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Sugar phosphates are important metabolic intermediates in organisms and play a vital role in energy and central carbon metabolism. Profiling of sugar phosphates is of great significance but full of challenges due to their high structural similarity and low sensitivities in liquid chromatography (LC)-mass spectrometry (MS). In this study, we developed a novel stable isotope chemical labeling combined with the reversed-phase (RP)LC-MS method for ultrasensitive determination of sugar phosphates at the single-cell level. By chemical derivatization with 2-(diazo-methyl)

To evaluate the bone regeneration capacity of Zn-2Ag-0.04Mg alloy scaffold in vivo. Zn, Zn-2Ag and Zn-2Ag-0.04Mg scaffolds were implanted in the femur of New Zealand rabbits, and the degradation of the scaffolds and the regeneration of the bone were observed at 6th week and 6th month. Two-dimensional and three-dimensional micro-CT results showed the new bone in Zn-2Ag-0.04Mg alloy scaffold group was significant more than Zn scaffold group, the bone volume in Zn-2Ag-0.04Mg was higher. Moreover, the osteogenic index in the Zn-2Ag-0.04Mg alloy scaffold group was also higher than Zn scaffold group. At 6th month, the scaffold of Zn-2Ag-0.04Mg was smaller than Zn group or Zn-2Ag group. HE staining of the liver, kidney, and heart did not detect any abnormalities, confirmed the biosafety of the Zn-2Ag-0.04Mg alloy scaffold. The Zn-Ag-0.04Mg alloy scaffold exhibits good biocompatibility and bone regeneration ability in vivo.

The emergence of intelligent applications produces the demand for computing. How to reduce the computation pressure in mobile edge computing (MEC) under massive computation demand is an urgent problem to solve. Specifically, the allocation of heterogeneous resources including communication resources and computing resources needs to be optimized simultaneously. From the perspective of joint optimization of channel allocation, device-to-device (D2D) pairing, and offloading mode, this paper studies the multi-user computing task offloading problem in device-enhanced MEC. The objective is maximizing the aggregate offloading benefits, i.e., the tradeoff between delay and energy consumption, of all compute-intensive users in the network. By introducing game theory, the problem is modeled as a multi-user computation task offloading game, which is proved to be an exact potential game (EPG) with at least one pure-strategy Nash equilibrium (NE) solution. In order to find a desirable solution, this paper proposes a better reply based distributed multi-user computation task offloading algorithm (BR-DMCTO). Simulation results show that the proposed offloading mechanism can improve the benefit of users, and verify the effectiveness and convergence of the proposed algorithm.

Hermansky-Pudlak syndrome (HPS) is characterized by defects of multiple tissue-specific lysosome-related organelles (LROs), typically manifesting with oculocutaneous albinism or ocular albinism, bleeding tendency, and in some cases with pulmonary fibrosis, inflammatory bowel disease or immunodeficiency, neuropsychological disorders. Eleven HPS subtypes in humans and at least 15 subtypes in mice have been molecularly identified. Current understanding of the underlying mechanisms of HPS is focusing on the defective biogenesis of LROs. Compelling evidences have shown that HPS protein-associated complexes (HPACs) function in cargo transport, cargo recycling, and cargo removal to maintain LRO homeostasis. Further investigation on the molecular and cellular mechanism of LRO biogenesis and secretion will be helpful for better understanding of its pathogenesis and for the precise intervention of HPS.

BACKGROUND: The ability of circulating tumor cells (CTCs) to identify lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) could improve pathological diagnosis and the selection of treatments for non-small cell lung cancer (NSCLC). Previous studies have shown that deoxyribonucleic acid (DNA) methylation exhibits cell and tissue specificity. Thus, we aimed to explore the methylation status of CTCs in LUAD and LUSC and identify the potential biomarkers. METHODS: We first analyzed Infinium 450K methylation profiles obtained from The Cancer Genome Atlas and Gene Expression Omnibus. We then performed whole-genome sequencing of CTCs in tumor and matched normal lung tissues and white blood cells from 6 NSCLC patients. RESULTS: The bioinformatics analysis revealed a NSCLC-specific DNA methylation marker panel, which could accurately distinguish between LUAD and LUSC with high diagnostic accuracy. The whole-genome sequencing of CTCs in NSCLC patients also showed 100% accuracy for distinguishing between LUAD and LUSC based on the CTC methylation profiles. To investigate the function of CTCs, we further analyzed similar and different methylation profiles between the CTCs and their primary tumors, and found very high similarities between the CTCs and their primary tumor tissues, indicating that these cells inherit information from primary tumors. However, the CTCs also displayed some characteristics that differed to those of primary tumor tissues, which suggest that CTCs acquire some unique characteristics after migrating from the primary tumor; these characteristics may partly explain the ability of tumor cells to evade immune surveillance. CONCLUSIONS: Our findings provide insights into the potential use of CTCs in the pathological classification of NSCLC patients. Our findings also show how CTC primary tumor inheritance and CTC evolution affect metastasis and immune escape.

Potyviral coat protein (CP) is involved in the replication and movement of potyviruses. However, little information is available on the roles of CP-coding sequence in potyviral infection. Here, we introduced synonymous substitutions to the codon C574G575C576 coding conserved residue arginine at position 192 (R192) of tobacco vein banding mosaic virus (TVBMV) CP. Substitution of the codon C574G575C576 to A574G575A576 or A574G575G576, but not C574G575A576, C574G575T576, or C574G575G576, reduced the replication, cell-to-cell movement, and accumulation of TVBMV in Nicotiana benthamiana plants, suggesting that C574 was critical for replication of TVBMV. Nucleotides 531 to 576 of the TVBMV CP-coding sequence were predicted to form a stem-loop structure, in which four consecutive C-G base pairs (C576-G531, C532-G575, C574-G533, and C534-G573) were located at the stem. Synonymous substitutions of R178-codon C532G533C534 to A532G533A534 and A532G533G534, but not C532G533A534, C532G533T534, or C532G533G534, reduced the replication levels, cell-to-cell, and systemic movement of TVBMV, suggesting that C532 was critical for TVBMV replication. Synonymous substitutions disrupting base pairs C576-G531 and C534-G573 did not affect viral accumulation. After three serial-passage inoculations, the accumulation of spontaneous mutant viruses was restored, and codons A532G533A534, A532G533G534, A574G575A576, or A574G575G576 of mutants were each separately changed to C532G533A534, C532G533G534, C574G575A576, or C574G575G576. Synonymous mutation of R178 and R192 also reduced viral accumulation in N. tabacum plants. Therefore, we concluded that the two consecutive C532-G575 and C574-G533 base pairs played critical roles in TVBMV replication via maintaining the stability of the stem-loop structures formed by nucleotides 531 to 576 of the CP-coding sequence.

In the 5 years since the fourth edition of the WHO Classification of Tumors of the Central Nervous System (CNS) (revised) was released, the development of targeted sequencing and omics technology has helped researchers in the field of neuro-oncology to identify some new tumor types in clinical practice, as well as a series of genetic parameters related to tumor occurrence and development, poor prognosis, treatment response, etc. These findings not only provide basic knowledge for the classification of glioma, but also promote the progress of the treatment of gliomas. As a revolution in cancer treatment, immunotherapy has become a promising strategy since the pioneering discovery of lymphatics in the CNS. The advancement and clinical application of immunotherapy have strengthened the demand for accurate classification of glioma. In June 2021, the WHO and the International Agency for Research on Cancer (IARC) published the fifth edition of the WHO Classification of Tumors of the CNS. The fifth edition focuses on advancing the role of genetic parameters in the classification of glioma and divides glioma into more biologically and molecularly defined entities, with better natural history characteristics, and introduced new tumor types and subtypes, especially in the pediatric population. Most importantly, these updated classifications will enable clinicians to better assess the prognosis and formulate the optimal treatment of gliomas.

Visual quality of images captured by mobile devices is often inferior to that of images captured by a Digital Single Lens Reflex (DSLR) camera. This paper presents a novel generative adversarial network-based mobile image enhancement method, referred to as MIEGAN. It consists of a novel multi-module cascade generative network and a novel adaptive multi-scale discriminative network. The multi-module cascade generative network is built upon a two-stream encoder, a feature transformer, and a decoder. In the two-stream encoder, a luminance-regularizing stream is proposed to help the network focus on low-light areas. In the feature transformation module, two networks effectively capture both global and local information of an image. To further assist the generative network to generate the high visual quality images, a multi-scale discriminator is used instead of a regular single discriminator to distinguish whether an image is fake or real globally and locally. To balance the global and local discriminators, an adaptive weight allocation is proposed. In addition, a contrast loss is proposed, and a new mixed loss function is developed to improve the visual quality of the enhanced images. Extensive experiments on the popular DSLR photo enhancement dataset and MIT-FiveK dataset have verified the effectiveness of the proposed MIEGAN.

Objective: CircCCDC66 is involved in cancer progression, but its role in osteoarthritis (OA) remains unknown. This study was carried out to explore the biological role of circCCDC66 in OA and its underlying mechanism. Methods: The expression levels of miR-3622b-5p and circCCDC66 in OA cartilage tissues were detected by qRT-PCR. Cell Counting Kit-8 (CCK8) and flow cytometry were used to detect the chondrocyte viability and apoptosis. The expression of chondrocyte inflammatory factors (IL-6 and TNF-α) was measured by ELISA. The target genes of circCCDC66 and miR-3622b-5p were analyzed by bioinformatics analysis and luciferase reporter gene assay. The relationship between circCCDC66 and miR-3622b-5p was analyzed by bioinformatics analysis and luciferase reporter gene assay. Results: It was found that circCCDC66 expression in OA cartilage tissues was upregulated. CircCCDC66 overexpression inhibited proliferation and promoted apoptosis of chondrocytes and increased IL-6 and TNF-α levels in chondrocytes. miR-3622b-5p was predicted to be a downstream target gene of circCCDC66, and circCCDC66 overexpression inhibited miR-3622b-5p expression in chondrocytes. Moreover, miR-3622b-5p expression was downregulated in OA cartilage tissues. miR-3622b-5p overexpression increased chondrocyte proliferation, inhibited chondrocyte apoptosis, and enhanced the expression of IL-6 and TNF-α in chondrocytes. In addition, circCCDC66 overexpression enhanced SIRT3 expression in chondrocytes, while miR-3622b-5p overexpression inhibited SIRT3 expression in chondrocytes. Conclusion: CircCCDC66 promoted OA chondrocyte apoptosis by regulating the miR-3622b-5p/SIRT3 axis. CircCCDC66 may be a new therapeutic target of OA.

The discovery of 5-hydroxymethylcytosine (5hmC) in mammalian genomes is a landmark in epigenomics study. Similar to 5-methylcytosine (5mC), 5hmC is viewed as a critical epigenetic modification. Deciphering the functions of 5hmC necessitates the location analysis of 5hmC in genomes. Here, we proposed an engineered deaminase-mediated sequencing (EDM-seq) method for the quantitative detection of 5hmC in DNA at single-nucleotide resolution. This method capitalizes on the engineered human apolipoprotein B mRNA-editing catalytic polypeptide-like 3A (A3A) protein to produce differential deamination activity toward cytosine, 5mC, and 5hmC. In EDM-seq, the engineered A3A (eA3A) protein can deaminate C and 5mC but not 5hmC. The original C and 5mC in DNA are deaminated by eA3A to form U and T, both of which are read as T during sequencing, while 5hmC is resistant to deamination by eA3A and is still read as C during sequencing. Therefore, the remaining C in the sequence manifests the original 5hmC. By EDM-seq, we achieved the quantitative detection of 5hmC in genomic DNA of lung cancer tissue. The EDM-seq method is bisulfite-free and does not require DNA glycosylation or chemical treatment, which offers a valuable tool for the straightforward and quantitative detection of 5hmC in DNA at single-nucleotide resolution.

The first total synthesis of two macrocyclic Lycopodium alkaloids, huperserratines A and B, in 12 steps.

Multifunctional phototherapy nanoagents for imaging-guided synergistic photothermal therapy (PTT) and photodynamic therapy (PDT) are highly desirable in the field of solid tumor therapy. Nevertheless, the tumor microenvironment (TME) inherently associated with hypoxia significantly hampers the photodynamic effect of these multifunctional nanoagents. Herein, Pd nanocubes coated with an ultrathin Pt shell were prepared and further conjugated with fluorescein labeled and thiol functionalized polyethylene glycol (FITC-PEG-SH) (denoted as Pd@Pt-PEG). The deposition of a Pt shell on Pd nanocubes not only enhances the photothermal performance, exhibiting excellent hyperthermia outcomes and impressive photothermal (PT) imaging quality, but also leads to the formation of singlet oxygen (1O2) induced by plasmonic excitation. In the meantime, the catalytic activity of the Pt layer is enhanced by electronic coupling and the plasmonic effect, which induces the decomposition of endogenous overexpressed hydrogen peroxide (H2O2) in tumors to generate O2 for conquering TME and augmenting 1O2 generation for efficacious tumor cell apoptosis. The modification of FITC-PEG-SH improves the biocompatibility and provides outstanding fluorescence (FL) imaging properties. Upon NIR laser irradiation, Pd@Pt-PEG allows in situ O2 generation and dual-mode imaging-guided synergistic PTT/PDT that effectively kills hypoxic tumor cells, which makes it a promising nanotherapeutic agent for enhanced tumor therapy.

Genome-wide mapping of N4-methylcytosine (4mC) at single-base resolution with APOBEC3A-mediated deamination sequencing (4mC-AMD-seq).

This paper uses a combination of EDXRF and LA-ICP-MS to analyse the chemical components including major elements and REE composition of the accompanying celadon from four different periods of tomb at the Yutu Hill burial complex on the Xunyang city site for sourcing their provenance. The combination of the two analytical methods not only provides additional data and information to explore the provenance of the accompanying celadon in the burials, but also validates the data’s accuracy. A comparison with the chemical composition of the products from several kiln sites producing celadon revealed that burials from the Eastern Han period (25–220 A.D) to the Tang dynasty (618–907 A.D) included celadon from the Hongzhou kiln, indicating the connection between the Xunyang city site and the Hongzhou kiln during these two periods. In addition, the REE composition of the accompanying celadon in tombs from the Six Dynasties (222–589 A.D) and the Sui dynasty (581–618 A.D) is very similar to that of Yue kiln celadon, despite their strikingly different appearance and shape. This paper deduces, based on the previous distribution of Yue kiln products in the Jiangxi region, that only the upper classes collected Yue kiln products during the initial period of their entry into Jiangxi during the Jin dynasty (266–420 A.D), but that during the later period of the Six Dynasties, the commoner classes also began to collect Yue kiln products.

Drug use is a worldwide issue, and how to treat it is even a greater challenge. It is important for drug dependences to receive interventions and treatments in time. Before receiving treatments, an effective screening or diagnosis assessment is necessary, and patients should have an assessment to understand the severity of drug use–related disorders. For more than 40 years, the instruments to assess the severity of drug dependence have been developed well, and different quantitative methods can cover almost every field of the symptoms in different periods and stages of drug addiction. This chapter reviews more than 20 drug dependence screening and diagnosis assessments and different types of treatments. These quantitative assessments can provide drug dependences a comprehensive diagnosis of their drug use–related disorders. The treatments should be designed for different level of drug dependence.

Background The use of machine learning has the potential to estimate the probability of a second classification event more accurately than traditional statistical methods, and few previous studies on predicting new fractures after osteoporotic vertebral compression fractures (OVCFs) have focussed on this point. The aim of this study was to explore whether several different machine learning models could produce better predictions than logistic regression models and to select an optimal model. Methods A retrospective analysis of 529 patients who underwent percutaneous kyphoplasty (PKP) for OVCFs at our institution between June 2017 and June 2020 was performed. The patient data were used to create machine learning (including decision trees (DT), random forests (RF), support vector machines (SVM), gradient boosting machines (GBM), neural networks (NNET), and regularized discriminant analysis (RDA)) and logistic regression models (LR) to estimate the probability of new fractures occurring after surgery. The dataset was divided into a training set (75%) and a test set (25%), and machine learning models were built in the training set after ten cross-validations, after which each model was evaluated in the test set, and model performance was assessed by comparing the area under the curve (AUC) of each model. Results Among the six machine learning algorithms, except that the AUC of DT [0.775 (95% CI 0.728–0.822)] was lower than that of LR [0.831 (95% CI 0.783–0.878)], RA [0.953 (95% CI 0.927–0.980)], GBM [0.941 (95% CI 0.911–0.971)], SVM [0.869 (95% CI 0.827–0.910), NNET [0.869 (95% CI 0.826–0.912)], and RDA [0.890 (95% CI 0.851–0.929)] were all better than LR. Conclusions For prediction of the probability of new fracture after PKP, machine learning algorithms outperformed logistic regression, with random forest having the strongest predictive power. Graphical Abstract

The Catellani reaction, i.e., the Pd/NBE catalysis, has been evolved into a versatile approach to multisubstituted arenes via the ortho-functionalization/ipso-termination process of a haloarene. Despite significant advances over the past 25 years, this reaction still suffered from an intrinsic limitation in the substitution pattern of the aryl halide, referred to as “ortho-constraint”. When an ortho substituent is absent, the haloarene substrate often fails to undergo effective mono ortho-functionalization process, and either ortho-difunctionalization products or NBE-embedded byproducts predominate. To tackle this challenge, structurally-modified NBEs (smNBEs) have been developed, which were proved effective for the mono ortho-aminative, -acylative, and -arylative Catellani reactions of ortho-unsubstituted haloarenes. However, the smNBE strategy is incompetent for solving the ortho-constraint in Catellani reactions with ortho-alkylation, and to date there lacks a general solution to this challenging but synthetically useful transformation. Recently, our group developed the Pd/olefin catalysis, in which an unstrained hybrid cycloolefin ligand served as a covalent catalytic module to enable the ortho-alkylative Catellani reaction without an NBE mediator. In this work, we show that this chemistry could afford a new solution to ortho-constraint in the Catellani reaction. A functionalized hybrid cycloolefin ligand bearing an amide group as the internal base was designed, which allowed for mono ortho-alkylative Catellani reaction of iodoarenes suffering from ortho-constraint before. Mechanistic study revealed that the newly designed ligand is capable of both accelerating the C−H activation and inhibiting side reactions, which accounts for its superior performance. The present work showcased the uniqueness of the Pd/olefin catalysis as well as the power of rational ligand design in metal catalysis.

Injuries to the central nervous system (CNS) often lead to severe neurological dysfunction and even death. However, there are still no effective measures to improve functional recovery following CNS injuries. Optogenetics, an ideal method to modulate neural activity, has shown various advantages in controlling neural circuits, promoting neural remapping, and improving cell survival. In particular, the emerging optogenetics has exhibited promising therapeutic methods for CNS injuries. In this review, we introduced the light-sensitive proteins and light stimulation system which are important components of optogenetic technology in detail and summarized the development trends. Meanwhile, we constructed a comprehensive picture of the current application of optogenetics in CNS injuries and highlighted recent advances for the treatment and functional recovery of neurological deficits. Finally, we discussed the therapeutic challenges and prospective uses of optogenetics therapy by photostimulation/photoinhibition modalities that would be suitable for clinical applications.

Background Hepatocellular Carcinoma (HCC) is one of the major malignant tumors threatening human health. Lenvatinib resistance seriously restricts the efficacy of HCC, but the specific mechanism is not clear. Circular RNA (circRNA) plays an important role in the regulation of tumor drug resistance. Methods Key circRNA was screened by bioinformatics methods, and further identified by relevant validation experiments and HCC tissue samples. And, circRNA was evaluated as a diagnostic and prognostic marker for HCC progression at the clinical level. After then, through in vivo and in vitro experiments, the specific mechanism of the circRNA on the progression of HCC and lenvatinib resistance was explored at the molecular level. Results circRNA_0009792 (circRNA-mTOR) was highly expressed in HCC and is closely related to the prognosis of patients, which has good diagnostic value and clinical significance. In vivo and in vitro experiments showed that circRNA-mTOR could promote the progression of hepatocellular carcinoma and promote lenvatinib resistance by improving the stemness of HCC cells. Mechanismly, circRNA-mTOR could affect RNA-binding protein (PSIP1) nuclear translocation by specifically binding to it, and then which enhanced the stemness of HCC cells through PSIP1/c-Myc axis, hence promoting the progression of HCC and lenvatinib resistance. And furthermore, circRNA-mTOR at least partially induce lenvatinib resistance by increasing the expression of EGFR in HCC. Conclusions In conclusion, this study suggests that circRNA-mTOR can affect PSIP1/c-myc axis nuclear translocation, to make progress of HCC and the maintenance of steness of liver cancer cell to aggravate lenvatinib resistance, And partially increased EGFR over-expression to making chemo-resistance worse. CircRNA-mTOR has the potential to be a biomarker for the diagnosis and prognosis of HCC. This study provides a certain experimental basis for the targeted drug therapy of HCC, and puts forward new ideas, new insights and new methods in understanding the occurrence and development of HCC, and it is of great significance to seek new markers and targets for the diagnosis and treatment of HCC and reduce drug resistance.

The present study aimed to explore the targets and mechanism of Mailuo Shutong Pills(MSP) in the treatment of ischemic stroke by network pharmacology, and verify the key targets through molecular docking and animal experiment, so as to provide a theoretical basis for the clinical application of MSP. The main chemical ingredients of MSP were obtained by searching against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and relevant literature. The potential targets of the ingredients of MSP in treating ischemic stroke were obtained from SwissTargetPrediction and DisGeNET. Protein-protein interaction(PPI) network was analyzed in STRING and plotted in Cytoscape. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were carried out with DAVID. Molecular docking was simulated to determine the binding activity of active ingredients to key targets in AutoDock Vina. The mouse model of ischemic stroke was established. The mice were classified into a sham group, a model group, and an MSP group. After the administration, cerebral infarction volume was detected by 2,3,5-triphenyltetrazoliumchloride(TTC) staining, and Western blot was performed to determine the levels of phosphatidylinositol 3-kinase(PI3 K), protein kinase B(AKT), nuclear factor-κB(NF-κB) and their phosphorylated proteins. A total of 222 ingredients of MSP were screened out, including beta-sitosterol, quercetin, licochalcone B, and lupiwighteone, which acted on 701 targets. Totally 1 079 targets associated with ischemic stroke were retrieved, among which 192 common targets were shared by MSP and ischemic stroke. The key targets included AKT1, phosphatidylinositol 3-kinase catalytic subunit alpha(PIK3 CA), phosphatidylinositol 3-kinase regulatory subunit 1(PIK3 R1), and nuclear factor-κB p65 subunit(RELA), which were mainly involved in PI3 K/AKT, tumor necrosis factor(TNF), and NF-κB signaling pathways. The results of molecular docking revealed that PI3 K, AKT1, and RELA had good binding ability to the active ingredients of MSP. The animal experiment results showed that compared with the model group, MSP decreased cerebral infarction volume, down-regulated the expression of p-NF-κB, and up-regulated the expression of p-PI3 K and p-AKT in mouse brain. In summary, the active ingredients in MSP may treat cerebral injury by activating PI3 K/AKT signaling pathway and inhibiting NF-κB signaling pathway.

Current quantum devices impose strict connectivity constraints on quantum circuits, making circuit transformation necessary before running logical circuits on real quantum devices. Many quantum circuit transformation (QCT) algorithms have been proposed in the past several years. This paper proposes a novel method for constructing benchmark circuits and uses these benchmark circuits to evaluate state-of-the-art QCT algorithms, including TKET from Cambridge Quantum Computing, Qiskit from IBM, and three academic algorithms SABRE, SAHS, and MCTS. These benchmarks have known near-optimal transformation costs and thus are called QUEKNO (for quantum examples with known near-optimality). Compared with QUEKO benchmarks designed by Tan and Cong (2021), which all have zero optimal transformation costs, QUEKNO benchmarks are more general and can provide a more faithful evaluation for QCT algorithms (like TKET) which use subgraph isomorphism to find the initial mapping. Our evaluation results show that SABRE can generate transformations with conspicuously low average costs on the 53-qubit IBM Q Rochester and Google's Sycamore in both gate size and depth objectives., Comment: 14 pages, 7 figures, code and benchmarks available at https: //github.com/ebony72/quekno

Ongoing advances in superconductors continue to revolutionize technology thanks to the increasingly versatile and robust availability of lossless supercurrent. In particular high supercurrent density can lead to more efficient and compact power transmission lines, high-field magnets, as well as high-performance nanoscale radiation detectors and superconducting spintronics. Here, we report the discovery of an unprecedentedly high superconducting critical current density (17 MA/cm2 at 0 T and 7 MA/cm2 at 8 T) in 1T'-WS2, exceeding those of all reported two-dimensional superconductors to date. 1T'-WS2 features a strongly anisotropic (both in- and out-of-plane) superconducting state that violates the Pauli paramagnetic limit signaling the presence of unconventional superconductivity. Spectroscopic imaging of the vortices further substantiates the anisotropic nature of the superconducting state. More intriguingly, the normal state of 1T'-WS2 carries topological properties. The band structure obtained via angle-resolved photoemission spectroscopy and first-principles calculations points to a Z2 topological invariant. The concomitance of topology and superconductivity in 1T'-WS2 establishes it as a topological superconductor candidate, which is promising for the development of quantum computing technology.

Oxide heterostructures have shown rich physics phenomena, particularly in the conjunction of exotic insulator-metal transition (IMT) at the interface between polar insulator LaAlO3 and non-polar insulator SrTiO3 (LaAlO3/SrTiO3). Polarization catastrophe model has suggested an electronic reconstruction yielding to metallicity at both the interface and surface. Another scenario is the occurrence of surface oxygen vacancy at LaAlO3 (surface-Ov), which has predicted surface-to-interface charge transfer yielding metallic interface but insulating surface. To clarify the origin of IMT, one should probe surface-Ov and the associated electronic structures at both the surface and the buried interface simultaneously. Here, using low-angle resonant soft X-ray scattering (LA-RSXS) supported with first-principles calculations, we reveal the co-existence of the surface-Ov state and the interface conducting state only in conducting LaAlO3/SrTiO3 (001) films. Interestingly, both the surface-Ov state and the interface conducting state are absent for the insulating film. As a function of Ov density, while the surface-Ov state is responsible for the IMT, the spatial charge distribution is found responsible for a transition from two-dimensional-like to three-dimensional-like conducting accompanied by spectral weight transfer, revealing the importance of electronic correlation. Our results show the importance of surface-Ov in determining interface properties and provides a new strategy in utilizing LA-RSXS to directly probe the surface and buried interface electronic properties in complex oxide heterostructures.

AC-coupled LGAD(AC-LGAD) Strip is a new design of LGAD that allows high-precision detection of particle spatiotemporal information whereas reducing the density of readout electronics. For AC-LGAD Strips, there is limited research on the impact of different strip pitches on the spatiotemporal detection performance at the small amount of injected charge. The Institute of High Energy Physics has designed an AC-LGAD Strip prototype with pitches of 150 $\mu m$, 200 $\mu m$, and 250 $\mu m$. The spatial and timing resolutions of the prototype are studied through the laser Transient Current Technique (TCT) scan with different amounts of injected charge. The results show that both the spatial and timing resolution improves as the strip pitch decreases. Increases in both temporal and spatial resolutions as the amount of charge injected increases are observed. The spatial and timing resolution is better than 60 ps and 40 $\mu m$ at 1 Minimum Ionizing Particle (MIP), and better than 10 ps and 5 $\mu m$ at 40 MIPs. Increasing Signal-to-Noise Ratio (SNR) is the key to improving spatial and temporal resolution, whereas increasing the signal attenuation rate by reducing the gap between adjacent electrodes also helps to improve spatial resolution. The enhancements of spatial and timing resolutions by both SNR and signal attenuation rate decrease with increasing amount of MIP. This study can help design and optimize the AC-LGAD Strip detectors and readout electronics.

We perform high-resolution hydrodynamical simulations using the framework of {\it MACER} to investigate supermassive black hole (SMBH) feeding and feedback in a massive compact galaxy, which has a small effective radius but a large stellar mass, with a simulation duration of 10 Gyr. We compare the results with a reference galaxy with a similar stellar mass but a less concentrated stellar density distribution, as typically found in local elliptical galaxies. We find that about 10% of the time, the compact galaxy develops multi-phase gas within a few kpc, but the accretion flow through the inner boundary below the Bondi radius is always a single phase. The inflow rate in the compact galaxy is several times larger than in the reference galaxy, mainly due to the higher gas density caused by the more compact stellar distribution. Such a higher inflow rate results in stronger SMBH feeding and feedback and a larger fountain-like inflow-outflow structure. Compared to the reference galaxy, the star formation rate in the compact galaxy is roughly two orders of magnitude higher but is still low enough to be considered quiescent. Over the whole evolution period, the black hole mass grows by $\sim$50% in the compact galaxy, much larger than the value of $\sim$ 3% in the reference galaxy., Comment: 7 pages, 6 figures

Additional file 1: SPIRIT checklist.

Funding Information: The Event Horizon Telescope Collaboration thanks the following organizations and programs: the Academia Sinica; the Academy of Finland (projects 274477, 284495, 312496, 315721); the Agencia Nacional de Investigación y Desarrollo (ANID), Chile via NCN19_058 (TITANs) and Fondecyt 1221421, the Alexander von Humboldt Stiftung; an Alfred P. Sloan Research Fellowship; Allegro, the European ALMA Regional Centre node in the Netherlands, the NL astronomy research network NOVA and the astronomy institutes of the University of Amsterdam, Leiden University and Radboud University; the ALMA North America Development Fund; the black hole Initiative, which is funded by grants from the John Templeton Foundation and the Gordon and Betty Moore Foundation (although the opinions expressed in this work are those of the author(s) and do not necessarily reflect the views of these Foundations); Chandra DD7-18089X and TM6-17006X; the China Scholarship Council; China Postdoctoral Science Foundation fellowship (2020M671266); Consejo Nacional de Ciencia y Tecnología (CONACYT, Mexico, projects U0004-246083, U0004-259839, F0003-272050, M0037-279006, F0003-281692, 104497, 275201, 263356); the Consejería de Economía, Conocimiento, Empresas y Universidad of the Junta de Andalucía (grant P18-FR-1769), the Consejo Superior de Investigaciones Científicas (grant 2019AEP112); the Delaney Family via the Delaney Family John A. Wheeler Chair at Perimeter Institute; Dirección General de Asuntos del Personal Académico-Universidad Nacional Autónoma de México (DGAPA-UNAM, projects IN112417 and IN112820); the Dutch Organization for Scientific Research (NWO) VICI award (grant 639.043.513) and grant OCENW.KLEIN.113; the Dutch National Supercomputers, Cartesius and Snellius (NWO Grant 2021.013); the EACOA Fellowship awarded by the East Asia Core Observatories Association, which consists of the Academia Sinica Institute of Astronomy and Astrophysics, the National Astronomical Observatory of Japan, Center for Astronomical Mega-Science, Chinese Academy of Sciences, and the Korea Astronomy and Space Science Institute; the European Research Council (ERC) Synergy Grant “BlackHoleCam: Imaging the Event Horizon of Black Holes” (grant 610058); the European Union Horizon 2020 research and innovation program under grant agreements RadioNet (No. 730562) and M2FINDERS (No. 101018682); the Horizon ERC Grants 2021 program under grant agreement No. 101040021; the Generalitat Valenciana postdoctoral grant APOSTD/2018/177 and GenT Program (project CIDEGENT/2018/021); MICINN Research Project PID2019-108995GB-C22; the European Research Council for advanced grant “JETSET: Launching, propagation and emission of relativistic jets from binary mergers and across mass scales” (grant No. 884631); the Institute for Advanced Study; the Istituto Nazionale di Fisica Nucleare (INFN) sezione di Napoli, iniziative specifiche TEONGRAV; the International Max Planck Research School for Astronomy and Astrophysics at the Universities of Bonn and Cologne; DFG research grant “Jet physics on horizon scales and beyond” (grant No. FR 4069/2-1); Joint Columbia/Flatiron Postdoctoral Fellowship, research at the Flatiron Institute is supported by the Simons Foundation; the Japan Ministry of Education, Culture, Sports, Science and Technology (MEXT; grant JPMXP1020200109); the Japanese Government (Monbukagakusho: MEXT) Scholarship; the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for JSPS Research Fellowship (JP17J08829); the Joint Institute for Computational Fundamental Science, Japan; the Key Research Program of Frontier Sciences, Chinese Academy of Sciences (CAS, grants QYZDJ-SSW-SLH057, QYZDJSSW-SYS008, ZDBS-LY-SLH011); the Leverhulme Trust Early Career Research Fellowship; the Max-Planck-Gesellschaft (MPG); the Max Planck Partner Group of the MPG and the CAS; the MEXT/JSPS KAKENHI (grants 18KK0090, JP21H01137, JP18H03721, JP18K13594, 18K03709, JP19K14761, 18H01245, 25120007); the Malaysian Fundamental Research Grant Scheme (FRGS) FRGS/1/2019/STG02/UM/02/6; the MIT International Science and Technology Initiatives (MISTI) Funds; the Ministry of Science and Technology (MOST) of Taiwan (103-2119-M-001-010-MY2, 105-2112-M-001-025-MY3, 105-2119-M-001-042, 106-2112-M-001-011, 106-2119-M-001-013, 106-2119-M-001-027, 106-2923-M-001-005, 107-2119-M-001-017, 107-2119-M-001-020, 107-2119-M-001-041, 107-2119-M-110-005, 107-2923-M-001-009, 108-2112-M-001-048, 108-2112-M-001-051, 108-2923-M-001-002, 109-2112-M-001-025, 109-2124-M-001-005, 109-2923-M-001-001, 110-2112-M-003-007-MY2, 110-2112-M-001-033, 110-2124-M-001-007, and 110-2923-M-001-001); the Ministry of Education (MoE) of Taiwan Yushan Young Scholar Program; the Physics Division, National Center for Theoretical Sciences of Taiwan; the National Aeronautics and Space Administration (NASA, Fermi Guest Investigator grants 80NSSC20K1567 and 80NSSC22K1571, NASA Astrophysics Theory Program grant 80NSSC20K0527, NASA NuSTAR award 80NSSC20K0645); NASA Hubble Fellowship grants HST-HF2-51431.001-A, HST-HF2-51482.001-A awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for NASA, under contract NAS5-26555; the National Institute of Natural Sciences (NINS) of Japan; the National Key Research and Development Program of China (grant 2016YFA0400704, 2017YFA0402703, 2016YFA0400702); the National Science Foundation (NSF, grants AST-0096454, AST-0352953, AST-0521233, AST-0705062, AST-0905844, AST-0922984, AST-1126433, AST-1140030, DGE-1144085, AST-1207704, AST-1207730, AST-1207752, MRI-1228509, OPP-1248097, AST-1310896, AST-1440254, AST-1555365, AST-1614868, AST-1615796, AST-1715061, AST-1716327, AST-1716536, OISE-1743747, AST-1816420, AST-1935980, AST-2034306); NSF Astronomy and Astrophysics Postdoctoral Fellowship (AST-1903847); the Natural Science Foundation of China (grants 11650110427, 10625314, 11721303, 11725312, 11873028, 11933007, 11991052, 11991053, 12192220, 12192223); the Natural Sciences and Engineering Research Council of Canada (NSERC, including a Discovery grant and the NSERC Alexander Graham Bell Canada Graduate Scholarships-Doctoral Program); the National Youth Thousand Talents Program of China; the National Research Foundation of Korea (the Global PhD Fellowship grant: grants NRF-2015H1A2A1033752, the Korea Research Fellowship Program: NRF-2015H1D3A1066561, Brain Pool Program: 2019H1D3A1A01102564, Basic Research Support grant 2019R1F1A1059721, 2021R1A6A3A01086420, 2022R1C1C1005255); Netherlands Research School for Astronomy (NOVA) Virtual Institute of Accretion (VIA) postdoctoral fellowships; Onsala Space Observatory (OSO) national infrastructure, for the provisioning of its facilities/observational support (OSO receives funding through the Swedish Research Council under grant 2017-00648); the Perimeter Institute for Theoretical Physics (research at Perimeter Institute is supported by the Government of Canada through the Department of Innovation, Science and Economic Development and by the Province of Ontario through the Ministry of Research, Innovation and Science); the Princeton Gravity Initiative; the Spanish Ministerio de Ciencia e Innovación (grants PGC2018-098915-B-C21, AYA2016-80889-P, PID2019-108995GB-C21, PID2020-117404GB-C21); the University of Pretoria for financial aid in the provision of the new Cluster Server nodes and SuperMicro (USA) for a SEEDING grant approved toward these nodes in 2020; the Shanghai Pilot Program for Basic Research, Chinese Academy of Science, Shanghai Branch (JCYJ-SHFY-2021-013); the State Agency for Research of the Spanish MCIU through the “Center of Excellence Severo Ochoa” award for the Instituto de Astrofísica de Andalucía (SEV-2017-0709); the Spinoza Prize SPI 78-409; the South African Research Chairs Initiative, through the South African Radio Astronomy Observatory (SARAO, grant ID 77948), which is a facility of the National Research Foundation (NRF), an agency of the Department of Science and Innovation (DSI) of South Africa; the Toray Science Foundation; the Swedish Research Council (VR); the US Department of Energy (USDOE) through the Los Alamos National Laboratory (operated by Triad National Security, LLC, for the National Nuclear Security Administration of the USDOE (Contract 89233218CNA000001); and the YCAA Prize Postdoctoral Fellowship. Funding Information: We thank the staff at the participating observatories, correlation centers, and institutions for their enthusiastic support. This paper makes use of the following ALMA data: ADS/JAO.ALMA#2016.1.01154.V. ALMA is a partnership of the European Southern Observatory (ESO; Europe, representing its member states), NSF, and National Institutes of Natural Sciences of Japan, together with National Research Council (Canada), Ministry of Science and Technology (MOST; Taiwan), Academia Sinica Institute of Astronomy and Astrophysics (ASIAA; Taiwan), and Korea Astronomy and Space Science Institute (KASI; Republic of Korea), in cooperation with the Republic of Chile. The Joint ALMA Observatory is operated by ESO, Associated Universities, Inc. (AUI)/NRAO, and the National Astronomical Observatory of Japan (NAOJ). The NRAO is a facility of the NSF operated under cooperative agreement by AUI. This research used resources of the Oak Ridge Leadership Computing Facility at the Oak Ridge National Laboratory, which is supported by the Office of Science of the U.S. Department of Energy under contract No. DE-AC05-00OR22725. We also thank the Center for Computational Astrophysics, National Astronomical Observatory of Japan. The computing cluster of Shanghai VLBI correlator supported by the Special Fund for Astronomy from the Ministry of Finance in China is acknowledged. This work was supported by FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) under grant 2021/01183-8. Funding Information: APEX is a collaboration between the Max-Planck-Institut für Radioastronomie (Germany), ESO, and the Onsala Space Observatory (Sweden). The SMA is a joint project between the SAO and ASIAA and is funded by the Smithsonian Institution and the Academia Sinica. The JCMT is operated by the EastAsian Observatory on behalf of the NAOJ, ASIAA, and KASI, as well as the Ministry of Finance of China, Chinese Academy of Sciences, and the National Key Research and Development Program (No. 2017YFA0402700) of China and Natural Science Foundation of China grant 11873028. Additional funding support for the JCMT is provided by the Science and Technologies Facility Council (UK) and participating universities in the UK and Canada. The LMT is a project operated by the Instituto Nacional de Astrófisica, Óptica, y Electrónica (Mexico) and the University of Massachusetts at Amherst (USA). The IRAM 30 m telescope on Pico Veleta, Spain is operated by IRAM and supported by CNRS (Centre National de la Recherche Scientifique, France), MPG (Max-Planck-Gesellschaft, Germany) and IGN (Instituto Geográfico Nacional, Spain). The SMT is operated by the Arizona Radio Observatory, a part of the Steward Observatory of the University of Arizona, with financial support of operations from the State of Arizona and financial support for instrumentation development from the NSF. Support for SPT participation in the EHT is provided by the National Science Foundation through award OPP-1852617 to the University of Chicago. Partial support is also provided by the Kavli Institute of Cosmological Physics at the University of Chicago. The SPT hydrogen maser was provided on loan from the GLT, courtesy of ASIAA. Funding Information: This work used the Extreme Science and Engineering Discovery Environment (XSEDE), supported by NSF grant ACI-1548562, and CyVerse, supported by NSF grants DBI-0735191, DBI-1265383, and DBI-1743442. XSEDE Stampede2 resource at TACC was allocated through TG-AST170024 and TG-AST080026N. XSEDE JetStream resource at PTI and TACC was allocated through AST170028. This research is part of the Frontera computing project at the Texas Advanced Computing Center through the Frontera Large-Scale Community Partnerships allocation AST20023. Frontera is made possible by National Science Foundation award OAC-1818253. This research was carried out using resources provided by the Open Science Grid, which is supported by the National Science Foundation and the U.S. Department of Energy Office of Science. Additional work used ABACUS2.0, which is part of the eScience center at Southern Denmark University. Simulations were also performed on the SuperMUC cluster at the LRZ in Garching, on the LOEWE cluster in CSC in Frankfurt, on the HazelHen cluster at the HLRS in Stuttgart, and on the Pi2.0 and Siyuan Mark-I at Shanghai Jiao Tong University. The computer resources of the Finnish IT Center for Science (CSC) and the Finnish Computing Competence Infrastructure (FCCI) project are acknowledged. This research was enabled in part by support provided by Compute Ontario ( http://computeontario.ca ), Calcul Quebec ( http://www.calculquebec.ca ), and Compute Canada ( http://www.computecanada.ca ). Funding Information: The EHTC has received generous donations of FPGA chips from Xilinx Inc., under the Xilinx University Program. The EHTC has benefited from technology shared under open-source license by the Collaboration for Astronomy Signal Processing and Electronics Research (CASPER). The EHT project is grateful to T4Science and Microsemi for their assistance with Hydrogen Masers. This research has made use of NASA’s Astrophysics Data System. We gratefully acknowledge the support provided by the extended staff of the ALMA, both from the inception of the ALMA Phasing Project through the observational campaigns of 2017 and 2018. We would like to thank A. Deller and W. Brisken for EHT-specific support with the use of DiFX. We thank Martin Shepherd for the addition of extra features in the Difmap software that were used for the CLEAN imaging results presented in this paper. We acknowledge the significance and cultural reverance that Maunakea, where the SMA and JCMT EHT stations are located, has always held within the indigenous Hawaiian people. Publisher Copyright: © 2023. The Author(s). Published by the American Astronomical Society. We report on the observations of the quasar NRAO 530 with the Event Horizon Telescope (EHT) on 2017 April 5−7, when NRAO 530 was used as a calibrator for the EHT observations of Sagittarius A*. At z = 0.902, this is the most distant object imaged by the EHT so far. We reconstruct the first images of the source at 230 GHz, at an unprecedented angular resolution of ∼20 μas, both in total intensity and in linear polarization (LP). We do not detect source variability, allowing us to represent the whole data set with static images. The images reveal a bright feature located on the southern end of the jet, which we associate with the core. The feature is linearly polarized, with a fractional polarization of ∼5%-8%, and it has a substructure consisting of two components. Their observed brightness temperature suggests that the energy density of the jet is dominated by the magnetic field. The jet extends over 60 μas along a position angle ∼ −28°. It includes two features with orthogonal directions of polarization (electric vector position angle), parallel and perpendicular to the jet axis, consistent with a helical structure of the magnetic field in the jet. The outermost feature has a particularly high degree of LP, suggestive of a nearly uniform magnetic field. Future EHT observations will probe the variability of the jet structure on microarcsecond scales, while simultaneous multiwavelength monitoring will provide insight into the high-energy emission origin.

With an increasing elderly population worldwide, the incidence of spine degenerative diseases with neck and shoulder pain as the main symptom is rising obviously, which has now become one of the important and difficult problems in sociomedical science. This study was to explore the effects of different ratios of recombinant human bone morphogenetic protein-2 (rhBMP-2) compound to the autogenous bone on cervical interbody fusion. 90 cervical degeneration patients with the need of surgical treatment admitted to our hospital from January 2019 to January 2020 were selected as the research objects and equally divided into group A, group B, and group C according to the order of admission, with 30 cases in each group and the ratios of rhBMP-2 compound to autogenous bone being 2 : 1, 1 : 1, and 1 : 2 respectively, and standard anterior cervical diskectomy and fusion (ACDF) treatment was performed to all patients to compare their surgery-related indexes, the Japanese Orthopaedic Association (JOA) score, the visual analog scale (VAS) score, the effect of cervical interbody fusion, and the postoperative complication rate (CR). Compared with group A and group C, group B achieved the significantly better surgery-related indexes ( P < 0.05 ), significantly higher postoperative JOA scores ( P < 0.05 ), significantly lower postoperative neck and upper limb VAS scores ( P < 0.05 ), significantly better effect of cervical interbody fusion ( P < 0.05 ), and significantly lower postoperative CR ( P < 0.05 ). 1 : 1 is the best ratio of rhBMP-2 compound to the autogenous bone, for it can optimize patients’ perioperative indexes, reduce the postoperative pain, lower the possibility of complications, and improve the effect of cervical interbody fusion, which should be promoted and applied in practice.

The present study aims to apply an electrostatic dry powder coating process to coat aspirin tablets with polymer blends to produce a single-layer coating film, which potentially allows an advantageous delayed sustained drug release profile. The coating formulations containing polymer blends of enteric polymer (hydroxypropyl methylcellulose phthalate or hydroxypropyl methyl cellulose acetate-succinate) and insoluble polymer (Eudragit® RL) were successfully developed and optimized. Results of scanning electron microscopy and acid resistance test demonstrated that curing conditions had a significant impact on the qualities of the produced film. Drug dissolution experiments revealed that changes in the coating level and the coating formulation with different ratios of the enteric polymer to the insoluble polymer achieved an altered and adjustable drug release profile. All of the results suggested that electrostatic powder coating technology is capable to produce a satisfactory coating film with polymer blends, allowing an advantageous functionality of delayed sustained drug release.

Purpose Heterogeneity assessment can be applied for medical imaging analysis. Here, we evaluated first-order and texture analysis (TA) metrics in 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging for classification of metastatic and benign bone lesions in patients with cervical cancer. Methods The data of 18F-FDG PET studies performed on a specific PET/CT system from 2016 to 2018 in patients with cervical cancer were retrieved. The data of bone lesions extracted from studies over 2016–2017 and 2018 were used as training and validation datasets, respectively. Metastatic bone lesions were identified in each dataset, with an equal number of benign bone lesions selected. Cuboid volume of interest (VOI) consisting of 3 × 3 × 5 reconstructed voxels was applied for first-order metrics, and cubic VOI consisting of smaller voxels with trilinear interpolation of standardized uptake value (SUV) was adopted for TA metrics. First-order metrics included the maximum SUV (SUVmax) of lesions and the mean voxel SUV and its standard deviation (SUVsd), skewness, and kurtosis in VOI. In total, 4464 TA metrics based on 62 texture features were evaluated. Logistic regression was used for classification with area under the receiver operating characteristic curve (AUC) as the performance measure. Results From the training and validation datasets, 98 and 42 metastatic bone lesions were identified, respectively. SUVsd demonstrated higher performance than did SUVmax in both the training (AUC .798 vs .732, P = .001) and validation (AUC .786 vs .684, P Conclusion A simple first-order measure of heterogeneity, SUVsd, was found to be superior to SUVmax for the classification of metastatic and benign bone lesions. Multiple hypothesis testing can result in false-positive findings in TA with multiple features and parameters; careful validation is required.