Terahertz metalens for generating multi-polarized focal points and images with uniform intensity distributions.

Metasurfaces have provided a flexible platform for designing ultracompact metalenses with unusual functionalities. However, traditional multi-foci metalenses are limited to generating circularly polarized (CP) or linearly polarized (LP) focal points, and the intensity distributions are always inhomogeneous/chaotical between the multiple focal points. Here, an inverse design approach is proposed to optimize the in-plane orientation of each meta-atom in a terahertz (THz) multi-foci metalens that can generate multi-polarized focal points with nearly uniform intensity distributions. As a proof-of-principle example, we numerically and experimentally demonstrate an inversely designed metalens for simultaneously generating multiple CP- and LP-based focal points with homogeneous intensity distributions, leading to a multi-polarized image (rather than the holography). Furthermore, the multi-channel and multi-polarized images consisting of multiple focal points with homogeneous intensity distributions are also numerically demonstrated. The unique approach for inversely designing multi-foci metalens that can generate multi-polarized focal points and images with uniform intensity distributions will enable potential applications in imaging and sensing.

Analysis of sustainable water resource management and driving mechanism in arid region: a case study of Xinjiang, China, from 2005 to 2020.

The long-term dynamic comprehensive evaluation of the water resource carrying capacity (WRCC) and the analysis of its potential driving mechanism in arid areas are contemporary research issues and technical means of mitigating and coordinating the conflict between severe resource shortages and human needs. The purpose of this study was to explore the distribution of the WRCC and the spatiotemporal heterogeneity of drivers in arid areas based on an improved two-dimensional spatiotemporal dynamic evaluation model. The results show that (1) the spatial distribution of the WRCC in Xinjiang, China, is high in the north, low in the south, high in the west, and low in the east. (2) From 2005 to 2020, the centers of gravity of the WRCC in northern and southern Xinjiang moved to the southeast and west, respectively, and the spatial distribution exhibited slight diffusion. (3) The factors influencing the WRCC exhibit more obvious spatial and temporal heterogeneity. The domestic waste disposal rate and ecological water use rate were the main factors influencing the WRCC in the early stage, while the GDP per capita gradually played a dominant role in the later stage. (4) In the next 30 years, the WRCC in Xinjiang will increase. The results provide a theoretical reference for the sustainable development of water resources in arid areas.

Clinical significance of peripheral T-cell receptor repertoire profiling and individualized nomograms in patients with gastrointestinal cancer treated with anti-programmed death 1 antibody.

Background: Immune checkpoint inhibitors (ICIs) have significant clinical benefit for a subset of patients with gastrointestinal cancers (GICs) including esophageal cancer, gastric cancer and colorectal cancer. However, it is difficult to predict which patients will respond favorably to immune checkpoint blockade therapy. Thus, this study was initiated to determine if peripheral T-cell receptor (TCR) repertoire profiling could predict the clinical efficacy of anti-programmed death 1 (PD-1) treatment. Methods: Blood samples from 31 patients with GICs were collected before anti-PD-1 antibody treatment initiation. The clinical significance of the combinatorial diversity evenness of the TCR repertoire [the diversity evenness 50 (DE50), with high values corresponding to less clonality and higher TCR diversity] from peripheral blood mononuclear cells (PBMCs) was evaluated in all the enrolled patients. A highly predictive nomogram was set up based on peripheral TCR repertoire profiling. The performance of the nomogram was assessed by receiver operating characteristic (ROC) curve, concordance index (C-index), and calibration curves, and decision curve analysis (DCA) was used to assess its clinical applicability. Results: Compared to non-responders [progression disease (PD)], the DE50 scores were significantly higher in responders [stable disease (SD) and partial response (PR)] (P=0.018). Patients with a high DE50 score showed better progression-free survival (PFS) than those with a low DE50 score (P=0.0022). The multivariable Cox regression demonstrated that high DE50 and low platelet-lymphocyte ratio (PLR) were significant independent predictors for better PFS when treated with anti-PD-1 antibody. Furthermore, a highly predictive nomogram was set up based on peripheral TCR repertoire profiling. The area under the curves (AUCs) of this system at 3-, 6- and 12-month PFS reached 0.825, 0.802, and 0.954, respectively. The nomogram had a C-index of 0.768 [95% confidence interval (CI): 0.658-0.879]. Meanwhile, the calibration curves also demonstrated the reliability and stability of the model. Conclusions: High DE50 scores were predictive of a favorable response and longer PFS to anti-PD-1 treatment in GIC patients. The nomogram based on TCR repertoire profiling was a reliable and practical tool, which could provide risk assessment and clinical decision-making for individualized treatment of patients.

Integrated multi-omics profiling to dissect the spatiotemporal evolution of metastatic hepatocellular carcinoma.

Comprehensive molecular analyses of metastatic hepatocellular carcinoma (HCC) are lacking. Here, we generate multi-omic profiling of 257 primary and 176 metastatic regions from 182 HCC patients. Primary tumors rich in hypoxia signatures facilitated polyclonal dissemination. Genomic divergence between primary and metastatic HCC is high, and early dissemination is prevalent. The remarkable neoantigen intratumor heterogeneity observed in metastases is associated with decreased T cell reactivity, resulting from disruptions to neoantigen presentation. We identify somatic copy number alterations as highly selected events driving metastasis. Subclones without Wnt mutations show a stronger selective advantage for metastasis than those with Wnt mutations and are characterized by a microenvironment rich in activated fibroblasts favoring a pro-metastatic phenotype. Finally, metastases without Wnt mutations exhibit higher enrichment of immunosuppressive B cells that mediate terminal exhaustion of CD8+ T cells via HLA-E:CD94-NKG2A checkpoint axis. Collectively, our results provide a multi-dimensional dissection of the complex evolutionary process of metastasis.