Construction of T cell exhaustion model for predicting survival and immunotherapy effect of bladder cancer based on WGCNA

IntroductionThe prognosis of bladder cancer (BLCA) and response to immune checkpoint inhibitors (ICIs) are determined by multiple factors. Existed biomarkers for predicting the effect of immunotherapy cannot accurately predict the response of BLCA patients to ICIs.MethodsTo further accurately stratify patients’ response to ICIs and identify potential novel predictive biomarkers, we used the known T cell exhaustion (TEX)-related specific pathways, including tumor necrosis factor (TNF), interleukin (IL)-2, interferon (IFN)-g, and T- cell cytotoxicpathways, combined with weighted correlation network analysis (WGCNA) to analyze the characteristics of TEX in BLCA in detail, constructed a TEX model.ResultsThis model including 28 genes can robustly predict the survival of BLCA and immunotherapeutic efficacy. This model could divide BLCA into two groups, TEXhigh and TEXlow, with significantly different prognoses, clinical features, and reactivity to ICIs. The critical characteristic genes, such as potential biomarkers Charged Multivesicular Body Protein 4C (CHMP4C), SH2 Domain Containing 2A (SH2D2A), Prickle Planar Cell Polarity Protein 3 (PRICKLE3) and Zinc Finger Protein 165 (ZNF165) were verified in BLCA clinical samples by real-time quantitative chain reaction (qPCR) and immunohistochemistry (IHC).DiscussionOur findings show that the TEX model can serve as biological markers for predicting the response to ICIs, and the involving molecules in the TEX model might provide new potential targets for immunotherapy in BLCA

Mode-matching metasurfaces: coherent reconstruction and multiplexing of surface waves

Metasurfaces are promising two-dimensional metamaterials that are engineered to provide unique properties or functionalities absent in naturally occurring homogeneous surfaces. Here, we report a type of metasurface for tailored reconstruction of surface plasmon waves from light. The design is generic in a way that one can selectively generate different surface plasmon waves through simple variation of the wavelength or the polarization state of incident light. The ultra-thin metasurface demonstrated in this paper provides a versatile interface between the conventional free-space optics and a two-dimensional platform such as surface plasmonics.Comment: 7 figures, supplementary information at the end of the documen

Synchronous Microwave Ablation Combined With Cisplatin Intratumoral Chemotherapy for Large Non-Small Cell Lung Cancer

BackgroundMicrowave ablation (MWA) and intratumoral chemotherapy (ITC) are useful for treating tumors in animal models; however, their clinical use in patients with large non−small cell lung cancer (NSCLC) remains unknown. This retrospective study aimed to evaluate preliminary outcomes of MWA + ITC for large NSCLC.MethodsFrom November 2015 to April 2020, a total of 44 NSCLC patients with a mean lesion diameter of 6.1 ± 1.5 cm were enrolled and underwent synchronous MWA + ITC procedures. The primary endpoint was local progression-free survival (LPFS); secondary endpoints were progression-free survival (PFS), complications, overall survival (OS), and associated prognostic factors.ResultsThe median follow-up time was 19.0 months. At the 1-month CT scan, complete tumor ablation was observed in 47.7% of cases. Median LPFS was 12.1 months; 1-, 2-, and 3-year LPFS rates were 51.2%, 27.9%, and 13.6%, respectively. A shorter LPFS was significantly associated with large lesions (HR 1.23, 95% CI 1.02–1.49; p = 0.032). Median PFS was 8.1 months; 1-, 2-, and 3-year PFS rates were 29.5%, 18.2%, and 9.1%, respectively. LPFS was significantly superior to PFS (p = 0.046). Median OS was 18.8 months. The 1-, 2-, 3-, and 5-year OS rates were 65.9%, 43.2%, 26.4%, and 10.0%, respectively. In univariate comparisons, high performance status (PS) score, smoking, and larger lesions were significantly correlated with poor survival. In multivariate analysis, advanced age, higher PS score, higher stage, larger lesion, and prior systematic treatment were independent prognostic factors for shorter OS. Adverse events were well tolerated and all patients recovered after appropriate intervention.ConclusionsMWA + ITC is a safe and effective new modality of local treatment for large NSCLC and can significantly prolong LPFS

Toward 6G TKμ\mu Extreme Connectivity: Architecture, Key Technologies and Experiments

Sixth-generation (6G) networks are evolving towards new features and order-of-magnitude enhancement of systematic performance metrics compared to the current 5G. In particular, the 6G networks are expected to achieve extreme connectivity performance with Tbps-scale data rate, Kbps/Hz-scale spectral efficiency, and $\mu$s-scale latency. To this end, an original three-layer 6G network architecture is designed to realise uniform full-spectrum cell-free radio access and provide task-centric agile proximate support for diverse applications. The designed architecture is featured by super edge node (SEN) which integrates connectivity, computing, AI, data, etc. On this basis, a technological framework of pervasive multi-level (PML) AI is established in the centralised unit to enable task-centric near-real-time resource allocation and network automation. We then introduce a radio access network (RAN) architecture of full spectrum uniform cell-free networks, which is among the most attractive RAN candidates for 6G TK$\mu$ extreme connectivity. A few most promising key technologies, i.e., cell-free massive MIMO, photonics-assisted Terahertz wireless access and spatiotemporal two-dimensional channel coding are further discussed. A testbed is implemented and extensive trials are conducted to evaluate innovative technologies and methodologies. The proposed 6G network architecture and technological framework demonstrate exciting potentials for full-service and full-scenario applications.Comment: 15 pages, 12 figure

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Sulfur-Directed Ligand-Free C–H Borylation by Iridium Catalysis

An iridium-catalyzed <i>ortho</i> C–H borylation reaction directed by cyclic dithioacetal moiety is disclosed. A series of borylation products were obtained in moderate to good yields under mild conditions in exclusive mono- and <i>ortho</i>-regioselectivity. Thus, the 1,3-dithiane or 1,3-dithiolane group serves as a remarkable effective directing group for C–H borylation without any ligand assistance. The further transformations of the borylation products are also carried out to change boryl group to other functional groups

Quantitative Analysis of Rapid Siltation and Erosion Caused Coastline Evolution in the Coastal Mudflat Areas of Jiangsu

Muddy coast due to natural and human-induced factors can be variable over a wide range of different spatiotemporal scales. Our limited capability to understand and especially predict this variability can lead to misinterpretation of muddy coastal change information, which hampers informed decision-making and subsequent design and implementation of engineering interventions. Therefore, the research on the evolution of the historical coastline is particularly important. In this study, annual mean coastlines and causes for the variability and possible evolutions are analyzed in a manner that avoids these effects by averaging the instantaneous coastline positions registered during the same year. A set of coastlines is obtained from Landsat MSS/TM/OLI series of remote sensing images taken between 1985 and 2020 in the Google Earth Engine at Jiangsu muddy coast of China Yellow Sea. The coastline is extracted based on the water body index and the Otsu method, and is classified by fractal dimension, annual rate of change, area calculation, center of gravity shift, and artificial index to calculate the temporal and spatial changes in the coastline. The results showed that most of the coastline advanced seaward due to rapid siltation and coastal development in the past 35 years with only a small portion receding landward. The entire coast experienced segmental changes and different evolutionary characteristics and the coastline shifted from rapid erosion to siltation. The silted banks were mainly distributed in the middle section of the coastline in the radial sandbank. The annual change rate in the coast section was 82.21 m/a and the average annual area increased by 18.07 km2. The artificial coastline increased substantially, while the natural coastline gradually decreased due to rapid erosion. From 1985 to 2020, the proportion of artificial coastline in Jiangsu rose from 14% to 77%. The coastline became more curved and the center of gravity of the coastline moved 5.13 km to the northwest by 61°. Before 2000, the driving force affecting the coastline variability was mainly rapid siltation, while the impact of rapid erosion and human activities gradually increased after 2000 with the natural coastline being continuously cut and straightened. Overall, Jiangsu’s muddy coast was the site with the highest anthropogenic pressure and highest vulnerability. However, it is difficult to generalize the results under other conditions, especially on decadal time scales. Scientific and engineering improvements still require more quantitative insight into the physical mechanisms behind the natural and forced shore behavior responsible for the variability to better explain the change process of the coastline and provide a basis for coastal management and sustainable development

Regulating Cell Apoptosis on Layer-by-Layer Assembled Multilayers of Photosensitizer-Coupled Polypeptides and Gold Nanoparticles

The design of advanced, nanostructured materials by layer-by-layer (LbL) assembly at the molecular level is of great interest because of the broad application of these materials in the biomedical field especially in regulating cell growth, adhesion, movement, differentiation and detachment. Here, we fabricated functional hybrid multilayer films by LbL assembly of biocompatible photosensitizer-coupled polypeptides and collagen-capped gold nanoparticles. The resulting multilayer film can well accommodate cells for adhesion, growth and proliferation. Most significantly, controlled cell apoptosis (detachment) and patterning of the multilayer film is achieved by a photochemical process yielding reactive oxygen species (ROS). Moreover, the site and shape of apoptotic cells can be controlled easily by adjusting the location and shape of the laser beam. The LbL assembled multilayer film with integration of functions provides an efficient platform for regulating cell growth and apoptosis (detachment)