Hydrogen sulfide-mediated persulfidation regulates homocysteine metabolism and enhances ferroptosis in non-small cell lung cancer.

Hydrogen sulfide (H2S), a metabolite of the transsulfuration pathway, has been implicated in ferroptosis, a unique form of cell death caused by lipid peroxidation. While the exact mechanisms controlling ferroptosis remain unclear, our study reveals that H2S sensitizes human non-small cell lung cancer (NSCLC) cells to this process, particularly when cysteine levels are low. Combining H2S with cystine depletion significantly enhances the effectiveness of ferroptosis-based cancer therapy. Mechanistically, H2S persulfidates the 195th cysteine on S-adenosyl homocysteine hydrolase (SAHH), reducing its enzymatic activity. This leads to decreased homocysteine levels, subsequently lowering cysteine and glutathione concentrations under cystine depletion conditions. These changes ultimately increase the vulnerability of NSCLC cells to ferroptosis. Our findings establish H2S as a key regulator of homocysteine metabolism and a critical factor in determining NSCLC cell susceptibility to ferroptosis. These results highlight the potential of H2S-based therapies to improve the efficacy of ferroptosis-targeted cancer treatments for NSCLC.

Machine Learning Assisted Stability Analysis of Blue Quantum Dot Light-Emitting Diodes.

The operational stability of the blue quantum dot light-emitting diode (QLED) has been one of the most important obstacles to initialize its industrialization. In this work, we demonstrate a machine learning assisted methodology to illustrate the operational stability of blue QLEDs by analyzing the measurements of over 200 samples (824 QLED devices) including current density-voltage-luminance (J-V-L), impedance spectra (IS), and operational lifetime (T95@1000 cd/m2). The methodology is able to predict the operational lifetime of the QLED with a Pearson correlation coefficient of 0.70 with a convolutional neural network (CNN) model. By applying a classification decision tree analysis of 26 extracted features of J-V-L and IS curves, we illustrate the key features in determining the operational stability. Furthermore, we simulated the device operation using an equivalent circuit model to discuss the device degradation related operational mechanisms.

Tunable grating surfaces with high diffractive efficiency optimized by deep neural networks.

High diffractive efficiency gratings, as a core component in optics, can engineer light transport and separation. This Letter predicts a grating surface with high diffractive efficiency within the visible light wave band with the aid of deep neural networks (DNNs). The predicted grating surface can have more than 99% diffractive efficiency for the -1th order within the bandwidth of ∼100 nm in the visible wave band, outperforming previously reported structures. Accordingly, the strategy of the DNN-aided design is an efficient and feasible method for optical devices. Moreover, changing the period of the predicted grating surfaces can shift the workable wave band, not only exhibiting the tunability but also bringing about the predicted gratings with more than 90% diffractive efficiency within the whole visible light wave band.

Two-photon scattering and correlation in a four-terminal waveguide system.

Scattering and correlation properties of a two-photon (TP) pulse are studied in a four-terminal waveguide system, i.e., two one-dimensional waveguides connected by a Jaynes-Cummings emitter (JCE). The wave function approach is utilized to exactly calculate the real-time dynamic evolution of the TP transport. When the width of the incident TP Gaussian pulse is much larger than the photon wavelength, the TP transmission spectra approach that of the corresponding single photon cases and are almost independent of the pulse width. On the contrary, as the pulse width is comparable to the photon wavelength, the TP transmission and correlation both show strong dependence on the pulse width. The resonant scattering due to the JCE and the photon interference together determine the TP correlation. When the distance between the TPs is small, the TP correlations between any two terminals for the scattered TP pulse are much different from those for the incident TP pulse and therefore, such a four-terminal waveguide system provides a way to control the TP correlation.

Structural Insights into Novel 15-Prostaglandin Dehydrogenase Inhibitors.

We discovered SW033291 in a high throughput chemical screen aimed at identifying 15-prostaglandin dehydrogenase (15-PGDH) modulators. The compound exhibited inhibitory activity in in vitro biochemical and cell-based assays of 15-PGDH activity. We subsequently demonstrated that this compound, and several analogs thereof, are effective in in vivo mouse models of bone marrow transplant, colitis, and liver regeneration, where increased levels of PGE2 positively potentiate tissue regeneration. To better understand the binding of SW033291, we carried out docking studies for both the substrate, PGE2, and an inhibitor, SW033291, to 15-PGDH. Our models suggest similarities in the ways that PGE2 and SW033291 interact with key residues in the 15-PGDH-NAD+ complex. We carried out molecular dynamics simulations (MD) of SW033291 bound to this complex, in order to understand the dynamics of the binding interactions for this compound. The butyl side chain (including the sulfoxide) of SW033291 participates in crucial binding interactions that are similar to those observed for the C15-OH and the C16-C20 alkyl chain of PGE2. In addition, interactions with residues Ser138, Tyr151, and Gln148 play key roles in orienting and stabilizing SW033291 in the binding site and lead to enantioselectivity for the R-enantiomer. Finally, we compare the binding mode of (R)-S(O)-SW033291 with the binding interactions of published 15-PGDH inhibitors.

Optical Josephson oscillation achieved by two coupled exciton-polariton condensates.

Two coupled exciton-polariton condensates (EPCs) in a double-well photonic potential are suggested to form the optical Josephson oscillation (JO) whose dependences on the pump arrangement, the potential geometry, and the exciton-photon detuning are studied through the Gross-Pitaevskii equations. When the pump detuning is slightly positive with respect to the polariton energy and the phase difference between the two EPCs is near π/2 (both are controlled by the pump beams), the system demonstrates the optical JO. The optical JO tunneling strength (J) depends on the distance (d) and barrier (Λ) between the two wells, for which an empirical formula is fitted, i.e., J≈0.42exp⁡(-d Λ/18.4) with the energy and length units in meV and µm. Since the double-well potential adopted is general, this fitting relation can show a guidance in practice for designing the optical devices based on the optical JO.

Kohn-Luttinger Mechanism Driven Exotic Topological Superconductivity on the Penrose Lattice.

The Kohn-Luttinger mechanism for unconventional superconductivity (SC) driven by weak repulsive electron-electron interactions on a periodic lattice is generalized to the quasicrystal (QC) via a real-space perturbative approach. The repulsive Hubbard model on the Penrose lattice is studied as an example, on which a classification of the pairing symmetries is performed and a pairing phase diagram is obtained. Two remarkable properties of these pairing states are revealed, due to the combination of the presence of the point-group symmetry and the lack of translation symmetry on this lattice. First, the spin and spacial angular momenta of a Cooper pair is decorrelated: for each pairing symmetry, both spin-singlet and spin-triplet pairings are possible even in the weak-pairing limit. Second, the pairing states belonging to the 2D irreducible representations of the D_{5} point group can be time-reversal-symmetry-breaking topological SCs carrying spontaneous bulk super current and spontaneous vortices. These two remarkable properties are general for the SCs on all QCs, and are rare on periodic lattices. Our work starts the new area of unconventional SCs driven by repulsive interactions on the QC.

Generation of optical vortices by exciton polaritons in pillar semiconductor microcavities.

We propose a scheme to generate optical vortices through exciting exciton polariton vortices by a Gaussian beam in a pillar microcavity. With coupled Gross-Piteavskii equations we find that the structure of the exciton polariton vortices and antivortices shows a strong dependence on the microcavity radius, pump geometry, and nonlinear exciton-exciton interaction. Due to the nonlinear exciton-exciton interaction the strong Gaussian beam cannot excite more exciton polariton vortices or antivortices with respect to the weak one. The calculation demonstrates that the weak Gaussian beam can excite vortex-antivortex pairs, vortices with high total orbital angular momentum, and superposition states of vortex and antivortex with high total opposite orbital angular momentum. The pump geometry for the Gaussian beam to excite these vortex structures is analyzed in detail, which shows a potential application for generating optical vortex beams.

A second-generation 15-PGDH inhibitor promotes bone marrow transplant recovery independently of age, transplant dose and granulocyte colony-stimulating factor support.

Hematopoietic stem cell transplantation following myeloablative chemotherapy is a curative treatment for many hematopoietic malignancies. However, profound granulocytopenia during the interval between transplantation and marrow recovery exposes recipients to risks of fatal infection, a significant source of transplant-associated morbidity and mortality. We have previously described the discovery of a small molecule, SW033291, that potently inhibits the prostaglandin degrading enzyme 15-PGDH, increases bone marrow prostaglandin E2, and accelerates hematopoietic recovery following murine transplant. Here we describe the efficacy of (+)-SW209415, a second-generation 15-PGDH inhibitor, in an expanded range of models relevant to human transplantation. (+)-SW209415 is 10,000-fold more soluble, providing the potential for intravenous delivery, while maintaining potency in inhibiting 15-PGDH, increasing in vivo prostaglandin E2, and accelerating hematopoietic regeneration following transplantation. In additional models, (+)-SW209415: (i) demonstrated synergy with granulocyte colony-stimulating factor, the current standard of care; (ii) maintained efficacy as transplant cell dose was escalated; (iii) maintained efficacy when transplant donors and recipients were aged; and (iv) potentiated homing in xenotransplants using human hematopoietic stem cells. (+)-SW209415 showed no adverse effects, no potentiation of in vivo growth of human myeloma and leukemia xenografts, and, on chronic high-dose administration, no toxicity as assessed by weight, blood counts and serum chemistry. These studies provide independent chemical confirmation of the activity of 15-PGDH inhibitors in potentiating hematopoietic recovery, extend the range of models in which inhibiting 15-PGDH demonstrates activity, allay concerns regarding potential for adverse effects from increasing prostaglandin E2, and thereby, advance 15-PGDH as a therapeutic target for potentiating hematopoietic stem cell transplantation.

Spin-Charge Separation in Finite Length Metallic Carbon Nanotubes.

Using time-dependent density functional theory, we study the optical excitations in finite length carbon nanotubes. Evidence of spin-charge separation is given in the spacetime domain. We demonstrate that the charge density wave is due to collective excitations of electron singlets, while the accompanying spin density wave is due to those of electron triplets. The Tomonaga-Luttinger liquid parameter and density-density interaction are extrapolated from the first-principles excitation energies. We show that the density-density interaction increases with the length of the nanotube. The singlet and triplet excitation energies, on the other hand, decrease for increasing length of the nanotube. Their ratio is used to establish a first-principles approach for deriving the Tomonaga-Luttinger parameter (in excellent agreement with experimental data). Time evolution analysis of the charge and spin line densities evidences that the charge and spin density waves are elementary excitations of metallic carbon nanotubes. Their dynamics show no dependence on each other.

Optically programmable encoder based on light propagation in two-dimensional regular nanoplates.

We design an efficient optically controlled microdevice based on CdSe nanoplates. Two-dimensional CdSe nanoplates exhibit lighting patterns around the edges and can be realized as a new type of optically controlled programmable encoder. The light source is used to excite the nanoplates and control the logical position under vertical pumping mode by the objective lens. At each excitation point in the nanoplates, the preferred light-propagation routes are along the normal direction and perpendicular to the edges, which then emit out from the edges to form a localized lighting section. The intensity distribution around the edges of different nanoplates demonstrates that the lighting part with a small scale is much stronger, defined as '1', than the dark section, defined as '0', along the edge. These '0' and '1' are the basic logic elements needed to compose logically functional devices. The observed propagation rules are consistent with theoretical simulations, meaning that the guided-light route in two-dimensional semiconductor nanoplates is regular and predictable. The same situation was also observed in regular CdS nanoplates. Basic theoretical analysis and experiments prove that the guided light and exit position follow rules mainly originating from the shape rather than material itself.

Sulindac reversal of 15-PGDH-mediated resistance to colon tumor chemoprevention with NSAIDs.

Non-steroidal anti-inflammatory drugs prevent colorectal cancer by inhibiting cyclooxygenase (COX) enzymes that synthesize tumor-promoting prostaglandins. 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is a tumor suppressor that degrades tumor-promoting prostaglandins. Murine knockout of 15-PGDH increases susceptibility to azoxymethane-induced colon tumors. It also renders these mice resistant to celecoxib, a selective inhibitor of inducible COX-2 during colon neoplasia. Similarly, humans with low colonic 15-PGDH are also resistant to colon adenoma prevention with celecoxib. Here, we used aspirin and sulindac, which inhibit both COX-1 and COX-2, in order to determine if these broader COX inhibitors can prevent colon tumors in 15-PGDH knockout (KO) mice. Unlike celecoxib, sulindac proved highly effective in colon tumor prevention of 15-PGDH KO mice. Significantly, however, aspirin demonstrated no effect on colon tumor incidence in either 15-PGDH wild-type or KO mice, despite a comparable reduction in colonic mucosal Prostaglandin E2 (PGE2) levels by both sulindac and aspirin. Notably, colon tumor prevention activity by sulindac was accompanied by a marked induction of lymphoid aggregates and proximal colonic inflammatory mass lesions, a side effect seen to a lesser degree with celecoxib, but not with aspirin. These findings suggest that sulindac may be the most effective agent for colon cancer prevention in humans with low 15-PGDH, but its use may also be associated with inflammatory lesions in the colon.

Ray-trace simulation of CuInS(Se)2 quantum dot based luminescent solar concentrators.

To enhance the performance of luminescent solar concentrator (LSC), there is an increased need to search novel emissive materials with broad absorption and large Stokes shifts. I-III-VI colloidal CuInS2 and CuInSe2 based nanocrystals, which exhibit strong photoluminescence emissions in the visible to near infrared region with large Stokes shifts, are expected to improve performance in luminescent solar concentrator applications. In this work, the performance of CuInS(Se)2 quantum dots in simple planar LSC is evaluated by applying Monte-Carlo ray-trace simulation. A systematic parameters study was conducted to optimize the performance. An optimized photon concentration ratio of 0.34 for CuInS2 nanocrystals and 1.25 for CuInSe2 nanocrystals doping LSC are obtained from the simulation. The results demonstrated that CuInSe2 based nanocrystals are particularly interesting for luminescent solar concentrator applications, especially to combine with low price Si solar cells.

Mst1 and Mst2 protein kinases restrain intestinal stem cell proliferation and colonic tumorigenesis by inhibition of Yes-associated protein (Yap) overabundance.

Ablation of the kinases Mst1 and Mst2, orthologs of the Drosophila antiproliferative kinase Hippo, from mouse intestinal epithelium caused marked expansion of an undifferentiated stem cell compartment and loss of secretory cells throughout the small and large intestine. Although median survival of mice lacking intestinal Mst1/Mst2 is 13 wk, adenomas of the distal colon are common by this age. Diminished phosphorylation, enhanced abundance, and nuclear localization of the transcriptional coactivator Yes-associated protein 1 (Yap1) is evident in Mst1/Mst2-deficient intestinal epithelium, as is strong activation of ß-catenin and Notch signaling. Although biallelic deletion of Yap1 from intestinal epithelium has little effect on intestinal development, inactivation of a single Yap1 allele reduces Yap1 polypeptide abundance to nearly wild-type levels and, despite the continued Yap hypophosphorylation and preferential nuclear localization, normalizes epithelial structure. Thus, supraphysiologic Yap polypeptide levels are necessary to drive intestinal stem cell proliferation. Yap is overexpressed in 68 of 71 human colon cancers and in at least 30 of 36 colon cancer-derived cell lines. In colon-derived cell lines where Yap is overabundant, its depletion strongly reduces ß-catenin and Notch signaling and inhibits proliferation and survival. These findings demonstrate that Mst1 and Mst2 actively suppress Yap1 abundance and action in normal intestinal epithelium, an antiproliferative function that frequently is overcome in colon cancer through Yap1 polypeptide overabundance. The dispensability of Yap1 in normal intestinal homeostasis and its potent proliferative and prosurvival actions when overexpressed in colon cancer make it an attractive therapeutic target.

Machine Learning-Enabled Optical Architecture Design of Perovskite Solar Cells.

Perovskite solar cells, emerging as a cutting-edge solar energy technology, have demonstrated a power conversion efficiency (PCE) of >26%, which is below the theoretical limit of 33%. This study, employing a combination of neural network models and high-throughput simulation calculations, taking the single-junction FAPbI3 cell as an illustrative example, indicates that a pyramid structure, in comparison of a planar one, can increase the highest Jsc to 27.4 mA/cm2 and the PCE to 28.4%. Both Jsc and PCE surpass the currently reported experimental results. The optimized periodicity and tilt angle of the pyramid structure align with the textured structure of crystalline silicon solar cells. These results underscore the substantial development potential of neural network inverse design based on high-throughput calculations in the field of optoelectronic devices and provide theoretical guidance for the design of monolithic perovskite-silicon tandem solar cells.

METTL17 coordinates ferroptosis and tumorigenesis by regulating mitochondrial translation in colorectal cancer.

Ferroptosis, an iron-dependent lipid peroxidation-induced form of regulated cell death, shows great promise as a cancer therapy strategy. Despite the critical role of mitochondria in ferroptosis regulation, the underlying mechanisms remain elusive. This study reveals that the mitochondrial protein METTL17 governs mitochondrial function in colorectal cancer (CRC) cells through epigenetic modulation. Bioinformatic analysis establishes that METTL17 expression positively correlates with ferroptosis resistance in cancer cells and is up-regulated in CRC. Depletion of METTL17 sensitizes CRC cells to ferroptosis, impairs cell proliferation, migration, invasion, xenograft tumor growth, and AOM/DSS-induced CRC tumorigenesis. Furthermore, suppression of METTL17 disrupts mitochondrial function, energy metabolism, and enhances intracellular and mitochondrial lipid peroxidation and ROS levels during ferroptotic stress. Mechanistically, METTL17 inhibition significantly reduces mitochondrial RNA methylation, including m4C, m5C, m3C, m7G, and m6A, leading to impaired translation of mitochondrial protein-coding genes. Additionally, the interacting proteins associated with METTL17 are essential for mitochondrial gene expression, and their knockdown sensitizes CRC cells to ferroptosis and inhibits cell proliferation. Notably, combined targeting of METTL17 and ferroptosis in a therapeutic approach effectively suppresses CRC xenograft growth in vivo. This study uncovers the METTL17-mediated defense mechanism for cell survival and ferroptosis in mitochondria, highlighting METTL17 as a potential therapeutic target for CRC.

Characterization and humanization of VNARs targeting human serum albumin from the whitespotted bamboo shark (Chiloscyllium plagiosum).

The Shark-derived immunoglobulin new antigen receptors (IgNARs) have gained increasing attention for their high solubility, exceptional thermal stability, and intricate sequence variation. In this study, we immunized whitespotted bamboo shark (Chiloscyllium plagiosum) to create phage display library of variable domains of IgNAR (VNARs) for screening against Human Serum Albumin (HSA), a versatile vehicle in circulation due to its long in vivo half-life. We identified two HSA-binding VNAR clones, 2G5 and 2G6, and enhanced their expression in E. coli with the FKPA chaperone. 2G6 exhibited a strong binding affinity of 13 nM with HSA and an EC50 of 1 nM. In vivo study with a murine model further provided initial validation of 2G6's ability to prolong circulation time by binding to HSA. Additionally, we employed computational molecular docking to predict the binding affinities of both 2G6 and its humanized derivative, H2G6, to HSA. Our analysis unveiled that the complementarity-determining regions (CDR1 and CDR3) are pivotal in the antigen recognition process. Therefore, our study has advanced the understanding of the potential applications of VNARs in biomedical research aimed at extending drug half-life, holding promise for future therapeutic and diagnostic progressions.

ATF3-CBS signaling axis coordinates ferroptosis and tumorigenesis in colorectal cancer.

The induction of ferroptosis is promising for cancer therapy. However, the mechanisms enabling cancer cells to evade ferroptosis, particularly in low-cystine environments, remain elusive. Our study delves into the intricate regulatory mechanisms of Activating transcription factor 3 (ATF3) on Cystathionine ß-synthase (CBS) under cystine deprivation stress, conferring resistance to ferroptosis in colorectal cancer (CRC) cells. Additionally, our findings establish a positively correlation between this signaling axis and CRC progression, suggesting its potential as a therapeutic target. Mechanistically, ATF3 positively regulates CBS to resist ferroptosis under cystine deprivation stress. In contrast, the suppression of CBS sensitizes CRC cells to ferroptosis through targeting the mitochondrial tricarboxylic acid (TCA) cycle. Notably, our study highlights that the ATF3-CBS signaling axis enhances ferroptosis-based CRC cancer therapy. Collectively, the findings reveal that the ATF3-CBS signaling axis is the primary feedback pathway in ferroptosis, and blocking this axis could be a potential therapeutic approach for colorectal cancer.

CovidShiny: An Integrated Web Tool for SARS-CoV-2 Mutation Profiling and Molecular Diagnosis Assay Evaluation In Silico.

The coronavirus disease 2019 (COVID-19) pandemic is still ongoing, with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continuing to evolve and accumulate mutations. While various bioinformatics tools have been developed for SARS-CoV-2, a well-curated mutation-tracking database integrated with in silico evaluation for molecular diagnostic assays is currently unavailable. To address this, we introduce CovidShiny, a web tool that integrates mutation profiling, in silico evaluation, and data download capabilities for genomic sequence-based SARS-CoV-2 assays and data download. It offers a feasible framework for surveilling the mutation of SARS-CoV-2 and evaluating the coverage of the molecular diagnostic assay for SARS-CoV-2. With CovidShiny, we examined the dynamic mutation pattern of SARS-CoV-2 and evaluated the coverage of commonly used assays on a large scale. Based on our in silico analysis, we stress the importance of using multiple target molecular diagnostic assays for SARS-CoV-2 to avoid potential false-negative results caused by viral mutations. Overall, CovidShiny is a valuable tool for SARS-CoV-2 mutation surveillance and in silico assay design and evaluation.

Tailoring of optical modes of semiconductor microcavities via metal and dielectric gratings.

We investigate optical mode tailoring in a semiconductor microcavity with a metal grating on top and a dielectric grating (DG) on the bottom. Strong coupling between microcavity and grating-diffraction modes is explained in the Fano-picture. The Fano resonance shows a weak dependence upon grating height and duty ratio, but is strong upon grating period. The microcavity transmission line shapes are "S" and anti "S"-type for the metal and DGs, respectively. Together with these two types of Fano resonances, the transmission spectra have been tailored into very sharp peaks with FWHM being up to 0.1 nm. We prove that this optical mode tailoring method is quite applicable for other waveguide-grating structures too.