Color gamut extension algorithm for various images based on laser display.

In pursuit of enhancing the display performance of gamut extension algorithms across diverse image types while minimizing image dependency, this study introduces a dynamic gamut extension algorithm. The algorithm is designed to extend the sRGB source gamut towards the wide gamut of a laser display. To evaluate its effectiveness, psychophysical experiments were conducted using four distinct image categories: complexions, scenery, objects, and color blocks and bars. The performance of the proposed algorithm was benchmarked against four established color gamut mapping algorithms. The comparative analysis revealed that our algorithm excels in handling wide color gamuts, outperforming the alternatives in terms of preference and the preservation of detail richness.

Variation characteristics of acid rain in Zhuzhou, Central China over the period 2011-2020.

Zhuzhou was one of the most polluted cities in China with the serious acid rain. Due to the implementation of air pollution control measures from 2016 to 2018, the acid rain pollution in this city has reduced. In order to understand the recent situation, a comprehensive study on the acid rain was carried out from January 2011 to December 2020. The pH values during the study period varied from 3.3 to 7.5, with a volume-weighted mean value of 4.7. The predominant acidic components of the precipitation were SO42- and NO3-, accounting for 89.3% of the total anions. The ratio of non-sea-salt SO42- to NO3- showed a decreasing trend, revealing that the pollution type of acid rain changed from sulfuric acid type to sulfuric acid and nitric acid compound type. The correlation analysis (p < 0.05) showed that SO42- was positively correlated with NH4+, Ca2+, and Mg2+; hence, it predominated in precipitation as (NH4)2SO4, NH4HSO4, CaSO4, and MgSO4. Significant positive correlation of Ca2+ with Mg2+ shows that they may originated mainly from crust. Significant positive correlation between SO42- and F- and Cl- indicate that their source may be related to the non-ferrous metal smelting industry in Zhuzhou. Further correlation analysis shows that emissions from the non-ferrous metal smelting industry in the area have a large significant on SO42- and F- in precipitation, while Cl- may still be emitted from other anthropogenic sources.

Conjugation with glucagon like peptide-1 enables targeted protein degradation.

Lysosome-targeting chimeras (LYTACs) have emerged as a promising technique to extend the scope of targeted protein degradation to extracellular proteins, e.g., secreted proteins and membrane-anchored proteins. However, up to now, only a small number of lysosomal targeting receptors (LTRs), such as cation-independent mannose 6-phosphate receptor (CI-M6PR) and asialoglycoprotein receptor (ASGPR), were reported to build LYTACs for degradation of extracellular proteins. Therefore, it is important to explore more functionalized ligands for the relevant LTRs to expand the LYTAC framework. Herein, we demonstrate a new LTR ligand-glucagon like peptide 1 (GLP-1) based targeted degradation platform, termed GLP-1 receptor-targeting chimeras (GLP-1-LYTAC). GLP-1-LYTACs are formed by conjugating GLP-1 with targeted binder (such as antibody) through Click Chemistry, showing efficiently lysosomal degradation of both extracellular proteins (GFP and Neutravidin) as well as cell membrane proteins (EGFR and PD-L1). We believe that this novel GLP-1-LYTAC will open up a new dimension for targeted protein breakdown.

Insulin-like Growth Factor 2 (IGF2)-Fused Lysosomal Targeting Chimeras for Degradation of Extracellular and Membrane Proteins.

Targeted degradation of the cell-surface and extracellular proteins via the endogenous lysosomal degradation pathways, such as lysosome-targeting chimeras (LYTACs), has recently emerged as an attractive tool to expand the scope of extracellular chemical biology. Herein, we report a series of recombinant proteins genetically fused to insulin-like growth factor 2 (IGF2), which we termed iLYTACs, that can be conveniently obtained in high yield by standard cloning and bacterial expression in a matter of days. We showed that both type-I iLYTACs, in which IGF2 was fused to a suitable affibody or nanobody capable of binding to a specific protein target, and type-II iLYTAC (or IGF2-Z), in which IGF2 was fused to the IgG-binding Z domain that served as a universal antibody-binding adaptor, could be used for effective lysosomal targeting and degradation of various extracellular and membrane-bound proteins-of-interest. These heterobifunctional iLYTACs are fully genetically encoded and can be produced on a large scale from conventional E. coli expression systems without any form of chemical modification. In the current study, we showed that iLYTACs successfully facilitated the cell uptake, lysosomal localization, and efficient lysosomal degradation of various disease-relevant protein targets from different mammalian cell lines, including EGFR, PD-L1, CD20, and α-synuclein. The antitumor properties of iLYTACs were further validated in a mouse xenograft model. Overall, iLYTACs represent a general and modular strategy for convenient and selective targeted protein degradation, thus expanding the potential applications of current LYTACs and related techniques.

Potential application of a green fiber laser in laser display systems.

This study explores the application of optical fiber lasers in display systems by integrating a P r3+-doped green all-fiber laser into a laser projection display system. As a control group to compare the results, a 520 nm semiconductor green laser diode module was integrated, similar to the experimental group. The color gamut and speckle performances were studied and compared. The results showed that the experimental group performed slightly better in the color gamut volume. The speckle contrast decreased rapidly in the experimental group when power increased. To our knowledge, this is the first study to apply a fiber laser to a laser display system. The results shed light on developing laser display systems with fewer or no speckle reduction elements.

Research on the color gamut volume and light efficiency in four-primary laser display systems.

The color gamut volume (CGV) and light efficiency of a four-primary display system were theoretically simulated with different wavelength configuration. Given the wavelengths of the blue and red primaries, we optimized the other two primary colors; the wavelength set with the largest CGV was chosen. The maximum CGV, 2.346 × 106, was obtained at (660, 530, 507, 465) nm. The maximum light efficiency was also determined. A trade-off between CGV and light efficiency should be made according to the requirement of the devices. This study provides guidance for the construction of a four-primary laser display system and the optimization of the CGV in multi-primary display systems.

Ugi reaction-assisted assembly of covalent PROTACs against glutathione peroxidase 4.

Inducing cell ferroptosis by inactivating glutathione peroxidase 4 (GPX4) is a popular cancer treatment strategy. However, only few GPX4 inhibitors have been developed to date. PROteolysis Targeting Chimera (PROTAC) is a promising approach to provide new opportunities to overcome limitations of traditional therapeutics. Herein, a PROTAC-like activity-based probe PD-Q2 was first assembled using Ugi reaction, consisting of a known GPX4 inhibitor ML-162 homolog to the E3 ligase cereblon ligand-pomalidomide. Pull-down and immunoblotting analysis revealed that GPX4 was a covalent target of PD-Q2, but the degradation efficiency was weak. Therefore, a series of degraders was further synthesized by varying the linkers of heterofunctional PROTACs. Among these degraders, PD-4 and PD-P2 were found to promote effective GPX4 degradation via the ubiquitin-proteasome system and cause lipid ROS accumulation. PD-4 and PD-P2 showed potent inhibitory of colony formation and cell growth. Furthermore, we found that with pomalidomide, the degraders exhibit a high fluorescent signal that is mostly localized in the lysosome, which may affect the effectiveness of anti-cell proliferation. Overall, we provide GPX4 degraders for further exploring therapeutic potential of regulating ferroptosis.

Establishment of an acquired lorlatinib-resistant cell line of non-small cell lung cancer and its mediated resistance mechanism

Although lorlatinib, the third generation of echinoderm microtubule protein 4-anaplastic lymphoma kinase (EML4-ALK) tyrosine kinase inhibitor (TKI), overcame the previous generation ALK-TKIs’ drug resistance problems, but the mechanism of lorlatinib resistance remained unclear. Furthermore, optimal chemotherapy for lorlatinib-resistant non-small cell lung cancer (NSCLC) patients was still unknown.MethodsA lorlatinib-resistant NSCLC cell line SNU-2535LR was generated by gradually increasing dose of lorlatinib to crizotinib-resistant cell line SNU-2535 in vitro. To study the resistance mechanism of SNU-2535LR cells, we applied CCK-8 assay to detect the sensitivity of crizotinib and the reverse effect of APR-246, a p53 activator, on lorlatinib-induced resistance and different chemotherapy drugs to SNU-2535LR cells. We also detected the expressions of EML4-ALK-related proteins of SNU-2535LR cells via western blot.Please confirm that author names have been identified correctly and are presented in the right order. (AU)

Color-speckle assessment in multi-primary laser-projection systems based on a 3D Jzazbz color space.

We propose and demonstrate a color-speckle assessment method based on a three-dimensional Jzazbz color space, which is appropriate for both three-primary and multi-primary systems. In the proposed scheme, new physical quantities are defined to describe the color-speckle characteristics, which provides a general and intuitive color-speckle evaluation for different laser projectors. Experimental verification is also performed using three-primary and six-primary laser projectors. The simulation and measurement results are consistent.

Evaluation of gamut enhancement in yellow regions and a choice of optimal wavelength for a RGBY four-primary laser display system.

To improve the color rendering ability in yellow color regions, the inclusion of yellow among the primary colors is commonly proposed. In this study, an algorithm for evaluating gamut enhancement in yellow regions is developed. The performance of different wavelength sets of RGBY four-primary system is studied theoretically in terms of various aspects, including the color gamut volume, gamut coverages, and gamut enhancement ratio in yellow regions. The optimal wavelength set and its optimal luminance ratio are then determined. This research provides strong guidance for the construction of practical four-primary-laser display systems.

Upper limit of gamut volumes in multi-primary display systems.

Based on the difference between multi-primary displays (MPDs) and three-primary displays, we propose a new definition for evaluating the color gamut volume (CGV) to explore the upper limit of MPDs, which could theoretically represent all colors that MPDs can display. The proposed definition corrects the defects in the L*a*b* color space that arise when calculating the CGV of MPDs. In view of the high computational complexity of this method, we propose a simplified scheme with a small margin of error. Additionally, we verify the new definition with experiments on a six-primary projector. This method is helpful in guiding the selection of light sources and the evaluation of MPDs, and also has great reference value to calculate the target gamut for gamut mapping in MPDs.

Establishment of an acquired lorlatinib-resistant cell line of non-small cell lung cancer and its mediated resistance mechanism.

PURPOSE: Although lorlatinib, the third generation of echinoderm microtubule protein 4-anaplastic lymphoma kinase (EML4-ALK) tyrosine kinase inhibitor (TKI), overcame the previous generation ALK-TKIs' drug resistance problems, but the mechanism of lorlatinib resistance remained unclear. Furthermore, optimal chemotherapy for lorlatinib-resistant non-small cell lung cancer (NSCLC) patients was still unknown. METHODS: A lorlatinib-resistant NSCLC cell line SNU-2535LR was generated by gradually increasing dose of lorlatinib to crizotinib-resistant cell line SNU-2535 in vitro. To study the resistance mechanism of SNU-2535LR cells, we applied CCK-8 assay to detect the sensitivity of crizotinib and the reverse effect of APR-246, a p53 activator, on lorlatinib-induced resistance and different chemotherapy drugs to SNU-2535LR cells. We also detected the expressions of EML4-ALK-related proteins of SNU-2535LR cells via western blot.Please confirm that author names have been identified correctly and are presented in the right order.Dear Editor:     I have carefully confirmed that the author names have been identified correctly and are presented in right order.Thank you very much!                                                                     Your sincerely BoXie RESULTS: The sensitivity of SNU-2535LR cells to lorlatinib was decreased significantly than that of SNU-2535 cells. EML4-ALK fusion was decreased both at protein level and DNA level in SNU-2535LR cells. More interesting, the crizotinib-resistant mutation ALK p.G1269A disappeared, while new TP53 mutation emerged in SNU-2535LR cells. APR-246 can reverse the lorlatinib resistance in SNU-2535LR cells, with a reversal index of 4.768. Compared with SNU-2535 cells, the sensitivity of SNU-2535LR cells to gemcitabine, docetaxel and paclitaxel was significantly increased (P < 0.05), but decreased to cisplatin (P < 0.05). CONCLUSION: This study demonstrated that the combination of p53 protein agonist and lorlatinib may provide a new therapeutic strategy for NSCLC patients with lorlatinib resistance and TP53 mutation. Furthermore, the results also provide guidance for selecting optimal chemo-regimens for NSCLC patients after ALK-TKIs failure.

Recent advances in the development of EGFR degraders: PROTACs and LYTACs.

Epidermal Growth Factor Receptor (EGFR), a transmembrane tyrosine kinase receptor, belongs to the ErbB receptor family, also known as HER1 or ErbB1. Its abnormal expression and activation contribute to tumor development, especially in non-small cell lung cancer (NCSCL). The first-to fourth-generation inhibitors of EGFR were developed to solve mutations at different sites, but the problem of resistance has not been fundamentally addressed. Targeted protein degradation (TPD) technologies, including PROteolysis Targeting Chimeras (PROTACs) and LYsosome Targeting Chimeras (LYTACs), take advantages of protein destruction mechanism in cells, which make up for shortcomings of traditional small molecular occupancy-driven inhibitors. PROTACs based heterobifunctional EGFR degraders were recently developed by making use of wild-type (WT) and mutated EGFR inhibitors. These degraders compared with EGFR inhibitors showed better efficiency in their cellular potency, inhibition and toxicity profiles. In this review, we first introduce the structural properties of EGFR, the inhibitors that have been developed against WT/mutated EGFR, and then mainly focuses on the recent advances of EGFR-targeting degraders along with its limitations and unlimited prospects.

Fluorogenic and Mitochondria-Localizable Probe Enables Selective Labeling and Imaging of Nitroreductase.

Nitroreductase (NTR), one of the flavin-dependent enzymes and an upregulated enzyme under tumor hypoxia, has been studied for decades. Many fluorescent probes were developed to detect NTR activity; however, these probes tend to diffuse away from their reaction site (NTR) inevitably, leading to inappropriate sample fixation, lower accuracy of NTR localization, and weaker signal-to-noise ratio. Herein, we present the design, synthesis, in vitro evaluation, and biological applications of an NTR-activatable fluorogenic and labeling probe FY. By integrating with quinone methide (QM) proximity-based protein labeling, the additional fluoromethyl group on FY serves as a potential origin of QM. Compared with conventional fluorescent probes, this new NTR probe not only offers mitochondrial localizable and fluorogenic response but also achieves permanent retention on the site of activation with an enhanced spatial resolution to improve the detection sensitivity even after cell fixation. We believe our work could offer an expandable synthetic approach to develop these permanent labeling and imaging fluorescence probes for deciphering complex biological events.

Resolution-preserving passive 2D/3D convertible display based on holographic optical elements.

We propose and demonstrate a resolution-preserving passive 2D/3D convertible display by two individual wavelengths. It uses a holographic optical element to generate two images and passively separate the exit pupils for these two wavelengths, which forms two viewpoints for each of the observer's eyes. Due to Bragg-mismatched reconstruction of two similar but distinct wavelengths, the images are separated in space. They can be fused into one through the convergence function of human eyes. By switching the input image source, the conversion between 2D and 3D mode can be realized. This method is resolution-preserving and 2D/3D convertible with no extra active components. For experimental verification, a proof-of-concept projection-type prototype is assessed.

General solution to the calculation of peak luminance of primaries in multi-primary display systems.

For a display system, a wide-color gamut can significantly improve the viewing experience. It is known that an ultra-wide color gamut can be achieved using more primaries. However, for multi-primary displays (MPDs), choosing the parameters of the primaries (e.g., wavelength and luminance) is not trivial because the necessary theoretical foundation is still lacking. In this study, starting from three-primary display, we proposed a method for calculating all possible peak luminances of MPDs. This is done by mathematically representing the added new primaries with the original three primaries. Of all the possible results, by optimizing the peak luminance of each primary color, the theoretical gamut volume satisfying specific requirements could be obtained. The method provided can be extended to N primaries (N > 6). Using this method, we have successfully built a six-primary display system and used it to verify the validity of the method. Combined with the calculation of color gamut volume, the theoretical framework provided can be used to guide the selection of wavelength, spectrum width, and luminances of primaries in MPDs.

Cell-penetrating poly(disulfide)-based nanoquenchers (qCPDs) for self-monitoring of intracellular gene delivery.

Monitoring gene delivery has significant benefits in gene therapy. Herein, we report a nanoquencher system by doping a FRET pair during nucleic acid-assisted cell penetrating poly(disulfide) (CPD) formation. Our results show that this strategy not only produces an efficient gene delivery polymer with minimal endolysosomal trapping, but also enables monitoring the release of the gene from the vehicle in live cells. This study further expanded the application of CPDs as promising tools in gene delivery.

Feasibility evaluation of a Cu-38 Zn alloy for intrauterine devices: In vitro and in vivo studies.

The existing adverse effects of copper in copper-containing intrauterine devices (Cu-IUDs) have raised concerns regarding their use. These adverse effects include burst release of cupric ions (Cu2+) at the initial stage and an increasingly rough surface of the Cu-IUDs. In this study, we investigated the use of two copper alloys, Cu-38 Zn and H62 as the new upgrading or alternative material for IUDs. Their corrosive properties were studied in simulated uterine fluid (SUF) by using electrochemical methods, with pure Cu as a control. We studied the in vitro long-term corrosion behaviors in SUF, cytotoxicity to uterine cells (human endometrial epithelial cells and human endometrial stromal cells), in vivo biocompatibility and contraceptive efficacy of pure Cu, H62, and Cu-38 Zn. In the first month, the burst release rate of Cu2+ in the Cu-38 Zn group was significantly lower than those in the pure Cu and H62 groups. The in vitro cytocompatibility Cu-38 Zn was better than that of pure Cu and H62. Moreover, Cu-38 Zn showed improved tissue biocompatibility in vivo experiments. Therefore, the contraceptive efficacy of the Cu-38 Zn is still maintained as high as the pure Cu while the adverse effects are significantly eased, suggesting that Cu-38 Zn can be a suitable potential candidate material for IUDs. STATEMENT OF SIGNIFICANCE: The existing adverse effects associated with the intrinsic properties of copper materials for copper-containing intrauterine devices (Cu-IUD) are of concern in their employment. Such as, burst release of cupric ions (Cu2+) at the initial stage and an increasingly rough surface of the Cu-IUD. In this work, Cu alloyed with a high amount of bioactive Zn was used for a Cu-IUD. The Cu-38 Zn alloy exhibited reduced burst release of Cu2+ within the first month compared with the pure Cu and H62. Furthermore, the Cu-38 Zn alloy displayed significantly improved biocompatibility and a much smoother surface. Therefore, high antifertility efficacy of the Cu-38 Zn alloy was well maintained, while the adverse effects are significantly eased, suggesting that the Cu-38 Zn alloy is promising for a Cu-IUD.

Analysis of SI-Related BoGAPDH Family Genes and Response of BoGAPC to SI Signal in Brassica oleracea L.

Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is not only involved in carbohydrate metabolism, but also plays an important role in stress resistance. However, it has not been reported in Brassica oleracea. In this study, we performed a genome-wide identification of BoGAPDH in B. oleracea and performed cloning and expression analysis of one of the differentially expressed genes, BoGAPC. A total of 16 members of the BoGAPDH family were identified in B. oleracea, which were conserved, distributed unevenly on chromosomes and had tandem repeat genes. Most of the genes were down-regulated during self-pollination, and the highest expression was found in stigmas and sepals. Different transcriptome data showed that BoGAPDH genes were differentially expressed under stress, which was consistent with the results of qRT-PCR. We cloned and analyzed the differentially expressed gene BoGAPC and found that it was in the down-regulated mode 1 h after self-pollination, and the expression was the highest in the stigma, which was consistent with the result of GUS staining. The promoter region of the gene not only has stress response elements and plant hormone response elements, but also has a variety of specific elements for regulating floral organ development. Subcellular localization indicates that the BoGAPC protein is located in the cytoplasm and belongs to the active protein in the cytoplasm. The results of prokaryotic expression showed that the size of the BoGAPC protein was about 37 kDa, which was consistent with the expected results, indicating that the protein was induced in prokaryotic cells. The results of yeast two-hybrid and GST pull-down showed that the SRK kinase domain interacted with the BoGAPC protein. The above results suggest that the BoGAPDH family of B. oleracea plays an important role in the process of plant stress resistance, and the BoGAPC gene may be involved in the process of self-incompatibility in B. oleracea, which may respond to SI by encoding proteins directly interacting with SRK.

Recent advances in construction of small molecule-based fluorophore-drug conjugates.

As a powerful tool to advance drug discovery, molecular imaging may provide new insights into the process of drug effect and therapy at cellular and molecular levels. When compared with other detection methods, fluorescence-based strategies are highly attractive and can be used to illuminate pathways of drugs' transport, with multi-color capacity, high specificity and good sensitivity. The conjugates of fluorescent molecules and therapeutic agents create exciting avenues for real-time monitoring of drug delivery and distribution, both in vitro and in vivo. In this short review, we discuss recent developments of small molecule-based fluorophore-drug conjugates, including non-cleavable and cleavable ones, that are capable of visualizing drug delivery.