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Virtual reality is a kind of application technology combining computer application, multimedia, information technology and simulation technology, which provides a broad development prospect for advertising, sports and game design. At present, in the United States and Europe and other developed countries and regions have been used in many fields of production, and achieved good economic and social benefits, but the research in this field is not obvious in China. It is very important to explore the technical advantages of virtual reality in game design and improve the overall application level of virtual reality. This paper summarizes and analyses the history and technological development of VR immersive experience, the application of VR in game production, and the application of VR in film production, and critically reviews and understands the application potential of VR technology as an interactive medium.

Immune selection drives tumor cells to acquire refractory phenotypes. We previously demonstrated that cytotoxic T lymphocyte (CTL)-mediated immune pressure enriches NANOG(+) tumor cells with stem-like and immune-refractory properties that make them resistant to CTLs. Here, we report that the emergence of refractory phenotypes is highly associated with an aberrant macroautophagic/autophagic state of the NANOG(+) tumor cells and that the autophagic phenotype arises through transcriptional induction of MAP1LC3B/LC3B by NANOG. Furthermore, we found that upregulation of LC3B expression contributes to an increase in EGF secretion. The subsequent hyperactivation of EGFR-AKT signaling rendered NANOG(+) tumor cells resistant to CTL killing. The NANOG-LC3B-p-EGFR axis was preserved across various types of human cancer and correlated negatively with the overall survival of cervical cancer patients. Inhibition of LC3B in immune-refractory tumor models rendered tumors susceptible to adoptive T-cell transfer, as well as PDCD1/PD-1 blockade, and led to successful, long-term control of the disease. Thus, our findings demonstrate a novel link among immune-resistance, stem-like phenotypes, and LC3B-mediated autophagic secretion in immune-refractory tumor cells, and implicate the LC3B-p-EGFR axis as a central molecular target for controlling NANOG(+) immune-refractory cancer. Abbreviations: ACTB: actin beta; ATG7: autophagy related 7; BafA1: bafilomycin A(1); CASP3: caspase 3; CFSE: carboxyfluorescein succinimidyl ester; ChIP: chromatin immunoprecipitation; CI: confidence interval; CIN: cervical intraepithelial neoplasia; CSC: cancer stem cell; CTL: cytotoxic T lymphocyte; EGF: epidermal growth factor; EGFR: epidermal growth factor receptor; FIGO: International Federation of Gynecology and Obstetrics; GFP: green fluorescent protein; GZMB: granzyme B; HG-CIN: high-grade CIN; IHC: immunohistochemistry; LG-CIN: low-grade CIN; LN: lymph node; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MCL1: myeloid cell leukemia sequence 1; MLANA/MART-1: melanoma antigen recognized by T cells 1; MUT: mutant; NANOG: Nanog homeobox; PDCD1/PD-1: programmed cell death 1; PMEL/gp100: premelanosome protein; RTK: receptor tyrosine kinase; TMA: tissue microarray; WT: wild type

Cancer immunotherapy has emerged as a promising cancer treatment. However, the presence of immune-refractory tumor cells limits its clinical success by blocking amplification of anti-tumor immunity. Previously, we found that immune selection by immunotherapy drives the evolution of tumors toward multi-modal resistant and stem-like phenotypes via transcription induction of AKT co-activator TCL1A by NANOG. Here, we report a crucial role of HSP90A at the crossroads between NANOG-TCL1A axis and multi-aggressive properties of immune-edited tumor cells by identifying HSP90AA1 as a NANOG transcriptional target. Furthermore, we demonstrate that HSP90A potentiates AKT activation through TCL1A-stabilization, thereby contributing to the multi-aggressive properties in NANOGhigh tumor cells. Importantly, HSP90 inhibition sensitized immune-refractory tumor to adoptive T cell transfer as well as PD-1 blockade, and re-invigorated the immune cycle of tumor-reactive T cells. Our findings implicate that the HSP90A-TCL1A-AKT pathway ignited by NANOG is a central molecular axis and a potential target for immune-refractory tumor., Nanog can confer resistance to cancer immunotherapy by promoting AKT activity. Here, the authors demonstrate that HSP90A is a Nanog target that stabilizes the AKT coactivator TCL1, thereby activating AKT, and that HSP90A inhibition can enhance the anti-tumor efficacy of adoptive T cell transfer and checkpoint blockade.

Since mid-December of 2019, coronavirus disease 2019 (COVID-19) infection has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 infection in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, β-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.

Transient electronics represents an emerging technology whose defining feature is an ability to dissolve, disintegrate or otherwise physically disappear in a controlled manner. Envisioned applications include resorbable/degradable biomedical implants, hardware-secure memory devices, and zero-impact environmental sensors. 2D materials may have essential roles in these systems due to their unique mechanical, thermal, electrical, and optical properties. Here, we study the bioabsorption of CVD-grown monolayer MoS2, including long-term cytotoxicity and immunological biocompatibility evaluations in biofluids and tissues of live animal models. The results show that MoS2 undergoes hydrolysis slowly in aqueous solutions without adverse biological effects. We also present a class of MoS2-based bioabsorbable and multi-functional sensor for intracranial monitoring of pressure, temperature, strain, and motion in animal models. Such technology offers specific, clinically relevant roles in diagnostic/therapeutic functions during recovery from traumatic brain injury. Our findings support the broader use of 2D materials in transient electronics and qualitatively expand the design options in other areas.

Circulating cell-free DNA (cfDNA) is currently recognized as a key non-invasive biomarker for cancer diagnosis and progression and therapeutic efficacy monitoring. Because cfDNA has been detected in patients with diverse types of cancers, the use of efficient strategies to isolate cfDNA not only provides valuable insights into tumour biology, but also offers the potential for developing new cancer-specific targets. However, the challenges associated with conventional cfDNA extraction methods prevent their further clinical applications. Here, we developed a nanostructured conductive polymer platform for the efficient capture and release of circulating cfDNA and demonstrated its potential clinical utility using unprocessed plasma samples from patients with breast and lung cancers. Our results confirmed that the platform's enhanced efficiency allows tumor-specific circulating cfDNA to be recovered at high yield and purity.

In this paper, we propose a rotated bounding box based convolutional neural network (RBox-CNN) for arbitrary-oriented ship detection. RBox-CNN is an end-to-end model based on Faster R-CNN. The region proposal network generates proposals as the rotated bounding box, and then the rotation region-of-interest (RRoI) pooling layer is applied to extract region features corresponding the proposals. In addition, the diagonal region-of-interest (DRoI) pooling layer is applied simultaneously to extract context features and alleviate the problem of misalignment in RRoI pooling layer. To stably predict locations with the angle, we apply the regression of distance's projection in width/height. Experiments on HRSC2016 show that our model achieves state-of-the-art detection accuracy on ship detection. Furthermore, RBox-CNN achieves a significant improvement on DOTA for oriented general object detection in remote sensing images.

This paper reviews the 2nd NTIRE challenge on single image super-resolution (restoration of rich details in a low resolution image) with focus on proposed solutions and results. The challenge had 4 tracks. Track 1 employed the standard bicubic downscaling setup, while Tracks 2, 3 and 4 had realistic unknown downgrading operators simulating camera image acquisition pipeline. The operators were learnable through provided pairs of low and high resolution train images. The tracks had 145, 114, 101, and 113 registered participants, resp., and 31 teams competed in the final testing phase. They gauge the state-of-the-art in single image super-resolution.

Transient electronics represents an emerging technology whose defining feature is an ability to dissolve, disintegrate or otherwise physically disappear in a controlled manner. Envisioned applications include resorbable/degradable biomedical implants, hardware-secure memory devices, and zero-impact environmental sensors. 2D materials may have essential roles in these systems due to their unique mechanical, thermal, electrical, and optical properties. Here, we study the bioabsorption of CVD-grown monolayer MoS2, including long-term cytotoxicity and immunological biocompatibility evaluations in biofluids and tissues of live animal models. The results show that MoS2 undergoes hydrolysis slowly in aqueous solutions without adverse biological effects. We also present a class of MoS2-based bioabsorbable and multi-functional sensor for intracranial monitoring of pressure, temperature, strain, and motion in animal models. Such technology offers specific, clinically relevant roles in diagnostic/therapeutic functions during recovery from traumatic brain injury. Our findings support the broader use of 2D materials in transient electronics and qualitatively expand the design options in other areas., Transient electronics entails the capability of electronic components to dissolve or reabsorb in a controlled manner when used in biomedical implants. Here, the authors perform a systematic study of the processes of hydrolysis, bioabsorption, cytotoxicity and immunological biocompatibility of monolayer MoS2.

Clozapine is an atypical antipsychotic agent used in the treatment of schizophrenia and severe mood disorders. Accumulating evidence suggests that neuroinflammation is closely associated with the pathogenesis of various neurodegenerative diseases and psychiatric disorders. Clozapine exerts anti-inflammatory activity. However, the molecular mechanism underlying the anti-inflammatory activity of clozapine is poorly understood. In this study, we found that clozapine suppressed lipopolysaccharide (LPS)-induced phosphorylation of IκBα at Ser-32 and of p65/RelA at Ser-468, as well as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-dependent transcriptional activity in microglial cells. Clozapine downregulated LPS-induced Akt phosphorylation at Ser-473. Pharmacological Akt inhibitors ameliorated LPS-induced NF-κB activation. Removal of extracellular Ca2 + by EGTA or sequestration of intracellular Ca2 + by BAPTA-AM attenuated LPS-induced Akt phosphorylation. Treatment with calmodulin (CaM) antagonists and the CaM kinase inhibitor, KN-93, also prevented LPS-induced Akt and NF-κB activation, suggesting that Ca2 +/CaM-dependent Akt activation is critical in LPS-induced NF-κB activation in microglia. These results suggest that clozapine exhibits anti-inflammatory activity through the inhibition of Ca2 +/CaM/Akt-mediated NF-κB activation.

Here, we propose an integrated multifunctional system constructed by conductive disulfide-biotin-doped polypyrrole nanowires (SS-biotin-Ppy NWs) for capture, release, and in situ quantification of circulating tumor cells (CTCs). A well-ordered three-dimensional nanowire structure equipped with a monoclonal antibody offers a significant impact on the cell-capture efficiency, as well as on electrical- or glutathione (GSH)-mediated release of the captured cells. In addition, the electrochemical identification/detection of the captured cancer cells can be directly conducted on the same Ppy NW platform by using horseradish peroxidase (HRP)-labeled and anti-EpCAM-conjugated nanoparticles (HRP/anti-EpCAM Ppy NPs), showing very high sensitivity and specificity. The signal amplification can be clearly attributed to the catalytic response resulting from enzymatic reduction of hydrogen peroxide on Ppy NWs, consequently generating a greatly increased amperometric response with a detection range of 10 to 1 × 10 4 cells and a detection limit of as low as 10 cells. Overall, the proposed Ppy NWs not only present a promising platform for effective cell capture and release but also permit cytosensing capability for on-site analysis.

We have developed a reusable nanostructured polypyrrole nanochip and demonstrated its use in the electric field-mediated recovery of circulating cell-free DNA (cfDNA) from the plasma of lung cancer patients. Although cfDNA has been recognized and widely studied as a versatile and promising biomarker for the diagnosis and prognosis of cancers, the lack of efficient strategies to directly isolate cfDNA from the plasma has become a great hindrance to its potential clinical use. As a proof-of-concept study, we demonstrated a technique for the rapid and efficient isolation of cfDNA with high yield and purity. In particular, the synergistic effects of the electro-activity and the nanostructured features of the polypyrrole polymer enabled repeated retrieval of cfDNA using a single platform. Moreover, polypyrrole nanochip facilitated the amplification of tumor-specific DNA fragments from the plasma samples of patients with lung cancer characterized by mutations in exons 21 of the epidermal growth factor receptor gene (EGFR). Overall, the proposed polypyrrole nanochip has enormous potential for industrial and clinical applications with significantly enhanced efficiency in the recovery of tumor-associated circulating cfDNA. This may ultimately contribute to more robust and reliable evaluation of gene mutations in peripheral blood.

Tumor infiltrating lymphocytes (TILs) are found in advanced pancreatic ductal adenocarcinoma (PDAC) patients and shown to correlate with overall survival (OS) rate. Although majority of TILs consisted of CD8+/CD4+T cells, the presence of NK cells and their role in the pathogenesis of PDAC remains elusive. We performed comprehensive analyses of TIL and PBMC to explore the role of NK cells in the newly developed PDAC patients. Multiple defects in cell migration and effector function were observed in NK cells of patients’ peripheral blood. Extremely low frequencies of NK cells (

An electroresponsive drug release system based on polypyrrole (Ppy) nanowires was developed to induce the local delivery of anticancer drug, doxorubicin (DOX), according to the applied electric field. DOX-conjugated Ppy nanowire (NW) (DOX/Ppy NW) array was initially prepared by electrochemical deposition of a mixture of pyrrole monomers and biotin as dopants in the anodic alumina oxide membrane as a sacrificial template. Morphological observation by scanning electron microscopy revealed free-standing and 3D nanotopographical features with large surface area and high density. In addition, we investigated the antitumor efficacy of DOX released from DOX/Ppy NW array in response to the external electric field using two kinds of cancer cell lines, human oral squamous carcinoma cells (KB cells) and human breast cancer cells (MCF7 cells). Meanwhile, strong photothermal effect as a result of a near-infrared absorbing ability of Ppy synergistically maximizes the chemotherapeutic efficacy. Our results suggested that the proposed multifunctional Ppy platform possessing several beneficial features is very promising for many therapeutic applications including cancer.

The specific capture and remotely controlled release of the EpCAM-positive cancer cells from biotin-doped polypyrrole (Ppy) films in response to an electrical potential is presented. As Ppy allows the direct incorporation of biotin molecules during the electrochemical process, densely packed biotin molecules can serve as the binding sites for streptavidin-tagged biomolecular complexes. This study demonstrates not only the enhanced capture and enrichment of EpCAM-positive cancer cells but also "on-demand" release of the viable cells from conductive Ppy in an electrical-potential-dependent way. This novel approach is of great importance in a diverse range of applications, and in particular in cancer diagnostics and screening.

In this study, we investigated the antitumor effects of the tricyclic antidepressant 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethylpropan-1-amine (imipramine) on glioma cells. We found that exposure of U-87MG cells to imipramine resulted in the inhibition of PI3K/Akt/mTOR signaling, reduction of clonogenicity, and induction of cell death. Imipramine stimulated the formation of acidic vesicular organelles, the conversion of LC3-I to LC3-II, and the redistribution of LC3 to autophagosomes, suggesting that it stimulates the progression of autophagy. It did not, however, induce apoptosis. We further showed that knockdown of Beclin-1 using siRNA abrogated imipramine-induced cell death. These results suggest that imipramine exerts antitumor effects on PTEN-null U-87MG human glioma cells by inhibiting PI3K/Akt/mTOR signaling and by inducing autophagic cell death.

Microglial cells are the resident innate immune cells that sense pathogens and tissue injury in the central nervous system (CNS). Microglial activation is critical for neuroinflammatory responses. The synthetic compound 2-hydroxy-3',5,5'-trimethoxychalcone (DK-139) is a novel chalcone-derived compound. In this study, we investigated the effects of DK-139 on Toll-like receptor 4 (TLR4)-mediated inflammatory responses in BV2 microglial cells. DK-139 inhibited lipopolysaccharide (LPS)-induced TLR4 activity, as determined using a cell-based assay. DK-139 blocked LPS-induced phosphorylation of IκB and p65/RelA NF-κB, resulting in inhibition of the nuclear translocation and trans-acting activity of NF-κB in BV2 microglial cells. We also found that DK-139 reduced the expression of NF-κB target genes, such as those for COX-2, iNOS, and IL-1β, in LPS-stimulated BV2 microglial cells. Interestingly, DK-139 blocked LPS-induced Akt phosphorylation. Inhibition of Akt abrogated LPS-induced phosphorylation of p65/RelA, while overexpression of dominant- active p110CAAX enhanced p65/RelA phosphorylation as well as iNOS and COX2 expression. These results suggest that DK-139 exerts an anti-inflammatory effect on microglial cells by inhibiting the Akt/IκB kinase (IKK)/NF-κB signaling pathway.