[Expression of hypoxia-inducible factor-1 in mice infected with Toxoplasma gondii during pregnancy].

OBJECTIVE: To investigate the expression and possible role of hypoxia-inducible factor-1 (HIF-1) at the maternal-fetal interface following Toxoplasma gondii infection during early pregnancy. METHODS: Twenty pregnant C57BL/6 mice, each weighing 16 to 20 g, were randomly divided into 4 groups, including the 12-d control group, 12-d infection group, 18-d control group and 18-d infection group. Mice in the 12-d and 18-d infection groups were injected intraperitoneally with 150 tachyzoites of the T. gondii PRU strain on day 6 of pregnancy, while mice in the 12-d control and 18-d control groups were injected with the same volume of phosphate buffered saline (PBS). Mice in the control and infection groups were sacrificed on days 12 and 18 of pregnancy, and the placental and uterine specimens of the pregnant mice in each group were sampled for pathological examinations. The mRNA expression of HIF-1α, HIF-1ß and vascular endothelial growth factor (VEGF) was quantified using quantitative fluorescent real-time PCR (qPCR) assay in the placental and uterine specimens, and the correlation between HIF-1α and VEGF mRNA expression was examined. In addition, and the HIF-1α expression was detected using immunohistochemical staining in the placental and uterine specimens of pregnant mice. RESULTS: Compared with the 12-d and 18-d control groups, adverse pregnant outcomes were observed in mice in 12-d and 18-d infection groups, such as teratism and placental dysplasia. HE staining showed swelling and blood stasis of cells, sinusoid reduction and inflammatory cell infiltration in the labyrinth area of the placenta specimens of mice in 12-d and 18-d infection groups relative to 12-d and 18-d control groups, and columnar epithelial cell injury and inflammatory cell infiltration were seen in the mouse uterine specimens in both infection groups. qPCR assay detected significantly higher HIF-1α (F = 132.6, P < 0.05) and HIF-1ß mRNA expression (F = 286.9, P < 0.05) in the placental specimens and lower HIF-1α (F = 111.5, P < 0.05) and HIF-1ß mRNA expression (F = 55.2, P < 0.05) in the uterine specimens in the 12-d infection group than in the 12-day control group, and significantly lower HIF-1α and HIF-1ß mRNA expression was detected in the placental and uterine specimens in the 18-d infection group than in the 18-day control group (F = 215.8, 418.9, 156.8 and 200.1; all P values < 0.05). Significantly lower VEGF-A (F = 426.2, P < 0.05), VEGF-B (F = 104.6, P < 0.05) and VEGF-C mRNA expression (F = 566.9, P < 0.05) in the placental specimens and higher VEGF-A (F = 426.2, P < 0.05), VEGF-B (F = 104.6, P < 0.05) and VEGF-C mRNA expression (F = 566.9, P < 0.05) in the uterine specimens were detected in the 12-d infection group than in the 12-d control group, and higher VEGF-A, VEGF-B and VEGF-C mRNA expression was found in the placental and uterine specimens in the 18-d infection group than in the 18-d control group (F = 521.9, 100.6, 275.9, 224.6, 108.2 and 333.4; all P values < 0.05). Immunohistochemical staining showed strongly and mildly positive HIF-1α expression in the mouse placental labyrinth area in the 12-d and 18-d infection groups relative to 12-d and 18-d control groups, while no HIF-1α expression was detected in mouse uterine specimens. CONCLUSIONS: HIF-1α expression appears a tendency towards a rise in the second trimester and a reduction in the third trimester in mice following T. gondii infection during early pregnancy, which is contrary to the changing tendency of VEGF-A, VEGF-B, and VEGF-C expression. It is hypothesized that HIF-1α inhibits placental angiogenesis in mice during pregnancy through suppressing VEGF expression, resulting in adverse pregnant outcomes.

LncRNA MALAT1 knockdown alleviates myocardial apoptosis in rats with myocardial ischemia-reperfusion through activating PI3K/AKT signaling pathway.

OBJECTIVE: To observe the effect of long non-coding ribonucleic acid metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) on the myocardial ischemia-reperfusion (I/R) injury in rats and to explore its potential mechanism, to provide certain references for clinical prevention and treatment of myocardial I/R injury. MATERIALS AND METHODS: A total of 60 male Wistar rats were randomly divided into the Control group (n=20), I/R group (n=20) and I/R + MALAT1 small-interfering RNA (siRNA) group (n=20) using a random number table. The I/R model was established through recanalization after ligation of left anterior descending coronary artery (LAD), and the MALAT1 knockdown model was established via tail intravenous injection of MALAT1 siRNA in the I/R + MALAT1 siRNA group. The ejection fraction (EF%) and fractional shortening (FS%) of rats in each group were detected via echocardiography and the infarction area in each group was detected using 2,3,5-triphenyl tetrazolium chloride (TTC) assay. Moreover, the morphological changes in myocardial cells in each group were detected via hematoxylin-eosin (H&E) staining, and the myocardial apoptosis level was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. At the same time, the expression levels of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) and pro-apoptotic protein Bcl-2 associated X protein (Bax) in myocardial tissues in each group were determined via Western blotting. Finally, the effect of MALAT1 knockdown on the phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/AKT) protein expression was detected via Western blotting. RESULTS: The expression level of lncRNA MALAT1 in myocardial tissues was significantly higher in the I/R group than that in the Control group (p<0.05). The MALAT1 knockdown could significantly improve the cardiac insufficiency caused by I/R injury, and increase both EF% and FS% in rats (p<0.05). In addition, the MALAT1 knockdown could markedly inhibit myocardial infarction caused by I/R injury and reduce the infarction area from (62.12 ± 1.29) to (27.66 ± 3.58; p<0.05). The results of the H&E staining showed that the myofilaments were arranged more orderly, the degrees of degradation and necrosis were lower and the cellular edema was significantly alleviated in the I/R + MALAT1 siRNA group compared with those in the I/R group. According to the results of TUNEL staining, the rats in I/R + MALAT1 siRNA group had a markedly lower level of myocardial apoptosis than the I/R group (p<0.05), and the Bax/Bcl-2 ratio also remarkably declined in the I/R + MALAT1 siRNA group (p<0.05). Furthermore, the results of Western blotting revealed that MALAT1 siRNA could significantly reverse the I/R injury-induced inhibition on the AKT phosphorylation (p<0.05). CONCLUSIONS: The MALAT1 knockdown can markedly improve the I/R-induced myocardial injury and promote the cardiac function of rats, whose mechanism may be related to the activation of the AKT signaling pathway by MALAT1 siRNA. Therefore, lncRNA MALAT1 is expected to be a new therapeutic target for myocardial I/R injury.

[Association between 24 h urinary sodium excretion and microalbuminuria among Chinese people aged from 18 to 69 years old].

Objective: To analyze the association between 24 h urinary sodium excretion and microalbuminuria (MAU) among Chinese people aged from 18 to 69 years old. Methods: 2 400 subjects aged from 18 to 69 years old were selected form Gaomi and Fushan sites of Shandong Province and Xinyi and Ganyu sites of Jiangsu Province in 2013 by using multi-stage stratified cluster random sampling method. Questionnaire survey, physical measurement and 24 h urine collection were conducted. 2 262 subjects were finally included in the analysis. According to the quartile of 24 h urinary sodium, all subjects were divided into Q1-Q4 groups and the levels of urinary microalbumin and MAU among different groups were compared. The relationship between urinary sodium and MAU was analyzed by multivariate logistic regression analysis. Results: The age of subjects was (42.1±13.5) years old, including 1 124 males (49.7%). The 24 h urine volume, urinary sodium, urine albumin M (P(25), P(75)) and MAU detection rate were (1 411±495) ml, (166.4±71.6) mmol/d, 12.5 (9.6, 17.4) mg/d and 9.0% (203 cases), respectively. With the increase of urinary sodium level, the level of urinary albumin increased (P(trend)<0.001), and the prevalence of MAU also showed an upward trend (P(trend)<0.001). Multivariate logistic regression analysis showed that after adjusting for age, gender, smoking, alcohol consumption, BMI, hypertension and diabetes, the risk of MAU in Q4 group increased by 174% compared with Q1 group, and OR (95%CI) value was 2.74 (1.80-4.16). Conclusion: 24 h urinary sodium is associated with the prevalence of MAU and salt reduction can help reduce MAU.

[Diagnostic and prognostic implications of MAML2 gene translocation in primary pulmonary mucoepidermoid carcinoma].

Objective: To investigate MAML2 gene-translocation in primary pulmonary mucoepidermoid carcinoma (PMEC) and pulmanary adenosquamous carcinoma, and the optimal diagnostic immunohistiochemical (IHC) panel in distinguishing PMEC from adenosqumous carcinoma. Methods: Twenty-four cases of PMEC and 44 adenosqumous carcinoma diagnosed in the Guangdong General Hospital were tested for MAML2 translocation by fluorescent in-situ hybridization (FISH) using tissue array. An IHC panel including TTF1, Napsin A, CK5/6, p63, p40 and Ki-67 was performed on the cohort. The clinical data for all cases were collected and all PMEC patients had follow-up information. Results: The patients' age ranged form 6 to 73 years, with a median age of 32 years. The male to female ratio was 1.4∶1.0. MAML2 translocation was found in 16/24 (66.7%) cases of PMEC whereas all 44 cases adenosqumous carcinoma were negative for translocation. All the cases of the PMEC were negative for TTF1 and Napsin A but positive for CK5/6, p63 and p40 in the intermediate cells and epidermal-like cells. In most PMEC cases, the Ki-67 expression index was lower than 10%. In contrast, most cases of adenosqumous carcinomas expressed TTF1 and Napsin A in the adenomatous component and CK5/6, p63 and p40 in the squamous component, which expression pattern was different from that of PMEC. Based on IHC staining, 2 cases of highly invasive ALK-positive adenocarcinoma mimicing PMEC were also found in the study. Conclusions: MAML2 gene translocation can be detected in about two-third of PMEC. Translocation of MAML2 gene and lower morphology grading are associated with good prognosis. The combined use of IHC antibodies panel is helpful to distinguish PMEC from the adenosqumous carcinoma and adenocarcinoma mimicing PMEC.

[Detection and application of bcl-2/IgH gene translocation and immunoglobulin gene rearrangement in follicular lymphoma].

Objective: To evaluate the application of FISH testing of bcl-2/IgH gene translocation and IgH/L gene rearrangement in different stages of follicular lymphoma. Methods: In 32 follicular lymphoma cases, which were collected at Guangdong General Hospital from September 2014 to December 2016, the bcl-2/IgH gene ectopic state was detected by FISH while the IgH/L gene rearrangement was tested using PCR-GeneScan to analyze the relationship between bcl-2/IgH gene translocation, different stages of follicular lymphoma and clonal immunoglobulin (IgH/L) gene rearrangements. Results: From the paraffin sections of all 32 follicular lymphomas, 17 cases showed bcl-2/IgH gene translocation, and the percentages of FL1, FL2 and FL3 translocation were 12/13, 3/5 and 2/14, respectively. Among the 24 cases of IgH/L gene arrangements identified from the total sample, the occurrence rates of FL1, FL2 and FL3 gene arrangement were 7/13, 4/5 and 13/14, respectively. Spearman's rank correlation analysis and χ(2) analysis showed that bcl-2/IgH gene translocation was negatively correlated with follicular lymphoma stage and the association was statistically significant. In more advanced stages of follicular lymphoma, the occurrence of bcl-2/IgH gene translocation tended to decrease with distinct FL1, FL2 and Fl3 gene expression (P<0.05). As IgH/L gene rearrangement in FL3 was higher than that in FL1 and FL2, its detection may be complimentary to FISH test for bcl-2/IgH gene translocation in diagnosing follicular lymphoma. Conclusions: The combined use of FISH and PCR-GeneScan increases the positive rate of follicular lymphoma diagnosis, and this combination is more sensitive than FISH or clonal analysis only to detect the chromosomal abnormality or the gene rearrangement.

Unique genetic profiles from cerebrospinal fluid cell-free DNA in leptomeningeal metastases of EGFR-mutant non-small-cell lung cancer: a new medium of liquid biopsy.

Background: Leptomeningeal metastases (LM) are more frequent in non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM. Patients and methods: Primary tumor, CSF, and plasma in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients with suspected LM underwent lumbar puncture, and those with EGFR mutations diagnosed with LM were enrolled. Results: A total of 28 patients were enrolled in this cohort; CSF and plasma were available in 26 patients, respectively. Driver genes were detected in 100% (26/26), 84.6% (22/26), and 73.1% (19/26) of samples comprising CSF cell-free DNA (cfDNA), CSF precipitates, and plasma, respectively; 92.3% (24/26) of patients had much higher allele fractions in CSF cfDNA than the other two media. Unique genetic profiles were captured in CSF cfDNA compared with those in plasma and primary tissue. Multiple copy number variations (CNVs) were mainly identified in CSF cfDNA, and MET copy number gain identified in 47.8% (11/23) of patients was the most frequent one, while other CNVs included ERBB2, KRAS, ALK, and MYC. Moreover, loss of heterozygosity (LOH) of TP53 was identified in 73.1% (19/26) CSF cfDNA, which was much higher than that in plasma (2/26, 7.7%; P < 0.001). There was a trend towards a higher frequency of concomitant resistance mutations in patients with TP53 LOH than those without (70.6% versus 33.3%; P = 0.162). EGFR T790M was identified in CSF cfDNA of 30.4% (7/23) of patients who experienced TKI progression. Conclusion: CSF cfDNA could reveal the unique genetic profiles of LM and should be considered as the most representative liquid biopsy medium for LM in EGFR-mutant NSCLC.

A model of ion transport processes along and across the neuronal membrane.

In this study, we provide a foundational model of ion transport processes in the intracellular and extracellular compartments of neurons at the nanoscale. There are two different kinds of ionic transport processes: (i) ionic transport across the neuronal membrane (trans-membrane), and (ii) ionic transport along both the intracellular and extracellular surfaces of the membrane. Brownian dynamics simulations are used to give a description of ionic trans-membrane transport. Electro-diffusion is used to model ion transport along the membrane surface, and the two transport processes can be linked analytically. In our model, we found that the interactions between ions and ion channels result in high-frequency ionic oscillations during trans-membrane transport. In ion transport along the membrane, high-frequency ionic oscillations may be evoked on both the intracellular and extracellular surfaces of the plasma membrane. The electric field caused by Coulomb interactions between the ions is found to be the most likely origin of those ionic oscillations.

S-shaped non-paraxial corrections to general astigmatic beams.

Non-paraxial perturbation wave equations are solved for general astigmatic Gaussian beams for the first time, to the best of our knowledge, in the angular spectrum representation by taking into account generic boundary conditions. Expressions for second-order corrections are derived and exemplified with an optical cavity made of two cylindrical mirrors. Non-paraxial corrections can lead, depending on the choice of boundary conditions, to a transverse S-shaped beam mode, which has been qualitatively been observed in a highly divergent non-planar four-mirror cavity.

High finesse pulsed optical cavity locking by tilt-locking technique.

We report the Tilt-Locking (TL) technique applied to lock a laser in pulsed regime to a 28,000 high finesse Fabry-Perot cavity. Preliminary experimental results show that TL technique is comparable with the well-known Pound-Drever-Hall technique. This study is the first to implement the TL technique to lock a pulsed laser to a high-finesse optical cavity. Very high and stable coupling is obtained. The coupling rate is ~80%, and locking can last for more than 1 h. Furthermore, while previously published papers have focused on near field case, in this study we will give the error signal shape simulation for the far field case. We will show that for different types of error sources, the split photodiode transverse position can be carefully adjusted to obtain a symmetrical error signal. Our experimental results are consistent with the simulations.

Phase-space dynamics of ionization injection in plasma-based accelerators.

The evolution of beam phase space in ionization injection into plasma wakefields is studied using theory and particle-in-cell simulations. The injection process involves both longitudinal and transverse phase mixing, leading initially to a rapid emittance growth followed by oscillation, decay, and a slow growth to saturation. An analytic theory for this evolution is presented and verified through particle-in-cell simulations. This theory includes the effects of injection distance (time), acceleration distance, wakefield structure, and nonlinear space charge forces, and it also shows how ultralow emittance beams can be produced using ionization injection methods.

Generating high-brightness electron beams via ionization injection by transverse colliding lasers in a plasma-wakefield accelerator.

The production of ultrabright electron bunches using ionization injection triggered by two transversely colliding laser pulses inside a beam-driven plasma wake is examined via three-dimensional particle-in-cell simulations. The relatively low intensity lasers are polarized along the wake axis and overlap with the wake for a very short time. The result is that the residual momentum of the ionized electrons in the transverse plane of the wake is reduced, and the injection is localized along the propagation axis of the wake. This minimizes both the initial thermal emittance and the emittance growth due to transverse phase mixing. Simulations show that ultrashort (~8 fs) high-current (0.4 kA) electron bunches with a normalized emittance of 8.5 and 6 nm in the two planes, respectively, and a brightness of 1.7×10(19) A rad(-2) m(-2) can be obtained for realistic parameters.

Generating ultrabroadband terahertz radiation based on the under-compression mode of velocity bunching.

We propose and analyze a scheme to generate enhanced ultrabroadband terahertz (THz) radiation through coherent transition radiation emitted by ultrashort electron beams based on a 10.5 m beamline at Tsinghua University. The proposed scheme involves the initial compression of the electron beam with a few hundred pC charges using a velocity bunching scheme (i.e., RF compression) in an under-compression mode instead of the usual critical-compression mode in order to maintain a positive energy chirp at the exit of the traveling wave accelerator. After a long drift segment, the particles in the tail catch up with the bunch head. More than 80% of the particles are distributed in a spike with an rms length less than 20 fs. Such beams correspond to an ultrabroadband coherent transition radiation (CTR) spectrum of 0.1 THz to 25 THz, with the single-pulse THz radiation energy of up to 50 µJ. The principle of CTR and under-compression mode of velocity bunching are introduced in this paper. And the ASTRA simulation parameters and the stability of the system are also discussed.

HLA-A*31:56 and HLA-A*31:59 were identified by polymerase chain reaction sequence-based typing in Chinese individuals.

Compared with HLA-A*31:01:02, HLA-A*31:56 shows one nucleotide difference at position 706 G>A and HLA-A*31:59 has a single nucleotide polymorphism at position 626 C>T.

A novel allele HLA-DRB1*11:119 was identified by polymerase chain reaction sequence-based typing in a Chinese individual.

HLA-DRB1*11:119 has one nucleotide difference from HLA-DRB1*11:25 at position 286 T>A in exon 2.

Characterization of a novel allele, HLA-DQB1*05:03:05.

HLA-DQB1*05:03:05 differs from DQB1*05:03:01 at nucleotide position 336 A>G in exon 2.

Identification of a novel HLA-DQB1*03:03:04 allele by polymerase chain reaction sequence-based typing in a Chinese leukemia patient.

Nucleotide sequence of HLA-DQB1*03:03:04 allele was different from that of HLA-DQB1*03:03:02 by a single nucleotide substitution at position 603 C>T.

Identification of a novel HLA-C*07:02:25 allele by polymerase chain reaction sequence-based typing in a Chinese leukemia patient.

Nucleotide sequence of HLA-C*07:02:25 allele was different from that of HLA-C*07:02:01:01 by a single nucleotide substitution at position 78C>G.

Identification of a novel HLA-DRB1 allele, HLA-DRB1*12:27, in a Chinese individual.

Nucleotide sequence of HLA-DRB1*12:27 allele was different from that of HLA-DRB1*12:02:01 by three-nucleotide substitution at position 165A>C, 171G>C, and 175C>T.