Loss of lncRNA LINC01056 leads to sorafenib resistance in HCC.

BACKGROUND AND AIMS: Sorafenib is a major nonsurgical option for patients with advanced hepatocellular carcinoma (HCC); however, its clinical efficacy is largely undermined by the acquisition of resistance. The aim of this study was to identify the key lncRNA involved in the regulation of the sorafenib response in HCC. MATERIALS AND METHODS: A clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) single-guide RNA (sgRNA) synergistic activation mediator (SAM)-pooled lncRNA library was applied to screen for the key lncRNA regulated by sorafenib treatment. The role of the identified lncRNA in mediating the sorafenib response in HCC was examined in vitro and in vivo. The underlying mechanism was delineated by proteomic analysis. The clinical significance of the expression of the identified lncRNA was evaluated by multiplex immunostaining on a human HCC microtissue array. RESULTS: CRISPR/Cas9 lncRNA library screening revealed that Linc01056 was among the most downregulated lncRNAs in sorafenib-resistant HCC cells. Knockdown of Linc01056 reduced the sensitivity of HCC cells to sorafenib, suppressing apoptosis in vitro and promoting tumour growth in mice in vivo. Proteomic analysis revealed that Linc01056 knockdown in sorafenib-treated HCC cells induced genes related to fatty acid oxidation (FAO) while repressing glycolysis-associated genes, leading to a metabolic switch favouring higher intracellular energy production. FAO inhibition in HCC cells with Linc01056 knockdown significantly restored sensitivity to sorafenib. Mechanistically, we determined that PPARα is the critical molecule governing the metabolic switch upon Linc01056 knockdown in HCC cells and indeed, PPARα inhibition restored the sorafenib response in HCC cells in vitro and HCC tumours in vivo. Clinically, Linc01056 expression predicted optimal overall and progression-free survival outcomes in HCC patients and predicted a better sorafenib response. Linc01056 expression indicated a low FAO level in HCC. CONCLUSION: Our study identified Linc01056 as a critical epigenetic regulator and potential therapeutic target in the regulation of the sorafenib response in HCC.

Validation of Artificial Intelligence-based Bowel Preparation Assessment in Screening Colonoscopy.

BACKGROUND AND AIMS: Accurate bowel preparation assessment is essential for determining colonoscopy screening intervals. Patients with suboptimal bowel preparation are at a high risk of missing >5mm adenomas, and should undergo an early repeat colonoscopy. In this study, we employed artificial intelligence (AI) to evaluate bowel preparation and validated the ability of the system in accurately identifying patients who are at high risk of missing >5mm adenoma due to inadequate bowel preparation. PATIENTS AND METHODS: This prospective, single-center, observational study was conducted at the Eighth Affiliated Hospital, Sun Yat-sen University from October 8, 2021, to November 9, 2022. Eligible patients underwent screening colonoscopy were consecutively enrolled. The AI assessed bowel preparation using e-Boston Bowel Preparation Scale (BBPS) while endoscopists evaluated using BBPS. If both BBPS and e-BBPS deemed preparation adequate, the patient immediately underwent a second colonoscopy, otherwise the patient underwent bowel re-cleansing before the second colonoscopy. RESULTS: Among the 393 patients, 72 ＞5mm adenomas were detected, while 27 ＞5mm adenomas were missed. In unqualified-AI patients, the >5mm AMR was significantly higher than in qualified-AI patients (35.71% vs 13.19%, p=0.0056, OR 0.2734, 95% CI 0.1139, 0.6565), as were the AMR (50.89% vs 20.79%, p<0.001, OR 0.2532, 95% CI 0.1583, 0.4052) and >5mm PMR (35.82% vs 19.48%, p=0.0152, OR 0.4335, 95% CI 0.2288, 0.8213). CONCLUSIONS: This study confirmed that patients classified as inadequate by AI showed unacceptable >5mm AMR, provided key evidence for implementing AI in guiding the bowel re-cleansing, potentially standardizing the future colonoscopy screening; ClincialTrials.gov, NCT05145712.

Synthesis of Quantum-Confined Borophene Nanoribbons.

Borophene nanoribbons (BNRs) are one-dimensional strips of atomically thin boron expected to exhibit quantum-confined electronic properties that are not present in extended two-dimensional borophene. While the parent material borophene has been experimentally shown to possess anisotropic metallicity and diverse polymorphic structures, the atomically precise synthesis of nanometer-wide BNRs has not yet been achieved. Here, we demonstrate the synthesis of multiple BNR polymorphs with well-defined edge configurations within the nanometer-scale terraces of vicinal Ag(977). Through atomic-scale imaging, spectroscopy, and first-principles calculations, the synthesized BNR polymorphs are characterized and found to possess distinct edge structures and electronic properties. For single-phase BNRs, v1/6-BNRs and v1/5-BNRs adopt reconstructed armchair edges and sawtooth edges, respectively. In addition, the electronic properties of single-phase v1/6-BNRs and v1/5-BNRs are dominated by Friedel oscillations and striped moiré patterns, respectively. On the other hand, mixed-phase BNRs possess quantum-confined states with increasing nodes in the electronic density of states at elevated biases. Overall, the high degree of polymorphism and diverse edge topologies in borophene nanoribbons provide a rich quantum platform for studying one-dimensional electronic states.

CRISPR/Cas9 screens unravel miR-3689a-3p regulating sorafenib resistance in hepatocellular carcinoma via suppressing CCS/SOD1-dependent mitochondrial oxidative stress.

AIMS: Therapeutic outcome of sorafenib in hepatocellular carcinoma (HCC) is undermined by the development of drug resistance. This study aimed to identify the critical microRNA (miRNA) which is responsible for sorafenib resistance at the genomic level. METHODS: CRISPR/Cas9 screen followed by gain- and loss-of-function assays both in vitro and in vivo were applied to identify the role of miR-3689a-3p in mediating sorafenib response in HCC. The upstream and downstream molecules of miR-3689a-3p and their mechanism of action were investigated. RESULTS: CRISPR/Cas9 screening identified miR-3689a-3p was the most up-regulated miRNA in sorafenib sensitive HCC. Knockdown of miR-3689a-3p significantly increased sorafenib resistance, while its overexpression sensitized HCC response to sorafenib treatment. Proteomic analysis revealed that the effect of miR-3689a-3p was related to the copper-dependent mitochondrial superoxide dismutase type 1 (SOD1) activity. Mechanistically, miR-3689a-3p targeted the 3'UTR of the intracellular copper chaperone for superoxide dismutase (CCS) and suppressed its expression. As a result, miR-3689a-3p disrupted the intracellular copper trafficking and reduced SOD1-mediated scavenge of mitochondrial oxidative stress that eventually caused HCC cell death in response to sorafenib treatment. CCS overexpression blunted sorafenib response in HCC. Clinically, miR-3689a-3p was down-regulated in HCC and predicted favorable prognosis for HCC patients. CONCLUSION: Our findings provide comprehensive evidence for miR-3689a-3p as a positive regulator and potential druggable target for improving sorafenib treatment in HCC.

Exosomes as a modulator of immune resistance in human cancers.

In the tumor microenvironment (TME), exosomes secreted by cells form interactive networks between the tumor cells and immune cells, thereby regulating immune signaling cascades in the TME. As key messengers of cell-to-cell communication in the TME, exosomes not only take charge of tumor cell antigen presentation to the immune cells, but also regulate the activities of immune cells, inhibit immune function, and, especially, promote immune resistance, all of which affects the therapeutic outcomes of tumors. Exosomes, which are small-sized vesicles, possess some remarkable advantages, including strong biological activity, a lack of immunogenicity and toxicity, and a strong targeting ability. Based on these characteristics, research on exosomes as biomarkers or carriers of tumor therapeutic drugs has become a research hotspot in related fields. This review describes the role of exosomes in cell communications in the TME, summarizes the effectiveness of exosome-based immunotherapy in overcoming immune resistance in cancer treatment, and systematically summarizes and discusses the characteristics of exosomes from different cell sources. Furthermore, the prospects and challenges of exosome-related therapies are discussed.

How attachment affects users' continued use intention of tourism mobile platform: A user experience perspective.

Continued use intention of customers is a critical factor in the development of tourism mobile platforms (TMP), which reflects the degree of users' attachment to the platforms. However, existing research in this field intends to investigate users' attachment to a TMP by focusing on the overall cognitive satisfaction of the users, which deviates from the "cognition-affect" framework in psychology. Following the stimulus-organism-response (S-O-R) framework, this paper draws upon the attachment theory and the user experience theory, and proposes a model depicting how service experience of TMP affects users' intention to keep using the TMP through the mediation effect of platform attachment. The empirical results (N = 276) showed that functional experience and social experience positively affect TMP users' development of platform attachment (i.e., platform dependence and platform identity), which in turn enhance their intention to continuously obtain and provide tourism information via the TMP. This study expands the research on the continued use of TMP from an attachment perspective and contributes to the field in both theoretical and practical levels.

Ingrained: An Automated Framework for Fusing Atomic-Scale Image Simulations into Experiments.

To fully leverage the power of image simulation to corroborate and explain patterns and structures in atomic resolution microscopy, an initial correspondence between the simulation and experimental image must be established at the outset of further high accuracy simulations or calculations. Furthermore, if simulation is to be used in context of highly automated processes or high-throughput optimization, the process of finding this correspondence itself must be automated. In this work, "ingrained," an open-source automation framework which solves for this correspondence and fuses atomic resolution image simulations into the experimental images to which they correspond, is introduced. Herein, the overall "ingrained" workflow, focusing on its application to interface structure approximations, and the development of an experimentally rationalized forward model for scanning tunneling microscopy simulation are described.

Isolation of a degrading strain of Fusarium verticillioides and bioremediation of glyphosate residue.

Glyphosate is a broad-spectrum and nonselective organophosphorus herbicide that inhibits 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), an enzyme in the shikimate pathway in plants. A glyphosate-resistant fungus identified as Fusarium verticillioides was screened from soil subjected to long-term glyphosate application, and this fungus could grow in inorganic salt medium containing 90 mmol/L glyphosate. The optimum culture conditions identified via the response surface curve method were 28 °C and pH 7.0. The target gene epsps was cloned in this study, and the open reading frame contained 1170 nucleotides and putatively encoded 389 amino acid residues. Phylogenetic analysis showed that this gene belonged to class I, genes naturally sensitive to glyphosate. q-PCR confirmed that the relative expression level of the epsps gene was low, and no significant difference in expression was observed among different glyphosate concentrations at 12 h or 48 h. On day 28, the degradation by Fusarium verticillioides C-2 of sterilized soil and unsterilized soil supplemented with 60 mg/kg glyphosate reached 72.17% and 89.07%, respectively, and a significant difference was observed between the treatments with and without the glyphosate-degrading strain. The recovery of soil dehydrogenase activity after the addition of Fusarium verticillioides was significantly higher than that in the absence of the degrading fungus on the 28th day. The results showed that C-2 is a highly effective glyphosate-degrading strain with bioremediation potential for glyphosate-contaminated soil.

Borophene synthesis beyond the single-atomic-layer limit.

Synthetic two-dimensional (2D) materials have no bulk counterparts and typically exist as single atomic layers due to substrate-stabilized growth. Multilayer formation, although broadly sought for structure and property tuning, has not yet been achieved in the case of synthetic 2D boron: that is, borophene1,2. Here, we experimentally demonstrate the synthesis of an atomically well-defined borophene polymorph beyond the single-atomic-layer (SL) limit. The structure of this bilayer (BL) borophene is consistent with two covalently bonded α-phase layers (termed BL-α borophene) as evidenced from bond-resolved scanning tunnelling microscopy, non-contact atomic force microscopy and density functional theory calculations. While the electronic density of states near the Fermi level of BL-α borophene is similar to SL borophene polymorphs, field-emission resonance spectroscopy reveals distinct interfacial charge transfer doping and a heightened local work function exceeding 5 eV. The extension of borophene polymorphs beyond the SL limit significantly expands the phase space for boron-based nanomaterials.

Self-Assembled Borophene/Graphene Nanoribbon Mixed-Dimensional Heterostructures.

Atomically thin metal-semiconductor heterojunctions are highly desirable for nanoelectronic applications. However, coherent lateral stitching of distinct two-dimensional (2D) materials has traditionally required interfacial lattice matching and compatible growth conditions, which remains challenging for most systems. On the other hand, these constraints are relaxed in 2D/1D mixed-dimensional lateral heterostructures due to the increased structural degree of freedom. Here, we report the self-assembly of mixed-dimensional lateral heterostructures consisting of 2D metallic borophene and 1D semiconducting armchair-oriented graphene nanoribbons (aGNRs). With the sequential ultrahigh vacuum deposition of boron and 4,4″-dibromo-p-terphenyl as precursors on Ag(111) substrates, an on-surface polymerization process is systematically studied and refined including the transition from monomers to organometallic intermediates and finally demetallization that results in borophene/aGNR lateral heterostructures. High-resolution scanning tunneling microscopy and spectroscopy resolve the structurally and electronically abrupt interfaces in borophene/aGNR heterojunctions, thus providing insight that will inform ongoing efforts in pursuit of atomically precise nanoelectronics.

Synthesis of borophane polymorphs through hydrogenation of borophene.

Synthetic two-dimensional polymorphs of boron, or borophene, have attracted attention because of their anisotropic metallicity, correlated-electron phenomena, and diverse superlattice structures. Although borophene heterostructures have been realized, ordered chemical modification of borophene has not yet been reported. Here, we synthesize "borophane" polymorphs by hydrogenating borophene with atomic hydrogen in ultrahigh vacuum. Through atomic-scale imaging, spectroscopy, and first-principles calculations, the most prevalent borophane polymorph is shown to possess a combination of two-center-two-electron boron-hydrogen and three-center-two-electron boron-hydrogen-boron bonds. Borophane polymorphs are metallic with modified local work functions and can be reversibly returned to pristine borophene through thermal desorption of hydrogen. Hydrogenation also provides chemical passivation because borophane reduces oxidation rates by more than two orders of magnitude after ambient exposure.

Nitrogen cluster doping for high-mobility/conductivity graphene films with millimeter-sized domains.

Directly incorporating heteroatoms into the hexagonal lattice of graphene during growth has been widely used to tune its electrical properties with superior doping stability, uniformity, and scalability. However the introduction of scattering centers limits this technique because of reduced carrier mobilities and conductivities of the resulting material. Here, we demonstrate a rapid growth of graphitic nitrogen cluster-doped monolayer graphene single crystals on Cu foil with remarkable carrier mobility of 13,000 cm2 V-1 s-1 and a greatly reduced sheet resistance of only 130 ohms square-1. The exceedingly large carrier mobility with high n-doping level was realized by (i) incorporation of nitrogen-terminated carbon clusters to suppress the carrier scattering and (ii) elimination of all defective pyridinic nitrogen centers by oxygen etching. Our study opens up an avenue for the growth of high-mobility/conductivity doped graphene with tunable work functions for scalable graphene-based electronic and device applications.

Plasmon-Free Surface-Enhanced Raman Spectroscopy Using Metallic 2D Materials.

Two dimensional (2D) materials-based plasmon-free surface-enhanced Raman scattering (SERS) is an emerging field in nondestructive analysis. However, impeded by the low density of state (DOS), an inferior detection sensitivity is frequently encountered due to the low enhancement factor of most 2D materials. Metallic transition-metal dichalcogenides (TMDs) could be ideal plasmon-free SERS substrates because of their abundant DOS near the Fermi level. However, the absence of controllable synthesis of metallic 2D TMDs has hindered their study as SERS substrates. Here, we realize controllable synthesis of ultrathin metallic 2D niobium disulfide (NbS2) (<2.5 nm) with large domain size (>160 µm). We have explored the SERS performance of as-obtained NbS2, which shows a detection limit down to 10-14 mol·L-1. The enhancement mechanism was studied in depth by density functional theory, which suggested a strong correlation between the SERS performance and DOS near the Fermi level. NbS2 features the most abundant DOS and strongest binding energy with probe molecules as compared with other 2D materials such as graphene, 1T-phase MoS2, and 2H-phase MoS2. The large DOS increases the intermolecular charge transfer probability and thus induces prominent Raman enhancement. To extend the results to practical applications, the resulting NbS2-based plasmon-free SERS substrates were applied for distinguishing different types of red wines.

Scalable Salt-Templated Synthesis of Nitrogen-Doped Graphene Nanosheets toward Printable Energy Storage.

Mass production of graphene powders affording high quality and environmental benignancy serves as a prerequisite for the practical usage of graphene in multiple energy storage applications. Herein, we exploit a salt-templated CVD approach to harness the direct synthesis of nitrogen-doped graphene (NG) nanosheets and related ink dispersions in a scalable, safe, efficient, and green fashion. Thus-fabricated NG accompanying large productivity, excellent electrical conductivity, and favorable solution processability possesses implications in printable energy storage devices. With the NG-based ink in hand, self-standing 3D architectures with programmable patterns can be directly printed over a myriad of substrates. Accordingly, both electrode preparation for flexible supercapacitors and separator modification in Li-S batteries can be enabled via printing by employing our NG-based composite inks. This work thus represents a practical route for mass production of graphene inks with cost-effectiveness and eco-friendliness for emerging energy storage technology.

A comparison of hazard perception and hazard prediction tests across China, Spain and the UK.

Hazard perception (HP) is the ability to spot on-road hazards in time to avoid a collision. This skill is traditionally measured by recording response times to hazards in video clips of driving, with safer, experienced drivers often out-performing inexperienced drivers. This study assessed whether HP test performance is culturally specific by comparing Chinese, Spanish and UK drivers who watched clips filmed in all three countries. Two test-variants were created: a traditional HP test (requiring timed hazard responses), and a hazard prediction test, where the film is occluded at hazard-onset and participants predict what happens next. More than 300 participants, across the 3 countries, were divided into experienced and inexperienced-driver groups. The traditional HP test did not discriminate between experienced and inexperienced drivers, though participant nationality influenced the results with UK drivers reporting more hazards than Chinese drivers. The hazard prediction test, however, found experienced drivers to out-perform inexperienced drivers. No differences were found for nationality, with all nationalities being equally skilled at predicting hazards. The results suggest that drivers' criterion level for responding to hazards is culturally sensitive, though their ability to predict hazards is not. We argue that the more robust, culturally-agnostic, hazard prediction test appears better suited for global export.

Biotemplating Growth of Nepenthes-like N-Doped Graphene as a Bifunctional Polysulfide Scavenger for Li-S Batteries.

The practical application of lithium-sulfur (Li-S) batteries is hindered by their poor cycling stabilities that primarily stem from the "shuttle" of dissolved lithium polysulfides. Here, we develop a nepenthes-like N-doped hierarchical graphene (NHG)-based separator to realize an efficient polysulfide scavenger for Li-S batteries. The 3D textural porous NHG architectures are realized by our designed biotemplating chemical vapor deposition (CVD) approach via the employment of naturally abundant diatomite as the growth substrate. Benefiting from the high surface area, devious inner-channel structure, and abundant nitrogen doping of CVD-grown NHG frameworks, the derived separator favorably synergizes bifunctionality of physical confinement and chemical immobilization toward polysulfides, accompanied by smooth lithium ion diffusions. Accordingly, the batteries with the NHG-based separator delivers an initial capacity of 868 mAh g-1 with an average capacity decay of only 0.067% per cycle at 2 C for 800 cycles. A capacity of 805 mAh g-1 can further be achieved at a high sulfur loading of ∼7.2 mg cm-2. The present study demonstrates the potential in constructing high-energy and long-life Li-S batteries upon separator modification.

Recent progress in the tailored growth of two-dimensional hexagonal boron nitride via chemical vapour deposition.

Recent years have witnessed many advances in two-dimensional (2D) hexagonal boron nitride (h-BN) materials in both fundamental research and practical applications. This has ultimately been inspired by the unique electrical and optical properties, as well as the excellent thermal and chemical stability of h-BN. However, controllable and scalable preparation of 2D h-BN materials has been challenging. Very recently, the chemical vapour deposition (CVD) technique has shown great promise for achieving high-quality h-BN samples with excellent layer-number selectivity and large-area uniformity, considerably contributing to the latest advancements of 2D material research. In this tutorial review, we provide a systematic summary of the state-of-the-art in the tailored production of 2D h-BN on various substrates by virtue of CVD routes.

Caging Nb2 O5 Nanowires in PECVD-Derived Graphene Capsules toward Bendable Sodium-Ion Hybrid Supercapacitors.

Sodium-ion hybrid supercapacitors (Na-HSCs) by virtue of synergizing the merits of batteries and supercapacitors have attracted considerable attention for high-energy and high-power energy-storage applications. Orthorhombic Nb2 O5 (T-Nb2 O5 ) has recently been recognized as a promising anode material for Na-HSCs due to its typical pseudocapacitive feature, but it suffers from intrinsically low electrical conductivity. Reasonably high electrochemical performance of T-Nb2 O5 -based electrodes could merely be gained to date when sufficient carbon content was introduced. In addition, flexible Na-HSC devices have scarcely been demonstrated by far. Herein, an in situ encapsulation strategy is devised to directly grow ultrathin graphene shells over T-Nb2 O5 nanowires (denoted as Gr-Nb2 O5 composites) by plasma-enhanced chemical vapor deposition, targeting a highly conductive anode material for Na-HSCs. The few-layered graphene capsules with ample topological defects would enable facile electron and Na+ ion transport, guaranteeing rapid pseudocapacitive processes at the Nb2 O5 /electrolyte interface. The Na-HSC full-cell comprising a Gr-Nb2 O5 anode and an activated carbon cathode delivers high energy/power densities (112.9 Wh kg-1 /80.1 W kg-1 and 62.2 Wh kg-1 /5330 W kg-1 ), outperforming those of recently reported Na-HSC counterparts. Proof-of-concept Na-HSC devices with favorable mechanical robustness manifest stable electrochemical performances under different bending conditions and after various bending-release cycles.

Vanadium Dioxide-Graphene Composite with Ultrafast Anchoring Behavior of Polysulfides for Lithium-Sulfur Batteries.

The lithium-sulfur (Li-S) battery has been deemed as one of the most promising energy-storage systems owing to its high energy density, low cost, and environmental benignancy. However, the capacity decay and kinetic sluggishness stemming from polysulfide shuttle effects have by far posed a great challenge to practical performance. We herein demonstrate the employment of low-cost, wet-chemistry-derived VO2 nanobelts as the effective host additives for the graphene-based sulfur cathode. The VO2 nanobelts displayed an ultrafast anchoring behavior of polysulfides, managing to completely decolor the polysulfide solution in 50 s. Such a fast and strong anchoring ability of VO2 was further investigated and verified by experimental and theoretical investigations. Benefitting from the synergistic effect exerted by VO2 in terms of chemical confinement and catalytic conversion of polysulfides, the Li-S batteries incorporating VO2 and graphene manifested excellent cycling and rate performances. Notably, the batteries delivered an initial discharge capacity of 1405 mAh g-1 when cycling at 0.2 C, showed an advanced rate performance of ∼830 mAh g-1 at 2 C, and maintained a stable cycling performance at high current densities of 1, 2, and 5 C over 200 cycles, paving a practical route toward cost-effective and environmentally benign cathode design for high-energy Li-S batteries.

Nickelocene-Precursor-Facilitated Fast Growth of Graphene/h-BN Vertical Heterostructures and Its Applications in OLEDs.

The direct growth of high-quality, large-area, uniform, vertically stacked Gr/h-BN heterostructures is of vital importance for applications in electronics and optoelectronics. However, the main challenge lies in the catalytically inert nature of the hexagonal boron nitride (h-BN) substrates, which usually afford a rather low decomposition rate of carbon precursors, and thus relatively low growth rate of graphene. Herein, a nickelocene-precursor-facilitated route is developed for the fast growth of Gr/h-BN vertical heterostructures on Cu foils, which shows much improved synthesis efficiency (8-10 times faster) and crystalline quality of graphene (large single-crystalline domain up to ≈20 µm). The key advantage of our synthetic route is the utilization of nickel atoms that are decomposed from nickelocene molecules as the gaseous catalyst, which can decrease the energy barrier for graphene growth and facilitate the decomposition of carbon sources, according to our density functional theory calculations. The high-quality Gr/h-BN stacks are proved to be perfect anode/protecting layers for high-performance organic light-emitting diode devices. In this regard, this work offers a brand-new route for the fast growth of Gr/h-BN heterostructures with practical scalability and high crystalline quality, thus should propel its wide applications in transparent electrodes, high-performance electronic devices, and energy harvesting/transition directions.