Free-space coupled, large-active-area superconducting microstrip single-photon detector for photon-counting time-of-flight imaging.

Numerous applications at the photon-starved regime require a free-space coupling single-photon detector with a large active area, low dark count rate (DCR), and superior time resolutions. Here, we developed a superconducting microstrip single-photon detector (SMSPD), with a large active area of 260 µm in diameter, a DCR of ∼5k c p s, and a low time jitter of ∼171p s, operated at a near-infrared of 1550 nm and a temperature of ∼2.0K. As a demonstration, we applied the detector to a single-pixel galvanometer scanning system and successfully reconstructed the object information in depth and intensity using a time-correlated photon counting technology.

Discovery of Novel 4-Hydroxyquinazoline Derivatives: In Silico, In Vivo and In Vitro Studies Using Primary PARPi-Resistant Cell Lines.

A series of novel 4-Hydroxyquinazoline derivatives were designed and synthesized to enhance sensitivity in primary PARPi-resistant cells. Among them, the compound B1 has been found to have superior cytotoxicity in primary PARPi-resistant HCT-15 and HCC1937 cell lines, and dose-dependently suppressed the intracellular PAR formation and enhanced the γH2AX aggregation. Mechanistic study showed that B1 stimulated the formation of intracellular ROS and the depolarization of the mitochondrial membrane, which could increase apoptosis and cytotoxicity. An in vivo study showed that B1 significantly suppressed tumor growth at a dose of 25 mg/kg, and an acute toxicity study confirmed its safety. Molecular docking and dynamics simulations revealed that hydrogen bonding between B1 and ASP766 may be helpful to enhance anti-drug resistance ability. This study suggests that B1 is a potent PARP inhibitor that can overcome PARPi resistance and deserves further investigation.

Millimeter-scale active area superconducting microstrip single-photon detector fabricated by ultraviolet photolithography.

The effective and convenient detection of single photons via advanced detectors with a large active area is becoming significant for quantum and classical applications. This work demonstrates the fabrication of a superconducting microstrip single-photon detector (SMSPD) with a millimeter-scale active area via the use of ultraviolet (UV) photolithography. The performances of NbN SMSPDs with different active areas and strip widths are characterized. SMSPDs fabricated by UV photolithography and electron beam lithography with small active areas are also compared from the aspects of the switching current density and line edge roughness. Furthermore, an SMSPD with an active area of 1 mm × 1 mm is obtained via UV photolithography, and during operation at 0.85 K, it exhibits near-saturated internal detection efficiency at wavelengths up to 800 nm. At a wavelength of 1550 nm, the detector exhibits a system detection efficiency of ∼5% (7%) and a timing jitter of 102 (144) ps, when illuminated with a light spot of ∼18 (600) µm in diameter, respectively.

GRAS-domain transcription factor PAT1 regulates jasmonic acid biosynthesis in grape cold stress response.

Cultivated grapevine (Vitis) is a highly valued horticultural crop, and cold stress affects its growth and productivity. Wild Amur grape (Vitis amurensis) PAT1 (Phytochrome A signal transduction 1, VaPAT1) is induced by low temperature, and ectopic expression of VaPAT1 enhances cold tolerance in Arabidopsis (Arabidopsis thaliana). However, little is known about the molecular mechanism of VaPAT1 during the cold stress response in grapevine. Here, we confirmed the overexpression of VaPAT1 in transformed grape calli enhanced cold tolerance. Yeast two-hybrid and bimolecular fluorescence complementation assays highlighted an interaction between VaPAT1 with INDETERMINATE-DOMAIN 3 (VaIDD3). A role of VaIDD3 in cold tolerance was also indicated. Transcriptome analysis revealed VaPAT1 and VaIDD3 overexpression and cold treatment coordinately modulate the expression of stress-related genes including lipoxygenase 3 (LOX3), a gene encoding a key jasmonate biosynthesis enzyme. Co-expression network analysis indicated LOX3 might be a downstream target of VaPAT1. Both electrophoretic mobility shift and dual luciferase reporter assays showed the VaPAT1-IDD3 complex binds to the IDD-box (AGACAAA) in the VaLOX3 promoter to activate its expression. Overexpression of both VaPAT1 and VaIDD3 increased the transcription of VaLOX3 and JA levels in transgenic grape calli. Conversely, VaPAT1-SRDX (dominant repression) and CRISPR/Cas9-mediated mutagenesis of PAT1-ED causing the loss of the C-terminus in grape calli dramatically prohibited the accumulation of VaLOX3 and JA levels during cold treatment. Together, these findings point to a pivotal role of VaPAT1 in the cold stress response in grape by regulating JA biosynthesis.

Transcriptomic analysis of grapevine Dof transcription factor gene family in response to cold stress and functional analyses of the VaDof17d gene.

MAIN CONCLUSION: Dof genes enhance cold tolerance in grapevine and VaDof17d is tightly associated with the cold-responsive pathway and with the raffinose family oligosaccharides. DNA-binding with one finger (Dof) proteins comprise a large family that plays important roles in the regulation of abiotic stresses. No in-depth analysis of Dof genes has been performed in the grapevine. In this study, we analyzed a total of 25 putative Dof genes in grapevine at genomic and transcriptomic levels, compiled expression profiles of 11 selected VaDof genes under cold stress and studied the potential function of the VaDof17d gene in grapevine calli. The 25 Dof proteins can be classified into four phylogenetic groups. RNA-seq and qRT-PCR results demonstrated that a total of 11 VaDof genes responded to cold stress. Comparative mRNA sequencing of 35S::VaDof17d grape calli showed that VaDof17d was tightly associated with the cold-responsive pathway and with the raffinose family oligosaccharides (RFOs), as observed by the up-regulation of galactinol synthase (GolS) and raffinose synthase genes. We found that the Dof17d-ED (CRISPR/Cas9-mediated mutagenesis of Dof17d-ED) mutant had low cold tolerance with a decreased RFOs level during cold stress. These results formed the fundamental knowledge for further analysis of the biological roles of Dof genes in the grapevine's adaption to cold stresses.

Polarization resolving and imaging with a single-photon sensitive superconducting nanowire array.

Superconducting nanowire single-photon detectors (SNSPDs) have attracted remarkable interest for visible and near-infrared single-photon detection due to their outstanding performance. However, conventional SNSPDs are generally used as binary photon-counting detectors. Another important characteristic of light, i.e., polarization, which can provide additional information of the object, has not been resolved using the standalone SNSPD. In this work, we present a first prototype of the polarimeter based on a four-pixel superconducting nanowire array, capable of resolving the polarization state of linearly-polarized light at the single-photon level. The detector array design is based on a division of focal plane configuration in which the orientation of each nanowire division (pixel) is offset by 45°. Each single nanowire pixel operates as a combination of a photon detector and almost linear polarization filter, with an average polarization extinction ratio of ∼10. The total system detection efficiency of the array is ∼1% at a total dark count rate of 680 cps, with a timing jitter of 126 ps, when the detector array is free-space coupled and illuminated with 1550-nm photons. The mean errors of the measured angle of polarization and degree of linear polarization were about -3° and 0.12, respectively. Furthermore, we successfully demonstrated polarization imaging at low-light level using the proposed detector. Our results pave the way for the development of a single-photon sensitive, fast, and large-scale integrated polarization polarimeter or imager. Such detector may find promising application in photon-starved polarization resolving and imaging with high spatial and temporal resolution.

Waveguide-coupled superconducting nanowire single-photon detectors based on femtosecond laser direct writing.

The implementation of quantum information technologies requires the development of integrated quantum chips. Femtosecond laser direct writing (FLDW) waveguides and superconducting nanowire single-photon detectors (SNSPDs) have been widely applied in integrated quantum photonic circuits. In this work, a novel FLDW waveguide-coupled SNSPD was designed and realized by integrating FLDW waveguides and conventional SNSPDs together. Through a COMSOL simulation, a waveguide end face-nanowire optical coupling structure was designed and verified. The simulation results showed that the FLDW waveguide-coupled SNSPD device, which had a target wavelength of 780 nm, can achieve 87% optical absorption. Then the preparation process of the FLDW waveguide-coupled SNSPD device was developed, and the fabricated device achieved a system detection efficiency of 1.7% at 10 Hz dark count rate. Overall, this method provides a feasible single-photon detector solution for future on-chip integrated quantum photonic experiments and applications.

Sixteen-channel fiber array-coupled superconducting single-photon detector array with average system detection efficiency over 60% at telecom wavelength.

We report a compact, scalable, and high-performance superconducting nanowire single-photon detector (SNSPD) array by using a multichannel optical fiber array-coupled configuration. For single pixels with an active area of 18 µm in diameter and illuminated at the telecom wavelength of 1550 nm, we achieved a pixel yield of 13/16 on one chip, an average system detection efficiency of 69% at a dark count rate of 160 cps, a minimum timing jitter of 74 ps, and a maximum count rate of ∼40Mcps. The optical crosstalk coefficient between adjacent channels is better than -60dB. The performance of the fiber array-coupled detectors is comparable with a standalone detector coupled to a single fiber. Our method is promising for the development of scalable, high-performance, and high-yield SNSPDs.

The ethylene response factor VaERF092 from Amur grape regulates the transcription factor VaWRKY33, improving cold tolerance.

Cold stress is a major limiting factor in grape (Vitis) productivity. In this study, we characterized a cold-responsive ethylene response factor (ERF) transcription factor, VaERF092, from Amur grape (Vitis amurensis). VaERF092 expression was induced by both low temperatures and the ethylene precursor 1-aminocyclopropane-1-carboxylate (ACC), but was suppressed by treatment with the ethylene inhibitor aminoethoxyvinylglycine (AVG) under cold conditions. Ectopic expression of VaERF092 in Arabidopsis thaliana enhanced cold tolerance. Co-expression network analysis of V. vinifera genes indicated that WRKY33 might be a downstream target of VaERF092. This hypothesis was supported by the fact that VaWRKY33 was expressed temporally after VaERF092 expression and could also be induced by cold and ACC, and inhibited by AVG. Yeast one-hybrid, transient ß-glucuronidase (GUS) and dual-luciferase reporter assays provided evidence for an interaction between VaERF092 and a GCC-box element in the VaWRKY33 promoter. In addition, heterologous overexpression of VaWRKY33 in A. thaliana resulted in enhanced cold tolerance. VaERF092- and VaWRKY33 overexpressing grape calli showed lower low-temperature exothermic values than the empty vector (EV) calli, indicating enhanced tolerance to cold. Together, these results indicated that VaERF092 regulates VaWRKY33 through binding to its promoter GCC-box, leading to enhanced cold stress tolerance.

Transcriptomic Analysis of the Grapevine LEA Gene Family in Response to Osmotic and Cold Stress Reveals a Key Role for VamDHN3.

Late embryogenesis abundant (LEA) proteins comprise a large family that plays important roles in the regulation of abiotic stress, however, no in-depth analysis of LEA genes has been performed in grapevine to date. In this study, we analyzed a total of 52 putative LEA genes in grapevine at the genomic and transcriptomic level, compiled expression profiles of four selected (V. amurensis) VamLEA genes under cold and osmotic stresses, and studied the potential function of the V. amurensis DEHYDRIN3 (VamDHN3) gene in grapevine callus. The 52 LEA proteins were classified into seven phylogenetic groups. RNA-seq and quantitative real-time PCR results demonstrated that a total of 16 and 23 VamLEA genes were upregulated under cold and osmotic stresses, respectively. In addition, overexpression of VamDHN3 enhanced the stability of the cell membrane in grapevine callus, suggesting that VamDHN3 is involved in osmotic regulation. These results provide fundamental knowledge for the further analysis of the biological roles of grapevine LEA genes in adaption to abiotic stress.

Genome-wide identification and expression analysis of HKT transcription factor under salt stress in nine plant species.

High-affinity K+ (HKT) gene family is regulated the transport of Na+ and maintain the balance between Na+ and K+ in the process of plant growth, development and response to abiotic stress. Despite this fact, systemic and comprehensive studies on HKT in multiply plants remains unknown. A total of 29 HKT genes distributed on nine species were identified. Phylogenetic tree analysis results indicated that HKT genes were divided into five homology subfamilies. Combining structural analysis with protein contains five highly conservative motifs, HKT family has similar gene structures and special gene characteristics. Finally, the expression patterns of HKT showed two different dramatic changes in different organs and tissues under different salt stress in multiply plants. This study has many implications for research into the comparative genomics analysis of HTK gene family, which revealed regulation mechanism of HKT genes, is valuable for understanding development and response to abiotic stress in plant.

Discovery of (2-(4-Substituted phenyl)quinolin-4-yl)(4-isopropylpiperazin-1-yl)methanone Derivatives as Potent Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors.

Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an increasingly important role in the treatment of hyperlipidemia. In pursuit of potent small molecules that block the PCSK9/low-density lipoprotein receptor (LDLR) protein-protein interaction (PPI), a series of 2-phenylquinoline-4-carboxylic acid derivatives were designed and synthesized based on previously derived molecules. In the in vitro PPI inhibition test, compounds M1, M12, M14, M18 and M27 exhibited potent activities with IC50 values of 6.25 µM, 0.91 µM, 2.81 µM, 4.26 µM and 0.76 µM, respectively, compared with SBC-115337 (IC50 value of 9.24 µM). Molecular docking and molecular dynamics simulations revealed the importance of hydrophobic interactions in the binding of inhibitors to the PPI interface of PCSK9. In LDLR expression and LDL uptake assays, the tested compounds M1, M12 and M14 were found to restore LDLR expression levels and to increase the extracellular LDL uptake capacity of HepG2 cells in the presence of exogenous PCSK9. Collectively, novel small-molecule PCSK9/LDLR PPI inhibitors (especially M12) with in vitro lipid lowering ability, were discovered as lead compounds for further development of hypolipidemic drugs.

Population structure and genetic diversity of mango (Mangifera indica L.) germplasm resources as revealed by single-nucleotide polymorphism markers.

Introduction: Mango is a vital horticultural fruit crop, and breeding is an essential strategy to enhance ongoing sustainability. Knowledge regarding population structure and genetic diversity in mango germplasm is essential for crop improvement. Methods: A set of 284 mango accessions from different regions of the world were subjected to high-throughput sequencing and specific-locus amplified fragment (SLAF) library construction to generate genomic single-nucleotide polymorphism (SNP). Results: After filtering, raw data containing 539.61 M reads were obtained. A total of 505,300 SLAFs were detected, of which, 205,299 were polymorphic. Finally, 29,136 SNPs were employed to dissect the population structure, genetic relationships, and genetic diversity. The 284 mango accessions were divided into two major groups: one group consisted mainly of mango accessions from Australia, the United States, Cuba, India, Caribbean, Israel, Pakistan, Guinea, Burma, China, and Sri Lanka, which belonged to the Indian type (P1); the other group contained mango accessions from the Philippines, Thailand, Indonesia, Vietnam, Cambodia, Malaysia, and Singapore, which belonged to Southeast Asian type (P2). Genetic diversity, principal component analysis (PCA), and population structure analyses revealed distinct accession clusters. Current results indicated that the proposed hybridization occurred widely between P1 and P2. Discussion: Most of the accessions (80.99%) were of mixed ancestry, perhaps including multiple hybridization events and regional selection, which merits further investigation.

Cryoprotectant-Mediated Cold Stress Mitigation in Litchi Flower Development: Transcriptomic and Metabolomic Perspectives.

Temperature is vital in plant growth and agricultural fruit production. Litchi chinensis Sonn, commonly known as litchi, is appreciated for its delicious fruit and fragrant blossoms and is susceptible to stress when exposed to low temperatures. This study investigates the effect of two cryoprotectants that counteract cold stress during litchi flowering, identifies the genes that generate the cold resistance induced by the treatments, and hypothesizes the roles of these genes in cold resistance. Whole plants were treated with Bihu and Liangli cryoprotectant solutions to protect inflorescences below 10 °C. The soluble protein, sugar, fructose, sucrose, glucose, and proline contents were measured during inflorescence. Sucrose synthetase, sucrose phosphate synthetase, antioxidant enzymes (SOD, POD, CAT), and MDA were also monitored throughout the flowering stage. Differentially expressed genes (DEGs), gene ontology, and associated KEGG pathways in the transcriptomics study were investigated. There were 1243 DEGs expressed after Bihu treatment and 1340 in the control samples. Signal transduction pathways were associated with 39 genes in the control group and 43 genes in the Bihu treatment group. The discovery of these genes may contribute to further research on cold resistance mechanisms in litchi. The Bihu treatment was related to 422 low-temperature-sensitive differentially accumulated metabolites (DAMs), as opposed to 408 DAMs in the control, mostly associated with lipid metabolism, organic oxidants, and alcohols. Among them, the most significant differentially accumulated metabolites were involved in pathways such as ß-alanine metabolism, polycyclic aromatic hydrocarbon biosynthesis, linoleic acid metabolism, and histidine metabolism. These results showed that Bihu treatment could potentially promote these favorable traits and increase fruit productivity compared to the Liangli and control treatments. More genomic research into cold stress is needed to support the findings of this study.

Glutathione-Sensitive Photosensitizer-Drug Conjugates Target the Mitochondria to Overcome Multi-Drug Resistance in Cancer.

Multi-drug resistance (MDR) is a major cause of cancer therapy failure. Photodynamic therapy (PDT) is a promising modality that can circumvent MDR and synergize with chemotherapies, based on the generation of reactive oxygen species (ROS) by photosensitizers. However, overproduction of glutathione (GSH) by cancer cells scavenges ROS and restricts the efficacy of PDT. Additionally, side effects on normal tissues are unavoidable after PDT treatment. Here, to develop organic systems that deliver effective anticancer PDT and chemotherapy simultaneously with very little side effects, three GSH-sensitive photosensitizer-drug conjugates (CyR-SS-L) are designed and synthesized. CyR-SS-L localized in the mitochondria then is cleaved into CyR-SG and SG-L parts by reacting with and consuming high levels of intracellular GSH. Notably, CyR-SG generates high levels of ROS in tumor cells instead of normal cells and be exploited for PDT and the SG-L part is used for chemotherapy. CyR-SS-L inhibits better MDR cancer tumor inhibitory activity than indocyanine green, a photosensitizer (PS) used for PDT in clinical applications. The results appear to be the first to show that CyR-SS-L may be used as an alternative PDT agent to be more effective against MDR cancers without obvious damaging normal cells by the combination of PDT, GSH depletion, and chemotherapy.

Solvent-Controlled Regioselective Reaction of 2-Methyleneaziridines with Acrylic/Propargylic Acids: Synthesis of Carboxylate Aziridine/Acetone Esters.

Herein, we report a convenient solvent-controlled regioselective esterification to access two types of carboxylate esters without any additive or non-green activation strategy. In this transformation, 2-methyleneaziridines served as an ester reagent, providing two alternative electrophilic carbon centers. Notably, this protocol is suitable for some structure-complicated clinical molecules with a carboxylic acid group, presenting remarkable application potential.