Supercritical fluid in deep subduction zones as revealed by multiphase fluid inclusions in an ultrahigh-pressure metamorphic vein.

Due to their low viscosity, high mobility, and high element contents, supercritical fluids are important agents in the cycling of elements. However, the chemical composition of supercritical fluids in natural rocks is poorly understood. Here, we investigate well-preserved primary multiphase fluid inclusions (MFIs) from an ultrahigh-pressure (UHP) metamorphic vein of the Bixiling eclogite in Dabieshan, China, thus providing direct evidence for the components of supercritical fluid occurring in a natural system. Via the 3D modeling of MFIs by Raman scanning, we quantitatively determined the major composition of the fluid trapped in the MFIs. Combined with the peak-metamorphic pressure-temperature conditions and the cooccurrence of coesite, rutile, and garnet, we suggest that the trapped fluids in the MFIs represent supercritical fluids in a deep subduction zone. The strong mobility of the supercritical fluids with respect to carbon and sulfur suggests that such fluids have profound effects on global carbon and sulfur cycling.

Linc-NSC affects cell differentiation, apoptosis and proliferation in mouse neural stem cells and embryonic stem cells in vitro and in vivo.

BACKGROUND: Stem cell therapy is a promising therapeutic strategy. In a previous study, we evaluated tumorigenicity by the stereotactic transplantation of neural stem cells (NSCs) and embryonic stem cells (ESCs) from experimental mice. Twenty-eight days later, there was no evidence of tumor formation or long-term engraftment in the NSCs transplantation group. In contrast, the transplantation of ESCs caused tumor formation; this was due to their high proliferative capacity. Based on transcriptome sequencing, we found that a long intergenic non-coding RNA (named linc-NSC) with unknown structure and function was expressed at 1100-fold higher levels in NSCs than in ESCs. This finding suggested that linc-NSC is negatively correlated with stem cell pluripotency and tumor development, but positively correlated with neurogenesis. In the present study, we investigated the specific role of linc-NSC in NSCs/ESCs in tumor formation and neurogenesis. METHODS: Whole transcriptome profiling by RNA sequencing and bioinformatics was used to predict lncRNAs that are widely associated with enhanced tumorigenicity. The expression of linc-NSC was assessed by quantitative real-time PCR. We also performed a number of in vitro methods, including cell proliferation assays, differentiation assays, immunofluorescence assays, flow cytometry, along with in vivo survival and immunofluorescence assays to investigate the impacts of linc-NSC on tumor formation and neurogenesis in NSCs and ESCs. RESULTS: Following the knockdown of linc-NSC in NSCs, NSCs cultured in vitro and those transplanted into the cortex of mice showed stronger survival ability (P < 0.0001), enhanced proliferation(P < 0.001), and reduced apoptosis (P < 0.05); the opposite results were observed when linc-NSC was overexpressed in ESCs. Furthermore, the overexpression of linc-NSC in ECSs induced enhanced apoptosis (P < 0.001) and differentiation (P < 0.01), inhibited tumorigenesis (P < 0.05) in vivo, and led to a reduction in tumor weight (P < 0.0001). CONCLUSIONS: Our analyses demonstrated that linc-NSC, a promising gene-edited target, may promote the differentiation of mouse NSCs and inhibit tumorigenesis in mouse ESCs. The knockdown of linc-NSC inhibited the apoptosis in NSCs both in vitro and in vivo, and prevented tumor formation, revealing a new dimension into the effect of lncRNA on low survival NSCs and providing a prospective gene manipulation target prior to transplantation. In parallel, the overexpression of linc-NSC induced apoptosis in ESCs both in vitro and in vivo and attenuated the tumorigenicity of ESCs in vivo, but did not completely prevent tumor formation.

A virus-borne DNA damage signaling pathway controls the lysogeny-induction switch in a group of temperate pleolipoviruses.

Many prokaryotic viruses are temperate and their reactivation is tightly regulated. However, except for a few bacterial model systems, the regulatory circuits underlying the exit from lysogeny are poorly understood, especially in archaea. Here, we report a three-gene module which regulates the switch between lysogeny and replicative cycle in a haloarchaeal virus SNJ2 (family Pleolipoviridae). The SNJ2 orf4 encodes a winged helix-turn-helix DNA binding protein which maintains lysogeny through repressing the expression of the viral integrase gene intSNJ2. To switch to the induced state, two other SNJ2-encoded proteins, Orf7 and Orf8, are required. Orf8 is a homolog of cellular AAA+ ATPase Orc1/Cdc6, which is activated upon mitomycin C-induced DNA damage, possibly through posttranslational modification. Activated Orf8 initiates the expression of Orf7 which, in turn, antagonizes the function of Orf4, leading to the transcription of intSNJ2, thereby switching SNJ2 to the induced state. Comparative genomics analysis revealed that the SNJ2-like Orc1/Cdc6-centered three-gene module is common in haloarchaeal genomes, always present in the context of integrated proviruses. Collectively, our results uncover the first DNA damage signaling pathway encoded by a temperate archaeal virus and reveal an unexpected role of the widely distributed virus-encoded Orc1/Cdc6 homologs.

Atomic-resolution chemical characterization of (2x)72-kDa tryptophan synthase via four- and five-dimensional 1H-detected solid-state NMR.

NMR chemical shifts provide detailed information on the chemical properties of molecules, thereby complementing structural data from techniques like X-ray crystallography and electron microscopy. Detailed analysis of protein NMR data, however, often hinges on comprehensive, site-specific assignment of backbone resonances, which becomes a bottleneck for molecular weights beyond 40 to 45 kDa. Here, we show that assignments for the (2x)72-kDa protein tryptophan synthase (665 amino acids per asymmetric unit) can be achieved via higher-dimensional, proton-detected, solid-state NMR using a single, 1-mg, uniformly labeled, microcrystalline sample. This framework grants access to atom-specific characterization of chemical properties and relaxation for the backbone and side chains, including those residues important for the catalytic turnover. Combined with first-principles calculations, the chemical shifts in the ß-subunit active site suggest a connection between active-site chemistry, the electrostatic environment, and catalytically important dynamics of the portal to the ß-subunit from solution.

Trailblazing in adjuvant research: succinate's uncharted territory with neutrophils.

The purpose of this study is to investigate the previously unknown connection that succinate has with neutrophils in the setting of adjuvant-mediated immunological enhancement. It has been discovered that succinates stimulate the recruitment of neutrophils in immunization sites, which in turn induces the expression of what is known as neutrophil-derived B cell-activating factor (BAFF). Further amplification of vaccine-induced antibody responses is provided via the succinate receptor 1-interferon regulatory factor 5 (SUCNR1-IRF5)-BAFF signaling pathway, which provides insights into a unique mechanism for immunological enhancement.NEW & NOTEWORTHY This study explores the role of succinate as a vaccine adjuvant, revealing its capacity to enhance neutrophil recruitment at immunization sites, which boosts B cell activation through the succinate receptor 1-interferon regulatory factor 5-B cell-activating factor (SUCNR1-IRF5-BAFF) signaling pathway. Results demonstrate succinate's potential to amplify vaccine-induced antibody responses, highlighting its significance in immunological enhancement and offering new insights into the adjuvant mechanisms of action, particularly in neutrophil-mediated immune responses.

Nitrogen-Anchored Boridene Enables Mg-CO2 Batteries with High Reversibility.

Nanoscale defect engineering plays a crucial role in incorporating extraordinary catalytic properties in two-dimensional materials by varying the surface groups or site interactions. Herein, we synthesized high-loaded nitrogen-doped Boridene (N-Boridene (Mo4/3(BnN1-n)2-mTz), N-doped concentration up to 26.78 at %) nanosheets by chemical exfoliation followed by cyanamide intercalation. Three different nitrogen sites are observed in N-Boridene, wherein the site of boron vacancy substitution mainly accounts for its high chemical activity. Attractively, as a cathode for Mg-CO2 batteries, it delivers a long-term lifetime (305 cycles), high-energy efficiency (93.6%), and ultralow overpotential (∼0.09 V) at a high current of 200 mA g-1, which overwhelms all Mg-CO2 batteries reported so far. Experimental and computational studies suggest that N-Boridene can remarkably change the adsorption energy of the reaction products and lower the energy barrier of the rate-determining step (*MgCO2 → *MgCO3·xH2O), resulting in the rapid reversible formation/decomposition of new MgCO3·5H2O products. The surging Boridene materials with defects provide substantial opportunities to develop other heterogeneous catalysts for efficient capture and converting of CO2.

Cobalt-Catalyzed Carbon-Heteroatom Transfer Enables Regioselective Tricomponent 1,4-Carboamination.

Tricomponent cobalt(salen)-catalyzed carbofunctionalization of unsaturated substrates by radical-polar crossover has the potential to streamline access to broad classes of heteroatom-functionalized synthetic targets, yet the reaction platform has remained elusive, despite the well-developed analogous hydrofunctionalizations mediated by high-valent alkylcobalt intermediates. We report herein the development of a cobalt(salen) catalytic system that enables carbofunctionalization. The reaction entails a tricomponent decarboxylative 1,4-carboamination of dienes and provides a direct route to aromatic allylic amines by obviating preformed allylation reagents and protection of oxidation-sensitive aromatic amines. The catalytic system merges acridine photocatalysis with cobalt(salen)-catalyzed regioselective 1,4-carbofunctionalization that facilitates the crossover of the radical and polar phases of the tricomponent coupling process, revealing critical roles of the reactants, as well as ligand effects and the nature of the formal high-valent alkylcobalt species on the chemo- and regioselectivity.

A Synergistically Regulated Cathode/Electrolyte Interphase With High Stability and Rapid Zn2+ Migration Toward Advanced Flexible Zinc-Ion Batteries.

Na3V2(PO4)3(NVP), as a representative sodium superionic conductor with a stable polyanion framework, is considered a cathode candidate for aqueous zinc-ion batteries attributed to their high discharge platform and open 3D structure. Nevertheless, the structural stability of NVP and the cathode-electrolyte interphase (CEI) layer formed on NVP can be deteriorated by the aqueous electrolyte to a certain extent, which will result in slow Zn2+ migration. To solve these problems, doping Si elements to NVP and adding sodium acetate (NaAc) to the electrolyte are utilized as a synergistic regulation route to enable a highly stable  CEI with rapid Zn2+ migration. In this regard, Ac- competitively takes part in the solvation structure of Zn2+ in aqueous electrolyte, weakening the interaction between water and Zn2+, and meanwhile a highly stable CEI is formed to avoid structural damage and enable rapid Zn2+ migration. The NVPS/C@rGO electrode exhibits a notable capacity of 115.5 mAh g-1 at a current density of 50 mA g-1 in the mixed electrolyte (3 M ZnOTF2+3 M NaAc). Eventually, a collapsible "sandwich" soft pack battery is designed and fabricated and can be used to power small fans and LEDs, which proves the practical application of aqueous zinc-ion batteries in flexible batteries.

LINC00858 facilitates formation of hepatic metastases from colorectal cancer via regulating the miR-132-3p/IGF2BP1 axis.

Hepatic metastasis is a major cause of colorectal cancer (CRC)-related deaths. Presently, the role of long non-coding RNAs (lncRNAs) in hepatic metastases from CRC is elusive. We dissected possible interplay between LINC00858/miR-132-3p/IGF2BP1 via bioinformatics approaches. Subsequently we analyzed mRNA expression of LINC00858, miR-132-3p and IGF2BP1 through qRT-PCR. Western blot was used to detect protein expression of IGF2BP1. RNA immunoprecipitation chip and dual-luciferase assay validated interaction between LINC00858 and miR-132-3p, as well as miR-132-3p and IGF2BP1. Cell viability, invasion, and migration were examined via CCK-8, colony formation, transwell and wound healing assays. Effect of LINC00858 on CRC hepatic metastases was validated via in vivo assay. Upregulated LINC00858 and IGF2BP1, and downregulated miR-132-3p were predicted in tumor tissues of patients with hepatic metastases from CRC. There were targeting relationships between LINC00858 and miR-132-3p, as well as miR-132-3p and IGF2BP1. Besides, LINC00858 facilitated progression of CRC cells. Rescue assay suggested that silencing LINC00858 suppressed CRC cell progression, while further silencing miR-132-3p or overexpressing IGF2BP1 reversed such effects. LINC00858 could facilitate CRC tumor growth and hepatic metastases. LINC00858 induced CRC hepatic metastases via regulating miR-132-3p/ IGF2BP1, and this study may deliver a new diagnostic marker for the disease.

A 4D single-cell protein atlas of transcription factors delineates spatiotemporal patterning during embryogenesis.

Complex biological processes such as embryogenesis require precise coordination of cell differentiation programs across both space and time. Using protein-fusion fluorescent reporters and four-dimensional live imaging, we present a protein expression atlas of transcription factors (TFs) mapped onto developmental cell lineages during Caenorhabditis elegans embryogenesis, at single-cell resolution. This atlas reveals a spatiotemporal combinatorial code of TF expression, and a cascade of lineage-specific, tissue-specific and time-specific TFs that specify developmental states. The atlas uncovers regulators of embryogenesis, including an unexpected role of a skin specifier in neurogenesis and the critical function of an uncharacterized TF in convergent muscle differentiation. At the systems level, the atlas provides an opportunity to model cell state-fate relationships, revealing a lineage-dependent state diversity within functionally related cells and a winding trajectory of developmental state progression. Collectively, this single-cell protein atlas represents a valuable resource for elucidating metazoan embryogenesis at the molecular and systems levels.

Ubiquitin E3 ligase SPOP is a host negative regulator of enterovirus 71-encoded 2A protease.

IMPORTANCE: EV71 poses a significant health threat to children aged 5 and below. The process of EV71 infection and replication is predominantly influenced by ubiquitination modifications. Our previous findings indicate that EV71 prompts the activation of host deubiquitinating enzymes, thereby impeding the host interferon signaling pathway as a means of evading the immune response. Nevertheless, the precise mechanisms by which the host employs ubiquitination modifications to hinder EV71 infection remain unclear. The present study demonstrated that the nonstructural protein 2Apro, which is encoded by EV71, exhibits ubiquitination and degradation mediated by the host E3 ubiquitin ligase SPOP. In addition, it is the first report, to our knowledge, that SPOP is involved in the host antiviral response.

Predictive model for CAR-T cell therapy success in patients with relapsed/refractory B-cell acute lymphoblastic leukaemia.

Chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated remarkable efficacy in treating relapsed/refractory acute B-cell lymphoblastic leukaemia (R/R B-ALL). However, a subset of patients does not benefit from CAR-T therapy. Our study aims to identify predictive indicators and establish a model to evaluate the feasibility of CAR-T therapy. Fifty-five R/R B-ALL patients and 22 healthy donors were enrolled. Peripheral blood lymphocyte subsets were analysed using flow cytometry. Sensitivity, specificity, accuracy, positive and negative predictive values and receiver operating characteristic (ROC) areas under the curve (AUC) were determined to evaluate the predictive values of the indicators. We identified B lymphocyte, regulatory T cell (Treg) and peripheral blood minimal residual leukaemia cells (B-MRD) as indicators for predicting the success of CAR-T cell preparation with AUC 0.936, 0.857 and 0.914. Furthermore, a model based on CD3+ T count, CD4+ T/CD8+ T ratio, Treg and extramedullary diseases (EMD) was used to predict the response to CAR-T therapy with AUC of 0.938. Notably, a model based on CD4+ T/CD8+ T ratio, B, Treg and EMD were used in predicting the success of CAR-T therapy with AUC 0.966 [0.908-1.000], with specificity (92.59%) and sensitivity (91.67%). In the validated group, the predictive model predicted the success of CAR-T therapy with specificity (90.91%) and sensitivity (100%). We have identified several predictive indicators for CAR-T cell therapy success and a model has demonstrated robust predictive capacity for the success of CAR-T therapy. These results show great potential for guiding informed clinical decisions in the field of CAR-T cell therapy.

Metformin monotherapy versus predominantly older non-metformin antidiabetic medications for cerebrovascular risk in early type 2 diabetes management.

AIM: Choosing the initial treatment for type 2 diabetes (T2D) is pivotal, requiring consideration of solid clinical evidence and patient characteristics. Despite metformin's historical preference, its efficacy in preventing cerebrovascular events lacked empirical validation. This study aimed to evaluate the associations between first-line monotherapy (metformin or non-metformin antidiabetic medications) and cerebrovascular complications in patients with T2D without diabetic complications. METHODS: We analysed 9090 patients with T2D without complications who were prescribed either metformin or non-metformin medications as initial therapy. Propensity score matching ensured group comparability. Cox regression analyses, stratified by initial metformin use, assessed cerebrovascular disease risk, adjusting for multiple covariates and using competing risk analysis. Metformin exposure was measured using cumulative defined daily doses. RESULTS: Metformin users had a significantly lower crude incidence of cerebrovascular diseases compared with non-users (p < .0001). Adjusted hazard ratios (aHRs) consistently showed an association between metformin use and a lower risk of overall cerebrovascular diseases (aHRs: 0.67-0.69) and severe events (aHRs: 0.67-0.69). The association with reduced risk of mild cerebrovascular diseases was significant across all models (aHRs: 0.73-0.74). Higher cumulative defined daily doses of metformin correlated with reduced cerebrovascular risk (incidence rate ratio: 0.62-0.94, p < .0001), indicating a dose-dependent effect. CONCLUSION: Metformin monotherapy is associated with a reduced risk of cerebrovascular diseases in early-stage T2D, highlighting its dose-dependent efficacy. However, the observed benefits might also be influenced by baseline differences and the increased risks associated with other medications, such as sulphonylureas. These findings emphasize the need for personalized diabetes management, particularly in mitigating cerebrovascular risk in early T2D stages.

The influence of elongation-induced concentration fluctuations on segmental friction in polymer blends.

Recent experimental studies have revealed a lack of universality in the extensional behavior of linear polymers, which is not envisioned by classical molecular theories. These surprising findings, particularly the sharp contrast between polymer melts and solutions, have catalyzed the development of new theoretical ideas, including the concept of friction reduction in highly stretched polymer melts. By presenting evidence from rheology and small-angle neutron scattering, this work shows that deformation-induced demixing, which is due to the viscoelastic asymmetry in binary mixtures, contributes to the observed nonuniversality. In the case of polystyrene/oligostyrene blends, demixing increases the effective glass transition temperature of the long chain, leading to an apparent friction enhancement. On the other hand, the opposite case is found for the polystyrene/poly(α-methylstyrene) blend. These results highlight the important influence of deformation-induced concentration fluctuations on polymer segmental friction.

Cu2O-catalyzed cascade phosphinylation/cyclization of 2'-aminochalcones for the synthesis of hemi-indigo derivatives.

A Cu2O-catalyzed cascade phosphinylation/cyclization reaction of 2'-aminochalcones and diphenylphosphine oxides to produce hemi-indigo derivatives has been developed. This strategy facilitates the sequential formation of a C-P bonds and a C-N bond in a single reaction step. Notably, the approach features one-pot operation, an earth-abundant copper catalyst, readily available starting materials, a broad substrate scope and high compatibility with functional groups, providing 33 compounds in acceptable yields.

Promoting smartphone-based keratitis screening using meta-learning: A multicenter study.

OBJECTIVE: Keratitis is the primary cause of corneal blindness worldwide. Prompt identification and referral of patients with keratitis are fundamental measures to improve patient prognosis. Although deep learning can assist ophthalmologists in automatically detecting keratitis through a slit lamp camera, remote and underserved areas often lack this professional equipment. Smartphones, a widely available device, have recently been found to have potential in keratitis screening. However, given the limited data available from smartphones, employing traditional deep learning algorithms to construct a robust intelligent system presents a significant challenge. This study aimed to propose a meta-learning framework, cosine nearest centroid-based metric learning (CNCML), for developing a smartphone-based keratitis screening model in the case of insufficient smartphone data by leveraging the prior knowledge acquired from slit-lamp photographs. METHODS: We developed and assessed CNCML based on 13,009 slit-lamp photographs and 4,075 smartphone photographs that were obtained from 3 independent clinical centers. To mimic real-world scenarios with various degrees of sample scarcity, we used training sets of different sizes (0 to 20 photographs per class) from the HUAWEI smartphone to train CNCML. We evaluated the performance of CNCML not only on an internal test dataset but also on two external datasets that were collected by two different brands of smartphones (VIVO and XIAOMI) in another clinical center. Furthermore, we compared the performance of CNCML with that of traditional deep learning models on these smartphone datasets. The accuracy and macro-average area under the curve (macro-AUC) were utilized to evaluate the performance of models. RESULTS: With merely 15 smartphone photographs per class used for training, CNCML reached accuracies of 84.59%, 83.15%, and 89.99% on three smartphone datasets, with corresponding macro-AUCs of 0.96, 0.95, and 0.98, respectively. The accuracies of CNCML on these datasets were 0.56% to 9.65% higher than those of the most competitive traditional deep learning models. CONCLUSIONS: CNCML exhibited fast learning capabilities, attaining remarkable performance with a small number of training samples. This approach presents a potential solution for transitioning intelligent keratitis detection from professional devices (e.g., slit-lamp cameras) to more ubiquitous devices (e.g., smartphones), making keratitis screening more convenient and effective.

Risk assessment and prediction of occult uterine sarcoma in patients with presumed uterine fibroids before high-intensity focused ultrasound treatment.

OBJECTIVE: To develop a diagnostic model for predicting occult uterine sarcoma in patients with presumed uterine fibroids. MATERIALS AND METHODS: We retrospectively reviewed 41631 patients with presumed uterine fibroids who presented for HIFU treatment in 13 hospitals between November 2008 and October 2023. Of these patients, 27 with occult uterine sarcoma and 54 with uterine fibroids were enrolled. Univariate analysis and multivariate logistics regression analysis were used to determine the independent risk factors for the diagnosis of occult uterine sarcoma. A prediction model was constructed based on the coefficients of the risk factors. RESULTS: The multivariate analysis revealed abnormal vaginal bleeding, ill-defined boundary of tumor, hyperintensity on T2WI, and central unenhanced areas as independent risk factors. A scoring system was created to assess for occult uterine sarcoma risk. The score for abnormal vaginal bleeding was 56. The score for ill-defined lesion boundary was 90. The scores for lesions with hypointensity, isointensity signal/heterogeneous signal intensity, and hyperintensity on T2WI were 0, 42, and 93, respectively. The scores for lesions without enhancement on the mass margin, uniform enhancement of tumor, and no enhancement in the center of tumor were 0, 20, and 100, respectively. Patients with a higher total score implied a higher likelihood of a diagnosis of occult uterine sarcoma than that of patients with a lower score. The established model showed good predictive efficacy. CONCLUSIONS: Our results demonstrated that the diagnostic prediction model can be used to evaluate the risk of uterine sarcoma in patients with presumed uterine fibroids.

A novel scoring system based on magnetic resonance imaging for the prediction of the difficulty of ultrasound-guided high-intensity focused ultrasound ablation for uterine fibroids.

OBJECTIVE: To develop a novel scoring system based on magnetic resonance imaging (MRI) for predicting the difficulty of ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for uterine fibroids. MATERIALS AND METHODS: A total of 637 patients with uterine fibroids were enrolled. Sonication time, non-perfused volume ratio (NPVR), and ultrasound energy delivered for ablating 1 mm3 of fibroid tissue volume (E/V) were each classified as three levels and assigned scores from 0 to 2, respectively. Treatment difficulty level was then assessed by adding up the scores of sonication time, NPVR and E/V for each patient. The patients with score lower than 3 were categorized into low difficulty group, with score equal to or greater than 3 were categorized into high difficulty group. The potential predictors for treatment difficulty were compared between the two groups. Multifactorial logistic regression analysis model was created by analyzing the variables. The difficulty score system was developed using the beta coefficients of the logistic model. RESULTS: Signal intensity on T2WI, fibroid location index, largest diameter of fibroids, abdominal wall thickness, homogeneity of the signal of fibroids, and uterine position were independent influencing factors for the difficulty of USgHIFU for uterine fibroids. A prediction equation was obtained: difficulty score = 17 × uterine position (anteverted =0, retroverted =1)+71 × signal intensity (hypointense = 0, isointense/hyperintense = 1) +8 × enhancement (homogenous = 0, heterogeneous = 1)+25×(largest diameter of fibroids-20) +35 × (fibroid location index -0.2) +1×(abdominal wall thickness -5). CONCLUSIONS: This scoring system established based on MRI findings can be used to reliably predict the difficulty level of USgHIFU treatment of uterine fibroids.

Risk factors affecting long-term efficacy of ultrasound-guided high-intensity focused ultrasound treatment for multiple uterine fibroids.

OBJECTIVES: To investigate the long-term efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for multiple uterine fibroids and the factors associated with recurrence. MATERIALS AND METHODS: Five hundred and forty-nine patients with multiple uterine fibroids treated with USgHIFU from June 2017 to June 2019 were retrospectively analyzed. The Pictorial Blood Loss Assessment Chart (PBAC) was used to assess menstrual blood loss. The patients were asked to undergo pre- and post-USgHIFU magnetic resonance imaging (MRI) and complete routine follow-up after USgHIFU. Cox regression analysis was used to investigate the risk factors associated with recurrence. RESULTS: The median number of fibroids per patient was 3 (interquartile range: 3-4), and a total of 1371 fibroids were treated. Among them, 446 patients completed 3 years follow-up. Recurrence, defined as PBAC score above or equal to 100 and/or the residual fibroid volume increased by 10%, was detected in 90 patients within 3 years after USgHIFU, with a cumulative recurrence rate of 20.2% (90/446). The multi-factor Cox analysis showed that age was a protective factor for recurrence. Younger patients have a greater chance of recurrence than older patients. Mixed hyperintensity of fibroids on T2WI and treatment intensity were risk factors for recurrence. Patients with hyperintense uterine fibroids and treated with lower treatment intensity were more likely to experience recurrence than other patients after USgHIFU. No major adverse effects occurred. CONCLUSIONS: USgHIFU can be used to treat multiple uterine fibroids safely and effectively. The age, T2WI signal intensity and treatment intensity are factors related to recurrence.

Viscoelastic relaxation and topological fluctuations in glass-forming liquids.

A method for characterizing the topological fluctuations in liquids is proposed. This approach exploits the concept of the weighted gyration tensor of a collection of particles and permits the definition of a local configurational unit (LCU). The first principal axis of the gyration tensor serves as the director of the LCU, which can be tracked and analyzed by molecular dynamics simulations. Analysis of moderately supercooled Kob-Andersen mixtures suggests that orientational relaxation of the LCU closely follows viscoelastic relaxation and exhibits a two-stage behavior. The slow relaxing component of the LCU corresponds to the structural, Maxwellian mechanical relaxation. Additionally, it is found that the mean curvature of the LCUs is approximately zero at the Maxwell relaxation time with the Gaussian curvature being negative. This observation implies that structural relaxation occurs when the configurationally stable and destabilized regions interpenetrate each other in a bicontinuous manner. Finally, the mean and Gaussian curvatures of the LCUs can serve as reduced variables for the shear stress correlation, providing a compelling proof of the close connection between viscoelastic relaxation and topological fluctuations in glass-forming liquids.