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.

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.

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.

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.

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.

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.

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.

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.

The mechanisms and functions of TGF-ß1 in tendon healing.

Tendon injury accounts for 30% of musculoskeletal diseases and often leads to disability, pain, healthcare cost, and lost productivity. Following injury to tendon, tendon healing proceeds via three overlapping healing processes. However, due to the structural defects of the tendon itself, the tendon healing process is characterized by the formation of excessive fibrotic scar tissue, and injured tendons rarely return to native tendons, which can easily contribute to tendon reinjury. Moreover, the resulting fibrous scar is considered to be a precipitating factor for subsequent degenerative tendinopathy. Despite this, therapies are almost limited because underlying molecular mechanisms during tendon healing are still unknown. Transforming Growth Factor-ß1 (TGF-ß1) is known as one of most potent profibrogenic factors during tendon healing process. However, blockage TGF-ß1 fails to effectively enhance tendon healing. A detailed understanding of real abilities of TGF-ß1 involved in tendon healing can bring promising perspectives for therapeutic value that improve the tendon healing process. Thus, in this review, we describe recent efforts to identify and characterize the roles and mechanisms of TGF-ß1 involved at each stage of the tendon healing and highlight potential roles of TGF-ß1 leading to the fibrotic response to tendon injury.

Progress of research on molecular targeted therapies for colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignancies, accounting for approximately 10% of global cancer incidence and mortality. Approximately 20% of patients with CRC present metastatic disease (mCRC) at the time of diagnosis. Moreover, up to 50% of patients with localized disease eventually metastasize. mCRC encompasses a complex cascade of reactions involving multiple factors and processes, leading to a diverse array of molecular mechanisms. Improved comprehension of the pathways underlying cancer cell development and proliferation, coupled with the accessibility of relevant targeted agents, has propelled advancements in CRC treatment, ultimately leading to enhanced survival rates. Mutations in various pathways and location of the primary tumor in CRC influences the efficacy of targeted agents. This review summarizes available targeted agents for different CRC pathways, with a focus on recent advances in anti-angiogenic and anti-epidermal growth factor receptor agents, BRAF mutations, and human epidermal growth factor receptor 2-associated targeted agents.

RBM38 Reverses Sorafenib Resistance in Hepatocellular Carcinoma Cells by Combining and Promoting lncRNA-GAS5.

BACKGROUND: Hepatocellular carcinoma (HCC) is a life-threatening human malignancy and the fourth leading cause of cancer-related deaths worldwide. Patients with HCC are often diagnosed at an advanced stage with a poor prognosis. Sorafenib is a multikinase inhibitor used as the first-line treatment for patients with advanced HCC. However, acquired resistance to sorafenib in HCC leads to tumor aggression and limits the drug's survival benefits; the underlying molecular mechanisms for this resistance remain unclear. METHODS: This study aimed to examine the role of the tumor suppressor RBM38 in HCC, and its potential to reverse sorafenib resistance. In addition, the molecular mechanisms underlying the binding of RBM38 and the lncRNA GAS5 were examined. The potential involvement of RBM38 in sorafenib resistance was examined using both in vitro and in vivo models. Functional assays were performed to assess whether RBM38: binds to and promotes the stability of the lncRNA GAS5; reverses the resistance of HCC to sorafenib in vitro; and suppresses the tumorigenicity of sorafenib-resistant HCC cells in vivo. RESULTS: RBM38 expression was lower in HCC cells. The IC50 value of sorafenib was significantly lower in cells with RBM38 overexpression than in control cells. RBM38 overexpression improved sorafenib sensitivity in ectopic transplanted tumors and suppressed the growth rate of tumor cells. RBM38 could bind to and stabilize GAS5 in sorafenib-resistant HCC cells. In addition, functional assays revealed that RBM38 reversed sorafenib resistance both in vivo and in vitro in a GAS5-dependent manner. CONCLUSIONS: RBM38 is a novel therapeutic target that can reverse sorafenib resistance in HCC by combining and promoting the lncRNA GAS5.

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.

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.

Prognosis-Related Molecular Subtypes and Immune Features Associated with Hepatocellular Carcinoma.

Bioinformatics tools were used to identify prognosis-related molecular subtypes and biomarkers of hepatocellular carcinoma (HCC). Differential expression analysis of four datasets identified 3330 overlapping differentially expressed genes (DEGs) in the same direction in all four datasets. Those genes were involved in the cell cycle, FOXO signaling pathway, as well as complement and coagulation cascades. Based on non-negative matrix decomposition, two molecular subtypes of HCC with different prognoses were identified, with subtype C2 showing better overall survival than subtype C1. Cox regression and Kaplan-Meier analysis showed that 217 of the overlapping DEGs were closely associated with HCC prognosis. The subset of those genes showing an area under the curve >0.80 was used to construct random survival forest and least absolute shrinkage and selection operator models, which identified seven feature genes (SORBS2, DHRS1, SLC16A2, RCL1, IGFALS, GNA14, and FANCI) that may be involved in HCC occurrence and prognosis. Based on the feature genes, risk score and recurrence models were constructed, while a univariate Cox model identified FANCI as a key gene involved mainly in the cell cycle, DNA replication, and mismatch repair. Further analysis showed that FANCI had two mutation sites and that its gene may undergo methylation. Single-sample gene set enrichment analysis showed that Th2 and T helper cells are significantly upregulated in HCC patients compared to controls. Our results identify FANCI as a potential prognostic biomarker for HCC.

Whether and When Superhydrophobic/Superoleophobic Surfaces Are Fingerprint Repellent.

Driven by the ever-increasing demand for fingerprint-resistant techniques in modern society, numerous researches have proposed to develop innovative antifingerprint coatings based on superhydrophobic/superoleophobic surface design. However, whether superhydrophobic/superoleophobic surfaces have favorable repellency to the microscopic fingerprint is in fact an open question. Here, we establish a reliable method that enables evaluating the antifingerprint capability of various surfaces in a quantitative way. We show that superhydrophobicity is irrelevant with fingerprint repellency. Regarding superoleophobic surfaces, two distinct wetting states of microscopic fingerprint residues, i.e., the "repellent" and the "collapsed" states, are revealed. Only in the "repellent" state, in which the fingerprint residues remain atop surface textures upon being pressed, superoleophobic surfaces can bring about favorable antifingerprint repellency, which correlates positively with their receding contact angles. A finger-deformation-dependent intrusion mechanism is proposed to account for the formation of different fingerprint wetting states. Our findings offer important insights into the mechanism of fingerprint repellency and will help the design of high-performance antifingerprint surfaces for diverse applications.

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.

Suppressing the Universal Occurrence of Microscopic Liquid Residues on Super-Liquid-Repellent Surfaces.

Super-liquid-repellent (SLR) surfaces based on surface micro/nanotextures are generally regarded as "non-wettable", though careful examination shows that residual microdroplets remain atop surface textures upon drop shedding-off. Despite its great importance, the origin of microscopic liquid residues remains poorly explored, and how to suppress residue formation is an open question. Herein, on the basis of high-speed microscopic imaging and numerical simulations, we resolve the fast formation dynamics of liquid residues on micropillared SLR surfaces and show that the competition of contact line receding on micropillars and the pinch-off of microcapillary bridges governs residue formation. The local receding angle can temporarily reduce to be drastically lower than the intrinsic one accompanying occurrence of accelerated contact line receding, inevitably leading to capillary bridge pinch-off and residue formation. We further show a liquid-like coating can delay capillary bridge pinch-off and reduce residue volume on SLR surfaces by more than 80% compared to those with conventional perfluoroalkylsilane coatings.