METTL14/miR-29c-3p axis drives aerobic glycolysis to promote triple-negative breast cancer progression though TRIM9-mediated PKM2 ubiquitination.

The energy metabolic rearrangement of triple-negative breast cancer (TNBC) from oxidative phosphorylation to aerobic glycolysis is a significant biological feature and can promote the malignant progression. However, there is little knowledge about the functional mechanisms of methyltransferase-like protein 14 (METTL14) mediated contributes to TNBC malignant progression. Our study found that METTL14 expression was significantly upregulated in TNBC tissues and cell lines. Silencing METTL14 significantly inhibited TNBC cell growth and invasion in vitro, as well as suppressed tumour growth. Mechanically, METTL14 was first found to activate miR-29c-3p through m6A and regulate tripartite motif containing 9 (TRIM9) to promote ubiquitination of pyruvate kinase isoform M2 (PKM2) and lead to its transition from tetramer to dimer, resulting in glucose metabolic reprogramming from oxidative phosphorylation to aerobic glycolysis to promote the progress of TNBC. Taken together, these findings reveal important roles of METTL14 in TNBC tumorigenesis and energy metabolism, which might represent a novel potential therapeutic target for TNBC.

Ultrahigh-Precision Hamiltonian Parameter Estimation in a Superconducting Circuit.

The Hamiltonian, which determines the evolution of a quantum system, is fundamental in quantum physics. Therefore, it is crucial to implement high-precision generation and measurement of the Hamiltonian in a practical quantum system. Here, we experimentally demonstrate ultrahigh-precision Hamiltonian parameter estimation with a significant quantum advantage in a superconducting circuit via sequential control. We first observe the commutation relation for noncommuting operations determined by the system Hamiltonian, both with and without adding quantum control, verifying the commuting property of controlled noncommuting operations. Based on this control-induced commuting property, we further demonstrate Hamiltonian parameter estimation for polar and azimuth angles in superconducting circuits, achieving ultrahigh metrological gains in measurement precision exceeding the standard quantum limit by up to 16.0 and 16.1 dB at N=100, respectively.

Seasonal plasticity of stem embolism resistance and its potential driving factors in six temperate woody species.

The seasonal plasticity of resistance to xylem embolism has been demonstrated in leaves of some tree species, but is controversial in stems. In this study, we investigated the seasonality of stem xylem resistance to embolism in six temperate woody species (four deciduous and two evergreen tree species) that were grown at the same site. The xylem conduit anatomy, the concentrations, and ratios of the main cation in the xylem sap, as well as the content of nonstructural carbohydrates (including soluble sugars and starch) were measured in each species under each season to reveal the potential mechanisms of seasonal change in embolism resistance. The stem of all species showed increasing resistance to embolism as seasons progressed, with more vulnerable xylem in spring, but no significant adjustment in the other three seasons. The seasonal plasticity of stem embolism resistance was greater in deciduous species than in evergreen. On a seasonal scale, conduit diameter and conduit implosion resistance, the ratios of K+/Ca2+ and K+/Na+, and starch content were generally not correlated with embolism resistance, suggesting that these are probably not the main drivers of seasonal plasticity of stem embolism resistance. The seasonality of embolism resistance provides critical information for better understanding plant hydraulics in response to seasonal environments, especially under climate change.

Catalyst- and base-free visible light-enabled radical relay trihalomethylation/functional group-migration/carbonylation with CX3SO2Cl.

Herein, we report a visible light-enabled radical trihalomethylation/cyano-migration/carbonylation cascade reaction of 2-hydroxy-2-hex-5-enenitrile with CX3SO2Cl as the CX3-source (X = F, Cl) to obtain 5-oxo-2-(2,2,2-trihaloethyl)pentanenitrile compounds in the absence of a photocatalyst, transition metal and base. This reaction system is also effective to convert (benzo[d]thiazol-2-yl)-pent-4-enol to the corresponding 4-(benzo[d]thiazol-2-yl)-6,6,6-trihalo-hexanone products. These reactions occur under mild conditions, tolerate a wide range of functional groups, and provide alternative approaches for the 1,2-bifunctionalization reaction of unactivated olefins.

Screening and Evaluation of Children's Sensitively Toxic Chemicals in New Mosquito Repellent Products Based on a Nationwide Investigation.

New mosquito repellent products (NMRPs) are emerging popular repellents among children. There are increasing reports on children's sensitization reactions caused by NMRPs, while regulations on their productions, sales, or usage are still lacking. One of the reasons could be the missing comprehensive risk assessment. We first conducted a nationwide investigation on children's NMRP usage preferences. Then, we high-throughput screened volatile or semivolatile organic chemicals (VOCs/SVOCs) in five representative NMRPs by the headspace gas chromatography-orbitrap high-resolution mass spectrometry analytical method. After that, toxic compounds were recognized based on the toxicity forecaster (ToxCast) database. A total of 277 VOCs/SVOCs were recognized, and 70 of them were identified as toxic compounds. In a combination of concentrations, toxicities, absorption, distribution, metabolism, and excretion characteristics in the body, 28 chemicals were finally proposed as priority-controlled compounds in NMRPs. Exposure risks of recognized toxic chemicals through NMRPs by inhalation and dermal intake for children across the country were also assessed. Average daily intakes were in the range of 0.20-7.31 mg/kg/day for children in different provinces, and the children in southeastern coastal provinces were found to face higher exposure risks. By controlling the high-priority chemicals, the risks were expected to be reduced by about 46.8% on average. Results of this study are therefore believed to evaluate exposure risks, encourage safe production, and promote reasonable management of NMRPs.

Transthoracic echocardiographic Doppler metrics in evaluating bioprosthetic tricuspid valve dysfunction.

PURPOSE: There is currently limited information on the utility of transthoracic echocardiography (TTE)-derived Doppler parameters for assessing bioprosthetic tricuspid valve (BTV) dysfunction. Our study aimed to establish the precision and appropriate reference ranges for routinely collected transthoracic Doppler parameters in the assessment of BTV dysfunction. METHODS: We retrospectively evaluated 100 BTV patients who underwent TTE. Based on redo surgical confirmation or more than 2 repeat TTE or transesophageal echocardiography (TEE) examinations, patients were allocated to normal (n = 61), regurgitant (n = 24), or stenotic (n = 15) BTV group. Univariate and multivariate binary logistic regression were performed to identify TTE Doppler parameters that detected BTV dysfunction. RESULTS: The VTI ratio (VTITV/VTILVOT) was the most accurate Doppler parameter for detecting BTV dysfunction, with a ratio of >2.8 showing 84.6% sensitivity and 90.2% specificity. VTI ratio > 3.2, mean gradient (MGTV) > 6.2 mmHg and pressure half-time > 218 ms detected significant BTV stenosis, with sensitivities of 100%, 93.3% and 93.3% and specificities of 82.4%, 75.3% and 87.1%, respectively. After multivariate analysis, the VTI ratio > 2.8 (OR = 9.00, 95% CI = 2.13-41.61, p = .003) and MGTV > 5.1 mmHg (OR = 6.50, 95% CI = 1.69-27.78, p = .008) were the independent associations of BTV dysfunction. With these cutoff values, 75.0%-92.2% of normal and 62.5%-96.0% of dysfunctional BTV were identified. CONCLUSIONS: Doppler parameters from TTE can accurately identify BTV dysfunction, particularly with VTI ratio > 2.8 and MGTV > 5.1 mmHg, to assess the need for additional testing with TEE.

Application of apical myocardial perfusion quantitative analysis by contrast-enhanced ultrasound utilizing high-frequency linear probe.

BACKGROUND: Due to insufficient near-field resolution and artifacts, it is challenging to evaluate the left ventricular apical perfusion with phased-array probes. By combining high-frequency linear probe and contrast-enhanced ultrasound (CEUS), imaging of apical myocardial perfusion could be improved. The study aims to evaluate the preliminary application of CEUS by high-frequency linear probes to assess the apical perfusion. METHODS: The study enrolled retrospectively 91 patients to test the feasibility of the novel method. In protocol 1, patients were stratified into a group with left anterior descending artery (LAD) stenosis (N = 40) and a group without LAD stenosis or coronary artery disease (N = 41) based on the degree of coronary artery narrowing, quantified by >50% stenosis in coronary angiography. Receiver operating characteristics (ROC) analysis was performed to test the diagnostic value of perfusion parameters. In protocol 2, the reproducibility of high-frequency linear probe in apical perfusion analysis was compared with the conventional phased-array probe in 30 patients. RESULTS: (1) The novel method is feasible in 81(89.01%) patients. (2) In protocol 1, to detect LAD stenosis, the best cut-off of ß, T, A, and MBF were 10.32, 3.28, 9.39, and 4.99, respectively. Area under the curve of ß, T, A, and MBF were .880, .881, .761, and .880, respectively. (3) In protocol 2, compared with phased-array probe, the quantitative analysis of high-frequency linear probe is of high reproducibility and could get good curve fitting (R2 = .29 vs. R2 = .71, P < .01). CONCLUSION: Observation of apical perfusion using this method is feasible and quantitative analysis allows an accurate and convenient identification of LAD stenosis. This method provides an alternative for patients who have difficulties in visualizing the apical region with a phased-array probe.

Minimally Invasive and Innovative Management of Prosthesis Infections in Endoscopic-Assisted Breast Reconstruction.

BACKGROUND: Implant infection continues to be the most common complication of breast reconstruction, and it can lead to serious consequences of implant loss. Recently, endoscopic-assisted nipple-sparing mastectomy with direct-to-implant breast reconstruction is being performed more frequently, with similar prosthetic infection incidence compared to conventional techniques. But there is little information published in the literature on the management of periprosthetic infection in endoscopic-assisted breast reconstruction. METHODS: A retrospective review was performed of patients who underwent endoscope-assisted breast reconstruction and developed periprosthetic infection between January 2020 and December 2022. Prosthesis infection was defined as any case where antibiotics were given, beyond the surgeon's standard perioperative period, in response to clinical signs such as swelling, pain, erythema, increased temperature, fever, etc. We summarized our clinical approach and treatment protocol for periprosthetic infection patients. Collected data include preoperative basic information, surgical details, postoperative data, and outcomes. RESULTS: A total of 580 patients (713 reconstructions) underwent endoscopic-assisted immediate breast reconstruction. There were 58 patients developed periprosthetic infection, 14 of whom had bilateral prosthesis reconstruction with unilateral prosthesis infection. The incidence of infection was 10.0%. Average follow-up was 17.3 ± 8.9 months (range = 2-37 months). Of the 58 patients, 53 (91.4%) patients successful salvaged implant and 5(8.6%) patients removed prosthesis. During follow-up, Baker III capsular contracture occurred in 2 patients (3.8%) who had radiotherapy. CONCLUSION: Our management of prosthesis infections in endoscopic-assisted breast reconstruction is easy, minimally invasive, and inexpensive. This method can be repeated if the implant infection does not improve after the first drainage. What's more, our data suggest that our prosthesis salvage of periprosthetic infection is effective. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Noninvasive ultrasound stimulation to treat myocarditis through splenic neuro-immune regulation.

BACKGROUND: The cholinergic anti-inflammatory pathway (CAP) has been widely studied to modulate the immune response. Current stimulating strategies are invasive or imprecise. Noninvasive low-intensity pulsed ultrasound (LIPUS) has become increasingly appreciated for targeted neuronal modulation. However, its mechanisms and physiological role on myocarditis remain poorly defined. METHODS: The mouse model of experimental autoimmune myocarditis was established. Low-intensity pulsed ultrasound was targeted at the spleen to stimulate the spleen nerve. Under different ultrasound parameters, histological tests and molecular biology were performed to observe inflammatory lesions and changes in immune cell subsets in the spleen and heart. In addition, we evaluated the dependence of the spleen nerve and cholinergic anti-inflammatory pathway of low-intensity pulsed ultrasound in treating autoimmune myocarditis in mice through different control groups. RESULTS: The echocardiography and flow cytometry of splenic or heart infiltrating immune cells revealed that splenic ultrasound could alleviate the immune response, regulate the proportion and function of CD4+ Treg and macrophages by activating cholinergic anti-inflammatory pathway, and finally reduce heart inflammatory injury and improve cardiac remodeling, which is as effective as an acetylcholine receptor agonists GTS-21. Transcriptome sequencing showed significant differential expressed genes due to ultrasound modulation. CONCLUSIONS: It is worth noting that the ultrasound therapeutic efficacy depends greatly on acoustic pressure and exposure duration, and the effective targeting organ was the spleen but not the heart. This study provides novel insight into the therapeutic potentials of LIPUS, which are essential for its future application.

Enhanced Local Delivery of microRNA-145a-5P into Mouse Aorta via Ultrasound-Targeted Microbubble Destruction Inhibits Atherosclerotic Plaque Formation.

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) play a key role in the formation and rupture of atherosclerotic plaques. Previous studies have confirmed that microRNA-145 (miR-145) is involved in the phenotypic regulation of VSMCs and reduction of atherosclerosis. At present, seeking safe and effective gene delivery remains a key problem restricting the development of gene therapy. In recent years, ultrasound-targeted microbubble destruction (UTMD) has become a safe and effective transfection method that is widely used in the basic research of gene therapy for heart and tumor diseases. Here, we synthesized cationic microbubbles to encapsulate miR-145 and targeted their release into VSMCs in vitro and in vivo using ultrasound. The feasibility of this gene therapy was verified by fluorescence microscopy and an in vivo imaging system. The results showed that treatment with miR-145 delivered via UTMD considerably improved the gene transfection efficiency and promoted the contraction phenotype of VSMCs in vitro. In vivo, this treatment reduced the atherosclerotic plaque area by 48.04% compared with treatment with free miR-145. Therefore, UTMD-mediated miRNA therapy may provide a new targeted therapeutic approach for atherosclerotic plaques.

Prognostic value of feature-tracking right ventricular longitudinal strain in heart transplant recipients.

OBJECTIVES: The prognostic value of cardiac magnetic resonance feature tracking (CMR-FT)-derived right ventricular longitudinal strain (RVLS) post-heart transplantation has not been studied. This study aimed to evaluate the prognostic significance of CMR-FT-derived RVLS, in patients post- heart transplantation and to directly compare its value with that of conventional RV ejection fraction (RVEF). METHODS: In a cohort of consecutive heart transplantation recipients who underwent CMR for surveillance, RVLS from the free wall was measured by CMR-FT. The composite endpoint was all-cause death or major adverse cardiac events. The Cox regression model was used to examine the independent association between RVLS and the endpoint. RESULTS: A total of 96 heart transplantation recipients were retrospectively included. Over a median follow-up of 41 months, 20 recipients reached the composite endpoint. The multivariate Cox analysis showed that the model with RVLS (hazard ratio [HR]:1.334; 95% confidence interval [CI]:1.148 to 1.549; p < 0.001; Akaike information criterion [AIC] = 140, C-index = 0.831) was better in predicting adverse events than the model with RVEF (HR:0.928; 95% CI: 0.868 to 0.993; p = 0.030; AIC = 149, C-index = 0.751). Furthermore, receiver operating characteristic curves revealed that the accuracy for predicting adverse events was greater for RVLS than RVEF (area under the curve: 0.85 vs 0.76, p = 0.03). CONCLUSIONS: CMR-FT-derived RVLS is an independent predictor of adverse events in post-heart transplantation, and its predictive value was better than RVEF. Therefore, our study highlighted the importance of evaluating RVLS for risk stratification after heart transplantation. KEY POINTS: • CMR-RVLS is an independent predictor of adverse events post-heart transplantation and provides greater predictive value. • CMR-RVLS may help clinicians to risk stratification in heart transplantation recipients.

Does Primary Tumor Resection Induce Accelerated Metastasis in Breast Cancer? A Review.

INTRODUCTION: Over a century of cumulative experimental results and clinical data have suggested that surgical procedures of primary tumors promote tumor progression and metastasis in breast cancer and other cancer patients, suggesting a potential interplay linking primary tumors and distant lesions that lead to metastasis development triggered by primary tumor removal. Such evidence may generate a departure in terms of our attitude toward the surgery. However, the reliability and prognostic benefits of tumor surgery, especially for chemotherapy-resistant patients, are indisputable. Thus, it is important to explore the mechanism underlying this surgery-induced cancer progression to guide individual clinical treatment and improve tumor control. MATERIALS AND METHODS: We conducted a comprehensive review in PubMed in October 2021 to determine the article outline. Non-English and repetitive articles were excluded. The year, topic, key findings, and opinions of each article were gathered. RESULTS: This review not only comprehensively summarizes the potential mechanisms of primary tumors interacting with the growth of metastases but also discusses whether and how surgical resection of primary lesions can trigger tumor metastasis and development. At the same time, this article also provides our understanding of clinical findings and future directions on this topic. In addition, the combination of surgery and some potentially beneficial therapeutic interventions for postoperative tumor metastasis control was also mentioned. CONCLUSIONS: There are viewpoints supporting an acceleration of metastasis after surgery for breast cancer and fundamental research on relevant therapies, although controversial. Further attention should be focused on the gap between current preclinical data and the complicated clinical therapeutic combination during surgery in metastatic breast cancer patients.

Ultrasound-targeted microbubble destruction promotes PDGF-primed bone mesenchymal stem cell transplantation for myocardial protection in acute Myocardial Infarction in rats.

BACKGROUND: Ultrasound-targeted microbubble destruction (UTMD) has emerged as a promising strategy for the targeted delivery of bone marrow mesenchymal stem cells (MSCs) to the ischemic myocardium. However, the limited migration capacity and poor survival of MSCs remains a major therapeutic barrier. The present study was performed to investigate the synergistic effect of UTMD with platelet-derived growth factor BB (PDGF-BB) on the homing of MSCs for acute myocardial infarction (AMI). METHODS: MSCs from male donor rats were treated with PDGF-BB, and a novel microbubble formulation was prepared using a thin-film hydration method. In vivo, MSCs with or without PDGF-BB pretreatment were transplanted by UTMD after inducing AMI in experimental rats. The therapeutic efficacy of PDGF-BB-primed MSCs on myocardial apoptosis, angiogenesis, cardiac function and scar repair was estimated. The effects and molecular mechanisms of PDGF-BB on MSC migration and survival were explored in vitro. RESULTS: The results showed that the biological effects of UTMD increased the local levels of stromal-derived factor-1 (SDF-1), which promoted the migration of transplanted MSCs to the ischemic region. Compared with UTMD alone, UTMD combined with PDGF-BB pretreatment significantly increased the cardiac homing of MSCs, which subsequently reduced myocardial apoptosis, promoted neovascularization and tissue repair, and increased cardiac function 30 days after MI. The vitro results demonstrated that PDGF-BB enhanced MSC migration and protected these cells from H2O2-induced apoptosis. Mechanistically, PDGF-BB pretreatment promoted MSC migration and inhibited H2O2-induced MSC apoptosis via activation of the phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/Akt) pathway. Furthermore, crosstalk between PDGF-BB and stromal-derived factor-1/chemokine receptor 4 (SDF-1/CXCR4) is involved in the PI3K/AKT signaling pathway. CONCLUSION: The present study demonstrated that UTMD combined with PDGF-BB treatment could enhance the homing ability of MSCs, thus alleviating AMI in rats. Therefore, UTMD combined with PDGF-BB pretreatment may offer exciting therapeutic opportunities for strengthening MSC therapy in ischemic diseases.

Application of validated migration models for the risk assessment of styrene and acrylonitrile in ABS plastic toys.

With styrene and acrylonitrile in ABS plastic toys as examples, this paper introduces to the development of a systematic strategy for studying the chemical migration risk in toys. The approach, included the detection method, establishment of migration model, model verification, and the practical application of the model in risk assessment. First, simple and sensitive methods for detecting analyte residues and migration were developed by headspace GC-MS. Then, the migration models were established based on the migration data from 5 min to 168 h and verified using 11 ABS samples. The results showed that the predicted values of the models and the experimental values had a good fit (RMSE=0.10-8.72 %). Subsequently, the migration of analytes in 94 ABS toys was predicted with these models at specific migration times. The daily average exposure level to styrene and acrylonitrile were estimated for children (3 months to 3 years). At last, the migration models reasonably predicted that the cancer risk of styrene and acrylonitrile in ABS toys were 1.6 × 10-8-1.4 × 10-6 and 3.1 × 10-8-1.6 × 10-6, respectively. This research contributes to promote toy safety and child health by enriching migration models and risk assessments.

Echocardiography of a left ventricular apical thrombus after myocardial infarction: A complementary role of the linear transducer array.

We presented a 28-year-old man with myocardial infarction with an apical mass detected by echocardiography. Compared with routine imaging using a phased transducer array, linear transducer arrays were used in two-dimensional and contrast echocardiography to enhance apical visualization and successfully demonstrated the shape and blood perfusion of apical thrombus with precision. We successfully explored the feasibility of imaging the apical thrombus with a linear transducer array.

Effects of plastic contamination on carbon fluxes in a subtropical coastal wetland of East China.

Coastal wetlands are recognized as carbon sinks that play an important role in mitigating global climate change because of the strong carbon uptake by vegetation and high carbon sequestration in the soil. Over the last few decades, plastic waste pollution in coastal zones has become increasingly serious owing to high-intensity anthropogenic activities. However, the influence of plastic waste (including foam waste) accumulation in coastal wetlands on carbon flux remains unclear. In the Yangtze Estuary, we investigated the variabilities of vegetation growth, carbon dioxide (CO2) and methane (CH4) fluxes, and soil properties in a clean Phragmites australis marsh and mudflat and a plastic-polluted marsh during summer and autumn. The clean marsh showed a strong CO2 uptake capacity (a carbon sink), and the clean mudflat showed a weak CO2 sink during the measurement period. However, polluted marshes are a significant source of CO2 emissions. Regardless of the season, the gross primary production and vegetation biomass of the polluted marshes were on average 9.5 and 1.1 times lower than those in the clean marshes, respectively. Ecosystem respiration and CH4 emissions in polluted marshes were significantly higher than those in clean marshes and mudflats. Generally, the soil bulk density and salinity in polluted marshes were lower, whereas the median particle size was higher at the polluted sites than at the clean sites. Increased soil porosity and decreased salinity may favor CO2 and CH4 emissions through gas diffusion pathways and microbiological behavior. Moreover, the concentrations of heavy metals in the soil of plastic-polluted marshes were 1.24-1.49 times higher than those in the clean marshes, which probably limited vegetation growth and CO2 uptake. Our study highlights the adverse effects of plastic pollution on the carbon sink functions of coastal ecosystems, which should receive global attention in coastal environmental management.

Nanoparticle-assisted axillary staging: an alternative approach after neoadjuvant chemotherapy in patients with pretreatment node-positive breast cancers.

PURPOSE: In order to achieve an optimized method of axillary staging after neoadjuvant chemotherapy (NAC) in breast cancer patients with pretreatment positive axillary lymph nodes, we evaluated the feasibility and accuracy of nanoparticle-assisted axillary staging (NAAS) which combines carbon nanoparticles with standard sentinel lymph node biopsy (SLNB) with radioisotope and blue dye. METHODS: Invasive breast cancer patients with pre-NAC positive axillary lymph nodes who converted to ycN0 and received surgeries from November 2020 to March 2021 were included. All patients underwent ipsilateral NAAS followed by axillary lymph node dissection. Detection rate (DR), false-negative rate (FNR), negative predictive value (NPV) and accuracy of axillary staging were calculated. RESULTS: Eighty of 136 (58.8%) breast cancer patients converted to ycN0 after NAC and received NAAS. The DR, NPV and accuracy was 95.0%, 93.3% and 97.4% for NAAS, respectively. And the FNR was 4.2% (2/48) for NAAS, which was lower than that of standard dual-tracer SLNB (SD-SLNB) (9.5%, 4/42). Pretreatment clinical T4 classification was a risk factor for detection failure in NAAS (p = 0.016). When patients with pretreatment inflammatory breast cancers were excluded from analysis, FNR dropped to 2.2% (1/45) for NAAS. CONCLUSION: NAAS revealed great performance in invasive breast cancer patients with pre-NAC positive axillary lymph nodes who converted to ycN0. The application of NAAS reached a better balance between more accurate axillary evaluation and less intervention. Trial registration Chictr.org.cn (ChiCTR2000039814). Registered Nov 11, 2020.

Synthetic Topological Vacua of Yang-Mills Fields in Bose-Einstein Condensates.

Topological vacua are a family of degenerate ground states of Yang-Mills fields with zero field strength but nontrivial topological structures. They play a fundamental role in particle physics and quantum field theory, but have not yet been experimentally observed. Here we report the first theoretical proposal and experimental realization of synthetic topological vacua with a cloud of atomic Bose-Einstein condensates. Our setup provides a promising platform to demonstrate the fundamental concept that a vacuum, rather than being empty, has rich spatial structures. The Hamiltonian for the vacuum of topological number n=1 is synthesized and the related Hopf index is measured. The vacuum of topological number n=2 is also realized, and we find that vacua with different topological numbers have distinctive spin textures and Hopf links. Our Letter opens up opportunities for exploring topological vacua and related long-sought-after instantons in tabletop experiments.

MYBL2 regulates de novo purine synthesis by transcriptionally activating IMPDH1 in hepatocellular carcinoma cells.

BACKGROUND: Metabolic reprogramming is a hallmark of cancer, alteration of nucleotide metabolism of hepatocellular carcinoma (HCC) is not well-understood. MYBL2 regulates cell cycle progression and hepatocarcinogenesis, its role in metabolic regulation remains elusive. PATIENTS AND METHODS: Copy number, mRNA and protein level of MYBL2 and IMPDH1 were analyzed in HCC, and correlated with patient survival. Chromatin Immunoprecipitation sequencing (Chip-seq) and Chromatin Immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR) were used to explore the relationship between MYBL2 and IMPDH1. Metabolomics were used to analyze how MYBL2 affected purine metabolism. The regulating effect of MYBL2 in HCC was further validated in vivo using xenograft models. RESULTS: The Results showed that copy-number alterations of MYBL2 occur in about 10% of human HCC. Expression of MYBL2, IMPDH1, or combination of both were significantly upregulated and associated with poor prognosis in HCC. Correlation, ChIP-seq and ChIP-qPCR analysis revealed that MYBL2 activates transcription of IMPDH1, while knock-out of MYBL2 retarded IMPDH1 expression and inhibited proliferation of HCC cells. Metabolomic analysis post knocking-out of MYBL2 demonstrated that it was essential in de novo purine synthesis, especially guanine nucleotides. In vivo analysis using xenograft tumors also revealed MYBL2 regulated purine synthesis by regulating IMPDH1, and thus, influencing tumor progression. CONCLUSION: MYBL2 is a key regulator of purine synthesis and promotes HCC progression by transcriptionally activating IMPDH1, it could be a potential candidate for targeted therapy for HCC.

circRNA_101277 Influences Cisplatin Resistance of Colorectal Cancer Cells by Modulating the miR-370/IL-6 Axis.

Background: Colorectal cancer (CRC) is among the most prevalent malignancies globally. Early detection of precancerous lesions through routine colonoscopy has led to a dramatic reduction in CRC-related incidence and mortality among those between the ages of 50 and 70. However, in those where the disease progresses to an advanced stage, chemotherapy remains the primary available treatment option, and the associated 5-year survival rate remains low. The identification of genes associated with CRC chemoresistance would thus be a beneficial approach to identifying novel treatments for this deadly disease. Methods: The expression of circRNA_101277, miR-370, and IL-6 was assessed via qRT-PCR. IL-6 levels were measured with a human IL-6 ELISA kit based on the provided protocols. CRC cellular proliferation and cisplatin IC50 values were quantified via MTT assays. Luciferase assays were used to detect circRNA_101277 and miR-370 binding sites or miR-370 and IL-6 binding sites. Results: circRNA_101277 was increased in CRC tissues compared with control samples. circRNA_101277 overexpression was evident in CRC cells, and knockdown of this circRNA suppressed cellular proliferation and cisplatin resistance in these cancer cells. At a mechanistic level, circRNA_101277 was found to function by sequestering miR-370, thereby upregulating the miR-370 target gene IL-6 and promoting cisplatin resistance via this miR-370/IL-6 axis. Conclusion: In summary, our data highlight circRNA_101277 as a novel driver of CRC cell cisplatin resistance that functions by sequestering miR-370 and thereby enhancing IL-6 expression. These findings suggest that this circRNA_101277/miR-370/IL-6 axis may represent a critical axis of chemoresistance in CRC that can be targeted to diagnose and/or treat this cancer.