Precise Detection of Viral RNA by Programming Multiplex Rolling Circle Amplification and Strand Displacement.

Detection of viral infections (e.g., SARS-CoV-2) with high precision is critical to disease control and treatment. There is an urgent need to develop point-of-care detection methods to complement the gold standard laboratory-based PCR assay with comparable sensitivity and specificity. Herein, we developed a method termed mCAD to achieve ultraspecific point-of-care detection of SARS-CoV-2 RNA while maintaining high sensitivity by programming multiplex rolling circle amplification and toehold-mediated strand displacement reactions. RCA offers sufficient amplification of RNA targets for subsequent detection. Most importantly, a multilayer of detection specificity is implemented into mCAD via sequence-specific hybridization of nucleic acids across serial steps of this protocol to fully eliminate potential false-positive detections. Using mCAD, we demonstrated a highly specific, sensitive, and convenient visual detection of SARS-CoV-2 RNA from both synthetic and clinical samples, exhibiting performance comparable to qPCR. We envision that mCAD will find its broad applications in clinical prospects for nucleic acid detections readily beyond SARS-CoV-2 RNA.

Two-color unidirectional reflections by modulating the spatial susceptibility in a homogeneous atomic medium.

Non-reciprocal reflections of optical signals are unusual yet fascinating to achieve the imminent applications of non-reciprocal photonic devices and circuits. The complete non-reciprocal reflection (unidirectional reflection) was recently found to be achievable in a homogeneous medium, if the real and imaginary parts of the probe susceptibility satisfy the spatial Kramers-Kronig (KK) relation. We propose a coherent four-level tripod model for realizing dynamically tunable two-color non-reciprocal reflections by applying two control fields with linearly modulated intensities. We found that, the unidirectional reflection can be obtained if the non-reciprocal frequency regions are located in the electromagnetically induced transparency (EIT) windows. This mechanism is to break the spatial symmetry by the spatial modulation of susceptibility to induce unidirectional reflections, the real and imaginary parts of the probe susceptibility are no longer required to satisfy the spatial KK relation.

Quantum Simulation of Topological Zero Modes on a 41-Qubit Superconducting Processor.

Quantum simulation of different exotic topological phases of quantum matter on a noisy intermediate-scale quantum (NISQ) processor is attracting growing interest. Here, we develop a one-dimensional 43-qubit superconducting quantum processor, named Chuang-tzu, to simulate and characterize emergent topological states. By engineering diagonal Aubry-André-Harper (AAH) models, we experimentally demonstrate the Hofstadter butterfly energy spectrum. Using Floquet engineering, we verify the existence of the topological zero modes in the commensurate off-diagonal AAH models, which have never been experimentally realized before. Remarkably, the qubit number over 40 in our quantum processor is large enough to capture the substantial topological features of a quantum system from its complex band structure, including Dirac points, the energy gap's closing, the difference between even and odd number of sites, and the distinction between edge and bulk states. Our results establish a versatile hybrid quantum simulation approach to exploring quantum topological systems in the NISQ era.

What is new in cancer-associated fibroblast biomarkers?

The tumor microenvironment is one of the important drivers of tumor development. Cancer-associated fibroblasts (CAFs) are a major component of the tumor stroma and actively participate in tumor development, invasion, metastasis, drug resistance, and other biological behaviors. CAFs are a highly heterogeneous group of cells, a reflection of the diversity of their origin, biomarkers, and functions. The diversity of CAF origin determines the complexity of CAF biomarkers, and CAF subpopulations expressing different biomarkers may play contrasting roles in tumor progression. In this review, we provide an overview of these emerging CAF biomarkers and the biological functions that they suggest, which may give a better understanding of the relationship between CAFs and tumor cells and be of great significance for breakthroughs in precision targeted therapy for tumors. Video Abstract.

GhCNGC13 and 32 Act as Critical Links between Growth and Immunity in Cotton.

Cyclic nucleotide-gated ion channels (CNGCs) remain poorly studied in crop plants, most of which are polyploid. In allotetraploid Upland cotton (Gossypium hirsutum), silencing GhCNGC13 and 32 impaired plant growth and shoot apical meristem (SAM) development, while triggering plant autoimmunity. Both growth hormones (indole-3-acetic acid and gibberellin) and stress hormones (abscisic acid, salicylic acid, and jasmonate) increased, while leaf photosynthesis decreased. The silenced plants exhibited an enhanced resistance to Botrytis cinerea; however, Verticillium wilt resistance was weakened, which was associated with LIPOXYGENASE2 (LOX2) downregulation. Transcriptomic analysis of silenced plants revealed 4835 differentially expressed genes (DEGs) with functional enrichment in immunity and photosynthesis. These DEGs included a set of transcription factors with significant over-representation in the HSF, NAC, and WRKY families. Moreover, numerous members of the GhCNGC family were identified among the DEGs, which may indicate a coordinated action. Collectively, our results suggested that GhCNGC13 and 32 functionally link to photosynthesis, plant growth, and plant immunity. We proposed that GhCNGC13 and 32 play a critical role in the "growth-defense tradeoff" widely observed in crops.

Regulation of bla system in ST59-related oxacillin-susceptible mecA-positive Staphylococcus aureus.

OBJECTIVES: Oxacillin-susceptible mecA-positive Staphylococcus aureus (OS-MRSA) is clinically significant and isolated globally but the mechanism of its occurrence remains indistinct. We sought to assess the mechanism of regulating oxacillin susceptibility in OS-MRSA isolates by evaluating the evolutionary dynamics of OS-MRSA and the discrepancies of mecA-regulating genes in OS-MRSA and oxacillin-resistant MRSA (OR-MRSA). METHODS: Nine OS-MRSA isolates and 77 OR-MRSA isolates were sequenced using next-generation sequencing (NGS) platforms. Two representative OS-MRSA isolates (ET-13, ET-16) were induced to be oxacillin resistant and sequenced also. OS-MRSA ET-16 and its counterpart isolate with induced oxacillin resistance, ET-16I, and their mutants were used to confirm the role of the bla system in regulating methicillin susceptibility. Oxacillin MICs were determined using Etests. Expression of mecA and blaR1 was quantified by quantitative RT-PCR. RESULTS: A deletion in blaR1 in most OS-MRSA isolates (7/9; 77.78%) was found using NGS data, and overexpression of OR-blaR1 in OS-MRSA isolate ET-16 restored its oxacillin resistance. OS-MRSA could be induced to be oxacillin resistant, while growth was suppressed in the induced isolates. Plasmid containing the bla locus was lost in most induced isolates during the induction process and complementation of blaR1-blaI from OS-MRSA ET-16 to the induced isolate ET-16I converted its oxacillin susceptibility. CONCLUSIONS: Deletion in blaR1 resulted in oxacillin susceptibility in OS-MRSA, and loss of the bla regulator in OS-MRSA restored oxacillin resistance. The bla system played a crucial role in regulating oxacillin susceptibility in OS-MRSA isolates.

Three-color reflections in one-dimensional ordered and disordered atomic lattices with trapped N-type cold atoms.

Investigating and controlling light propagation in one-dimensional (1D) ordered and disordered atomic lattices is critical both fundamentally and for applications. In this study, cold atoms are trapped in 1D optical lattice and driven to the four-level N configuration. In each period, the atoms exhibit a Gaussian density distribution with the average atomic density N0 (1 + Δk). When the random number Δk = 0 (the atomic density Nk(z)) corresponding to an ordered 1D atomic lattice, there are three reflection regions of high reflectivity located in two EIT windows and one large detuning range. However, the atomic density may increase (N k+(z) with Δk > 0) or decrease (N k-(z) with Δk < 0) owing to the imperfect manufacturing process or random distribution of atoms corresponding to a disordered atomic lattice. The results show that the width and height of reflections can be raised (reduced) by the increased (decreased) ratio of N k+(z)/N k (z) (N k-(z)/N k (z)) with the random distribution of lattice cells with N k+(z) (N k-(z)). When a cluster of disordered lattice cells with N k+(z) and N k-(z) is located at the front or tail of the atomic lattice, reflection symmetry can be broken. However, the symmetry and robustness can be well preserved with the random fluctuation of the average atomic density in each lattice cell.

Multiplication-free timing phase error detector for Nyquist and non-Nyquist optical signals.

A versatile digital coherent receiver capable of handling optical signals with different kinds of pulse shaping schemes (PSSs) is indispensable for future flexible and heterogeneous coherent optical communication networks. Therefore, a low-complexity timing phase error detector (TPED) versatile for all PSSs is of particular interest. In this paper, we propose a TPED suitable for both Nyquist signals with different roll-off factors and non-Nyquist signals. It requires two samples per symbol and involves no multiplications. As far as we know, it has the lowest computation complexity compared with the existing TPEDs used in coherent systems, while incurring no receiver sensitivity penalty. Numerical simulations and experiments are carried out to demonstrate the superior timing performance and PSS versatility of the proposed TPED in both open-loop and closed-loop working conditions. We also implement the novel TPED in a field programmable gate array (FPGA) and verify its real-time clock recovery performance using the 10 Gbaud very low roll-off Nyquist and non-Nyquist quadrature phase shift keying (QPSK) signals.

Dynamic Expression, Differential Regulation and Functional Diversity of the CNGC Family Genes in Cotton.

Cyclic nucleotide-gated channels (CNGCs) constitute a family of non-selective cation channels that are primarily permeable to Ca2+ and activated by the direct binding of cyclic nucleotides (i.e., cAMP and cGMP) to mediate cellular signaling, both in animals and plants. Until now, our understanding of CNGCs in cotton (Gossypium spp.) remains poorly addressed. In the present study, we have identified 40, 41, 20, 20, and 20 CNGC genes in G. hirsutum, G. barbadense, G. herbaceum, G. arboreum, and G. raimondii, respectively, and demonstrated characteristics of the phylogenetic relationships, gene structures, chromosomal localization, gene duplication, and synteny. Further investigation of CNGC genes in G. hirsutum, named GhCNGC1-40, indicated that they are not only extensively expressed in various tissues and at different developmental stages, but also display diverse expression patterns in response to hormones (abscisic acid, salicylic acid, methyl jasmonate, ethylene), abiotic (salt stress) and biotic (Verticillium dahlia infection) stimuli, which conform with a variety of cis-acting regulatory elements residing in the promoter regions; moreover, a set of GhCNGCs are responsive to cAMP signaling during cotton fiber development. Protein-protein interactions supported the functional aspects of GhCNGCs in plant growth, development, and stress responses. Accordingly, the silencing of the homoeologous gene pair GhCNGC1&18 and GhCNGC12&31 impaired plant growth and development; however, GhCNGC1&18-silenced plants enhanced Verticillium wilt resistance and salt tolerance, whereas GhCNGC12&31-silenced plants had opposite effects. Together, these results unveiled the dynamic expression, differential regulation, and functional diversity of the CNGC family genes in cotton. The present work has laid the foundation for further studies and the utilization of CNGCs in cotton genetic improvement.

Dynamic manipulation of three-color light reflection in a defective atomic lattice.

We extend a recent theoretical work [Phys. Rev. A101, 053856 (2020)10.1103/PhysRevA.101.053856] by replacing disorders characterized by varied atomic densities with defects characterized by vacant lattice cells to evaluate again three-color reflection in a one-dimensional optical lattice filled with cold 87Rb atoms. This is based on the consideration that trapped atoms may escape from some lattice cells and effects of vacant cells on light propagation are of major importance from both fundamental and applied research viewpoints. We consider two types of defective atomic lattices where vacant cells are randomly or continuously distributed among filled cells. Numerical results show that the wider reflection band in a large detuning region of negligible off-resonance absorption is quite sensitive to, while the narrower reflection bands in two near-resonant regions of electromagnetically induced transparency are rather robust against, the number of random vacant cells. In contrast, all three reflection bands exhibit strong robustness against the number of continuous vacant cells. Note, however, that both narrower reflection bands may become widened and exhibit a blue shift when continuous vacant cells appear in the front of our atomic lattice due to the joint contributions of Bragg scattering and quantum interference.

miR24-2 Promotes Malignant Progression of Human Liver Cancer Stem Cells by Enhancing Tyrosine Kinase Src Epigenetically.

MicroRNA24-2 (miR24-2) is associated with human tumorigenesis; however, its molecular mechanisms are poorly understood. Herein, our findings demonstrate that miR24-2 promotes the proliferation ability in vitro and the tumorigenic ability in vivo in human liver cancer stem cells (hLCSCs). Mechanically, the miR24-2 targets for 3' UTR (2,627-2,648) of protein arginine methyltransferase 7 (PRMT7) inhibit the translational ability of prmt7 gene. Moreover, miR24-2 inhibits the di-/tri-methylation of histone H4 arginine 3 by reducing PRMT7 and then promotes the expression of Nanog via long noncoding RNA HULC. Notably, miR24-2 inhibits histone deacetylase HDAC3 through miR675, which promotes the acetylation of histone H4 at lysine 16. Subsequently, miR24-2 enhances the interaction between LC3 and ATG4 dependent on PI3K and triggers cellular autophagy. Strikingly, miR24-2 inhibits the degradation of pyruvate kinase M1 via autophagosome-P62 in hLCSCs. Furthermore, miR24-2 enhances the activity of Src by promoting the binding of PKM1 to the Src promoter regions in hLCSCs. In particular, our results also indicate that src gene determines the oncogenic functions of miR24-2. These results provided a valuable theoretical basis for the discovery of liver cancer therapeutic targets and diagnosis markers based on miR24-2.

Compression Behavior and Vibrational Properties of New Energetic Material LLM-105 Analyzed Using the Dispersion-Corrected Density Functional Theory.

The 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105) is a newly energetic material with an excellent performance and low sensitivity and has attracted considerable attention. On the basis of the dispersion-corrected density functional theory (DFT-D), the high-pressure responses of vibrational properties, in conjunction with structural properties, are used to understand its intermolecular interactions and anisotropic properties under hydrostatic and uniaxial compressions. At ambient and pressure conditions, the DFT-D scheme could reasonably describe the structural parameters of LLM-105. The hydrogen bond network, resembling a parallelogram shape, links two adjacent molecules and contributes to the structure stability under hydrostatic compression. The anisotropy of LLM-105 is pronounced, especially for Raman spectra under uniaxial compression. Specifically, the red-shifts of modes are obtained for [100] and [010] compressions, which are caused by the pressure-induced enhance of the strength of the hydrogen bonds. Importantly, coupling modes and discontinuous Raman shifts are observed along [010] and [001] compressions, which are related to the intramolecular vibrational redistribution and possible structural transformations under uniaxial compressions. Overall, the detailed knowledge of the high-pressure responses of LLM-105 is established from the atomistic level. Uniaxial compression responses provide useful insights for realistic shock conditions.

miR24-2 accelerates progression of liver cancer cells by activating Pim1 through tri-methylation of Histone H3 on the ninth lysine.

Several microRNAs are associated with carcinogenesis and tumour progression. Herein, our observations suggest both miR24-2 and Pim1 are up-regulated in human liver cancers, and miR24-2 accelerates growth of liver cancer cells in vitro and in vivo. Mechanistically, miR24-2 increases the expression of N6-adenosine-methyltransferase METTL3 and thereafter promotes the expression of miR6079 via RNA methylation modification. Furthermore, miR6079 targets JMJD2A and then increased the tri-methylation of histone H3 on the ninth lysine (H3K9me3). Therefore, miR24-2 inhibits JMJD2A by increasing miR6079 and then increases H3K9me3. Strikingly, miR24-2 increases the expression of Pim1 dependent on H3K9me3 and METTL3. Notably, our findings suggest that miR24-2 alters several related genes (pHistone H3, SUZ12, SUV39H1, Nanog, MEKK4, pTyr) and accelerates progression of liver cancer cells through Pim1 activation. In particular, Pim1 is required for the oncogenic action of miR24-2 in liver cancer. This study elucidates a novel mechanism for miR24-2 in liver cancer and suggests that miR24-2 may be used as novel therapeutic targets of liver cancer.

Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a.

BACKGROUND: Long noncoding RNA HULC is highly up-regulation in human hepatocellular carcinoma (HCC). However, the functions of HULC in hepatocarcinogenesis remains unclear. METHODS: RT-PCR, Western blotting, Chromatin immunoprecipitation (CHIP) assay, RNA Immunoprecipitation (RIP) and tumorignesis test in vitro and in vivo were performed. RESULTS: HULC is negatively associated with expression of PTEN or miR15a in patients of human liver cancer. Moreover, HULC accelerates malignant progression of liver cancer cells in vitro and in vivo. Mechanistically, HULC increasesthe expression of P62 via decreasing mature miR15a. On the other hand, excessive HULC increases the expression of LC3 on the level of transcription and then activates LC3 through Sirt1 (a deacetylase). Notably, HULC enhanced the interplay between LC3 and ATG3. Furthermore, HULC also increases the expression of becline-1(autophagy related gene). Therefore, HULC increases the cellular autophagy by increasing LC3II dependent on Sirt1.Noteworthy, excessive HULC reduces the expression of PTEN, ß-catenin and enhances the expression of SAPK/JUNK, PKM2, CDK2, NOTCH1, C-Jun in liver cancer cells. Of significance, our observations also revealed that HULC inhibited PTEN through ubiquitin-proteasome system mediated by autophagy-P62.Ultimately,HULC activates AKT-PI3K-mTOR pathway through inhibiting PTEN in human liver cancer cells. CONCLUSIONS: This study elucidates a novel mechanism that lncRNA HULC produces a vital function during hepatocarcinogenesis.

Multifunctional paper strip based on GO-veiled Ag nanoparticles with highly SERS sensitive and deliverable properties for high-performance molecular detection.

The development of paper-based SERS substrates that can allow multi-component detection in real-word scenarios is of great value for applications in molecule detection under complex conditions. Here, a multifunctional SERS-based paper sensing substrate has been developed through the uniform patterning of high-density arrays of GO-isolated Ag nanoparticles on the hydrophilic porous cellulose paper strip (GO@AgNP@paper). Wet-chemical synthesis was used to provide the cover of SERS hot spots on any part of the paper, not just limited surface deposition. In virtue of the inherent ability of paper to deliver analytes by the capillary force, the detection ability of the GO@AgNP@paper substrate was greatly promoted, allowing as low as 10-19M R6G detection from microliter-volume (50 µL) samples. For the components with different polarity, the paper substrate can be used as an all-in-one machine to achieve the integration of separation and high-sensitive detection for ultralow mixture components, which improves the practical application value of SERS-based paper devices.

RETRACTED: SET1A Cooperates With CUDR to Promote Liver Cancer Growth and Hepatocyte-like Stem Cell Malignant Transformation Epigenetically

Long noncoding RNA CUDR plays an important role during tumorigenesis. Herein, we demonstrate that SET1A cooperates with CUDR to accelerate hepatocarcinogenesis and promote malignant transformation of hepatocyte-like stem cells. Mechanistically, CUDR enhances the phosphorylation of RB1, C-myc expression, and the interplay between the SET1A and pRB1. Notably, CUDR acts as a sponge cushion that shows a link between SET1A and pRB1, producing a activated pRB1-SET1A complex. On the other hand, the pRB1-SET1A complex may carry methyls(me) to occupy the position of H3K4, resulting in specific tri-methylation of forth lysine of histone H3 (H3K4me3). Thereby, the H3K4me3 loads on the TRF2 promoter region which causes the TRF2 overexpression. Ultimately, the excessive TRF2 binds to telomere repeat DNA, prolonging the telomere length. These findings provide the first demonstration that SET1A cooperates with CUDR to play a positive potential role during hepatocarcinogenesis and hepatocyte-like stem cells' malignant transformation epigenetically.

Increased Community-Associated Infections Caused by Panton-Valentine Leukocidin-Negative MRSA, Shanghai, 2005-2014.

During 2005-2014, community-associated methicillin-resistant Staphylococcus aureus infections increased in Shanghai, China. Most infections were caused by sequence type 59 S. aureus that lacked Panton-Valentine leukocidin. This finding challenges the notion that Panton-Valentine leukocidin is necessary for epidemiologic success of community-associated methicillin-resistant S. aureus.

Long Noncoding RNA CUDR Regulates HULC and ß-Catenin to Govern Human Liver Stem Cell Malignant Differentiation.

Long noncoding RNA cancer upregulated drug resistant (CUDR) is overexpressed in many tumors and promotes tumorigenesis. Herein, we demonstrate CUDR could enhance the human embryonic stem cells (ESC) differentiation into hepatocyte-like cells by reducing trimethylation on histone H3 twenty-seventh lysine (H3K27me3). On the other hand, excessive CUDR triggers hepatocyte-like cells malignant transformation. Mechanistically, we identify CUDR causes highly upregulated in liver cancer (HULC) and ß-catenin abnormal expression by inhibiting HULC promoter methylation and promoting ß-catenin promoter-enhancer chromatin looping formation mediated by CUDR-ccctc-binding factor (CTCF) complex, which recruits more RNA polII and P300. Strikingly, HULC and ß-catenin activity are crucial for CUDR oncogenic function. These findings provide the first demonstration that CUDR plays a positive potential role in liver cancer stem cell through the cascade of CUDR-HULC/CUDR-ß-catenin signaling, and offer insights into a novel link between long noncoding RNA (lncRNA) and the epigenetic modification in cancer stem cells.

Targeting surface protein SasX by active and passive vaccination to reduce Staphylococcus aureus colonization and infection.

SasX is a recently described surface protein of Staphylococcus aureus that is linked to the epidemic success of hospital-associated methicillin-resistant clones, in particular in Asia. It enhances nasal colonization and virulence in skin and lung infection models. Here, we evaluated the potential of SasX as a vaccine component in passive and active immunization efforts using mouse infection models. We found that SasX induced a specific immune response predominantly based on IgG1 antibodies. Active immunization with recombinant SasX or passive immunization with rabbit polyclonal anti-SasX IgG significantly decreased the size of lesions caused by S. aureus in a skin infection model. Furthermore, active immunization reduced acute lung injury in a lung infection model. Moreover, active or passive immunization significantly reduced S. aureus colonization in a nasal colonization model. Finally, anti-SasX IgG enhanced the susceptibility of S. aureus to killing by human neutrophils. We conclude that SasX is a potential target for therapeutics or vaccines designed to moderate colonization and infection by sasX-positive epidemic strains of S. aureus.