VEGF and EGFR signaling pathways are involved in the baicalein attenuation of OVA-induced airway inflammation and airway remodeling in mice.

BACKGROUND: Although Traditional Chinese Medicine (TCM) has been used for treating asthma for centuries, the understanding of its mechanism of action is still limited. Thus, the purpose of this study was to explore the possible therapeutic effects, and underlying mechanism of baicalein in the treatment of asthma. METHODS: Freely availabled atabases (e.g. OMIM, TTD, Genecards, BATMAN-TCM, STITCH 5.0, SEA, SwissTargetPrediction) and software (e.g. Ligplot 2.2.5 and PyMoL) were used for disease drug target prediction and molecular docking by network pharmacology. The efficacy and mechanism of action of baicalein in the treatment of asthma were validated using an ovalbumin (OVA)-induced asthma mouse model and molecular biology techniques. RESULTS: A total of 1655 asthma-related genes and 161 baicalein-related targets were identified from public databases. Utilizing common databases and software for network pharmacology and molecular docking analysis, seven potential target proteins for the therapeutic effects of baicalein on asthma were selected, including v-akt murine thymoma viral oncogene homolog 1 (AKT1), vascular endothelial growth factor A (VEGFA), epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase Src (SRC), mitogen-activated protein kinase 3 (MAPK3), matrix metallopeptidase 9 (MMP9), and MAPK1. In vivo, baicalein treatment via intraperitoneal injection at a dose of 50 mg/kg significantly reduced airway inflammation, collagen deposition, smooth muscle thickness, lung interleukin (IL)-4 and IL-13 levels, peripheral blood immunoglobulin (Ig)E levels, as well as the count and ratio of eosinophils in bronchoalveolar lavage fluid (BALF) in an OVA-induced asthma mouse model. Further validation by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting analysis revealed that the VEGF and EGFR signaling pathways involving VEGFA, MAPK1, MAPK3, and EGFR were inhibited by baicalein in the asthma mouse model. CONCLUSION: Baicalein attenuates airway inflammation and airway remodeling through inhibition of VEGF and EGFR signaling pathways in an OVA-induced asthma mouse model. This will provide a new basis for the development of baicalein as a treatment for asthma and highlights the potential of network pharmacology and molecular docking in drug discovery and development.

Comparison of the surgical outcomes of the posterior approach, video-assisted thoracic surgery, and combined approach for thoracic dumbbell tumors based on a new classification: a retrospective study.

The appropriate surgical treatment strategy was based on the regions of tumor invasion. There is no classification to aid the surgeon in selection. A retrospective study of the clinical data of patients who underwent resection of thoracic dumbbell tumors at the Neurosurgery and Thoracic Surgery Department of Hospital between January 1, 2016, and December 31, 2021 was conducted. Patient data, images, and surgical outcome data were collected. The thoracic spine was divided into areas A, B, and C with respect to the line through the middle of the intervertebral foramen and the line of the costo-transverse joint lateral margin in the horizontal plane. Type I tumors were located in areas A or A and B, type II tumors were located in areas B or B and C, and type III tumors were located in areas A, B, and C. Fifty-five patients with thoracic dumbbell tumors were surgically treated (mean age, 43.1 years; 22 (40%) female). The patients with type I and III tumors underwent the posterior approach, type III tumors had more bleeding during the operation and longer operation times than type I. Among the patients with type II tumors who underwent video-assisted thoracic surgery and the posterior approach, the posterior group had more bleeding and a longer operation time than the others. The patients with type III tumors underwent the combined approach and the posterior approach; although there was no clear difference in the bleeding volume or operation time, the combined approach group had a lower incidence of complications. The new classification of different types of thoracic dumbbell tumors can simply and effectively guide the selection of surgery.

[Mechanism of Fuzheng Huayu Tablets against hepatic fibrosis based on transcriptome and single-cell sequencing].

This study aimed to investigate the role of macrophage polarization in the treatment of liver fibrosis by Fuzheng Huayu Tablets(FZHY) through single-cell, transcriptome sequencing and in vitro and in vivo experiments. Liver fibrosis-related datasets, transcriptomic datasets, and single-cell sequencing datasets were obtained from the Gene Expression Omnibus(GEO) database to screen differential genes. Liver fibrosis-related genes were obtained from GeneCards, DisGeNET, NCBI, PharmgKB, TTD and OMIM databases. Macrophage polarization-related genes were obtained from the GeneCards database. The above three gene sets were intersected to construct a protein-protein interaction(PPI) network. Cytoscape software was used to screen core proteins, and the expression pattern of core proteins was visualized by single-cell sequencing. A mouse model of liver fibrosis was constructed using carbon tetrachloride(CCl_4). Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological morphology of liver tissues. The expressions of α-smooth muscle actin(α-SMA) and transforming growth factor-ß1(TGF-ß1) were detected by immunohistochemistry. The levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected by colorimetry. The le-vels of inflammatory factors in serum were detected by the enzyme-linked immunosorbent assay(ELISA). Furthermore, the expressions of α-SMA, TGF-ß1, cluster of differentiation 86(CD86) and thrombospondin 1(THBS1) in liver tissues were detected by Western blot(WB). Lipopolysaccharide(LPS) was used to stimulate RAW264.7 cells to construct the M1 macrophage polarization model. The cell counting kit-8(CCK-8) method was used to detect cell viability. WB was used to detect the protein expressions of CD86 and THBS1 in cells, and the messenger ribonucleic acid(mRNA) expression levels of tumor necrosis factor-α(TNF-α) and interleukin(IL)-1ß by real-time fluorescent quantitative reverse transcription polymerase chain reaction(RT-qPCR). The results showed that a total of 26 potential genes related to the polarization of liver fibrosis macrophages were obtained, and 10 core proteins related to the polarization of liver fibrosis macrophages such as THBS1, lumican(LUM) and fibulin-5(FBLN5) were screened. Single-cell data analysis indicated that THBS1, ranking highest, may be expressed by M1 macrophages. Animal experiments demonstrated that FZHY reduced inflammatory cell infiltration and collagen deposition in CCl_4-induced mouse liver, relieved liver injury and inflammation levels, and inhibited the expressions of α-SMA, TGF-ß1, CD86, and THBS1 proteins. Cell experiments revealed that FZHY significantly reduced intracellular expression of CD86 and THBS1 proteins and mRNA levels of TNF-α and IL-1ß. In conclusion, FZHY may ameliorate liver fibrosis by inhibiting THBS1 protein expression, suppressing M1 macrophage polarization, and reducing inflammation.

The stromal-tumor amplifying STC1-Notch1 feedforward signal promotes the stemness of hepatocellular carcinoma.

BACKGROUND: Cancer-associated fibroblasts (CAFs), an important component of the tumor microenvironment (TME), play crucial roles in tumor stemness. It has been shown in various cancer studies that stanniocalcin-1 (STC1) is secreted by CAFs, however, its function in HCC is still not clear. METHODS: The serum concentration and intracellular expression level of STC1 were quantified by ELISA and western blotting, respectively. The role of CAF-derived STC1 in HCC stemness was investigated by sphere formation, sorafenib resistance, colony formation, and transwell migration and invasion assays in vitro and in an orthotopic liver xenograft model in vivo. An HCC tissue microarray containing 72 samples was used to evaluate the expression of STC1 and Notch1 in HCC tissues. Coimmunoprecipitation (CoIP) and dual-luciferase reporter assays were performed to further explore the underlying mechanisms. ELISAs were used to measure the serum concentration of STC1 in HCC patients. RESULTS: We demonstrated that CAFs were the main source of STC1 in HCC and that CAF-derived STC1 promoted HCC stemness through activation of the Notch signaling pathway. In HCC patients, the expression of STC1 was positively correlated with Notch1 expression and poor prognosis. The co-IP assay showed that STC1 directly bound to Notch1 receptors to activate the Notch signaling pathway, thereby promoting the stemness of HCC cells. Our data further demonstrated that STC1 was a direct transcriptional target of CSL in HCC cells. Furthermore, ELISA revealed that the serum STC1 concentration was higher in patients with advanced liver cancer than in patients with early liver cancer. CONCLUSIONS: CAF-derived STC1 promoted HCC stemness via the Notch1 signaling pathway. STC1 might serve as a potential biomarker for the prognostic assessment of HCC, and the stromal-tumor amplifying STC1-Notch1 feedforward signal could constitute an effective therapeutic target for HCC patients.

A lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly.

The HIV capsid self-assembles a protective conical shell that simultaneously prevents host sensing whilst permitting the import of nucleotides to drive DNA synthesis. This is accomplished through the construction of dynamic, highly charged pores at the centre of each capsid multimer. The clustering of charges required for dNTP import is strongly destabilising and it is proposed that HIV uses the metabolite IP6 to coordinate the pore during assembly. Here we have investigated the role of inositol phosphates in coordinating a ring of positively charged lysine residues (K25) that forms at the base of the capsid pore. We show that whilst IP5, which can functionally replace IP6, engages an arginine ring (R18) at the top of the pore, the lysine ring simultaneously binds a second IP5 molecule. Dose dependent removal of K25 from the pore severely inhibits HIV infection and concomitantly prevents DNA synthesis. Cryo-tomography reveals that K25A virions have a severe assembly defect that inhibits the formation of mature capsid cones. Monitoring both the kinetics and morphology of capsids assembled in vitro reveals that while mutation K25A can still form tubes, the ability of IP6 to drive assembly of capsid cones has been lost. Finally, in single molecule TIRF microscopy experiments, capsid lattices in permeabilised K25 mutant virions are rapidly lost and cannot be stabilised by IP6. These results suggest that the coordination of IP6 by a second charged ring in mature hexamers drives the assembly of conical capsids capable of reverse transcription and infection.

Optimizing retrieval spaces of bio-optical models for remote sensing of ocean color.

We investigated the optimal number of independent parameters required to accurately represent spectral remote sensing reflectances (R rs) by performing principal component analysis on quality controlled in situ and synthetic R rs data. We found that retrieval algorithms should be able to retrieve no more than four free parameters from R rs spectra for most ocean waters. In addition, we evaluated the performance of five different bio-optical models with different numbers of free parameters for the direct inversion of in-water inherent optical properties (IOPs) from in situ and synthetic R rs data. The multi-parameter models showed similar performances regardless of the number of parameters. Considering the computational cost associated with larger parameter spaces, we recommend bio-optical models with three free parameters for the use of IOP or joint retrieval algorithms.

Boron nitride nanocage as drug delivery systems for chloroquine, as an effective drug for treatment of coronavirus disease: A DFT study.

Research has shown that chloroquine (CQ) can effectively help control COVID-19 infection. B24N24 nanocage is a drug delivery system. Thus, through density functional theory, the present study analyzed pristine nanocage-CQ interaction and CQ interaction with Si- and Al -doped nanocage. The findings revealed that nanocage doping, particularly with Si and Al, yields more satisfactory drug delivery for CQ due to their greater electronic and energetic characteristics with CQ.

Construction of a predictive model for cognitive impairment risk in patients with advanced cancer.

AIMS: The purpose of this study was to identify risk factors for cognitive impairment in advanced cancer patients and to develop predictive models based on these risk factors. BACKGROUND: Cancer-related cognitive impairment seriously affects the quality of life of advanced cancer patients. However, neural network models of cognitive impairment in patients with advanced cancer have not yet been identified. DESIGN: A cross-sectional design was used. METHODS: This study collected 494 questionnaires between January and June 2022. Statistically significant clinical indicators were selected by univariate analysis, and the artificial neural network model and logistic regression model were used for multivariate analysis. The predicted value of the model was estimated using the area under the subject's working characteristic curve. RESULT: The artificial neural network and the logistic regression models suggested that cancer course, anxiety and age were the major risk factors for cognitive impairment in advanced cancer patients. All the indexes of artificial neural network model constructed in this study are better than those of the logistic model. CONCLUSION: The artificial neural network model can better predict the risk factors of cognitive impairment in patients with advanced cancer. Better prediction will enable nurses and other healthcare professionals to provide better targeted and timely support.

Instantaneous photosynthetically available radiation models for ocean waters using neural networks.

Instantaneous photosynthetically available radiation (IPAR) at the ocean surface and its vertical profile below the surface play a critical role in models to calculate net primary productivity of marine phytoplankton. In this work, we report two IPAR prediction models based on the neural network (NN) approach, one for open ocean and the other for coastal waters. These models are trained, validated, and tested using a large volume of synthetic datasets for open ocean and coastal waters simulated by a radiative transfer model. Our NN models are designed to predict IPAR under a large range of atmospheric and oceanic conditions. The NN models can compute the subsurface IPAR profile very accurately up to the euphotic zone depth. The root mean square errors associated with the diffuse attenuation coefficient of IPAR are less than 0.011m-1 and 0.036m-1 for open ocean and coastal waters, respectively. The performance of the NN models is better than presently available semi-analytical models, with significant superiority in coastal waters.

The prevalence of hyperuricemia and its correlates in Zhuang nationality, Nanning, Guangxi Province.

BACKGROUND: Hyperuricemia has an increasing incidence in various regions year by year, in this study, we evaluated the prevalence of hyperuricemia in a routine physical examination in Nanning, Guangxi Province, and analyzed the influencing factors of hyperuricemia, aiming to provide evidence for the prevention and treatment of hyperuricemia and related diseases. METHODS: Data were collected from 1957 patients who underwent physical examinations at the First Affiliated Hospital of Guangxi Medical University in China since 2017. Questionnaires were structured, including subjects' demographics, lifestyle, personal history, chronic disease history, medication history, etc. UA (uricase method), TC (cholesterol oxidase method), TG (glycerol phosphate oxidase method), HDL-C (direct method), LDL-C (direct method), BUN (rate method), creatinine (sarine oxidase method), and GLU (oxidase-peroxidase method) were detected. Independent risk factors for hyperuricemia were determined by bivariate non-conditional logistic regression analysis. RESULTS: The overall prevalence of hyperuricemia was 16.6% (19.5% in males and 14.9% in females). Gender, waist circumference, BMI, the proportion of drinking, hypertension, high education, serum concentrations of TC, TG, LDL-C, BUN, and creatinine were significantly higher and the serum concentration of HDL-C was significantly lower in patients with and without hyperuricemia (all p < 0.05). Waist circumference, BMI, BUN, and creatinine were independent risk factors for hyperuricemia. CONCLUSION: The prevalence of hyperuricemia is very high in Guangxi. Public health lectures should be conducted to encourage people to establish a healthy lifestyle and strengthen early intervention for hyperuricemia to reduce the risk of cardio-cerebrovascular and other related diseases.

Atmospheric correction over the ocean for hyperspectral radiometers using multi-angle polarimetric retrievals.

We developed a fast and accurate polynomial based atmospheric correction (POLYAC) algorithm for hyperspectral radiometric measurements, which parameterizes the atmospheric path radiances using aerosol properties retrieved from co-located multi-wavelength multi-angle polarimeter (MAP) measurements. This algorithm has been applied to co-located spectrometer for planetary exploration (SPEX) airborne and research scanning polarimeter (RSP) measurements, where SPEX airborne was used as a proxy of hyperspectral radiometers, and RSP as the MAP. The hyperspectral remote sensing reflectance obtained from POLYAC is accurate when compared to Aerosol Robotic Network (AERONET), and Visible Infrared Imaging Radiometer Suite (VIIRS) ocean color products. POLYAC provides a robust alternative atmospheric correction algorithm for hyperspectral or multi-spectral radiometric measurements for scenes involving coastal oceans and/or absorbing aerosols, where traditional atmospheric correction algorithms are less reliable.

Targeted intervention of eIF4A1 inhibits EMT and metastasis of pancreatic cancer cells via c-MYC/miR-9 signaling.

BACKGROUND: Owing to the lack of effective treatment options, early metastasis remains the major cause of pancreatic ductal adenocarcinoma (PDAC) recurrence and mortality. However, the molecular mechanism of early metastasis is largely unknown. We characterized the function of eukaryotic translation initiation factors (eIFs) in epithelial-mesenchymal-transition (EMT) and metastasis in pancreatic cancer cells to investigate whether eIFs and downstream c-MYC affect EMT and metastasis by joint interference. METHODS: We used The Cancer Genome Atlas (TCGA) and Genome Tissue Expression (GTEx) databases to analyze eIF4A1 expression in PDAC tissues and further validated the findings with a microarray containing 53 PDAC samples. Expression regulation and pharmacological inhibition of eIF4A1 and c-MYC were performed to determine their role in migration, invasion, and metastasis in pancreatic cancer cells in vitro and in vivo. RESULTS: Elevated eIF4A1 expression was positively correlated with lymph node infiltration, tumor size, and indicated a poor prognosis. eIF4A1 decreased E-cadherin expression through the c-MYC/miR-9 axis. Loss of eIF4A1 and c-MYC decreased the EMT and metastasis capabilities of pancreatic cancer cells, whereas upregulation of eIF4A1 attenuated the inhibition of EMT and metastasis induced by c-MYC downregulation. Treatment with the eIF4A1 inhibitor rocaglamide (RocA) or the c-MYC inhibitor Mycro3 either alone or in combination significantly decreased the expression level of EMT markers in pancreatic cancer cells in vitro. However, the efficiency and safety of RocA alone were not inferior to those of the combination treatment in vivo. CONCLUSION: Overexpression of eIF4A1 downregulated E-cadherin expression through the c-MYC/miR-9 axis, which promoted EMT and metastasis of pancreatic cancer cells. Despite the potential feedback loop between eIF4A1 and c-MYC, RocA monotherapy is a promising treatment inhibiting eIF4A1-induced PDAC metastasis.

Preconceptional and prenatal exposure to diurnal temperature variation increases the risk of childhood pneumonia.

BACKGROUND: Pneumonia is the leading cause of death and hospitalization among young children worldwide, but its risk factors remain unclear. OBJECTIVE: To evaluate the effect of maternal exposure to diurnal temperature variation (DTV) during preconceptional and prenatal periods on childhood pneumonia. METHODS: A retrospective cohort study by case-control design was conducted for pneumonia (N = 699) and normal (N = 811) children under age of 14 who were enrolled in XiangYa Hospital, Changsha, China from May 2017 to April 2019. Demographic data including gender, age, birth season, gestational age, parity, mode of delivery, and parental atopy were collected from the electronic medical records in the hospital system. We obtained the data of daily DTV in Changsha during 2003-2019 from China Meteorological Administration. Maternal exposure to DTV during preconceptional and prenatal periods was respectively calculated by the average of daily DTV during one year and three months before conception and entire pregnancy as well as the three trimesters. The association between maternal exposure to outdoor DTV and childhood pneumonia was analyzed by multiple logic regression model. RESULTS: We found that childhood pneumonia was significantly associated with exposure to an increase in DTV during one year before conception and entire pregnancy, with ORs (95 % CI) = 2.53 (1.56-4.10) and 1.85 (1.24-2.76). We further identified a significant risk of pneumonia of DTV exposure during the first and second trimester of pregnancy. Sensitivity analysis showed that boys were more susceptible to the effect of prenatal exposure to outdoor DTV during pregnancy particularly in the first two trimesters compared to girls. CONCLUSIONS: Preconceptional and prenatal exposure to DTV plays an important role in development of childhood pneumonia, especially during the first and second trimesters of pregnancy.

Preconceptional and prenatal exposure to air pollution increases incidence of childhood pneumonia: A hypothesis of the (pre-)fetal origin of childhood pneumonia.

BACKGROUND: Increasing evidence has linked childhood pneumonia with early exposure to ambient air pollution. However, the impact of exposure to air pollutants before birth is unclear. OBJECTIVE: To further clarify whether exposure to a particular pollutant during preconceptional and prenatal periods, may pose a higher risk of developing childhood pneumonia. METHODS: This case-control cohort study consisted of 1510 children aged 0-14 years in Changsha, China between 2017 and 2019. Data of children's history of pneumonia and blood biomarkers were obtained from the XiangYa Hospital records. Each child's exposure to air pollutants, including nitrogen dioxide (NO2), sulfur dioxide (SO2), and particulate matter with an aerodynamic diameter ≤ 10 µm (PM10), was calculated using data from ten air pollution monitoring stations. A multivariate logistic regression model was used to quantify the relationship between childhood pneumonia and exposure to ambient air pollution during the preconceptional and prenatal periods. RESULTS: Childhood pneumonia was significantly associated with preconceptional and prenatal exposure to the industrial-related air pollutant, SO2, for 1 year before conception, for 3 months before conception and for the entire pregnancy, with ORs(95% CI)= 4.01(3.17-5.07), 4.06(3.29-5.00) and 6.51(4.82-8.79). Also, children who were sick with pneumonia had higher white blood cell and neutrophil counts, and children with low eosinophil count or hemoglobin are likely to get pneumonia. Sensitivity analysis showed that boys, and children in high temperature area were susceptible to the effect of both preconceptional and prenatal exposure to industrial SO2. CONCLUSION: Preconceptional and prenatal exposure to industrial-related air pollution plays a significant role in the incidence and progression of childhood pneumonia, supporting the hypothesis of "(pre-)fetal origin of childhood pneumonia".

PTEN-silencing combined with ChABC-overexpression in adipose-derived stem cells promotes functional recovery of spinal cord injury in rats.

The efficiency of cell therapy after spinal cord injury (SCI) depend on the survival of transplanted cells. However, sterile microenvironment and glial scar hyperplasia extremely reduce their numbers. Our previous study found overexpression of ChABC gene is positively correlated to migration ability. Expression of PTEN gene is closely associated with proliferation. However, whether manipulation of PTEN and ChABC on adipose-derived mesenchymal stem cells (ADSCs) promote motor recovery is unknown. This study aimed to promote hindlimb function recovery in SCI rats by enhancing proliferation and migration ability of ADSCs, transiently silencing expression of PTEN following overexpression of ChABC (double-gene modified ADSCs, DG-ADSCs). After PTEN silencing, we observed strong proliferation and accelerated G1-S transition in DG-ADSCs using CCK8 assay and flow cytometry. In addition, we demonstrated that migration numbers of DG-ADSCs were higher than control group using Transwell assay. The protein and mRNA levels of MAP2 and ßⅢ-tubulin in DG-ADSCs were increased compared with ADSCs. These results were further confirmed in SCI rats. Increased survival cells and reduction of glial scars were quantitatively analyzed in DG-ADSCs groups, which is definitely correlated to function recovery. Recovery of motor function was observed in DG-ADSCs treatment rats using BBB score, which emphasized that improved viability of transplanted cells and reduction of glial scars were an effective strategy for enhancing recovery of neurological function after SCI.

Alveolar mimics with periodic strain and its effect on the cell layer formation.

We report on the development of a new model of alveolar air-tissue interface on a chip. The model consists of an array of suspended hexagonal monolayers of gelatin nanofibers supported by microframes and a microfluidic device for the patch integration. The suspended monolayers are deformed to a central displacement of 40-80 µm at the air-liquid interface by application of air pressure in the range of 200-1,000 Pa. With respect to the diameter of the monolayers, that is, 500 µm, this displacement corresponds to a linear strain of 2-10% in agreement with the physiological strain range in the lung alveoli. The culture of A549 cells on the monolayers for an incubation time of 1-3 days showed viability in the model. We exerted a periodic strain of 5% at a frequency of 0.2 Hz for 1 hr to the cells. We found that the cells were strongly coupled to the nanofibers, but the strain reduced the coupling and induced remodeling of the actin cytoskeleton, which led to a better tissue formation. Our model can serve as a versatile tool in lung investigations such as in inhalation toxicology and therapy.

Forkhead box a2 (FOXA2) is essential for uterine function and fertility.

Establishment of pregnancy is a critical event, and failure of embryo implantation and stromal decidualization in the uterus contribute to significant numbers of pregnancy losses in women. Glands of the uterus are essential for establishment of pregnancy in mice and likely in humans. Forkhead box a2 (FOXA2) is a transcription factor expressed specifically in the glands of the uterus and is a critical regulator of postnatal uterine gland differentiation in mice. In this study, we conditionally deleted FOXA2 in the adult mouse uterus using the lactotransferrin Cre (Ltf-Cre) model and in the neonatal mouse uterus using the progesterone receptor Cre (Pgr-Cre) model. The uteri of adult FOXA2-deleted mice were morphologically normal and contained glands, whereas the uteri of neonatal FOXA2-deleted mice were completely aglandular. Notably, adult FOXA2-deleted mice are completely infertile because of defects in blastocyst implantation and stromal cell decidualization. Leukemia inhibitory factor (LIF), a critical implantation factor of uterine gland origin, was not expressed during early pregnancy in adult FOXA2-deleted mice. Intriguingly, i.p. injections of LIF initiated blastocyst implantation in the uteri of both gland-containing and glandless adult FOXA2-deleted mice. Although pregnancy was rescued by LIF and was maintained to term in uterine gland-containing adult FOXA2-deleted mice, pregnancy failed by day 10 in neonatal FOXA2-deleted mice lacking uterine glands. These studies reveal a previously unrecognized role for FOXA2 in regulation of adult uterine function and fertility and provide original evidence that uterine glands and, by inference, their secretions play important roles in blastocyst implantation and stromal cell decidualization.

Functional analysis of the secondary HIV-1 capsid binding site in the host protein cyclophilin A.

BACKGROUND: Efficient HIV-1 replication depends on interaction of the viral capsid with the host protein cyclophilin A (CypA). CypA, a peptidylprolyl isomerase, binds to an exposed loop in the viral CA protein via the enzyme's active site. Recent structural analysis of CypA in complex with CA tubes in conjunction with molecular dynamics simulations identified a secondary CA binding site on CypA that allows a bridging interaction with two hexameric subunits of the assembled CA lattice, leading to capsid stabilization (Liu et al. in Nat Commun 7:10714, 2016). RESULTS: We performed mutational analysis of residues that have been proposed to mediate CA binding at the secondary binding site on CypA (A25, K27, P29 and K30) and tested the effects of the amino acid substitutions using interaction assays and HIV-1 infection assays in cells. The binding of recombinant CypA to self-assembled CA tubes or native HIV-1 capsids was measured in vitro using a quantitative fluorescence microscopy binding assay revealing that affinity and stoichiometry of CypA to the CA lattice was not affected by the substitutions. To test for functionality of the CypA secondary CA-binding site in HIV-1 infection, mutant CypA proteins were expressed in cells in which endogenous CypA was deleted, and the effects on HIV-1 infection were assayed. In normal HeLa-P4 cells, infection with HIV-1 bearing the A92E substitution in CA is inhibited by endogenous CypA and was inhibited to the same extent by expression of CypA mutants in CypA-null HeLa-P4 cells. Expression of the mutant CypA proteins in CypA-null Jurkat cells restored their permissiveness to infection by wild type HIV-1. CONCLUSIONS: The amino acid changes at A25, K27, P29 and K30 did not affect the affinity of CypA for the CA lattice and did not impair CypA function in infection assays suggesting that these residues are not part of a secondary CA binding site on CypA.

Multi-parallax views synthesis for three-dimensional light-field display using unsupervised CNN.

Multi-view applications have been used in a wide range, especially Three-Dimensional (3D) display. Since capturing dense multiple views for 3D light-field display is still a difficult work, view synthesis becomes an accessible way. Convolutional neural networks (CNN) has been used to synthesize new views of the scene. However, training targets are sometimes difficult to obtain, and it views are very difficult to synthesize at arbitrary positions. Here, an unsupervised network of Multi-Parallax View Net (MPVN) is proposed, which can synthesize multi-parallax views for 3D light-field display. Existing parallax views are re-projected to the target position to build input towers. The network is operated on these towers, and outputs a color tower and a selection tower. These two towers yield the final output image by per-pixel weight summing. MPVN adopts end-to-end unsupervised training to minimize prediction errors at existing positions. It can predict virtual views at any parallax position between existing views in a high quality. Experimental results demonstrate the validation of our proposed network, and SSIM of synthetic views are mostly over 0.95. We believe that this method can effectively provide enough views for 3D light-field display in the future work.

Single scattering properties of non-spherical hydrosols modeled by spheroids.

The single scattering properties of hydrosols play an important role in the study of ocean optics, ocean color remote sensing, and ocean biogeochemistry research. Measurements show that hydrosols can be of various sizes and shapes, suggesting general non-spherical models should be considered for the study of single scattering properties of hydrosols. In this work, light scattering by non-spherical hydrosols are modeled by randomly oriented spheroids with the Amsterdam discrete dipole approximation (ADDA) code. We have defined two new parameters to quantify the degree of optical non-sphericity (DONS) and investigated the dependence of DONS on refractive index, size, and aspect ratio. For particles with non-unitary aspect ratios, the magnitude of DONS increases as the refractive index and particle size increase. The dependence of the backscattering fraction on the non-sphericity, size, and refractive index of hydrosols is also studied. It is found that the backscattering fraction is larger for smaller particles as well as for particles with higher refractive indices. Absorptive hydrosols generally have a lower backscattering fraction than non-absorptive hydrosols. This study of light scattering by non-spherical hydrosols would lead to better radiative transfer models in ocean waters and new remote sensing techniques of hydrosol compositions.