Improved redox homeostasis owing to the up-regulation of one-carbon metabolism and related pathways is crucial for yeast heterosis at high temperature.

Heterosis or hybrid vigor is a common phenomenon in plants and animals; however, the molecular mechanisms underlying heterosis remain elusive, despite extensive studies on the phenomenon for more than a century. Here we constructed a large collection of F1 hybrids of Saccharomyces cerevisiae by spore-to-spore mating between homozygous wild strains of the species with different genetic distances and compared growth performance of the F1 hybrids with their parents. We found that heterosis was prevalent in the F1 hybrids at 40°C. A hump-shaped relationship between heterosis and parental genetic distance was observed. We then analyzed transcriptomes of selected heterotic and depressed F1 hybrids and their parents growing at 40°C and found that genes associated with one-carbon metabolism and related pathways were generally up-regulated in the heterotic F1 hybrids, leading to improved cellular redox homeostasis at high temperature. Consistently, genes related with DNA repair, stress responses, and ion homeostasis were generally down-regulated in the heterotic F1 hybrids. Furthermore, genes associated with protein quality control systems were also generally down-regulated in the heterotic F1 hybrids, suggesting a lower level of protein turnover and thus higher energy use efficiency in these strains. In contrast, the depressed F1 hybrids, which were limited in number and mostly shared a common aneuploid parental strain, showed a largely opposite gene expression pattern to the heterotic F1 hybrids. We provide new insights into molecular mechanisms underlying heterosis and thermotolerance of yeast and new clues for a better understanding of the molecular basis of heterosis in plants and animals.

Tyrosine kinase receptor B attenuates liver fibrosis by inhibiting TGF-ß/SMAD signaling.

BACKGROUND AND AIMS: Liver fibrosis is a leading indicator for increased mortality and long-term comorbidity in NASH. Activation of HSCs and excessive extracellular matrix production are the hallmarks of liver fibrogenesis. Tyrosine kinase receptor (TrkB) is a multifunctional receptor that participates in neurodegenerative disorders. However, paucity of literature is available about TrkB function in liver fibrosis. Herein, the regulatory network and therapeutic potential of TrkB were explored in the progression of hepatic fibrosis. METHODS AND RESULTS: The protein level of TrkB was decreased in mouse models of CDAHFD feeding or carbon tetrachloride-induced hepatic fibrosis. TrkB suppressed TGF-ß-stimulated proliferation and activation of HSCs in 3-dimensional liver spheroids and significantly repressed TGF-ß/SMAD signaling pathway either in HSCs or in hepatocytes. The cytokine, TGF-ß, boosted Nedd4 family interacting protein-1 (Ndfip1) expression, promoting the ubiquitination and degradation of TrkB through E3 ligase Nedd4-2. Moreover, carbon tetrachloride intoxication-induced hepatic fibrosis in mouse models was reduced by adeno-associated virus vector serotype 6 (AAV6)-mediated TrkB overexpression in HSCs. In addition, in murine models of CDAHFD feeding and Gubra-Amylin NASH (GAN), fibrogenesis was reduced by adeno-associated virus vector serotype 8 (AAV8)-mediated TrkB overexpression in hepatocytes. CONCLUSION: TGF-ß stimulated TrkB degradation through E3 ligase Nedd4-2 in HSCs. TrkB overexpression inhibited the activation of TGF-ß/SMAD signaling and alleviated the hepatic fibrosis both in vitro and in vivo . These findings demonstrate that TrkB could be a significant suppressor of hepatic fibrosis and confer a potential therapeutic target in hepatic fibrosis.

Additive effect of admission hyperglycemia on left ventricular stiffness in patients following acute myocardial infarction verified by CMR tissue tracking.

BACKGROUND: Stress hyperglycemia occurs frequently in patients following acute myocardial infarction (AMI) and may aggravate myocardial stiffness, but relevant evidence is still lacking. Accordingly, this study aimed to examine the impact of admission stress hyperglycemia on left ventricular (LV) myocardial deformation in patients following AMI. METHODS: A total of 171 patients with first AMI (96 with normoglycemia and 75 with hyperglycemia) underwent cardiac magnetic resonance (CMR) examination were included. AMI patients were classified according to admission blood glucose level (aBGL): < 7.8 mmol/L (n = 96), 7.8-11.1 mmol/L (n = 41) and ≥ 11.1 mmol/L (n = 34). LV strains, including global radial/circumferential/longitudinal peak strain (PS)/peak systolic strain rate (PSSR)/peak diastolic strain rate (PDSR), were measured and compared between groups. Further, subgroup analyses were separately conducted for AMI patients with and without diabetes. Multivariate analysis was employed to assess the independent association between aBGL and LV global PS in AMI patients. RESULTS: LV global PS, PSSR and PDSR were decreased in radial, circumferential and longitudinal directions in hyperglycemic AMI patients compared with normoglycemic AMI patients (all P < 0.05). These differences were more obvious in patients with diabetes than those without diabetes. AMI patients with aBGL between 7.8 and 11.1 mmol/L demonstrated significant decreased radial and longitudinal PS, radial PSSR, and radial and longitudinal PDSR than those with aBGL < 7.8 mmol/L (all P < 0.05). AMI patients with aBGL ≥ 11.1 mmol/L showed significantly decreased PS, PSSR and PDSR in all three directions than those with aBGL < 7.8 mmol/L, and decreased longitudinal PSSR than those with aBGL between 7.8 and 11.1 (all P < 0.05). Further, aBGL was significantly and independently associated with radial (ß = - 0.166, P = 0.003) and longitudinal (ß = 0.143, P = 0.008) PS. CONCLUSIONS: Hyperglycemia may exacerbate LV myocardial stiffness in patients experienced first AMI, leading to reduction in LV strains. aBGL was an independent indicator of impaired LV global PS in AMI patients. Blood glucose monitoring is more valuable for AMI patients with diabetes.

DNMT1 determines osteosarcoma cell resistance to apoptosis by associatively modulating DNA and mRNA cytosine-5 methylation.

Cellular apoptosis is a central mechanism leveraged by chemotherapy to treat human cancers. 5-Methylcytosine (m5C) modifications installed on both DNA and mRNA are documented to regulate apoptosis independently. However, the interplay or crosstalk between them in cellular apoptosis has not yet been explored. Here, we reported that promoter methylation by DNMT1 coordinated with mRNA methylation by NSun2 to regulate osteosarcoma cell apoptosis. DNMT1 was induced during osteosarcoma cell apoptosis triggered by chemotherapeutic drugs, whereas NSun2 expression was suppressed. DNMT1 was found to repress NSun2 expression by methylating the NSun2 promoter. Moreover, DNMT1 and NSun2 regulate the anti-apoptotic genes AXL, NOTCH2, and YAP1 through DNA and mRNA methylation, respectively. Upon exposure to cisplatin or doxorubicin, DNMT1 elevation drastically reduced the expression of these anti-apoptotic genes via enhanced promoter methylation coupled with NSun2 ablation-mediated attenuation of mRNA methylation, thus rendering osteosarcoma cells to apoptosis. Collectively, our findings establish crosstalk of importance between DNA and RNA cytosine methylations in determining osteosarcoma resistance to apoptosis during chemotherapy, shedding new light on future treatment of osteosarcoma, and adding additional layers to the control of gene expression at different epigenetic levels.

Transcriptome-wide analysis of a superior xylan degrading isolate Penicillium oxalicum 5-18 revealed active lignocellulosic degrading genes.

Lignocellulose biomass raw materials have a high value in energy conversion. Recently, there has been growing interest in using microorganisms to secret a series of enzymes for converting low-cost biomass into high-value products such as biofuels. We previously isolated a strain of Penicillium oxalicun 5-18 with promising lignocellulose-degrading capability. However, the mechanisms of lignocellulosic degradation of this fungus on various substrates are still unclear. In this study, we performed transcriptome-wide profiling and comparative analysis of strain 5-18 cultivated in liquid media with glucose (Glu), xylan (Xyl) or wheat bran (WB) as sole carbon source. In comparison to Glu culture, the number of differentially expressed genes (DEGs) induced by WB and Xyl was 4134 and 1484, respectively, with 1176 and 868 genes upregulated. Identified DEGs were enriched in many of the same pathways in both comparison groups (WB vs. Glu and Xly vs. Glu). Specially, 118 and 82 CAZyme coding genes were highly upregulated in WB and Xyl cultures, respectively. Some specific pathways including (Hemi)cellulose metabolic processes were enriched in both comparison groups. The high upregulation of these genes also confirmed the ability of strain 5-18 to degrade lignocellulose. Co-expression and co-upregulated of genes encoding CE and AA CAZy families, as well as other (hemi)cellulase revealed a complex degradation strategy in this strain. Our findings provide new insights into critical genes, key pathways and enzyme arsenal involved in the biomass degradation of P. oxalicum 5-18.

Saturnispora sinensis sp. nov., a new ascomycetous yeast species from soil and rotten wood.

A yeast strain (CGMCC 2.6937T) belonging to the ascomycetous yeast genus Saturnispora was recently isolated from soil collected in Xinghuacun, Shanxi Province, PR China. The strain produces one or two ellipsoid or spherical ascospores in asci formed by the conjugation between a cell and its bud. Phylogenetic analyses of the internal transcribed spacer (ITS) region and the D1/D2 domain of the large subunit rRNA gene suggest that this strain is conspecific with strains NYNU 14639 isolated from rotten wood collected in Funiu Mountain, Henan province and ES13S05 from soil collected in Nantou County, Taiwan. The CGMCC 2.6937T group is most closely related to Saturnispora dispora and Saturnispora zaruensis. However, strain CGMCC 2.6937T differs from S. dispora by 17 (3.2 %, 13 substitutions and four gaps) and 77 (18.8 %, 52 substitutions and 25 gaps) mismatches, and from S. zaruensis by 15 (2.9 %, 12 substitutions and three gaps) and 64 (15.6 %, 44 substitutions and 20 gaps) mismatches, in the D1/D2 domain and ITS region, respectively. The results suggest that the CGMCC 2.6937T group represents an undescribed species in the genus Saturnispora, for which the name Saturnispora sinensis sp. nov. is proposed. The holotype strain is CGMCC 2.6937T.

A newly discovered glycosyltransferase gene UGT88A1 affects growth and polysaccharide synthesis of Grifola frondosa.

Grifola frodosa polysaccharides, especially ß-D-glucans, possess significant anti-tumor, antioxidant and immunostimulatory activities. However, the synthesis mechanism remains to be elucidated. A newly discovered glycosyltransferase UGT88A1 was found to extend glucan chains in vitro. However, the role of UGT88A1 in the growth and polysaccharide synthesis of G. frondosa in vivo remains unclear. In this study, the overexpression of UGT88A1 improved mycelial growth, increased polysaccharide production, and decreased cell wall pressure sensitivity. Biomass and polysaccharide production decreased in the silenced strain, and the pressure sensitivity of the cell wall increased. Overexpression and silencing of UGT88A1 both affected the monosaccharide composition and surface morphology of G. frondosa polysaccharides and influenced the antioxidant activity of polysaccharides from different strains. The messenger RNA expression of glucan synthase (GLS), UTP-glucose-1-phosphate uridylyltransferase (UGP), and UDP-xylose-4-epimerase (UXE) related to polysaccharide synthesis, and genes related to cell wall integrity increased in the overexpression strain. Overall, our study indicates that UGT88A1 plays an important role in the growth, stress, and polysaccharide synthesis of G. frondosa, providing a reference for exploring the pathway of polysaccharide synthesis and metabolic regulation. KEY POINTS: •UGT88A1 plays an important role in the growth, stress response, and polysaccharide synthesis in G. frondosa. •UGT88A1 affected the monosaccharide composition, surface morphology and antioxidant activity of G. frondosa polysaccharides. •UGT88A1 regulated the mRNA expression of genes related to polysaccharide synthesis and cell wall integrity.

Use of 1.5-Stage Functional Articulating Hip Spacers for Two-Stage Treatment of Hip Infection.

BACKGROUND: A two-stage treatment is commonly used for chronic hip infections. This study compared the clinical efficacy and complications associated with 1.5-stage functional articulating hip spacers (FAHS) and handmade spacers utilized during two-stage treatment. METHODS: This retrospective study included 50 patients who had hip infections, of which 41 were periprosthetic joint infections, 3 were internal fixation infections, and 6 had septic arthritis. They were divided into two groups according to the spacer type: 23 patients treated with handmade spacers comprising 1 to 2 Kirschner wires as an endoskeleton (group A) and 27 patients treated with 1.5-stage FAHS comprising a cemented femoral stem, metal femoral head, and polyethylene acetabular liner or cemented acetabular cup (group B). Clinical characteristics, surgical data, infection control rate, spacer complications, modified Harris hip, visual analog scale, and 36-item short-form physical functioning scale scores were compared between the groups. All patients were followed up for at least 24 months after the last surgical procedure. RESULTS: No significant differences were noted in the infection eradication rate between the two groups (100 versus 96.30%, P = 1.0). The incidence of mechanical complications, especially spacer fracture, was significantly lower in group B than in group A (P = .044). Hip function and quality of life were significantly better in group B during the interim period. Group B patients had a longer interval time (median 7.40 versus 4.30 months, P = .004) and a lower reimplantation rate than group A patients (42.31 versus 82.61%, P = .004). CONCLUSIONS: The 1.5-stage FAHS surgical technique is feasible for the treatment of hip infection, with a lower mechanical complication rate, better hip function, and better quality of life during the interim period compared to that of handmade spacers. The 1.5-stage FAHS with maintained function could delay or negate the need for second-stage revision.

Yueomyces silvicola sp. nov., a novel ascomycetous yeast species unable to utilize ammonium, glutamate, and glutamine as sole nitrogen sources.

Five yeast strains isolated from tree bark and rotten wood collected in central and southwestern China, together with four Brazilian strains (three from soil and rotting wood collected in an Amazonian rainforest biome and one from Bromeliad collected in Alagoas state) and one Costa Rican strain isolated from a flower beetle, represent a new species closely related with Yueomyces sinensis in Saccharomycetaceae, as revealed by the 26S ribosomal RNA gene D1/D2 domain and the internal transcribed spacer region sequence analysis. The name Yueomyces silvicola sp. nov. is proposed for this new species with the holotype China General Microbiological Culture Collection Center 2.6469 (= Japan Collection of Microorganisms 34885). The new species exhibits a whole-genome average nucleotide identity value of 77.8% with Y. sinensis. The two Yueomyces species shared unique physiological characteristics of being unable to utilize ammonium and the majority of the amino acids, including glutamate and glutamine, as sole nitrogen sources. Among the 20 amino acids tested, only leucine and tyrosine can be utilized by the Yueomyces species. Genome sequence comparison showed that GAT1, which encodes a GATA family protein participating in transcriptional activation of nitrogen-catabolic genes in Saccharomyces cerevisiae, is absent in the Yueomyces species. However, the failure of the Yueomyces species to utilize ammonium, glutamate, and glutamine, which are generally preferred nitrogen sources for microorganisms, implies that more complicated alterations in the central nitrogen metabolism pathway might occur in the genus Yueomyces.

Free-breathing 3D CEST MRI of human liver at 3.0 T.

PURPOSE: To develop a novel 3D abdominal CEST MRI technique at 3 T using MR multitasking, which enables entire-liver coverage with free-breathing acquisition. METHODS: k-Space data were continuously acquired with repetitive steady-state CEST (ss-CEST) modules. The stack-of-stars acquisition pattern was used for k-space sampling. MR multitasking was used to reconstruct motion-resolved 3D CEST images of 53 frequency offsets with entire-liver coverage and 2.0 × 2.0 × 6.0 mm3 spatial resolution. The total scan time was 9 min. The sensitivity of amide proton transfer (APT)-CEST (magnetization transfer asymmetry [MTRasym ] at 3.5 ppm) and glycogen CEST (glycoCEST) (mean MTRasym around 1.0 ppm) signals generated with the proposed method were tested with fasting experiments. RESULTS: Both APT-CEST and glycoCEST signals showed high sensitivity between post-fasting and post-meal acquisitions. APT-CEST and glycoCEST MTRasym signals from post-mean scans were significantly increased (APT-CEST: -0.019 ± 0.017 in post-fasting scans, 0.014 ± 0.021 in post-meal scans, p < 0.01; glycoCEST: 0.003 ± 0.009 in post-fasting scans, 0.027 ± 0.021 in post-meal scans, p < 0.01). CONCLUSION: The proposed 3D abdominal steady-state CEST method using MR multitasking can generate CEST images of the entire liver during free breathing.

Quantum metric and metrology with parametrically-driven Tavis-Cummings models.

We study the quantum metric in a driven Tavis-Cummings model, comprised of multiple qubits interacting with a quantized photonic field. The parametrical driving of the photonic field breaks the system's U(1) symmetry down to a Z2 symmetry, whose spontaneous breaking initiates a superradiant phase transition. We analytically solved the eigenenergies and eigenstates, and numerically simulated the system behaviors near the critical point. The critical behaviors near the superradiant phase transition are characterized by the quantum metric, defined in terms of the response of the quantum state to variation of the control parameter. In addition, a quantum metrological protocol based on the critical behaviors of the quantum metric near the superradiant phase transition is proposed, which enables greatly the achievable measurement precision.

Exceptional Entanglement Phenomena: Non-Hermiticity Meeting Nonclassicality.

Non-Hermitian (NH) extension of quantum-mechanical Hamiltonians represents one of the most significant advancements in physics. During the past two decades, numerous captivating NH phenomena have been revealed and demonstrated, but all of which can appear in both quantum and classical systems. This leads to the fundamental question: what NH signature presents a radical departure from classical physics? The solution of this problem is indispensable for exploring genuine NH quantum mechanics, but remains experimentally untouched so far. Here, we resolve this basic issue by unveiling distinct exceptional entanglement phenomena, exemplified by an entanglement transition, occurring at the exceptional point of NH interacting quantum systems. We illustrate and demonstrate such purely quantum-mechanical NH effects with a naturally dissipative light-matter system, engineered in a circuit quantum electrodynamics architecture. Our results lay the foundation for studies of genuinely quantum-mechanical NH physics, signified by exceptional-point-enabled entanglement behaviors.

Prognostic Value of Left Atrial Reservoir Strain in Left Ventricular Myocardial Noncompaction: A 3.0 T Cardiac Magnetic Resonance Feature Tracking Study.

BACKGROUND: The relationship of left atrial (LA) strain to high-risk heart failure (HF) events in patients with left ventricular myocardial noncompaction (LVNC) remains to be thoroughly investigated. PURPOSE: To evaluate the LA performance in patients with LVNC, and to investigate the prognostic value of LA phasic strain on high-risk HF events, and its influencing factors. STUDY TYPE: Retrospective. POPULATION: A total of 95 LVNC patients (74 with LA enlargement [LAE] and 21 without LAE) and 50 healthy controls. FIELD STRENGTH/SEQUENCE: A 3.0 T, balanced steady-state free-precession cine imaging. ASSESSMENT: LA longitudinal strains were measured by cardiac MRI feature tracking technique. LA volume index (LAVI) and LA ejection fraction (LAEF) were calculated. Their intraobserver and interobserver reproducibility were evaluated. The primary outcome was high-risk HF events, a composite of first HF hospitalization, hospitalization for worsening HF and death from HF. STATISTICAL TESTS: Student's t/Mann-Whitney U, one-way analysis of variance/Kruskal-Wallis, Chi-squared, receiver operating characteristic, Kaplan-Meier, log-rank, Cox regression, Pearson and Spearman correlation and linear regression analyses were performed. The significance threshold was set at P < 0 .05. RESULTS: LAEF and LA longitudinal strains decreased in LVNC patients irrespective of the presence of LAE. During a median follow-up of 32.17 months, high-risk HF occurred in 13 (13.68%) patients. Patients with increased LAVI, decreased LAEF and decreased LA longitudinal strain had significantly higher risks of high-risk HF events. In patients with LVNC, LA reservoir strain (εs) was independently associated with high-risk HF (hazard ratio = 23.208 [95% CI: 2.993-179.967]). LV global longitudinal strain (LV GLS) (ß = -1.783 [95% CI: -2.493 to -1.073]) was significantly and independently associated with εs. Intraobserver and interobserver reproducibility was excellent for LAVI, LAEF, and LA strain. CONCLUSION: In patients with LVNC, εs was an independent predictor for high-risk HF events. LV GLS was an independent determinant of εs in LVNC. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 4.

Right-Left Ventricular Interdependence in Repaired Tetralogy of Fallot Patients With Right Ventricular Heart Failure.

BACKGROUND: Patients with repaired tetralogy of Fallot (rTOF) continue to face a heightened risk of deteriorating cardiac function, and quantitative techniques of cardiac MRI-derived cardiac structure and function provide an opportunity to explore the causes and mechanisms of cardiac deterioration. PURPOSE: To explore right-left ventricular interdependence in rTOF patients before and after the onset of right ventricular (RV) heart failure. STUDY TYPE: Retrospective. POPULATION: One hundred eighteen rTOF patients (21.85 [16.74, 29.20] years, 58 females) and 34 controls (23.5 [21, 26.5] years, 17 females) that underwent cardiac MRI were analyzed, with rTOF patients being further subdivided into those with preserved RV function (N = 54) and those that experienced RV heart failure (N = 64). FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady-state free precession sequence. ASSESSMENT: RV, left ventricular (LV), and septal strain; RV and LV volume. STATISTICAL TESTS: Chi-squared tests or Fisher's exact test, One-way ANOVAs with Bonferroni's post hoc test, Pearson/Spearman correlation, and multivariate backward linear regression analysis. A two-tailed P < 0.05 was deemed as the significance threshold. RESULTS: The MRI-derived RV, LV, and septal strain decreased sequentially in controls, patients with preserved RV function, and patients with RV heart failure, with a good intra-observer (0.909-0.964) and inter-observer (0.879-0.937) agreement. Correlations between LV and RV strain were found to change sequentially with RV function and were the closest in rTOF patients with RV heart failure (r = -0.270 to 0.506). Correlations between RV volume and septal strain was variable in controls (r = 0.483 to -0.604), patients with preserved RV function (r = -0.034 to -0.295), and patients with RV heart failure (r = -0.026 to 0.500). Multivariate analyses revealed that the RV longitudinal strain was independently correlated with LV strain in three directions in rTOF patients with RV heart failure (Radial -0.70 [-1.33, -0.06]; Circumferential 0.44 [0.17, 0.72]; Longitudinal 0.54 [0.26, 0.81]). DATA CONCLUSION: In rTOF patients, the coupling between RV volume and septal strain was broken during RV function compensation, and the adverse effect of RV on LV deformation was highest in patients with RV heart failure. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 5.

Perivascular fat attenuation index value and plaque volume increased in non-target lesions of coronary arteries after stenting.

BACKGROUND: Progression of non-target lesions (NTLs) after stenting has been reported and is associated with the triggering of an inflammatory response. The perivascular fat attenuation index (FAI) may be used as a novel imaging biomarker for the direct quantification of coronary inflammation. OBJECTIVES: To investigate whether FAI values can help identify changes in inflammation status in patients undergoing stent implantation, especially in NTLs. METHODS: Patients who underwent pre- and post-stenting coronary computed tomography angiography (CCTA) examination between January 2015 and February 2021 were consecutively enrolled. The pre- and post-stenting FAIs of the full coronary arteries were compared in both the non- and stent-implanted coronary arteries. Moreover, local FAI values were measured and compared between the NTLs and target lesions in the stent implantations. We also compared changes in plaque type and volume in NTLs before and after stenting. RESULTS: A total of 89 patients (mean age 61 years; male 59) were enrolled. The perivascular FAI values in the full coronary arteries decreased after stenting in both the non- and stent-implanted coronary arteries, similar to those in the target lesions. Conversely, the perivascular FAI values in the NTLs increased after stenting (p < 0.05). In addition, the plaque volumes significantly increased in the NTLs after stenting, regardless of whether they were non-calcified, mixed, or calcified (p < 0.05). CONCLUSION: Perivascular FAI values and plaque volumes increased in the NTLs after stenting. Perivascular FAI can be a promising imaging biomarker for monitoring coronary inflammation after stenting and facilitate long-term monitoring in clinical settings. CLINICAL RELEVANCE STATEMENT: Perivascular fat attenuation index, a non-invasive imaging biomarker, may help identify coronary arteries with high inflammation in non-target lesions and facilitate long-term monitoring, potentially providing an opportunity for more targeted treatment. KEY POINTS: • Perivascular fat attenuation index (FAI) values and plaque volumes increased in the non-target lesions (NTLs) after stenting, suggesting potential focal inflammation progression after stenting. However, stenting along with anti-inflammatory treatment ameliorated inflammation in the full coronary arteries. • Perivascular FAI, a non-invasive imaging biomarker, may help identify coronary arteries with high inflammation in NTLs and facilitate long-term monitoring, potentially providing an opportunity for more targeted treatment.

Trends in microbiological epidemiology of orthopedic infections: a large retrospective study from 2008 to 2021.

BACKGROUND: This study assessed the distribution characteristics of pathogens isolated from cases of orthopedic infections and focused on the antimicrobial susceptibility of the main pathogens. METHODS: This retrospective study involved patients with orthopedic infection in a tertiary medical center located in Shanghai, China, from 2008 to 2021.Pathogen information and the basic information of patients were identified from clinical microbiology laboratory data and the institutional medical record system. RESULTS: In total, the pathogen information of 2821 patients were enrolled in the study. S. aureus (37.71%) was the main causative pathogen responsible for orthopedic infection. Gender, pathogens distribution and polymicrobial infection rates were significantly different (P < 0.05) among patients with different orthopedic infection diseases.The trends in the distribution of pathogens in the total cohort, implant-related infection group (Group A), non-implant-related infection group (Group B), and the sub-group of cases with arthroplasty showed significant linear changes over time. And the polymicrobial infection rates of the total cohort (from 17.17% to 11.00%), Group B(from 24.35% to 14.47%), and the sub-group of cases with internal fixation (from 10.58% to 4.87%) decreased significantly. The antimicrobial susceptibility showed changing trends with time for some main pathogens, especially for S.aureus and Enterobacter spp. CONCLUSIONS: Our research indicated that the pathogen distribution and antimicrobial susceptibility in orthopedic infections changed over time. And the distribution of pathogens varied significantly among different types of orthopedic infectious diseases. These findings may serve as a reference for prophylaxis and empirical treatment strategies of orthopedic infection.

Development and validation of a gene model predicting lymph node metastasis and prognosis of oral squamous cell carcinoma based on single-cell and bulk RNA-seq analysis.

BACKGROUND: Lymph node metastasis can independently predict oral squamous cell carcinoma patients' survival. This study would investigate the genetic and cellular differences between oral squamous cell carcinoma with positive and negative lymph node metastases. METHODS: We gathered single-cell RNA sequencing and bulk gene expression data from the Cancer Genome Atlas and Gene Expression Omnibus databases. Sixty lymph node-metastasis-related genes were discovered with refined single-cell RNA sequencing data analysis, and consensus clustering provided three molecular subtypes of oral squamous cell carcinoma. Least absolute shrinkage and selection operator analyses were then utilized to establish a five-gene risk model. CIBERSORT analysis revealed the immune infiltration profile of different risk subgroups. RESULTS: Oral squamous cell carcinoma patients were classified into three subtypes based on the 60 lymph node-metastasis-related key genes identified by single-cell RNA sequencing data. Patients in Subtype 3 showed a tendency for lymph node metastasis and poorer prognosis. Moreover, five biomarkers were selected from the 60 genes to construct a five-gene risk model evaluating the risk of lymph node metastasis. A lower probability of lymph node metastasis and a better prognosis was observed in the low-risk group. The immune infiltration of three different risk groups was explored with CIBERSORT. Besides, further analysis implied different sensitivities of anticancer drugs, including immunotherapy drugs and targeted compounds, in the three risk groups. CONCLUSION: In view of intratumoral heterogeneity, we found 60 genes associated with lymph node metastasis of oral squamous cell carcinoma. Subsequently, we constructed a five-gene signature that could improve the prediction of lymph node metastasis, clinical outcome, and promote individualized treatment strategies for oral squamous cell carcinoma.

Fabrication of glass-based analytical devices by immobilizing nanomaterials on glass substrate with a fluorescent glue for the highly sensitive determination of mercury ions.

A facile method is reported to develop glass-based analytical devices (GADs) based on immobilizing nanomaterials on a glass substrate with fluorescent glue. The fluorescent glue was first prepared by coupling bovine serum albumin (BSA)-protected Au nanoclusters (NCs) and sugars (i.e., ascorbic acid, AA). The glue was then used to immobilize carbon dots (C-dots) on glass substrates to fabricate the portable GADs. The liquid glue-C-dots mixture and probable GADs were developed for Hg2+ detection. Under 365-nm excitation wavelength, the emission at 652 nm from the glue is gradually quenched with increasing concentrations of Hg2+. This quenching is explained in terms of the Stern-Volmer equation and is ascribed to static quenching. The fluorescent color of the glue and GADs gradually changes from pink to blue, with increasing concentrations of Hg2+. The limits of detection (LODs) for Hg2+ determination by bare eyes are 1 nM both for the glue and GADs, suggesting an uncompromised sensing capability even after immobilization. The detection sensitivity of GADs shows a significant improvement compared with the same material-based papers (5 µM). A linear relationship is observed between the total Euclidean distances (EDs) and Hg2+ concentration in the range 0-100 nM, providing the potential for Hg2+ quantification using GADs. The LOD is estimated to be 0.84 nM. To show a potentially practical application, the GADs were used to detect Hg2+ in certified reference material and lake water.

Highly diverged lineages of Saccharomyces paradoxus in temperate to subtropical climate zones in China.

The wild yeast Saccharomyces paradoxus has become a new model in ecology and evolutionary biology. Different lineages of S. paradoxus have been recognized across the world, but the distribution and genetic diversity of the species remain unknown in China, where the origin of its sibling species S. cerevisiae lies. In this study, we investigated the ecological and geographic distribution of S. paradoxus through an extensive field survey in China and performed population genomic analysis on a set of S. paradoxus strains, including 27 strains, representing different geographic and ecological origins within China, and 59 strains representing all the known lineages of the species recognized in the other regions of the world so far. We found two distinct lineages of S. paradoxus in China. The majority of the Chinese strains studied belong to the Far East lineage, and six strains belong to a novel highly diverged lineage. The distribution of these two lineages overlaps ecologically and geographically in temperate to subtropical climate zones in China. With the addition of the new China lineage, the Eurasian population of S. paradoxus exhibits higher genetic diversity than the American population. We observed more possible lineage-specific introgression events from the Eurasian lineages than from the American lineages. Our results expand the knowledge on ecology, genetic diversity, biogeography, and evolution of S. paradoxus.

Whole-brain steady-state CEST at 3 T using MR Multitasking.

PURPOSE: To perform fast 3D steady-state CEST (ss-CEST) imaging using MR Multitasking. METHODS: A continuous acquisition sequence with repetitive ss-CEST modules was developed. Each ss-CEST module contains a single-lobe Gaussian saturation pulse, followed by a spoiler gradient and eight FLASH readouts (one "training line" + seven "imaging lines"). Three-dimensional Cartesian encoding was used for k-space acquisition. Reconstructed CEST images were quantified with four-pool Lorentzian fitting. RESULTS: Steady-state CEST with whole-brain coverage was performed in 5.6 s per saturation frequency offset at the spatial resolution of 1.7 × 1.7 × 3.0 mm3 . The total scan time was 5.5 min for 55 different frequency offsets. Quantitative CEST maps from multipool fitting showed consistent image quality across the volume. CONCLUSION: Three-dimensional ss-CEST with whole-brain coverage can be done at 3 T within 5.5 min using MR Multitasking.