Maternal androgen excess inhibits fetal cardiomyocytes proliferation through RB-mediated cell cycle arrest and induces cardiac hypertrophy in adulthood.

PURPOSE: Maternal hyperandrogenism during pregnancy is associated with adverse gestational outcomes and chronic non-communicable diseases in offspring. However, few studies are reported to demonstrate the association between maternal androgen excess and cardiac health in offspring. This study aimed to explore the relation between androgen exposure in utero and cardiac health of offspring in fetal and adult period. Its underlying mechanism is also illustrated in this research. METHODS: Pregnant mice were injected with dihydrotestosterone (DHT) from gestational day (GD) 16.5 to GD18.5. On GD18.5, fetal heart tissue was collected for metabolite and morphological analysis. The hearts from adult offspring were also collected for morphological and qPCR analysis. H9c2 cells were treated with 75 µM androsterone. Immunofluorescence, flow cytometry, qPCR, and western blot were performed to observe cell proliferation and explore the underlying mechanism. RESULTS: Intrauterine exposure to excessive androgen led to thinner ventricular wall, decreased number of cardiomyocytes in fetal offspring and caused cardiac hypertrophy, compromised cardiac function in adult offspring. The analysis of steroid hormone metabolites in fetal heart tissue by ultra performance liquid chromatography and tandem mass spectrometry showed that the content of androgen metabolite androsterone was significantly increased. Mechanistically, H9c2 cells treated with androsterone led to a significant decrease in phosphorylated retinoblastoma protein (pRB) and cell cycle-related protein including cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), and cyclin D1 (CCND1) in cardiomyocytes. This resulted in cell cycle arrest at G1-S phase, which in turn inhibited cardiomyocyte proliferation. CONCLUSION: Taken together, our results indicate that in utero exposure to DHT, its metabolite androsterone could directly decrease cardiomyocytes proliferation through cell cycle arrest, which has a life-long-lasting effect on cardiac health. Our study highlights the importance of monitoring sex hormones in women during pregnancy and the follow-up of cardiac function in offspring with high risk of intrauterine androgen exposure.

Coherent Microwave Emission of Gain-Driven Polaritons.

By developing a gain-embedded cavity magnonics platform, we create a gain-driven polariton (GDP) that is activated by an amplified electromagnetic field. Distinct effects of gain-driven light-matter interaction, such as polariton auto-oscillations, polariton phase singularity, self-selection of a polariton bright mode, and gain-induced magnon-photon synchronization, are theoretically studied and experimentally manifested. Utilizing the gain-sustained photon coherence of the GDP, we demonstrate polariton-based coherent microwave amplification (∼40 dB) and achieve high-quality coherent microwave emission (Q>10^{9}).

[Influence of sleep fragmentation in infancy and toddler period on emotional and behavioral problem at the age of 6 years: a birth cohort study].

Objective: To investigate the influence of sleep fragmentation in infancy and toddler period on emotional and behavioral problems at the age of 6 years. Methods: Using a prospective cohort design, 262 children were extracted from mother-child birth cohort recruited from May 2012 to July 2013 in Renji Hospital, School of Medicine, Shanghai Jiao Tong University. Children's sleep and physical activities were assessed using actigraphy at 6, 12, 18, 24, and 36 months of age, from which the sleep fragmentation index (FI) at each follow-up point was calculated. Children's emotional and behavioral problems at 6 years of age were assessed using the strengths and difficulties questionnaire. Group-based trajectory model was applied to determine sleep FI in infancy and toddler period trajectory groups with Bayesian information criteria being used to determine the best fitting model. Children's emotional and behavioral problems between groups were examined with independent t test and linear regression models, etc. Results: A total of 177 children, with 91 boys and 86 girls, were included in the final analysis and were divided into 2 groups: high FI group (n=30) and low FI group (n=147). Compared with children in the low FI group, those in the high FI group presents with higher total difficulties score and higher hyperactivity or inattention score ((11.0±4.9) vs. (8.9±4.1), (4.9±2.7) vs. (3.7±2.3) scores, t=2.17, 2.23, both P<0.05, respectively), with the differences remaining significant after adjusting for covariates (t=2.08, 2.09, both P<0.05 respectively). Conclusion: High sleep fragmentation in infancy and toddler period is associated with more emotional and behavioral problems, especially hyperactivity or inattention problems, at 6 years of age.

[Hospitalization costs of pediatric community-acquired pneumonia in Shanghai].

Objective: To investigate the epidemiology and hospitalization costs of pediatric community-acquired pneumonia (CAP) in Shanghai. Methods: A retrospective case summary was conducted on 63 614 hospitalized children with CAP in 59 public hospitals in Shanghai from January 2018 to December 2020. These children's medical records, including their basic information, diagnosis, procedures, and costs, were extracted. According to the medical institutions they were admitted, the patients were divided into the children's hospital group, the tertiary general hospital group and the secondary hospital group; according to the age, they were divided into <1 year old group, 1-<3 years old group, 3-<6 years old group, 6-<12 years old group and 12-18 years old group; according to the CAP severity, they were divided into severe pneumonia group and non-severe pneumonia group; according to whether an operation was conducted, the patients were divided into the operation group and the non-operation group. The epidemiological characteristics and hospitalization costs were compared among the groups. The χ2 test or Wilcoxon rank sum test was used for the comparisons between two groups as appropriate, and the Kruskal-Wallis H test was conducted for comparisons among multiple groups. Results: A total of 63 614 hospitalized children with CAP were enrolled, including 34 243 males and 29 371 females. Their visiting age was 4 (2, 6) years. The length of stay was 6 (5, 8) days. There were 17 974 cases(28.3%) in the secondary hospital group, 35 331 cases (55.5%) in the tertiary general hospital group and 10 309 cases (16.2%) in the children's hospital group. Compared with the hospitalizations cases in 2018 (27 943), the cases in 2019 (29 009) increased by 3.8% (1 066/27 943), while sharply declined by 76.2% (21 281/27 943) in 2020 (6 662). There were significant differences in the proportion of patients from other provinces and severe pneumonia cases, and the hospitalization costs among the children's hospital, secondary hospital and tertiary general hospital (7 146 cases(69.3%) vs. 2 202 cases (12.3%) vs. 9 598 cases (27.2%), 6 929 cases (67.2%) vs. 2 270 cases (12.6%) vs. 9 397 cases (26.6%), 8 304 (6 261, 11 219) vs. 1 882 (1 304, 2 796) vs. 3 195 (2 364, 4 352) CNY, χ2=10 462.50, 9 702.26, 28 037.23, all P<0.001). The annual total hospitalization costs of pediatric CAP from 2018 to 2020 were 110 million CNY, 130 million CNY and 40 million CNY, respectively. And the cost for each hospitalization increased year by year, which was 2 940 (1 939, 4 438), 3 215 (2 126, 5 011) and 3 673 (2 274, 6 975) CNY, respectively. There were also significant differences in the hospitalization expenses in the different age groups of <1 year old, 1-<3 years old, 3-<6 years old, 6-<12 years old and 12-18 years old (5 941 (2 787, 9 247) vs. 2 793 (1 803, 4 336) vs. 3 013 (2 070, 4 329) vs. 3 473 (2 400, 5 097) vs. 4 290 (2 837, 7 314) CNY, χ2=3 462.39, P<0.001). The hospitalization cost of severe pneumonia was significantly higher than that of non-severe cases (5 076 (3 250, 8 364) vs. 2 685 (1 780, 3 843) CNY, Z=109.77, P<0.001). The cost of patients who received operation was significantly higher than that of whom did not (10 040 (4 583, 14 308) vs. 3 083 (2 025, 4 747) CNY, Z=44.46, P<0.001). Conclusions: The number of children hospitalized with CAP in Shanghai decreased significantly in 2020 was significantly lower than that in 2018 and 2019.The proportion of patients from other provinces and with severe pneumonia are mainly admitted in children's hospitals. Hospitalization costs are higher in children's hospitals, and also for children younger than 1 year old, severe cases and patients undergoing operations.

Interferometric control of magnon-induced nearly perfect absorption in cavity magnonics.

The perfect absorption of electromagnetic waves has promoted many applications, including photovoltaics, radar cloaking, and molecular detection. Unlike conventional methods of critical coupling that require asymmetric boundaries or coherent perfect absorption that require multiple coherent incident beams, here we demonstrate single-beam perfect absorption in an on-chip cavity magnonic device without breaking its boundary symmetry. By exploiting magnon-mediated interference between two internal channels, both reflection and transmission of our device can be suppressed to zero, resulting in magnon-induced nearly perfect absorption (MIPA). Such interference can be tuned by the strength and direction of an external magnetic field, thus showing versatile controllability. Furthermore, the same multi-channel interference responsible for MIPA also produces level attraction (LA)-like hybridization between a cavity magnon polariton mode and a cavity photon mode, demonstrating that LA-like hybridization can be surprisingly realized in a coherently coupled system.

Two-beam coupling by a hot electron nonlinearity.

Transparent conductive oxides such as indium tin oxide (ITO) bear the potential to deliver efficient all-optical functionality due to their record-breaking optical nonlinearity at epsilon near zero (ENZ) wavelengths. All-optical applications generally involve more than one beam, but, to our knowledge, the coherent interaction between beams has not previously been discussed in these materials, which have a hot electron nonlinearity. Here we study the optical nonlinearity at ENZ in ITO and show that spatial and temporal interference has important consequences in a two-beam geometry. Our pump-probe results reveal a polarization-dependent transient that is explained by diffraction of pump light into the probe direction by a temperature grating produced by pump-probe interference. We further show that this effect allows tailoring the nonlinearity by tuning the frequency or chirp. Having fine control over the strong and ultrafast ENZ nonlinearity may enable applications in all-optical neural networks, nanophotonics, and spectroscopy.

Hybrid perfect metamaterial absorber for microwave spin rectification applications.

Metamaterials provide compelling capabilities to manipulate electromagnetic waves beyond the natural materials and can dramatically enhance both their electric and magnetic fields. The enhanced magnetic fields, however, are far less utilized than the electric counterparts, despite their great potential in spintronics. In this work, we propose and experimentally demonstrate a hybrid perfect metamaterial absorbers which combine the artificial metal/insulator/metal (MIM) metamaterial with the natural ferromagnetic material permalloy (Py) and realize remarkably larger spin rectification effect. Magnetic hot spot of the MIM metamaterial improves considerably electromagnetic coupling with spins in the embedded Py stripes. With the whole hybridized structure being optimized based on coupled-mode theory, perfect absorption condition is approached and an approximately 190-fold enhancement of spin-rectifying photovoltage is experimentally demonstrated at the ferromagnetic resonance at 7.1 GHz. Our work provides an innovative solution to harvest microwave energy for spintronic applications, and opens the door to hybridized magnetism from artificial and natural magnetic materials for emergent applications such as efficient optospintronics, magnonic metamaterials and wireless energy transfer.

Unconventional Singularity in Anti-Parity-Time Symmetric Cavity Magnonics.

By engineering an anti-parity-time (anti-PT) symmetric cavity magnonics system with precise eigenspace controllability, we observe two different singularities in the same system. One type of singularity, the exceptional point (EP), is produced by tuning the magnon damping. Between two EPs, the maximal coherent superposition of photon and magnon states is robustly sustained by the preserved anti-PT symmetry. The other type of singularity, arising from the dissipative coupling of two antiresonances, is an unconventional bound state in the continuum (BIC). At the settings of BICs, the coupled system exhibits infinite discontinuities in the group delay. We find that both singularities coexist at the equator of the Bloch sphere, which reveals a unique hybrid state that simultaneously exhibits the maximal coherent superposition and slow light capability.

Nonreciprocity and Unidirectional Invisibility in Cavity Magnonics.

We reveal the cooperative effect of coherent and dissipative magnon-photon couplings in an open cavity magnonic system, which leads to nonreciprocity with a considerably large isolation ratio and flexible controllability. Furthermore, we discover unidirectional invisibility for microwave propagation, which appears at the zero-damping condition for hybrid magnon-photon modes. A simple model is developed to capture the generic physics of the interference between coherent and dissipative couplings, which accurately reproduces the observations over a broad range of parameters. This general scheme could inspire methods to achieve nonreciprocity in other systems.

[The inhibition of 18ß-sodium glycyrrhetinic acid on thymic stromal lymphopoietin expression in the nasal mucosa of allergic rhinitis rats].

Objective: To explore the effect of 18ß-sodium glycyrrhetinic acid on thymic stromal lymphopoietin (TSLP) in nasal mucosa of allergic rhinitis (AR) rats. Methods: One hundred Wistar rats,half male and half female,were randomly divided into 5 groups by random number table method: control group, AR model group,budesonide group,18ß-sodium glycyrrhetinic acid at dose of 20 mg/kg and 40 mg/kg groups, with 20 rats in each group. AR animal models were established by ovalbumin (OVA) sensitization in the other four experimental groups. After successful modeling, budesonide and 18ß-sodium glycyrrhetinic acid were given in each group,and the detection time points were 2 weeks and 4 weeks. The distribution of TSLP in rat nasal mucosa was detected by immunohistochemistry,and the expression of TSLP in rat nasal mucosa was determined by Western blot at the protein level. The expression of TSLP-mRNA in rat nasal mucosa was detected and compared by real-time fluorescence quantitative PCR (RT-PCR) at mRNA level. The concentrations of IL-4 and OVA-sIgE in rat serum were measured and compared by ELISA. One-way analysis of variance and the least significant difference method were used for the comparison among groups, LSD t test was used for the comparison between the two groups,and the difference was statistically significant (P<0.05). Results: Immunohistochemistry confirmed existence of TSLP in rat nasal mucosa, especially in epithelial cells,endothelial cells and epithelial cilia. Western blot and RT-PCR suggested that the expression of TSLP and TSLP-mRNA in nasal mucosa of AR model group was significantly higher than that of control group (2 weeks TSLP: 1.795 9±0.131 4 vs 0.990 5±0.164 2, 4 weeks TSLP: 1.809 7±0.253 4 vs 0.870 3±0.124 4; 2 weeks TSLP-mRNA:4.582 9±0.697 7 vs 1.108 7±0.081 1, 4 weeks TSLP-mRNA:4.814 4±0.662 8 vs 1.001 0±0.155 3; all P<0.05). After 2 weeks and 4 weeks of drug intervention,the expression of TSLP and TSLP-mRNA was inhibited in nasal mucosa of budesonide group,18ß-sodium sodium glycyrrhetinic acid at dose of 20 mg/kg and 40 mg/kg group,which was significantly different from that of AR model group (2 weeks TSLP: (0.897 8±0.081 8)/(1.072 1±0.113 6)/(1.396 6±0.133 9) vs 1.795 9±0.131 4; 4 weeks TSLP: (1.191 0±0.161 3)/(1.141 0±0.152 3)/(1.200 5±0.189 6) vs 1.809 7±0.253 4; 2 weeks TSLP-mRNA: (1.175 6±0.100 9)/(1.254 4±0.078 2)/(2.037 2±0.559 2) vs 4.582 9±0.697 7; 4 weeks TSLP-mRNA: (1.158 3±0.104 3)/(1.224 0±0.034 0)/(1.275 2±0.099 6) vs 4.814 4±0.662 8; all P<0.05), and not significantly different from control group. With the inhibition of TSLP, the concentrations of IL-4 and OVA-sIgE in rat serum were also decreased. Conclusion: 18ß-sodium glycyrrhetinic acid has obvious inhibitory effect on TSLP in nasal mucosa of AR rats, which can control Th2 type immune inflammatory reaction.

Analogue of dynamic Hall effect in cavity magnon polariton system and coherently controlled logic device.

Cavity magnon polaritons are mixed quasiparticles that arise from the strong coupling between cavity photons and quantized magnons. Combining high-speed photons with long-coherence-time magnons, such polaritons promise to be a potential candidate for quantum information processing. For harnessing coherent information contained in spatially distributed polariton states, it is highly desirable to manipulate cavity magnon polaritons in a two-dimensional system. Here, we demonstrate that tunable cavity magnon polariton transport can be achieved by strongly coupling magnons to microwave photons in a cross-cavity. An analog to the dynamic Hall effect has been demonstrated in a planar cavity spintronic device, where the propagation of cavity-magnon-polaritons is deflected transversally due to hybrid magnon-photon dynamics. Implementing this device as a Michelson-type interferometer using the coherent nature of the dynamic Hall and longitudinal signals, we have developed a proof-of-principle logic device to control the amplitude of cavity-magnon-polaritons by encoding the input microwave phase.

[Effects of 18ß-sodium glycyrrhetinic acid on TNF-α expression in rats with allergic rhinitis].

Objective:To observe the effect of 18ß-sodium glycyrrhetinic acid(18ß-SGA) on the expression of TNF-α in nasal mucosa of rats with allergic rhinitis（AR）, and explore the intervention mechanism of 18ß-SGA on AR. Method:One hundred and six SPF-level Wistar rats were randomly divided into control group, AR group, budesonide group, 18ß-SGA low dose group and high dose group. After the AR rat model was constructed by ovalbumin, the rats were given drug intervention and sacrificed after 2 and 4 weeks of intervention. The nasal mucosa of the rats was taken for immunohistochemical staining, RT-qPCR and Western-blotting to localize and quantify the expression of TNF-α. Result:By immunohistochemistry, Western-blotting and RT-PCR, TNF-α was mainly found in the columnar epithelium, vascular endothelium, glandular and some inflammatory cytoplasm of nasal mucosa. And the expression of TNF-α in the nasal mucosa of AR rats was significantly increased than the normal group at the protein and mRNA levels (P<0.01). After intervention with different doses of 18ß-SGA, the expression of TNF-α was significantly decreased (P<0.01), especially after 4 weeks of 18ß-SGA low dose group(P<0.01). Conclusion:Different doses of 18ß-SGA have therapeutic effects on AR, and its mechanism of action may be related to the inhibition of TNF-α expression.

Level Attraction Due to Dissipative Magnon-Photon Coupling.

We report dissipative magnon-photon coupling caused by the cavity Lenz effect, where the magnons in a magnet induce a rf current in the cavity, leading to a cavity backaction that impedes the magnetization dynamics. This effect is revealed in our experiment as level attraction with a coalescence of hybridized magnon-photon modes, which is distinctly different from level repulsion with mode anticrossing caused by coherent magnon-photon coupling. We develop a method to control the interpolation of coherent and dissipative magnon-photon coupling, and observe a matching condition where the two effects cancel. Our work sheds light on the so-far hidden side of magnon-photon coupling, opening a new avenue for controlling and utilizing light-matter interactions.

[Expression of Fermintin family homologous protein 2 in non-small cell lung cancer and its clinical significance].

Objective: To investigate the expression of Fermintin family homologous protein 2 (FERMT2) in non-small cell lung cancer and its clinical significance. Methods: Seventy-two patients with non-small cell lung cancer were collected at Xinxiang Central Hospital, Henan Province, from January 2015 to January 2017.There were 48 male and 24 female patients, the age ranged from 37 to 78 years (mean 58 years). The expression of FERMT2 in tumor samples and para-cancerous tissues were detected by immunohistochemistry. Protein and mRNA expression of FERMT2 were detected by Western blot and real-time fluorescence quantitative PCR, respectively. Western blot method was also used to detect integrin-related protein expression, including integrin beta 1 (CD29), vascular cell adhesion molecule (VCAM1), and mobile related protein-1 (MRP1). Results: Immunohistochemistry showed that the positive rates of FERMT2 expression were 81.9%(59/72)in carcinoma tissue and 15.4%(11/72) in para-cancerous tissues, and the difference was statistically significant (P<0.01). Positive FERMT2 expression was different in tumors at different tumor stages: 11/17 at stage Ⅰ, 16/20(80.0%)at stage Ⅱ, 17/20(85.0%)at stage Ⅲ, and 15/15 at stage Ⅳ, and there was a significant difference between each stage (P<0.01). By real-time PCR and Western blot, the expression of FERMT2 in non-small cell lung cancer tissues was significantly higher than that of para-cancerous tissue (P<0.01). The expression levels of integrin related proteins (integrin ß1, VCAM1 and MRP1) in tumor tissues were significantly higher than those in para-cancerous tissues, and positively correlated with the expression of FERMT2 (r=0.531, P<0.01; r=0.483, P<0.01; r=0.612, P<0.01). Conclusions: FERMT2 is highly expressed in non-small cell lung carcinomas. Its expression is closely correlated with the tumor clinical stage. It is hypothesized that FERMT2 may promote tumor metastasis through interactions with integrin-like protein.

Clinical value of combined tests for tumor markers for gastric cancer.

To study the clinical diagnostic value of treating gastric cancer (GC) with combined tests for tumor markers (CEA, CA199, CA242 and CA724), fifty healthy subjects, 50 patients with GC at different stages and 50 patients with benign GC were randomly selected from our hospital. These subjects were divided into a normal group A, an experimental group B and a control group C. Venous blood was drawn and tested for four serum tumor markers. The SPSS 18.0 analytic system was then used to analyze the data. Tumor markers for GC at different stages, different pathological patterns and tumor incidence are discussed. The difference in expression levels of tumor markers between group C and group A was not statistically significant (P>0.05). The differences in expression levels between group B in stage I and stage II and those of groups A and C was statistically significant (P less than 0.05). At the same time, the differences in expression levels of group B in stage III and stage IV and those of groups A and C were also statistically significant (P less than 0.01). For different sizes of tumors, taking 5 cm as a maximum, normal expression and abnormal expression of the four tumor markers was different (P less than 0.05). The tumor incidence of the combined test for the four tumor markers was conspicuously higher than that of single tests. Moreover, the difference between the tumor incidence of the combined test in stages I, II and III and that of single tests in the same stages was of statistical significance (P less than 0.05); however, the difference was not statistically significant in stage IV (P>0.05). The combined testing for tumor markers is useful for clinical diagnosis of GC.

Collective effects of common single nucleotide polymorphisms and genetic risk prediction in type 1 diabetes.

Type 1 diabetes (T1D) is a common autoimmune disease and may be related to multiple genetic and environmental risk factors. Previous genetic studies have focused on looking for individual polymorphic risk variants. Here, we studied the overall levels of genetic diversity in T1D patients by making use of a previously published study including 1865 cases and 2828 reference samples with genotyping data for 500 K common single nucleotide polymorphisms (SNPs). We determined the minor allele (MA) status of each SNP in the reference samples and calculated the total number of MAs or minor allele contents (MAC) of each individual. We found the average MAC of cases to be greater than that of the reference samples. By focusing on MAs with strong linkage to cases, we further identified a set of 112 SNPs that could predict 19.19% of cases. These results suggest that overall genetic variation over a threshold level may be a risk factor in T1D and provide a new genetic method for predicting the disorder.

Cooperative polariton dynamics in feedback-coupled cavities.

The emerging field of cavity spintronics utilizes the cavity magnon polariton (CMP) induced by magnon Rabi oscillations. In contrast to a single-spin quantum system, such a cooperative spin dynamics in the linear regime is governed by the classical physics of harmonic oscillators. It makes the magnon Rabi frequency independent of the photon Fock state occupation, and thereby restricts the quantum application of CMP. Here we show that a feedback cavity architecture breaks the harmonic-oscillator restriction. By increasing the feedback photon number, we observe an increase in the Rabi frequency, accompanied with the evolution of CMP to a cavity magnon triplet and a cavity magnon quintuplet. We present a theory that explains these features. Our results reveal the physics of cooperative polariton dynamics in feedback-coupled cavities, and open up new avenues for exploiting the light-matter interactions.

[Primary malignant tumor of uvula: report of 3 cases and review of the literature].

We retrospectively analyzed 3 middle-aged male patients of primary malignant tumor of uvula. There was a long history of smoking and drinking for the patients. All of them came to the hospital with the syptoms of pharyngeal foreign body sensation and two of them had pharyngeal sore. The patients appeared well, new neoplasm at the apex of the uvula. Diameter of 2 cases were less than 1 cm without invading the midline of the soft palate. Another patient's diameter was more than 1 cm with invading the midline of the soft palate. Preoperative pathology diagnosis of 3 patients was squamous cell carcinoma of uvula. The pharyngeal CT of the patient with invading the midline of the soft palate showed nodules at the end of the soft palate, obviously enhancement and small lymph node in left neck.