h after birth. It was implied that individuals with cord blood glucose levels above the threshold were at lower risk for hypoglycemia. UACBG monitoring provides evidence for subsequent classified management of hypoglycemia.

An SCD1-dependent mechanoresponsive pathway promotes HCC invasion and metastasis through lipid metabolic reprogramming.

Matrix stiffness promotes hepatocellular carcinoma (HCC) metastasis. This study examined the contribution of lipid metabolic reprogramming to matrix stiffness-induced HCC metastasis. HCC cells were cultured on mechanically tunable polyacrylamide gels and subjected to lipidomic analysis. The key enzyme that responded to matrix stiffness and regulated lipid metabolism was identified. The comparative lipidomic screening revealed that stearoyl-CoA desaturase 1 (SCD1) is a mechanoresponsive enzyme that reprogrammed HCC cell lipid metabolism. The genetic and pharmacological inhibition of SCD1 expression/activity altered the cellular lipid composition, which in turn impaired plasma membrane fluidity and inhibited in vitro invasive motility of HCC cells in response to high matrix stiffness. Knockdown of SCD1 suppressed HCC invasion and metastasis in vivo. Conversely, the overexpression of SCD1 or exogenous administration of its product oleic acid augmented plasma membrane fluidity and rescued in vitro invasive migration in HCC cells cultured on soft substrates, mimicking the effects imposed by high matrix stiffness. In human HCC tissues, collagen content, a marker of increasing matrix stiffness, and increased expression of SCD1 together predicted poor survival of HCC patients. An SCD1-dependent mechanoresponsive pathway that responds to increasing matrix stiffness in the tumor microenvironment promotes HCC invasion and metastasis through lipid metabolic reprogramming.

Outcomes of vertex-vertex vs. vertex-breech presentation in twin pregnancy after vaginal delivery in China.

OBJECTIVE: To compare the maternal and neonatal outcomes of twin pregnancies between vertex and nonvertex presentations of the second twin in vaginal delivery. METHODS: In this unicentric retrospective cohort study, we collected data from 213 cases of vaginal twin deliveries from January 2016 to July 2020. Participants were divided into the vertex-vertex presentation group (VV) and vertex-breech presentation group (VB). Data on maternal and neonatal outcomes were compared between groups. RESULTS: Among the 213 mothers and 426 infants (213 twin pairs), there were 140 women in the VV group and 73 women in the VB group (65.73% vs. 34.27%). Infants in the VB group had a higher incidence of admission to NICU (51.43% vs. 68.49%, p = 0.017), lower 1-min (11.43% vs. 28.77%, p < 0.001) and 5-minute Apgar scores (1.43% vs. 4.11%, p = 0.043) for the second twin. However, after the adjustment for sex of the twin, birth weight, chorionicity, and gestational age, the greater risk of admission to NICU and low 5-min Apgar score was no longer significantly different. CONCLUSION: VB twins are at no greater overall risk of a poor outcome due to breech presentation in the second twin. However, the presentation of the second fetus represents a risk factor for a low 1-min Apgar score. Obstetricians and midwives should consider appropriate interventions for second twins who present breech versus vertex.

Development of nurses' knowledge questionnaire of chest tube maintenance and management.

OBJECTIVE: The lack of chest tube maintenance and management knowledge in nurses can lead to serious adverse consequences. The purpose of this study was to develop a chest tube maintenance and management knowledge questionnaire for clinical nurses, and to verify its reliability and validity. METHODS: Based on literature review and expert consultation, a questionnaire on chest tube maintenance and management knowledge of clinical nurses was designed, and the reliability and validity of the questionnaire were tested in 60 clinical nurses. RESULTS: The initial questionnaire of chest tube maintenance and management knowledge for clinical nurses included 20 items, and three dimensions were finally determined by expert consultation method, including 15 items. The Cronbach's α coefficient of the questionnaire was 0.850, and the Cronbach's α coefficient of each dimension ranged from 0.704 to 0.743. Spearman-brown's split reliability was 0.756. The content validity (content validity index [CVI]) of each item of the questionnaire ranged from 0.833 to 1.000, and the total CVI was 0.978. CONCLUSIONS: The clinical nurses' knowledge questionnaire developed in this study has good reliability and validity, which can effectively and objectively evaluate clinical nurses' mastery of chest tube maintenance and management knowledge.

One-pot multi-step cascade protocols toward ß-indolyl sulfoximidoyl amides via intermolecular trapping of an α-indolylpalladium complex by CO.

Various ß-indolyl sulfoximidoyl amides were efficiently prepared from ortho-iodoanilines, propargyl bromides, 1 atm of CO, and substituted NH-sulfoximines, through a palladium-catalyzed indole annulation/carbonyl insertion/C-N bond formation cascade. Mostly good to high yields of the products were obtained through this multi-step, one-pot reaction protocol under very gentle reaction conditions. The obtained ß-indolyl sulfoximidoyl amides could be converted into biologically interesting sulfoximine analogues that contain a tryptamine moiety.

Treatment-damaged hepatocellular carcinoma promotes activities of hepatic stellate cells and fibrosis through GDF15.

The aim of this study was to investigate whether treatment-damaged hepatocellular carcinoma (HCC) would accelerate liver cirrhosis through promoting the activities of hepatic stellate cells (HSCs). HCC cells were exposed to chemotherapeutic agent or hypoxia to mimic the transarterial chemoembolization (TACE)-like treatment. Growth differentiation factor 15 (GDF15) expression was increased in cisplatin- or hypoxia-treated HCC cells. Treatment-induced GDF15 increase in HCC cells was mediated by p38MAPK, JNK, ERK1/2 activation. GDF15 from treatment-damaged HCC cells enhanced the proliferation and collagen synthesis of HSCs through ERK1/2- and Smad3-dependent pathways. Metformin significantly reduced the GDF15 production from treatment-damaged HCC cells by targeting JNK. The use of metformin could attenuate the in vivo fibrotic activities of HSCs promoted by treatment-damaged HCC cells and inhibit GDF15 expression. In conclusion, treatment-damaged HCC accelerates fibrosis by promoting the activities of HSCs via GDF15 secretion, which could be reversed by metformin. This provides a potential therapeutic target for alleviating TACE-aggravated liver cirrhosis.

Activated hepatic stellate cells promote progression of post-heat residual hepatocellular carcinoma from autophagic survival to proliferation.

BACKGROUND: Microscopic residual tumor often occurs after thermal ablation for medium-large hepatocellular carcinoma (HCC), leading to early aggressive recurrence or late relapse during follow-up. The mechanism how microscopic residual HCC cells survive sublethal heat stress and develop rapid outgrowth remains poorly understood. METHODS: HCC cells were exposed to sublethal heat treatment and co-cultured with conditioned media from activated HSCs (HSC-CM). Changes of cell proliferation, parameters of cell autophagy and activation of signaling pathways in heat-treated residual HCC cells were analyzed. An HCC orthotopic model was subjected to partial thermal ablation and antitumor effects of a combined treatment regimen were studied. RESULTS: HCC cells survived sublethal heat stress via activation of autophagy. HSC-CM enhanced autophagic survival within 24 h and then promoted proliferation of heat-treated residual HCC cells through HGF/c-Met signaling. Inhibition of autophagy or c-Met increased apoptosis of heat-treated residual HCC cells and reversed the protective effect of HSC-CM. HGF modulated biological status in autophagic survival or proliferation of heat-treated residual HCC through HGF/c-Met/ERK signaling and downstream components of ATG5/Beclin1 or cyclinD1. In an animal model, inhibiting autophagy in combination with c-Met inhibitor significantly thwarted tumor progression of residual HCC after incomplete thermal ablation via the suppressed autophagy, the decreased proliferation and the increased apoptosis. CONCLUSIONS: Activated HSCs promote progression of residual HCC cells after sublethal heat treatment from autophagic survival to proliferation via HGF/c-Met signaling. A combined treatment regimen of inhibiting autophagy and c-Met signaling could be used to suppress tumor progression of residual HCC after incomplete thermal ablation.

Folic acid delays development of atherosclerosis in low-density lipoprotein receptor-deficient mice.

Many studies support the cardioprotective effects of folic acid (FA). We aimed to evaluate the utility of FA supplementation in preventing the development of atherosclerotic in low-density lipoprotein receptor-deficient (LDLR-/-) mice and to elucidate the molecular processes underlying this effect. LDLR-/- mice were randomly distributed into four groups: control group, HF group, HF + FA group and the HF + RAPA group. vascular smooth muscle cells (VSMCs) were divided into the following four groups: control group, PDGF group, PDGF + FA group and PDGF + FA + RAPA group. Blood lipid levels, oxidative stress and inflammatory cytokines were measured. Atherosclerosis severity was evaluated with oil red O staining. Haematoxylin and eosin (H&E) staining was used to assess atherosclerosis progression. Immunohistochemical staining was performed with antismooth muscle α-actin (α-SMA) antibodies and anti-osteopontin (OPN) antibodies that demonstrate VSMC dedifferentiation. The protein expression of α-SMA, OPN and mechanistic target of rapamycin (mTOR)/p70S6K signalling was detected by Western blot analysis. FA and rapamycin reduced serum levels of total cholesterol, triacylglycerol, LDL, inhibiting oxidative stress and the inflammatory response. Oil red O and H&E staining demonstrated that FA and rapamycin inhibited atherosclerosis. FA and rapamycin treatment inhibited VSMC dedifferentiation in vitro and in vivo, and FA and rapamycin attenuated the mTOR/p70S6K signalling pathway. Our findings suggest that FA attenuates atherosclerosis development and inhibits VSMC dedifferentiation in high-fat-fed LDLR-/- mice by reduced lipid levels and inhibiting oxidative stress and the inflammatory response through mTOR/p70S6K signalling pathway.

Extracellular matrix collagen I promotes the tumor progression of residual hepatocellular carcinoma after heat treatment.

BACKGROUND: Accelerated malignant behaviors induced by insufficient thermal ablation have been increasingly reported, however, the exact mechanisms are still unclear. Here, we investigated the importance of the extracellular matrix (ECM) in modulating the progression of residual hepatocellular carcinoma (HCC) after heat treatment. METHODS: Heat-exposed residual HCC cells were cultured in different ECM gels. We used basement membrane gel (Matrigel) to simulate the normal microenvironment and collagen I to model the pathological stromal ECM. The alterations of morphology and parameters of proliferation, epithelial-mesenchymal transition (EMT) and stemness were analyzed in vitro and in vivo. RESULTS: Increased collagen I deposition was observed at the periablational zone after incomplete RFA of HCC in a xenograft model. The markers of cell proliferation, EMT, motility and progenitor-like traits of heat-exposed residual HCC cells were significantly induced by collagen I as compared to Matrigel (p values all < 0.05). Importantly, collagen I induced the activation of ERK phosphorylation in heat-exposed residual HCC cells. ERK1/2 inhibitor reversed the collagen I-promoted ERK phosphorylation, cell proliferative, protrusive and spindle-like appearance of heat-treated residual HCC cells in vitro. Moreover, collagen I promoted the in vivo tumor progression of heat-exposed residual HCC cells, and sorafenib markedly reversed the collagen I-mediated protumor effects. CONCLUSIONS: Our findings demonstrate that collagen I could enhance the aggressive progression of residual HCC cells after suboptimal heat treatment and sorafenib may be a treatment approach to thwart this process.

[Comparative metabolomics analysis of metabolic pathways in the high-yielding mutant strain of avilamycin].

Avilamycin (AVI) is an oligosaccharide antibiotic that has strong inhibitory effect on Gram-positive bacteria. It is widely used in livestock and poultry farming. However, the use of traditional breeding techniques and immature fermentation process have become the key factors limiting its commercialization. In this study, we used comparative metabolomics techniques to examine the difference in intracellular metabolism between a high-yield AVI mutant strain modified by ribosome engineering technology and the parental strain. GC-MS analysis was conducted on mycelia samples taken on days 4, 6, and 8 of fermentation, resulting in the detection of a total of 112 compounds. After comparison with the NIST library, 29 intracellular metabolites were accurately identified. Two-dimensional principal component analysis (PCA) revealed significant differences in metabolites between the mutant strain and the parental strain at different time points. Orthogonal partial least squares-discriminant analysis (OPLS-DA) identified 11 intracellular metabolites that were closely related to AVI biosynthesis. KEGG metabolic pathway enrichment analysis showed that avilamycin synthesis was closely related to carbohydrate metabolism and amino acid metabolism. Six key differential metabolites were selected: L-valine, L-serine, L-alanine, D-galactose, D-cellobiose, and D-glucose. Upregulation of these metabolites in the mutant strain enhanced its metabolic flow for AVI synthesis. After 8 days of fermentation, the mutant strain produced 76.86% more AVI than the parental strain. The findings of this study serve as reference for the future rational optimization of avilamycin fermentation.

The efficacy and safety of CT-guided localization of pulmonary nodules by medical adhesives containing methylene blue before surgery.

Background: The accurate preoperative localization of pulmonary nodules is essential for a successful video-assisted thoracic surgery (VATS). The aim of this research was to clarify the efficacy and safety of CT-guided localization of pulmonary nodules by mixture of methylene blue and medical adhesive. Methods: Between January 2020 and January 2021, 103 subjects who have received the CT-guidance pulmonary nodules localization operation were included and retrospectively analyzed. The data on efficiency and complications of preoperative localization using medical adhesives mixed with methylene blue mixture were collected and analyzed. Results: 103 patients with 111 localized pulmonary nodules were included, 95 of whom had one nodule and 8 of whom had two nodules. The nodule localization success rate reaches as high as 100 %. The mean diameter of pulmonary nodules was 9.50 ± 3.67 mm. The mean distance of pulmonary nodule and pleural surface was 19.95 ± 14.92 mm. The mean depth of localized adhesive in the lung parenchyma was 18.99 ± 11.62 mm, and the mean time required for localization was 16.98 ± 5.72 min. The average time from the nodule localization to VATS surgery was 16.97 ± 7.34 h. The common complications of localization were minor pulmonary hemorrhage (9.74 %) and mild pneumothorax (15.53 %). Besides, pulmonary hemorrhage was related with depths of medical adhesives and nodules in lung parenchyma (p = 0.018 and 0.002, respectively). Conclusion: Medical adhesive mixed with methylene blue is safe and effective in pulmonary nodules localization for VATS, and surgeons have flexibility in scheduling the procedure.

Prenatal endocrine-disrupting chemicals exposure and impact on offspring neurodevelopment: A systematic review and meta-analysis.

PURPOSE: Considering that endocrine disruptors have certain effects on fetal growth, we conducted a systematic review of epidemiological literature to elucidate the correlation between exposure to endocrine-disrupting chemicals during pregnancy and the neurodevelopment of offspring. METHOD: We systematically explored PubMed, Web of Science, and CINAHL databases from inception to April 4, 2023. References from pertinent studies were reviewed, and data regarding the link between maternal prenatal EDC exposure and offspring neurological development were compiled. A domain-based approach was used to evaluate studies of neurodevelopmental effects in children ≤3 years old by two reviewers, including cognition, motor, behavior, language, and non-verbal ability. RESULTS: A comprehensive search yielded 45,373 articles, from which 48 articles, involving 26,005 mother-child pairs, met the criteria and were subsequently included in our analysis. The results revealed that EDC exposure during pregnancy had a significant impact on offspring neurobehavior development, especially in cognition, motor, and language. Our findings indicated adverse associations between prenatal exposure to metals and offspring cognition (before 12 months: ß coefficient: -0.28; 95 % CI, -0.50 to -0.06; 1-3 years old: ß coefficient: -0.55; 95 % CI: -1.08 to -0.02). Furthermore, metals (ß coefficient: -0.71; 95 % CI: -1.23 to -0.19) and phthalates (ß coefficient: -0.69; 95 % CI: -1.05 to -0.33) exposure exhibited detrimental effects on motor development from1-3 years old, while poly-fluoroalkyl substances were linked to the disruption of offspring language development (ß coefficient: -1.01; 95 % CI: -1.90 to -0.11) within this timeframe. Additionally, exposure to EDCs during pregnancy had a negative impact on cognition development among girls from 12 to 36 months of age (ß coefficient: -0.53; 95 % CI: -1.01 to -0.06). CONCLUSION: Prenatal exposure to EDCs, especially metals, phthalates and, poly-fluoroalkyl substances, was associated with disrupting the development of offspring neurobehavior in the short and long term. Additionally, cognitive development showed gender differences due to prenatal endocrine-disrupting chemicals exposure.

Physical activity trajectory during pregnancy and associations with maternal fatigue using a growth mixture modeling approach.

The purpose of this study was to investigate the associations of physical activity trajectories with maternal fatigue. Pregnant women provided objectively assessed physical activity data by Pregnancy Physical Activity Questionnaire four times. Fatigue scale-14 was used to assess fatigue during pregnancy. Growth mixture modelling characterized physical activity trajectories across pregnancy. The generalized estimating equations was used to analyze the relationship between different physical activity profiles and fatigue in pregnant women. A total of 626 pregnant women were included in analysis in a teaching hospital in Nantong city. Fatigue (total, mental and physical) was not different between two groups based on total energy expenditure of PA (constantly high vs. constantly low). The pregnant women in "constantly high household PA" group had the higher fatigue compared to "constantly low household PA" (P < 0.05) and "constantly medium household PA" (P < 0.05). The pregnant women in "constantly high sport PA" group had lower fatigue compared to "constantly low sport PA" (P < 0.05). Household PA and sport PA were still an independent influencing factor for fatigue after controlling for confounding variables. Specifically, we observed that higher household PA and lower sport PA were associated with higher fatigue during pregnancy.

Epigenetic repression of Cend1 by lysine-specific demethylase 1 is essential for murine heart development.

Epigenetic regulation of heart development remains incompletely understood. Here we show that LSD1, a histone demethylase, plays a crucial role in regulating cardiomyocyte proliferation during heart development. Cardiomyocyte-specific deletion of Lsd1 in mice inhibited cardiomyocyte proliferation, causing severe growth defect of embryonic and neonatal heart. In vivo RNA-seq and in vitro functional studies identified Cend1 as a target suppressed by LSD1. Lsd1 loss resulted in elevated Cend1 transcription associated with increased active histone mark H3K4me2 at Cend1 promoter. Cend1 knockdown relieved the cell-cycle arrest and proliferation defect caused by LSD1 inhibition in primary rat cardiomyocytes. Moreover, genetic deletion of Cend1 rescued cardiomyocyte proliferation defect and embryonic lethality in Lsd1 null embryos. Consistently, LSD1 promoted the cell cycle of cardiomyocytes derived from human-induced pluripotent stem cells by repressing CEND1. Together, these findings reveal an epigenetic regulatory mechanism involving the LSD1-CEND1 axis that controls cardiomyocyte proliferation essential for murine heart development.

Early ambulation and postoperative recovery of patients with lung cancer under thoracoscopic surgery-an observational study.

BACKGROUND: Enhanced recovery after surgery guidelines in China recommend early ambulation within 24 h after surgery. The aims of this audit were to investigate the early ambulation of patients with lung cancer under thoracoscopic surgery, and to explore the influence of different ambulation time on postoperative rehabilitation of patients. METHODS: Using observational study method, observe and record of 226 cases under the thoracoscope surgery early ambulation of patients with lung cancer. Data collected included postoperative bowel movements, chest tube extubation time, length of hospital stay, postoperative pain and the incidence of postoperative complications. RESULTS: The time of first ambulation was (34.18 ± 17.18) h, the duration was (8.26 ± 4.62) min, and the distance was (54.94 ± 46.06) m. The time of first postoperative defecation, the time of chest tube extubation and the length of hospital stay were significantly shortened in patients who ambulate within 24 h, and the pain score on the third day after surgery was decreased, and the incidence of postoperative complications was reduced, with statistical significance (P < 0.05). CONCLUSION: Early ambulation within 24 h after thoracoscopic surgery for lung cancer patients can promote the recovery of intestinal function, early removal of chest tube, shorten the length of hospital stay, relieve pain, reduce the incidence of complications, and facilitate the rapid recovery of patients.

Short C-terminal Musashi-1 proteins regulate pluripotency states in embryonic stem cells.

The RNA-binding protein Musashi-1 (MSI1) regulates the proliferation and differentiation of adult stem cells. However, its role in embryonic stem cells (ESCs) and early embryonic development remains poorly understood. Here, we report the presence of short C-terminal MSI1 (MSI1-C) proteins in early mouse embryos and mouse ESCs, but not in human ESCs, under conventional culture conditions. In mouse embryos and mESCs, deletion of MSI1-C together with full-length MSI1 causes early embryonic developmental arrest and pluripotency dissolution. MSI1-C is induced upon naive induction and facilitates hESC naive pluripotency acquisition, elevating the pluripotency of primed hESCs toward a formative-like state. MSI1-C proteins are nuclear localized and bind to RNAs involved in DNA-damage repair (including MLH1, BRCA1, and MSH2), conferring on hESCs better survival in human-mouse interspecies cell competition and prolonged ability to form blastoids. This study identifies MSI1-C as an essential regulator in ESC pluripotency states and early embryonic development.

ß-Catenin regulates endocardial cushion growth by suppressing p21.

Endocardial cushion formation is essential for heart valve development and heart chamber separation. Abnormal endocardial cushion formation often causes congenital heart defects. ß-Catenin is known to be essential for endocardial cushion formation; however, the underlying cellular and molecular mechanisms remain incompletely understood. Here, we show that endothelial-specific deletion of ß-catenin in mice resulted in formation of hypoplastic endocardial cushions due to reduced cell proliferation and impaired cell migration. By using a ß-catenin DM allele in which the transcriptional function of ß-catenin is selectively disrupted, we further reveal that ß-catenin regulated cell proliferation and migration through its transcriptional and non-transcriptional function, respectively. At the molecular level, loss of ß-catenin resulted in increased expression of cell cycle inhibitor p21 in cushion endocardial and mesenchymal cells in vivo. In vitro rescue experiments with HUVECs and pig aortic valve interstitial cells confirmed that ß-catenin promoted cell proliferation by suppressing p21. In addition, one savvy negative observation is that ß-catenin was dispensable for endocardial-to-mesenchymal fate change. Taken together, our findings demonstrate that ß-catenin is essential for cell proliferation and migration but dispensable for endocardial cells to gain mesenchymal fate during endocardial cushion formation. Mechanistically, ß-catenin promotes cell proliferation by suppressing p21. These findings inform the potential role of ß-catenin in the etiology of congenital heart defects.