Receptor–ligand pair typing and prognostic risk model of response or resistance to immune checkpoint inhibitors in lung adenocarcinoma

IntroductionCurrently, programmed cell death-1 (PD-1)-targeted treatment is ineffective for a sizable minority of patients, and drug resistance still cannot be overcome.MethodsTo explore the mechanisms of immunotherapy and identify new therapeutic opportunities in lung adenocarcinoma (LUAD), data from patients who did and did not respond to the anti-PD-1 treatment were evaluated using single-cell RNA sequencing, and bulk RNA sequencing were collected.ResultsWe investigated the gene expression that respond or not respond to immunotherapy in diverse cell types and revealed transcriptional characteristics at the single-cell level. To ultimately explore the molecular response or resistance to anti-PD-1 therapy, cell-cell interactions were carried out to identify the different LRIs (ligand-receptor interactions) between untreated patients vs. no-responders, untreated patients vs. responders, and responders vs. non-responders. Next, two molecular subgroups were proposed based on 73 LRI genes, and subtype 1 had a poor survival status and was likely to be the immunosuppressive tumor subtype. Furthermore, based on the LASSO Cox regression analysis results, we found that TNFSF13, AXL, KLRK1, FAS, PROS1, and CDH1 can be distinct prognostic biomarkers, immune infiltration levels, and responses to immunotherapy in LUAD.DiscussionAltogether, the effects of immunotherapy were connected to LRIs scores, indicating that potential medications targeting these LRIs could contribute to the clinical benefit of immunotherapy. Our integrative omics analysis revealed the mechanisms underlying the anti-PD-1 therapy response and offered abundant clues for potential strategies to improve precise diagnosis and immunotherapy

Quantification of transient increase of the blood–brain barrier permeability to macromolecules by optimized focused ultrasound combined with microbubbles

Radioimmunotherapy using a radiolabeled monoclonal antibody that targets tumor cells has been shown to be efficient for the treatment of many malignant cancers, with reduced side effects. However, the blood–brain barrier (BBB) inhibits the transport of intravenous antibodies to tumors in the brain. Recent studies have demonstrated that focused ultrasound (FUS) combined with microbubbles (MBs) is a promising method to transiently disrupt the BBB for the drug delivery to the central nervous system. To find the optimal FUS and MBs that can induce reversible increase in the BBB permeability, we employed minimally invasive multiphoton microscopy to quantify the BBB permeability to dextran-155 kDa with similar molecular weight to an antibody by applying different doses of FUS in the presence of MBs with an optimal size and concentration. The cerebral microcirculation was observed through a section of frontoparietal bone thinned with a micro-grinder. About 5 minutes after applying the FUS on the thinned skull in the presence of MBs for 1 minute, TRITC (tetramethylrhodamine isothiocyanate)-dextran-155 kDa in 1% bovine serum albumin in mammalian Ringer’s solution was injected into the cerebral circulation via the ipsilateral carotid artery by a syringe pump. Simultaneously, the temporal images were collected from the brain parenchyma ~100–200 μm below the pia mater. Permeability was determined from the rate of tissue solute accumulation around individual microvessels. After several trials, we found the optimal dose of FUS. At the optimal dose, permeability increased by ~14-fold after 5 minutes post-FUS, and permeability returned to the control level after 25 minutes. FUS without MBs or MBs injected without FUS did not change the permeability. Our method provides an accurate in vivo assessment for the transient BBB permeability change under the treatment of FUS. The optimal FUS dose found for the reversible BBB permeability increase without BBB disruption is reliable and can be applied to future clinical trials

Ror2 modulates the canonical Wnt signaling in lung epithelial cells through cooperation with Fzd2

<p>Abstract</p> <p>Background</p> <p>Wnt signaling is mediated through 1) the beta-catenin dependent canonical pathway and, 2) the beta-catenin independent pathways. Multiple receptors, including Fzds, Lrps, Ror2 and Ryk, are involved in Wnt signaling. Ror2 is a single-span transmembrane receptor-tyrosine kinase (RTK). The functions of Ror2 in mediating the non-canonical Wnt signaling have been well established. The role of Ror2 in canonical Wnt signaling is not fully understood.</p> <p>Results</p> <p>Here we report that Ror2 also positively modulates Wnt3a-activated canonical signaling in a lung carcinoma, H441 cell line. This activity of Ror2 is dependent on cooperative interactions with Fzd2 but not Fzd7. In addition, Ror2-mediated enhancement of canonical signaling requires the extracellular CRD, but not the intracellular PRD domain of Ror2. We further provide evidence that the positive effect of Ror2 on canonical Wnt signaling is inhibited by Dkk1 and Krm1 suggesting that Ror2 enhances an Lrp-dependent STF response.</p> <p>Conclusion</p> <p>The current study demonstrates the function of Ror2 in modulating canonical Wnt signaling. These findings support a functional scheme whereby regulation of Wnt signaling is achieved by cooperative functions of multiple mediators.</p

Three-dimensional steady and transient fully coupled electro-thermal simulation of AlGaN/GaN high electron mobility transistors: Effects of lateral heat dissipation and thermal crosstalk between gate fingers

In this paper, we develop three-dimensional fully coupled electro-thermal (ET) simulation for AlGaN/GaN high electron mobility transistors (HEMTs), which is a relative complete and accurate simulation compared to the current existed simulations, capable of describing the lateral ET behavior of the device. As applications of this simulation, we investigate impact of the gate width (WG) and number of the gate fingers (NG) on the steady and transient ET behavior of the device. The steady results show that the lateral heat dissipation and thermal crosstalk between the gate fingers significantly affects the ET behavior for the device with narrow gate and multifinger, respectively. However, the transient results show that, within a time scale after the device switching on, the ET behavior is not influenced by WG and NG, i.e., the lateral heat dissipation and thermal crosstalk have no effects. This indicates that when the device operating in high frequency, increasing WG and NG to improve the power output is not restricted by the self-heating

Modification of strain and 2DEG density induced by wafer bending of AlGaN/GaN heterostructure: Influence of edges caused by processing

Due to the piezoelectricity, the density of 2DEG (NS) formed in the AlGaN/GaN heterostructure can be altered when it is deformed externally, which may be exploited to develop pressure sensors and to enhance the performance of power devices by stress engineering based on the heterostructure. In this paper, a 3D electro-mechanical simulation is presented to study how the induced strains and NS for the AlGaN/GaN wafer under bending exerted uniaxial stress are influenced by the edges caused by processing: the fabrication of the mesa used for isolation, the ohmic contact metal, the gate metal, and the passivation. Results show that the influences are dependent on distance between the edges, depth of the edges, and direction of the exerted uniaxial stress

Correlation between women's sub-health and reproductive diseases with pregnancies and labors

AbstractObjectiveTo investigate whether female sub-health conditions and reproductive diseases are associated with pregnancies and labors.MethodsA cross-sectional survey was performed by using a structured questionnaire. A total of 1343 women aged 35 years or younger in six urban areas of Chengdu were included in the study. According to the Screening Criteria of sub-health conditions, these women were categorized into three groups: postpartum healthy group, sub-healthy group, and reproductive disease group. Data were double-entered using EpiData and then analyzed by SPSS.ResultsPregnancy and labor were correlated with postpartum sub-health conditions. The number of pregnancies was negatively correlated with women's postnatal health but was positively correlated with the incidence of postpartum reproductive diseases.ConclusionsThe number of pregnancies and labors is probably an important factor leading to sub-health conditions and the occurrence of reproductive diseases in women. Avoiding or reducing unwanted pregnancies and labors, enhancing the awareness of health among childbearing-age women are effective measures for preventing sub-health conditions

Moving Target Detection and Tracking

Abstract: This study proposes a background update algorithm based on the correlation coefficient, overcome the shortcomings of fuzzy image of the average background updating. Then, it uses subtraction background method to detect moving targets and record the moving target region and use projection histogram to resize the center of the target and calculate the confidence coefficient of the current frame and the subsequent frame to research the center of the target in the subsequent frames. Then, the moving target could be tracked in the subsequent frames. The experimental results show that the algorithm can accurately detect and automatically track moving targets

Particle sticking behavior near the throat of a low-NOx axial-swirl coal burner

The results of numerical simulations of particle sticking behavior near the throat of a low-NOx axial-swirl burner in a 600-MWe bituminous coal burned boiler are presented. A comparison of simulation results with measurements using a probe with hot-film sensors shows that the numerical model offers a reasonable description. Calculated results of slagging show that slag build-up is substantial near the throat of the designed burner and that the sticking-particle ratio is as much as 33.2%. Because central and primary air streams remain unchanged, the mass flux of the inner secondary air is 3.25 kg s-1 while that of the outer secondary air is 12.16 kg s-1; however, the sticking-particle ratio can still be lowered to as little as 9.6%. By adjusting the outer secondary air blade angle to 15°, the sticking-particle ratio can be further lowered to 8.73%.Swirl burner Numerical simulation Particle sticking behavior