Salvage chemotherapy regimens with arsenic trioxide for relapsed or refractory neuroblastoma: a promising approach.

In patients with relapsed or refractory neuroblastoma (NB), the limited efficacy of conventional chemotherapies necessitates the exploration of new treatment options. Previous studies have highlighted the anti-tumor properties of arsenic trioxide (ATO) in high-risk NB (HR-NB). This study aims to assess the effectiveness and safety of ATO combined with salvage chemotherapy regimens, featuring cyclophosphamide and topotecan, as a foundational treatment for children with relapsed or refractory NB. Eleven patients (four relapsed, seven refractory NB) were retrospectively analyzed for efficacy and treatment relevance. Salvage treatments, incorporating ATO (0.18 mg/kg daily for 8 h intravenously on days 1 to 10), were administered upon disease progression or relapse, with assessments conducted every two cycles. Treatments had 63.6% efficacy, with six cases of partial response, one case of stable disease, and four cases of disease progression. The overall response rate was 54.5%, and the disease control rate was 63.6%. Importantly, the systemic toxicity experienced by patients following salvage chemotherapy with ATO was mild. Salvage chemotherapy regimens featuring ATO demonstrated potential for prolonging disease stabilization for relapsed or refractory HR-NB patients, exhibiting both favorable efficacy and safety profiles. This suggests further clinical exploration and promotion of this therapeutic approach in the treatment of NB.

Point 1. The inadequate effectiveness of traditional chemotherapy in individuals with recurrent or resistant neuroblastoma (NB) necessitates the investigation of novel therapeutic approaches. Point 2. Arsenic trioxide (ATO)-based salvage treatments are both effective and less toxic in relapsed or refractory NB. Point 3. Salvage chemotherapy regimens incorporating ATO have shown promise in extending disease stabilization in relapsed or refractory high-risk NB patients, with favorable efficacy and safety profiles, which suggests further clinical exploration and promotion of this therapeutic approach in the treatment of NB.

Local Treatment of Children Suffering From Parameningeal Rhabdomyosarcoma: A Retrospective Single-Center Study From China.

BACKGROUND: Treatment for parameningeal rhabdomyosarcoma (PM-RMS) has been a challenge since local control is difficult. The goal of this study was to analyse the impact of different local treatment approaches on childhood PM-RMS patients and help dispel the doubt that whether secondary radical surgery (SRS) should be encouraged in the management of PM-RMS. METHODS: A total of 17 children with PM-RMS who received unified systemic chemotherapy and individualized local therapy such as radiotherapy (RT) and/or SRS were included in this retrospective study. The overall survival (OS) and event free survival (EFS) were compared between groups adopting different local strategies. RESULTS: The 3-year OS and EFS of our PM-RMS patients was 75.5% and 56.5% respectively. The OS and EFS of patients who received SRS were both significantly lower than that of the non-SRS group (3-year OS: 50.0% vs 90.0%, P = .031; 3-year EFS: 33.3% vs 60.6%, P = .020). The OS and EFS of the patients who received RT was higher than that of the patients of the non-RT group (3-year OS: 85.6% vs 0%, P = .001; 3-year EFS: 64.0% vs 0%, P = .011). CONCLUSION: This study illustrates that SRS was associated with poor prognosis of PM-RMS and should not be routinely performed. Optimized RT strategies along with more intensive chemotherapy may be alternative options to improve the survival of patients with PM-RMS. Multi-center, large sample and prospective studies are needed to further validate these findings.

Ternary Ag3AuS2 Nanocrystals for Thin-Film Solar Cells.

The concept of clean and pollution-free energy development has promoted the rise of environmentally friendly silver-based chalcogenide nanocrystal (NC) solar cells, but currently reported silver-based NCs need complex synthesis processes at high temperatures that may bring zerovalent noble metal impurities for their high redox potentials. In this study, we report a facile synthesis of novel Ag3AuS2 NCs by injecting highly active oleylamine sulfur complexes as sulfur sources into metal precursor solutions at low temperatures of 60 °C. The obtained Ag3AuS2 NCs exhibit broad absorption spectra and high molar extinction coefficients (106 M-1 cm-1). Then, the Ag3AuS2 NCs are applied as the light-absorbing active layer in environmentally friendly thin-film solar cells. By introducing a hybrid mixture of charge acceptors and donors (NCs/P3HT hybrid film) at the interface, the device gains an absorption increment and enhanced charge extraction, achieving a final power conversion efficiency of 3.38%. This work demonstrates the enormous potential of Ag3AuS2 NCs from low-temperature preparation for photovoltaic applications.

Community Composition and Functional Characterization of Microorganisms in Surface Sediment of the New Britain Trench.

The deep-sea harbors abundant prokaryotic biomass is a major site of organic carbon remineralization and long-term carbon burial in the ocean. Deep-sea trenches are the deepest part of the ocean, and their special geological and morphological features promoting the accumulation of organic matter and active organic carbon turnover. Despite the expanding reports about the organic matter inputs, limited information is known regarding microbial processes in deep-sea trenches. In this study, we investigated the species composition and metabolic potential in surface sediment of the New Britain Trench (NBT), using a metagenomic approach. The predominant microbial taxa in NBT sediment include Proteobacteria, Acidobacteria, Planctomycetes, Actinobacteria and Chloroflexota. The microbial communities showed highly diverse metabolic potentials. Particularly, genes encoding enzymes for degradation of aromatic compounds, as well as those encoding haloalkane dehalogenase and haloacetate dehalogenase were annotated in the NBT surface sediment, which indicate the potential of microorganisms to degrade different types of refractory organic matter. The functional genes encoding enzymes for dissimilatory nitrate reduction, denitrification, and nitrification were also represented in the NBT metagenome. Overall, the microbial communities show high diversity of heterotrophic lineages and metabolic features, supporting their potential contributions in organic carbon metabolism. Meanwhile, Nitrosopumilus, a dominant genus in the surface sediment of the NBT, is a typical ammonia-oxidizing archaea (AOA), with autotrophic CO2 fixation pathways including the 3-hydroxypropionate/4-hydroxybutylate (3HP/4HB) cycle, the reductive TCA (rTCA) cycle. The results demonstrate that autotrophic metabolic processes also play an important role in the surface sediment, by providing newly synthesized organic matter.

Rapid discovery of a new antifoulant: From in silico studies targeting barnacle chitin synthase to efficacy against barnacle settlement.

Due to the adverse environmental impacts of toxic heavy metal-based antifoulants, the screening of environmentally friendly antifoulants has become important for the development of marine antifouling technology. Compared with the traditional lengthy and costly screening method, computer-aided drug design (CADD) offers a promising and efficient solution that can accelerate the screening process of green antifoulants. In this study, we selected barnacle chitin synthase (CHS, an important enzyme for barnacle settlement and development) as the target protein for docking screening. Three CHS genes were identified in the barnacle Amphibalanus amphitrite, and their encoded proteins were found to share a conserved glycosyltransferase domain. Molecular docking of 31,561 marine natural products with AaCHSs revealed that zoanthamine alkaloids had the best binding affinity (-11.8 to -12.6 kcal/mol) to AaCHSs. Considering that the low abundance of zoanthamine alkaloids in marine organisms would limit their application as antifoulants, a marine fungal-derived natural product, mycoepoxydiene (MED), which has a similar chemical structure to zoanthamine alkaloids and the potential for large-scale production by fermentation, was selected and validated for stable binding to AaCHS2L2 using molecular docking and molecular dynamics simulations. Finally, the efficacy of MED in inhibiting cyprid settlement of A. amphitrite was confirmed by a bioassay that demonstrated an EC50 of 1.97 µg/mL, suggesting its potential as an antifoulant candidate. Our research confirmed the reliability of using AaCHSs as antifouling targets and has provided insights for the efficient discovery of green antifoulants by CADD.

Modification and Application Performance Study of Ultra-Fine Dry Powder Extinguishing Agent.

Ultra-fine dry powder extinguishing agent (UDPEA) is a promising alternative to Halon agents in aviation firefighting. The formulation of UDPEAs should balance environmental friendliness and practical engineering requirements, including high extinguishing efficiency, excellent flowability, and prolonged anti-reignition. This study investigates the effects of three modification methods (single perfluorooctyl triethoxysilane (FOTS), single N-(3-Triethoxysilylpropyl)perfluoro(2,5-dimethyl-3,6-dioxanonanoyl)amide (PFPE), and a combination of FOTS and PFPE at various mass ratios (2.0:0.4, 1.6:0.8, 1.2:1.2, 0.8:1.6, 0.4:2.0) (g)) on the performance of sodium bicarbonate-based UDPEA. The results indicate that using FOTS or PFPE alone improves the water and oil contact angles, but still fails to meet the required hydrophobicity and oleophobicity standards, and it also reduces the flowability and fire-extinguishing capability. A combination of FOTS and PFPE at the 1:2 ratio yields the best performance, with the water and oil contact angles of 145.169° and 143.542°, respectively, the lowest flowability index (0.224), minimal extinguishing concentration and time (14.183 g/m3 and 1.976 s, respectively), which is only 52.7% and 68.3% of those of the unmodified UDPEA's (26.927 g/m3 and 2.893 s), and the longest anti-reignition time (68.5 s). In addition, the fire-extinguishing mechanisms (chemical inhibition and physical heat absorption) and anti-reignition mechanisms of the modified UDPEA (with the FOTS to PFPE ratio of 1:2) were revealed. This research aims to design an eco-friendly, high-performance UDPEA as an effective substitute for Halon extinguishing agents. These findings can provide valuable insights for evaluating and selecting aviation fire-extinguishing agents.

Study on the Pyrolysis and Fire Extinguishing Performance of High-Temperature-Resistant Ultrafine Dry Powder Fire Extinguishing Agents for Aviation Applications.

Ultrafine KAl(OH)2CO3 dry powder (UDWP), as a novel high-temperature-resistant ultrafine dry powder fire extinguishing agent, has garnered significant attention in the field of aviation fire protection. However, its development has been hindered by its hydrophilicity, which leads to hygroscopicity, and its tendency for re-ignition due to oil deposition. Therefore, this study employs perfluorodecyltrimethoxysilane (PFDTMS) to modify the surface of UDWP, resulting in hydrophobic and oleophobic M-UDWP. The thermal stability and hydrophobicity of M-UDWP ensure its long-term stable storage in aircraft equipment compartments, thereby reducing aircraft maintenance costs. Additionally, its oleophobicity provides excellent anti-re-ignition performance, protecting aircraft power compartments from secondary fire damage. Energy-dispersive X-ray spectroscopy (EDS), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS) analyses indicate that the PFDTMS modifier was successfully grafted onto KAl(OH)2CO3. Furthermore, M-UDWP exhibits a three-stage thermal decomposition process. The first-stage decomposition can be regarded as a single-step reaction, and the calculated kinetic parameters provide accurate predictions. Thermogravimetric analysis-Fourier transform infrared spectroscopy-mass spectrometry (TG-FTIR-MS) results reveal that M-UDWP significantly produces H2O and CO2 during thermal decomposition, which is one of its core fire extinguishing mechanisms. For the combustion of #RP-3 and #RP-5 aviation kerosene, commonly found in aircraft engine nacelles, the extinguishing times required by M-UDWP are 243 ms and 224 ms, respectively, with minimum extinguishing concentrations (MEC) of 25.9 g/m3 and 23.4 g/m3, respectively. The study of M-UDWP's thermal stability aids in understanding its storage stability under high-temperature conditions and its fire extinguishing mechanisms in fire zones. Moreover, the research findings suggest that M-UDWP has the potential to replace Halon 1301 in aircraft engine nacelles.

Interface-Mediation-Enabled High-Performance Near-Infrared AgAuSe Quantum Dot Light-Emitting Diodes.

Near-infrared (NIR) quantum dot (QD) light-emitting diodes (LEDs) (NIR-QLEDs) for recognition and tracking applications underpin the future of night-vision technology. However, the performance of environmentally benign materials and devices has lagged far behind that of their Pb-containing counterparts. In this study, we demonstrate the superior performance of NIR-QLEDs based on efficient AgAuSe QDs with contact interface mediation. Consequently, we reveal that using cysteamine-treated QD film contact heterointerfaces can effectively eliminate contact defects in devices and preserve their excellent emissive properties. Additionally, the dipole moment orientation of the coordinated additives is inverse of the heterojunction potential difference, simultaneously blocking electrons and enhancing hole injection in operando, optimizing the LED charge injection balance. These devices exhibit a high external quantum efficiency (EQE) and a power conversion efficiency (PCE) of 15.8 and 12.7% at 1046 nm, respectively, a sub-band gap turn-on voltage of 0.9 V, and a low current density (over 10% of the EQE from 0.0017 to 0.31 mA cm-2). These are the highest EQE and PCE values ever reported for environmentally benign NIR-QLEDs. The results of this study can provide a general strategy for the practical application of QDs in electroluminescent devices.

Coordination-Induced Conformational Control Enables Highly Luminescent Metallo-Cages.

In recent years, luminescent materials have received a great deal of attention due to their wide range of applications. However, exploring a simple solution to overcome the fluorescence quenching resulting from the aggregation of conventional organic fluorophores remains a valuable area of investigation. In this study, we successfully constructed two metallo-cages, namely, SA and SB, through coordination-driven self-assemblies of the triphenylamine (TPA)-based donor L with different diplatinum(II) acceptors LA and LB, respectively. These metallo-cages take advantage of their steric nature and curved conformation to more effectively limit the free rotation of the benzene ring and hinder π-π stacking in the solid state, which successfully inhibited fluorescence quenching and realizing highly efficient luminescent properties. Therefore, this work offers a new design strategy for preparing materials with excellent luminescent properties.

Research on Mechanical Equipment Fault Diagnosis Method Based on Deep Learning and Information Fusion.

Solving the problem of the transmission of mechanical equipment is complicated, and the interconnection between equipment components in a complex industrial environment can easily lead to faults. A multi-scale-sensor information fusion method is proposed, overcoming the shortcomings of fault diagnosis methods based on the analysis of one signal, in terms of diagnosis accuracy and efficiency. First, different sizes of convolution kernels are applied to extract multi-scale features from original signals using a multi-scale one-dimensional convolutional neural network (1DCNN); this not only improves the learning ability of the features but also enables the fine characterization of the features. Then, using Dempster-Shafer (DS) evidence theory, improved by multi-sensor information fusion strategy, the feature signals extracted by the multi-scale 1DCNN are fused to realize the fault detection and location. Finally, the experimental results of fault detection on a flash furnace show that the accuracy of the proposed method is more than 99.65% and has better fault diagnosis, which proves the feasibility and effectiveness of the proposed method.

Antifouling activity of terpenoids from the corals Sinularia flexibilis and Muricella sp. against the bryozoan Bugula neritina.

Marine natural products are promising sources of green antifoulants. Here, a new compound (1) was isolated from the soft coral Sinularia flexibilis. This compound, another nine cembranoids (2-10) from S. flexibilis, and three eunicellin-type diterpenoids (11-13) from the gorgonian Muricella sp. were tested for antifouling activity against larval settlement of the bryozoan Bugula neritina. Compounds 2, 3, 4, 9, 12, and 13 exhibited significant antifouling activity, with EC50 values of 18.2, 99.7, 67.9, 35.6, 33.9, and 49.3 µM, respectively. Analysis of the structure-activity relationships suggested that the hydroxy group at C-13 in compound 4 reduced its antifouling activity.

TRPM7-Mediated Ca2+ Regulates Mussel Settlement through the CaMKKß-AMPK-SGF1 Pathway.

Many marine invertebrates have planktonic larval and benthic juvenile/adult stages. When the planktonic larvae are fully developed, they must find a favorable site to settle and metamorphose into benthic juveniles. This transition from a planktonic to a benthic mode of life is a complex behavioral process involving substrate searching and exploration. Although the mechanosensitive receptor in the tactile sensor has been implicated in sensing and responding to surfaces of the substrates, few have been unambiguously identified. Recently, we identified that the mechanosensitive transient receptor potential melastatin-subfamily member 7 (TRPM7) channel, highly expressed in the larval foot of the mussel Mytilospsis sallei, was involved in substrate exploration for settlement. Here, we show that the TRPM7-mediated Ca2+ signal was involved in triggering the larval settlement of M. sallei through the calmodulin-dependent protein kinase kinase ß/AMP-activated protein kinase/silk gland factor 1 (CaMKKß-AMPK-SGF1) pathway. It was found that M. sallei larvae preferred the stiff surfaces for settlement, on which TRPM7, CaMKKß, AMPK, and SGF1 were highly expressed. These findings will help us to better understand the molecular mechanisms of larval settlement in marine invertebrates, and will provide insights into the potential targets for developing environmentally friendly antifouling coatings for fouling organisms.

Transcriptome analysis reveals fluid shear stress (FSS) and atherosclerosis pathway as a candidate molecular mechanism of short-term low salinity stress tolerance in abalone.

BACKGROUND: Transcriptome sequencing is an effective tool to reveal the essential genes and pathways underlying countless biotic and abiotic stress adaptation mechanisms. Although severely challenged by diverse environmental conditions, the Pacific abalone Haliotis discus hannai remains a high-value aquaculture mollusk and a Chinese predominantly cultured abalone species. Salinity is one of such environmental factors whose fluctuation could significantly affect the abalone's cellular and molecular immune responses and result in high mortality and reduced growth rate during prolonged exposure. Meanwhile, hybrids have shown superiority in tolerating diverse environmental stresses over their purebred counterparts and have gained admiration in the Chinese abalone aquaculture industry. The objective of this study was to investigate the molecular and cellular mechanisms of low salinity adaptation in abalone. Therefore, this study used transcriptome analysis of the gill tissues and flow cytometric analysis of hemolymph of H. discus hannai (DD) and interspecific hybrid H. discus hannai ♀ x H. fulgens ♂ (DF) during low salinity exposure. Also, the survival and growth rate of the species under various salinities were assessed. RESULTS: The transcriptome data revealed that the differentially expressed genes (DEGs) were significantly enriched on the fluid shear stress and atherosclerosis (FSS) pathway. Meanwhile, the expression profiles of some essential genes involved in this pathway suggest that abalone significantly up-regulated calmodulin-4 (CaM-4) and heat-shock protein90 (HSP90), and significantly down-regulated tumor necrosis factor (TNF), bone morphogenetic protein-4 (BMP-4), and nuclear factor kappa B (NF-kB). Also, the hybrid DF showed significantly higher and sustained expression of CaM and HSP90, significantly higher phagocytosis, significantly lower hemocyte mortality, and significantly higher survival at low salinity, suggesting a more active molecular and hemocyte-mediated immune response and a more efficient capacity to tolerate low salinity than DD. CONCLUSIONS: Our study argues that the abalone CaM gene might be necessary to maintain ion equilibrium while HSP90 can offset the adverse changes caused by low salinity, thereby preventing damage to gill epithelial cells (ECs). The data reveal a potential molecular mechanism by which abalone responds to low salinity and confirms that hybridization could be a method for breeding more stress-resilient aquatic species.

Enhanced Adsorption of Polysulfides on Carbon Nanotubes/Boron Nitride Fibers for High-Performance Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries are one of the most promising high-energy-density storage systems. However, serious capacity attenuation and poor cycling stability induced by the shuttle effect of polysulfide intermediates can impede the practical application of Li-S batteries. Herein we report a novel sulfur cathode by intertwining multi-walled carbon nanotubes (CNTs) and porous boron nitride fibers (BNFs) for the subsequent loading of sulfur. This structural design enables trapping of active sulfur and serves to localize the soluble polysulfide within the cathode region, leading to low active material loss. Compared with CNTs/S, CNTs/BNFs/S cathodes deliver a high initial capacity of 1222 mAh g-1 at 0.1 C. Upon increasing the current density to 4 C, the cell retained a capacity of 482 mAh g-1 after 500 cycles with a capacity decay of only 0.044 % per cycle. The design of CNTs/BNFs/S gives new insight on how to optimize cathodes for Li-S batteries.

Quaternized Chitosan-Coated Montmorillonite Interior Antimicrobial Metal-Antibiotic in Situ Coordination Complexation for Mixed Infections of Wounds.

Conventional drug delivery systems for natural clay materials still face critical challenges in their practical application, including multiple bacterial infections, combined infection of bacteria and fungi, and low sterilization efficiency. In this work, we address these challenges using the multifunctional montmorillonite nanosheet-based (MMT-based) drug nanoplatform, which involves the antibiotic 5-fluorocytosine (5-FC), antibacterial metal copper ions, and quaternized chitosan (QCS). Composite material QCS/MMT/5-FCCu can can strongly inhibit Staphylococcus aureus (a typical Gram-positive bacterium), Escherichia coli (a typical Gram-negative bacterium), and Candida albicans (a fungus) because 5-FC coordinates with copper ions in situ and due to the deposition of QCS. The subsequent drug release behavior of 5-FCCu was studied, and the results show an initial high concentration kills microorganisms and long-acting sustained release inhibition. Moreover, in vivo wound experiments and toxicity experiments show the promotion of wound healing and excellent biocompatibility. As a demonstration of the utility of the latter, we have shown that the MMT-based smart platform can be used for the treatment of mixed infections of wounds.

Influence of lag length on repetition priming in emotional stimuli: ERP evidence.

BACKGROUND: Previous studies have demonstrated both behavioral and neural evidence for the potential mediations of lag length and pre-existing memory representation on repetition priming. However, such mediations on emotional stimuli have not been described. METHODS: The current experiment intended to disentangle lag length from pre-existing memory representation. A lexical decision task was performed, in which different emotional characters (either normal or transposed) were re-presented either immediately or delayed. RESULTS: In immediate repetition, one early and two late (ie, N400 and late positive complex) repetition-related event-related potential (ERP) effects were elicited, but these were not sensitive to pre-existing memory representation. The delayed repetition case merely observed the N400. CONCLUSION: These results suggest that the repetition-related priming effect is neutrally sensitive to lag length. Emotional information potentially exerts early and later influences in the processing underlying stimuli memory.

Sensitive Detection of Single-Nucleotide Mutation in the BRAF Mutation Site (V600E) of Human Melanoma Using Phosphate-Pyrene-Labeled DNA Probes.

A series of novel nucleotide phosphoramidites were rationally designed and synthesized and were then site-specifically incorporated in DNA oligonucleotide probes with pyrene-modified phosphate. These oligodeoxynucleotide (ODN) probes almost have no inherent fluorescence emission with pyrene modification at 3' phosphate of corresponding nucleotides as a result of the photoinduced electron-transfer quenching effect of nucleobases (thymidine ∼ cytidine > guanosine ≫ adenosine). However, strong fluorescence emission was observed only with the perfectly matched duplex for the probes with pyrene modified at 3' phosphate of thymidine and cytidine. These rationally designed ODN probes successfully worked as "turn on" fluorescence oligonucleotide sensors for single-nucleotide polymorphism (SNP) and were used for detecting a single BRAF mutation site (V600E) of human melanoma.

Palladium-Catalyzed Direct Cross-Coupling of Carboranyllithium with (Hetero)Aryl Halides.

A palladium-catalyzed direct C-arylation reaction of readily available cage carboranyllithium reagents with aryl halides has been developed for the first time. This method is applicable to a wide range of aryl halide substrates including aryl iodides, aryl bromides, and heteroaromatic halides.

Long non-coding RNA LNC-POTEM-4 promotes HCC progression via the LNC-POTEM-4/miR-149-5p/Wnt4 signaling axis.

Information on the potential role of the long non-coding RNA LNC-POTEM-4 in cancer progression is limited. Our preliminary study found that LNC-POTEM-4 was overexpressed in hepatocellular carcinoma (HCC) tissues, which led us to further investigate the biological function and molecular mechanism of LNC-POTEM-4 in HCC development. LNC-POTEM-4 expression in HCC tissues was examined using transcriptome sequencing and quantitative reverse transcription PCR. The relationships between LNC-POTEM-4 and the stage and prognosis of HCC in patient data from the TCGA database were analyzed. The effects of LNC-POTEM-4 on proliferation, invasion/migration, and epithelial-mesenchymal transition marker expression in HCC cells were evaluated in vitro using gain- and loss-of-function assays, while its effects on tumor growth and metastasis were explored through animal experiments. A LNC-POTEM-4/microRNA (miR)-149-5p/Wnt4 regulatory signaling axis was identified using bioinformatics analysis, and dual luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays. Co-transfection of LNC-POTEM-4 and Wnt4 expression plasmids was employed to confirm the new signaling pathway. We found that LNC-POTEM-4 was overexpressed in HCC tissues and was linked to poor staging and prognosis. LNC-POTEM-4 promoted proliferation, invasion, migration, and the epithelial-mesenchymal transition of HCC cells in vitro. Silencing of LNC-POTEM-4 inhibited HCC growth and distant metastasis in vivo. Mechanically, LNC-POTEM-4 was found to function as a competitive endogenous RNA, upregulating Wnt4 by sponging miR-149-5p to promote HCC progression. Wnt4 overexpression may have counteracted the tumor-inhibition effect of LNC-POTEM-4 silencing. In conclusion, LNC-POTEM-4 upregulated Wnt4 to activate the Wnt signaling pathway and stimulate the malignancy tendency of HCC by sponging miR-149-5p, providing a prospective target for the detection and therapy of HCC. However, the effects of LNC-POTEM-4 on the miR-149-5p/Wnt4 signaling axis should be further studied in animal experiments.

Mitogenome selection shaped the terrestrial adaptation of Grapsidae (Decapoda: Brachyura).

The colonization of aquatic to terrestrial habitats by brachyuran crabs requires genetic innovations as well as morphological adaptations to adapt to terrestrial environments. The genetic basis of such adaptive evolution, however, is largely unknown. This study focuses on terrestrialization in Geograpsus (Grapsidae) the only highly terrestrial genus in this family, which represents a notable example of terrestrial adaptive radiation. Here, we sequenced the mitogenomes of two Geograpsus species and used the mitogenomes of 215 representative crabs to construct phylogenetic and time frameworks that we used to infer terrestrial origins and evolution. Using mitochondrial genomic data, we demonstrated that marine crab ancestors began to settle on land during the early Eocene. Ocean acidification, the Paleocene-Eocene Thermal Maximum (PETM), and mangrove expansion at that time may have driven the diversification and ecological expansion of these terrestrial crabs. Evolutionary analyses reveal strong positive selection signals on monophyletic lineages of Grapsidae, especially the terrestrial species of Geograpsus. Positively selected sites in functionally important regions of ND5 and ND4 may imply enhanced energy metabolism in Grapsidae compared to other crabs, and may have played an important role in their terrestrial adaptation. Overall, our work provides valuable resources and opportunities to reveal the adaptation of crabs to complex terrestrial environments.