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Solid-state nanopores allow high-throughput single-molecule detection but identifying and even registering all translocating small molecules remain key challenges due to their high translocation speeds. We show here the same electric field that drives the molecules into the pore can be redirected to selectively pin and delay their transport. A thin high-permittivity dielectric coating on bullet-shaped polymer nanopores permits electric field leakage at the pore tip to produce a voltage-dependent surface field on the entry side that can reversibly edge-pin molecules. This mechanism renders molecular entry an activated process with sensitive exponential dependence on the bias voltage and molecular rigidity. This sensitivity allows us to selectively prolong the translocation time of short single-stranded DNA molecules by up to 5 orders of magnitude, to as long as minutes, allowing discrimination against their double-stranded duplexes with 97% confidence. Solid-state nanopores can serve as single molecule sensors for DNA sequencing, but the current designs suffer from fast DNA translocation so low detectivity. Wang et al. slow down and control the translocation speed by 5 orders of magnitude using a leakage field generated at the nanopore tip.

As most of the light and easy oil fields have been produced or are nearing their end-life, the emulsion stability is enhanced and water cut is increasing in produced fluid which have brought challenges to oil–water separation in onshore and offshore production trains. The conventional solution to these challenges includes a combination of higher chemical dosages, larger vessels and more separation stages, which often demands increased energy consumption, higher operating costs and larger space for the production facility. It is not always feasible to address the issues by conventional means, especially for the separation process on offshore platforms. Electrostatic coalescence is an effective method to achieve demulsification and accelerate the oil–water separation process. In this paper, a novel compact electrostatic coalescer with helical electrodes was developed and its performance on treatment of water-in-oil emulsions was investigated by experiments. Focused beam reflectance measurement (FBRM) was used to make real-time online measurements of water droplet sizes in the emulsion. The average water droplet diameters and number of droplets within a certain size range are set as indicators for evaluating the effect of coalescence. We investigated the effect of electric field strength, frequency, water content and fluid velocity on the performance of coalescence. The experimental results showed that increasing the electric field strength could obviously contribute to the growth of small water droplets and coalescence. The extreme value of electric field strength achieved in the high-frequency electric field was much higher than that in the power-frequency (50 Hz) electric field, which can better promote the growth of water droplets. The initial average diameters of water droplets increase with higher water content. The rate of increment in the electric field was also increased. Its performance was compared with that of the plate electrodes to further verify the advantages of enhancing electrostatic coalescence and demulsification with helical electrodes. The research results can provide guidance for the optimization and performance improvement of a compact electrocoalescer.

The Normalized Difference Vegetation Index (NDVI) is a fundamental metric for monitoring terrestrial ecosystem dynamics and assessing ecological responses to climate change. However, uncertainties persist across NDVI products, and a comprehensive assessment of their consistency is lacking. This study conducts a multi-faceted evaluation of three NDVI products, GIMMS V1.2 NDVI (NDVI3g+), PKU GIMMS NDVI (NDVIpku), and MODIS NDVI (NDVImod), to elucidate their performance across ecosystem applications. Our analysis encompasses a comparative analysis of NDVI values, trends, sensitivity to root-zone soil moisture (RSM), and performance in tracking photosynthesis benchmarked against solar-induced chlorophyll fluorescence (SIF). Our results reveal that NDVI3g+ deviates notably from NDVIpku and NDVImod over cold climates and Evergreen Broadleaf Forest (EBF). Additionally, NDVI3g+ exhibits significant global browning, in contrast to the significant greening observed for NDVIpku and NDVImod. Although their responses to RSM are generally uncertain, consistent positive responses appear in Drylands, with NDVImod showing the highest sensitivity. Additionally, the three NDVI products have high seasonality consistency with SIF, except over EBF, and NDVIpku and NDVI3g+ achieve the highest and lowest overall anomaly consistency with SIF, respectively. Furthermore, converting NDVI3g+, NDVIpku, and NDVImod to the corresponding kernel NDVIs improves seasonality consistency with SIF across 85% of the globe.

When a suspension of spherical or near-spherical particles passes through a constriction the particle volume fraction either remains the same or decreases. In contrast to these particulate suspensions, here we observe that an entangled fiber suspension increases its volume fraction up to 14-fold after passing through a constriction. We attribute this response to the entanglements among the fibers that allows the network to move faster than the liquid. By changing the fiber geometry, we find that the entanglements originate from interlocking shapes or high fiber flexibility. A quantitative poroelastic model is used to explain the increase in velocity and extrudate volume fraction. These results provide a new strategy to use fiber volume fraction, flexibility, and shape to tune soft material properties, e.g., suspension concentration and porosity, during delivery, as occurs in healthcare, three-dimensional printing, and material repair. When a suspension of particles passes through a constriction the particle volume fraction either decreases or remains the same. Pan et al. report that an entangled fiber suspension increases its volume fraction greater than a factor of 10 after passing through a constriction.

Osimertinib resistance is the main challenge in treating EGFR-mutant lung adenocarcinoma (LUAD). The role of N6-methyladenosine (m6A) modification of circular RNAs (circRNAs) in osimertinib-resistant LUAD remains largely unknown. We used MeRIP-seq and circRNA-seq to screen for potential circRNA candidates that influence osimertinib resistance. It was observed that circRNA LMNB1 (cLMNB1) increased the sensitivity of LUAD to osimertinib in vitro and in vivo. Mechanistically, cLMNB1 acts as a scaffold between fibroblast growth factor receptor 4 (FGFR4) and E3 ubiquitin-protein ligase CBL (c-Cbl), enhancing the ubiquitin-dependent degradation of FGFR4. Furthermore, METTL3 and YTHDF2 are responsible for increased m6A modification levels and decreased cLMNB1 expression in osimertinib-resistant LUAD without affecting its functions. Our findings demonstrate that cLMNB1, mediated by m6A modification, overcomes osimertinib resistance by destabilizing the FGFR4 protein in LUAD. cLMNB1 with an m6A modification site mutation (cLMNB1-mut) could be a promising nucleic acid drug, as it has shown excellent efficacy in osimertinib-resistant preclinical models of LUAD.

Current understanding of micropapillary (MP)‐subtype lung adenocarcinoma (LUAD) remains confined to biological activities and genomic landscapes. Unraveling the major regulatory programs underlying MP patterned malignancy offers opportunities to identify more feasible therapeutic targets for patients with MP LUAD. This study shows that patients with MP subtype LUAD have aberrant activation of the MYC pathway compared to patients with other subtypes. In vitro and xenograft mouse model studies reveal that MP pattern in malignancy cannot be solely due to aberrant MYC expression but requires the involvement of M2‐like macrophages. Excessively expressed MYC leads to the accumulation of M2‐like macrophages from the bone marrow, which secretes TGFβ, to induce the expression of FOSL2 in tumor cells, thereby remodeling chromatin accessibility at promoter regions of MP‐pattern genes to promote the MYC‐mediated de novo transcriptional regulation of these genes. Additionally, the MP‐pattern in malignancy can be effectively alleviated by disrupting the TGFβ‐FOSL2 axis. These findings reveal new functions for the M2‐like macrophage‐TGFβ‐FOSL2 axis in MYC‐overexpressing MP‐subtype LUAD, identifying targetable vulnerabilities in this pathway. Song et al. integrates an evaluating system to characterize malignancy of micropapillary (MP)‐pattern lung adenocarcinoma in vivo or in vitro. They have discovered that intrinsic MYC redundancy expression combined with extrinsic M2‐like macrophage jointly mediate MP‐pattern malignancy. Mechanically, M2‐like macrophages open MP‐pattern gene chromatin structure and recruit MYC to cooperatively regulate transcription.

Lidar and camera are essential sensors for environment perception in autonomous driving. However, fully fusing heterogeneous data from multiple sources remains a non-trivial challenge. As a result, 3D object detection based on multi-modal sensor fusion are often inferior to single-modal methods only based on Lidar, which indicates that multi-sensor machine vision still needs development. In this paper, we propose an adaptive fusion module based on cross-modal transformer block(AFMCT) for 3D object detection by utilizing a bidirectional enhancing strategy. Specifically, we first enhance image feature by extracting an attention-based point feature based on a cross-modal transformer block and linking them in a concatenation fashion, followed by another cross-modal transformer block acting on the enhanced image feature to strengthen the point feature with image semantic information. Extensive experiments operated on the 3D detection benchmark of the KITTI dataset reveal that our proposed structure can significantly improve the detection accuracy of Lidar-only methods and outperform the existing advanced multi-sensor fusion modules by at least 0.45%, which indicates that our method might be a feasible solution to improving 3D object detection based on multi-sensor fusion.

KRASG12C inhibitors exhibit conspicuous clinical response in KRASG12C‐mutant lung cancer, yet adaptive resistance, the rapid onset of intrinsic resistance, dampens their therapeutic success. Rational combination strategies could tackle this challenging problem. A high‐throughput screening of a pharmacological library with 423 compounds revealed that napabucasin, a signal transducer and activator of transcription 3 (STAT3) inhibitor, synergistically potentiated the growth inhibition effect of the KRASG12C inhibitor sotorasib in sensitive and resistant KRASG12C NSCLC cell lines. Functional assays further revealed that the coordinated targeting of KRAS with STAT3 improved the inhibitory effect on tumor growth and augmented the infiltration and activation of natural killer (NK) cells within the tumor microenvironment. Mechanistically, KRASG12C inhibition induced compensatory activation of STAT3, contingent on concomitant suppression of downstream ERK signaling, abrogated by napabucasin. Moreover, we unveiled and verified the binding site of phosphorylated STAT3 at the HLA‐B promoter, an inhibitor ligand for NK cells. Our study dissected an unknown mechanism of adaptive resistance to KRASG12C inhibitors, with the STAT3 activation sustaining the regrowth of tumor cells under KRAS inhibition and up‐regulating HLA‐B transcription to dampen the cytotoxicity of infiltrated NK cells. Napabucasin, combined with sotorasib, not only exerted tumor growth suppression via interruption of both KRAS and STAT3 pathways but also augmented the infiltration and activation of NK cells through down‐regulating inhibitory ligand HLA‐B transcription.

KRAS G12C inhibitors exhibit conspicuous clinical response in KRAS G12C ‐mutant lung cancer, yet adaptive resistance, the rapid onset of intrinsic resistance, dampens their therapeutic success. Rational combination strategies could tackle this challenging problem. A high‐throughput screening of a pharmacological library with 423 compounds revealed that napabucasin, a signal transducer and activator of transcription 3 (STAT3) inhibitor, synergistically potentiated the growth inhibition effect of the KRAS G12C inhibitor sotorasib in sensitive and resistant KRAS G12C NSCLC cell lines. Functional assays further revealed that the coordinated targeting of KRAS with STAT3 improved the inhibitory effect on tumor growth and augmented the infiltration and activation of natural killer (NK) cells within the tumor microenvironment. Mechanistically, KRAS G12C inhibition induced compensatory activation of STAT3, contingent on concomitant suppression of downstream ERK signaling, abrogated by napabucasin. Moreover, we unveiled and verified the binding site of phosphorylated STAT3 at the HLA‐B promoter, an inhibitor ligand for NK cells. Our study dissected an unknown mechanism of adaptive resistance to KRAS G12C inhibitors, with the STAT3 activation sustaining the regrowth of tumor cells under KRAS inhibition and up‐regulating HLA‐B transcription to dampen the cytotoxicity of infiltrated NK cells.

High-resolution bioanalysis has become increasingly important in recent years as the field of bioengineering advances to cellular and molecular level. Many new diagnostics technologies that can achieve highly sensitive and accurate biomolecular detection have been invented, such as digital polymerase chain reaction (dPCR), rapid sequencing and single molecule spectroscopy. All are supported by micro fluidic technologies that can partition and transport the molecules or their vehicles like vesicles and cells. These technologies, however, are still not widely adopted in the medical industry, due to their functionality and high-cost. For example, the commercial digital PCR system by Bio-Rad has a prohibitively high sample and equipment cost, because of its micro fluidic chip design and its precise micropump for droplet generation. Such cost issues render it noncompetitive to the existing real-time PCR system despite its superior quantification accuracy and sensitivity. Nanopore has been predominantly used for sequencing applications (Oxford Nanopore products) but its unique features also offer possibilities for precise identification of very few molecules using heat based phenomena such as thermophoresis and molecule hybridization. So far, these applications have not materialized due to a lack of control and understanding of a nanoscale hotspot inside a nanopore, although startups like NanoTemp Technologies have put larger-scale products on the market. Over 100 companies are developing Carbon Nanotube molecular sensor technologies but none has been commercially successful for the same cost issues in reagent, chip and equipment manufacturing. The edgling cellular 3-D printing, immunotherapy drug selection and tissue engineering industries will require bulk quantities of these molecular sensors, thus further elevating the need for low-cost but highly sensitive molecular diagnostics technologies.