Relationship between creatinine-cystatin C ratio and all-cause mortality in hospitalized patients with COVID-19: A prospective study in China.

Background: This study was conducted to investigate whether baseline creatinine-cystatin C ratio is associated with all-cause mortality in adult Chinese patients hospitalized with coronavirus disease 2019. Methods: This study included 933 patients with coronavirus disease 2019 who were admitted to The Affiliated Hospital of Guangdong Medical University between December 2022 and March 2023. All-cause mortality was determined by telephone follow-up after 28 days. Multivariate Cox proportional risk models were used to investigate the relationship between baseline creatinine-cystatin C ratio and all-cause mortality. Restricted cubic spline and two-piecewise Cox proportional hazards risk models were used to identify non-linear correlations. Results: Of the 933 patients, 128 died during the 28 days follow-up. The restricted cubic spline analysis of hospitalized patients with coronavirus disease 2019 revealed an L-shaped association between baseline creatinine-cystatin C ratio and all-cause mortality, with a threshold creatinine-cystatin C ratio of ≤0.93 predicting all-cause mortality. Specifically, a baseline creatinine-cystatin C ratio below this threshold value was negatively correlated with mortality (hazard ratio 0.12, 95 % confidence interval 0.03-0.48), but a creatinine-cystatin C ratio >0.93 was not correlated with mortality (hazard ratio 1.29, 95 % confidence interval 0.65-2.55). Conclusions: In Chinese adult patients hospitalized with coronavirus disease 2019, an L-shaped relationship was observed between the baseline creatinine-cystatin C ratio and all-cause mortality.

Refining silicon nitride waveguide quality through femtosecond laser annealing.

We present a method for modification of silicon nitride (Si3N4) waveguide resonators using femtosecond laser annealing. The quality (Q) factor of the waveguide resonators can be improved by approximately 1.3 times after annealing. Notably, waveguides that originally had a high Q value maintained their quality after the annealing process. However, those with a lower initial Q value experienced a noticeable improvement post-annealing. To characterize the annealing effect, the surface morphologies of Si3N4 films, both pre- and post-annealing, were analyzed using atomic force microscopy. The findings suggest a potential enhancement in surface refinement. Furthermore, Raman spectroscopy confirmed that the Si3N4 film's composition remains largely consistent with its original state within the annealing power range of 0.6-1.6 W. This research underscores the potential of femtosecond laser annealing as an efficient, cost-effective, and localized technique for fabricating low-loss integrated photonics.

ONC206 targeting ClpP induces mitochondrial dysfunction and protective autophagy in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for approximately 90 % of all cases. ONC201, a member of the imipridone drug family, has shown promising therapeutic potential and a good safety profile in both malignant pediatric central nervous system tumors (diffuse midline glioma [DMG]) and hematologic malignancies. ONC206 is a more potent analog of ONC201. However, the ONC206 potential and mechanism of action in HCC remain to be elucidated. We found that ONC206 hindered HCC growth by suppressing cell proliferation and inducing apoptosis. Moreover, ONC206 induced cytoprotective autophagy, and blocking autophagy enhanced the proapoptotic effect of ONC206. Additionally, ONC206 induced mitochondrial swelling, reduced the mitochondrial membrane potential (MMP), and led to the accumulation of mitochondrial ROS in HCC cells, ultimately resulting in mitochondrial dysfunction. The HCC patient samples exhibited notably elevated levels of caseinolytic protease proteolytic subunit (ClpP), which serves as a mediator of ONC206-induced mitochondrial dysfunction and the activation of protective autophagy. knockdown of ClpP reversed the cytotoxic effects of ONC206 on HCC cells. In summary, our results provide the first insight into the mechanism by which ONC206 exerts its anti-HCC effects and induces protective autophagy in HCC cells through ClpP.

Detection of Entangled States Supported by Reinforcement Learning.

Discrimination of entangled states is an important element of quantum-enhanced metrology. This typically requires low-noise detection technology. Such a challenge can be circumvented by introducing nonlinear readout process. Traditionally, this is realized by reversing the very dynamics that generates the entangled state, which requires a full control over the system evolution. In this Letter, we present nonlinear readout of highly entangled states by employing reinforcement learning to manipulate the spin-mixing dynamics in a spin-1 atomic condensate. The reinforcement learning found results in driving the system toward an unstable fixed point, whereby the (to be sensed) phase perturbation is amplified by the subsequent spin-mixing dynamics. Working with a condensate of 10 900 ^{87}Rb atoms, we achieve a metrological gain of 6.97_{-1.38}^{+1.30} dB beyond the classical precision limit. Our work will open up new possibilities in unlocking the full potential of entanglement caused quantum enhancement in experiments.

CD58 acts as a tumor promotor in hepatocellular carcinoma via activating the AKT/GSK-3ß/ß-catenin pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide because of rapid progression and high incidence of metastasis or recurrence. Accumulating evidence shows that CD58-expressing tumor cell is implicated in development of various cancers. The present study aimed to reveal the functional significance of CD58 in HCC progression and the underlying mechanisms. METHODS: Immunohistochemical staining (IHC), and western blotting were used to detect the expression of CD58 in HCC tissues and cells. The levels of sCD58 (a soluble form of CD58) in the cell supernatants and serum were assessed by ELISA. CCK-8, colony formation, and xenograft assays were used to detect the function of CD58 on proliferation in vitro and in vivo. Transwell assay and sphere formation assay were performed to evaluate the effect of CD58 and sCD58 on metastasis and self-renewal ability of HCC cells. Western blotting, immunofluorescence (IF), TOP/FOP Flash reporter assay, and subcellular fractionation assay were conducted to investigate the molecular regulation between CD58/sCD58 and AKT/GSK-3ß/ß-catenin axis in HCC cells. RESULTS: CD58 was significantly upregulated in HCC tissues. Elevation of CD58 expression correlated with more satellite foci and vascular invasion, and poorer tumor-free and overall survival in HCC patients. Higher sCD58 levels were in HCC patients' serum compared to healthy individuals. Functionally, CD58 promotes the proliferation of HCC cells in vitro and in vivo. Meanwhile, CD58 and sCD58 induce metastasis, self-renewal and pluripotency in HCC cells in vitro. Mechanistically, CD58 activates the AKT/GSK-3ß/ß-catenin signaling pathway by increasing phosphorylation of AKT or GSK3ß signaling, promoting expression of Wnt/ß-catenin target proteins and TCF/LEF-mediated transcriptional activity. Furthermore, AKT activator SC-79 or inhibitor LY294002 abolished the inhibitory effect of CD58 silencing on the proliferation, metastasis, and stemness of HCC cells. CONCLUSIONS: Taken together, CD58 promotes HCC progression and metastasis via activating the AKT/GSK-3ß/ß-catenin pathway, suggesting that CD58 is a novel prognostic biomarker and therapeutic target for HCC.

The multifaceted role of placental growth factor in the pathogenesis and progression of bronchial asthma and pulmonary fibrosis: Therapeutic implications.

Placental growth factor (PlGF) is a glycosylated dimeric protein that is homologous to vascular endothelial growth factor (VEGF). PlGF expression is upregulated in patients with bronchial asthma, suggesting that it plays a role in the pathogenesis of asthma. Bronchial asthma is characterized by chronic airway inflammation and airway hyperresponsiveness (AHR). After recurrent asthma attacks, pulmonary fibrosis develops and leads to airway remodeling and a further decline in lung function. In this review, we focused on the pivotal role of PlGF in chronic airway inflammation, AHR, and airway remodeling during bronchial asthma. Furthermore, we summarized data showing that PlGF may be a potential therapeutic target in bronchial asthma.

Elevated branched-chain amino acid promotes atherosclerosis progression by enhancing mitochondrial-to-nuclear H2O2-disulfide HMGB1 in macrophages.

As the essential amino acids, branched-chain amino acid (BCAA) from diets is indispensable for health. BCAA supplementation is often recommended for patients with consumptive diseases or healthy people who exercise regularly. Latest studies and ours reported that elevated BCAA level was positively correlated with metabolic syndrome, diabetes, thrombosis and heart failure. However, the adverse effect of BCAA in atherosclerosis (AS) and its underlying mechanism remain unknown. Here, we found elevated plasma BCAA level was an independent risk factor for CHD patients by a human cohort study. By employing the HCD-fed ApoE-/- mice of AS model, ingestion of BCAA significantly increased plaque volume, instability and inflammation in AS. Elevated BCAA due to high dietary BCAA intake or BCAA catabolic defects promoted AS progression. Furthermore, BCAA catabolic defects were found in the monocytes of patients with CHD and abdominal macrophages in AS mice. Improvement of BCAA catabolism in macrophages alleviated AS burden in mice. The protein screening assay revealed HMGB1 as a potential molecular target of BCAA in activating proinflammatory macrophages. Excessive BCAA induced the formation and secretion of disulfide HMGB1 as well as subsequent inflammatory cascade of macrophages in a mitochondrial-nuclear H2O2 dependent manner. Scavenging nuclear H2O2 by overexpression of nucleus-targeting catalase (nCAT) effectively inhibited BCAA-induced inflammation in macrophages. All of the results above illustrate that elevated BCAA promotes AS progression by inducing redox-regulated HMGB1 translocation and further proinflammatory macrophage activation. Our findings provide novel insights into the role of animo acids as the daily dietary nutrients in AS development, and also suggest that restricting excessive dietary BCAA consuming and promoting BCAA catabolism may serve as promising strategies to alleviate and prevent AS and its subsequent CHD.

Lenvatinib inhibited HCC cell migration and invasion through regulating the transcription and ubiquitination of UHRF1 and DNMT1.

Hepatocellular carcinoma (HCC) is one of the most common causes of malignancy-related deaths. Lenvatinib, as a multi-targeted tyrosine kinase inhibitor, has gained increasing attention for its antitumor activity. However, the effect and mechanisms of Lenvatinib on HCC metastasis are virtually unknown. In this study, we revealed that Lenvatinib inhibited HCC cell motility and epithelial mesenchymal transition (EMT), along with cell adhesion and extension. Concomitant high DNMT1 and UHRF1 mRNA levels were in HCC patients and indicated worse prognosis. On the one hand, Lenvatinib modulated the transcription of UHRF1 and DNMT1via negatively regulation of ERK/MAPK pathway. On the other hand, Lenvatinib downregulated DNMT1 and UHRF1 expression by promoting their protein degradation through ubiquitin-proteasome pathway, consequently, resulting in upregulation of E-Cadherin. Moreover, Lenvatinib attenuated Huh7 cell adhesion and metastasis in vivo. Our findings provided insight into the intriguing molecular mechanisms regarding the anti-metastasis effect of Lenvatinib in HCC.

Mitochondria-derived H2O2 triggers liver regeneration via FoxO3a signaling pathway after partial hepatectomy in mice.

Reactive oxygen species (ROS) can induce oxidative injury and are generally regarded as toxic byproducts, although they are increasingly recognized for their signaling functions. Increased ROS often accompanies liver regeneration (LR) after liver injuries, however, their role in LR and the underlying mechanism remains unclear. Here, by employing a mouse LR model of partial hepatectomy (PHx), we found that PHx induced rapid increases of mitochondrial hydrogen peroxide (H2O2) and intracellular H2O2 at an early stage, using a mitochondria-specific probe. Scavenging mitochondrial H2O2 in mice with liver-specific overexpression of mitochondria-targeted catalase (mCAT) decreased intracellular H2O2 and compromised LR, while NADPH oxidases (NOXs) inhibition did not affect intracellular H2O2 or LR, indicating that mitochondria-derived H2O2 played an essential role in LR after PHx. Furthermore, pharmacological activation of FoxO3a impaired the H2O2-triggered LR, while liver-specific knockdown of FoxO3a by CRISPR-Cas9 technology almost abolished the inhibition of LR by overexpression of mCAT, demonstrating that FoxO3a signaling pathway mediated mitochondria-derived H2O2 triggered LR after PHx. Our findings uncover the beneficial roles of mitochondrial H2O2 and the redox-regulated underlying mechanisms during LR, which shed light on potential therapeutic interventions for LR-related liver injury. Importantly, these findings also indicate that improper antioxidative intervention might impair LR and delay the recovery of LR-related diseases in clinics.

Leaf functional traits have more contributions than climate to the variations of leaf stable carbon isotope of different plant functional types on the eastern Qinghai-Tibetan Plateau.

Elucidating the mechanisms that control the leaf stable carbon isotope values (δ13Cleaf) is the prerequisite for the widespread application of δ13Cleaf. However, the competing effects of physiological and environmental factors on δ13Cleaf variations of the different plant functional types (PFTs) have not been disentangled, and the corresponding mechanisms remain unclear. Based on large-scale δ13Cleaf measurements on the eastern Qinghai-Tibetan Plateau, the relative contributions and regulatory pathways of leaf functional traits (LFTs) and climatic factors to δ13Cleaf variations of the different PFTs were investigated. We found that δ13Cleaf of the different PFTs was correlated with annual mean precipitation negatively, but not a simple linear relationship with annual mean temperature and varied by PFTs. Leaf nitrogen content per unit area and leaf mass per area (correlated with δ13Cleaf positively) had more substantial effects on the δ13Cleaf variations of the different PFTs than other LFTs. The relative contributions of LFTs to the δ13Cleaf variations were greater than that of climatic factors, and the direct and indirect effects of climatic factors on δ13Cleaf variations varied by PFTs. Our findings provide new insights into understanding key drivers of δ13Cleaf variations at the PFT level on a regional scale.

PhAAT1, encoding an anthocyanin acyltransferase, is transcriptionally regulated by PhAN2 in petunia.

Anthocyanins widely exist in plants and they are important pigments for color of petals and fruits. They are produced through a multi-step pathway controlled by transcription factor complexes. The anthocyanin skeleton modification is the last reaction in the anthocyanin synthesis pathway, which improves the stability of anthocyanins. Acylation modification is an important modification of anthocyanins. However, the identification and function of anthocyanin acyltransferase genes and their expression regulation are rarely reported. In this study, we identified the petunia anthocyanin acyltransferase gene, PhAAT1. PhAAT1 is located in the cytoplasm and PhAAT1 silencing changed flower color and reduced the stability of anthocyanin. Metabolomics analysis showed that PhAAT1 silencing led to the reduction of p-coumaroylated and caffeoylated anthocyanins. In addition, PhAAT1 was positively regulated by the MYB transcription factor, PhAN2, which directly interacts with the promoter of PhAAT1.

Calcium ion removal at different sodium chloride concentrations by free and immobilized halophilic bacteria.

Much attention has been paid to Ca2+ ion removal by biomineralization due to the dangers of Ca2+ on industrial processes and human health. However, Ca2+ removal from hypersaline water by biomineralization is quite difficult due to there being few halophilic bacteria tolerating higher salinities. In this study, free and immobilized Virgibacillus massiliensis C halophilic bacteria exhibiting carbonic anhydrase activity were used to remove Ca2+ ions from water at different NaCl concentrations. With increasing NaCl concentrations (10, 50, 100, 150 and 200 g/L), Ca2+ ion concentrations in the presence of free bacteria and in two groups of immobilized bacteria for a period of 6 days sharply decreased from 1200 mg/L to 219-562 mg/L, 71-214 mg/L and 21-159 mg/L, respectively; Ca2+ precipitation ratios were 55%-81%, 82%-94% and 87%-98%, respectively. The humic acid-like substances, protein, DNA and polysaccharide, released by the bacteria, promoted the Ca2+ ion removal. The immobilized bacteria were able to be recycled and precultured, which would save industry costs and increase Ca2+ ion removal efficiency. Biological processes for Ca2+ ion removal include cell surface, intracellular and extracellular biomineralization. The biogenesis of calcium carbonate was proved by SEM-EDS, FTIR, XPS and stable carbon isotope values. This study provides insights into the effective removal of Ca2+ ions by biomineralization in hypersaline water.

Mendelian randomization study highlights hypothyroidism as a causal determinant of alopecia areata.

Background: Although observational studies have found an association between hypothyroidism and alopecia areata, the causality of this relationship remains unclear. Objectives: This study aimed to investigate the genetic variants associated with hypothyroidism and their potential impact on the risk of developing alopecia areata. Methods: genome-wide association study summary statistics for hypothyroidism (30,155 cases and 379,986 controls) and alopecia areata (289 cases and 211,139 controls) were obtained from the IEU OpenGwas project. The inverse variance-weighted method was used as the primary analysis method to evaluate the causality between hypothyroidism and alopecia areata, supplemented by the weighted median, MR-Egger, simple mode and weighted mode. Furthermore, the function of causal SNPs was evaluated by gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction networks. Result: Utilizing two-sample Mendelian randomization analysis, we found that the single-nucleotide polymorphisms (SNPs) of hypothyroidism (OR = 1.40, 95% CI: 1.12-1.75, p = 3.03×10-3) significantly increased the risk of alopecia areata ( 289 cases and 211,139 controls ). KEGG pathway analysis showed that the candidate genes were mainly enriched in virion-herpesvirus, Th1 and Th2 cell differentiation, Th17 cell differentiation, T-cell receptor signaling pathway, PD-L1/PD-1 checkpoint pathway in cancer and Toll-like receptor signaling pathway. Protein-protein interaction networks results showed that CTLA4, STAT4, IL2RA, TYK2, IRF7, SH2B3, BACH2, TLR3, NOD2, and FLT3. Conclusion: This study provided compelling genetic evidence supporting a causative association between hypothyroidism and alopecia areata, which could potentially inform the development of more efficacious treatment strategies for patients afflicted by alopecia areata.

Ph5GT silencing alters flower color and flavonoids metabolome profile in petunia.

Anthocyanins are important pigments in plants and glycosylation plays an important role in the stability of anthocyanins. Anthocyanin 5-O-glucosyltransferase (5GT) can glycosylate anthocyanin at the 5-O-position. Till now, the enzymatic activity characteristics of 5GT had been studied in vitro in a variety of plants. However, the subcellular localization of 5GT protein still remained unclear, and little genetic evidence on the roles of 5GT in plants has been reported. The full-length Ph5GT gene from petunia (Petunia hybrida) was isolated in this study. Green fluorescent fusion protein assays revealed that Ph5GT protein was localized to the cytoplasm. Ph5GT was found to be highly expressed in flowers, with highest levels of expression occurring during the coloring stage of flower development. Furthermore, Ph5GT silencing led to the change in flower color from purple to light purple and a significant reduction in total anthocyanin content. The metabolome analysis revealed that the content of malvidins and petunidins modified by glycosylation at the 5-O-position was significantly reduced, while the content of their precursor without glycosylation was significantly increased, implying that Ph5GT could glycosylate malvidin and petunidin derivatives and that the substrate types of Ph5GT were expanded in comparison to previous studies.

PhRHMs play important roles in leaf and flower development and anthocyanin synthesis in petunia.

Anthocyanins, vital metabolites in plants, are formed by anthocyanidins combined with various monosaccharides, including glucose, rhamnose, and arabinose. Rhamnose contributes greatly to the glycosylation of anthocyanidins. There are two kinds of rhamnose synthase (RS): rhamnose biosynthesis (RHM), and nucleotide-RS/epimerase-reductase (UER1). Nevertheless, no RS isoform was reported to be involved in anthocyanin synthesis. Here, three homologous PhRHM genes, namely PhRHM1, PhRHM2, and PhRHM3, and one PhUER1 gene from petunia were cloned and characterized. Green fluorescent protein fusion protein assays revealed that PhRHMs and PhUER1 are localized in the cytoplasm. We obtained PhRHM1 or/and PhRHM2 or PhUER1 silenced petunia plants and did not attempt to obtain PhRHM3 silenced plants since PhRHM3 mRNA was not detected in petunia organs examined. PhRHM1 and PhRHM2 (PhRHM1-2) silencing induced abnormal plant growth and decreased the contents of l-rhamnose, photosynthetic pigments and total anthocyanins, while PhUER1 silencing did not cause any visible phenotypic changes. Flavonoid metabolome analysis further revealed that PhRHM1-2 silencing reduced the contents of anthocyanins with rhamnose residue. These results revealed that PhRHMs contribute to the biosynthesis of rhamnose and that PhRHMs participate in the anthocyanin rhamnosylation in petunia, while PhUER1 does not.

Negative impacts of human disturbances on the seed bank of subalpine forests are offset by climatic factors.

Precipitation and temperature in the subalpine region have increased dramatically in recent decades due to global warming, and human disturbances have continued to impact the vegetation in the region. Seed bank plays an important role in population recovery, but there are few studies on the synergistic effects of human disturbances and climate change on seed bank. We analyzed the synergistic effects of human disturbances and climate change on seed bank samples from 20 sites in the subalpine coniferous forest region using grazing and logging as the disturbance intensity gradient and precipitation and temperature as climate variables. The species diversity of aboveground vegetation all changed significantly (p < 0.05) with precipitation, temperature and disturbance level, while the seed bank richness and density did not. Furthermore, the species composition of the seed bank varied significantly less than that of the aboveground vegetation at different levels of disturbance (p < 0.001). Thus, seed bank showed a strong buffering capacity against the risk of local extinction caused by environmental changes that shift the species composition and diversity of aboveground vegetation. In addition, soil and litter are important influences controlling seed bank density in subalpine forests, and the results of structural equation modelling suggest that both disturbance and climate change can indirectly regulate the seed bank by changing the physicochemical properties of soil and litter. We conclude that increases in precipitation and temperature driven by climate change can buffer the negative effects of disturbances on the seed bank.

Faster State Preparation across Quantum Phase Transition Assisted by Reinforcement Learning.

An energy gap develops near quantum critical point of quantum phase transition in a finite many-body (MB) system, facilitating the ground state transformation by adiabatic parameter change. In real application scenarios, however, the efficacy for such a protocol is compromised by the need to balance finite system lifetime with adiabaticity, as exemplified in a recent experiment that prepares three-mode balanced Dicke state near deterministically [Y.-Q. Zou et al., Proc. Natl. Acad. Sci. U.S.A. 115, 6381 (2018)PNASA60027-842410.1073/pnas.1715105115]. Instead of tracking the instantaneous ground state as unanimously required for most adiabatic crossing, this work reports a faster sweeping policy taking advantage of excited level dynamics. It is obtained based on deep reinforcement learning (DRL) from a multistep training scheme we develop. In the absence of loss, a fidelity ≥99% between prepared and the target Dicke state is achieved over a small fraction of the adiabatically required time. When loss is included, training is carried out according to an operational benchmark, the interferometric sensitivity of the prepared state instead of fidelity, leading to better sensitivity in about half of the previously reported time. Implemented in a Bose-Einstein condensate of ∼10^{4} ^{87}Rb atoms, the balanced three-mode Dicke state exhibiting an improved number squeezing of 13.02±0.20 dB is observed within 766 ms, highlighting the potential of DRL for quantum dynamics control and quantum state preparation in interacting MB systems.

Enhanced photoluminescence of silicon quantum dots in the presence of both energy transfer enhancement and emission enhancement mechanisms assisted by the double plasmon modes of gold nanorods.

We propose a scheme utilizing the double plasmon modes of gold nanorods (GNRs) to efficiently increase the Förster resonant energy transfer (FRET) efficiency and enhance the photoluminescence (PL) of Si quantum dots (Si QDs) nearby. Detailed PL and decay dynamics studies are performed for the hybrid nanostructures composed of metallic nanoparticles (MNPs) coated with a Si QD-absorbed silica shell. Plasmon enhanced FRET between Si QDs has been observed and proposed as the third enhancement mechanism for the plasmon-enhanced photoluminescence in addition to excitation enhancement and emission enhancement mechanisms. A maximum FRET efficiency of 46.3% is obtained, which is enhanced by a factor of 8.7 compared to that of samples without MNPs. The dependence of the energy transfer efficiency and the enhancement of the acceptor emission on the surface plasmon resonance (SPR) wavelength, metal-QD distance and QD ratio is examined. The FRET enhancement mechanism dominates when the coupling of plasmon-donor is much stronger than that of plasmon-acceptor with a high acceptor/donor ratio.

Correction: Enhanced photoluminescence of silicon quantum dots in the presence of both energy transfer enhancement and emission enhancement mechanisms assisted by the double plasmon modes of gold nanorods.

[This corrects the article DOI: 10.1039/D1NA00287B.].

Beating the classical precision limit with spin-1 Dicke states of more than 10,000 atoms.

Interferometry is a paradigm for most precision measurements. Using N uncorrelated particles, the achievable precision for a two-mode (two-path) interferometer is bounded by the standard quantum limit (SQL), [Formula: see text], due to the discrete (quanta) nature of individual measurements. Despite being a challenging benchmark, the two-mode SQL has been approached in a number of systems, including the Laser Interferometer Gravitational-Wave Observatory and today's best atomic clocks. For multimode interferometry, the SQL becomes [Formula: see text] using M modes. Higher precision can also be achieved using entangled particles such that quantum noises from individual particles cancel out. In this work, we demonstrate an interferometric precision of [Formula: see text] dB beyond the three-mode SQL, using balanced spin-1 (three-mode) Dicke states containing thousands of entangled atoms. The input quantum states are deterministically generated by controlled quantum phase transition and exhibit close to ideal quality. Our work shines light on the pursuit of quantum metrology beyond SQL.