A chemical timer approach to delayed chemiluminescence.

Although the onset time of chemical reactions can be manipulated by mechanical, electrical, and optical methods, its chemical control remains highly challenging. Herein, we report a chemical timer approach for manipulating the emission onset time of chemiluminescence (CL) reactions. A mixture of Mn2+, NaHCO3, and a luminol analog with H2O2 produced reactive oxygen species (ROS) radicals and other superoxo species (superoxide containing complex) with high efficiency, accompanied by strong and immediate CL emission. Surprisingly, the addition of thiourea postponed CL emission in a concentration-dependent manner. The delay was attributed to a slow-generation-scavenging mechanism, which was found to be generally applicable not only to various types of CL reagents and ROS radical scavengers but also to popular chromogenic reactions. The precise regulation of CL kinetics was further utilized in dynamic chemical coding with improved coding density and security. This approach provides a powerful platform for engineering chemical reaction kinetics using chemical timers, which is of application potential in bioassays, biosensors, CL microscopic imaging, microchips, array chips, and informatics.

Time Crystal in a Single-Mode Nonlinear Cavity.

Time crystal is a class of nonequilibrium phases with broken time-translational symmetry. Here, we demonstrate the time crystal in a single-mode nonlinear cavity. The time crystal originates from the self-oscillation induced by a linear gain and is stabilized by a nonlinear damping. We show in the time crystal phase there are sharp dissipative gap closing and pure imaginary eigenvalues of the Liouvillian spectrum in the thermodynamic limit. Dynamically, we observe a metastable regime with the emergence of quantum oscillation, followed by a dissipative evolution with a timescale much longer than the oscillating period. Moreover, we show there is a dissipative phase transition at the Hopf bifurcation, which can be characterized by the photon number fluctuation in the steady state. These results pave a new promising way for further experiments and deepen our understanding of time crystals.

Yellow Petal locus GaYP promotes flavonol biosynthesis and yellow coloration in petals of Asiatic cotton (Gossypium arboreum).

KEY MESSAGE: Yellow Petal locus GaYP is located on chromosome 11 and encodes a Sg6 R2R3-MYB transcription factor, which promotes flavonol biosynthesis and yellow coloration in Asiatic cotton petals. Petal color is pivotal to ornamental value and reproduction of plants. Yellow coloration in plant petals is mainly attributed to colorants including carotenoids, aurones and some flavonols. To date, the genetic regulatory mechanism of flavonol biosynthesis in petals is still to be elucidated. Here, we employed Asiatic cottons with or without deep yellow coloration in petals to address this question. Multi-omic and biochemical analysis revealed significantly up-regulated transcription of flavonol structural genes and increased levels of flavonols, especially gossypetin and 6-hydroxykaempferol, in yellow petals of Asiatic cotton. Furthermore, the Yellow Petal gene (GaYP) was mapped on chromosome 11 by using a recombinant inbred line population. It was found that GaYP encoded a transcriptional factor belonging to Sg6 R2R3-MYB proteins. GaYP could bind to the promoter of flavonol synthase gene (GaFLS) and activate the transcription of downstream genes. Knocking out of GaYP or GaFLS homologs in upland cotton largely eliminated flavonol accumulation and pale yellow coloration in petals. Our results indicated that flavonol synthesis, up-regulated by the R2R3-MYB transcription activator GaYP, was the causative factor for yellow coloration of Asiatic cotton petals. In addition, knocking out of GaYP homologs also led to decrease in anthocyanin accumulation and petal size in upland cotton, suggesting that GaYP and its homologs might modulate developmental or physiological processes beyond flavonol biosynthesis.

Evaluation of a rail logistics transmission system for the transportation of blood components within a medical centre.

BACKGROUND AND OBJECTIVES: Rail logistics transmission systems (RLTSs) are commonly used for the transportation of blood samples, pathological specimens and other medical materials in many hospitals, as they are rapid, secure, cost-effective and intelligent. However, few studies have evaluated blood component transportation from blood banks to the patient care areas of hospitals using RLTS. In this study, we evaluate the RLTS used for the transportation of blood components within a medical centre. MATERIALS AND METHODS: The dispatch of blood components, including packed red blood cells (pRBCs), fresh frozen plasma (FFP), cryoprecipitate and platelet units, from a blood bank to critical care areas or general wards was done using RLTS. Parameters such as the delivery time, temperature, physical integrity and blood component quality were evaluated via analytical testing using specimens obtained before and after transportation by RLTS. RESULTS: The turnaround time and temperature of all tested blood units via RLTS transportation were able to meet the clinical demands of blood component delivery (median time: 323 s [118-668 s]; temperature variation: 4.5-8.9°C for pRBCs and FFP and 21.5-23.5°C for cryoprecipitate and platelet units). Furthermore, parameters of pRBC quality, including the haemolysis index and potassium and lactate dehydrogenase levels in plasma, were not significantly different before and after transportation through RLTS. Similarly, RLTS transportation affected neither the basic coagulation test results in FFP and cryoprecipitate specimens nor platelet aggregation and activation markers in apheresis platelet specimens. CONCLUSION: Hospital-wide delivery of blood components via RLTS seems to be safe, reliable and cost-effective and does not have any negative impact on blood quality. Therefore, the establishment of standard criteria, protocols and guidelines based on further studies is needed.

Visualizing the Intermittent Gating of Na+ /H+ Antiporters in Single Native Bioluminescent Bacteria.

While the intermittent gating of ion channels has been well studied for decades, dynamics of the action of secondary transporters, another major pathway for ion transmembrane transports, remains largely unexplored in living cells. Herein, intermittent blinking of the spontaneous bioluminescence (BL) from single native bacteria, P. phosphoreum, was reported, investigated and attributed to the intermittent gating of sodium/proton antiporters (NhaA) between the active and inactive conformations. Each gating event caused the rapid depolarization and recovery of membrane potential within several seconds, accompanying with the apparent BL blinking due to the transient inhibitions on the activity of the respiratory chain. Temperature-dependent measurements further obtained an activation energy barrier of the conformational change of 20.3 kJ mol-1 .

[Discuss Application of Real-world Data from the Boao Lecheng Pilot Zone to Support Premarket Clinical Evaluation of Medical Device].

The real-world data of Hainan Boao Lecheng International Tourism Pilot Zone has the advantage of supporting pre-market clinical evaluation of medical devices. Based on the relevant requirements of clinical evaluation of medical devices and based on the practical experience of pilot devices in the early stage, the application of Boao Lecheng real-world data in the pre-market clinical evaluation path of medical devices from the perspective of review is discussed. At the same time, the elements that should be considered in real-world study design and the way of data quality evaluation are proposed. Expect to provide a reference in order to allow registration applicants to use real world data wisely to help declare device registration for marketing.

MRCKß links Dasm1 to actin rearrangements to promote dendrite development.

Proper dendrite morphogenesis and synapse formation are essential for neuronal development and function. Dasm1, a member of the immunoglobulin superfamily, is known to promote dendrite outgrowth and excitatory synapse maturation in vitro. However, the in vivo function of Dasm1 in neuronal development and the underlying mechanisms are not well understood. To learn more, Dasm1 knockout mice were constructed and employed to confirm that Dasm1 regulates dendrite arborization and spine formation in vivo. We performed a yeast two-hybrid screen using Dasm1, revealing MRCKß as a putative partner; additional lines of evidence confirmed this interaction and identified cytoplasmic proline-rich region (823-947 aa) of Dasm1 and MRCKß self-activated kinase domain (CC1, 410-744 aa) as necessary and sufficient for binding. Using co-immunoprecipitation assay, autophosphorylation assay, and BS3 cross-linking assay, we show that Dasm1 binding triggers a change in MRCKß's conformation and subsequent dimerization, resulting in autophosphorylation and activation. Activated MRCKß in turn phosphorylates a class 2 regulatory myosin light chain, which leads to enhanced actin rearrangement, causing the dendrite outgrowth and spine formation observed before. Removal of Dasm1 in mice leads to behavioral abnormalities. Together, these results reveal a crucial molecular pathway mediating cell surface and intracellular signaling communication to regulate actin dynamics and neuronal development in the mammalian brain.

Measuring Single Bacterial Viability in Optical Traps with a Power Sweeping Technique.

Assessing bacterial viability is crucial in public health, food safety, environmental microbiology, and other relevant fields. The classical agar plate counting method and the popular dye-based assays have shown their strengths, but they also have limitations including high time consumption, relatively complex sample preparations, and cytotoxicity. In this work, we present a new bacterial viability assay based on optical tweezers utilizing a power sweeping strategy. By monitoring and analyzing bacterial nanomotion in optical traps under different trapping laser powers, the slope of the proportionality between the quantified extent of motion and the trapping laser power was defined as the mobility restriction coefficient (MRC) to quantify bacterial viability. We first established a firm correlation between the viability and MRC by measuring alive and dead Escherichia coli and Photobacterium phosphoreum. Then the capability of real-time long-term characterization of the assay was validated by measuring the viability of individual P. phosphoreum while regulating the viability with an inactivation light. Notably, a 'spinning-induced stabilization' mechanism was proposed to explain the surprising increase of apparent bacterial mobility after inactivation. Overall, the assay was proved to be a reliable label-free bacterial viability assay at a single-cell level, which holds potential in antibiotic susceptibility testing, drug screening, and rapid diagnostics.

Genome resequencing-based high-density genetic map and QTL detection for yield and fiber quality traits in diploid Asiatic cotton (Gossypium arboreum).

Cotton is the most important fiber crop in the world. Asiatic cotton (Gossypium arboreum, genome A2) is a diploid cotton species producing spinnable fibers and important germplasm for cotton breeding and a significant model for fiber biology. However, the genetic map of Asiatic cotton has been lagging behind tetraploid cottons, as well as other stable crops. This study aimed to construct a high-density SNP genetic map and to map QTLs for important yield and fiber quality traits. Using a recombinant inbred line (RIL) population and genome resequencing technology, we constructed a high-density genetic map that covered 1980.17 cM with an average distance of 0.61 cM between adjacent markers. QTL analysis revealed a total of 297 QTLs for 13 yield and fiber quality traits in three environments, explaining 5.0-37.4% of the phenotypic variance, among which 75 were stably detected in two or three environments. Besides, 47 QTL clusters, comprising 131 QTLs for representative traits, were identified. Our works laid solid foundation for fine mapping and cloning of QTL for yield and fiber quality traits in Asiatic cotton.

Gain-Loss-Induced Hybrid Skin-Topological Effect.

Non-Hermitian topological effects are of crucial importance both in fundamental physics and applications. Here we discover the gain-loss-induced hybrid second-order skin-topological effect and the PT phase transition in skin-topological modes. By studying a non-Hermitian Haldane model, we find that the topological edge modes are localized on a special type of corner, while the bulk modes remain extended. Such an effect originates from the interplay between gain, loss, and the chiral edge currents induced by the nonlocal flux, which can be characterized by considering the properties of the edge sites as a one-dimensional chain. We establish a relation between the skin-topological effect and the PT symmetries belonging to different edges. Moreover, we discover the PT phase transition with the emergence of exceptional points between pairs of skin-topological modes. Our results pave the way for the investigation of non-Hermitian topological physics and PT phase transition in higher-dimensional systems.

Bacterial bioluminescence assay for bioanalysis and bioimaging.

Bioluminescence occurs through a chemical reaction in organisms that spontaneously produce light. Luminescent bacteria are unique among bioluminescent organisms. Their bioluminescence intensity is an indicator of their metabolic activity, which can directly reflect the influence of environmental factors on cell viability. Moreover, the whole bioluminescence process is totally gene encoded without the addition of extra substrates. As a result, bacterial bioluminescence has been a powerful tool for whole-cell biosensors and bio-reporters in bioanalysis and bioimaging. This review aims to cover the applications of wild-type and recombinant luminescent bacteria to detect the toxicity of environmental pollutants and biological molecules. The bacterial bioluminescence analytical assay has characteristics such as high sensitivity, short-term detection, and easy operation. Meanwhile, due to the development of gene engineering and optical technology, bacterial luciferase as a reporter protein has been successfully expressed in prokaryotic and eukaryotic cells, tissues, and organs of animals. The major applications for bacterial luciferase-based bioluminescence imaging, such as infectious diseases, cancer therapy, and stem cell tracing, are discussed in this review.

Up-regulation of GhPAP1A results in moderate anthocyanin accumulation and pigmentation in sub-red cotton.

Anthocyanins are a group of important secondary metabolites, functioning as colorant in plant organs as well as protective agents against several stresses. Sub-red plant (Rs) cottons, accumulating moderate level of anthocyanins in shoots, had increased photosynthesis efficiency compared to green- (GL) and red-plant (R1) cottons. The present work aimed to clarify the molecular base of anthocyanin regulation in Rs cotton. It was found that GhPAP1A was significantly up-regulated in Rs plants compared to GL cottons, but its expression level is lower than that of GhPAP1D in R1 plants. Virus induced gene silencing of GhPAP1s inhibited the red pigmentation in Rs plants. Comparative cloning revealed a 50-bp tandem repeat in the promoter of GhPAP1A in Rs cotton, which showed stronger activity to drive the expression of downstream genes in petals. Considered that the coding sequence of GhPAP1As from Rs and GL cottons had similar functions to promote anthocyanin biosynthesis in transgenic tobaccos, we attributed moderate anthocyanin accumulation in Rs cotton to increased transcription of GhPAP1A, resulted from varied promoter structure. Our works suggested GhPAP1s as useful tool to manipulate anthocyanin level and several breeding targets, including herbivore- and pathogen- resistance, high photosynthesis efficiency and colored fibers.

Strong attractions and repulsions mediated by monovalent salts.

Controlling interactions between proteins and nanoparticles in electrolyte solutions is crucial for advancing biological sciences and biotechnology. The assembly of charged nanoparticles (NPs) and proteins in aqueous solutions can be directed by modifying the salt concentration. High concentrations of monovalent salt can induce the solubilization or crystallization of NPs and proteins. By using a multiscale coarse-grained molecular dynamics approach, we show that, due to ionic correlations in the electrolyte, NPs pairs at high monovalent salt concentrations interact via remarkably strong long-range attractions or repulsions, which can be split into three regimes depending on the surface charge densities of the NPs. NPs with zero-to-low surface charge densities interact via a long-range attraction that is stronger and has a similar range to the depletion attraction induced by polymers with radius of gyrations comparable to the NP diameter. On the other hand, moderately charged NPs with smooth surfaces as well as DNA-functionalized NPs with no possibility of hybridization between them interact via a strong repulsion of range and strength larger than the repulsion predicted by models that neglect ionic correlations, including the Derjaguin-Landau-Vervey-Overbeek (DLVO) model. Interactions between strongly charged NPs (>2 e/nm2), both types smooth and DNA-functionalized NPs, show an attractive potential well at intermediate-to-high salt concentrations, which demonstrates that electrolytes can induce aggregation of strongly charged NPs. Our work provides an improved understanding of the role of ionic correlations in NP assembly and design rules to utilize the salting-out process to crystallize NPs.

1H-NMR Metabolomics Analysis of the Effect of Rubusoside on Serum Metabolites of Golden Hamsters on a High-Fat Diet.

Rubusoside is a natural sweetener and the active component of Rubus suavissimus. The preventive and therapeutic effect of rubusoside on high-fat diet-induced (HFD) serum metabolite changes in golden hamsters was analyzed by 1H-NMR metabolomics to explore the underlying mechanism of lipid metabolism regulation. 1H-NMR serum metabolomics analyses revealed a disturbed amino acid-, sugar-, fat-, and energy metabolism in HFD animals. Animals supplemented with rubusoside can partly reverse the metabolism disorders induced by high-fat diet and exerted good anti-hypertriglyceridemia effect by intervening in some major metabolic pathways, involving amino acid metabolism, synthesis of ketone bodies, as well as choline and 4-hydroxyphenylacetate metabolism. This study indicates that rubusoside can interfere with and normalize high-fat diet-induced metabolic changes in serum and could provide a theoretical basis to establish rubusoside as a potentially therapeutic tool able to revert or prevent lipid metabolism disorders.

[Preliminary Review of Relationship between Medical Device Evaluation and Quality Management System in Premarket Approval].

This paper analyzed the current reform of review and approval mechanism for medical devices and discussed the method for technical review process extending to product quality controllable direction and found the measures and suggestions to strengthen technical review for quality management system with the help with complementary relationship between the technical review and the quality management system assessment of the pre-market registration. Nowadays, because of the demand of eRPS， MAH and the amendment of regulation, the integration of technical review and quality management system is more important, necessary and scientific. Scientific and systematic evaluation should be carried out to strengthen the pre-market approval of medical devices and ensure the safety and effectiveness of medical products.

[Application of International Medical Device Electronic Registration].

The eRPS system for medical device registration of National Medical Products Administration was officially launched on June 24, 2019. This paper focused on the following two aspects of the electronic declaration process of medical device regulatory agencies in the whole world:one is whether the electronic submission format is consistent, the other is whether the electronic submission path is convenient. Suggestions are put forward for the next nationwide implementation of the electronic submission so as to speed up the process of the electronization of medical device evaluation in China.

Over-expression of the red plant gene R1 enhances anthocyanin production and resistance to bollworm and spider mite in cotton.

Anthocyanins are a class of pigments ubiquitously distributed in plants and play roles in adoption to several stresses. The red plant gene (R1) promotes light-induced anthocyanin accumulation and red/purple pigmentation in cotton. Using 11 markers developed via genome resequencing, the R1 gene was located in an interval of approximately 136 kb containing three annotated genes. Among them, a PAP1 homolog, GhPAP1D (Gohir.D07G082100) displayed differential transcript level in the red- and green-plant leaves. GhPAP1D encoded a R2R3-MYB transcription factor and its over-expression resulted in increased anthocyanin accumulation in transgenic tobaccos and cottons. Dual luciferase assay indicated that GhPAP1D activated the promoters of several cotton anthocyanin structural genes in tobacco leaves. Importantly, we found that the GhPAP1D-overexpressing cotton leaves had increased resistance to both bollworm and spite mite. Our data demonstrated that GhPAP1D was the controlling gene of the red plant phenotype in cotton, and as the major anthocyanin regulator, this gene was potential to create transgenic cottons with resistance to a broad spectrum of herbivores.

A D-genome-originated Ty1/Copia-type retrotransposon family expanded significantly in tetraploid cottons.

Retrotransposons comprise of a major fraction of higher plant genomes, and their proliferation and elimination have profound effects on genome evolution and gene functions as well. Previously we found a D-genome-originated Ty1/Copia-type LTR (DOCL) retrotransposon in the chromosome A08 of upland cotton. To further characterize the DOCL retrotransposon family, a total of 342 DOCL retrotransposons were identified in the sequenced cotton genomes, including 73, 157, and 112 from Gossypium raimondii, G. hirsutum, and G. barbadense, respectively. According to phylogenetic analysis, the DOCL family was divided into nine groups (G1-G9), among which five groups (G1-G4 and G9, including 292 members) were proliferated after the formation of tetraploid cottons. It was found that the majority of DOCL retrotransposons (especially those in G2, G3 and G9) inserted in non-allelic loci in G. hirsutum and G. barbadense, suggesting that their proliferations were relatively independent in different tetraploid cottons. Furthermore, DOCL retrotransposons inserted in coding regions largely eliminated expression of the targeted genes in G. hirsutum or G. barbadense. Our data suggested that recent proliferation of retrotransposon families like DOCL was one of important evolutionary forces driving diversification and evolution of tetraploid cottons.

Up-regulation of GhTT2-3A in cotton fibres during secondary wall thickening results in brown fibres with improved quality.

Brown cotton fibres are the most widely used naturally coloured raw materials for the eco-friendly textile industry. Previous studies have indicated that brown fibre pigments belong to proanthocyanidins (PAs) or their derivatives, and fibre coloration is negatively associated with cotton productivity and fibre quality. To date, the molecular basis controlling the biosynthesis and accumulation of brown pigments in cotton fibres is largely unknown. In this study, based on expressional and transgenic analyses of cotton homologs of ArabidopsisPA regulator TRANSPARENT TESTA 2 (TT2) and fine-mapping of the cotton dark-brown fibre gene (Lc1), we show that a TT2 homolog, GhTT2-3A, controls PA biosynthesis and brown pigmentation in cotton fibres. We observed that GhTT2-3A activated GhbHLH130D, a homolog of ArabidopsisTT8, which in turn synergistically acted with GhTT2-3A to activate downstream PA structural genes and PA synthesis and accumulation in cotton fibres. Furthermore, the up-regulation of GhTT2-3A in fibres at the secondary wall-thickening stage resulted in brown mature fibres, and fibre quality and lint percentage were comparable to that of the white-fibre control. The findings of this study reveal the regulatory mechanism controlling brown pigmentation in cotton fibres and demonstrate a promising biotechnological strategy to break the negative linkage between coloration and fibre quality and/or productivity.