Preparation of convex edges in fused silica by single pass perforation with a 2D Airy-Gaussian beam.

Following ultrafast laser machining of fused silica, post-processing such as polishing and honing are typically required for edges. In this study, we employed a spatial light modulator (SLM) to generate the 2D Airy-Gaussian beam to prepare the convex edges in fused silica by using a single pass of a picosecond laser. It is found that, if the speed exceeds 5 mm/s, there would be plasma interference which is unfavorable for the separation process. A filament effect was observed when the internal laser peak power exceeds the damage threshold of fused silica. The shape of the convex edges was consistent with the propagation path of the 2D Airy-Gaussian beam inside the fused silica before separation. The inclination angle was 17° and 13°, respectively, on the upper and lower end of the edges. The results of this study provide a new, to our knowledge, method for the preparation of curved structures with different curvatures in transparent materials.

Identifying CD1c as a potential biomarker by the comprehensive exploration of tumor mutational burden and immune infiltration in diffuse large B cell lymphoma.

Background: Tumor mutational burden (TMB) is a valuable prognostic biomarker. This study explored the predictive value of TMB and the potential association between TMB and immune infiltration in diffuse large B-cell lymphoma (DLBCL). Methods: We downloaded the gene expression profile, somatic mutation, and clinical data of DLBCL patients from The Cancer Genome Atlas (TCGA) database. We classified the samples into high-and low-TMB groups to identify differentially expressed genes (DEGs). Functional enrichment analyses were performed to determine the biological functions of the DEGs. We utilized the cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm to estimate the abundance of 22 immune cells, and the significant difference was determined by the Wilcoxon rank-sum test between the high- and low-TMB group. Hub gene had been screened as the prognostic TMB-related immune biomarker by the combination of the Immunology Database and Analysis Portal (ImmPort) database and the univariate Cox analysis from the Gene Expression Omnibus (GEO) database including six DLBCL datasets. Various database applications such as Tumor Immune Estimation Resource (TIMER), CellMiner, konckTF, and Genotype-Tissue Expression (GTEx) verified the functions of the target gene. Wet assay confirmed the target gene expression at RNA and protein levels in DLBCL tissue and cell samples. Results: Single nucleotide polymorphism (SNP) occurred more frequently than insertion and deletion, and C > T was the most common single nucleotide variant (SNV) in DLBCL. Survival analysis showed that the high-TMB group conferred poor survival outcomes. A total of 62 DEGs were obtained, and 13 TMB-related immune genes were identified. Univariate Cox analysis results illustrated that CD1c mutation was associated with lower TMB and manifested a satisfactory clinical prognosis by analysis of large samples from the GEO database. In addition, infiltration levels of immune cells in the high-TMB group were lower. Using the TIMER database, we systematically analyzed that the expression of CD1c was positively correlated with B cells, neutrophils, and dendritic cells and negatively correlated with CD8+ T cells, CD4+ T cells, and macrophages. Drug sensitivity showed a significant positive correlation between CD1c expression level and clinical drug sensitivity from the CellMiner database. CREB1, AHR, and TOX were used to comprehensively explore the regulation of CD1c-related transcription factors and signaling pathways by the KnockTF database. We searched the GETx database to compare the mRNA expression levels of CD1c between DLBCL and normal tissues, and the results suggested a significant difference between them. Moreover, wet experiments were conducted to verify the high expression of CD1c in DLBCL at the RNA and protein levels. Conclusions: Higher TMB correlated with poor survival outcomes and inhibited the immune infiltrates in DLBCL. Our results suggest that CD1c is a TMB-related prognostic biomarker.

High CD8+tumor-infiltrating lymphocytes indicate severe exhaustion and poor prognosis in angioimmunoblastic T-cell lymphoma.

Background: Exhaustion of CD8+ tumor-infiltrating lymphocytes (TILs), characterized by the overexpression of immune checkpoints (IC), is a major impediment to anti-tumor immunity. However, the exhaustion status of CD8+TILs in angioimmunoblastic T cell lymphoma (AITL) remains unclear. Therefore, we aimed to elucidate the exhaustion status of CD8+TILs in AITL and its influence on prognosis. Methods: The correlation between CD8+TILs and IC expression in AITL was analyzed using single-cell RNA sequencing (n = 2), flow cytometry (n = 20), and RNA sequencing (n = 20). Biological changes related to CD8+TILs exhaustion at different cytotoxic T lymphocyte (CTL) levels (mean expression levels of CD8A, CD8B, GZMA, GZMB, and PRF1) in AITL were evaluated using RNA sequencing (n = 20) and further validated using the GEO dataset (n = 51). The impact of CD8 protein expression and CTL levels on patient prognosis was analyzed using flow cytometry and RNA sequencing, respectively. Results: Our findings demonstrated that the higher the infiltration of CD8+TILs, the higher was the proportion of exhausted CD8+TILs characterized by the overexpression of multiple IC. This was accompanied by extensive exhaustion-related biological changes, which suggested severe exhaustion in CD8+TILs and may be one of the main reasons for the poor prognosis of patients with high CD8+TILs and CTL. Conclusion: Our study comprehensively reveals the exhaustion status of CD8+TILs and their potential negative impact on AITL prognosis, which facilitates further mechanistic studies and is valuable for guiding immunotherapy strategies.

Single-Pixel-Adjustable Structural Color Fabricated Using a Spatially Modulated Femtosecond Laser.

Structural colors provide a highly stable and ecofriendly dyeing mechanism. The ability to adjust structural colors by a single pixel enhances their flexibility and application range. However, achieving single-pixel control and dynamic adjustment of structural colors remain a challenge yet. In this study, we propose a coloring method involving microcurve surfaces fabricated using a spatially modulated femtosecond laser hybrid technology, which combines spatially modulated femtosecond laser-assisted wet etching and molding. The fabricated microcurve surface exhibits bright colors under white light irradiation, and the color of each pixel can be adjusted independently by changing the morphology of the modified region inside fused silica using a femtosecond laser. With the high flexibility of femtosecond laser fabrication, color lightness can be accurately controlled through the quantitative adjustment of the arrangement of microcurve surfaces in an array, and various color patterns can be fabricated through the programmable arrangement of different microcurve surfaces. Additionally, the color exhibits strong dynamic characteristics, that is, different colors correspond to different external forces.

Four-Dimensional Micro/Nanorobots via Laser Photochemical Synthesis towards the Molecular Scale.

Miniaturized four-dimensional (4D) micro/nanorobots denote a forerunning technique associated with interdisciplinary applications, such as in embeddable labs-on-chip, metamaterials, tissue engineering, cell manipulation, and tiny robotics. With emerging smart interactive materials, static micro/nanoscale architectures have upgraded to the fourth dimension, evincing time-dependent shape/property mutation. Molecular-level 4D robotics promises complex sensing, self-adaption, transformation, and responsiveness to stimuli for highly valued functionalities. To precisely control 4D behaviors, current-laser-induced photochemical additive manufacturing, such as digital light projection, stereolithography, and two-photon polymerization, is pursuing high-freeform shape-reconfigurable capacities and high-resolution spatiotemporal programming strategies, which challenge multi-field sciences while offering new opportunities. Herein, this review summarizes the recent development of micro/nano 4D laser photochemical manufacturing, incorporating active materials and shape-programming strategies to provide an envisioning of these miniaturized 4D micro/nanorobots. A comparison with other chemical/physical fabricated micro/nanorobots further explains the advantages and potential usage of laser-synthesized micro/nanorobots.

Femtosecond laser printing-assisted etching tailored hard and brittle micro-convex surface.

We report a femtosecond laser print-assisted dry etching technology for high-efficiency, high-quality, and tailored fabricating of a micro-convex surface (MCS) on hard and brittle materials. Liquid ultraviolet curing adhesive (UVCA) was transferred from a donor substrate to a receiving substrate by femtosecond laser-induced forward transfer, and the transferred microdroplet spontaneously has a smooth surface under the action of surface tension. And then an MCS with a high-quality surface was formed on hard and brittle materials by UV curing and dry etching. The effects of laser parameters and receiving substrate surface free energy on MCS morphology were investigated. According to the variation of the numerical aperture, the two methods to change the morphology of the MCS were divided into independent/joint regulation of diameter and height. We showed that a hexagonal array containing a variety of MCS morphologies can be fabricated on a fused silica by setting the appropriate parameters. And the fabrication time of an MCS in a large-area array was only 1.1 s.

Autophagy-Interfering Nanoboat Drifting along CD44-Golgi-ER Flow as RNAi Therapeutics for Hepatic Fibrosis.

The upregulated autophagy fuels the activation of hepatic stellate cells (HSCs) to promote hepatic fibrosis. However, the lack of specific inhibitors targeting autophagy and high requirements for cell targeting impede the application of antifibrotic therapy that targets autophagy. RNA interference (RNAi)-based short interfering RNA (siRNA) provides an approach to specifically inhibit autophagy. The therapeutic potential of siRNA, however, is far from being exploited due to the lack of safe and effective delivery vehicles. The cytoplasmic delivery of siRNA is essential for RNAi, and the intracellular trafficking pathway of vehicles determines the fate of siRNA. Unfortunately, the lysosomal degradation pathway, the intracellular fate of most gene vehicles, impedes RNAi efficiency. Inspired by the trafficking pathway of some viruses infecting cells, KDEL-grafted chondroitin sulfate (CK) was designed to alter the intracellular delivery fate of siRNA. The well-designed CD44-Golgi-ER trafficking pathway of CK was realized by triple cascade targeting including (1) CD44 targeting mediated by chondroitin sulfate, (2) Golgi apparatus targeting mediated by the caveolin-mediated endocytic pathway, and (3) endoplasmic reticulum (ER) targeting mediated by coat protein I (COP I) vesicles. CK was adsorbed on the complex of cationic liposomes (Lip) encapsulating siRNA targeting autophagy-related gene 7 (siATG7) to afford Lip/siATG7/CK. Lip/siATG7/CK functions as a drifting boat that follows the CD44-Golgi-ER flow and travels downstream to its destination (ER), bypassing the lysosomal degradation pathway and endowing HSCs with excellent RNAi efficiency. The efficient downregulation of ATG7 leads to an excellent antifibrotic effect both in vitro and in vivo.

Depriving Tumor Cells of Ways to Metastasize: Ferroptosis Nanotherapy Blocks Both Hematogenous Metastasis and Lymphatic Metastasis.

Blood and lymph are two main pathways of tumor metastasis; however, hematogenous metastasis and lymphatic metastasis are difficult to inhibit simultaneously. Ferroptosis provides a new breakthrough for metastasis inhibition, but how to effectively trigger ferroptosis in tumor cells remains a major challenge. Metastatic tumor cells are prone to ferroptosis in blood, while they may be protected from ferroptosis in lymph. In this study, a nanoplatform DA/RSL3 was constructed for the intracellular codelivery of the polyunsaturated arachidonic acid (AA) and the GPX4 inhibitor RSL3, which could not only induce ferroptosis but also alleviate ferroptosis resistance. As a result, DA/RSL3 effectively triggered ferroptosis in tumor cells, thereby impairing the ability of tumor cells to metastasize in both blood and lymph. Furthermore, a fucoidan blocking strategy was proposed to maximize the efficacy of DA/RSL3. Fu+DA/RSL3 showed excellent efficacy in 4T1 tumor-bearing mice. This ferroptosis nanotherapy is promising for metastatic cancer treatment.

High responsivity of VIS-NIR photodetector based on Ag2S/P3HT heterojunction.

Ag2S quantum dot (QD) photodetectors (PDs) have attracted a lot of attention in the field of imaging system and optical communication. However, the current Ag2S PDs mainly works in the near-infrared band, and its detection ability in the visible band remains to be strengthened. In this paper, we used poly(3-hexylthiophene) (P3HT) with high carrier mobility and Ag2S QDs to construct heterojunction PD. Stronger absorption in blends with polymer P3HT compared to single Ag2S QDs. The optical absorption spectra show that the Ag2S/P3HT has strong light absorption peak at 394 and 598 nm. The results show that P3HT significantly enhances the absorption of Ag2S QDs from the visible to near-infrared band. The output characteristics, transfer characteristics and fast switching capability of the device at 405 nm, 532 nm and 808 nm were tested. The device has the responsivity of 6.05 A W-1, 83.72 A W-1and 37.31 A W-1under 405 nm, 532 nm and 808 nm laser irradiation. This work plays an important role in improving the detection performance of Ag2S QDs and broadening its applications in photoelectric devices for weak light and wide spectrum detection.

Silver nanoparticles-integrated terahertz metasurface for enhancing sensor sensitivity.

A silver nanoparticles (AgNPs)-integrated terahertz (THz) metasurface sensor was presented and applied to enhance the sensitivity of substance detection. Simulations and experiments were conducted to study the influence of AgNPs on the sensor performance. The enhancement of the local electric field excited by AgNPs can substantially strengthen the interaction between the THz waves and analytes, thereby increasing detection sensitivity. The experimental results indicate that the detection limit of the AgNPs-integrated metasurface sensor is improved by two orders of magnitude compared to that of the bare metasurface sensor without AgNPs. This study provides a convenient method to enhance the sensitivity of THz metasurface sensors.

Graphene-integrated toroidal resonance metasurfaces used for picogram-level detection of chlorothalonil in the terahertz region.

Toroidal dipole resonance can significantly reduce radiation loss of materials, potentially improving sensor sensitivity. Generally, toroidal dipole response is suppressed by electric and magnetic dipoles in natural materials, making it difficult to observe experimentally. However, as 2D metamaterials, metasurfaces can weaken the electric and magnetic dipole, enhancing toroidal dipole response. Here, we propose a new graphene-integrated toroidal resonance metasurface as an ultra-sensitive chemical sensor, capable of qualitative detection of chlorothalonil in the terahertz region, down to a detection limit of 100 pg/mL. Our results demonstrate graphene-integrated toroidal resonance metasurfaces as a promising basis for ultra-sensitive, qualitative detection in chemical and biological sensing.

Efficient mode converters and filters using asymmetrical directional couplers with subwavelength gratings.

Mode-division multiplexing (MDM) is a promising solution to improve data transmission capacity for future optical interconnect networks. Mode converters and mode filters play a key role in on-chip MDM systems. Here, we propose and experimentally demonstrate a device, enabling mode conversion and filtering simultaneously, which is composed of asymmetrical directional couplers with subwavelength gratings, in a small footprint of 14.7 µm × 1.42 µm. The device can realize optical mode conversion between the first-order transverse electric (TE) mode and the fundamental TE mode, and can also filter the fundamental TE mode efficiently. The conversion efficiency is over 95%, with a broad 1 dB bandwidth over 80 nm and a high mode extinction ratio of >29 dB. As a mode filter, strong mode elimination of >30 dB is achieved.

Detection of carbendazim in oranges with metal grating integrated microfluidic sensor in terahertz.

A novel microfluidic metal grating integrated terahertz sensor has been designed, which is composed of a metal microstructure array-dielectric layer-metal layer, where the dielectric layer is the microfluidic channel carrying the analyte. By adjusting the structural parameters of the metal grating sensor, a highly confined electromagnetic field can be obtained in the microfluidic channel, thereby significantly enhancing the interaction between the analyte and the terahertz wave and improving the terahertz detection sensitivity. The metal grating described in this paper is composed of an array of square holes, which is manufactured using laser micromachining technology, so that the measurement method is simplified and improved. The results show that the addition of different concentrations of carbendazim solution resulted in a redshift of the overall spectrum, with the highest sensitivity reaching 8.773 GHz/mg L-1, which is about eight times more sensitive than the traditional terahertz transmission sensor. The relative error of using this method to determine carbendazim levels in orange juice samples was less than 5.3%. The terahertz time-domain spectroscopy technology combined with the metal grating integrated microfluidic sensor can improve the sensitivity of sample detection and realize the rapid detection and analysis of trace elements.

Identification of FCER1G related to Activated Memory CD4+ T Cells Infiltration by Gene Co-expression Network and Construction of a Risk Prediction Module in Diffuse Large B-Cell Lymphoma.

Diffuse large B cell lymphoma (DLBCL) is a group of biologically heterogeneous tumors with different prognoses. The tumor microenvironment plays a vital role in the tumorigenesis and development of DLBCL, and activated memory CD4+ T cells are an essential component of immunological cells in the lymphoma microenvironment. So far, there are few reports about activated memory CD4+T cells infiltration and related genes in the DLBCL tumor microenvironment. This study obtained the mRNA expression profile information of the testing GSE87371 dataset and another six validation datasets (GSE53786, GSE181063, GSE10846, GSE32918, GSE32018, GSE9327, GSE3892, TCGA-DLBC) from the GEO and TCGA databases. Weighted Gene Co-expression Network Analysis (WGCNA) screened gene module associated with activated memory CD4+ T cells infiltration. CIBERSORT and TIMER (immune cells infiltrating estimation analysis tools) were used to identify the relationship between activated memory CD4+ T cells and genes associated with immune infiltrating cells in the tumor microenvironment. The least absolute shrinkage and selection operator (LASSO) built the risk prediction model and verified it using nomogram and Kaplan-Meier analysis. Further functional characterization includes Gene Ontology, KEGG pathway analysis and Gene Set Enrichment Analysis (GSEA) to investigate the role and underlying mechanisms of these genes. These results suggest that the expression of FCER1G can reflect the invasion of activated memory CD4+ T cells in DLBCL, which provides a new idea for studying the tumor microenvironment and may become a potential predictive biomarker for the assessment of DLBCL.

Dual-Stimulus Control for Ultra-Wideband and Multidimensional Modulation in Terahertz Metasurfaces Comprising Graphene and Metal Halide Perovskites.

Perovskites and graphene are receiving a meteoric rise in popularity in the field of active photonics because they exhibit excellent optoelectronic properties for dynamic manipulation of light-matter interactions. However, challenges still exist, such as the instability of perovskites under ambient conditions and the low Fermi level of graphene in experiments. These shortcomings limit the scope of applications when they are used alone in advanced optical devices. However, the combination of graphene and perovskites is still a promising route for efficient control of light-matter interactions. Here, we report a dual-optoelectronic metadevice fabricated by integrating terahertz metasurfaces with a sandwich complex composed of graphene, polyimide, and perovskites for ultra-wideband and multidimensional manipulation of higher-order Fano resonances. Owing to the photogenerated carriers and electrostatic doping effect, the dual optoelectronic metadevice showed different manipulation behavior at thermal imbalance (electrostatic doping state of the system). The modulation depth of the transmission amplitude reached 200%, the total resonant frequency shift was 800 GHz, and the tunable range of the resonant frequency was 68.8%. In addition, modulation of the maximum phase reached 346°. This work will inspire a new generation of metasurface-based optical devices that combine two active materials.

Selectivity mechanism of phosphodiesterase isoform inhibitor through in silico investigations.

Understanding the selectivity mechanism of inhibitors towards homology proteins helps to design selective candidates. Phosphodiesterase (PDE) family members act in the degradation of cAMP and cGMP, among which some isoforms such as PDE9A are attracting interest for Alzheimer's disease treatment, while PDE10A is used as target for treating schizophrenia. In this study, computational methods were used to investigate the major features of PDE9A/10A, with the purpose to provide deep understanding of the molecular mechanism of selective inhibition towards these two isoforms. Our result revealed that two conserved residues Gln453 and Phe456 were proven to be crucial for the binding affinity and inhibitory selectivity of PDE9A inhibitors. In addition, the high-affinity PDE9A inhibitors always interact with the conservative hydrophobic pocket as well as Tyr424 and Ala452 of PDE9A, while PDE10A selective inhibitors need to have two hydrophobic groups and two hydrogen bond donors to interact with the conservative Tyr693, Gln726, and Phe729 of PDE10A. This study provides valuable insights into the underlying mechanism of selective inhibition targeting PDE9A and PDE10A, for further search for potent and highly selective PDE9A/10A inhibitors.

Flow Cytometry-Assessed PD1/PDL1 Status in Tumor-Infiltrating Lymphocytes: A Link With the Prognosis of Diffuse Large B-Cell Lymphoma.

The PD1/PDL1 status of tumor-infiltrating lymphocytes (TILs) in diffuse large B-cell lymphoma (DLBCL) reflects immune function. However, the previously reported methods for evaluating this status are complex and may not be widely used in clinical practice. In addition, these studies did not introduce healthy controls to designate the cut-off when evaluating the prognostic value of the status. In this study, we retrospectively evaluated the PD1/PDL1 status in TILs of 24 DLBCL tissue samples and normal immune cells in 61 demographically matched healthy controls (tissue samples from patients with reactive hyperplasia [RH]) by flow cytometry. We investigated the prognostic value of the PD1/PDL1 status in TILs by precisely determining the cut-off value and assessing the reliability of flow cytometry. The mean fluorescence intensity (MFI) of PD1 in TIL-T-cells (TIL-Ts; median, 110) and CD8+TIL-Ts (median, 64) was significantly higher than that of CD3+T-cells (median, 64) and CD8+ T-cells (median, 34) in RH. The cut-off values of PD1/PDL1 status for analyzing prognostic values were defined considering the PD1/PDL1 status of samples from both patients with DLBCL and healthy controls. High MFI of PD1 in TIL-Ts (MFI >108, P = 0.022), high proportion of PD1+CD4+TIL-Ts (>1.1% of CD4+TIL-Ts, P = 0.049), high proportion of PD1+CD8+TIL-Ts (>2% of CD8+TIL-Ts, P = 0.025), and high MFI of PDL1 in TIL-Ts (MFI >83, P = 0.023) were risk factors for inferior prognosis of DLBCL. Our results indicate that flow cytometry is a reliable and convenient method for evaluating the immune-checkpoint status of TILs, which probably holds major implications in clinical practice.

Sensitivity influencing factors during pesticide residue detection research via a terahertz metasensor.

Two metamaterial sensors were designed to test three pesticide residues. The influences of the metamaterial structure, the analyte composition and volume on the sensitivity have been studied. The metamaterial field-enhancement ability has an important influence on the sensitivity within the high-concentration range, while the coincidence between the metamaterial resonant frequency and the analyte fingerprint peak plays a dominant role within the low-concentration range. These findings allow us to better understand the process and find a way to improve the sensitivity.

Time-Dependent Phosphorescence Colors from Carbon Dots for Advanced Dynamic Information Encryption.

The development of phosphorescent materials with time-dependent phosphorescence colors (TDPCs) is of considerable interest for application in advanced dynamic information encryption. In this study, TDPC is realized in carbon dots (CDs) synthesized by the one-pot hydrothermal treatment of levofloxacin. CD ink printed on paper (CD@paper) exhibits a change in phosphorescence color from orange to green, 1 s after irradiation with 395 nm light. However, when irradiated with wavelengths shorter or longer than 395 nm, the CD@paper exhibits only green or red phosphorescence, respectively. The red and green phosphorescence originates from the low-energy surface oxide triplet state and high-energy N-related triplet state, respectively. When irradiated with a suitable light energy (around 395 nm wavelength), the two phosphorescent centers can be simultaneously activated, emitting red and green phosphorescence with different decay rates. The red and green phosphorescence merge into an orange phosphorescence initially, exhibiting the TDPC phenomenon. Based on the unusual phosphorescent properties of the CDs, a kind of multilevel, dynamic phosphorescence colored 3D code is designed for advanced dynamic information encryption.

An Analytical Model for Estimating the Bending Curvatures of Metal Sheets in Laser Peen Forming.

Laser peen forming (LPF) is suitable for shaping sheet metals without the requirement for die/mold and without causing high temperatures. An analytical model for estimating the bending curvatures of LPF is convenient and necessary for better understanding of the physical processes involved. In this paper, we describe a new analytical model based on internal force balance and the energy transformation in LPF. Experiments on 2024 aluminum alloy sheets of 1-3 mm thickness were performed to validate the analytical model. The results showed that for 1 mm and 3 mm thick-thin plates, the curvature obtained by the analytical model changes from -14 × 10-4 mm-1 and -1 × 10-4 mm-1 to 55 × 10-4 mm-1 and -21 × 10-4 mm-1, respectively, with the increase of laser energy, which is consistent with the experimental trend. So, when either the stress gradient mechanism (SGM) or the shock bending mechanism (SBM) overwhelmingly dominated the forming process, the analytical model could give relatively accurate predicted curvatures compared with the experimental data. Under those conditions where SGM and SBM were comparable, the accuracy of the model was low, because of the complex stress distributions within the material, and the complex energy coupling process under these conditions.