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Word polysemy poses a formidable challenge in the semantic similarity task, especially for complex Chinese semantic information. However, most existing methods tend to emphasize information expansion, often overlooking the fact that the added information may be either irrelevant or only weakly correlated. In view of this, we propose a novel approach that fuses knowledge enhancement and context filtering to achieve self-selective semantic expansion. This approach, termed mutual-scenario-aware multimodal-enhanced representation learning (MuSAM), integrates information across multiple modalities. Specifically, we extend individual words within three modalities, and the extended information with weak correlation is filtered and denoised, to get the mutual-scenario extended information. The extended information with strong correlation in each modality will be fused to obtain the multimodal fusion representation vector of the word pair. Experimental evaluations conducted on five datasets underscore the superiority of the MuSAM model over state-of-the-art methods, showcasing a performance improvement ranging from a minimum of 4% to a maximum of 21%. Remarkably, our model is designed in a completely engineering manner, which can be applied to real scenarios directly without manual intervention.

Recently, with graph neural networks (GNNs) becoming a powerful technique for graph representation, many excellent GNN-based models have been proposed for processing heterogeneous graphs, which are termed Heterogeneous graph neural networks (HGNNs). However, existing HGNNs tend to aggregate information from either direct neighbors or those connected by short metapaths, thereby neglecting the higher-order information and global feature similarity information in heterogeneous graphs. In this paper, we propose a Multi-View Heterogeneous graph neural network (MV-HGNN) to aggregate these information. Firstly, two auxiliary views, specifically a global feature similarity view and a graph diffusion view, are generated from the original heterogeneous graph. Secondly, MV-HGNN performs two message-passing strategies to get the representation of different views. Subsequently, a transformer-based aggregator is used to get the semantic information. Subsequently, the representations of the three views are fused into a final composite representation. We evaluate our method on the node classification task over three commonly used heterogeneous graph datasets, and the results demonstrate that our proposed MV-HGNN significantly outperforms state-of-the-art baselines.

•Infection with drug-resistant bacteria decreased IMI and MEM PK/PD target attainment.•IMI concentration was associated with the ICU stay.•MEM concentration was not associated with ICU stay but associated with effectiveness.•Elevated doses of IMI and MEM should be given to patients with drug-resistant bacteria infection.

Pseudouridine (Ψ) is an abundant RNA modification that is present in and affects the functions of diverse non-coding RNA species, including rRNA, tRNA and small nuclear RNA. Ψ also exists in mammalian mRNA and probably exhibits functional roles; however, functional investigations of mRNA Ψ modifications in mammals have been hampered by the lack of a quantitative method that detects Ψ at base precision. We have recently developed bisulfite-induced deletion sequencing (BID-seq), which provides the community with a quantitative method to map RNA Ψ distribution transcriptome-wide at single-base resolution. Here, we describe an optimized BID-seq protocol for mapping Ψ distribution across cellular mRNAs, which includes fast steps in both library preparation and data analysis. This protocol generates highly reproducible results by inducing high deletion ratios at Ψ modification within diverse sequence contexts, and meanwhile displayed almost zero background deletions at unmodified uridines. When used for transcriptome-wide Ψ profiling in mouse embryonic stem cells, the current protocol uncovered 8,407 Ψ sites from as little as 10 ng of polyA+RNA input. This optimized BID-seq workflow takes 5 days to complete and includes four main sections: RNA preparation, library construction, next-generation sequencing (NGS) and data analysis. Library construction can be completed by researchers who have basic knowledge and skills in molecular biology and genetics. In addition to the experimental protocol, we provide BID-pipe (https://github.com/y9c/pseudoU-BIDseq), a user-friendly data analysis pipeline for Ψ site detection and modification stoichiometry quantification, requiring only basic bioinformatic and computational skills to uncover Ψ signatures from BID-seq data.

RNA molecules are not merely a combination of four bases of A, C, G, and U. Chemical modifications occur in almost all RNA species and play diverse roles in gene expression regulation. The abundant cellular RNAs, such as ribosomal RNA (rRNA) and transfer RNA (tRNA), are known to have the highest density of RNA modifications, which exert critical functions in rRNA and tRNA biogenesis, stability, and subsequent translation. In recent years, modifications on low-abundance RNA species in mammalian cells, such as messenger RNA (mRNA), regulatory noncoding RNA (ncRNA), and chromatin-associated RNA (caRNA), have been shown to contain multiple different chemical modifications with functional significance.

For the analysis in the acidic environment, the influence of different dosage of nanometre calcium carbonate on concrete durability, firstly, nano calcium carbonate concrete with different dosages was prepared using P·O42.5 cement, coarse and fine aggregates, and nano calcium carbonate as materials. Secondly, according to the ratio of 4,000 mL water, 5.6 mL SO42-solution and 3.2 g hydrooxidation, sulphate solution was prepared as an acidic erosion environment. Then, under the action of acid erosion, the durability of nanometre calcium carbonate concrete was analysed from five aspects: compressive strength, chloride ion penetration resistance, mass loss rate, erosion depth and dynamic elastic modulus. It is found that the durability of concrete specimens is the best when the dosage of nanometre calcium carbonate is 1.0%, and the durability of concrete specimens can be affected if the dosage is less or too much.

N1-methyl adenosine (m1A) is a widespread RNA modification present in tRNA, rRNA, and mRNA. m1A modification sites in tRNAs are evolutionarily conserved and its formation on tRNA is catalyzed by methyltransferase TRMT61A and TRMT6 complex. m1A promotes translation initiation and elongation. Due to its positive charge under physiological conditions, m1A can notably modulate RNA structure. It also blocks Watson–Crick–Franklin base-pairing and causes mutation and truncation during reverse transcription. Several misincorporation-based high-throughput sequencing methods have been developed to sequence m1A. In this study, we introduce a reduction-based m1A sequencing (red-m1A-seq). We report that NaBH4reduction of m1A can improve the mutation and readthrough rates using commercially available RT enzymes to give a better positive signature, while alkaline-catalyzed Dimroth rearrangement can efficiently convert m1A to m6A to provide good controls, allowing the detection of m1A with higher sensitivity and accuracy. We applied red-m1A-seq to sequence human small RNA, and we not only detected all the previously reported tRNA m1A sites, but also new m1A sites in mt-tRNAAsn-GTTand 5.8S rRNA.

Cavitating flows are dominated by large gradients of physical properties and quantities containing complicated interfacial structures and lots of multi-scale eddies that need to be accurately characterized using a high-resolution mesh. The present work, within OpenFOAM, proposes an effective modeling framework using the large eddy simulation (LES) approach along with the volume of fluid (VOF) method to simulate the two-phase flow system with applying the Schnerr-Sauer model to calculate the mass-transfer rate between water and vapor. The adaptive mesh refinement (AMR) which is a powerful tool for allocating high-resolution grids only to the region of the greatest concern is adopted for improving the solution of interfacial structures. The effect of grid size is firstly investigated and the time-averaged quantities are verified against the experimental data, and then simulations of cavitating flows are successfully achieved to precisely characterize the features of cavitation with automatically and dynamically refining the mesh. As the refinement only takes place in the interfacial region, high-precision simulations can be achieved within limited computational resources, and the method shows promising prospects for modeling of the multi-scale, time-critical and computationally intensive cavitating flows.

N1-methyladenosine (m1A) is a widespread modification in all eukaryotic, many archaeal, and some bacterial tRNAs. m1A is generally located in the T loop of cytosolic tRNA and between the acceptor and D stems of mitochondrial tRNAs; it is involved in the tertiary interaction that stabilizes tRNA. Human tRNA m1A levels are dynamically regulated that fine-tune translation and can also serve as biomarkers for infectious disease. Although many methods have been used to measure m1A, a PCR method to assess m1A levels quantitatively in specific tRNAs has been lacking. Here we develop a templated-ligation followed by a qPCR method (TL-qPCR) that measures m1A levels in target tRNAs. Our method uses the SplintR ligase that efficiently ligates two tRNA complementary DNA oligonucleotides using tRNA as the template, followed by qPCR using the ligation product as the template. m1A interferes with the ligation in specific ways, allowing for the quantitative assessment of m1A levels using subnanogram amounts of total RNA. We identify the features of specificity and quantitation for m1A-modified model RNAs and apply these to total RNA samples from human cells. Our method enables easy access to study the dynamics and function of this pervasive tRNA modification.

Surface plasmon polaritons and phonon polaritons offer a means of surpassing the diffraction limit of conventional optics and facilitate efficient energy storage, local field enhancement and highsensitivity sensing, benefiting from their subwavelength confinement of light. Unfortunately, losses severely limit the propagation decay length, thus restricting the practical use of polaritons. While optimizing the fabrication technique can help circumvent the scattering loss of imperfect structures, the intrinsic absorption channel leading to heat production cannot be eliminated. Here, we utilize synthetic optical excitation of complex frequency with virtual gain, synthesized by combining the measurements made at multiple real frequencies, to compensate losses in the propagations of phonon polaritons with dramatically enhanced propagation distance. The concept of synthetic complex frequency excitation represents a viable solution to the loss problem for various applications including photonic circuits, waveguiding and plasmonic/phononic structured illumination microscopy.

With the development of nanoscience and technology, it has become an essential part of various research directions, changing our way of life, such as advanced accurate manufacturing in nanotechnology that facilitates reducing chip sizes, progress made in health care via nanoscience that provides hope to patients, and so on. As the nation’s flagship institution of nanoscience and technology in China, the National Center for Nanoscience and Technology, China (NCNST), established in December 2003, has played a crucial role in promoting cutting-edge technologies in the field of nanoscience and expediting interdisciplinary fusion. With a strong research team and state-of-the-art research equipment, NCNST currently carries out frontier research and world-class technology innovation, including nanosystems and hierarchical fabrication, biological effects of nanomaterials and nanosafety, standardization and measurements for nanotechnology, as well as theoretical simulations. Serving as one of the most prestigious institutions in nanoscience and nanotechnology in China, NCNST will continue to foster impactful international cooperation, cultivate young talents, and boost inspiring innovation.

Morning commute problem has always been concerned by researchers in transportation research field. For the bottleneck existing in the road network between home and school, this paper studies the household travel with different kinds of activities, i.e., home-school-home trip and home-school-workplace trip. Individuals just send their children to school and then go home, which is named school travel. Individuals need to send their children to school firstly and then go to work, which is named household travel. Firstly, according to the proportions of two types of travelers and school-work start time difference, the possible equilibrium cases are solved and the conditions for the occurrence of each case are revealed. Different from the traditional bottleneck model with a unique equilibrium traffic pattern, the mixed travel case has six possible equilibrium traffic patterns. Secondly, the cost of traveler is analyzed for all possible equilibrium traffic patterns. Result shows that equilibrium trip costs of two types of travelers are more sensitive to the number of travelers in that class than the number in another class in all possible equilibrium cases. Finally, the influence of school-work start time difference on the total travel cost is discussed. Result shows that the total system travel cost can be reduced by appropriately adjusting the difference of school-work start time.

Light confinement in nanostructures produces an enhanced light–matter interaction that enables a vast range of applications including single-photon sources, nanolasers and nanosensors. In particular, nanocavity-confined polaritons display a strongly enhanced light–matter interaction in the infrared regime. This interaction could be further boosted if polaritonic modes were moulded to form whispering-gallery modes; but scattering losses within nanocavities have so far prevented their observation. Here, we show that hexagonal BN nanotubes act as an atomically smooth nanocavity that can sustain phonon-polariton whispering-gallery modes, owing to their intrinsic hyperbolic dispersion and low scattering losses. Hyperbolic whispering-gallery phonon polaritons on BN nanotubes of ～4 nm radius (sidewall of six atomic layers) are characterized by an ultrasmall nanocavity mode volume (Vm≈ 10–10λ03at an optical wavelength λ0≈ 6.4 μm) and a Purcell factor (Q/Vm) as high as 1012. We posit that BN nanotubes could become an important material platform for the realization of one-dimensional, ultrastrong light–matter interactions, with exciting implications for compact photonic devices.

We report a highly enhanced light extraction from a top emission organic light emitting diode with little image blurring. Integration of a high refractive index micro lens array on the top of the transparent indium zinc oxide top electrode of a green and blue OLED shows a significant EQE gain of 16% and 8%, respectively.

N6-methyladenosine (m6A) is the most abundant mRNA modification in mammalian cells, regulating many physiological processes. Here we describe a method for base-resolution, quantitative m6A sequencing in the whole transcriptome. The enzyme and small-molecule cofactor used in this protocol are prepared by recombinant protein expression and organic synthesis, respectively. Then the library can be prepared from various types of RNA samples using a ligation-based strategy, with m6A modifications being labeled by the enzyme and cofactor. Detailed instructions on ensuing data analysis are also included in this protocol. The method generates highly reproducible results, uncovering 31,233–129,263 sites using as little as 2 ng of poly A+RNA. These identified sites correspond well with previous m6A profiling results, covering over 65% of peaks detected by the antibody-based approaches. Compared with other currently available methods, this method can be applied to various types of biological samples, including fresh and frozen tissues as well as formalin-fixed paraffin-embedded samples, providing a quantitative method to uncover new insights into m6A biology. The protocol requires basic expertise in molecular biology, recombinant protein expression and organic synthesis. The whole protocol can be done in 15 days, with the library preparation taking 5 days.

N-Heterocyclic carbenes (NHCs) are established ligands for metal complexes and surfaces. Here we go beyond monomeric NHCs and report on the synthesis of NHC polymers on gold surfaces, consisting of ballbot-type repeating units bound to single Au adatoms. We designed, synthesized and deposited precursors containing different halogens on gold surfaces under ultrahigh vacuum. Conformational, electronic and charge transport properties were assessed by combining low-temperature scanning tunneling microscopy, non-contact atomic force microscopy, X-ray photoelectron spectroscopy, first-principles calculations and reactive force field simulations. The confirmed ballbot-type nature of the NHCs explains the high surface mobility of the incommensurate NHC polymers, which is prerequisite for their desired spatial alignment. The delicate balance between mobility and polymerization rate allows essential parameters for controlling polymer directionality to be derived. These polymers open up new opportunities in the fields of nanoelectronics, surface functionalization and catalysis.

N6-methyladenosine (m6A) methylation can be deposited on chromatin-associated RNAs (caRNAs) by the RNA methyltransferase complex (MTC) to regulate chromatin state and transcription. However, the mechanism by which MTC is recruited to distinct genomic loci remains elusive. Here we identify RBFOX2, a well-studied RNA-binding protein, as a chromatin factor that preferentially recognizes m6A on caRNAs. RBFOX2 can recruit RBM15, an MTC component, to facilitate methylation of promoter-associated RNAs. RBM15 also physically interacts with YTHDC1 and recruits polycomb repressive complex 2 (PRC2) to the RBFOX2-bound loci for chromatin silencing and transcription suppression. Furthermore, we found that this RBFOX2/m6A/RBM15/YTHDC1/PRC2 axis plays a critical role in myeloid leukaemia. Downregulation of RBFOX2 notably inhibits survival/proliferation of acute myeloid leukaemia cells and promotes their myeloid differentiation. RBFOX2 is also required for self-renewal of leukaemia stem/initiation cells and acute myeloid leukaemia maintenance. Our study presents a pathway of m6A MTC recruitment and m6A deposition on caRNAs, resulting in locus-selective chromatin regulation, which has potential therapeutic implications in leukaemia.

Methods for the precise detection and quantification of RNA modifications are critical to uncover functional roles of diverse RNA modifications. The internal m7G modification in mammalian cytoplasmic tRNAs is known to affect tRNA function and impact embryonic stem cell self-renewal, tumorigenesis, cancer progression, and other cellular processes. Here, we introduce m7G-quant-seq, a quantitative method that accurately detects internal m7G sites in human cytoplasmic tRNAs at single-base resolution. The efficient chemical reduction and mild depurination can almost completely convert internal m7G sites into RNA abasic sites (AP sites). We demonstrate that RNA abasic sites induce a mixed variation pattern during reverse transcription, including G → A or C or T mutations as well as deletions. We calculated the total variation ratio to quantify the m7G modification fraction at each methylated site. The calibration curves of all relevant motif contexts allow us to more quantitatively determine the m7G methylation level. We detected internal m7G sites in 22 human cytoplasmic tRNAs from HeLa and HEK293T cells and successfully estimated the corresponding m7G methylation stoichiometry. m7G-quant-seq could be applied to monitor the tRNA m7G methylation level change in diverse biological processes.

Control over charge carrier density provides an efficient way to trigger phase transitions and modulate the optoelectronic properties of materials. This approach can also be used to induce topological transitions in the optical response of photonic systems. Here we report a topological transition in the isofrequency dispersion contours of hybrid polaritons supported by a two-dimensional heterostructure consisting of graphene and α-phase molybdenum trioxide. By chemically changing the doping level of graphene, we observed that the topology of polariton isofrequency surfaces transforms from open to closed shapes as a result of doping-dependent polariton hybridization. Moreover, when the substrate was changed, the dispersion contour became dominated by flat profiles at the topological transition, thus supporting tunable diffractionless polariton propagation and providing local control over the optical contour topology. We achieved subwavelength focusing of polaritons down to 4.8% of the free-space light wavelength by using a 1.5-μm-wide silica substrate as an in-plane lens. Our findings could lead to on-chip applications in nanoimaging, optical sensing and manipulation of energy transfer at the nanoscale.

Sensors have emerged as indispensable analytical tools across a wide range of important fields, encompassing environmental monitoring, food safety, and public health. They facilitate early disease diagnosis, personalized medicine, and rapid detection of toxic agents. However, detecting trace molecules remains a significant challenge. Surface-enhanced infrared absorption (SEIRA) based on plasmonic nanostructures, particularly graphene, has emerged as a promising approach to enhance sensing sensitivity. While graphene-based SEIRA offers advantages such as high sensitivity and active tunability, intrinsic molecular damping weakens the interaction between vibrational modes and plasmons. Here, we demonstrate ultrahigh-sensitive molecular sensing based on synthesized complex-frequency waves (CFW). Our experiment shows that CFW can amplify the molecular signals (silk protein monolayer) detected by graphene-based sensor by at least an order of magnitude and can be universally applied to molecular sensing in different phases. Our approach is highly scalable and can facilitate the investigation of light-matter interactions, enabling diverse potential applications in fields such as optical spectroscopy, biomedicine and pharmaceutics.

Future terawatt-scale deployment of flow batteries will require substantial capital cost reduction, particularly low-cost electrolytes and hydrocarbon ion exchange membranes. However, integration of hydrocarbon membranes with novel flow battery chemistries in commercial-scale stacks is yet to be demonstrated. Here, we report the pilot-scale synthesis and roll-to-roll manufacturing of sulfonated poly(ether ether ketone) (SPEEK) membranes and demonstrate their high hydroxide conductivity and chemical stability in kW-scale alkaline-based flow batteries. The membrane was integrated in flow battery stacks with power up to 4,000 W, which demonstrated a high energy efficiency of 85.5% operated at 80 mA cm−2and long-term stable operation over 800 h as well as substantial cost savings relative to Nafion membranes. This work illustrates a potential pathway for manufacturing and upscaling of next-generation cost-effective flow batteries based on low-cost hydrocarbon membranes developed in the past decades to translate to large-scale applications for grid energy storage.

Quantitative and base-resolution sequencing methods are critical to investigations of the biological functions of diverse RNA modifications. These methods may also be employed for clinical studies and clinical applications in the future. In this In Focus article, we introduce and discuss the development of Bisulfite-Induced Deletion sequencing (BID-seq) for quantitatively detecting mRNA pseudouridine (Ψ) modifications at base resolution.

Various optical crystals possess permittivity components of opposite signs along different principal directions in the mid-infrared regime, exhibiting exotic anisotropic phonon resonances. Such materials with hyperbolic polaritons—hybrid light–matter quasiparticles with open isofrequency contours—feature large-momenta optical modes and wave confinement that make them promising for nanophotonic on-chip technologies. So far, hyperbolic polaritons have been observed and characterized in crystals with high symmetry including hexagonal (boron nitride), trigonal (calcite) and orthorhombic (α-MoO3or α-V2O5) crystals, where they obey certain propagation patterns. However, lower-symmetry materials such as monoclinic crystals were recently demonstrated to offer richer opportunities for polaritonic phenomena. Here, using scanning near-field optical microscopy, we report the direct real-space nanoscale imaging of symmetry-broken hyperbolic phonon polaritons in monoclinic CdWO4crystals, and showcase inherently asymmetric polariton excitation and propagation associated with the nanoscale shear phenomena. We also introduce a quantitative theoretical model to describe these polaritons that leads to schemes to enhance crystal asymmetry via the damping loss of phonon modes. Ultimately, our findings show that polaritonic nanophotonics is attainable using natural materials with low symmetry, favouring a versatile and general way to manipulate light at the nanoscale.

Metalloenzymes have critical roles in a wide range of biological processes and are directly involved in many human diseases; hence, they are considered as important targets for therapeutic intervention. The specific characteristics of metal ion(s)-containing active sites make exploitation of metal-binding pharmacophores (MBPs) critical to inhibitor development targeting metalloenzymes. This Perspective focuses on boron-containing MBPs, which display unique binding modes with metalloenzyme active sites, particularly via mimicking native substrates or tetrahedral transition states. The design concepts regarding boron-containing MBPs are highlighted through the case analyses on five distinct classes of clinically relevant nucleophilic metalloenzymes from medicinal chemistry perspectives. The challenges (e.g., selectivity) faced by some boron-containing MBPs and possible strategies (e.g., bioisosteres) for metalloenzyme inhibitor transformation are also discussed.

The major drawbacks of P-glycoprotein (P-gp) inhibitors at the clinical stage make the development of new P-gp inhibitors challenging and desirable. In this study, we reported our structure–activity relationship studies of 4-indolyl quinazoline, which led to the discovery of a highly effective and orally active P-gp inhibitor, YS-370. YS-370effectively reversed multidrug resistance (MDR) to paclitaxel and colchicine in SW620/AD300 and HEK293T-ABCB1 cells. YS-370bound directly to P-gp, did not alter expression or subcellular localization of P-gp in SW620/AD300 cells, but increased the intracellular accumulation of paclitaxel. Furthermore, YS-370stimulated the P-gp ATPase activity and had moderate inhibition against CYP3A4. Significantly, oral administration of YS-370in combination with paclitaxel achieved much stronger antitumor activity in a xenograft model bearing SW620/Ad300 cells than either drug alone. Taken together, our data demonstrate that YS-370is a promising P-gp inhibitor capable of overcoming MDR and represents a unique scaffold for the development of new P-gp inhibitors.

We aimed to assess the associations of large artery stenosis (LAS) and cerebral small vessel disease (CSVD) with the risk of ischemic stroke and to investigate their respective and combined contributions. In the prospective population-based Shunyi Study, 1,082 stroke-free participants aged 55.9±9.1 years were included. Participants were followed for incident stroke throughout the study period (2013–2019). Total small vessel disease score was used to measure CSVD burden. Cervico-cerebral large artery stenosis was evaluated via brain magnetic resonance angiography and carotid ultrasound. We estimated the risk of ischemic stroke in relation to LAS and CSVD with Cox regression models. During a mean follow-up of 4.2 years, 34 participants (3.1%) experienced at least one ischemic stroke. Severe LAS (≥50% stenosis versus no stenosis: HR=3.27 (95% CI: 1.31–8.18)) and high CSVD burden (total small vessel disease score 2–4 versus 0 point: HR=12.73 (4.83–33.53)) were associated with increased stroke risk independently. In multivariate models, CSVD burden (7.72%) explained a larger portion of the variation in stroke risk than severity of LAS (3.49%). Our findings identified that both LAS and CSVD were associated with future ischemic stroke in asymptomatic subjects, while those with high CSVD burden deserve more attention in primary prevention of stroke.

As a rare malformation of the female reproductive system, Herlyn‐Werner‐Wunderlich syndrome (HWWS) was categorized into 3 classifications. It was recommended recently that, on the basis of the past classification, cervicovaginal atresia without communicating uteri should be newly added as classification 4. The surgical intervention will differ by type. To better optimize patient counseling as well as the preoperative evaluation and planning, our objective was to describe the ultrasound characteristics of each type of HWWS, including the new type. From January 1995 to November 2015, 37 cases of HWWS in with complete ultrasound information confirmed by surgery in the Peking Union Medical College Hospital were reviewed. We analyzed their ultrasound features, including hematometra, hematocervix, hematocolpos, and an ovarian chocolate cyst. All of the ultrasound images of the 37 patients showed uterus didelphys with ipsilateral renal agenesis. Compared with the other 3 types, classification 4 showed distinctive ultrasound characteristics. Most cases of classification 4 showed hematometra (5 of 7 [71.4%]) and an ipsilateral ovarian chocolate cyst (6 of 7 [85.7%]), which was significantly higher than in the other 3. A rudimentary uterine horn was also a distinctive characteristic in this type. Meanwhile none of the classification 4 cases showed hematocervix or hydrocolpos, which were common signs of the other 3. According to this new classification criteria for HWWS, ultrasound characteristics of the new classification 4 differ from the others. As classification 4 was suggested to have a different surgical option, we should pay attention to its ultrasound characteristics, which might help in providing more information about the treatment and prognosis to the gynecologist. Access the CME test hereand search by article title.

Polaritons in anisotropic materials result in exotic optical features, which can provide opportunities to control light at the nanoscale1–10. So far these polaritons have been limited to two classes: bulk polaritons, which propagate inside a material, and surface polaritons, which decay exponentially away from an interface. Here we report a near-field observation of ghost phonon polaritons, which propagate with in-plane hyperbolic dispersion on the surface of a polar uniaxial crystal and, at the same time, exhibit oblique wavefronts in the bulk. Ghost polaritons are an atypical non-uniform surface wave solution of Maxwell’s equations, arising at the surface of uniaxial materials in which the optic axis is slanted with respect to the interface. They exhibit an unusual bi-state nature, being both propagating (phase-progressing) and evanescent (decaying) within the crystal bulk, in contrast to conventional surface waves that are purely evanescent away from the interface. Our real-space near-field imaging experiments reveal long-distance (over 20 micrometres), ray-like propagation of deeply subwavelength ghost polaritons across the surface, verifying long-range, directional and diffraction-less polariton propagation. At the same time, we show that control of the out-of-plane angle of the optic axis enables hyperbolic-to-elliptic topological transitions at fixed frequency, providing a route to tailor the band diagram topology of surface polariton waves. Our results demonstrate a polaritonic wave phenomenon with unique opportunities to tailor nanoscale light in natural anisotropic crystals.

The experience of a female political prisoner is presented. Basic courtesies were afforded her during her imprisonment and professionalism was maintained by the jail administrators in the disposal of their management and interrogation duties. This led her to re-evaluate her attitude towards her incarceration and towards the emerging changes in the Communist Party of China.

Members of the mammalian AlkB family are known to mediate nucleic acid demethylation1,2. ALKBH7, a mammalian AlkB homologue, localizes in mitochondria and affects metabolism3, but its function and mechanism of action are unknown. Here we report an approach to site-specifically detect N1-methyladenosine (m1A), N3-methylcytidine (m3C), N1-methylguanosine (m1G) and N2,N2-dimethylguanosine (m22G) modifications simultaneously within all cellular RNAs, and discovered that human ALKBH7 demethylates m22G and m1A within mitochondrial Ile and Leu1 pre-tRNA regions, respectively, in nascent polycistronic mitochondrial RNA4–6. We further show that ALKBH7 regulates the processing and structural dynamics of polycistronic mitochondrial RNAs. Depletion of ALKBH7 leads to increased polycistronic mitochondrial RNA processing, reduced steady-state mitochondria-encoded tRNA levels and protein translation, and notably decreased mitochondrial activity. Thus, we identify ALKBH7 as an RNA demethylase that controls nascent mitochondrial RNA processing and mitochondrial activity.

Vanadium flow batteries (VFBs) have drawn considerable attention as an emerging technology for large-scale energy storage systems (ESSs). One of the pivotal challenges is the availability of eligible ion exchange membranes (ICMs) that provide high ion selectivity, proton conductivity, and stability under rigorous condition. Herein, a ‘side-chain-type’ strategy has been employed to fabricate highly stable phenolphthalein-based cardo poly(arylene ether ketone)s (PAEKs) membrane with low area resistance (0.058 Ω cm2), in which flexible alkyl spacers effectively alleviated inductive withdrawing effect from terminal ion exchange groups thus enabling a stable backbone. The assembled VFBs based on PAEKs bearing pendent alkyl chain terminated with quaternary ammonium (Q-PPhEK) demonstrated an energy efficiency above 80% over 700 cycles at 160 mA/cm2. Such a remarkable results revealed that the side-chain-type strategy contributed to enhancing the ICMs stability in strong oxidizing environment, meanwhile, more interesting backbones would be woken with this design engaging in stable ICMs for VFBs.

Oxindoles and β-lactams are attractive structural motifs because of their unique biological importance. However, the fusion of the two moieties featuring 3,3′-spirocyclic scaffolds is a challenging task in organic synthesis. Herein we designed a novel type of oxindole-based azaoxyallyl cation synthons, which could readily participate in the [3 + 1] cyclization with sulfur ylides. With this protocol, a collection of 3,3-spiro[β-lactam]-oxindoles were facilely produced in up to 94% yield with perfect diastereoselectivity.

Phonon polaritons enable light confinement at deep subwavelength scales, with potential technological applications, such as subdiffraction imaging, sensing and engineering of spontaneous emission. However, the trade-off between the degree of confinement and the excitation efficiency of phonon polaritons prevents direct observation of these modes in monolayer hexagonal boron nitride (h-BN), where they are expected to reach ultrahigh confinement. Here, we use monochromatic electron energy-loss spectroscopy (about 7.5?meV energy resolution) in a scanning transmission electron microscope to measure phonon polaritons in monolayer h-BN, directly demonstrating the existence of these modes as the phonon Reststrahlen band (RS) disappears. We find phonon polaritons in monolayer h-BN to exhibit high confinement (>487 times smaller wavelength than that of light in free space) and ultraslow group velocity down to about 10-5c. The large momentum compensation provided by electron beams additionally allows us to excite phonon polaritons over nearly the entire RS band of multilayer h-BN. These results open up a broad range of opportunities for the engineering of metasurfaces and strongly enhanced light–matter interactions.

Graphene on SiO2enables fabrication of Si-technology-compatible devices, but a transfer of these devices from other substrates and direct growth have severe limitations due to a relatively small grain size or device-contamination. Here, we show an efficient, transfer-free way to integrate centimeter-scale, single-crystal graphene, of a quality suitable for electronic devices, on an insulating SiO2film. Starting with single-crystal graphene grown epitaxially on Ru(0001), a SiO2film is grown under the graphene by stepwise intercalation of silicon and oxygen. Thin (∼1 nm) crystalline or thicker (∼2 nm) amorphous SiO2has been produced. The insulating nature of the thick amorphous SiO2is verified by transport measurements. The device-quality of the corresponding graphene was confirmed by the observation of Shubnikov-de Haas oscillations, an integer quantum Hall effect, and a weak antilocalization effect within in situfabricated Hall bar devices. This work provides a reliable platform for applications of large-scale, high-quality graphene in electronics.

Aqueous organic-based flow batteries are increasingly receiving attention owing to their appealing traits of high safety and low cost. An economic and high-performance membrane is always regarded as the heart of the batteries. Here, we introduce a cost-effective, homemade porous membrane with high performance for alkaline quinone-based flow batteries. The membrane is constituted by highly stable poly(ether sulfone) (PES) and sulfonated poly(ether ether ketone) (SPEEK) that serves dual functions of (1) adjusting the membrane microstructure and (2) endowing the membrane with a charge trait. Benefiting from the well-tuned structure and charge property of the membrane, a high ion selectivity and transport of OH–with much higher mobility serving as the primary charge-balancing ion can be realized. By employing alkaline alizarin red (ARS)/ferro-ferricyanide flow battery as the platform, a battery delivers a coulombic efficiency (CE) of 98.28% and an energy efficiency (EE) of 85.81% at 40 mA cm–2, which is higher than that of the battery with a Nafion 212 membrane (CE ∼ 99.19%, EE ∼ 84.60%), however, with much lower cost. The successful application of homemade porous membrane may provide a new strategy to engineer and fabricate membranes with high efficiency for alkaline quinone-based flow batteries and further decrease the batteries’ cost.

Transcriptome-wide mapping of N6-methyladenosine (m6A) at base resolution remains an issue, impeding our understanding of m6A roles at the nucleotide level. Here, we report a metabolic labeling method to detect mRNA m6A transcriptome-wide at base resolution, called ‘m6A-label-seq’. Human and mouse cells could be fed with a methionine analog, Se-allyl-l-selenohomocysteine, which substitutes the methyl group on the enzyme cofactor SAM with the allyl. Cellular RNAs could therefore be metabolically modified with N6-allyladenosine (a6A) at supposed m6A-generating adenosine sites. We pinpointed the mRNA a6A locations based on iodination-induced misincorporation at the opposite site in complementary DNA during reverse transcription. We identified a few thousand mRNA m6A sites in human HeLa, HEK293T and mouse H2.35 cells, carried out a parallel comparison of m6A-label-seq with available m6A sequencing methods, and validated selected sites by an orthogonal method. This method offers advantages in detecting clustered m6A sites and holds promise to locate nuclear nascent RNA m6A modifications.

In this paper we introduce a thermally evaporated optical regulating layer (ORL) to adjust the optical cavity length of solution top‐emission devices. ORL has high conductivity in the thickness range up to 1500 Å, which can meet the requirements of large‐sized printing OLED product process. Interface improvement layer (IIL) is further introduced to improve the carrier injection and enhance efficiency. Compared with the bottom device, the efficiency of optimized device increases by 2.0 times, while the voltage does not increase. Compared with the traditional solution top‐emission device, which has a narrow process window, the efficiency of optimized device increases by 15% and the voltage decreases by 0.8 V.

Quartz crystal microbalance (QCM) has attracted extensive attention in the field of biological analysis and detection because of its high sensitivity, fast response, real-time measurement, good operability, and low-cost production. However, to detect the trace amounts of small molecules, such as low-concentration saliva glucose under physiological conditions, is still a major challenge. Herein, the surface of a QCM chip was coated with a poly(boric acid)-based hydrogel using UV pressing-assisted polymerization to obtain a simple device for glucose detection. The designed QCM sensor shows a record-low detection limit of glucose (3 mg/L at pH 7.5), which is ∼30 times lower than that of sensors fabricated by conventional surface initiation–spin coating. The outperformance of the poly(boric acid) hydrogel-coated QCM sensor is probably due to the uniform and compact microstructure, as well as the presence of sufficient glucose-binding sites resulting from the hydrogel coating generated by UV pressing-assisted polymerization. This method provides an important solution to detect the trace amounts of small organic molecules or ions and has the potential to push forward the practical applications of QCM sensors.

Monolayer transition-metal dichalcogenides show strong optical nonlinearity with great potential for various emerging applications. Here we demonstrate the gate-tunable interband resonant four-wave mixing and sum-frequency generation in monolayer MoS2. Up to 80% modulation depth in four-wave mixing is achieved when the generated signal is resonant with the A exciton at room temperature, corresponding to an effective third-order optical nonlinearity |χ(3)eff| tuning from (∼12.0 to 5.45) × 10–18m2/V2. The tunability of the effective second-order optical nonlinearity |χ(2)eff| at 440 nm C-exciton resonance wavelength is also demonstrated from (∼11.6 to 7.40) × 10–9m/V with sum-frequency generation. Such a large tunability in optical nonlinearities arises from the strong excitonic charging effect in monolayer transition-metal dichalcogenides, which allows for the electrical control of the interband excitonic transitions and thus nonlinear optical responses for future on-chip nonlinear optoelectronics.

DNA 5-methylcytosine (5mC)-specific mapping has been hampered by severe DNA degradation and the presence of 5-hydroxymethylcytosine (5hmC) using the conventional bisulfite sequencing approach. Here, we present a 5mC-specific whole-genome amplification method (5mC-WGA), with which we achieved 5mC retention during DNA amplification from limited input down to 10 pg scale with limited interference from 5hmC signals, providing DNA 5mC methylome with high reproducibility and accuracy.

The naturally occurring nucleobase 5-methylcytosine (mC) and its oxidized derivatives 5-hydroxymethylcytosine (hmC), 5-formylcytosine (fC), and 5-carboxylcytosine (caC) play important roles in epigenetic regulation and, along with cytosine (C), represent nucleobases currently implicated in the active cytosine demethylation pathway. Despite considerable interest in these modified bases, their impact on the thermodynamic stability of double-stranded DNA (dsDNA) remains ambiguous and their influence on hybridization kinetics and dynamics is even less well-understood. To address these unknowns, we employ steady-state and time-resolved infrared spectroscopy to measure the influence of cytosine modification on the thermodynamics and kinetics of hybridization by assessing the impact on local base pairing dynamics, shifts in the stability of the duplex state, and changes to the hybridization transition state. Modification with mC leads to more tightly bound base pairing below the melting transition and stabilizes the duplex relative to canonical DNA, but the free energy barrier to dehybridization at physiological temperature is nevertheless reduced slightly. Both hmC and fC lead to an increase in local base pair fluctuations, a reduction in the cooperativity of duplex melting, and a lowering of the dissociation barrier, but these effects are most pronounced when the 5-position is formylated. The caC nucleobase demonstrates little impact on dsDNA under neutral conditions, but we find that this modification can dynamically switch between C-like and fC-like behavior depending on the protonation state of the 5-position carboxyl group. Our results provide a consistent thermodynamic and kinetic framework with which to describe the modulation of the physical properties of double-stranded DNA containing these modified nucleobases.

Applications associated with nucleobase protonation events are grounded in their fundamental impact on DNA thermodynamics, structure, and hybridization dynamics. Of the canonical nucleobases, N3 protonation of cytosine (C) is the most widely utilized in both biology and nanotechnology. Naturally occurring C derivatives that shift the N3 pKaintroduce an additional level of tunability. The epigenetic nucleobase 5-carboxylcytosine (caC) presents a particularly interesting example since this derivative forms Watson–Crick base pairs of similar stability and displays pH-dependent behavior over the same range as the canonical nucleobase. However, the titratable group in caC corresponds to the exocyclic carboxyl group rather than N3, and the implications of these divergent protonation events toward DNA hybridization thermodynamics, kinetics, and base pairing dynamics remain poorly understood. Here, we study the pH dependence of these physical properties using model oligonucleotides containing C and caC with FTIR and temperature-jump IR spectroscopy. We demonstrate that N3 protonation of C completely disrupts duplex stability, leading to large shifts in the duplex/single-strand equilibrium, a reduction in the cooperativity of melting, and an acceleration in the rate of duplex dissociation. In contrast, while increasing 5-carboxyl protonation in caC-containing duplexes induces an increase in base pair fluctuations, the DNA duplex can tolerate substantial protonation without significant perturbation to the duplex/single-strand equilibrium. However, 5-carboxyl protonation has a large impact on hybridization kinetics by reducing the transition state free energy. Our thermodynamic and kinetic analysis provides new insight on the impact of two divergent protonation mechanisms in naturally occurring nucleobases on the biophysical properties of DNA.

A quite novel surface profilometry is proposed, which adopts a single optical grating projection setup with a small projection angle. The height distribution of the measured surface is retrieved by calculating the coordinates of the intersection between the projecting ray and the observing sight line. While the position of the observing point in the deformed fringe pattern can be detected by fringe optical flow. The relationship between optical flow and the height distribution of the tested surface is established. Simulations and some primary experiment results are completed to prove that the proposed method is feasible to measure a complex surface. The main advantage of the proposed method is obviously that the height distribution of the measured surface can be obtained directly without phase-to-height transformation.

Chemical modifications to messenger RNA are increasingly recognized as a critical regulatory layer in the flow of genetic information, but quantitative tools to monitor RNA modifications in a whole-transcriptome and site-specific manner are lacking. Here we describe a versatile platform for directed evolution that rapidly selects for reverse transcriptases that install mutations at sites of a given type of RNA modification during reverse transcription, allowing for site-specific identification of the modification. To develop and validate the platform, we evolved the HIV-1 reverse transcriptase against N1-methyladenosine (m1A). Iterative rounds of selection yielded reverse transcriptases with both robust read-through and high mutation rates at m1A sites. The optimal evolved reverse transcriptase enabled detection of well-characterized m1A sites and revealed hundreds of m1A sites in human mRNA. This work develops and validates the reverse transcriptase evolution platform, and provides new tools, analysis methods and datasets to study m1A biology.

5-Methylcytosine (mC) is an epigenetic mark that is written by methyltransferases, erased through passive and active mechanisms, and impacts transcription, development, diseases including cancer, and aging. Active DNA demethylation involves TET-mediated stepwise oxidation of mC to 5-hydroxymethylcytosine, 5-formylcytosine (fC), or 5-carboxylcytosine (caC), excision of fC or caC by thymine DNA glycosylase (TDG), and subsequent base excision repair. Many elements of this essential process are poorly defined, including TDG excision of caC. To address this problem, we solved high-resolution structures of human TDG bound to DNA with cadC (5-carboxyl-2′-deoxycytidine) flipped into its active site. The structures unveil detailed enzyme–substrate interactions that mediate recognition and removal of caC, many involving water molecules. Importantly, two water molecules contact a carboxylate oxygen of caC and are poised to facilitate acid-catalyzed caC excision. Moreover, a substrate-dependent conformational change in TDG modulates the hydrogen bond interactions for one of these waters, enabling productive interaction with caC. An Asn residue (N191) that is critical for caC excision is found to contact N3 and N4 of caC, suggesting a mechanism for acid-catalyzed base excision that features an N3-protonated form of caC but would be ineffective for C, mC, or hmC. We also investigated another Asn residue (N140) that is catalytically essential and strictly conserved in the TDG-MUG enzyme family. A structure of N140A-TDG bound to cadC DNA provides the first high-resolution insight into how enzyme–substrate interactions, including water molecules, are impacted by depleting the conserved Asn, informing its role in binding and addition of the nucleophilic water molecule.

An optimal single-photon source should deterministically deliver one, and only one, photon at a time, with no trade-off between the source’s efficiency and the photon indistinguishability. However, all reported solid-state sources of indistinguishable single photons had to rely on polarization filtering, which reduced the efficiency by 50%, fundamentally limiting the scaling of photonic quantum technologies. Here, we overcome this long-standing challenge by coherently driving quantum dots deterministically coupled to polarization-selective Purcell microcavities. We present two examples: narrowband, elliptical micropillars and broadband, elliptical Bragg gratings. A polarization-orthogonal excitation–collection scheme is designed to minimize the polarization filtering loss under resonant excitation. We demonstrate a polarized single-photon efficiency of 0.60?±?0.02 (0.56?±?0.02), a single-photon purity of 0.975?±?0.005 (0.991?±?0.003) and an indistinguishability of 0.975?±?0.006 (0.951?±?0.005) for the micropillar (Bragg grating) device. Our work provides promising solutions for truly optimal single-photon sources combining near-unity indistinguishability and near-unity system efficiency simultaneously.

The hot deformation behavior of AA5083 aluminum alloy was studied using isothermal compression tests with a Gleeble–3500 thermal simulator at strain rate of 0.01–10 s−1and at temperature of 300–500 °C. The experimental results indicate that dynamic recrystallization (DRX) tends to occur at high strain rates and temperatures, and therefore the flow stress is decreased. To predict the flow behavior under different deformation conditions, a strain-compensated constitutive equation based on Arrhenius-type equation and Zener–Hollomon parameters was proposed. The flow stresses obtained from the constitutive equation are consistent with the experimental results. The average absolute relative error is only 4.52% over the entire experimental range, indicating that the proposed constitutive equation exhibits high prediction precision for the hot deformation behavior of AA5083 aluminum alloy.

Pseudouridine (Ψ) is a widespread RNA modification found in various RNA species, including rRNA, tRNA, snRNA, mRNA, and long noncoding RNA (lncRNA). Understanding the function of Ψ in these RNA types requires a robust method for the detection and quantification of the Ψ level at single-nucleotide resolution. A previously used method utilizes Ψ labeling by N-cyclohexyl-N′-β-(4-methylmorpholinium)ethylcarbodiimide (CMC). The quantification of Ψ is based on the stop ratio after reverse transcription. However, the use of CMC followed by strong alkaline treatment causes severe RNA degradation, often requiring a large amount of RNA. The removal of CMC and recovery of RNA by ethanol precipitation are also time-consuming. Here, we introduce a Bisulfite Incorporation Hindered ligation-based method (BIHIND), which can detect and quantify Ψ sites on rRNA, mRNA, and noncoding RNA. BIHIND can be coupled with quantitative PCR (BIHIND-qPCR) for quantitative detection of Ψ fraction at individual modification sites, as well as with next-generation sequencing (BIHIND-seq) for high-throughput sequencing of Ψ without requiring reverse transcription. We validated the robustness of BIHIND with the elucidation of Ψ dynamics following pseudouridine synthase depletion.

In this protocol, we present a facile nanoscale thermal mapping technique for electronic devices by use of atomic force microscopy and a phase change material Ge2Sb2Te5. We describe steps for Ge2Sb2Te5thin film coating, Ge2Sb2Te5temperature calibration, thermal mapping by varying heater power, and thermal mapping by varying heating time. The protocol can be applied for resolving surface temperatures of various operational microelectronic devices with a nanoscale precision.