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.

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.

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.

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.

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.

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.

Irreparable Defects Produced by the Patching of h-BN Frontiers on Strongly Interacting Re(0001) and Their Electronic Properties.

Clarifying the origin and the electronic properties of defects in materials is crucial since the mechanical, electronic and magnetic properties can be tuned by defects. Herein, we find that, for the growth of h-BN monolayer on Re(0001), the patching frontiers of different domains can be classified into three types, i.e., the patching of B- and N-terminated (B|N-terminated) frontiers, B|B-terminated frontiers and N|N-terminated frontiers, which introduce three types of defects, i.e., the "heart" shaped moiré-level defect, the nonbonded and bonded line defects, respectively. These defects were found to bring significant modulations to the electronic properties of h-BN, by introducing band gap reductions and in-gap states, comparing with perfect h-BN on Re(0001) with a band gap of ∼3.7 eV. The intrinsic binary composition nature of h-BN and the strong h-BN-Re(0001) interaction are proposed to be cooperatively responsible for the formation of these three types of defects. The former one provides different types of h-BN frontiers for domain patching. And the later one induces multinucleation but aligned growth of h-BN domains on Re(0001), thus precluding their subsequent coalescence to some extent. This work offers a deep insight into the categories of defects introduced from the patching growth of two-dimensional layered materials, as well as their electronic property modulation through the defect engineering.

Hexagonal Boron Nitride-Graphene Heterostructures: Synthesis and Interfacial Properties.

Research on in-plane and vertically-stacked heterostructures of graphene and hexagonal boron nitride (h-BN) have attracted intense attentions for energy band engineering and device performance optimization of graphene. In this review article, recent advances in the controlled syntheses, interfacial structures, and electronic properties, as well as novel device constructions of h-BN and graphene heterostructures are highlighted. Firstly, diverse synthesis approaches for in-plane h-BN and graphene (h-BN-G) heterostructures are reviewed, and their applications in nanoelectronics are briefly introduced. Moreover, the interfacial structures and electronic properties of h-BN-G heterojunctions are discussed, and a zigzag type interface is found to preferentially evolve at the linking edge of the two structural analogues. Secondly, several synthetic routes for the vertically-stacked graphene/h-BN (G/h-BN) heterostructures are also reviewed. The role of h-BN as perfect dielectric layers in promoting the device performance of graphene is presented. Finally, future research directions in the synthesis and application of such heterostructures are discussed.

Colletotrichum gloeosporioides sensu stricto Is a Pathogen of Leaf Anthracnose on Evergreen Spindle Tree (Euonymus japonicus).

The genus Colletotrichum is considered the eighth most important group of plant-pathogenic fungi in the world due to its scientific and economic importance. Colletotrichum spp. cause anthracnose disease in a wide range of economically important plants. Euonymus japonicus Thunb. (Celastraceae) is a broad-leaved evergreen tree that is widely planted in the parks and landscapes of China. An anthracnose occurs on E. japonicus in China but there has been a disagreement on the identity of the fungal pathogen. In this study, the fungal isolate HYCG2-3 was determined by Koch's postulates to be a pathogen on E. japonicus. Based on the morphological and molecular methods, isolate HYCG2-3 was identified as Colletotrichum gloeosporioides sensu stricto within the C. gloeosporioides species complex.

Grain Boundary Structures and Electronic Properties of Hexagonal Boron Nitride on Cu(111).

Grain boundaries (GBs) of hexagonal boron nitride (h-BN) grown on Cu(111) were investigated by scanning tunneling microscopy/spectroscopy (STM/STS). The first experimental evidence of the GBs composed of square-octagon pairs (4|8 GBs) was given, together with those containing pentagon-heptagon pairs (5|7 GBs). Two types of GBs were found to exhibit significantly different electronic properties, where the band gap of the 5|7 GB was dramatically decreased as compared with that of the 4|8 GB, consistent with our obtained result from density functional theory (DFT) calculations. Moreover, the present work may provide a possibility of tuning the inert electronic property of h-BN via grain boundary engineering.

Quasi-freestanding monolayer heterostructure of graphene and hexagonal boron nitride on Ir(111) with a zigzag boundary.

In-plane heterostructure of hexagonal boron nitride and graphene (h-BN-G) has become a focus of graphene research owing to its tunable bandgap and intriguing properties. We report herein the synthesis of a quasi-freestanding h-BN-G monolayer heterostructure on a weakly coupled Ir(111) substrate, where graphene and h-BN possess distinctly different heights and surface corrugations. An atomically sharp zigzag type boundary has been found to dominate the patching interface between graphene and h-BN, as evidenced by high-resolution Scanning tunneling microscopy investigation as well as density functional theory calculation. Scanning tunneling spectroscopy studies indicate that the graphene and h-BN tend to exhibit their own intrinsic electronic features near the patching boundary. The present work offers a deep insight into the h-BN-graphene boundary structures both geometrically and electronically together with the effect of adlayer-substrate coupling.

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.

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.

Modeling assessment for ammonium nitrogen recovery from wastewater by chemical precipitation.

Chemical precipitation to form magnesium ammonium phosphate (MAP) is an effective technology for recovering ammonium nitrogen (NH4(+)-N). In the present research, we investigated the thermodynamic modeling of the PHREEQC program for NH4(+)-N recovery to evaluate the effect of reaction factors on MAP precipitation. The case study of NH4(+)-N recovery from coking wastewater was conducted to provide a comparison. Response surface methodology (RSM) was applied to assist in understanding the relative significance of reaction factors and the interactive effects of solution conditions. Thermodynamic modeling indicated that the saturation index (SI) of MAP followed a polynomial function of pH. The SI of MAP increased logarithmically with the Mg2+/NH4+ molar ratio (Mg/N) and the initial NH4(+)-N concentration (CN), respectively, while it decreased with an increase in Ca2+/NH4+ and CO3(2-)/NH4+ molar ratios (Ca/N and CO3(2-)/N), respectively. The trends for NH4(+)-N removal at different pH and Mg/N levels were similar to the thermodynamic modeling predictions. The RSM analysis indicated that the factors including pH, Mg/N, C(N), Ca/N, (Mg/N)x (CO3(2-)/N), (pH)2, (Mg/N)2, and (C(N))2 were significant. Response surface plots were useful for understanding the interaction effects on NH4(+)-N recovery.

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.

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.

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.