Singular dielectric nanolaser with atomic-scale field localization.

Compressing the optical field to the atomic scale opens up possibilities for directly observing individual molecules, offering innovative imaging and research tools for both physical and life sciences. However, the diffraction limit imposes a fundamental constraint on how much the optical field can be compressed, based on the achievable photon momentum1,2. In contrast to dielectric structures, plasmonics offer superior field confinement by coupling the light field with the oscillations of free electrons in metals3-6. Nevertheless, plasmonics suffer from inherent ohmic loss, leading to heat generation, increased power consumption and limitations on the coherence time of plasmonic devices7,8. Here we propose and demonstrate singular dielectric nanolasers showing a mode volume that breaks the optical diffraction limit. Derived from Maxwell's equations, we discover that the electric-field singularity sustained in a dielectric bowtie nanoantenna originates from divergence of momentum. The singular dielectric nanolaser is constructed by integrating a dielectric bowtie nanoantenna into the centre of a twisted lattice nanocavity. The synergistic integration surpasses the diffraction limit, enabling the singular dielectric nanolaser to achieve an ultrasmall mode volume of about 0.0005 λ3 (λ, free-space wavelength), along with an exceptionally small feature size at the 1-nanometre scale. To fabricate the required dielectric bowtie nanoantenna with a single-nanometre gap, we develop a two-step process involving etching and atomic deposition. Our research showcases the ability to achieve atomic-scale field localization in laser devices, paving the way for ultra-precise measurements, super-resolution imaging, ultra-efficient computing and communication, and the exploration of light-matter interactions within the realm of extreme optical field localization.

Reconfigurable moiré nanolaser arrays with phase synchronization.

Miniaturized lasers play a central role in the infrastructure of modern information society. The breakthrough in laser miniaturization beyond the wavelength scale has opened up new opportunities for a wide range of applications1-4, as well as for investigating light-matter interactions in extreme-optical-field localization and lasing-mode engineering5-19. An ultimate objective of microscale laser research is to develop reconfigurable coherent nanolaser arrays that can simultaneously enhance information capacity and functionality. However, the absence of a suitable physical mechanism for reconfiguring nanolaser cavities hinders the demonstration of nanolasers in either a single cavity or a fixed array. Here we propose and demonstrate moiré nanolaser arrays based on optical flatbands in twisted photonic graphene lattices, in which coherent nanolasing is realized from a single nanocavity to reconfigurable arrays of nanocavities. We observe synchronized nanolaser arrays exhibiting high spatial and spectral coherence, across a range of distinct patterns, including P, K and U shapes and the Chinese characters '' and '' ('China' in Chinese). Moreover, we obtain nanolaser arrays that emit with spatially varying relative phases, allowing us to manipulate emission directions. Our work lays the foundation for the development of reconfigurable active devices that have potential applications in communication, LiDAR (light detection and ranging), optical computing and imaging.

CDK11 requires a critical activator SAP30BP to regulate pre-mRNA splicing.

CDK11 is an emerging druggable target for cancer therapy due to its prevalent roles in phosphorylating critical transcription and splicing factors and in facilitating cell cycle progression in cancer cells. Like other cyclin-dependent kinases, CDK11 requires its cognate cyclin, cyclin L1 or cyclin L2, for activation. However, little is known about how CDK11 activities might be modulated by other regulators. In this study, we show that CDK11 forms a tight complex with cyclins L1/L2 and SAP30BP, the latter of which is a poorly characterized factor. Acute degradation of SAP30BP mirrors that of CDK11 in causing widespread and strong defects in pre-mRNA splicing. Furthermore, we demonstrate that SAP30BP facilitates CDK11 kinase activities in vitro and in vivo, through ensuring the stabilities and the assembly of cyclins L1/L2 with CDK11. Together, these findings uncover SAP30BP as a critical CDK11 activator that regulates global pre-mRNA splicing.

Attractant and repellent induce opposing changes in the four-helix bundle ligand-binding domain of a bacterial chemoreceptor.

Motile bacteria navigate toward favorable conditions and away from unfavorable environments using chemotaxis. Mechanisms of sensing attractants are well understood; however, molecular aspects of how bacteria sense repellents have not been established. Here, we identified malate as a repellent recognized by the MCP2201 chemoreceptor in a bacterium Comamonas testosteroni and showed that it binds to the same site as an attractant citrate. Binding determinants for a repellent and an attractant had only minor differences, and a single amino acid substitution in the binding site inverted the response to malate from a repellent to an attractant. We found that malate and citrate affect the oligomerization state of the ligand-binding domain in opposing way. We also observed opposing effects of repellent and attractant binding on the orientation of an alpha helix connecting the sensory domain to the transmembrane helix. We propose a model to illustrate how positive and negative signals might be generated.

The causes of sea-level rise since 1900.

The rate of global-mean sea-level rise since 1900 has varied over time, but the contributing factors are still poorly understood1. Previous assessments found that the summed contributions of ice-mass loss, terrestrial water storage and thermal expansion of the ocean could not be reconciled with observed changes in global-mean sea level, implying that changes in sea level or some contributions to those changes were poorly constrained2,3. Recent improvements to observational data, our understanding of the main contributing processes to sea-level change and methods for estimating the individual contributions, mean another attempt at reconciliation is warranted. Here we present a probabilistic framework to reconstruct sea level since 1900 using independent observations and their inherent uncertainties. The sum of the contributions to sea-level change from thermal expansion of the ocean, ice-mass loss and changes in terrestrial water storage is consistent with the trends and multidecadal variability in observed sea level on both global and basin scales, which we reconstruct from tide-gauge records. Ice-mass loss-predominantly from glaciers-has caused twice as much sea-level rise since 1900 as has thermal expansion. Mass loss from glaciers and the Greenland Ice Sheet explains the high rates of global sea-level rise during the 1940s, while a sharp increase in water impoundment by artificial reservoirs is the main cause of the lower-than-average rates during the 1970s. The acceleration in sea-level rise since the 1970s is caused by the combination of thermal expansion of the ocean and increased ice-mass loss from Greenland. Our results reconcile the magnitude of observed global-mean sea-level rise since 1900 with estimates based on the underlying processes, implying that no additional processes are required to explain the observed changes in sea level since 1900.

Pain symptoms are associated with two-point discrimination threshold in patients with temporomandibular disorders.

OBJECTIVE: This study aimed to explore the associations of orofacial two-point discrimination (2-PD) test result with pain symptoms and psychological factors in patients with Temporomandibular Disorders (TMDs). METHODS: 193 patients with TMDs were included in this study. Patients' demographics, pain intensity, and psychological status were recorded. The 2-PDs in the bilateral temporal, zygomatic, mandibular, and temporomandibular joint (TMJ) regions of the patients were measured. Statistical analyses were conducted to observe the associations between variables. RESULTS: For Pain-related TMDs (PT) patients, Monthly Visual Analogue Scale (VAS-M) and Current Analogue Scale (VAS-C) were correlated with TMJ, zygomatic and temporal 2-PDs. Patients with PT tended to have higher TMJ 2-PDs[Right: ß = 1.827 mm, 95%CI(0.107, 3.548), P = 0.038], zygomatic 2-PDs[Right: ß = 1.696 mm, 95%CI(0.344, 3.048), P = 0.014], temporal 2-PDs[Left: ß = 2.138 mm, 95%CI(0.127, 4.149), P = 0.037; Right: ß = 1.893 mm, 95%CI(0.011, 3.775), P = 0.049]. Associations were also observed between VAS-C and TMJ 2-PDs[Left: ß = 0.780, 95%CI(0.190, 1.370), P = 0.01; Right: ß = 0.885, 95%CI(0.406, 1.364), P = 0.001], Zygomatic 2-PDs[Right: ß = 0.555, 95%CI(0.172, 0.938), P = 0.005]; VAS-M and TMJ 2-PDs[Left: ß = 0.812, 95%CI(0.313, 1.311), P = 0.002; Right: ß = 0.567, 95%CI(0.152, 0.983), P = 0.008], zygomatic 2-PDs[Left: ß = 0.405, 95%CI(0.075, 0.735), P = 0.016; Right: ß = 0.545, 95%CI(0.221, 0.870), P = 0.001], and temporal 2-PDs [Left: ß = 0.741, 95%CI(0.258, 1.224), P = 0.003; Right: ß = 0.519, 95%CI(0.063, 0.975), P = 0.026]. CONCLUSION: TMJ, zygomatic, and temporal 2-PDs were significantly associated with PT and pain intensity. Age, gender and psychological factors were not associated with orofacial 2-PDs. PT patients exhibited weaker tactile acuity compared to Non-PT patients. Further discussion on the underlying mechanism is needed. CLINICAL RELEVANCE: Orofacial tactile acuity of TMDs patients was associated with their pain symptoms, which researchers should take account into when performing 2-PD tests for TMDs patients. The 2-PD test can be considered as a potential tool along with the current procedures for the differentiations of PT and Non-PT.

Contribution of inwardly rectifying K+ channel 4.1 of supraoptic astrocytes to the regulation of vasopressin neuronal activity by hypotonicity.

Astrocytic morphological plasticity and its modulation of adjacent neuronal activity are largely determined by astrocytic volume regulation, in which glial fibrillary acidic protein (GFAP), aquaporin 4 (AQP4), and potassium channels including inwardly rectifying K+ channel 4.1 (Kir4.1) are essential. However, associations of astrocyte-dominant Kir4.1 with other molecules in astrocytic volume regulation and the subsequent influence on neuronal activity remain unclear. Here, we report our study on these issues using primary cultures of rat pups' hypothalamic astrocytes and male adult rat brain slices. In astrocyte culture, hyposmotic challenge (HOC) significantly decreased GFAP monomer expression and astrocytic volume at 1.5 min and increased Kir4.1 expression and inwardly rectifying currents (IRCs) at 10 min. BaCl2 (100 µmol/l) suppressed the HOC-increased IRCs, which was simulated by VU0134992 (2 µmol/l), a Kir4.1 blocker. Preincubation of the astrocyte culture with TGN-020 (10 µmol/l, a specific AQP4 blocker) made the HOC-increased Kir4.1 currents insignificant. In hypothalamic brain slices, HOC initially decreased and then increased the firing rate of vasopressin (VP) neurons in the supraoptic nucleus. In the presence of BaCl2 or VU0134992, HOC-elicited rebound increase in VP neuronal activity was blocked. GFAP was molecularly associated with Kir4.1, which was increased by HOC at 20 min; this increase was blocked by BaCl2 . These results suggest that HOC-evoked astrocytic retraction or decrease in the volume and length of its processes is associated with increased Kir4.1 activity. Kir4.1 involvement in HOC-elicited astrocytic retraction is associated with AQP4 activity and GFAP plasticity, which together determines the rebound excitation of VP neurons.

Time course of changes in the transcriptome during russet induction in apple fruit.

BACKGROUND: Russeting is a major problem in many fruit crops. Russeting is caused by environmental factors such as wounding or moisture exposure of the fruit surface. Despite extensive research, the molecular sequence that triggers russet initiation remains unclear. Here, we present high-resolution transcriptomic data by controlled russet induction at very early stages of fruit development. During Phase I, a patch of the fruit surface is exposed to surface moisture. For Phase II, moisture exposure is terminated, and the formerly exposed surface remains dry. We targeted differentially expressed transcripts as soon as 24 h after russet induction. RESULTS: During moisture exposure (Phase I) of 'Pinova' apple, transcripts associated with the cell cycle, cell wall, and cuticle synthesis (SHN3) decrease, while those related to abiotic stress increase. NAC35 and MYB17 were the earliest induced genes during Phase I. They are therefore linked to the initial processes of cuticle microcracking. After moisture removal (Phase II), the expression of genes related to meristematic activity increased (WOX4 within 24 h, MYB84 within 48 h). Genes related to lignin synthesis (MYB52) and suberin synthesis (MYB93, WRKY56) were upregulated within 3 d after moisture removal. WOX4 and AP2B3 are the earliest differentially expressed genes induced in Phase II. They are therefore linked to early events in periderm formation. The expression profiles were consistent between two different seasons and mirrored differences in russet susceptibility in a comparison of cultivars. Furthermore, expression profiles during Phase II of moisture induction were largely identical to those following wounding. CONCLUSIONS: The combination of a unique controlled russet induction technique with high-resolution transcriptomic data allowed for the very first time to analyse the formation of cuticular microcracks and periderm in apple fruit immediately after the onset of triggering factors. This data provides valuable insights into the spatial-temporal dynamics of russeting, including the synthesis of cuticles, dedifferentiation of cells, and impregnation of cell walls with suberin and lignin.

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.

Effect of different substituents on the fluorescence properties of precursors of synthetic GFP analogues and a polarity-sensitive lipid droplet probe with AIE properties for imaging cells and zebrafish.

The green fluorescent protein (GFP) is a purely natural specialty protein that has been widely used to design synthetic fluorescent probes. In the present work we designed and synthesized a series of fluorescent compounds akin to GFP precursors by a one-step method, and investigated the luminescence properties of the fluorescent compounds by varying the substituents. We presented the first systematic summary of the photophysical data including extinction coefficients and fluorescence quantum yields for this class of fluorescent dyes. We also carried out density functional theory (DFT) calculations for these dyes to investigate the effect of electronic effects due to different substituents. These studied optical properties may provide a reference for later probe design. More interestingly, we have developed a polarity-sensitive lipid droplet probe T-LD with AIE properties on this basis. The probe exhibited not only favorable pH stability and kinetic stability in terms of optical properties, but also solvent discolouration and polarity-sensitive properties, and was able to label intracellular lipid droplets. We successfully applied the probe for intracellular lipid droplet level monitoring and zebrafish imaging.

Removal of nitrate by FeSiBC metallic glasses: high efficiency and superior reusability.

The development of sustainable technologies for efficient nitrate removal has attracted increasing attention, because excessive nitrate emissions can result in serious environmental, economic, and health effects. Herein, we propose to utilize FeSiBC metallic glass (MG) powders as a potential solution for nitrate removal. In terms of removal efficiency and reusability, our results show that the MG powders, as special zero-valent iron carriers, are 2-3 orders of magnitude more efficient in nitrate removal than the previous studies, while maintaining more than 50% nitrate removal efficiency after 9 cycles of reaction. Moreover, the optimal FeSiBC MG dosage, pH value, and temperature for nitrate removal are determined. The mechanism of nitrate removal is also revealed. The present study offers a promising approach to remediate nitrate, one of the world's most widespread water pollutants.

Fox transcription factor AccGRF1 in response to glyphosate stress in Apis cerana cerana.

Glyphosate is an herbicide commonly used in agriculture, and its widespread use has adversely affected the survival of nontarget organisms. Among these organisms, bees in particular are important pollinators, and declining bee populations have severely affected crop yields around the world. However, the molecular mechanism by which glyphosate harms bees remains unclear. In our experiment, we screened and cloned a glyphosate-induced gene in Apis cerana cerana (A. c. cerana) and named glyphosate response factor 1 (AccGRF1). Sequence analysis showed that AccGRF1 contains a winged-helix DNA binding domain, which suggests that it belongs to the Forkhead box (Fox) protein family. qRT-PCR and heterologous expression in Escherichia coli and yeast showed that AccGRF1 can respond to glyphosate and oxidative stress. After AccGRF1 knockdown by means of RNA interference (RNAi), the resistance of A. c. cerana to glyphosate stress improved. The results suggested that AccGRF1 is involved in A. c. cerana glyphosate stress tolerance. This study reveals the functions of Fox transcription factors in response to glyphosate stress and provides molecular insights into the regulation of glyphosate responses in honeybees.

Point-of-Care Ultrasonography Helped to Rapidly Detect Pneumomediastinum in a Vomiting Female.

Vomiting-induced pneumomediastinum is a rare presentation and can be a result of alveolar rupture (Mackler effect) or Boerhaave syndrome. Patients diagnosed with Boerhaave syndrome may present with the classic Mackler triad of vomiting, chest pain, and subcutaneous emphysema. However, there exists a large overlap of symptoms accompanying Boerhaave syndrome and the Macklin effect, including retrosternal chest pain, neck discomfort, cough, sore throat, dysphagia, dysphonia, and dyspnea. Boerhaave syndrome is a dangerous condition. Delayed diagnosis of Boerhaave syndrome may worsen sepsis and cause mortality. Therefore, early diagnosis and timely management are important to prevent further complications. Here, we present a case of vomiting-induced pneumomediastinum, which supports the use of bedside ultrasonography to aid in the diagnosis and rapid differentiation of etiology of pneumomediastinum.

[Role of autophagy in cadmium-induced damage to the blood-testis barrier in mice].

OBJECTIVE: To investigate the role of autophagy in cadmium chloride (CdCl2)-induced damage to the blood-testis barrier (BTB) in mice. METHODS: Twenty four-week-old male C57BL/6 mice were randomly divided into four groups and intraperitoneally injected with CdCl2 at 0 mg/kg/d (the control), 0.5 mg/kg/d (low-dose), 1.0 mg/kg/d (medium-dose) and 2.0 mg/kg/d (high-dose) respectively for 28 consecutive days. Then the morphological changes of the testis tissue was observed by HE staining, the integrity of BTB measured with the biotracer, and the expressions of the BTB components ZO-1 and N-Cadherin proteins detected by Western blot. The TM4 Sertoli cells were treated with CdCl2at 0, 2.5, 5 and 10 µmol/L respectively for 24 hours, followed by determination of the expression levels of ZO-1 and N-Cadherin as well as the autophagy-related proteins LC3II and p62. Then the cells were again treated with CdCl2 in the presence of the autophagy inhibitor chloroquine (CQ) at 5 µmol/L or the autophagy inducer rapamycin (Rap) at 50 nmol/L for 24 hours, followed by measurement of the expressions of LC3II, p62, ZO-1 and N-Cadherin by Western blot. RESULTS: Compared with the control group, the cadmium-exposed mice showed increased interstitial space in the seminiferous tubules, formation of intracellular cavitation in the germ cells with decreased layers and disordered arrangement, and damaged integrity of the BTB. The expressions of the ZO-1 and N-Cadherin proteins were significantly down-regulated in the testis tissue of the mice in the medium- and high-dose CdCl2 groups (P < 0.05), and even more significantly in the CdCl2-exposed cells in comparison with those in the control mice (P < 0.01), while the expressions of the LC3II and p62 proteins were remarkably up-regulated (P < 0.05). The expressions of ZO-1, N-Cadherin, LC3II and p62 were also up-regulated in the cells co-treated with CQ and CdCl2 (P < 0.01), those of ZO-1, N-Cadherin and p62 down-regulated (P< 0.05) and that of LC3II up-regulated (P < 0.05) in the cells co-treated with Rap and CdCl2. CONCLUSION: CdCl2 can damage the integrity of the mouse BTB, which may be attributed to its ability to enhance the autophagy in Sertoli cells and regulate the expressions of BTB proteins.

[HFD-induced obesity triggers testicular cell senescence and endoplasmic reticulum stress in male mice].

OBJECTIVE: To investigate high-fat diet-induced obesity-triggered testicular cell senescence and endoplasmic reticulum stress. METHODS: We randomly and equally divided 10 four-week-old male C57BL/6J mice into a control and a high-fat group, the former fed with a diet of 10% fat content while the latter with a diet of 60% fat content to establish an obesity model. After eight weeks of feeding, we observed the pathological changes in the testis tissue of the mice by HE staining, detected the serum T content by ELISA, measured the telomere length in the testis cells by RT-PCR, and examined the activity of senescence-associated ß-galactosidase (SA-ß-gal) by histochemical staining. Using RT-qPCR and Western blot, we determined the protein and mRNA expressions of the cell senescence markers p16 and p21 as well as the protein expressions of the endoplasmic reticulum stress markers GRP78 and CHOP in the testis tissue. RESULTS: Compared with the controls, the animals of the high-fat group showed a 45% increase in the body weight, disordered structure of the spermatogenic cells, reduced level of serum T and shortened telomere length of the testis cells (P < 0.01). The mRNA and protein expressions of p16 and p21 were dramatically higher in the high-fat than in the control group (P<0.01), so were the intracellular SA-ß-gal activity and the protein expressions of CHOP and GRP78 (P<0.01). CONCLUSION: High-fat diet-induced obesity triggers testicular cell senescence and endoplasmic reticulum stress in male mice.

Stable Isotope-Resolved Metabolomics Studies on Corticosteroid-Induced PC12 Cells: A Strategy for Evaluating Glucose Catabolism in an in Vitro Model of Depression.

Depression is a common psychopathological state or mood disorder syndrome. The serious risks to human life and the inadequacy of the existing antidepressant drugs have driven us to understand the pathogenesis of depression from a new perspective. Our research group has found disturbances in glucose catabolism in both depression and nephrotic syndrome. What are the specific metabolic pathways and specificities of glucose catabolism disorders caused by depression? To address the above scientific questions, we creatively combined traditional metabolomics technology with stable isotope-resolved metabolomics to research the glucose catabolism of the corticosterone-induced PC12 cell damage model and the adriamycin-induced glomerular podocyte damage model. The results showed an increased flux of pyruvate metabolism in depression. The increased flux of pyruvate metabolism led to an activation of gluconeogenesis in depression. The disturbed upstream metabolism of succinate caused the tricarboxylic acid cycle (TCA cycle) to be blocked in depression. In addition, there were metabolic disturbances in the purine metabolism and pentose phosphate pathways in depression. Compared with nephrotic syndrome, pyruvate metabolism, the TCA cycle, and gluconeogenesis metabolism in depression were specific. The metabolic pathways researched above are likely to be important targets for the efficacy of antidepressants.

Adaptive specialization of a unique sponge body from the Cambrian Qingjiang biota.

Sponge fossils from the Cambrian black shales have attracted attention from both palaeontologists and geochemists for many years in terms of their high diversity, beautiful preservation and perplexing adaptation to inhospitable living environments. However, the body shape of these sponges, which contributes to deciphering adaptive evolution, has not been scrutinized. New complete specimens of the hexactinellid sponge Sanshapentella tentoriformis sp. nov. from the Qingjiang biota (black shale of the Cambrian Stage 3 Shuijingtuo Formation, ca 518 Ma) allow recognition of a unique dendriform body characterized by a columnar trunk with multiple conical high peaks and distinctive quadripod-shaped dermal spicules that frame each high peak. The body shape of this new sponge along with other early Cambrian hexactinellids, is classified into three morpho-groups that reflect different levels of adaptivity to the environment. The cylindrical and ovoid bodies generally adapted to a large spectrum of environments; however, the dendriform body of S. tentoriformis was restricted to the relatively deep-water, oxygen-deficient environment. From a hindsight view, the unique body shape represents a consequence of adaptation that helps maintain an effective use of oxygen and a low energy cost in hypoxic conditions.

Deciphering Molecular Mechanism Underlying Self-Flocculation of Zymomonas mobilis for Robust Production.

Zymomonas mobilis metabolizes sugar anaerobically through the Entner-Doudoroff pathway with less ATP generated for lower biomass accumulation to direct more sugar for product formation with improved yield, making it a suitable host to be engineered as microbial cell factories for producing bulk commodities with major costs from feedstock consumption. Self-flocculation of the bacterial cells presents many advantages, such as enhanced tolerance to environmental stresses, a prerequisite for achieving high product titers by using concentrated substrates. ZM401, a self-flocculating mutant developed from ZM4, the unicellular model strain of Z. mobilis, was employed in this work to explore the molecular mechanism underlying this self-flocculating phenotype. Comparative studies between ZM401 and ZM4 indicate that a frameshift caused by a single nucleotide deletion in the poly-T tract of ZMO1082 fused the putative gene with the open reading frame of ZMO1083, encoding the catalytic subunit BcsA of the bacterial cellulose synthase to catalyze cellulose biosynthesis. Furthermore, the single nucleotide polymorphism mutation in the open reading frame of ZMO1055, encoding a bifunctional GGDEF-EAL protein with apparent diguanylate cyclase/phosphodiesterase activities, resulted in the Ala526Val substitution, which consequently compromised in vivo specific phosphodiesterase activity for the degradation of cyclic diguanylic acid, leading to intracellular accumulation of the signaling molecule to activate cellulose biosynthesis. These discoveries are significant for engineering other unicellular strains from Z. mobilis with the self-flocculating phenotype for robust production. IMPORTANCE Stress tolerance is a prerequisite for microbial cell factories to be robust in production, particularly for biorefinery of lignocellulosic biomass to produce biofuels, bioenergy, and bio-based chemicals for sustainable socioeconomic development, since various inhibitors are released during the pretreatment to destroy the recalcitrant lignin-carbohydrate complex for sugar production through enzymatic hydrolysis of the cellulose component, and their detoxification is too costly for producing bulk commodities. Although tolerance to individual stress has been intensively studied, the progress seems less significant since microbial cells are inevitably suffering from multiple stresses simultaneously under production conditions. When self-flocculating, microbial cells are more tolerant to multiple stresses through the general stress response due to enhanced quorum sensing associated with the morphological change for physiological and metabolic advantages. Therefore, elucidation of the molecular mechanism underlying such a self-flocculating phenotype is significant for engineering microbial cells with the unique multicellular morphology through rational design to boost their production performance.

Metrological Characterization of Non-Gaussian Entangled States of Superconducting Qubits.

Multipartite entangled states are significant resources for both quantum information processing and quantum metrology. In particular, non-Gaussian entangled states are predicted to achieve a higher sensitivity of precision measurements than Gaussian states. On the basis of metrological sensitivity, the conventional linear Ramsey squeezing parameter (RSP) efficiently characterizes the Gaussian entangled atomic states but fails for much wider classes of highly sensitive non-Gaussian states. These complex non-Gaussian entangled states can be classified by the nonlinear squeezing parameter (NLSP), as a generalization of the RSP with respect to nonlinear observables and identified via the Fisher information. However, the NLSP has never been measured experimentally. Using a 19-qubit programmable superconducting processor, we report the characterization of multiparticle entangled states generated during its nonlinear dynamics. First, selecting ten qubits, we measure the RSP and the NLSP by single-shot readouts of collective spin operators in several different directions. Then, by extracting the Fisher information of the time-evolved state of all 19 qubits, we observe a large metrological gain of 9.89_{-0.29}^{+0.28} dB over the standard quantum limit, indicating a high level of multiparticle entanglement for quantum-enhanced phase sensitivity. Benefiting from high-fidelity full controls and addressable single-shot readouts, the superconducting processor with interconnected qubits provides an ideal platform for engineering and benchmarking non-Gaussian entangled states that are useful for quantum-enhanced metrology.

Sodium channel 1 subunit alpha SCNN1A exerts oncogenic function in pancreatic cancer via accelerating cellular growth and metastasis.

The identification of new diagnostic and therapeutic biomarkers might be helpful to understand molecular mechanism of cancer pathogenesis and develop anti-cancer targets. This study reported the alteration of Sodium channel 1 subunit alpha (SCNN1A) expression, its prognostic significance and biological roles in pancreatic cancer. Bioinformatics database was searched to explore the expression of SCNN1A in pancreatic cancer specimens and analysis results were further validated by qRT-PCR and Western blot assay. The correlation between SCNN1A expression and clinicopathological characteristics and its impact on survival outcome of pancreatic cancer patients were investigated using GEPIA database and Kaplan-Meier plotter. Loss- and gain-of-functional experiments in vitro were done to investigate the biological function of SCNN1A in pancreatic cancer. Bioinformatics analysis and validation experiment showed that SCNN1A was frequently overexpressed in pancreatic cancer specimens and cell lines (P < 0.001), and there were significant relevance between high SCNN1A expression and TP53 mutation (P < 0.05) as well as unfavorable prognosis of pancreatic cancer patients (HR for overall survival: 1.9, P = 0.003 and HR for disease-free survival: 1.7, P = 0.014). The silencing of SCNN1A suppressed cell proliferation, migration and invasion and induced cell apoptosis (P < 0.05), while its overexpression promoted aggressive phenotypes of pancreatic cancer cells in vitro (P < 0.05). SCNN1A possessed oncogenic function and its dysregulation could be implicated in the development and metastasis of pancreatic cancer.