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.

Intermittent proton bursts of single lactic acid bacteria.

Lactic acid bacteria are a kind of probiotic microorganisms that efficiently convert carbohydrates to lactic acids, thus playing essential roles in fermentation and food industry. While conventional wisdom often suggests continuous release of protons from bacteria during acidification, here we developed a methodology to measure the dynamics of proton release at the single bacteria level, and report on the discovery of a proton burst phenomenon, i.e., the intermittent efflux of protons, of single Lactobacillus plantarum bacteria. When placing an individual bacterium in an oil-sealed microwell, efflux and accumulation of protons consequently reduced the pH in the confined extracellular medium, which was monitored with fluorescent pH indicators in a high-throughput and real-time manner. In addition to the slow and continuous proton release behavior (as expected), stochastic and intermittent proton burst events were surprisingly observed with a typical timescale of several seconds. It was attributed to the regulatory response of bacteria by activating H+-ATPase to compensate the stochastic and transient depolarizations of membrane potential. These findings not only revealed an unprecedented proton burst phenomenon in lactic acid bacteria, but also shed new lights on the intrinsic roles of H+-ATPase in membrane potential homeostasis, with implications for both fermentation industry and bacterial electrophysiology.

Nomogram for predicting severe abdominal pain after initial conventional transarterial chemoembolisation for hepatocellular carcinoma: a retrospective study.

Transarterial chemoembolisation (TACE) is a standard therapy for hepatocellular carcinoma (HCC). However, adverse events, including abdominal pain, are common. This study aimed to investigate and verify the feasibility of a nomogram model to predict severe abdominal pain after first conventional TACE (cTACE) among patients with HCC. Patients with HCC treated with cTACE between October 28, 2019, and August 5, 2022, at a single centre were enrolled (n = 216). Patients were divided into training and validation cohorts (ratio, 7:3). A visual analogue scale score between 7 and 10 was considered severe abdominal pain. A total of 127 (58.8%) patients complained of severe abdominal pain after first cTACE treatment. The nomogram considered age and tumour number and size. The nomogram demonstrated good discrimination, with a C-index of 0.749 (95% confidence interval [CI], 0.617, 0.881). Further, the C-index in the validation cohort reached 0.728 (95% CI 0.592, 0.864). The calibration curves showed ideal agreement between the prediction and real observations, and the nomogram decision curve analysis performed well. The nomogram model can provide an accurate prediction of severe abdominal pain in patients with HCC after first cTACE, aiding in the personalization of pain management and providing novel insights into hospital nursing.

Electrophoretic deposition of magnesium oxide coating on micro-arc oxidized titanium for antibacterial activity and biocompatibility.

Titanium (Ti) dental implants face risks of early failure due to bacterial adhesion and biofilm formation. It is thus necessary to endow the implant surface with antibacterial ability. In this study, magnesium oxide (MgO) coatings were prepared on Ti by combining micro-arc oxidation (MAO) and electrophoretic deposition (EPD). The MgO nanoparticles homogeneously deposited on the microporous surface of MAO-treated Ti, yielding increasing coverage with the EPD time increased to 15 to 60 s. After co-culture with Porphyromonas gingivalis (P. gingivalis) for 24 h, 48 h, and 72 h, the coatings produced antibacterial rates of 4-53 %, 27-71 %, and 39-79 %, respectively, in a dose-dependent manner. Overall, EPD for 45 s offered satisfactory comprehensive performance, with an antibacterial rate 79 % at 72 h and a relative cell viability 85 % at 5 d. Electron and fluorescence microscopies revealed that, both the density of adherent bacterial adhesion on the surface and the proportion of viable bacteria decreased with the EPD time. The morphology of cells on the surface of each group was intact and there was no significant difference among the groups. These results show that, the MgO coating deposited on MAO-treated Ti by EPD had reasonably good in vitro antibacterial properties and cytocompatibility.

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.

Protective effect of Helianthus annuus seed byproduct extract on ultraviolet radiation-induced injury in skin cells.

Helianthus annuus seed byproduct is a residual product obtained after seed oil extraction. The present study investigated the preventive and repair effects of the H. annuus seed byproduct ethanol extract (HSE) on ultraviolet radiation (UVR)-induced injury in human immortalized keratinocytes (HaCaTs) and human skin fibroblasts (HSFs). Results revealed that the total phenolic acid and oligosaccharide content in HSE was >50%. HSE had a stronger preventive effect on UVR-induced injury than the repair effect. Moreover, phenolic acids were the main active component of HSE mediating the preventative effect. In HaCaTs and HSFs, HSE prevented UVR-induced injury by inhibiting excessive ROS production. It reduced the secretion of tumor necrosis TNF-α, IL-1α, IL-1ß, IL-6, and IL-8 by inhibiting the level of ROS, thus reducing inflammation-mediated injury to skin cells. In addition, HSE inhibited the expression of various mRNA kinases in the MAPK-ERK/p38/JNK pathway. This downregulated the expression of activator protein-1 (AP-1) mRNA and further reduced the secretion of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-9 as well as reduced UVR-induced injury to the cells. In conclusion, HSE is a broad-spectrum, natural UV filter with high efficiency and low toxicity that has the potential to be used in sunscreen products.

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.

MPs-ACT, an Assay to Evaluate the Procoagulant Activity of Microparticles.

The procoagulant effect of microparticles (MPs) contributes to hypercoagulability-induced thrombosis. We provide preliminary findings of the MPs-Activated Clotting Time (MPs-ACT) assay to determine the procoagulant activity of MPs. MPs-rich plasma was obtained and recalcified. Changes in plasma viscoelasticity were evaluated and the time to the peak viscoelastic changes was defined as the MPs-ACT. MPs concentration was measured by flow cytometry. Coagulation products produced during plasma clotting were identified by fibrin and fibrinopeptide A. MPs were prepared in vitro and added to standard plasma to simulate pathological samples. In addition, reproducibility and sensitivity were evaluated. We confirmed the linear relationship between MPs-ACT and MP concentrations. Dynamic changes in fibrin production were depicted. We simulated the correlation between MPs-ACT and standard plasma containing MPs prepared in vitro. The reproducibility of high-value and low-value samples was 6.0% and 10.8%, respectively. MPs-ACT sensitively detected hypercoagulable samples from patients with pre-eclampsia, hip fractures, and lung tumors. MPs-ACT largely reflects the procoagulant effect of MPs. MPs-ACT sensitively and rapidly detects hypercoagulability with MPs-rich plasma. It may be promising for the diagnosis of hypercoagulable states induced by MPs.

[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.

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 .

Lycorine upregulates the expression of RMB10, promotes apoptosis and inhibits the proliferation and migration of cervical cancer cells.

Although there are numerous treatment strategies, including surgery and chemotherapy, the prognosis of cervical cancer remains far from satisfactory. There is an urgent need to develop more effective, more tolerable and safer therapeutics for the treatment of cervical cancer. Lycorine is a natural plantextract that has been previously found to confer anti­tumor activities. Therefore, in the present study, the effects of lycorine and its possible mechanism of action in cervical cancer were investigated. Cell Counting Kit­8, wound healing and Transwell assays were used to verify the proliferation and migration of HeLa cells following lycorine intervention. The results demonstrated that lycorine significantly inhibited the proliferation and migration of HeLa cells. RNA binding motif 10 (RBM10) is a protein associated with apoptosis. It has been suggested that lycorine can affect the expression of RBM10. Flow cytometry demonstrated that lycorine may inhibit the initiation and progression of cervical cancer by promoting apoptosis, which may be mediated through the upregulation of RBM10 expression and increasing TNF­α levels. Xenograft mouse experiments indicated that when lycorine was injected through the tail vein, HeLa tumor growth was inhibited. Mechanistically, western blotting demonstrated that lycorine significantly inhibited the activation of the Akt signaling pathway and potentially reversed epithelial­mesenchymal transition, which was also mediated by RBM10. Furthermore, following RBM10 knockdown with small interfering­RNA, the inhibitory effects of lycorine on cervical cancer was significantly abrogated. Overall, results of the present study suggest that lycorine can upregulate the expression of RBM10 and inhibit the proliferation and migration of cervical cancer cells.

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.

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.

Immunoglobulin superfamily 9 (IGSF9) is trans-activated by p53, inhibits breast cancer metastasis via FAK.

Metastasis of breast cancer represents the major reason for its poor prognosis, leading to high mortality. In breast cancer, a tumor suppressor gene TP53 is commonly mutated. TP53 mutation leads to an altered expression of various genes, an event that is associated with aggressive tumor and is a strong independent marker for survival. In this study, we identified a novel p53 target gene, immunoglobulin superfamily 9 (IGSF9). IGSF9 is generally down-regulated in breast cancer tissues. Loss of IGSF9 is associated with frequent metastasis and poor prognosis of breast cancer patients. Wild-type p53, but not R175H mutant, trans-activates the transcription of IGSF9 via binding to its promoter (-137 to -131 bp), inhibits epithelial-mesenchymal transition (EMT), consequently the inhibition of breast cancer cells migration and invasion. IGSF9 interacts with focal adhesion kinase (FAK) and inhibits FAK/AKT signaling activity. PND1186, FAK inhibitor, inhibits breast cancer metastasis induced by IGSF9 knockdown in vitro and in vivo. Taken together, IGSF9 is trans-activated by p53 and inhibits breast cancer metastasis by modulating FAK/AKT signaling pathway. IGSF9 could serve as a prognostic marker and potential therapeutic target for breast cancer.

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.

Vascular smooth muscle cell c-Fos is critical for foam cell formation and atherosclerosis.

BACKGROUND: Hyperlipidemia-induced vascular smooth muscle cell (VSMC)-derived foam cell formation is considered a crucial event in the development of atherosclerosis. Since c-Fos emerges as a key modulator of lipid metabolism, we investigated whether c-Fos plays a role in hyperlipidemia-induced VSMC-derived foam cell formation and atherosclerosis. APPROACH AND RESULTS: c-Fos expression was observed in VSMCs in atherosclerotic plaques from patients and western diet-fed atherosclerosis-prone LDLR-/- and ApoE-/- mice by immunofluorescence staining. To ascertain c-Fos's function in atherosclerosis development, VSMC-specific c-Fos deficient mice in ApoE-/- background were established. Western diet-fed c-FosVSMCKOApoE-/- mice exhibited a significant reduction of atherosclerotic lesion formation as measured by hematoxylin and eosin staining, accompanied by decreased lipid deposition within aortic roots as determined by Oil red O staining. Primary rat VSMCs were isolated to examine the role of c-Fos in lipid uptake and foam cell formation. oxLDL stimulation resulted in VSMC-derived foam cell formation and elevated intracellular mitochondrial reactive oxygen species (mtROS), c-Fos and LOX-1 levels, whereas specific inhibition of mtROS, c-Fos or LOX-1 lessened lipid accumulation in oxLDL-stimulated VSMCs. Mechanistically, oxLDL acts through mtROS to enhance transcription activity of c-Fos to facilitate the expression of LOX-1, exerting a feedforward mechanism with oxLDL to increase lipid uptake and propel VSMC-derived foam cell formation and atherogenesis. CONCLUSION: Our study demonstrates a fundamental role of mtROS/c-Fos/LOX-1 signaling pathway in promoting oxLDL uptake and VSMC-derived foam cell formation during atherosclerosis. c-Fos may represent a promising therapeutic target amenable to clinical translation in the future.

Adipose-derived stem cells promote the proliferation, migration, and invasion of oral squamous cell carcinoma cells by activating the Wnt/planar cell polarity signaling pathway.

Background: Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral and maxillofacial region. Adipose-derived stem cells (ADSCs) interact with a variety of malignant tumors to promote their proliferation and metastasis. Abnormalities in Wnt/planar cell polarity (PCP) signaling and overactivation of the signaling pathway are considered to be related to the occurrence and development of various malignant tumors. In order to determine whether ADSC can promote tumorigenesis in OSCC and its molecular mechanism, we conducted a series of studies. Methods: The effect of ADSCs on the occurrence and development of OSCC was studied in vivo and in vitro, and the molecular mechanism was investigated using Western blot and immunofluorescence (IHC) assays. Results: The results revealed that ADSCs could promote the proliferation, invasion, and migration of OSCC cells in a dose- and time-dependent manner. With regard to the mechanism, the expression of collagen triple helix repeat-containing protein 1 (CTHRC1) and phospho-c-Jun (p-c-Jun) increased significantly with enhancement of the interaction between ADSCs and OSCC cells, indicating that the Wnt/PCP signaling pathway was overactivated. Conclusions: ADSCs promote the pathogenesis of OSCC by activating the Wnt/PCP signaling pathway, suggesting that proteins related to this pathway may be potential therapeutic targets for OSCC.

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.

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.