Sensitizing tumors to anti-PD-1 therapy by promoting NK and CD8+ T cells via pharmacological activation of FOXO3.

BACKGROUND: Stimulating antitumor immunity by blocking programmed death-1 (PD-1) or its ligand (programmed death-ligand 1 (PD-L1) is a promising antitumor therapy. However, numerous patients respond poorly to PD-1/PD-L1 blockade. Unresponsiveness to immune-checkpoint blockade (ICB) can cast significant challenges to the therapeutic options for patients with hard-to-treat tumors. There is an unmet clinical need to establish new therapeutic approaches for mitigating ICB unresponsiveness in patients. In this study, we investigated the efficacy and role of low-dose antineoplastic agent SN-38 or metformin in sensitizing unresponsive tumors to respond to ICB therapy. METHODS: We assessed the significant pathological relationships between PD-L1 and FOXO3 expression and between PD-L1 and c-Myc or STAT3 expression in patients with various tumors. We determined the efficacy of low-dose SN-38 or metformin in sensitizing unresponsive tumors to respond to anti-PD-1 therapy in a syngeneic tumor system. We deciphered novel therapeutic mechanisms underlying the SN-38 and anti-PD-1 therapy-mediated engagement of natural killer (NK) or CD8+ T cells to infiltrate tumors and boost antitumor immunity. RESULTS: We showed that PD-L1 protein level was inversely associated with FOXO3 protein level in patients with ovarian, breast, and hepatocellular tumors. Low-dose SN-38 or metformin abrogated PD-L1 protein expression, promoted FOXO3 protein level, and significantly increased the animal survival rate in syngeneic mouse tumor models. SN-38 or metformin sensitized unresponsive tumors responding to anti-PD-1 therapy by engaging NK or CD8+ T cells to infiltrate the tumor microenvironment (TME) and secret interferon-γ and granzyme B to kill tumors. SN-38 suppressed the levels of c-Myc and STAT3 proteins, which controlled PD-L1 expression. FOXO3 was essential for SN38-mediated PD-L1 suppression. The expression of PD-L1 was compellingly linked to that of c-Myc or STAT3 in patients with the indicated tumors. CONCLUSION: We show that SN-38 or metformin can boost antitumor immunity in the TME by inhibiting c-Myc and STAT3 through FOXO3 activation. These results may provide novel insight into ameliorating patient response to overarching immunotherapy for tumors.

Effect of magnetic field on electroosmotic flow of viscoelastic fluids in a microchannel.

Electroosmotic flow is an efficient transportation technology driven by applying an external electric field across the microchannel, which has a great potential for future application. This work is presented to study the unsteady electroosmotic flow of viscoelastic fluids combined with a constant pressure gradient and a vertical magnetic field through a parallel plate microchannel. For the reason that the upper and bottom walls of the parallel plate microchannel in microfluidic devices can be made of different materials, this leads to different hydrophobic properties, asymmetric zeta wall potentials, and different slip boundary conditions. The Navier slip model with different slip coefficients at walls is considered. The generalized Maxwell fluid with fractional derivative is adopted for the constitutive equation of the fluid. The analytical and numerical solutions of velocity are derived by employing the integral transform method and finite difference method, respectively. Excellent agreement is found between the numerical solutions and analytical solutions. Finally, the effects of fractional parameter α , relaxation time λ , slip coefficients a and b , the ratio of wall zeta potentials Rξ , Hartmann number Ha , and electrical field strength parameter S on velocity profiles are interpreted graphically in detail.

Numerical study of electroosmotic slip flow of fractional Oldroyd-B fluids at high zeta potentials.

In this paper, an investigation of the electroosmotic flow of fractional Oldroyd-B fluids in a narrow circular tube with high zeta potential is presented. The Navier linear slip law at the walls is considered. The potential field is applied along the walls described by the nonlinear Poisson-Boltzmann equation. It's worth noting here that the linear Debye-Hückel approximation can't be used at the condition of high zeta potential and the exact solution of potential in cylindrical coordinates can't be obtained. Therefore, the Matlab bvp4c solver method and the finite difference method are employed to numerically solve the nonlinear Poisson-Boltzmann equation and the governing equations of the velocity distribution, respectively. To verify the validity of our numerical approach, a comparison has been made with the previous work in the case of low zeta potential and the excellent agreement between the solutions is clear. Then, in view of the obtained numerical solution for the velocity distribution, the numerical solutions of the flow rate and the shear stress are derived. Furthermore, based on numerical analysis, the influence of pertinent parameters on the potential distribution and the generation of flow is presented graphically.

Endothelin B Receptor is Involved in Endothelin-1 Induced Cell Response in Vascular Smooth Muscle Cells.

Cardiovascular disease is an important problem in developed countries and the effective target of treatment should be further developed. ETB receptor is one of receptor of ET system, which may affect the function of vascular smooth muscle cell via NO released. In order to clarify the theory, we had cell culture with or without ET-1 treatment. Flow cytometry had been used to prove cell apoptosis and transwell assay had been used to detect the ability of cell migration. The expression of ET-1, ICAM-1, VCAM-1, MMP-9 and CRP were detected by using qRT-PCR and Western blot assay. After we had found that RES-701-1 one of ETB receptor antagonists can induced VSMC apoptosis and migration. Also RES-701-1 can down regulated ICAM-1, VCAM-1, MMP-9 and CRP while ET-1 was the opposite. In a conclusion ETB receptor is one of the role target to mediate vascular smooth muscle cell through the ET system and it may be a significant treating target in cardiovascular disease in the future.

A comparative study of mitral valve replacement by right 3rd intercostal small incision and traditional median thoracotomy / 中国胸心血管外科临床杂志

@#Objective    To compare the safety and efficacy of simple mitral valve replacement with the third intercostal incision on the right side and the conventional midsternum incision. Methods    From February 2017 to February 2019, heart surgery in the Affiliated Hospital of Jining Medical College completed the first simple mitral valve replacement (MVR) operation in 103 patients, of whom 39 patients were received minimally invasive right third intercostal small incision (a minimally invasive surgery group). There were 10 males, 29 females at average age of 59.51 years. There were 64 patients with MVR via the middle section of the common sternum (a conventional surgery group), 22 males and 42 females, with an average age of 60.22 years. Types of lesions: 65 patients were with mitral stenosis, 22 patients with incomplete closure, 16 patients with incomplete closure. Results    There was no significant difference in preoperative clinical data between the two groups (P>0.05). The entire group of patients successfully completed the operation. Surgical replacement of mitral valve mechanical valve in 74 patients and biological valve in 29 patients. There was no significant difference between the two groups in the extracardiopulmonary cycle time, aortic blockade time and total hospitalization time. In the early stage of operation, 3 patients were examined for secondary hemostasis, 1 patient was minimally invasive surgery, and the remaining 2 patients were with routine surgery. The infection of incision occurred in 3 patients, all of them were in the routine operation group. All three patients died early after operation in the routine operation group: two were postoperative low cardiac volumetric syndrome leading to multiple organ failure, and the other was sternum infection accompanied by artificial valve endocarditis. Conclusion    There is no significant difference between MVR through the third rib of the right chest and traditional MVR in the safety. However, it has the advantages of small trauma, beauty, low incidence of incision infection and reduced postoperative pain.

Oxytocin receptor: Expression in the trigeminal nociceptive system and potential role in the treatment of headache disorders.

AIMS: Our studies investigated the location of oxytocin receptors in the peripheral trigeminal sensory system and determined their role in trigeminal pain. METHODS: Oxytocin receptor expression and co-localization with calcitonin gene-related peptide was investigated in rat trigeminal ganglion using immunohistochemistry. Enzyme-linked immunosorbent assay was used to determine the effects of facial electrocutaneous stimulation and adjuvant-induced inflammation of the temporomandibular joint on oxytocin receptor expression in the trigeminal ganglion. Finally, the effects of oxytocin on capsaicin-induced calcitonin gene-related peptide release from dural nociceptors were investigated using isolated rat dura mater. RESULTS: Oxytocin receptor immunoreactivity was present in rat trigeminal neurons. The vast majority of oxytocin receptor immunoreactive neurons co-expressed calcitonin gene-related peptide. Both electrocutaneous stimulation and adjuvant-induced inflammation led to a rapid upregulation of oxytocin receptor protein expression in trigeminal ganglion neurons. Oxytocin significantly and dose-dependently decreased capsaicin-induced calcitonin gene-related peptide release from dural nociceptors. CONCLUSION: Oxytocin receptor expression in calcitonin gene-related peptide containing trigeminal ganglion neurons, and the blockade of calcitonin gene-related peptide release from trigeminal dural afferents suggests that activation of these receptors may provide therapeutic benefit in patients with migraine and other primary headache disorders.

[Study on Asymmetric Spatial Heterodyne Spectroscopy].

Restrictive relationship exists between spectral resolution, spectral range and number of pixels of traditional Spatial Heterodyne Spectroscopy (SHS). The main difference between Asymmetric Spatial Heterodyne Spectroscopy (ASHS) and SHS accelerates the space of one grating from the beamsplitter. It greatly increases spectral resolution while system parameters remain unchanged. First of all, this paper elaborates the fundamentals of the ASHS, the derived formulas of the system parameters and theoretical relationship between grating offset and the spectral resolution increases. As an important parameter of the ASHS, offset is restricted by the pixel number of short double side interferogram and the spectral resolution requirements. According to the experimental breadboard parameters of laboratory, the selection principle and the results of the offset are presented. In the case of the same device parameters, two types of theoretical performance parameters are calculated. The simulation is carried out. The results show that two of them have the same spectral range, but the ASHS has a higher spectral resolution. The relationship between resolution and offset increased consistent with theoretical calculation. Finally the ASHS breadboard is calibrated with the monochromatic light scanning method. The derived spectral range and resolution are in good agreement with the theoretical value.

[Data Processing Method of Asymmetric Spatial Heterodyne Interferogram for Wind Measurement].

By using doppler asymmetric spatial heterodyne spectroscopy and doppler effect, the wind speed can be achieved through detecting the interferogram of airglow in the upper atmosphere. This paper mainly analyses the data processing method of the interferogram and then derive the interferometer phase in order to get the wind speed. Comparing with the traditional spatial heterodyne spectroscopy, not only the noise and error of the system should be taken into consideration, but the window function that used to isolate the spectrum has a great influence during the data processing. Then the effect of window type and window width on phase difference of interferogram and the wind error curve are simulated through software. On basis of this the wind error curve under the noise of system and flat field factor are simulated by choosing appropriate window function. The window function simulation indicates that although the joining of window leads to a distortion of the interferogam and phase, the wind speed error can be less than 0.5% with Hanning window in the appropriate optical path difference. The noise of the system simulation indicates that the wind speed error increases with the noise, so it is necessary to control the system noise and preprocess the sampling data. The research on data processing method has great theoretical significance and practical value for designing the system parameter and improving the precision of spatial heterodyne wind detection.

A Self-microemulsifying Drug Delivery System (SMEDDS) for a Novel Medicative Compound Against Depression: a Preparation and Bioavailability Study in Rats.

AJS is the code name of an untitled novel medicative compound synthesized by the Tasly Holding Group Company (Tianjin, China) based on the structure of cinnamamide, which is one of the Biopharmaceutics Classification System (BCS) class II drugs. The drug has better antidepressant effect, achieved by acting on the 5-hydroxytryptamine receptor. However, the therapeutic effects of the drug are compromised due to its poor water solubility and lower bioavailability. Herein, a self-microemulsifying drug delivery system (SMEDDS) was developed to improve its solubility and oral bioavailability. AJS-SMEDDS formulation was optimized in terms of drug solubility in the excipients, droplet size, stability, and drug precipitation using a pseudo-ternary diagram. The pharmacokinetic study was performed in rats, and the drug concentration in plasma samples was assayed using the high-performance liquid chromatography-electrospray tandem mass spectrometry (HPLC-MS/MS) method. The optimized formulation for SMEDDS has a composition of castor oil 24.5%, Labrasol 28.6%, Cremphor EL 40.8%, and Transcutol HP 2.7% (co-surfactant). No drug precipitation or phase separation was observed from the optimized formulation after 3 months of storing at 25°C. The droplet size of microemulsion formed by the optimized formulation was 26.08 ± 1.68 nm, and the zeta potential was -2.76 mV. The oral bioavailability of AJS-SMEDDS was increased by 3.4- and 35.9-fold, respectively, compared with the solid dispersion and cyclodextrin inclusion; meanwhile, the C max of AJS-SMEDDS was about 2- and 40-fold as great as the two controls, respectively. In summary, the present SMEDDS enhanced oral bioavailability of AJS and was a promising strategy to orally deliver the drug.

Minimally invasive video-assisted double-valve replacement through right anterolateral Minithoracotomy.

OBJECTIVE: This study aimed to investigate feasibility and safety of minimally invasive video-assisted surgery for double-valve (mitral and aortic) replacement through right anterolateral minithoracotomy. METHODS: Between February 2011 and April 2013, 60 patients with combined valvular disease underwent double valve replacement, 26 of them by minimally invasive video-assisted surgery through right anterolateral minithoracotomy (study group) and 34 by median sternotomy (control group). Peripheral cardiopulmonary bypass (CPB) was established through right femoral artery and vein. The incision was made around the right breast approximately 5 cm in length. Pericardiotomy, bicaval occlusion, atriotomy and aortotomy, and double valve replacement were performed with thoracoscope. RESULTS: In the study group, times of CPB and aortic cross-clamp were 146.5 ± 40.5 min and 91.5 ± 23.4 min, respectively, which were significantly different from those in the control group, 115.4 ± 26.5 min and 75.4 ± 16.5 min (P<0.05). Thoracic drainage in the study group was significantly lower than the control group, 587 ± 245 ml (study group) versus 756 ± 267 ml (control group) (P<0.05). Length of ICU and postoperative hospital stay were shorter in the study group, 1.9 ± 0.8 and 8.7 ± 4.5 days versus 2.8 ± 1.3 and 11.2 ± 5.6 days in the control group (P<0.05), respectively. There was no statistical difference in the postoperative results of TTE (transthoracic echocardiography) (P>0.05). All patients recovered smoothly with follow-up of six months to two years, with no severe complications. CONCLUSIONS: Minimally invasive video-assisted procedure through right anterolateral minithoracotomy is a new promising approach for double valve replacement. Our study suggested that this approach was feasible, safe and had cosmetic effects.

Totally thoracoscopic surgery for the treatment of atrial septal defect without of the robotic Da Vinci surgical system.

BACKGROUND: More and more surgeons and patients focus on the minimally invasive surgical techniques in the 21st century. Totally thoracoscopic operation provides another minimal invasive surgical option for patients with ASD (atrial septal defect). In this study, we reported our experience of 61 patients with atrial septal defect who underwent totally thoracoscopic operation and discussed the feasibility and safety of the new technique. METHODS: From January 2010 to October 2012, 61 patients with atrial septal defect underwent totally thoracoscopic closure but not traditional median sternotomy surgery. We divided the 61 patients into two groups based on the operation sequence. The data of group A (the first 30 cases) and group B (the last 31 cases). The mean age of the patients was 35.1 ± 12.8 years (range, 6.3 to 63.5 years), and mean weight was 52.7 ± 11.9 kg (range, 30.5 to 80 kg). Mean size of the atrial septal defect was 16.8 ± 11.3 mm (range, 13 to 39 mm) based on the description of the echocardiography. RESULTS: All patients underwent totally thoracoscopy successfully, 36 patients with pericardium patch and 25 patients were sutured directly. 7 patients underwent concomitant tricuspid valvuloplasty with Key technique. No death, reoperation or complete atrioventricular block occurred. The mean time of cardiopulmonary bypass was 68.5 ± 19.1 min (range, 31.0 to 153.0 min), the mean time of aortic cross-clamp was 27.2 ± 11.3 min (range, 0.0 to 80.0 min) and the mean time of operation was 149.8 ± 35.7 min (range, 63.0 to 300.0 min). Postoperative mechanical ventilation averaged 4.9 ± 2.5 hours (range, 3.5 to 12.6 hours), and the duration of intensive care unit stay 20.0 ± 4.8 hours (range, 15.5 to 25 hours). The mean volume of blood drainage was 158 ± 38 ml (range, 51 to 800 ml). No death, residual shunt, lung atelectasis or moderate tricuspid regurgitation was found at 3-month follow-up. CONCLUSION: The totally thoracoscopic operation is feasible and safe for patients with ASD, even with or without tricuspid regurgitation. This technique provides another minimal invasive surgical option for patients with atrial septal defect.

Herpes simplex virus 1 tropism for human sensory ganglion neurons in the severe combined immunodeficiency mouse model of neuropathogenesis.

The tropism of herpes simplex virus (HSV-1) for human sensory neurons infected in vivo was examined using dorsal root ganglion (DRG) xenografts maintained in mice with severe combined immunodeficiency (SCID). In contrast to the HSV-1 lytic infectious cycle in vitro, replication of the HSV-1 F strain was restricted in human DRG neurons despite the absence of adaptive immune responses in SCID mice, allowing the establishment of neuronal latency. At 12 days after DRG inoculation, 26.2% of human neurons expressed HSV-1 protein and 13.1% expressed latency-associated transcripts (LAT). Some infected neurons showed cytopathic changes, but HSV-1, unlike varicella-zoster virus (VZV), only rarely infected satellite cells and did not induce fusion of neuronal and satellite cell plasma membranes. Cell-free enveloped HSV-1 virions were observed, indicating productive infection. A recombinant HSV-1-expressing luciferase exhibited less virulence than HSV-1 F in the SCID mouse host, enabling analysis of infection in human DRG xenografts for a 61-day interval. At 12 days after inoculation, 4.2% of neurons expressed HSV-1 proteins; frequencies increased to 32.1% at 33 days but declined to 20.8% by 61 days. Frequencies of LAT-positive neurons were 1.2% at 12 days and increased to 40.2% at 33 days. LAT expression remained at 37% at 61 days, in contrast to the decline in neurons expressing viral proteins. These observations show that the progression of HSV-1 infection is highly restricted in human DRG, and HSV-1 genome silencing occurs in human neurons infected in vivo as a consequence of virus-host cell interactions and does not require adaptive immune control.

Totally thoracoscopic surgical treatment for atrial septal defect: mid-term follow-up results in 45 consecutive patients.

BACKGROUND: Totally thoracoscopic operation provides minimally invasive alternative for patients with atrial septal defect. In this study, we report the mid-term follow-up results of 45 patients with atrial septal defect who underwent totally thoracoscopic operation and discuss the feasibility and safety of this new technique. METHODS: From January 2010 to February 2012, 45 patients with atrial septal defect underwent totally thoracoscopic closure as an alternative to traditional median sternotomy surgery. The mean age of the patients was 33.2±12.5 years (range 6.3-61.5 years), and mean weight was 55.7±11.1 kg (range 30.5-80 kg). Based on echocardiography the mean size of the atrial septal defect was 16.0±10.8mm (range 13-39 mm). RESULTS: All patients underwent totally thoracoscopic repair. Twenty-five patients with a pericardial patch and 20 patients were sutured directly. Five patients underwent concomitant tricuspid valvuloplasty with Kay technique. No death, reoperation or complete atrioventricular block occurred. The mean time of cardiopulmonary bypass was 70.5±20.6 min (range 31.0-153.0 min), the mean time of aortic cross-clamp was 28.8±13.3 min (range 0.0-80.0 min) and the mean time of operation was 155.8±36.8 min (range 65.0-300.0 min). Postoperative mechanical ventilation averaged 5.1±2.8h (range 3.6-12.6h), and the duration of intensive care unit stay 20.0±5.6h (range 16.2-25 h). The mean volume of blood drainage was 156±36 ml (range 51-800 ml). No death, residual shunt, lung atelectasis or moderate tricuspid regurgitation was found at three-month follow-up. CONCLUSION: Totally thoracoscopic repair is feasible and safe for patients with ASD, even with or without tricuspid regurgitation however more clinical data is needed in the future study.

Genetic analysis of the TBX3 gene promoter in ventricular septal defects.

Congenital heart disease (CHD) is the most common birth defect in humans. Genetic causes and underlying molecular mechanisms for CHD remain largely unknown. T-box transcription factor 3 (TBX3) plays a critical role in the developing heart in a dose-dependent manner. TBX3 represses chamber myocardial gene expression. Mutations in TBX3 gene have been associated to ulnar-mammary syndrome with multiple developmental defects, including cardiac defects. We hypothesized that the sequence variants within TBX3 gene promoter that change TBX3 levels may mediate CHD development. In this study, TBX3 gene promoter was genetically analyzed in large cohorts of patients with ventricular septal defect (VSD) (n=325) and ethnic-matched healthy controls (n=359). Seven sequence variants, including two single-nucleotide polymorphisms (g.3863 C>T and g.4095G>T), three novel deletions (g.4433_4435del, g.4672_4675del and g.4820_4821del) and two novel insertions (g.3913_3914ins and g.4735_4736ins), were identified. Five of the seven variants were identified in VSD patients and controls with similar frequencies. Two other variants were found only in controls. These variants, which were observed in high frequencies, did not modify or interrupt the critical binding site for basic transcription factors. Taken together, these results suggested that the sequence variants within the TBX3 gene promoter did not contribute to VSD etiology.

Preprotachykinin-A gene disruption attenuates nociceptive sensitivity after opioid administration and incision by peripheral and spinal mechanisms in mice.

UNLABELLED: The preprotachykinin A gene (ppt-A) codes for Substance P (SP), supports nociceptive sensitization, and modulates inflammatory responses after incision. Repeated opioid use produces paradoxical pain sensitization-termed opioid-induced hyperalgesia (OIH) -which can exacerbate pain after incision. Here the contribution of SP to peri-incisional nociceptive sensitization and nociceptive mediator production after opioid treatment was examined utilizing ppt-A knockout (-/-) mice and the neurokinin (NK1) receptor antagonist LY303870. Less mechanical allodynia was observed in ppt-A(-/-) mice compared to wild types (wt) after morphine treatment both before and after incision. Moreover, LY303870 administered with morphine reduced incisional hyperalgesia in wt mice. Incision after saline or escalating morphine treatment upregulated skin IL-1ß, IL-6, G-CSF and MIP-1α levels in ppt-A(-/-) and wt mice similarly. However, chronic morphine treatment greatly exacerbated increases in skin nerve growth factor levels after incision, an effect entirely dependent upon intact SP signaling. Additionally, SP dependent upregulation of prodynorphin, NMDA1 and NK1 receptor expression in spinal cord was seen after morphine treatment and incision. A similar pattern was seen for 5-HT3 receptor expression in tissue from dorsal root ganglia. Therefore, SP may work at both central and peripheral sites to enhance nociceptive sensitization after morphine treatment and incision. PERSPECTIVE: These studies show that SP signaling modulates enhanced nerve growth factor production and changes in neuronal gene expression seen after incision in mice previously exposed to morphine.

Genetic and functional analysis of the NKX2-5 gene promoter in patients with ventricular septal defects.

The ventricular septal defect (VSD) is the most common type of congenital heart disease (CHD). The morbidity and mortality of CHD patients are significantly higher due to late cardiac complications, likely caused by genetic defects. Mutations in cardiac transcription factor genes such as GATA-4, TBX5, and NKX2-5 have been implicated in CHD cases. The NKX2-5 gene, a homeobox gene, is expressed in the developing heart and the adult heart. Because NKX2-5 is a dosage-sensitive regulator during embryonic development, the authors hypothesized that the expression levels of the NKX2-5 gene rather than the mutant protein may play important roles in CHD. In this study, the promoter regions and exon regions of the NKX2-5 gene were bidirectionally sequenced in large cohorts of VSD patients and healthy control subjects. The results showed that a novel sequence variant (g.4574c>deletion), found only in one VSD patient, and a single nucleotide polymorphism (rs118026695), the frequency of which was significantly higher in VSD patients, were identified within the promoter region. Functional analysis confirmed that these sequence variants significantly enhanced the transcriptional activities of the NKX2-5 gene promoter, altering the expression of the NKX2-5 gene and the cardiac gene regulatory network. In addition, a synonymous mutation in the second exon of the NKX2-5 gene was identified in one VSD patient, which may affect the translation process. Therefore, the authors' data provide supportive evidence that mutations in the coding region of the NKX2-5 gene and sequence variants within its promoter region may be among the contributors to the CHD etiology.

Genetic analysis of the TBX20 gene promoter region in patients with ventricular septal defects.

Congenital heart disease (CHD) is the most common human birth defect. The morbidity and mortality of CHD patients are significantly higher than normal population even after surgical correction of cardiac defects, which is likely caused by genetic defects. To date, genetic causes for CHD remain largely unknown. TBX20 gene encodes a T-box transcription factor that plays pivotal roles in cardiac morphogenesis and is required for maintaining adult heart function and maturation. Mutations in TBX20 gene have been reported in familiar and sporadic CHD patients. However, the promoter region of TBX20 gene has not been genetically analyzed in CHD patients. As TBX20 functions as a dosage-dependent regulator during the heart development, we hypothesized that the sequence variants within the promoter region of the TBX20 gene may contribute to CHD. In this study, we bi-directionally sequenced the promoter region of the TBX20 gene in 265 patients with ventricular septal defects (VSD) and 242 controls. Within the promoter region of the TBX20 gene, one single-nucleotide polymorphism (SNP), rs336284 (g.4740T>C), and one novel heterozygous variant g.4741 G>A, which was linked with rs336284 (g.4740 T>C), were found in both VSD patients and controls with similar frequencies. A novel heterozygous variant, g.4932 G>A, was found in one VSD patient, but in none of controls, which significantly inhibited the transcriptional activities of TBX20 gene promoter, suggesting that the variant may contribute to the VSD etiology. Therefore, our data provides new information with respect to TBX20 gene mutations in CHD patients.

[Inversion of the lake total nitrogen concentration by multiple regression kriging model based on hyperspectral data of HJ-1A].

The content of total nitrogen in the waters is an important index to measure lake water quality, and the technique of remote sensing plays a large role in quantitatively monitoring the dynamic change and timely grasping the status of lake pollution. Taking Chaohu as an example, quantitative inversion models of total nitrogen were established by multivariable regression Kriging under analyzing of an correlation between total nitrogen and chlorophyll-a or suspended solids by HIS hyperspectral remote sensing data of HJ-1A satellite. The result shows that the correlation of 0.76 was discovered between total nitrogen and the multiple combination with band 72, band 79 and band 97, while the correlation could be increased to 0.83 by applying combined model of multiple linear regression and ordinary Kriging. The optimization of the residuals of the conventional regression model can improve the accuracy of the inversion effectively. These results also provide useful exploration for further establishing a common model of quantitative inversion of lake total nitrogen concentration.

[Radiometric calibration of LCTF-based multispectral area CCD camera].

Multispectral area CCD camera based on liquid crystal tunable filter (LCTF) is a new spectral imaging system, which could record image of one wavelength on the area CCD by utilizing electrically controlled birefringence of liquid-crystal and interference principle of polarized light. Because of the special working principle of LCTF and frame transfer area CCD, the existing radiometric calibration method can not meet the precision need of remote sensing application if it is used for LCTF-camera. An improved radiometric calibration method is proposed, in which the camera performance test and calibration experiment are carried out relying on the devices of integrating sphere and standard detector, and the absolute calibration coefficient is calculated via correcting frame transfer smear and improving data process algorithm. Then the validity of the laboratory calibration coefficient is checked by a field validation experiment. Experimental result indicates that the calibration coefficient is valid, and the radiation information on the ground could be accurately inverted from the calibrated image data. With the resolution of radiometric calibration of LCTF-camera and the improvement of calibration precision, the application field of the image data acquired by the camera would be extended effectively.