Crosstalk mitigation of a controllable annular auto-focusing vortex beam array in a turbulent atmosphere.

In this paper, we introduce a new type of controllable auto-focusing vortex beam array named annular quasi-Airy vortex beam array (QAVBA), which can reduce the crosstalk among different orbital angular momentum (OAM) modes of optical vortex. The effects of initial beam parameters of annular QAVBA and propagation conditions on the OAM mode propagation performance are investigated. The results indicate that the topological angle θ, the topological charge m, and the decay parameter α could manipulate the auto-focusing characteristics of annular QAVBA and regulate the crosstalk of OAM modes. The crosstalk among OAM modes increases with the turbulence strength. Interestingly, the annular QAVBA with obtuse topological angle is favorable for the OAM mode transmitting at far propagation distance or in strong atmospheric turbulence when the decay parameter α is large enough for the energy of annular QAVBA mainly concentrating on the main light ring. Our research provides a reference for optimizing the design of light sources and free-space optical communication system with annular QAVBA.

Proteinase 3 depletion attenuates leukemia by promoting myeloid differentiation.

Hematopoietic stem and progenitor cells (HSPCs) that have impaired differentiation can transform into leukemic blasts. However, the mechanism that controls differentiation remains elusive. Here, we show that the genetic elimination of Proteinase 3 (PRTN3) in mice led to spontaneous myeloid differentiation. Mechanistically, our findings indicate that PRTN3 interacts with the N-terminal of STAT3, serving as a negative regulator of STAT3-dependent myeloid differentiation. Specifically, PRTN3 promotes STAT3 ubiquitination and degradation, while simultaneously reducing STAT3 phosphorylation and nuclear translocation during G-CSF-stimulated myeloid differentiation. Strikingly, pharmacological inhibition of STAT3 (Stattic) partially counteracted the effects of PRTN3 deficiency on myeloid differentiation. Moreover, the deficiency of PRTN3 in primary AML blasts promotes the differentiation of those cells into functional neutrophils capable of chemotaxis and phagocytosis, ultimately resulting in improved overall survival rates for recipients. These findings indicate PRTN3 exerts an inhibitory effect on STAT3-dependent myeloid differentiation and could be a promising therapeutic target for the treatment of acute myeloid leukemia.

Distinguishing features of Prunus humilis, P. japonica, P. pedunculata seeds and their adulterant based on DNA barcoding, morphological characterization, and chemical profiles.

Pruni Semen, the dried ripe seed of Prunus humilis, P. japonica, or P. pedunculata as recorded in the Chinese Pharmacopoeia, has been widely used in pharmaceutical and food industries. The adulteration of the marketed product with morphologically similar plants of the same genus has led to variable product quality and clinical effectiveness. This study systematically investigated the phylogenetic relationships, morphological traits, and chemical profiles of 37 Pruni Semen samples from planting bases, markets, and fields. DNA barcoding could successfully distinguish the genuine and counterfeit Pruni Semen, and the results indicated that there was almost no authentic Pruni Semen available in the market. The samples were divided into "big seed" (P. pedunculata and P. salicina seeds) and "small seed" (P. humilis, P. japonica, P. tomentosa, and P. avium seeds) categories based on morphology results. The notable discrepancy in the chemical characteristics of "big seed" and "small seed" was that "small seeds" were rich in flavonoids and low in amygdalin, whereas "big seeds" were the opposite. Furthermore, principal component analysis and clustered heatmap analysis verified the distinguishing features of "big seed" and "small seed" based on morphological and chemical characteristics. This study suggested that a combination of DNA barcoding and morphological and chemical characteristics can aid in the identification and quality evaluation of authentic and adulterated Pruni Semen. These findings may help standardize Pruni Semen available in the market and protect the rights and interests of customers.

Single-Cell Analysis Reveals Histone Deacetylation Factor Guide Intercellular Communication of Tumor Microenvironment that Contribute to Colorectal Cancer Progression and Immunotherapy.

In this study, single-cell RNA-seq data were collected to analyze the characteristics of Histone deacetylation factor (HDF). The tumor microenvironment (TME) cell clusters related to prognosis and immune response were identified by using CRC tissue transcriptome and immunotherapy cohorts from public repository. We explored the expression characteristics of HDF in stromal cells, macrophages, T lymphocytes, and B lymphocytes of the CRC single-cell dataset TME and further identified 4 to 6 cell subclusters using the expression profiles of HDF-associated genes, respectively. The regulatory role of HDF-associated genes on the CRC tumor microenvironment was explored by using single-cell trajectory analysis, and the cellular subtypes identified by biologically characterized genes were compared with those identified by HDF-associated genes. The interaction of HDF-associated gene-mediated microenvironmental cell subtypes and tumor epithelial cells were explored by using intercellular communication analysis, revealing the molecular regulatory mechanism of tumor epithelial cell heterogeneity. Based on the expression of feature genes mediated by HDF-related genes in the microenvironment T-cell subtypes, enrichment scoring was performed on the feature gene expression in the CRC tumor tissue transcriptome dataset. It was found that the feature gene scoring of microenvironment T-cell subtypes (HDF-TME score) has a certain predictive ability for the prognosis and immunotherapy benefits of CRC tumor patients, providing data support for precise immunotherapy in CRC tumors.

Ginseng-derived type I rhamnogalacturonan polysaccharide binds to galectin-8 and antagonizes its function.

Background: Panax ginseng Meyer polysaccharides exhibit various biological functions, like antagonizing galectin-3-mediated cell adhesion and migration. Galectin-8 (Gal-8), with its linker-joined N- and C-terminal carbohydrate recognition domains (CRDs), is also crucial to these biological processes, and thus plays a role in various pathological disorders. Yet the effect of ginseng-derived polysaccharides in modulating Gal-8 function has remained unclear. Methods: P. ginseng-derived pectin was chromatographically isolated and enzymatically digested to obtain a series of polysaccharides. Biolayer Interferometry (BLI) quantified their binding affinity to Gal-8, and their inhibitory effects on Gal-8 was assessed by hemagglutination, cell migration and T-cell apoptosis. Results: Our ginseng-derived pectin polysaccharides consist mostly of rhamnogalacturonan-I (RG-I) and homogalacturonan (HG). BLI shows that Gal-8 binding rests primarily in RG-I and its ß-1,4-galactan side chains, with sub-micromolar KD values. Both N- and C-terminal Gal-8 CRDs bind RG-I, with binding correlated with Gal-8-mediated function. Conclusion: P. ginseng RG-I pectin ß-1,4-galactan side chains are crucial to binding Gal-8 and antagonizing its function. This study enhances our understanding of galectin-sugar interactions, information that may be used in the development of pharmaceutical agents targeting Gal-8.

Mechanically Adaptive Polymers Constructed from Dynamic Coordination Equilibria.

Designing materials capable of adapting their mechanical properties in response to external stimuli is the key to preventing failure and extending their service life. However, existing mechanically adaptive polymers are hindered by limitations such as inadequate load-bearing capacity, difficulty in achieving reversible changes, high cost, and a lack of multiple responsiveness. Herein, we address these challenges using dynamic coordination bonds. A new type of mechanically adaptive material with both rate- and temperature-responsiveness was developed. Owing to the stimuli-responsiveness of the coordination equilibria, the prepared polymers, PBMBD-Fe and PBMBD-Co, exhibit mechanically adaptive properties, including temperature-sensitive strength modulation and rate-dependent impact hardening. Benefitting from the dynamic nature of the coordination bonds, the polymers exhibited impressive energy dissipation, damping capacity (loss factors of 1.15 and 2.09 at 1.0 Hz), self-healing, and 3D printing abilities, offering durable and customizable impact resistance and protective performance. The development of impact-resistant materials with comprehensive properties has potential applications in the sustainable and intelligent protection fields.

The OsEIL1-OsWOX11 transcription factor module controls rice crown root development in response to soil compaction.

Optimizing the root architecture of crops is an effective strategy for improving crop yields. Soil compaction is a serious global problem that limits crop productivity by restricting root growth, but the underlying molecular mechanisms are largely unclear. Here, we show that ethylene stimulates rice (Oryza sativa) crown root development in response to soil compaction. First, we demonstrate that compacted soil promotes ethylene production and the accumulation of ETHYLENE INSENSITIVE 3-LIKE 1 (OsEIL1) in rice roots, stimulating crown root primordia initiation and development, thereby increasing crown root number in lower stem nodes. Through transcriptome profiling and molecular analyses, we reveal that OsEIL1 directly activates the expression of WUSCHEL-RELATED HOMEOBOX 11 (OsWOX11), an activator of crown root emergence and growth, and that OsWOX11 mutations delay crown root development, thus impairing the plant's response to ethylene and soil compaction. Genetic analysis demonstrates that OsWOX11 functions downstream of OsEIL1. In summary, our results demonstrate that the OsEIL1-OsWOX11 module regulates ethylene action during crown root development in response to soil compaction, providing a strategy for the genetic modification of crop root architecture and grain agronomic traits.

Elucidating the mechanisms of ultrasound treatment combined with κ-carrageenan addition enhancing the gelling properties of heat-induced myofibrillar protein gel.

This work investigated the effect of ultrasound (US) treatment synergized with κ-carrageenan (KC) on the gel properties, structural characteristics and microstructures of myofibrillar protein (MP) gel. The results demonstrated that simply adding KC enhanced the gel strength and water holding capacity (WHC) of MP gels. Moreover, the gel strength and WHC of MP gels were increased by 56.67 % and 76.19 % via 20 min US treatment synergized with KC, which was mainly attributed to the changes in sulfhydryl content, surface hydrophobicity, and fluorescence intensity of MP gels. Based on the results of molecular docking and secondary structure, it can be hypothesized that the synergistic effect resulted in the rearrangement of the proteins, which altered the interaction site between MP gels and KC, accompanied by stronger binding. Furthermore, the microstructural results indicated that moderate US treatment (20 min) facilitated the production of a more compact and denser MP gels matrix with uniformly sized and distributed pores. However, excessive US treatment (40 and 50 min) caused the MP gels to form looser and disordered gel structure, which reduced the gel strength and WHC. This study suggested that combining of US and KC was a potential tactic to enhance the gelling properties of heat-induced MP gels.

Public environmental concern, government environmental regulation and urban carbon emission reduction-Analyzing the regulating role of green finance and industrial agglomeration.

In the multifaceted realm of environmental governance, emphasizing public environmental participation as an informal regulatory mechanism, alongside the influence of formal governmental environmental regulation on regional carbon emissions, contributes to providing empirical evidence and policy insights for China's "dual­carbon target" action plan. Using data from 282 prefecture-level cities in China from 2011 to 2020, this research develops an analytical framework for urban carbon emissions encompassing public environmental concern, environmental regulation, green finance, and industrial agglomeration. And through an amalgamation of theoretical insights and empirical validation, the study elucidates the mechanisms by which public environmental concern impact urban carbon emissions. It further delves into the mediating role of environmental regulation and the moderating effects of green finance and industrial agglomeration. It reveals that: (1) Public environmental concern significantly reduces urban carbon emissions, particularly in northern cities, non-environmental protection key cities, and resource regeneration cities. And this suppressive influence is markedly more potent via mobile platforms compared to PC channels; (2) Environmental regulation serves as a partially mediating role between public environmental concern and urban carbon emissions, suggesting that public environmental concern reduces emissions by amplifying governmental environmental oversight; (3) Both green finance and industrial agglomeration play a positive moderating role on the effect of public environmental concern in reducing urban carbon emissions.

An interpretable deep learning model for identifying the morphological characteristics of dMMR/MSI-H gastric cancer.

Accurate tumor diagnosis by pathologists relies on identifying specific morphological characteristics. However, summarizing these unique morphological features in tumor classifications can be challenging. Although deep learning models have been extensively studied for tumor classification, their indirect and subjective interpretation obstructs pathologists from comprehending the model and discerning the morphological features accountable for classifications. In this study, we introduce a new approach utilizing Style Generative Adversarial Networks, which enables a direct interpretation of deep learning models to detect significant morphological characteristics within datasets representing patients with deficient mismatch repair/microsatellite instability-high gastric cancer. Our approach effectively identifies distinct morphological features crucial for tumor classification, offering valuable insights for pathologists to enhance diagnostic accuracy and foster professional growth.

Combining cisplatin and a STING agonist into one molecule for metalloimmunotherapy of cancer.

Mounting evidence suggests that strategies combining DNA-damaging agents and stimulator of interferon genes (STING) agonists are promising cancer therapeutic regimens because they can amplify STING activation and remodel the immunosuppressive tumor microenvironment. However, a single molecular entity comprising both agents has not yet been developed. Herein, we designed two PtIV-MSA-2 conjugates (I and II) containing the DNA-damaging chemotherapeutic drug cisplatin and the innate immune-activating STING agonist MSA-2; these conjugates showed great potential as multispecific small-molecule drugs against pancreatic cancer. Mechanistic studies revealed that conjugate I upregulated the expression of transcripts associated with innate immunity and metabolism in cancer cells, significantly differing from cisplatin and MSA-2. An analysis of the tumor microenvironment demonstrated that conjugate I could enhance the infiltration of natural killer (NK) cells into tumors and promote the activation of T cells, NK cells and dendritic cells in tumor tissues. These findings indicated that conjugate I, which was created by incorporating a Pt chemotherapeutic drug and STING agonist into one molecule, is a promising and potent anticancer drug candidate, opening new avenues for small-molecule-based cancer metalloimmunotherapy.

High-Precision Inertial Sensor Charge Ground Measurement Method Based on Phase-Sensitive Demodulation.

Inertial sensors are the key payloads in space gravitational wave detection missions, and they need to ensure that the test mass (TM), which serves as the inertial reference, freely floats in the spacecraft without contact, so that the TM is not disturbed by the satellite platform and the cosmic environment. Space gravitational wave detection missions require that the residual acceleration of the TM should be less than 3×10-15ms-2Hz-1/2. However, the TM with charges will interact with surrounding conductors and magnetic fields, introducing acceleration noise such as electrostatic force and Lorentz force. Therefore, it is necessary to carry out charge management on the TM, in which the high-precision measurement of charge is crucial. Space gravitational wave detection missions require a residual charge measurement accuracy of 3×10-13C for the TM. In this paper, we design a high-precision inertial sensor charge measurement method based on phase-sensitive demodulation (PSD). By establishing a torsion pendulum rotation model based on the force modulation method, the characteristics of the TM torsion angle signal are analyzed. The PSD is used to extract the amplitude of the specific frequency signal component containing the charge information, and then to calculate the value of the accumulated charges. The method is compared with the Butterworth band-pass filtering method, and the simulation results show that the method has a higher measurement accuracy, shorter settling time, and stronger anti-interference ability, meeting the TM residual charge measurement accuracy index requirement.

Paraffin-Enabled Superlattice Customization for a Photostimulated Gradient-Responsive Artificial Reflex Arc.

The development of photostimulated-motion artificial reflex arcs - a neural circuit inspired by light-driven motion reflexes - holds significant promises for advancements in robotic perception, navigation, and motion control. However, the fabrication of such systems, especially those that accommodate multiple actions and exhibit gradient responses, remains challenging. Here, a gradient-responsive photostimulated-motion artificial reflex arc is developed by integrating a programmable and tunable photoreceptor based on folded MoS2 at different twist angles. The twisted folded bilayer MoS2 used as photoreceptors can be customized via the transfer technique using patternable paraffin, where the twist angle and fold-line could be controlled. The photoluminescence (PL) intensity is 3.7 times higher at a twist angle of 29° compared to that at 0°, showing a monotonically decreasing indirect bandgap. Through tunable interlayer carrier transport, photoreceptors fabricated using folded bilayer MoS2 at different twist angles demonstrate gradient response time, enabling the photostimulated-motion artificial reflex arc for multiaction responses. They are transformed to digital command flow and studied via machine learning to control the gestures of a robotic hand, showing a prototype of photostimulated gradient-responsive artificial reflex arcs for the first time. This work provides a unique idea for developing intelligent soft robots and next-generation human-computer interfaces.

A cellulosic multi-bands fluorescence probe for rapid detection of pH and glutathione.

The detection of pH and glutathione (GSH) is positively significant for the cell microenvironment imaging. Here, to assess the pH value and the concentration of GSH efficiently and visually, a cellulose-based multi-bands ratiometric fluorescence probe was designed by assembling MnO2-modified cellulose gold nanoclusters, fluorescein isothiocyanate-grafted cellulose nanocrystals (CNCs) and protoporphyrin IX-modified CNCs. The probe exhibits GSH-responsive, pH-sensitive and GSH/pH-independent fluorescent properties at 440 nm, 520 nm, and 633 nm, respectively. Furthermore, the probe identifies GSH within 4 s by degrading MnO2 into Mn2+ in response to GSH. Ingeniously, the green fluorescence of the probe at 520 nm was decreased with pH, and the red fluorescence at 633 nm remained stable. Therefore, the probe displayed distinguishing fluorescence colors from pink to blue and from green to blue for the synchronous detection of pH and GSH concentration within 4 s. The design strategy provides insights to construct multi-bands fluorescence probes for the rapid detection of multiple target analytes.

Patient-derived Immunocompetent Tumor Organoids: A Platform for Chemotherapy Evaluation in the Context of T-cell Recognition.

Most of the anticancer compounds synthesized by chemists are primarily evaluated for their direct cytotoxic effects at the cellular level, often overlooking the critical role of the immune system. In this study, we developed a patient-derived, T-cell-retaining tumor organoid model that allows us to evaluate the anticancer efficacy of chemical drugs under the synergistic paradigm of antigen-specific T-cell-dependent killing, which may reveal the missed drug hits in the simple cytotoxic assay. We evaluated clinically approved platinum (Pt) drugs and a custom library of twenty-eight PtIV compounds. We observed low direct cytotoxicity of Pt drugs, but variable synergistic effects in combination with immune checkpoint inhibitors (ICIs). In contrast, the majority of PtIV compounds exhibited potent tumor-killing capabilities. Interestingly, several PtIV compounds went beyond direct tumor killing and showed significant immunosynergistic effects with ICIs, outstanding at sub-micromolar concentrations. Among these, Pt-19, PtIV compounds with cinnamate axial ligands, emerged as the most therapeutically potent, demonstrating pronounced immunosynergistic effects by promoting the release of cytotoxic cytokines, activating immune-related pathways and enhancing T cell receptor (TCR) clonal expansion. Overall, this initiative marks the first use of patient-derived immunocompetent tumor organoids to explore and study chemotherapy, advancing their path toward more effective small molecule drug discovery.

Metasurface-Based Optical Logic Operators Driven by Diffractive Neural Networks.

In this paper, a novel optical logic operator based on the multifunctional metasurface driven by all-optical diffractive neural network is reported, which can perform four principal quantum logic operations (Pauli-X, Pauli-Y, Pauli-Z, and Hadamard gates). The two ground states | 0 ⟩ $|0 \rangle $ and | 1 ⟩ $|1 \rangle $  are characterized by two orthogonal linear polarization states. The proposed spatial- and polarization-multiplexed all-optical diffractive neural network only contains a hidden layer physically mapped as a metasurface with simple and compact unit cells, which dramatically reduces the volume and computing resources required for the system. The designed optical quantum operator is proven to achieve high fidelities for all four quantum logical gates, up to 99.96% numerically and 99.88% experimentally. The solution will facilitate the construction of large-scale optical quantum computing systems and scalable optical quantum devices.

Isomerization of proline-46 in the N-terminal tail of galectin-3 enhances T cell apoptosis via the ROS-ERK pathway.

Galectin-3 (Gal-3) is unique in the galectin family, due to the presence of a long N-terminal tail (NT) arising from its conserved carbohydrate recognition domain (CRD). Although functional significance of the NT has remained elusive, our previous studies demonstrated the importance of NT prolines to Gal-3 function. Here, we show that during the time Gal-3 stands in solution for three or more days, Gal-3 NT undergoes a slow, intra-molecular, time-dependent conformational/dynamical change associated with proline cis-trans isomerization. From initial dissolution of Gal-3 in buffer to three days in solution, Gal-3-mediated T cell apoptosis is enhanced from 23 % to 37 %. Western blotting and flow cytometry show that the enhancement occurs via the ROS-ERK pathway, and not by the PKC-ERK pathway. To assess which proline(s) is (are) responsible for this effect, we individually mutated all 14 NT prolines within the first 68 residues to alanines, and assessed their effect on ROS production. Our study shows that isomerization of P46 alone is responsible for the upregulation of ROS and T cell apoptosis. NMR studies show that this unique effect is mediated by a change in dynamic interactions between the NT and CRD F-face, which in turn leads to this change in Gal-3 function.

Arginine-Enhanced Antimicrobial Activity of Nanozymes against Gram-Negative Bacteria.

The continuous reduction of clinically available antibiotics has made it imperative to exploit more effective antimicrobial therapies, especially for difficult-to-treat Gram-negative pathogens. Herein, it is shown that the combination of an antimicrobial nanozyme with the clinically compatible basic amino acid L-arginine affords a potent treatment for infections with Gram-negative pathogens. In particular, the antimicrobial activity of the antimicrobial nanozyme is dramatically increased by ≈1000-fold after L-arginine stimulation. Specifically, the combination therapy enhances bacterial outer and inner membrane permeability and promotes intracellular reactive oxygen species (ROS) generation. Moreover, the metabolomic and transcriptomic results reveal that combination treatment leads to the increased ROS-mediated damage by inhibiting the tricarboxylic acid cycle and oxidative phosphorylation, thereby inducing an imbalance of the antioxidant and oxidant systems. Importantly, L-arginine dramatically significantly accelerates the healing of infected wounds in mouse models of multidrug-resistant peritonitis-sepsis and skin wound infection. Overall, this work demonstrates a novel synergistic antibacterial strategy by combining the antimicrobial nanozymes with L-arginine, which substantively facilitates the nanozyme-mediated killing of pathogens by promoting ROS production.

A time-multiplexed self-erasing nanopaper for water induced information transmission.

The progressive presentation of multilevel information enhances the security level of information storage and transmission. Here, a time-multiplexed self-erasing nanopaper was developed by integrating cellulose nanofiber (CNF)-stabilized gold nanoclusters and CNF-modified long afterglow materials. The orange fluorescence of gold nanoclusters on nanopaper was regulated by the reversible swelling and shrinking of CNF induced by water solution, while the cyan fluorescence of micron-long afterglow remained stable and acted as the background signal. It was noteworthy that the fluorescence colour and intensity of the nanopaper could be freely adjusted between orange and cyan on the time scale. Therefore, the array information on the nanopaper could be encoded by a water solution, iterated variation as the step-by-step solvent volatilized on the time scale measured by the time of the afterglow duration. This work provides a new approach for constructing time-multiplexed self-erasing nanopaper for confidential information storage and transmission.