The Effect of Platelet Fibrin Plasma (PFP) on Postoperative Refractory Wounds: Physiologically Concentrated Platelet Plasma in Wound Repair.

OBJECTIVE: Surgical wounds that can't complete primary healing three weeks after surgery are called postoperative refractory wounds. Postoperative refractory wounds would bring great physical and life burdens to the patients and seriously affect their quality of life. To investigate the effect of platelet fibrin plasma (PFP) on postoperative refractory wound healing. APPROACH: The composition of PFP was analyzed using blood routine and blood biochemicals. Clinical data were collected that met the inclusion criteria after treatment with PFP, and the efficacy of PFP was evaluated by wound healing rate and days to healing. Next, growth factor content in PFP, PRP, and PPP was analyzed using ELISA, and PFP-treated cells were applied to investigate the effect of PFP on fibroblast and endothelial cell function. RESULTS: PFP component analysis revealed no statistical difference between platelet concentration in PFP and physiological concentration. Clinical statistics showed that PFP treatment was effective in the postoperative refractory wound (four-week wound healing rate > 90%), significantly better than continuous wound dressing. Meanwhile, our result also proved that PFP treatment significantly enhanced vascularization by upregulated the expression level of CD31 and improved granulation tissue thickness. Activated PFP, PRP, and PPP could continuously release growth factors in vitro and the amount of growth factors released by PRP and PFP was significantly higher than PPP. In vitro studies demonstrated that active PFP could improve cell proliferation, migration, adhesion, and angiogenesis in fibroblasts and endothelial cells. INNOVATION: Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The modified PFP (responsible for accelerating wound healing and enhancing the migration and proliferation of fibroblasts and endothelial cells) was prepared and analyzed for its clinical effectiveness in postoperative refractory wounds. CONCLUSION: Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The preparation of PFP could significantly reduce the amount of prepared blood, with a good application value for postoperative wounds. PFP can be considered a treatment option, especially for postoperative refractory wounds.

The NSCLC immunotherapy response predicted by tumor-infiltrating T cells via a non-invasive radiomic approach.

Introductions: Identifying patients with non-small cell lung cancer (NSCLC) who are optimal candidates for immunotherapy is a cornerstone in clinical decision-making. The tumor immune microenvironment (TIME) is intricately linked with both the prognosis of the malignancy and the efficacy of immunotherapeutic interventions. CD8+ T cells, and more specifically, tissue-resident memory CD8+ T cells [CD8+ tissue-resident memory T (TRM) cells] are postulated to be pivotal in orchestrating the immune system's assault on tumor cells. Nevertheless, the accurate quantification of immune cell infiltration-and by extension, the prediction of immunotherapeutic efficacy-remains a significant scientific frontier. Methods: In this study, we introduce a cutting-edge non-invasive radiomic model, grounded in TIME markers (CD3+ T, CD8+ T, and CD8+ TRM cells), to infer the levels of immune cell infiltration in NSCLC patients receiving immune checkpoint inhibitors and ultimately predict their response to immunotherapy. Data from patients who had surgical resections (cohort 1) were employed to construct a radiomic model capable of predicting the TIME. This model was then applied to forecast the TIME for patients under immunotherapy (cohort 2). Conclusively, the study delved into the association between the predicted TIME from the radiomic model and the immunotherapeutic outcomes of the patients. Result: For the immune cell infiltration radiomic prediction models in cohort 1, the AUC values achieved 0.765, 0.763, and 0.675 in the test set of CD3+ T, CD8+ T, and CD8+ TRM, respectively. While the AUC values for the TIME-immunotherapy predictive value were 0.651, 0.763, and 0.829 in the CD3-immunotherapy response model, CD8-immunotherapy response model, and CD8+ TRM-immunotherapy response model in cohort 2, respectively. The CD8+ TRM-immunotherapy model exhibited the highest predictive value and was significantly better than the CD3-immunotherapy model in predicting the immunotherapy response. The progression-free survival (PFS) analysis based on the predicted levels of CD3+ T, CD8+ T, and CD8+ TRM immune cell infiltration showed that the CD8+ T cell infiltration level was an independent factor (P=0.014, HR=0.218) with an AUC value of 0.938. Discussion: Our empirical evidence reveals that patients with substantial CD8+ T cell infiltration experience a markedly improved PFS compared with those with minimal infiltration, asserting the status of the CD8+ T cell as an independent prognosticator of PFS in the context of immunotherapy. Although CD8+ TRM cells demonstrated the greatest predictive accuracy for immunotherapy response, their predictive strength for PFS was marginally surpassed by that of CD8+ T cells. These insights advocate for the application of the proposed non-invasive radiomic model, which utilizes TIME analysis, as a reliable predictor for immunotherapy outcomes and PFS in NSCLC patients.

Hybrid Anapole Induced Chirality in Metasurfaces.

The interaction between light and matter, particularly chirality, plays a pivotal role in modern science and technology. Typically, metasurfaces achieve chiro-optical effects by coupling electric and magnetic dipoles in specific orientations. In this work, the design and optimization of an asymmetric H-shaped metasurface is explored to induce hybrid anapole (HA) for optical activity. When the symmetry of the metasurface structure is disrupted, the design can simultaneously excite first-order and pseudo high-order HA under illumination with a specific circular polarization, both occurring within the same spectral regime. This results in high reflection for one circular polarization and a significant reduction in reflection for the orthogonal polarization, thereby exhibiting exceptional chiro-optical activity. Moreover, the HA-based chiral metasurface demonstrates strong polarization control capabilities, as verified by Stokes parameter analysis, revealing high birefringence and a pronounced dependence on the incident polarization angle. These results provide valuable insights for the design and optimization of HA metasurfaces for advanced optical applications and polarization control, paving the way for new developments in chiral nanophotonics.

Nonlocal meta-lens with Huygens' bound states in the continuum.

Meta-lenses composed of artificial meta-atoms have stimulated substantial interest due to their compact and flexible wavefront shaping capabilities, outperforming bulk optical devices. The operating bandwidth is a critical factor determining the meta-lens' performance across various wavelengths. Meta-lenses that operate in a narrowband manner relying on nonlocal effects can effectively reduce disturbance and crosstalk from non-resonant wavelengths, making them well-suitable for specialized applications such as nonlinear generation and augmented reality/virtual reality display. However, nonlocal meta-lenses require striking a balance between local phase manipulation and nonlocal resonance excitation, which involves trade-offs among factors like quality-factor, efficiency, manipulation dimensions, and footprint. In this work, we experimentally demonstrate the nonlocal meta-lens featuring Huygens' bound states in the continuum (BICs) and its near-infrared imaging application. All-dielectric integrated-resonant unit is particularly optimized to efficiently induce both the quasi-BIC and generalized Kerker effect, while ensuring the rotation-angle robustness for generating geometric phase. The experimental results show that the single-layer nonlocal Huygens' meta-lens possesses a high quality-factor of 104 and achieves a transmission polarization conversion efficiency of 55%, exceeding the theoretical limit of 25%. The wavelength-selective two-dimensional focusing and imaging are demonstrated as well. This work will pave the way for efficient nonlocal wavefront shaping and meta-devices.

Epithelium/imcDC2 axis facilitates the resistance of neoadjuvant anti-PD-1 in human NSCLC.

BACKGROUND: Therapeutic resistance is a main obstacle to achieve long-term benefits from immune checkpoint inhibitors. The underlying mechanism of neoadjuvant anti-PD-1 resistance remains unclear. METHODS: Multi-omics analysis, including mass cytometry, single-cell RNA-seq, bulk RNA-seq, and polychromatic flow cytometry, was conducted using the resected tumor samples in a cohort of non-small cell lung cancer (NSCLC) patients received neoadjuvant anti-PD-1 therapy. Tumor and paired lung samples acquired from treatment-naïve patients were used as a control. In vitro experiments were conducted using primary cells isolated from fresh tissues and lung cancer cell lines. A Lewis-bearing mouse model was used in the in vivo experiment. RESULTS: The quantity, differentiation status, and clonal expansion of tissue-resident memory CD8+ T cells (CD8+ TRMs) are positively correlated with therapeutic efficacy of neoadjuvant anti-PD-1 therapy in human NSCLC. In contrast, the quantity of immature CD1c+ classical type 2 dendritic cells (imcDC2) and galectin-9+ cancer cells is negatively correlated with therapeutic efficacy. An epithelium/imDC2 suppressive axis that restrains the antitumor response of CD8+ TRMs via galectin-9/TIM-3 was uncovered. The expression level of CD8+ TRMs and galectin-9+ cancer cell-related genes predict the clinical outcome of anti-PD-1 neoadjuvant therapy in human NSCLC patients. Finally, blockade of TIM-3 and PD-1 could improve the survival of tumor-bearing mouse by promoting the antigen presentation of imcDC2 and CD8+ TRMs-mediated tumor-killing. CONCLUSION: Galectin-9 expressing tumor cells sustained the primary resistance of neoadjuvant anti-PD-1 therapy in NSCLC through galectin-9/TIM-3-mediated suppression of imcDC2 and CD8+ TRMs. Supplement of anti-TIM-3 could break the epithelium/imcDC2/CD8+ TRMs suppressive loop to overcome anti-PD-1 resistance. TRIAL REGISTRATION NUMBER: NCT03732664.

Hypoxia inhibits the iMo/cDC2/CD8+ TRMs immune axis in the tumor microenvironment of human esophageal cancer.

BACKGROUND: Esophageal cancer (ESCA) is a form of malignant tumor associated with chronic inflammation and immune dysregulation. However, the specific immune status and key mechanisms of immune regulation in this disease require further exploration. METHODS: To investigate the features of the human ESCA tumor immune microenvironment and its possible regulation, we performed mass cytometry by time of flight, single-cell RNA sequencing, multicolor fluorescence staining of tissue, and flow cytometry analyses on tumor and paracancerous tissue from treatment-naïve patients. RESULTS: We depicted the immune landscape of the ESCA and revealed that CD8+ (tissue-resident memory CD8+ T cells (CD8+ TRMs) were closely related to disease progression. We also revealed the heterogeneity of CD8+ TRMs in the ESCA tumor microenvironment (TME), which was associated with their differentiation and function. Moreover, the subset of CD8+ TRMs in tumor (called tTRMs) that expressed high levels of granzyme B and immune checkpoints was markedly decreased in the TME of advanced ESCA. We showed that tTRMs are tumor effector cells preactivated in the TME. We then demonstrated that conventional dendritic cells (cDC2s) derived from intermediate monocytes (iMos) are essential for maintaining the proliferation of CD8+ TRMs in the TME. Our preliminary study showed that hypoxia can promote the apoptosis of iMos and impede the maturation of cDC2s, which in turn reduces the proliferative capacity of CD8+ TRMs, thereby contributing to the progression of cancer. CONCLUSIONS: Our study revealed the essential antitumor roles of CD8+ TRMs and preliminarily explored the regulation of the iMo/cDC2/CD8+ TRM immune axis in the human ESCA TME.

Streamlined spatial and environmental expression signatures characterize the minimalist duckweed Wolffia australiana.

Single-cell genomics permits a new resolution in the examination of molecular and cellular dynamics, allowing global, parallel assessments of cell types and cellular behaviors through development and in response to environmental circumstances, such as interaction with water and the light-dark cycle of the Earth. Here, we leverage the smallest, and possibly most structurally reduced, plant, the semiaquatic Wolffia australiana, to understand dynamics of cell expression in these contexts at the whole-plant level. We examined single-cell-resolution RNA-sequencing data and found Wolffia cells divide into four principal clusters representing the above- and below-water-situated parenchyma and epidermis. Although these tissues share transcriptomic similarity with model plants, they display distinct adaptations that Wolffia has made for the aquatic environment. Within this broad classification, discrete subspecializations are evident, with select cells showing unique transcriptomic signatures associated with developmental maturation and specialized physiologies. Assessing this simplified biological system temporally at two key time-of-day (TOD) transitions, we identify additional TOD-responsive genes previously overlooked in whole-plant transcriptomic approaches and demonstrate that the core circadian clock machinery and its downstream responses can vary in cell-specific manners, even in this simplified system. Distinctions between cell types and their responses to submergence and/or TOD are driven by expression changes of unexpectedly few genes, characterizing Wolffia as a highly streamlined organism with the majority of genes dedicated to fundamental cellular processes. Wolffia provides a unique opportunity to apply reductionist biology to elucidate signaling functions at the organismal level, for which this work provides a powerful resource.

JAML promotes the antitumor role of tumor-resident CD8+ T cells by facilitating their innate-like function in human lung cancer.

Tissue-resident memory CD8+T cells (CD8+TRMs) are thought to play a crucial role in cancer immunosurveillance. However, the characteristics of CD8+TRMs in the tumor microenvironment (TME) of human non-small cell lung cancer (NSCLC) remain unclear. Here, we report that CD8+TRMs accumulate explicitly and exhibit a unique gene expression profile in the TME of NSCLC. Interestingly, these tumor-associated CD8+TRMs uniquely exhibit an innate-like phenotype. Importantly, we found that junction adhesion molecule-like (JAML) provides an alternative costimulatory signal to activate tumor-associated CD8+TRMs via combination with cancer cell-derived CXADR (CXADR Ig-like cell adhesion molecule). Furthermore, we demonstrated that activating JAML could promote the expression of TLR1/2 on CD8+TRMs, inhibit tumor progression and prolong the survival of tumor-bearing mice. Finally, we found that higher CD8+TRMs and JAML expression in the TME could predict favorable clinical outcomes in NSCLC patients. Our study reveals an intrinsic bias of CD8+TRMs for receiving the tumor-derived costimulatory signal in the TME, which sustains their innate-like function and antitumor role. These findings will shed more light on the biology of CD8+TRMs and aid in the development of potential targeted treatment strategies for NSCLC.

One-tube B7-H3 detection based on isothermal exponential amplification and dendritic hybridization chain reaction.

We have developed a one-tube fluorescence strategy for the detection of B7-H3 based on a proximity hybridization-mediated protein-to-DNA signal transducer, isothermal exponential amplification (EXPAR), and dendritic hybridization chain reaction (D-HCR). In this assay, a protein signal transducer was employed to convert the input protein to output single-stranded DNA with a nicking site. Antibody-conjugated DNA1 was first hybridized with the output DNA (DNA3). The binding of antibodies conjugated DNA1 and DNA2 to the same protein was able to increase the local concentrations, resulting in strand displacement between DNA3 and DNA2. DNA3 with a nicking endonuclease recognition sequence at the 5' end then hybridized with hairpin probe 1 to mediate EXPAR in the presence of nicking endonuclease and DNA polymerase. A large number of single-strand DNA were produced in the circle of nicking, polymerization, and strand displacement. The resulting ssDNA products were further amplified by D-HCR to produce many large-molecular concatemers. The resulting DNA products can be monitored in real-time fluorescence signaling. Our proposed assay can realize one-tube detection due to the same reaction temperature of the protein-to-DNA signal transducer, EXPAR, and DHCR. This assay has a linear range from 100 fg mL-1 to 1 µg mL-1 with a detection limit down to 100 fg mL-1. This work shows a good performance in clinical specimen detection.

Targeting pro-inflammatory T cells as a novel therapeutic approach to potentially resolve atherosclerosis in humans.

Atherosclerosis (AS), a leading cause of cardio-cerebrovascular disease worldwide, is driven by the accumulation of lipid contents and chronic inflammation. Traditional strategies primarily focus on lipid reduction to control AS progression, leaving residual inflammatory risks for major adverse cardiovascular events (MACEs). While anti-inflammatory therapies targeting innate immunity have reduced MACEs, many patients continue to face significant risks. Another key component in AS progression is adaptive immunity, but its potential role in preventing AS remains unclear. To investigate this, we conducted a retrospective cohort study on tumor patients with AS plaques. We found that anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) significantly reduces AS plaque size. With multi-omics single-cell analyses, we comprehensively characterized AS plaque-specific PD-1+ T cells, which are activated and pro-inflammatory. We demonstrated that anti-PD-1 mAb, when captured by myeloid-expressed Fc gamma receptors (FcγRs), interacts with PD-1 expressed on T cells. This interaction turns the anti-PD-1 mAb into a substitute PD-1 ligand, suppressing T-cell functions in the PD-1 ligands-deficient context of AS plaques. Further, we conducted a prospective cohort study on tumor patients treated with anti-PD-1 mAb with or without Fc-binding capability. Our analysis shows that anti-PD-1 mAb with Fc-binding capability effectively reduces AS plaque size, while anti-PD-1 mAb without Fc-binding capability does not. Our work suggests that T cell-targeting immunotherapy can be an effective strategy to resolve AS in humans.

ROCK1 inhibition improves wound healing in diabetes via RIPK4/AMPK pathway.

Refractory wounds are a severe complication of diabetes mellitus that often leads to amputation because of the lack of effective treatments and therapeutic targets. The pathogenesis of refractory wounds is complex, involving many types of cells. Rho-associated protein kinase-1 (ROCK1) phosphorylates a series of substrates that trigger downstream signaling pathways, affecting multiple cellular processes, including cell migration, communication, and proliferation. The present study investigated the role of ROCK1 in diabetic wound healing and molecular mechanisms. Our results showed that ROCK1 expression significantly increased in wound granulation tissues in diabetic patients, streptozotocin (STZ)-induced diabetic mice, and db/db diabetic mice. Wound healing and blood perfusion were dose-dependently improved by the ROCK1 inhibitor fasudil in diabetic mice. In endothelial cells, fasudil and ROCK1 siRNA significantly elevated the phosphorylation of adenosine monophosphate-activated protein kinase at Thr172 (pThr172-AMPKα), the activity of endothelial nitric oxide synthase (eNOS), and suppressed the levels of mitochondrial reactive oxygen species (mtROS) and nitrotyrosine formation. Experiments using integrated bioinformatics analysis and coimmunoprecipitation established that ROCK1 inhibited pThr172-AMPKα by binding to receptor-interacting serine/threonine kinase 4 (RIPK4). These results suggest that fasudil accelerated wound repair and improved angiogenesis at least partially through the ROCK1/RIPK4/AMPK pathway. Fasudil may be a potential treatment for refractory wounds in diabetic patients.

Wemics: A Single-Base Resolution Methylation Quantification Method for Enhanced Prediction of Epigenetic Regulation.

DNA methylation, an epigenetic mechanism that alters gene expression without changing DNA sequence, is essential for organism development and key biological processes like genomic imprinting and X-chromosome inactivation. Despite tremendous efforts in DNA methylation research, accurate quantification of cytosine methylation remains a challenge. Here, a single-base methylation quantification approach is introduced by weighting methylation of consecutive CpG sites (Wemics) in genomic regions. Wemics quantification of DNA methylation better predicts its regulatory impact on gene transcription and identifies differentially methylated regions (DMRs) with more biological relevance. Most Wemics-quantified DMRs in lung cancer are epigenetically conserved and recurrently occurred in other primary cancers from The Cancer Genome Atlas (TCGA), and their aberrant alterations can serve as promising pan-cancer diagnostic markers. It is further revealed that these detected DMRs are enriched in transcription factor (TF) binding motifs, and methylation of these TF binding motifs and TF expression synergistically regulate target gene expression. Using Wemics on epigenomic-transcriptomic data from the large lung cancer cohort, a dozen novel genes with oncogenic potential are discovered that are upregulated by hypomethylation but overlooked by other quantification methods. These findings increase the understanding of the epigenetic mechanism by which DNA methylation regulates gene expression.

Microbial metabolite enhances immunotherapy efficacy by modulating T cell stemness in pan-cancer.

The immune checkpoint blockade (ICB) response in human cancers is closely linked to the gut microbiota. Here, we report that the abundance of commensal Lactobacillus johnsonii is positively correlated with the responsiveness of ICB. Supplementation with Lactobacillus johnsonii or tryptophan-derived metabolite indole-3-propionic acid (IPA) enhances the efficacy of CD8+ T cell-mediated αPD-1 immunotherapy. Mechanistically, Lactobacillus johnsonii collaborates with Clostridium sporogenes to produce IPA. IPA modulates the stemness program of CD8+ T cells and facilitates the generation of progenitor exhausted CD8+ T cells (Tpex) by increasing H3K27 acetylation at the super-enhancer region of Tcf7. IPA improves ICB responsiveness at the pan-cancer level, including melanoma, breast cancer, and colorectal cancer. Collectively, our findings identify a microbial metabolite-immune regulatory pathway and suggest a potential microbial-based adjuvant approach to improve the responsiveness of immunotherapy.

High-security learning-based optical encryption assisted by disordered metasurface.

Artificial intelligence has gained significant attention for exploiting optical scattering for optical encryption. Conventional scattering media are inevitably influenced by instability or perturbations, and hence unsuitable for long-term scenarios. Additionally, the plaintext can be easily compromised due to the single channel within the medium and one-to-one mapping between input and output. To mitigate these issues, a stable spin-multiplexing disordered metasurface (DM) with numerous polarized transmission channels serves as the scattering medium, and a double-secure procedure with superposition of plaintext and security key achieves two-to-one mapping between input and output. In attack analysis, when the ciphertext, security key, and incident polarization are all correct, the plaintext can be decrypted. This system demonstrates excellent decryption efficiency over extended periods in noisy environments. The DM, functioning as an ultra-stable and active speckle generator, coupled with the double-secure approach, creates a highly secure speckle-based cryptosystem with immense potentials for practical applications.

Inflammatory dendritic cells restrain CD11b+CD4+ CTLs via CD200R in human NSCLC.

CD4+ cytotoxic T lymphocytes (CD4+ CTLs) are suggested to play a crucial role in inflammatory diseases, including cancer, but their characteristics in human non-small cell lung cancer (NSCLC) remain unknown. Here, using the cell surface marker CD11b, we identify CD11b+CD4+ CTLs as a cytotoxic subset of CD4+ T cells in multiple tissues of NSCLC patients. In addition, tumor-infiltrating CD11b+CD4+ CTLs show a dysfunctional phenotype with elevated expression of CD200 receptor (CD200R), a negatively immunomodulatory receptor. CD4+ regulatory T (Treg) cells restrain the anti-tumor role of CD11b+CD4+ CTLs via CD200. Mechanistically, inflammatory dendritic cells promote the CD200R expression of CD11b+CD4+ CTLs by secreting interleukin-1ß (IL-1ß). Finally, we demonstrate that CD200 blockade can revive the tumor-killing role of CD11b+CD4+ CTLs and prolong the survival of tumor-bearing mice. Taken together, our study identifies CD11b+CD4+ CTLs in NSCLC with decreased cytotoxicity that can be reinvigorated by CD200 blockade, suggesting that targeting CD200 is a promising immunotherapy strategy in NSCLC.

LASSO-derived model for the prediction of lean-non-alcoholic fatty liver disease in examinees attending a routine health check-up.

BACKGROUND: Lean individuals with non-alcohol fatty liver disease (NAFLD) often have normal body size but abnormal visceral fat. Therefore, an alternative to body mass index should be considered for prediction of lean-NAFLD. This study aimed to use representative visceral fat links with other laboratory parameters using the least absolute shrinkage and selection operator (LASSO) method to construct a predictive model for lean-NAFLD. METHODS: This retrospective cross-sectional analysis enrolled 2325 subjects with BMI < 24 kg/m2 from medical records of 51,271 examinees who underwent a routine health check-up. They were randomly divided into training and validation cohorts at a ratio of 1:1. The LASSO-derived prediction model used LASSO regression to select 23 clinical and laboratory factors. The discrimination and calibration abilities were evaluated using the Hosmer-Lemeshow test and calibration curves. The performance of the LASSO model was compared with the fatty liver index (FLI) model. RESULTS: The LASSO-derived model included four variables-visceral fat, triglyceride levels, HDL-C-C levels, and waist hip ratio-and demonstrated superior performance in predicting lean-NAFLD with high discriminatory ability (AUC, 0.8416; 95% CI: 0.811-0.872) that was comparable with the FLI model. Using a cut-off of 0.1484, moderate sensitivity (75.69%) and specificity (79.86%), as well as high negative predictive value (95.9%), were achieved in the LASSO model. In addition, with normal WC subgroup analysis, the LASSO model exhibits a trend of higher accuracy compared to FLI (cut-off 15.45). CONCLUSIONS: We developed a LASSO-derived predictive model with the potential for use as an alternative tool for predicting lean-NAFLD in clinical settings.

Researchers developed a model to predict a type of liver disease called non-alcoholic fatty liver disease (NAFLD) in lean individuals.The model accurately detects NAFLD in lean individuals using factors like visceral fat, triglyceride levels, and waist-to-hip ratio, aiding in identifying the disease in normal-weight people with abnormal fat distribution.

Association between polycyclic aromatic hydrocarbons exposure with red cell width distribution and ischemic heart disease: insights from a population-based study.

This study investigates the association between polycyclic aromatic hydrocarbon (PAH) exposure, red blood cell distribution width (RDW), and ischemic heart disease (IHD) in a sample of 3003 participants from the National Health and Nutrition Examination Survey (NHANES). We hypothesize that RDW may mediate the effect of hydroxylated PAHs (OH-PAH) on IHD. Logistic regression models reveal significant associations between increased urinary PAH metabolite concentrations and IHD, as well as positive associations between PAH metabolites and RDW. Weighted Quantile Sum (WQS) regression and Bayesian Kernel Machine Regression (BKMR) analyses confirm the significant associations of the OH-PAH mixture with IHD and RDW. Mediation analysis demonstrates that RDW partially mediates the relationship between PAH exposure and IHD, accounting for 2-4.6% of the total effects. Our findings highlight the potential underlying mechanisms linking PAH exposure, RDW, and IHD and emphasize the importance of addressing environmental pollutants like PAHs in maintaining cardiovascular health and informing public health policies.

Creating pairs of exceptional points for arbitrary polarization control: asymmetric vectorial wavefront modulation.

Exceptional points (EPs) can achieve intriguing asymmetric control in non-Hermitian systems due to the degeneracy of eigenstates. Here, we present a general method that extends this specific asymmetric response of EP photonic systems to address any arbitrary fully-polarized light. By rotating the meta-structures at EP, Pancharatnam-Berry (PB) phase can be exclusively encoded on one of the circular polarization-conversion channels. To address any arbitrary wavefront, we superpose the optical signals originating from two orthogonally polarized -yet degenerate- EP eigenmodes. The construction of such orthogonal EP eigenstates pairs is achieved by applying mirror-symmetry to the nanostructure geometry flipping thereby the EP eigenmode handedness from left to right circular polarization. Non-Hermitian reflective PB metasurfaces designed using such EP superposition enable arbitrary, yet unidirectional, vectorial wavefront shaping devices. Our results open new avenues for topological wave control and illustrate the capabilities of topological photonics to distinctively operate on arbitrary polarization-state with enhanced performances.

Asymmetric Full-Color Vectorial Meta-holograms Empowered by Pairs of Exceptional Points.

Holography holds tremendous promise in applications such as immersive virtual reality and optical communications. With the emergence of optical metasurfaces, planar optical components that have the remarkable ability to precisely manipulate the amplitude, phase, and polarization of light on the subwavelength scale have expanded the potential applications of holography. However, the realization of metasurface-based full-color vectorial holography remains particularly challenging. Here, we report a general approach utilizing a modified Gerchberg-Saxton algorithm to achieve spatially aligned full-color display and incorporating wavelength information with an image compensation strategy. We combine the Pancharatnam-Berry phase and pairs of exceptional points to address the issue of redundant twin images that generally appear for the two orthogonal circular polarizations and to enable full polarization control of the vectorial field. Our results enable the realization of an asymmetric full-color vectorial meta-hologram, paving the way for the development of full-color display, complex beam generation, and secure data storage applications.