FLIBase: a comprehensive repository of full-length isoforms across human cancers and tissues.

Regulatory processes at the RNA transcript level play a crucial role in generating transcriptome diversity and proteome composition in human cells, impacting both physiological and pathological states. This study introduces FLIBase (www.FLIBase.org), a specialized database that focuses on annotating full-length isoforms using long-read sequencing techniques. We collected and integrated long-read (351 samples) and short-read (12 469 samples) RNA sequencing data from diverse normal and cancerous human tissues and cells. The current version of FLIBase comprises a total of 983 789 full-length spliced isoforms, identified through long-read sequences and verified using short-read exon-exon splice junctions. Of these, 188 248 isoforms have been annotated, while 795 541 isoforms remain unannotated. By overcoming the limitations of short-read RNA sequencing methods, FLIBase provides an accurate and comprehensive representation of full-length transcripts. These comprehensive annotations empower researchers to undertake various downstream analyses and investigations. Importantly, FLIBase exhibits a significant advantage in identifying a substantial number of previously unannotated isoforms and tumor-specific RNA transcripts. These tumor-specific RNA transcripts have the potential to serve as a source of immunogenic recurrent neoantigens. This remarkable discovery holds tremendous promise for advancing the development of tailored RNA-based diagnostic and therapeutic strategies for various types of human cancer.

Development of Multimodal Fusion Technology for Tomato Maturity Assessment.

The maturity of fruits and vegetables such as tomatoes significantly impacts indicators of their quality, such as taste, nutritional value, and shelf life, making maturity determination vital in agricultural production and the food processing industry. Tomatoes mature from the inside out, leading to an uneven ripening process inside and outside, and these situations make it very challenging to judge their maturity with the help of a single modality. In this paper, we propose a deep learning-assisted multimodal data fusion technique combining color imaging, spectroscopy, and haptic sensing for the maturity assessment of tomatoes. The method uses feature fusion to integrate feature information from images, near-infrared spectra, and haptic modalities into a unified feature set and then classifies the maturity of tomatoes through deep learning. Each modality independently extracts features, capturing the tomatoes' exterior color from color images, internal and surface spectral features linked to chemical compositions in the visible and near-infrared spectra (350 nm to 1100 nm), and physical firmness using haptic sensing. By combining preprocessed and extracted features from multiple modalities, data fusion creates a comprehensive representation of information from all three modalities using an eigenvector in an eigenspace suitable for tomato maturity assessment. Then, a fully connected neural network is constructed to process these fused data. This neural network model achieves 99.4% accuracy in tomato maturity classification, surpassing single-modal methods (color imaging: 94.2%; spectroscopy: 87.8%; haptics: 87.2%). For internal and external maturity unevenness, the classification accuracy reaches 94.4%, demonstrating effective results. A comparative analysis of performance between multimodal fusion and single-modal methods validates the stability and applicability of the multimodal fusion technique. These findings demonstrate the key benefits of multimodal fusion in terms of improving the accuracy of tomato ripening classification and provide a strong theoretical and practical basis for applying multimodal fusion technology to classify the quality and maturity of other fruits and vegetables. Utilizing deep learning (a fully connected neural network) for processing multimodal data provides a new and efficient non-destructive approach for the massive classification of agricultural and food products.

Shear-Stable Polymer Brush Surfaces.

Research on polymer brushes (PBs) has aroused great interest due to their wide range of applications in lubrication, antifogging, antifouling, self-cleaning, antiadhesion, antibacterial effects, and so forth. However, the weak mechanical strength, especially the low bond strength between the PBs and the substrate surface, is a long-standing challenge for its practical applications, which is directly related to the service life of the PB surface. Fortunately, the imperfection of the PB surface was gradually solved by researchers by combining the action of the chemical and physical anchoring strength, and many shear-stable PB surfaces were developed. In this Perspective, we present recent developments in the studies of shear-stable PBs. Conventional strategies that altered the structure of PB chain methods, including increasing grafted density, cross-linking of PBs, cyclic PBs, and so forth, are introduced briefly. The systematic subsurface grafting of the polymer brush (SSPB) strategy was introduced emphatically. The SSPB method grafted PB into the subsurface with considerable depth and gave a robust and reusable PB layer, which provided an approach for tackling the shear-resistance issue. Besides, the robust hydrophobic poly(dimethylsiloxane) (PDMS) brush surface that lubricated itself in air was also introduced. Finally, we provide a synopsis and discuss the outlook of the shear-stable PB surface.

Freestanding 2D NiFe Metal-Organic Framework Nanosheets: Facilitating Proton Transfer via Organic Ligands for Efficient Oxygen Evolution Reaction.

The oxygen evolution reaction (OER) is crucial to electrochemical hydrogen production. However, designing and fabricating efficient electrocatalysts still remains challenging. By confinedly coordinating organic ligands with metal species in layered double hydroxides (LDHs), an innovative LDHs-assisted approach is developed to facilely synthesize freestanding bimetallic 2D metal-organic framework nanosheets (2D MOF NSs), preserving the metallic components and activities in OER. Furthermore, the research has demonstrated that the incorporation of carboxyl organic ligands coordinated with metal atoms as proton transfer mediators endow 2D MOF NSs with efficient proton transfer during the electrochemical OHads  â†’ Oads transition. These freestanding NiFe-2D MOF NSs require a small overpotential of 260 mV for a current density of 10 mA cm-2 . When this strategy is applied to LDH nanosheets grown on nickel foam, the overpotential can be reduced to 221 mV. This outstanding OER activity supports the capability of multimetallic organic frameworks for the rational design of water oxidation electrocatalysts. This strategy provides a universal path to the synthesis of 2D MOF NSs that can be used as electrocatalysts directly.

Organic-Inorganic Hybrid Polysiloxane Brushes with Improved Lubrication and Load-Bearing Capacity.

With the development of microelectromechanical systems (MEMS), ultrathin dry lubrication coatings have received significant attention. In this study, a nanoscale organic-inorganic hybrid lubricative coating (OHL) with a low friction coefficient and wear resistance was developed by grafting polysiloxane brushes on an inorganic silica sol layer. Friction evaluations, including the friction coefficient, load-bearing capacity, abrasion, and durability, were conducted. Compared with the surface of polysiloxane brushes without a silica sol layer, the introduction of a silica sol interlayer can effectively improve the mechanical stability of polysiloxane brushes; namely, the friction coefficient under high load pressure was able to remain low for a long time. In addition, the lubrication performance can also further improve by modifying the upper friction pair surface with the OHL. More importantly, the OHL has an excellent stability and general applicability. The OHL coating can be applied to various solid surfaces that provide a similar lubrication performance, which may provide a new vision for reducing the friction coefficient and enhancing the wear resistance, especially under dry friction conditions.

Off-axis common-path digital holography using a cube beam splitter.

An off-axis common-path digital holography is built up by inserting a 45° tilted cube beam splitter (CBS) into a 4f system that is described in this paper. Two apertures are set as the input of the 4f system, where one supports the object, and the other is vacant. The CBS divides the incoming beam into two copies, which are symmetrical with each other along the semi-reflecting layer. Due to the separation of two beams in a Fourier plane and the flipping of the field of view induced by the CBS, an off-axis hologram can be captured. Moreover, the carrier frequency can be easily modulated by translating the CBS perpendicular to the optical axis. The new proposed scheme has high light utilization, a compact setup, and high temporal stability. The experiments are carried out to demonstrate the validity and stability of the proposed method.

Unilateral Approach to Primary Bilateral Trigeminal Neuralgia Via Bilateral Microvascular Decompression.

BACKGROUND: Primary bilateral trigeminal neuralgia is a rare disease characterized by paroxysmal bilateral facial pain confined to the somatosensory distribution of the trigeminal nerve. Nonetheless, while treatment of bilateral trigeminal neuralgia with microvascular decompression (MVD) has been reported, there have been no trials of a unilateral approach for bilateral MVD. METHODS: The authors retrospectively analyzed the outcomes and complications of 2 cases of bilateral trigeminal neuralgia treated with MVD by unilateral craniotomy. The 2 patients were followed up for 27 and 32 months, with satisfactory results. One patient developed facial numbness on 1 side postoperatively, which disappeared 3 months later. CONCLUSIONS: Microvascular decompression is an effective and safe opinion for primary bilateral trigeminal neuralgia that fails to respond adequately to medical therapy. The authors suggest that the initial surgery be performed on the more seriously affected side. Unilateral craniotomy for bilateral MVD represents a new therapeutic approach in patients with an enlarged superior trigeminal nerve space.

Repeatedly Regenerating Mechanically Robust Polymer Brushes from Persistent Initiator Coating (PIC).

In this study, a novel surface initiated polymerization (SIP) method was developed from organic-inorganic hybrid persistent initiator coating (PIC) that embeds initiator molecules into inorganic silica sol-gel layer. Comparing with traditional silane initiator surface that prepared by chemical vapor deposition (CVD) method, the PIC can effectively improve the mechanical stability of initiator that was able to endure ten-thousand times of friction cycles. Besides, it allows polymer grafting from sub-surface and so the grafted brushes, poly 3-sulfopropyl methacrylate potassium salt (pSPMA) on the PIC were also much more wear-resisting than those prepared by the traditional ways. More importantly, the PIC could still trigger new polymerization reaction when the grafted brushes were worn off. In addition, the PIC is universal and can be covered on different substrates including glass, metals and plastics, etc. to realize functionalization of these materials. The approach may pave technological way for the application of surface grafted polymer brushes.

Inflammation-Induced Long Intergenic Noncoding RNA (LINC00665) Increases Malignancy Through Activating the Double-Stranded RNA-Activated Protein Kinase/Nuclear Factor Kappa B Pathway in Hepatocellular Carcinoma.

BACKGROUND AND AIMS: The nuclear factor kappa B (NF-κB) signaling pathway is important for linking inflammation and tumorigenesis. Here, we characterized an NF-κB signaling activation-induced long intergenic noncoding (LINC) RNA in hepatocellular carcinoma (HCC), LINC00665, that contributes to the enhanced cell proliferation of HCC cells both in vitro and in vivo. APPROACH AND RESULTS: LINC00665 physically interacts with the double-stranded RNA (dsRNA)-activated protein kinase (PKR), enhances its activation, and maintains its protein stability by blocking ubiquitin/proteasome-dependent degradation, resulting in a positive feedback regulation of NF-κB signaling in HCC cells. Notably, patients with HCC and higher LINC00665 have poorer outcomes in the clinic. CONCLUSIONS: Our findings indicate that LINC00665 is involved in the NF-κB signaling activation in HCC cells and that the inflammatory LINC00665/PKR/NF-κB loop plays important oncogenic roles in hepatic cancer progression and may be a potential therapeutic target.

Gender-specific differences in associations of overweight and obesity with asthma and asthma-related symptoms in 30 056 children: result from 25 districts of Northeastern China.

OBJECTIVE: The relationship between obesity and allergic respiratory diseases in childhood is still controversial. Furthermore, significant debate on the issue of whether or not gender modifies this association also exists due to inconsistent findings. The objective of this study is to evaluate the association between obesity and respiratory health in children, and to investigate the modifications of gender on this association. METHODS: 30 056 children (aged 2-14 years) were randomly selected from 25 districts within 7 cities in Northeastern China in 2009. A standard questionnaire from the American Thoracic Society was used to characterize the children's histories of respiratory symptoms and illnesses. Child weight and height were measured, and obesity was calculated with an age and sex-specific body mass index. RESULTS: The overall prevalence rates of obesity and overweightness were 14.08% and 12.32%, respectively. Compared to the children with normal body weights, asthma and asthma-related symptoms were more prevalent in overweight and obese children. Analysis stratified by gender showed that obesity was associated with more respiratory symptoms and diseases in females than in males. A significant association between obesity and diagnosed asthma [adjusted odds ratio (aOR) = 1.28; 95% confidence interval (CI): 1.02-1.60], as well as current wheezing (aOR = 1.46; 95%CI: 1.20-1.79) was found in females but not in males. CONCLUSIONS: There is an association between asthma symptoms and obesity in these Chinese children, and obesity had a significantly larger effect on females than males.

Carbon-Enhanced Hydrated Salt Phase Change Materials for Thermal Management Applications.

Inorganic hydrated salt phase change materials (PCMs) hold promise for improving the energy conversion efficiency of thermal systems and facilitating the exploration of renewable thermal energy. Hydrated salts, however, often suffer from low thermal conductivity, supercooling, phase separation, leakage and poor solar absorptance. In recent years, compounding hydrated salts with functional carbon materials has emerged as a promising way to overcome these shortcomings and meet the application demands. This work reviews the recent progress in preparing carbon-enhanced hydrated salt phase change composites for thermal management applications. The intrinsic properties of hydrated salts and their shortcomings are firstly introduced. Then, the advantages of various carbon materials and general approaches for preparing carbon-enhanced hydrated salt PCM composites are briefly described. By introducing representative PCM composites loaded with carbon nanotubes, carbon fibers, graphene oxide, graphene, expanded graphite, biochar, activated carbon and multifunctional carbon, the ways that one-dimensional, two-dimensional, three-dimensional and hybrid carbon materials enhance the comprehensive thermophysical properties of hydrated salts and affect their phase change behavior is systematically discussed. Through analyzing the enhancement effects of different carbon fillers, the rationale for achieving the optimal performance of the PCM composites, including both thermal conductivity and phase change stability, is summarized. Regarding the applications of carbon-enhanced hydrate salt composites, their use for the thermal management of electronic devices, buildings and the human body is highlighted. Finally, research challenges for further improving the overall thermophysical properties of carbon-enhanced hydrated salt PCMs and pushing towards practical applications and potential research directions are discussed. It is expected that this timely review could provide valuable guidelines for the further development of carbon-enhanced hydrated salt composites and stimulate concerted research efforts from diverse communities to promote the widespread applications of high-performance PCM composites.

Heat shock transcription factor 1 facilitates liver cancer progression by driving super-enhancer-mediated transcription of MYCN.

BACKGROUND: Heat shock transcription factors (HSFs) play crucial roles in the development of malignancies. However, the specific roles of HSFs in hepatocellular carcinoma (HCC) have yet to be fully elucidated. AIMS: To explore the involvement of the HSF family, particularly HSF1, in the progression and prognosis of HCC. MATERIALS & METHODS: We conducted a thorough analysis of HSF expression and copy number variations across various cancer datasets. Specifically focusing on HSF1, we examined its expression levels and prognostic implications in HCC. In vitro and in vivo experiments were carried out to evaluate the impact of HSF1 on liver cancer cell proliferation. Additionally, we utilized CUT&Tag, H3K27 acetylation enrichment, and RNA sequencing (RNA-seq) to investigate the super-enhancer (SE) regulatory landscapes of HSF1 in liver cancer cell lines. RESULTS: HSF1 expression is elevated in HCC and is linked to poor prognosis in several datasets. HSF1 stimulates liver cancer cell proliferation both in vitro and in vivo, partly through modulation of H3K27ac levels, influencing enhancer distribution. Mechanistically, our findings demonstrate that HSF1 transcriptionally activates MYCN expression by binding to its promoter and SE elements, thereby promoting liver cancer cell proliferation. Moreover, increased MYCN expression was detected in HCC tumors and correlated with unfavorable patient outcomes. DISCUSSION: Our study sheds light on previously unexplored aspects of HSF1 biology, identifying it as a transcription factor capable of shaping the epigenetic landscape in the context of HCC. Given HSF1's potential as an epigenetic regulator, targeting the HSF1-MYCN axis could open up new therapeutic possibilities for HCC treatment. CONCLUSION: The HSF1-MYCN axis constitutes a transcription-dependent regulatory mechanism that may function as both a prognostic indicator and a promising therapeutic target in liver cancer. Further exploration of this axis could yield valuable insights into novel treatment strategies for HCC.

Robust Transparent Photothermal Omniphobic Coating for Efficient Anti/Deicing and Antifogging.

Icing and fogging on optical material surfaces bring various problems in daily life. Recently, some photothermal coatings have been reported to prevent the condensation or freeze of water droplets by increasing the surface temperature. However, it is a great challenge to apply them in practical conditions due to their opaqueness and poor mechanical wear-resistant property. In this work, we constructed a robust transparent photothermal omniphobic coating with a simple dip-coating technique. In the coating system, photothermal polypyrrole nanoparticles are introduced into inorganic silica networks, and then polydimethylsiloxane (PDMS) brushes were grafted on the inorganic silica layer to endow the surface with omniphobicity and stain resistance. The transparency and photothermal capacity of the coating can be regulated by the deposition times of the coating. In addition, the coating has an excellent anti/deicing property and reduces ice adhesion obviously due to the existence of "liquid-like" PDMS brushes. More importantly, the coating presents outstanding mechanical wear-resistant and self-lubricating properties that can endure several thousand friction cycles without performance loss. The mechanically robust photothermal omniphobic coating gives a feasible approach to anti-icing and antifogging of transparent substrates under sunlight irradiation.

Advancing Energy Sustainability Through Solar-to-Fuel Technologies: From Materials to Devices and Systems.

To achieve carbon neutrality and sustainable development, innovative solar-to-fuel systems have been designed through the integration of solar energy harvesting and electrochemical devices. Over the last decade, there have been notable advancements in enhancing the efficiency and durability of these solar-to-fuel systems. Despite the advancements, there remains significant potential for further improvements in the performance of systems. Enhancements can be achieved by optimizing electrochemical catalysts, advancing the manufacturing technologies of photovoltaics and electrochemical cells, and refining the overall design of these systems. In the realm of catalyst optimization, the effectiveness of materials can be significantly improved through active site engineering and strategic use of functional groups. Similarly, the performance of electrochemical devices can be enhanced by incorporating specific additives into electrolytes and optimizing gas diffusion electrodes. Improvements in solar harvesting devices are achievable through efficient passivant and self-assembled monolayers, which enhance the overall quality and efficiency of these systems. Additionally, optimizing the energy conversion efficiency involves the strategic use of DC converters, photoelectrodes, and redox media. This review aims to provide a comprehensive overview of the advancements in solar-powered electrochemical energy conversion systems, laying a solid foundation for future research and development in the field of energy sustainability.

Fibrillarin reprograms glucose metabolism by driving the enhancer-mediated transcription of PFKFB4 in liver cancer.

DNA- and RNA-binding proteins (DRBPs) are versatile proteins capable of binding to both DNA and RNA molecules. In this study, we identified fibrillarin (FBL) as a key DRBP that is upregulated in liver cancer tissues vs. normal tissues and is correlated with patient prognosis. FBL promotes the proliferation of liver cancer cells both in vitro and in vivo. Mechanistically, FBL interacts with the transcription factor KHSRP, thereby regulating the expression of genes involved in glucose metabolism and leading to the reprogramming of glucose metabolism. Specifically, FBL and KHSRP work together to transcriptionally activate the glycolytic enzyme PFKFB4 by co-occupying enhancer and promoter elements, thereby further promoting liver cancer growth. Collectively, these findings provide compelling evidence highlighting the role of FBL as a transcriptional regulator in liver cancer cells, working in conjunction with KHSRP. The FBL/KHSRP-PFKFB4 regulatory axis holds potential as both a prognostic indicator and a therapeutic target for liver cancer. SIGNIFICANCE: A novel role of FBL in the transcriptional activation of PFKFB4, leading to glucose metabolism reprogramming in liver cancer.

Distribution, sources, partition behavior and risk assessment of polycyclic aromatic hydrocarbons (PAHs) in the waters and sediments of Lake Ulansuhai, China.

This study represents the first comprehensive investigation of 16 polycyclic aromatic hydrocarbons (PAHs) in the waters and sediments of Lake Ulansuhai. It explores their occurrence, sources, transport behavior, and associated risks to human health and ecosystems. The results revealed that concentrations of ∑PAHs in dissolved phase and sediment with no significant seasonal differences. In contrast, ∑PAHs concentrations in suspended particulate matter were significantly higher during the ice-free period compared to the ice period. Spatially, the northern part of Lake Ulansuhai displayed higher PAHs content. Diagnostic isomeric ratios and PMF models indicated that the PAHs were primarily derived from combustion sources. The distribution of PAHs within water-sediment demonstrated that non-equilibrium status. Fugacity calculations indicated that 2-4 rings PAHs acted as secondary sources of sediment emissions. Toxicity assessment, indicated that PAHs posed no significant carcinogenic risk to humans. Risk quotient values showed that PAHs as low to high ecological risk.

Elevated choline drives KLF5-dominated transcriptional reprogramming to facilitate liver cancer progression.

An increase in the total choline-containing compound content is a common characteristic of cancer cells, and aberrant choline metabolism in cancer is closely associated with malignant progression. However, the potential role of choline-induced global transcriptional changes in cancer cells remains unclear. In this study, we reveal that an elevated choline content facilitates hepatocellular carcinoma (HCC) cell proliferation by reprogramming Krüppel-like factor 5 (KLF5)-dominated core transcriptional regulatory circuitry (CRC). Mechanistically, choline administration leads to elevated S-adenosylmethionine (SAM) levels, inducing the formation of H3K4me1 within the super-enhancer (SE) region of KLF5 and activating its transcription. KLF5, as a key transcription factor (TF) of CRC established by choline, further transactivates downstream genes to facilitate HCC cell cycle progression. Additionally, KLF5 can increase the expression of choline kinase-α (CHKA) and CTP:phosphocholine cytidylyltransferase (CCT) resulting in a positive feedback loop to promote HCC cell proliferation. Notably, the histone deacetylase inhibitor (HDACi) vorinostat (SAHA) significantly suppressed KLF5 expression and liver tumor growth in mice, leading to a prolonged lifespan. In conclusion, these findings highlight the epigenetic regulatory mechanism of the SE-driven key regulatory factor KLF5 conducted by choline metabolism in HCC and suggest a potential therapeutic strategy for HCC patients with high choline content.

Selective Synthesis of Organonitrogen Compounds via Electrochemical C-N Coupling on Atomically Dispersed Catalysts.

The C-N coupling reaction demonstrates broad application in the fabrication of a wide range of high value-added organonitrogen molecules including fertilizers (e.g., urea), chemical feedstocks (e.g., amines, amides), and biomolecules (e.g., amino acids). The electrocatalytic C-N coupling pathways from waste resources like CO2, NO3-, or NO2- under mild conditions offer sustainable alternatives to the energy-intensive thermochemical processes. However, the complex multistep reaction routes and competing side reactions lead to significant challenges regarding low yield and poor selectivity toward large-scale practical production of target molecules. Among diverse catalyst systems that have been developed for electrochemical C-N coupling reactions, the atomically dispersed catalysts with well-defined active sites provide an ideal model platform for fundamental mechanism elucidation. More importantly, the intersite synergy between the active sites permits the enhanced reaction efficiency and selectivity toward target products. In this Review, we systematically assess the dominant reaction pathways of electrocatalytic C-N coupling reactions toward various products including urea, amines, amides, amino acids, and oximes. To guide the rational design of atomically dispersed catalysts, we identify four key stages in the overall reaction process and critically discuss the corresponding catalyst design principles, namely, retaining NOx/COx reactants on the catalyst surface, regulating the evolution pathway of N-/C- intermediates, promoting C-N coupling, and facilitating final hydrogenation steps. In addition, the advanced and effective theoretical simulation and characterization technologies are discussed. Finally, a series of remaining challenges and valuable future prospects are presented to advance rational catalyst design toward selective electrocatalytic synthesis of organonitrogen molecules.

Revamping Triboelectric Output by Deep Trap Construction.

High output performance is critical for building triboelectric nanogenerators (TENGs) for future multifunctional applications. Unfortunately, the high triboelectric charge dissipation rate has a significant negative impact on its electrical output performance. Herein, a new tribolayer is designed through introducing self-assembled molecules with large energy gaps on commercial PET fibric to form carrier deep traps, which improve charge retention while decreasing dissipation rates. The deep trap density of the PET increases by two orders of magnitude, resulting in an 86% reduction in the rate of charge dissipation and a significant increase in the charge density that can be accumulated on tribolayer during physical contact. The key explanation is that increasing the density of deep traps improves the dielectric's ability to store charges, making it more difficult for the triboelectric charges trapped by the tribolayer to escape from the deep traps, lowering the rate of charge dissipation. This TENG has a 1300% increase in output power density as a result of altering the deep trap density, demonstrating a significant improvement. This work describes a simple yet efficient method for building TENGs with ultra-high electrical output and promotes their practical implementation in the sphere of the Internet of Things.

Long-read transcriptome landscapes of primary and metastatic liver cancers at transcript resolution.

BACKGROUND: The liver ranks as the sixth most prevalent site of primary cancer in humans, and it frequently experiences metastases from cancers originating in other organs. To facilitate the development of effective treatments and improve survival rates, it is crucial to comprehend the intricate and diverse transcriptome landscape of primary and metastatic liver cancers. METHODS: We conducted long-read isoform sequencing and short-read RNA sequencing using a cohort of 95 patients with primary and secondary liver cancer who underwent hepatic resection. We compared the transcriptome landscapes of primary and metastatic liver cancers and systematically investigated hepatocellular carcinoma (HCC), paired primary tumours and liver metastases, and matched nontumour liver tissues. RESULTS: We elucidated the full-length isoform-level transcriptome of primary and metastatic liver cancers in humans. Our analysis revealed isoform-level diversity in HCC and identified transcriptome variations associated with liver metastatis. Specific RNA transcripts and isoform switching events with clinical implications were profound in liver cancer. Moreover, we defined metastasis-specific transcripts that may serve as predictors of risk of metastasis. Additionally, we observed abnormalities in adjacent paracancerous liver tissues and characterized the immunological and metabolic alterations occurring in the liver. CONCLUSIONS: Our findings underscore the power of full-length transcriptome profiling in providing novel biological insights into the molecular mechanisms underlying tumourigenesis. These insights will further contribute to improving treatment strategies for primary and metastatic liver cancers.