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Tertiary lymphoid structures (TLSs) have been associated with favorable immunotherapy responses and prognosis in various cancers. Despite their significance, their quantification using multiplex immunohistochemistry (mIHC) staining of T and B lymphocytes remains labor-intensive, limiting its clinical utility. To address this challenge, we curated a dataset from matched mIHC and H&E whole-slide images (WSIs) and developed a deep learning model for automated segmentation of TLSs. The model achieved Dice coefficients of 0.91 on the internal test set and 0.866 on the external validation set, along with intersection over union (IoU) scores of 0.819 and 0.787, respectively. The TLS ratio, defined as the segmented TLS area over the total tissue area, correlated with B lymphocyte levels and the expression of CXCL13, a chemokine associated with TLS formation, in 6140 patients spanning 16 tumor types from The Cancer Genome Atlas (TCGA). The prognostic models for overall survival indicated that the inclusion of the TLS ratio with TNM staging significantly enhanced the models' discriminative ability, outperforming the traditional models that solely incorporated TNM staging, in 10 out of 15 TCGA tumor types. Furthermore, when applied to biopsied treatment-naïve tumor samples, higher TLS ratios predicted a positive immunotherapy response across multiple cohorts, including specific therapies for esophageal squamous cell carcinoma, non-small cell lung cancer, and stomach adenocarcinoma. In conclusion, our deep learning-based approach offers an automated and reproducible method for TLS segmentation and quantification, highlighting its potential in predicting immunotherapy response and informing cancer prognosis. [ABSTRACT FROM AUTHOR]

Spider pulsars are millisecond pulsars in short-period (≲12-h) orbits with low-mass (~0.01–0.4 M⊙) companion stars. The pulsars ablate plasma from the companion star, causing time delays and eclipses of the radio emission from the pulsar. The magnetic field of the companion has been proposed to strongly influence both the evolution of the binary system1 and the eclipse properties of the pulsar emission2. Changes in the rotation measure (RM) have been seen in a spider system, implying that there is an increase in the magnetic field near the eclipse3. Here we report a diverse range of evidence for a highly magnetized environment in the spider system PSR B1744 – 24A4, located in the globular cluster Terzan 5. We observe semi-regular profile changes to the circular polarization, V, when the pulsar emission passes close to the companion. This suggests that there is Faraday conversion where the radio wave tracks a reversal in the parallel magnetic field and constrains the companion magnetic field, B (> 10 G). We also see irregular, fast changes in the RM at random orbital phases, implying that the magnetic strength of the stellar wind, B, is greater than 10 mG. There are similarities between the unusual polarization behaviour of PSR B1744 – 24A and some repeating fast radio bursts (FRBs)5–7. Together with the possible binary-produced long-term periodicity of two active repeating FRBs8,9, and the discovery of a nearby FRB in a globular cluster10, where pulsar binaries are common, these similarities suggest that a proportion of FRBs have binary companions.The observation of pulsar emission at various orbital phases of a companion star probes the diverse magnetic structure in a binary system, and exhibits varying polarization behavior, akin to that observed in certain fast radio bursts. [ABSTRACT FROM AUTHOR]

Ceria nanorods (NRs) with an average length of 23, 73, 115, 131, and 192 nm were synthesized separately by a facile hydrothermal method and then were roasted at 600 °C in air, 50% H2, and pure H2 to generate various concentrations of surface oxygen vacancies (OVs). OVs concentration in ceria lattice is firstly increasing and then trends to decrease with the rising of ceria NRs length, while the band gap of ceria NRs expands with length increasing and slightly widens with the elevation of surface OVs concentration. Separation efficiency of photo-excited electrons/holes (e−/h+) and photodegradation ratio of methylene blue (MB) with ceria NRs elevate firstly and then decrease with the length increasing, while the generated OVs promote the photocatalytic activity of ceria. The ceria NRs with an average length of 115 nm and calcined in hydrogen show a better photocatalytic activity with the MB degradation ratio of 86.32%. [ABSTRACT FROM AUTHOR]

Several clinical trials have shown the safety and effectiveness of PD-1/PD-L1 inhibitors in neoadjuvant therapy in resectable non-small cell lung cancer (NSCLC). However, 18–83% patients can benefit from it. In this study, we aimed to assess the association of PD-L1 expression, tumor mutation burden, copy number alteration (CNA, including copy number gain and loss) burden with the pathologic response to neoadjuvant PD-1 blockade and investigate the changes in the tumor immune microenvironment (TIME) during neoadjuvant immunotherapy in NSCLC. Pre-immunotherapy treatment tumor samples from twenty-nine NSCLC patients who received neoadjuvant immunotherapy with sintilimab, an anti-PD-1 drug, were subjected to targeted DNA sequencing and PD-L1 immunochemistry staining. The pathological response was positively correlated with tumor proportion score (TPS) of PD-L1 and negatively correlated with copy number gain (CNgain) burden. Of note, the combination of CNgain burden and TPS can better stratify major pathological response (MPR) patients than did CNgain or TPS alone. Whereas, TMB showed a limited correlation with pathological regression. Additionally, PD-1 blockade led to an increase in CD8+PD-1−T cells which was clinically relevant to MPR as evaluated by multiplex immunofluorescence. A significant reduction in CD19+ cells was observed in the Non-MPR group but not in the MPR group, indicating the involvement of B cells in improving neoadjuvant immunotherapy response in NSCLC. Together, our study provides new data for the correlation of PD-L1 expression and genomic factors with drug response in neoadjuvant immunotherapy settings in NSCLC. The changes of TIME may provide novel insight into the immune responses to neoadjuvant anti-PD-1 therapy. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic and progressive process. It is the most important pathological basis of cardiovascular disease and stroke. Vascular smooth muscle cells (VSMCs) are an essential cell type in atherosclerosis. Previous studies have revealed that VSMCs undergo phenotypic transformation in atherosclerosis to participate in the retention of atherogenic lipoproteins as well as the formation of the fibrous cap and the underlying necrotic core in plaques. The emergence of lineage-tracing studies indicates that the function and number of VSMCs in plaques have been greatly underestimated. In addition, recent studies have revealed that VSMCs make up at least 50% of the foam cell population in human and mouse atherosclerotic lesions. Therefore, understanding the formation of lipid-loaded VSMCs and their regulatory mechanisms is critical to elucidate the pathogenesis of atherosclerosis and to explore potential therapeutic targets. Moreover, combination of many complementary technologies such as lineage tracing, single-cell RNA sequencing (scRNA-seq), flow cytometry, and mass cytometry (CyTOF) with immunostaining has been performed to further understand the complex VSMC function. Correct identification of detrimental and beneficial processes may reveal successful therapeutic treatments targeting VSMCs and their derivatives during atherosclerosis. The purpose of this review is to summarize the process of lipid-loaded VSMC formation in atherosclerosis and to describe novel insight into VSMCs gained by using multiple advanced methods. [ABSTRACT FROM AUTHOR]

The microreactor with two types of immobilized enzymes, exhibiting excellent orthogonal performance, represents an effective approach to counteract the reduced digestion efficiency resulting from the absence of a single enzyme cleavage site, thereby impacting protein identification. In this study, we developed a hydrophilic dual-enzyme microreactor characterized by rapid mass transfer and superior enzymatic activity. Initially, we selected KIT-6 molecular sieve as the carrier for the dual-IMER due to its three-dimensional network pore structure. Modification involved co-deposition of polyethyleneimine (PEI) and acrylamide (AM) as amine donors, along with dopamine to enhance material hydrophilicity. Remaining amino and double bond functional groups facilitated stepwise immobilization of trypsin and Glu-C. Digestion times for bovine serum albumin (BSA) and bovine hemoglobin (BHb) on the dual-IMER were significantly reduced compared to solution-based digestion (1 min vs. 36 h), resulting in improved sequence coverage (91.30% vs. 82.7% for BSA; 90.24% vs. 89.20% for BHb). Additionally, the dual-IMER demonstrated excellent durability, retaining 96.08% relative activity after 29 reuse cycles. Enhanced protein digestion efficiency can be attributed to several factors: (1) KIT-6’s large specific surface area, enabling higher enzyme loading capacity; (2) Its three-dimensional network pore structure, facilitating faster mass transfer and substance diffusion; (3) Orthogonality of trypsin and Glu-C enzyme cleavage sites; (4) The spatial effect introduced by the chain structure of PEI and glutaraldehyde’s spacing arm, reducing spatial hindrance and enhancing enzyme–substrate interactions; (5) Mild and stable enzyme immobilization. The KIT-6-based dual-IMER offers a promising technical tool for protein digestion, while the PDA/PEI/AM-KIT-6 platform holds potential for immobilizing other proteins or active substances. [ABSTRACT FROM AUTHOR]

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Multiple objectives optimization of frequency selective surface (FSS) structures is challenging in electromagnetic wave filter design. For example, one of the sub-objectives, the sidelobe level (SLL), is critical to directional anti-interference, which is complicated and becomes the bottleneck for radar design. Here, we established a dynamic algorithm for fitness function to automatically adjust the weights of multiple objectives in the optimization process of FSS structures. The dynamic algorithm could efficiently evaluate the achieving probability of sub-objectives according to the statistical analysis of the latest individual distribution so that the fitness function could automatically adjusted to focus on the sub-objective difficult to optimize, such as SLL. Computational results from the dynamic algorithm showed that the efficiency of multi-objective optimization was greatly improved by 213%, as compared to the fixed-weighted algorithm of the fitness function. Specifically for SLL, the efficiency rate increased even better, up to 315%. More interestingly, the FSS structures were most improved while picking median value or golden section value as the reference value. Taken together, the current study indicated that the dynamic algorithm with fitness function might be a better choice for FSS structural optimization with SLL suppression and potentially for the better design of lower SLL radar. [ABSTRACT FROM AUTHOR]