Prenatal, perinatal and parental risk factors for autism spectrum disorder in China: a case- control study.

BACKGROUND: Autism spectrum disorder (ASD) is heritable neurodevelopmental disorders (NDDs), but environmental risk factors have also been suggested to a play a role in its development. Prenatal, perinatal and parental factors have been associated with an increased risk of ASD in children. The aim of the present study was to explore the prenatal, perinatal, and parenting risk factors in children with autism spectrum disorder (ASD) from Beijing, China by comparing them with typically developing (TD) children. METHODS: A sample of 151 ASD children's parents who from rehabilitation institutions in Beijing were enrolled in this study, and an additional 151 children from kindergartens in Beijing were recruited as a control group (child age: mean = 4.4 years). TD children were matched according to age, sex and maternal education. We explored the maternal AQ (Autism Spectrum Quotient) scores (mean:19.40-19.71, no significant difference between two groups) to referring the genetic baseline. This study evaluated 17 factors with unadjusted and adjusted analyses. RESULTS: Birth asphyxia was associated with a more than a thirteen-fold higher risk of ASD (adjusted odds ratio (AOR) = 13.42). Breastfeeding difficulties were associated with a higher risk of ASD(AOR = 3.46). Parenting influenced the risk of ASD, with low responding (LR) and harsh or neglectful parenting associated with a higher risk of ASD in offspring (AOR = 2.37 for LR, AOR = 3.42 for harsh parenting and AOR = 3.01 for neglectful parenting). Maternal fever during pregnancy was associated with a higher risk of ASD in offspring (AOR = 3.81). CONCLUSIONS: Many factors were associated with ASD in offspring. Further assessment is needed to elucidate the role of modifiable environmental factors to inform prevention strategies.

Biomedical application of terahertz imaging technology: a narrative review.

Background and Objective: Terahertz (THz) imaging has wide applications in biomedical research due to its properties, such as non-ionizing, non-invasive and distinctive spectral fingerprints. Over the past 6 years, the application of THz imaging in tumor tissue has made encouraging progress. However, due to the strong absorption of THz by water, the large size, high cost, and low sensitivity of THz devices, it is still difficult to be widely used in clinical practice. This paper provides ideas for researchers and promotes the development of THz imaging in clinical research. Methods: The literature search was conducted in the Web of Science and PubMed databases using the keywords "Terahertz imaging", "Breast", "Brain", "Skin" and "Cancer". A total of 94 English language articles from 1 January, 2017 to 30 December, 2022 were reviewed. Key Content and Findings: In this review, we briefly introduced the recent advances in THz near-field imaging, single-pixel imaging and real-time imaging, the applications of THz imaging for detecting breast, brain and skin tissues in the last 6 years were reviewed, and the advantages and existing challenges were identified. It is necessary to combine machine learning and metamaterials to develop real-time THz devices with small size, low cost and high sensitivity that can be widely used in clinical practice. More powerful THz detectors can be developed by combining graphene, designing structures and other methods to improve the sensitivity of the devices and obtain more accurate information. Establishing a THz database is one of the important methods to improve the repeatability and accuracy of imaging results. Conclusions: THz technology is an effective method for tumor imaging. We believe that with the joint efforts of researchers and clinicians, accurate, real-time, and safe THz imaging will be widely applied in clinical practice in the future.

Electrosynthesis of 5-Aminocoumaran Derivatives from Olefins and Aminophenols.

The electrochemical synthesis of 5-aminocoumaran derivatives from easily oxidizable aminophenols and readily available olefins is described. The reaction efficiently produces 5-aminocoumarans in high yield under mild and environmentally friendly conditions without the necessity of catalysts, additives, oxidizing agents, or sacrificial reagents. Hydrogen as the sole byproduct of the reaction makes the method clean, highly atom-efficient, and step-economical.

Electrochemical C(sp2)-H/N-H "formal" cross-dehydrogenative coupling of olefins with benzotriazoles for synthesis of N-vinyl benzotriazoles.

The paper details an electrochemical method that couples olefins with benzotriazoles to form C(sp2)-N bonds, enabling the synthesis of N-vinyl benzotriazoles in moderate to good yields. nBu4NI functions as both an electrolyte and an iodine mediator, and the method does not require oxidants or metals. It is a highly atom-economical and clean reaction, with hydrogen as the sole byproduct.

Immunochemotherapy alone or immunochemotherapy plus subsequent locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma.

BACKGROUND: To demonstrate whether the benefit of locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma remains in the immunotherapy era and which patients can benefit from radiotherapy. MATERIALS AND METHODS: A total of 273 histopathology-confirmed de novo metastatic nasopharyngeal carcinoma was enrolled between May 2017 and October 2021 if receiving immunochemotherapy with or without subsequent intensity-modulated radiotherapy to the nasopharynx and neck. We compared the progression-free survival, overall survival, and safety between the two groups. Additionally, subgroup analysis was conducted and a scoring model was developed to identify suitable patients for radiation. RESULTS: There were 95 (34.8 %) patients with immunochemotherapy alone, and 178 (65.2 %) with immunochemotherapy plus subsequent locoregional radiotherapy. With a median follow-up time of 18 months, patients with immunochemotherapy plus subsequent radiotherapy had higher 1-year progression-free survival (80.6 % vs. 65.1 %, P < 0.001) and overall survival (98.3 % vs. 89.5 %, P = 0.001) than those with immunochemotherapy alone. The benefit was retained in multivariate analysis and propensity score-matched analysis. Mainly, it was more significant in patients with oligometastases, EBV DNA below 20,200 copies/mL, and complete or partial relapse after immunochemotherapy. The combined treatment added grade 3 or 4 anemia and radiotherapy-related toxicities. CONCLUSION: Immunochemotherapy plus subsequent locoregional radiotherapy prolonged the survival of de novo metastatic nasopharyngeal carcinoma with tolerable toxicities. A scoring model based on oligometastases, EBV DNA level, and response after immunochemotherapy could facilitate individualized management.

Artificial intelligence aided precise detection of local recurrence on MRI for nasopharyngeal carcinoma: a multicenter cohort study.

Background: MRI is the routine examination to surveil the recurrence of nasopharyngeal carcinoma, but it has relatively lower sensitivity than PET/CT. We aimed to find if artificial intelligence (AI) could be competent pre-inspector for MRI radiologists and whether AI-aided MRI could perform better or even equal to PET/CT. Methods: This multicenter study enrolled 6916 patients from five hospitals between September 2009 and October 2020. A 2.5D convolutional neural network diagnostic model and a nnU-Net contouring model were developed in the training and test cohorts and used to independently predict and visualize the recurrence of patients in the internal and external validation cohorts. We evaluated the area under the ROC curve (AUC) of AI and compared AI with MRI and PET/CT in sensitivity and specificity using the McNemar test. The prospective cohort was randomized into the AI and non-AI groups, and their sensitivity and specificity were compared using the Chi-square test. Findings: The AI model achieved AUCs of 0.92 and 0.88 in the internal and external validation cohorts, corresponding to the sensitivity of 79.5% and 74.3% and specificity of 91.0% and 92.8%. It had comparable sensitivity to MRI (e.g., 74.3% vs. 74.7%, P = 0.89) but lower sensitivity than PET/CT (77.9% vs. 92.0%, P < 0.0001) at the same individual-specificities. The AI model achieved moderate precision with a median dice similarity coefficient of 0.67. AI-aided MRI improved specificity (92.5% vs. 85.0%, P = 0.034), equaled PET/CT in the internal validation subcohort, and increased sensitivity (81.9% vs. 70.8%, P = 0.021) in the external validation subcohort. In the prospective cohort of 1248 patients, the AI group had higher sensitivity than the non-AI group (78.6% vs. 67.3%, P = 0.23), albeit nonsignificant. In future randomized controlled trials, a sample size of 3943 patients in each arm would be required to demonstrate the statistically significant difference. Interpretation: The AI model equaled MRI by expert radiologists, and AI-aided MRI by expert radiologists equaled PET/CT. A larger randomized controlled trial is warranted to demonstrate the AI's benefit sufficiently. Funding: The Sun Yat-sen University Clinical Research 5010 Program (2015020), Guangdong Basic and Applied Basic Research Foundation (2022A1515110356), and Guangzhou Science and Technology Program (2023A04J1788).

Seasonal dynamics of soil nitrogen mineralization and their influencing factors during shrub anthropogenic introduction in desert steppe.

We selected enclosed grassland, grazed grassland and shrublands with different planting years (3, 12, 22 years)/densities (intervals of 2, 6, 40 m) to investigate soil N mineralization dynamics in the growing season (April-October) and its influencing factors during the process of desert steppe-degradation-shrub introduction. The results showed that soil moisture at 0-200 cm layer was decreased with increases of shrub age and density, and that the variations of soil moisture at 0-10 cm layer coincided with seasonal change. Compared with grazed grassland and enclosed grassland, the positive effect of shrubs on soil carbon, nitrogen and phosphorus contents first increased and then decreased with the increases of age and density. Moreover, soil N mineralization significantly varied across months and sites. Soil NO3- content and microbial biomass carbon and nitrogen were significantly higher from June to August. The proportion of NO3- to inorganic nitrogen significantly increased from 30.5% in enclosed grassland to 69.5% in shrublands. NH4+ content was mainly affected by months compared with sites. In the process of steppe-degradation-shrub introduction, the increases of shrub age and density significantly enhanced seasonal differences of soil nitrification and ammonification, but not on the seasonal mineralization of microbial biomass carbon and nitrogen. Soil NH4+ and NO3- contents were significantly and positively correlated with total nitrogen, organic carbon and N/P. Soil stoichiometric ratios (C/N and N/P) directly regulated N mineralization process.

Body composition in healthy singleton term infants using the three-dimensional photonic scanning method: A multicenter cross-sectional study.

OBJECTIVES: Body composition is an integral part of the nutritional assessment during infancy as it is closely related to future health. The three-dimensional photonic body surface scanning (3-DPS) method is a promising new technique for measuring body composition in children because of its advantages of easy operation, low cost, and no exposure to radiation. Using 3-DPS, this study aimed to illustrate the growth trajectories of body composition indicators during infancy according to sex and age. METHODS: This was a multicenter cross-sectional study. The body compositions of 9644 singleton term infants from four centers in Shandong Province, China, were assessed using 3-DPS. The data of 8769 healthy infants (52.0% boys), whose z scores of weight-for-length, length-for-age, and weight-for-age, according to World Health Organization standards, were in the range of -2 to 2, -3 to 3, and -3 to 3, respectively, were sampled to construct percentile curves of fat mass (FM), fat-free mass (FFM), FM percentage (FM%), FM index (FMI), and FFM index (FFMI) with the generalized additive model for location, scale, and shape method. RESULTS: Percentile charts for FM, FFM, FM%, FMI, and FFMI were developed based on age and sex. FM and FFM presented consistent trajectories with that of weight, with the fastest growth occurring at 1 to 3 mo of age. FM%, FMI, and FFMI increased with age, peaked at 6 mo, and gradually declined, which was consistent with the body mass index trend. All indicators, except for FFMI, were always significantly higher in boys than in girls ages 1 to 12 mo, indicating that sex differences in body composition existed mainly in FM rather than in lean body mass. CONCLUSIONS: The body composition of healthy singleton term infants during infancy varies with age; boys may have more FM accumulation than girls.

A/B-Site Management Strategy to Boost Electrocatalytic Overall Water Splitting on Perovskite Oxides in an Alkaline Medium.

In this paper, Pr0.7Sr0.3Co1-xRuxO3 perovskite oxides were synthesized by the sol-gel method as bifunctional catalysts for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). The overpotentials of PSCR0.05 against HER and OER at 10 mA cm-2 were 319 and 321 mV in alkaline medium, respectively. The Tafel slopes of HER and OER were 87.32 and 118.1 mV/dec, respectively. PSCR0.05 showed the largest electrochemical active area, the smallest charge transfer resistance, and excellent long-term durability. Meanwhile, the PSCR0.05 electrocatalyst was applied for overall water splitting and its cell voltage was maintained at 1.77 V at 10 mA cm-2. The super-exchange interaction between adjacent RuO6-CoO6 octahedra in perovskite made of PSCR0.05 contains sufficient active sites (such as Co2+/Co3+, Ru3+/Ru4+, and O22-/O-). The increase of surface oxygen vacancy and active site is the main reason for the improvement of difunctional catalyst performance. In this work, the electrocatalytic performance of perovskite-type oxides was further optimized by the method of A- and B-site cationic doping regulation, which provides a new idea for perovskite-type bifunctional electrocatalysts.

Pulmonary hypertension, nephrotic syndrome, and polymyositis due to hepatitis C virus infection: A case report.

BACKGROUND: Hepatitis C infection not only damages the liver but also often accompanies many extrahepatic manifestations. Incidences of pulmonary hypertension (PH) caused by hepatitis C are rare, and incidences of concurrent nephrotic syndrome and polymyositis are even rarer. CASE SUMMARY: Herein we describe the case of a 57-year-old woman who was admitted to our department for intermittent chest tightness upon exertion for 5 years, aggravated with dyspnea for 10 d. After relevant examinations she was diagnosed with PH, nephrotic syndrome, and polymyositis due to chronic hepatitis C infection. A multi-disciplinary recommendation was that the patient should be treated with sildenafil and macitentan in combination and methylprednisolone. During treatment autoimmune symptoms, liver function, hepatitis C RNA levels, and cardiac parameters of right heart catheterization were monitored closely. The patient showed significant improvement in 6-min walking distance from 100 to 300 m at 3-mo follow-up and pulmonary artery pressure drops to 50 mmHg. Long-term follow-up is needed to confirm further efficacy and safety. CONCLUSION: Increasing evidence supports a relationship between hepatitis C infection and diverse extrahepatic manifestations, but it is very rare to have PH, nephrotic syndrome, and polymyositis in a single patient. We conducted a literature review on the management of several specific extrahepatic manifestations of hepatitis C.

Immune-related adverse events as independent prognostic factors for camrelizumab in patients with esophageal squamous cell carcinoma: a retrospective cohort study.

Background: While programmed cell death protein 1 (PD-1) blockade has demonstrated varying effectiveness in treating advanced esophageal squamous cell carcinoma (ESCC), no validated prognostic factors have been identified. Immune-related adverse events (irAEs) have been shown to predict immunotherapy outcomes in multiple cancers, but their relationship with ESCC remains unclear. This study aims to evaluate the prognostic value of irAEs in patients with advanced ESCC treated with camrelizumab. Methods: We conducted a retrospective chart review of patients with recurrent or metastatic ESCC who were treated with single-agent camrelizumab at the Department of Oncology and Hematology in China-Japan Union Hospital of Jilin University between 2019 and 2022. The study's primary endpoint was objective response rate (ORR), while secondary endpoints included disease control rate (DCR), overall survival (OS), and safety. We used the chi-squared test and odds ratio (OR) to evaluate any relationships between the occurrence of irAEs and ORR. Prognostic factors for OS were identified through survival analysis using the Kaplan-Meier method and multivariate Cox regression. Results: The study included 136 patients with a median age of 60 years, of whom 81.6% were male and 89.7% received platinum-based chemotherapy as their first-line therapy. Among these patients, 128 irAEs were observed in 81 patients (59.6%). Patients who experienced irAEs achieved a significantly better ORR [39.5% vs. 14.5%; OR =3.84; 95% confidence interval (CI): 1.60-9.18; P=0.003] and longer OS [13.5 vs. 5.6 months; adjusted hazard ratio (HR) =0.56, 95% CI: 0.41-0.76; P=0.0013] than those who did not experience irAEs. Multivariate analysis identified the presence of irAEs as an independent prognostic factor for OS (HR =0.57, 95% CI: 0.42-0.77; P=0.0002). Conclusions: The presence of irAEs in ESCC patients treated with anti-PD-1 therapy (camrelizumab) may serve as a clinical prognostic factor, indicating improved therapeutic effectiveness. These findings suggest that irAEs could be used as a potential marker to predict outcomes in this patient population.

Mapping the modulating effect of transcutaneous auricular vagus nerve stimulation on voxel-based analyses in patients with first-episode major depressive disorder: a resting-state functional magnetic resonance imaging study.

INTRODUCTION: Seed-based analysis has shown that transcutaneous auricular vagus nerve stimulation (taVNS) can modulate the dysfunctional brain network in patients with major depressive disorder (MDD). However, the voxel-based neuropsychological mechanism of taVNS on patients with first-episode MDD is poorly understood. The objective of this study was to assess the effects of an 8-week course of taVNS on patients with first-episode MDD. METHODS: Twenty-two patients with first-episode MDD accepted an 8-week course of taVNS treatment. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed before and after treatment. Voxel-based analyses were performed to characterize spontaneous brain activity. Healthy controls (n=23) were recruited to minimize test-retest effects. Analysis of covariance (ANCOVA) was performed to ascertain treatment-related changes. Then, correlations between changes in brain activity and the Hamilton Depression Rating Scale (HAM-D)/Hamilton Anxiety Scale (HAM-A) remission rate were estimated. RESULTS: Significant group-by-time interactions on voxel-based analyses were observed in the inferior ventral striatum (VSi) and precuneus. Post-hoc analyses showed that taVNS inhibited higher brain activity in the VSi, while upregulating it in the precuneus. Functional connectivity (FC) between the VSi and precuneus decreased. Positive correlations were found between the HAM-D remission rate and changes in brain activity in the VSi. CONCLUSION: taVNS reduced the FC between VSi and precuneus by normalizing the abnormal spontaneous brain activity of VSi in first-episode MDD patients.

Optimizing the modulation paradigm of transcutaneous auricular vagus nerve stimulation in patients with disorders of consciousness: A prospective exploratory pilot study protocol.

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique. Several studies have reported the effectiveness of taVNS in patients with disorders of consciousness (DOC); however, differences in the modulation paradigm have led to inconsistent treatment outcomes. Methods/design: This prospective exploratory trial will include 15 patients with a minimally conscious state (MCS) recruited according to the coma recovery scale-revised (CRS-R). Each patient will receive 5 different frequencies of taVNS (1, 10, 25, 50, and 100 Hz); sham stimulation will be used as a blank control. The order of stimulation will be randomized, and the patients' CRS-R scores and resting electroencephalography (EEG) before and after stimulation will be recorded. Discussion: The overall study of taVNS used in treating patients with DOC is still in the preliminary stage of exploration. Through this experiment, we aim to explore the optimal stimulation frequency parameters of taVNS for the treatment of DOC patients. Furthermore, we expect to achieve a stable improvement of consciousness in DOC patients by continuously optimizing the neuromodulation paradigm of taVNS for the treatment of DOC patients. Clinical trial registration: https://www.chictr.org.cn/index.aspx, identifier ChiCTR 2200063828.

Deep learning-based precise prediction and early detection of radiation-induced temporal lobe injury for nasopharyngeal carcinoma.

Background: Radiotherapy is the mainstay of treatment for nasopharyngeal carcinoma. Radiation-induced temporal lobe injury (TLI) can regress or resolve in the early phase, but it is irreversible at a later stage. However, no study has proposed a risk-based follow-up schedule for its early detection. Planning evaluation is difficult when dose-volume histogram (DVH) parameters are similar and optimization is terminated. Methods: This multicenter retrospective study included 6065 patients between 2014 and 2018. A 3D ResNet-based deep learning model was developed in training and validation cohorts and independently tested using concordance index in internal and external test cohorts. Accordingly, the patients were stratified into risk groups, and the model-predicted risks were used to develop risk-based follow-up schedules. The schedule was compared with the Radiation Therapy Oncology Group (RTOG) recommendation (every 3 months during the first 2 years and every 6 months in 3-5 years). Additionally, the model was used to evaluate plans with similar DVH parameters. Findings: Our model achieved concordance indexes of 0.831, 0.818, and 0.804, respectively, which outperformed conventional prediction models (all P < 0.001). The temporal lobes in all the cohorts were stratified into three groups with discrepant TLI-free survival. Personalized follow-up schedules developed for each risk group could detect TLI 1.9 months earlier than the RTOG recommendation. According to a higher median predicted 3-year TLI-free survival (99.25% vs. 99.15%, P < 0.001), the model identified a better plan than previous models. Interpretation: The deep learning model predicted TLI more precisely. The model-determined risk-based follow-up schedule detected the TLI earlier. The planning evaluation was refined because the model identified a better plan with a lower risk of TLI. Funding: The Sun Yat-sen University Clinical Research 5010 Program (2015020), Guangdong Basic and Applied Basic Research Foundation (2022A1515110356), Medical Scientific Research Foundation of Guangdong Province (A2022367), and Guangzhou Science and Technology Program (2023A04J1788).

PCK1 activates oncogenic autophagy via down-regulation Serine phosphorylation of UBAP2L and antagonizes colorectal cancer growth.

Phosphoenolpyruvate carboxykinase 1 (PCK1) is the rate-limiting enzyme in gluconeogenesis. PCK1 is considered an anti-oncogene in several human cancers. In this study, we aimed to determine the functions of PCK1 in colorectal cancer (CRC). PCK1 expression in CRC tissues was tested by western blot and immunohistochemistry analyses and associations of PCK1 level with clinicopathological characteristics and disease survival evaluated. Further, we studied the effect of PCK1 on CRC cell proliferation and the underlying mechanisms. Our results show that PCK1 is expressed at significantly lower levels in CRC than in control tissues. High PCK1 expression was correlated with smaller tumor diameter and less bowel wall invasion (T stage). Overexpression and knockdown experiments demonstrated that PCK1 inhibits CRC cell growth both in vitro and in vivo. Mechanistically, PCK1 antagonizes CRC growth via inactivating UBAP2L phosphorylation at serine 454 and enhancing autophagy. Overall, our findings reveal a novel molecular mechanism involving PCK1 and autophagy, and highlight PCK1 as a promising candidate therapeutic target in CRC.

Mapping the modulating effect of transcutaneous auricular vagus nerve stimulation on voxel-based analyses in patients with first-episode major depressive disorder: a resting-state functional magnetic resonance imaging study

Introduction: Seed-based analysis has shown that transcutaneous auricular vagus nerve stimulation (taVNS) can modulate the dysfunctional brain network in patients with major depressive disorder (MDD). However, the voxel-based neuropsychological mechanism of taVNS on patients with first-episode MDD is poorly understood. The objective of this study was to assess the effects of an 8-week course of taVNS on patients with first-episode MDD. Methods: Twenty-two patients with first-episode MDD accepted an 8-week course of taVNS treatment. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed before and after treatment. Voxel-based analyses were performed to characterize spontaneous brain activity. Healthy controls (n=23) were recruited to minimize test-retest effects. Analysis of covariance (ANCOVA) was performed to ascertain treatment-related changes. Then, correlations between changes in brain activity and the Hamilton Depression Rating Scale (HAM-D)/Hamilton Anxiety Scale (HAM-A) remission rate were estimated. Results: Significant group-by-time interactions on voxel-based analyses were observed in the inferior ventral striatum (VSi) and precuneus. Post-hoc analyses showed that taVNS inhibited higher brain activity in the VSi, while upregulating it in the precuneus. Functional connectivity (FC) between the VSi and precuneus decreased. Positive correlations were found between the HAM-D remission rate and changes in brain activity in the VSi. Conclusion: taVNS reduced the FC between VSi and precuneus by normalizing the abnormal spontaneous brain activity of VSi in first-episode MDD patients.

Electrochemical Synthesis of ß-Iodoesters by 1,2-Iodoesterization of Unactivated Alkenes with Carboxylic Acids and Tetrabutylammonium Iodide.

We report a novel and highly selective electrochemical method for the synthesis of ß-iodoesters via difunctionalization of alkenes. The reaction is carried out in an undivided cell under constant current conditions without any additives, catalysts, oxidants, and sacrificial reagents. Inexpensive and readily available tetrabutylammonium iodide not only acts as an electrolyte but also serves as an iodine source. The reaction shows high selectivity and good functional group tolerance, providing products in yields of up to 98%. This method is applicable not only to the iodofunctionalization of alkenes but also to the chloro- and bromofunctionalization of alkenes. The successful modification of drugs and natural products demonstrates the potential utility of this approach.

IL-6 promotes pluripotency of mouse embryonic stem cells and regulates cardiac differentiation in a development-dependent manner.

Interleukin 6 (IL-6), an important component of cardiac microenvironment, favors cardiac repair by improving cardiomyocyte regeneration in different models. This study aimed to investigate the effects of IL-6 on stemness maintenances and cardiac differentiation of mouse embryonic stem cells (mESCs). The mESCs were treated with IL-6 for two days, and then subjected to CCK-8 essay for proliferation analysis and quantitative real-time PCR (qPCR) to evaluate the mRNA expression of genes related to stemness and germinal layers differentiation. Phosphorylation levels of stem cell-related signal pathways were detected by Western blot. siRNA was used to interfere the function of STAT3 phosphorylation. Cardiac differentiation was investigated by the percentage of beating embryoid bodies (EBs) and qPCR analysis of cardiac progenitor markers and cardiac ion channels. IL-6 neutralization antibody was applied to block the endogenous IL-6 effects since the onset of cardiac differentiation (embryonic day of 0, EB0). The EBs were collected on EB7, EB10 and EB15 to investigate the cardiac differentiation by qPCR. On EB15, Western blot was applied to investigate the phosphorylation of several signaling pathways, and immunochemistry staining was adopted to trace the cardiomyocytes. IL-6 antibody was administered for two days (short term) on EB4, EB7, EB10 or EB15, and percentages of beating EBs at late developmental stage were recorded. The results showed that exogenous IL-6 promoted mESCs proliferation and favored maintenances of pluripotency, evidenced by up-regulated mRNA expression of oncogenes (c-fos, c-jun) and stemness markers (oct4, nanog), down-regulated mRNA expression of germ layer genes (branchyury, FLK-1, pecam, ncam, sox17), and increased phosphorylation of ERK1/2 and STAT3. siRNA targeting JAK/STAT3 partially attenuated the effects of IL-6 on cell proliferation and mRNA expression of c-fos and c-jun. During differentiation, long term IL-6 neutralization antibody application decreased the percentage of beating EBs, down-regulated mRNA expression of ISL1, GATA4, α-MHC, cTnT, kir2.1, cav1.2, and declined the fluorescence intensity of cardiac α actinin in EBs and single cell. Long term IL-6 antibody treatment decreased the phosphorylation of STAT3. In addition, short term (2 d) IL-6 antibody treatment starting from EB4 significantly reduced the percentage of beating EBs in late development stage, while short term IL-6 antibody treatment starting from EB10 significantly increased the percentage of beating EBs on EB16. These results suggest that exogenous IL-6 promotes mESCs proliferation and favors stemness maintenance. Endogenous IL-6 regulates mESC cardiac differentiation in a development-dependent manner. These findings provide important basis for the study of microenvironment on cell replacement therapy, as well as a new perspective for understanding the pathophysiology of heart diseases.

Helicity-resolved Raman scattering of MoS2 bulk crystal.

Helicity-resolved Raman spectroscopy (HRRS) can effectively distinguish the Raman modes of two-dimensional (2D) layered materials by phonon symmetry. In this paper, we systematically investigated the phonon helicity selection of basal and edge planes of MoS2 bulk by HRRS. We find that the symmetry of the crystal structure changes the helicity selection of the E1g, E1 2g, and A1g modes in the edge plane. The theoretical calculation results confirm that the E1 2g and A1g modes of the basal plane exhibit a perfect helicity exchange, and the helicity selections of the E1 2g and A1g modes of the edge plane are eliminated or weakened. Our study provides references for phonon helicity selection of 2D layered materials represented by MoS2.

Electroreductive Hydroxymethylation of Imines with Ketones To Access ß-Amino Alcohols.

In this article, an electrochemical method for the direct synthesis of ß-amino alcohols from imines and ketones is described. Mechanistic studies, including a radical trapping experiment, electron paramagnetic resonance, cyclic voltammetry, and divided-cell electrolysis experiment, support the radical-involved reductive cross coupling of imines with ketones at the cathode. The use of abundant and easily prepared starting materials, high atom- and step-economy, and insensitivity to air and moisture make this synthetic strategy more efficient for the construction of various ß-amino alcohol derivatives.