Research progress of the netrins and their receptors in cancer.

Netrins, a family of secreted and membrane-associated proteins, can regulate axonal guidance, morphogenesis, angiogenesis, cell migration, cell survival, and tumorigenesis. Four secreted netrins (netrin 1, 3, 4 and 5) and two glycosylphosphatidylinositols-anchored membrane proteins, netrin-G1 and G2, have been identified in mammals. Netrins and their receptors can serve as a biomarker and molecular therapeutic target for pathological differentiation, diagnosis and prognosis of malignant cancers. We review here the potential roles of the netrins family and their receptors in cancer.

Integrative single-cell transcriptomic analyses reveal the cellular ontological and functional heterogeneities of primary and metastatic liver tumors.

BACKGROUND: The global cellular landscape of the tumor microenvironment (TME) combining primary and metastatic liver tumors has not been comprehensively characterized. METHODS: Based on the scRNA-seq and spatial transcriptomic data of non-tumor liver tissues (NTs), primary liver tumors (PTs) and metastatic liver tumors (MTs), we performed the tissue preference, trajectory reconstruction, transcription factor activity inference, cell-cell interaction and cellular deconvolution analyses to construct a comprehensive cellular landscape of liver tumors. RESULTS: Our analyses depicted the heterogeneous cellular ecosystems in NTs, PTs and MTs. The activated memory B cells and effector T cells were shown to gradually shift to inhibitory B cells, regulatory or exhausted T cells in liver tumors, especially in MTs. Among them, we characterized a unique group of TCF7+ CD8+ memory T cells specifically enriched in MTs that could differentiate into exhausted T cells likely driven by the p38 MAPK signaling. With regard to myeloid cells, the liver-resident macrophages and inflammatory monocyte/macrophages were markedly replaced by tumor-associated macrophages (TAMs), with TREM2+ and UBE2C+ TAMs enriched in PTs, while SPP1+ and WDR45B+ TAMs in MTs. We further showed that the newly identified WDR45B+ TAMs exhibit an M2-like polarization and are associated with adverse prognosis in patients with liver metastases. Additionally, we addressed that endothelial cells display higher immune tolerance and angiogenesis capacity, and provided evidence for the source of the mesenchymal transformation of fibroblasts in tumors. Finally, the malignant hepatocytes and fibroblasts were prioritized as the pivotal cell populations in shaping the microenvironments of PTs and MTs, respectively. Notably, validation analyses by using spatial or bulk transcriptomic data in clinical cohorts concordantly emphasized the clinical significance of these findings. CONCLUSIONS: This study defines the ontological and functional heterogeneities in cellular ecosystems of primary and metastatic liver tumors, providing a foundation for future investigation of the underlying cellular mechanisms.

A Case of Curative Treatment with Apatinib and Camrelizumab Following Liver Resection for Advanced Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC), a highly malignant digestive system tumor, poses substantial challenges due to its intricate underlying causes and pronounced post-surgery recurrence. Consequently, the prognosis for HCC remains notably unfavorable. The endorsement of sorafenib and PD-L1 inhibitors for HCC signifies the onset of a new era embracing immunotherapy and targeted treatment approaches for this condition. Hence, comprehending the mechanisms underpinning targeted immune combination therapy has become exceedingly vital for the prospective management of HCC patients. This article initially presents a triumphant instance of curative treatment involving the combination of TKI and PD-1 inhibitor subsequent to liver resection, targeting an advanced stage HCC as classified by the BCLC staging system. The case patient carries a decade-long history of hepatitis B, having undergone a regimen of 20 courses of treatments involving apatinib and camrelizumab. Throughout the treatment period, no occurrences of grade 3 or 4 adverse events (AE) were noted. Subsequently, the patient underwent a left hepatectomy. Following the hepatectomy, their serum AFP levels have consistently remained within normal limits, and CT imaging has indicated the absence of tumor recurrence over a span of 36 months. The patient had been reviewed on time for two years after the operation. The last time a CT was performed for this patient in our hospital was 7 May 2021, and no new tumors were found. Follow-up is still ongoing. When applying combined targeted immune transformation therapy using TKI and ICI for a patient with BCLC advanced stage HCC, apatinib treatment serves a dual purpose. It inhibits the survival and angiogenesis of tumor cells, while also enhancing the efficacy of camrelizumab in obstructing the interaction between PD-1 and PD-L1. This restoration of T cell cytotoxicity subsequently facilitates the elimination of tumor cells, leading to an enhanced anticancer effect.

Crosstalk Suppression in Individually Addressed Two-Qubit Gates in a Trapped-Ion Quantum Computer.

Crosstalk between target and neighboring spectator qubits due to spillover of control signals represents a major error source limiting the fidelity of two-qubit entangling gates in quantum computers. We show that in our laser-driven trapped-ion system coherent crosstalk error can be modeled as residual Xσ[over ^]_{ϕ} interaction and can be actively canceled by single-qubit echoing pulses. We propose and demonstrate a crosstalk suppression scheme that eliminates all first-order crosstalk utilizing only local control of target qubits, as opposed to an existing scheme which requires control over all neighboring qubits. We report a two-qubit Bell state fidelity of 99.52(6)% with the echoing pulses applied after collective gates and 99.37(5)% with the echoing pulses applied to each gate in a five-ion chain. This scheme is widely applicable to other platforms with analogous interaction Hamiltonians.

Between Shor and Steane: A Unifying Construction for Measuring Error Syndromes.

Fault-tolerant quantum error correction requires the measurement of error syndromes in a way that minimizes correlated errors on the quantum data. Steane and Shor ancilla are two well-known methods for fault-tolerant syndrome extraction. In this Letter, we find a unifying construction that generates a family of ancilla blocks that interpolate between Shor and Steane. This family increases the complexity of ancilla construction in exchange for reducing the rounds of measurement required to fault tolerantly measure the error. We then apply this construction to the toric code of size L×L and find that blocks of size m×m can be used to decode errors in O(L/m) rounds of measurements. Our method can be applied to any Calderbank-Shor-Steane code and presents a new direction for optimizing fault-tolerant quantum computation.

Dynamic Poly(dimethylsiloxane) Brush Coating Shows Even Better Antiscaling Capability than the Low-Surface-Energy Fluorocarbon Counterpart.

Scale formation is a significant problem in a wide range of industries, including water treatment, food processing, power plants, and oilfield production. While surface modification provides a promising methodology to address this challenge, it has generally been believed that surface coatings with the lowest surface energy, such as fluorocarbon coatings, are most suitable for antiscaling applications. In contrast to this general knowledge, here we show that a liquid-like coating featuring highly mobile linear poly(dimethylsiloxane) (LPDMS) brush chains can bring an even better antiscaling performance than conventional perfluoroalkylsilane coatings, despite the fact that the former has much higher surface energy than the latter. We demonstrate that the LPDMS brush coating can more effectively inhibit heterogeneous nucleation of scale on a substrate compared with common perfluoroalkylsilane or alkylsilane coatings, and the dynamic liquid-like characteristic of the LPDMS brush coating is speculated to be responsible for its excellent nucleation inhibiting ability by reducing the affinity and effective interface interaction between the substrate and the scale nucleus. Our findings reveal the great prospect of using liquid-like coating to replace environmentally hazardous fluorine-containing organic ones as a green and cost-effective solution to address the scale problem with enhanced antiscaling performance.

High-Fidelity Two-Qubit Gates Using a Microelectromechanical-System-Based Beam Steering System for Individual Qubit Addressing.

In a large scale trapped atomic ion quantum computer, high-fidelity two-qubit gates need to be extended over all qubits with individual control. We realize and characterize high-fidelity two-qubit gates in a system with up to four ions using radial modes. The ions are individually addressed by two tightly focused beams steered using microelectromechanical system mirrors. We deduce a gate fidelity of 99.49(7)% in a two-ion chain and 99.30(6)% in a four-ion chain by applying a sequence of up to 21 two-qubit gates and measuring the final state fidelity. We characterize the residual errors and discuss methods to further improve the gate fidelity towards values that are compatible with fault-tolerant quantum computation.

Effects of Spacers on Photoinduced Reversible Solid-to-Liquid Transitions of Azobenzene-Containing Polymers.

Photoisomerization in some azobenzene-containing polymers (azopolymers) results in reversible solid-to-liquid transitions because trans- and cis-azopolymers have different glass transition temperatures. This property enables photoinduced healing and processing of azopolymers with high spatiotemporal resolution. However, a general lack of knowledge about the influence of the polymer structure on photoinduced reversible solid-to-liquid transitions hinders the design of such novel polymers. Herein, the synthesis and photoresponsive behavior of new azopolymers with different lengths of spacers between the polymer backbone and the azobenzene group on the side chain are reported. Azopolymers with no and 20 methylene spacers did not show photoinduced solid-to-liquid transitions. Azopolymers with 6 or 12 methylene spacers showed photoinduced solid-to-liquid transitions. This study demonstrates that spacers are essential for azopolymers with photoinduced reversible solid-to-liquid transitions, and thus, gives an insight into how to design azopolymers for photoinduced healing and processing.

Reversible magnetomechanical collapse: virtual touching and detachment of rigid inclusions in a soft elastic matrix.

Soft elastic composite materials containing particulate rigid inclusions in a soft elastic matrix are candidates for developing soft actuators or tunable damping devices. The possibility to reversibly drive the rigid inclusions within such a composite together to a close-to-touching state by an external stimulus would offer important benefits. Then, a significant tuning of the mechanical properties could be achieved due to the resulting mechanical hardening. For a long time, it has been argued whether a virtual touching of the embedded magnetic particles with subsequent detachment can actually be observed in real materials, and if so, whether the process is reversible. Here, we present experimental results that demonstrate this phenomenon in reality. Our system consists of two paramagnetic nickel particles embedded at finite initial distance in a soft elastic polymeric gel matrix. Magnetization in an external magnetic field tunes the magnetic attraction between the particles and drives the process. We quantify our experimental results by different theoretical tools, i.e., explicit analytical calculations in the framework of linear elasticity theory, a projection onto simplified dipole-spring models, as well as detailed finite-element simulations. From these different approaches, we conclude that in our case the cycle of virtual touching and detachment shows hysteretic behavior due to the mutual magnetization between the paramagnetic particles. Our results are important for the design and construction of reversibly tunable mechanical damping devices. Moreover, our projection on dipole-spring models allows the formal connection of our description to various related systems, e.g., magnetosome filaments in magnetotactic bacteria.

Forces on Rigid Inclusions in Elastic Media and Resulting Matrix-Mediated Interactions.

To describe many-particle systems suspended in incompressible low-Reynolds-number fluids, effective hydrodynamic interactions can be introduced. Here, we consider particles embedded in elastic media. The effective elastic interactions between spherical particles are calculated analytically, inspired by the approach in the fluid case. Our experiments on interacting magnetic particles confirm the theory. In view of the huge success of the method in hydrodynamics, we similarly expect many future applications in the elastic case, e.g., for elastic composite materials.

Microgels at the Water/Oil Interface: In Situ Observation of Structural Aging and Two-Dimensional Magnetic Bead Microrheology.

Stimuli-responsive microgels can be used as stabilizers for emulsions. However, the details of structure and the viscoelastic property of the microgel-laden interface are still not well-known. We synthesized fluorescently labeled microgels and used confocal microscopy to observe their arrangement at the water/oil interface. The microgels aggregated spontaneously at the interface, and the aggregated structure reorganized due to thermal motion. The structure of the interfacial layer formed by microgels depended on the microgel concentration at the interface. We suggest that the structure was controlled by the aggregation and adsorption of microgels at the interface. The interparticle separation between microgels at the interface decreased over time, implying a slow aging process of the microgels at the interface. Magnetic beads were introduced at the interface and used to trigger deformation of the microgel layer. Under compression and shear the microgels in the aggregated structure rearranged, leading to plastic deformation, and some elastic responses were also observed.

Buckling of paramagnetic chains in soft gels.

We study the magneto-elastic coupling behavior of paramagnetic chains in soft polymer gels exposed to external magnetic fields. To this end, a laser scanning confocal microscope is used to observe the morphology of the paramagnetic chains together with the deformation field of the surrounding gel network. The paramagnetic chains in soft polymer gels show rich morphological shape changes under oblique magnetic fields, in particular a pronounced buckling deformation. The details of the resulting morphological shapes depend on the length of the chain, the strength of the external magnetic field, and the modulus of the gel. Based on the observation that the magnetic chains are strongly coupled to the surrounding polymer network, a simplified model is developed to describe their buckling behavior. A coarse-grained molecular dynamics simulation model featuring an increased matrix stiffness on the surfaces of the particles leads to morphologies in agreement with the experimentally observed buckling effects.

Unconventional Dually-Mobile Superrepellent Surfaces.

The ability of water droplets to move freely on superrepellent surfaces is a crucial feature that enables effective liquid repellency. Common superrepellent surfaces allow free motion of droplets in the Cassie state, with the liquid resting on the surface textures. However, liquid impalement into the textures generally leads to a wetting transition to the Wenzel state and droplet immobilization on the surface, thereby destroying the liquid repellency. This study reports the creation of a novel type of superrepellent surface through rational structural control combined with liquid-like surface chemistry, which allows for the free movement of water droplets and effective repellency in both the Cassie and Wenzel states. Theoretical guidelines for designing such surfaces are provided, and experimental results are consistent with theoretical analysis. Furthermore, this work demonstrates the enhanced ice resistance of the dually-mobile superrepellent surfaces, along with their distinctive self-cleaning capability to eliminate internal contaminants. This study expands the understanding of superrepellency and offers new possibilities for the development of repellent surfaces with exceptional anti-wetting properties.

Magnetic-Actuated Jumping of Droplets on Superhydrophobic Grooved Surfaces: A Versatile Strategy for Three-Dimensional Droplet Transportation.

On-demand droplet transportation is of great significance for numerous applications. Although various strategies have been developed for droplet transportation, out-of-surface three-dimensional (3D) transportation of droplets remains challenging. Here, a versatile droplet transportation strategy based on magnetic-actuated jumping (MAJ) of droplets on superhydrophobic grooved surfaces (SHGSs) is presented, which enables 3D, remote, and precise manipulation of droplets even in enclosed narrow spaces. To trigger MAJ, an electromagnetic field is utilized to deform the droplet on the SHGS with the aid of an attached magnetic particle, thereby the droplet acquires excess surface energy. When the electromagnetic field is quickly removed, the excess surface energy is partly converted into kinetic energy, allowing the droplet to jump atop the surface. Through high-speed imaging and numerical simulation, the working mechanism and size matching effect of MAJ are unveiled. It is found that the MAJ behavior can only be observed if the sizes of the droplets and the superhydrophobic grooves are matched, otherwise unwanted entrapment or pinch-off effects would lead to failure of MAJ. A regime diagram which serves as a guideline to design SHGSs for MAJ is proposed. The droplet transportation capacities of MAJ, including in-surface and out-of-surface directional transportation, climbing stairs, and crossing obstacles, are also demonstrated. With the ability to remotely manipulate droplets in enclosed narrow spaces without using any mechanical moving parts, MAJ can be used to design miniaturized fluidic platforms, which exhibit great potential for applications in bioassays, microfluidics, droplet-based switches, and microreactions.

Anti-fogging/dry-dust transparent superhydrophobic surfaces based on liquid-like molecule brush modified nanofiber cluster structures.

Transparent protective coatings capable of preventing fog and dust accumulation have broad application prospect in photovoltaic systems, optical devices and consumer electronics. Although a number of superhydrophobic coatings have been developed for self-cleaning purpose over the past three decades, there is still a lack of surfaces that can simultaneously possess high transparency, remarkable superhydrophobicity, and excellent fog and dust resistance. In this study, we have prepared surfaces featuring sub-wavelength nanofiber cluster structures through a facile plasma etching method, and further modified the surface with liquid-like perfluoropolyether (PFPE) brushes. The prepared PFPE modified nanofibrous surface (PFPE-NS) exhibits superior optical transparency (transmittance 90.4 % ± 0.7 %) and water repellency, with a water contact angle as high as 171.0° ± 0.6° and sliding angle down to 0.5° ± 0.1° (5 µL). More importantly, benefitted from the nanofiber cluster structures and the slippery liquid-like surface chemistry, the adhesion and accumulation of fog droplets and dust particles on PFPE-NS is greatly inhibited. As a consequence, PFPE-NS can keep excellent optical clearness after 2 h fogging test and maintain an average transmittance above 87 % after 24 h dusting test. Our study provides a promising strategy through constructing liquid-like nanofibrous coating for optical protection that could be applicable in practical rainy, foggy, and dusty environments.

Design of highly robust super-liquid-repellent surfaces that can resist high-velocity impact of low-surface-tension liquids.

Super-liquid-repellent surfaces capable of preventing wetting with various liquids have tremendous application. However, high liquid repellency relies on surface texturing to minimize the solid-liquid interfacial contact, which generally results in impaired interface robustness and pressure resistance. Consequently, the surface tends to undergo a Cassie-Baxter to Wenzel wetting transition and loses liquid repellency under high-velocity liquid impact, especially for low-surface-tension liquids. Here, surface design through combining the nanoscale effect and doubly reentrant structure is demonstrated to solve the above challenge. By utilizing a facile colloidal lithography process, robust liquid repellent surfaces featuring nanoscale doubly reentrant (NDR) structures are constructed. The nanoscale features ensure sufficient triple contact line density at a low solid-liquid contact fraction to enhance the capillary force for liquid suspension. In conjunction with the doubly reentrant topography that maximizes the upward component of capillary force, such NDR surfaces enable an extremely robust solid-liquid-gas composite interface. As a result, the prepared NDR surface maintain excellent repellency upon high-velocity impact of various liquids, including ethylene glycol drops with a Weber number (We) above 306 and ethanol drops with a We of 57. The above findings can help the development of super-liquid-repellent surfaces applicable to harsh conditions of high-velocity liquid impact or high hydrostatic pressure.

Integrating Single-Cell and Spatial Transcriptomics to Uncover and Elucidate GP73-Mediated Pro-Angiogenic Regulatory Networks in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) was characterized as being hypervascular. In the present study, we generated a single-cell spatial transcriptomic landscape of the vasculogenic etiology of HCC and illustrated overexpressed Golgi phosphoprotein 73 (GP73) HCC cells exerting cellular communication with vascular endothelial cells with high pro-angiogenesis potential via multiple receptor-ligand interactions in the process of tumor vascular development. Specifically, we uncovered an interactive GP73-mediated regulatory network coordinated with c-Myc, lactate, Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway, and endoplasmic reticulum stress (ERS) signals in HCC cells and elucidated its pro-angiogenic roles in vitro and in vivo. Mechanistically, we found that GP73, the pivotal hub gene, was activated by histone lactylation and c-Myc, which stimulated the phosphorylation of downstream STAT3 by directly binding STAT3 and simultaneously enhancing glucose-regulated protein 78 (GRP78)-induced ERS. STAT3 potentiates GP73-mediated pro-angiogenic functions. Clinically, serum GP73 levels were positively correlated with HCC response to anti-angiogenic regimens and were essential for a prognostic nomogram showing good predictive performance for determining 6-month and 1-year survival in patients with HCC treated with anti-angiogenic therapy. Taken together, the aforementioned data characterized the pro-angiogenic roles and mechanisms of a GP73-mediated network and proved that GP73 is a crucial tumor angiogenesis niche gene with favorable anti-angiogenic potential in the treatment of HCC.

[Photochemotherapy with psoralen and ultraviolet A induced apoptosis of NB4 cells and its effects on caspase-8 and caspase-8 protein expressions].

OBJECTIVE: To study the regulatory effects of psoralen (PSO) plus ultraviolet A (UVA), which is PUVA, on cell apoptosis of human leukemia cell line NB4 and signal pathway of cell apoptosis. METHODS: Human leukemia cell line NB4 was cultured in vitro. The NB4 cells were treated with PSO extracted from Chinese medicine psoralea fruits at different concentrations (0, 5, 10, 20 and 40 microL) plus UVA of wave length 360 nm at different irradiation time points (0 and 5 min). The apoptosis ratio was detected by flow cytometry (FCM). The ultrastructure changes were observed using transmission electron microscope (TEM). The expressions of Caspase-8 and Caspase-8 protein were detected by immunocytochemical method (ICC). RESULTS: After treatment of PSO at different concentrations with a 0 and 5-min exposure of UVA, the apoptosis rate of NB4 cells increased dose-and time-dependently, and was up to peak after treatment of PSO at 40 microg/mL with 5-min exposure of UVA. An interaction was shown between the two factors (P <0. 01). There were obvious morphological apoptosis of NB4 cells under TEM after treated with PUVA. The expressions of Caspase-3 and Caspase-8 protein were up-regulated by PSO, UVA, and PUVA, but the effects of PUVA on Caspase-3 protein were stronger than PSO and UVA at 12 h time-dependently (P <0.01).An interaction was shown between the concentration of PSO and time of UVA (P <0.01). CONCLUSIONS: The optimal combination of PUVA was PSO in 40 microg/mL and 5-min exposure of UVA. PUVA could induce the apoptosis of NB4 cells and in vitro activate Caspase-3 and Caspase-8 genes.

Omniphobic liquid-like surfaces.

Liquid-repellent surfaces, especially smooth solid surfaces with covalently grafted flexible polymer brushes or alkyl monolayers, are the focus of an expanding research area. Surface-tethered flexible species are highly mobile at room temperature, giving solid surfaces a unique liquid-like quality and unprecedented dynamical repellency towards various liquids regardless of their surface tension. Omniphobic liquid-like surfaces (LLSs) are a promising alternative to air-mediated superhydrophobic or superoleophobic surfaces and lubricant-mediated slippery surfaces, avoiding fabrication complexity and air/lubricant loss issues. More importantly, the liquid-like molecular layer controls many important interface properties, such as slip, friction and adhesion, which may enable novel functions and applications that are inaccessible with conventional solid coatings. In this Review, we introduce LLSs and their inherent dynamic omniphobic mechanisms. Particular emphasis is given to the fundamental principles of surface design and the consequences of the liquid-like nature for task-specific applications. We also provide an overview of the key challenges and opportunities for omniphobic LLSs.

Transcriptome analysis reveals ZmERF055 contributes to waterlogging tolerance in sweetcorn.

Waterlogging is a major disaster damaging crop production. However, most sweetcorn cultivars are not tolerant to waterlogging, which severely threatens their production. In order to understand the genetic mechanisms underlying waterlogging tolerance in sweetcorn, this study conducted a comprehensive investigation of sweetcorn waterlogging tolerance at the levels of physiology, biochemistry, and transcriptome in two sweetcorn CSSLs (chromosome segment substitution lines), D120 and D81. We found that D120 showed increased plant height, root length, root area, adventitious root numbers, antioxidant enzyme activities, and aerenchyma area ratio compared to D81. The transcriptome results showed that 2492 and 2351 differentially expressed genes (DEGs) were obtained at 4 h and 8 h of waterlogging treatment, respectively. Genes involved in reactive oxygen species (ROS) homeostasis, photosynthesis, and alcohol fermentation are sensitive in the waterlogging tolerant genotype D120, resulting in enhanced ROS scavenging ability, adventitious roots, and aerenchyma formation. Additionally, ethylene-, auxin-, and ABA-related genes exhibited different responses to waterlogging stress in sweetcorn. We integrated transcriptome and differential chromosomal fragments data and identified that ZmERF055 on chromosome 9 was directly involved in waterlogging stress. ZmERF055-overexpressing plants consistently exhibited significantly increased waterlogging tolerance and ROS homeostasis in Arabidopsis. These results offer a network of plant hormone signaling, ROS homeostasis, and energy metabolism co-modulating waterlogging tolerance in sweetcorn. Additionally, the findings support ZmERF055 as a potential ideal target gene in crop breeding to improve plant waterlogging tolerance.