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Abstract Background The metabolomic profiles of individuals with different clinical manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have not been clearly characterized. Methods We performed metabolomics analysis of 166 individuals, including 62 healthy controls, 16 individuals with asymptomatic SARS-CoV-2 infection, and 88 patients with moderate (n = 42) and severe (n = 46) symptomatic 2019 coronavirus disease (COVID-19; 17 with short-term and 34 with long-term nucleic-acid test positivity). By examining differential expression, we identified candidate metabolites associated with different SARS-CoV-2 infection presentations. Functional and machine learning analyses were performed to explore the metabolites’ functions and verify their candidacy as biomarkers. Results A total of 417 metabolites were detected. We discovered 70 differentially expressed metabolites that may help differentiate asymptomatic infections from healthy controls and COVID-19 patients with different disease severity. Cyclamic acid and N-Acetylneuraminic Acid were identified to distinguish symptomatic infected patients and asymptomatic infected patients. Shikimic Acid, Glycyrrhetinic acid and 3-Hydroxybutyrate can supply significant insights for distinguishing short-term and long-term nucleic-acid test positivity. Conclusion Metabolomic profiling may highlight novel biomarkers for the identification of individuals with asymptomatic SARS-CoV-2 infection and further our understanding of the molecular pathogenesis of COVID-19.

Carbon dots (CDs) show great application potential with their unique and excellent performances. Coal and its derivatives are rich in aromatic ring structure, which is suitable for preparing CDs in microstructure. Coal‐burning dust from coal‐fired power plants can be utilized as a rich resource to separate and extract CDs. It is shown in the results that there are two main possible mechanisms for the formation of CDs in coal‐burning dust. One is the self‐assembly of polycyclic aromatic hydrocarbons contained in coal or produced by incomplete combustion of coal. The other mechanism is that the bridge bonds linking different aromatic structures in coal break, which will form CDs with different functional groups when the coals burn at high temperature. Under violet light excitation at 310–340 nm or red light at 610–640 nm, CDs extracted from coal‐burning dust can emit purple fluorescence around 410 nm. The mechanism of up‐conversion fluorescence emission of CDs is due to a two‐photon absorption process. The recycling of CDs from coal‐burning dust from coal‐fired power plants are not only good to protect environment but will also be helpful for mass production of CDs.

Media multitasking is widespread, yet its relationship with creativity remains unclear. This study employs a combination of measures, including the media multitasking questionnaire, alternative uses task (AUT) for divergent thinking, Chinese compound remote association task (CCRAT) for convergent thinking, and a creative problem-solving task, to examine the relationship between media multitasking and creativity. Extreme values grouping [one standard deviation above or below the mean of the media multitasking index (MMI)], median value grouping, and regression analysis were used to explore the relationship between media multitasking and creativity. The results revealed the following findings: (1) across the three analysis methods, there was no significant relationship between media multitasking and performance on the AUT task. However, within the range of one standard deviation above or below the mean of the MMI, media multitasking showed a significant positive correlation with fluency, flexibility, and total scores on the AUT task. (2) Media multitasking significantly predicted the accuracy of responses on the CCRAT task positively. (3) Media multitasking significantly predicted lower scores on the applicability of creative problem-solving tasks.

ObjectiveEmerging evidence suggests alterations in gut microbiota (GM) composition following thyroid nodules (TNs) development, yet the causal relationship remains unclear. Utilizing Mendelian Randomization (MR), this study aims to elucidate the causal dynamics between GM and TNs.MethodsEmploying summary statistics from the MiBioGen consortium (n=18,340) and FinnGen consortium (1,634 TNs cases, 263,704 controls), we conducted univariable and multivariable MR analyses to explore the GM-TNs association. Techniques including inverse variance weighted, MR-Egger regression, weighted median, and MR-PRESSO were utilized for causal inference. Instrumental variable heterogeneity was assessed through Cochran’s Q statistic and leave-one-out analysis. Reverse MR was applied for taxa showing significant forward MR associations, with multivariate adjustments for confounders.ResultsOur findings suggest that certain microbiota, identified as Ruminococcaceae_NK4A214_group (OR, 1.89; 95%CI, 0.47-7.64; p = 0.040), Senegalimassilia (OR, 1.72; 95%CI, 1.03-2.87; p =0.037), Lachnospiraceae (OR,0.64; 95%CI,0.41-0.99; p =0.045), exhibit a protective influence against TNs’ development, indicated by negative causal associations. In contrast, microbiota categorized as Desulfovibrionales (OR, 0.63; 95%CI, 0.41-0.95; p =0.028), Prevotella_7 (OR, 0.79; 95%CI, 0.63-1.00; p =0.049), Faecalibacterium (OR, 0.66; 95%CI, 0.44-1.00; p =0.050), Desulfovibrionaceae (OR, 0.55; 95%CI, 0.35-0.86; p =0.008), Deltaproteobacteria (OR, 0.65; 95%CI, 0.43-0.97; p =0.036) are have a positive correlation with with TNs, suggesting they may serve as risk factors. Reverse MR analyses did not establish significant causal links. After comprehensive adjustment for confounders, taxa Desulfovibrionales (Order), Desulfovibrionaceae (Family), Deltaproteobacteria (Class) remain implicated as potential contributors to TNs’ risk.DiscussionThis study substantiates a significant causal link between GM composition and TNs development, underscoring the thyroid-gut axis’s relevance. The findings advocate for the integration of GM profiles in TNs’ prevention and management, offering a foundation for future research in this domain.

SARS-CoV-2 evolves constantly with various novel mutations. Due to their enhanced infectivity, transmissibility and immune evasion, a comprehensive understanding of the association between these mutations and the respective functional changes is crucial. However, previous mutation studies of major SARS-CoV-2 variants remain limited. Here, we performed systematic analyses of full-length amino acids mutation, phylogenetic features, protein physicochemical properties, molecular dynamics and immune escape as well as pseudotype virus infection assays among thirteen major SARS-CoV-2 variants. We found that Omicron exhibited the most abundant and complex mutation sites, higher indices of hydrophobicity and flexibility than other variants. The results of molecular dynamics simulation suggest that Omicron has the highest number of hydrogen bonds and strongest binding free energy between the S protein and ACE2 receptor. Furthermore, we revealed 10 immune escape sites in 13 major variants, some of them were reported previously, but four of which (i.e. 339/373/477/496) are first reported to be specific to Omicron, whereas 462 is specific to Epslion. The infectivity of these variants was confirmed by the pseudotype virus infection assays. Our findings may help us understand the functional consequences of the mutations within various variants and the underlying mechanisms of the immune escapes conferred by the S proteins.

Abstract Background Cholangiocarcinoma (CCA) is a biliary epithelial malignant tumor with an increasing incidence worldwide. Therefore, further understanding of the molecular mechanisms of CCA progression is required to identify new therapeutic targets. Methods The expression of RPL35A in CCA and para-carcinoma tissues was detected by immunohistochemical staining. IP-MS combined with Co-IP identified downstream proteins regulated by RPL35A. Western blot and Co-IP of CHX or MG-132 treated CCA cells were used to verify the regulation of HSPA8 protein by RPL35A. Cell experiments and subcutaneous tumorigenesis experiments in nude mice were performed to evaluate the effects of RPL35A and HSPA8 on the proliferation, apoptosis, cell cycle, migration of CCA cells and tumor growth in vivo. Results RPL35A was significantly upregulated in CCA tissues and cells. RPL35A knockdown inhibited the proliferation and migration of HCCC-9810 and HUCCT1 cells, induced apoptosis, and arrested the cell cycle in G1 phase. HSPA8 was a downstream protein of RPL35A and overexpressed in CCA. RPL35A knockdown impaired HSPA8 protein stability and increased HSPA8 protein ubiquitination levels. RPL35A overexpression promoted CCA cell proliferation and migration. HSPA8 knockdown inhibited CCA cell proliferation and migration, and reversed the promoting effect of RPL35A. Furthermore, RPL35A promoted tumor growth in vivo. In contrast, HSPA8 knockdown suppressed tumor growth, while was able to restore the effects of RPL35A overexpression. Conclusion RPL35A was upregulated in CCA tissues and promoted the progression of CCA by mediating HSPA8 ubiquitination.

Abstract Background Acetyl-CoA acetyltransferase 2 (ACAT2) is a lipid metabolism enzyme and rarely was researched in epithelial ovarian cancer (EOC). Methods ACAT2 expressions were confirmed in two pairs of cell lines (A2780 and A2780/DDP, OVCAR8 and OVCAR8/DDP) from Gene Expression Omnibus database by bioinformatics analysis, and in A2780 and A2780/DDP cell lines by quantitative real-time polymerase chain reaction and western blotting. Tissue samples were stained by immunohistochemistry and scored for ACAT2 expression. The relationships between ACAT2 expression and clinicopathological characteristics were analyzed by χ2 test. The prognosis of ACAT2 was analyzed by the log-rank tests and Cox regression models. Results ACAT2 was remarkably upregulated in the above drug-resistant cell lines by mRNA (all P

Abstract This study aims to develop a trigger operator based on the Overlap Volume Histogram (OVH) and examined its effectiveness in enhancing plan quality to minimize radiation-induced lung injury in postoperative radiotherapy for breast cancer. This trigger operator was applied for plan re-optimization to the previous Volumetric Modulated Arc Therapy (VMAT) plans of 16 left breast conserving surgery cases. These cases were categorized into a Contiguous Group (CG) and a Separated Group (SG) based on the relative position between the target and the Left-Lung (L-Lung). We investigated the changes in Vx, mean dose, and Normal Tissue Complication Probability (NTCP) values of organs-at-risk (OARs) before and after using the trigger operator. The Pairwise Sample T test was employed to evaluate the differences in indices between the two groups before and after optimizations. The trigger operator effectively initiated plan re-optimization. The values of V5, V10, V20, V30, and V40 of the L-Lung, as well as the mean dose of the heart, all decreased after re-optimization. The Pairwise Sample T test results showed statistically significant differences in the V20, V30, and V40 of the L-Lung in the CG (P

The droop-controlled inverters (DCIs), which can simulate synchronous generators’ frequency and voltage behavior and provide active and reactive power support for the utility grid, are universally regarded as grid-friendly interfaces. This paper aims to give a general parameter design outline for the DCIs to simplify the complicated parameter tuning task while assuring good performances. For this purpose, the DCIs’ equivalent output impendence and admittance models are first developed, based on which the effects of parameters on impedance characteristics and power stability are analyzed in detail. Afterward, the general parameter design outline with a comprehending parameter tuning scheme is proposed based on the impedance analysis results. In the end, a 15-kVA prototype is established and tested in the laboratory. The experimental results verified the effectiveness of the proposed parameter design and optimization method.

Abstract Introduction Laccase is a copper-containing polyphenolic oxidase widely found in bacteria, archaea, fungi, animals, and plants. As a green biocatalyst with considerable potential for numerous environmental and industrial applications, the enzyme production efficiency of laccase in nature is low, and the cost is high. Purpose To examine the characterization and potential applications of laccase in this study, a novel laccase from Halomonas alkaliantartica (LacHa) was cloned and heterologously expressed it in Escherichia coli. Results To achieve heterologous and efficient laccase expression, a bacterial laccase gene designed as LacHa from Halomonas alkaliantartica of deep sea was cloned and expressed in E. coli. The results showed that the optimum temperature and pH of the enzyme reaction were 45 °C and 7.5. The 100 μM Cu2+ and Fe2+ ions had the strongest stimulatory effect on laccase activity, the surface-active agent SDS and organic solvent 5% ethanol had opposite effect. EDTA, and 5% DMSO have no effect on LacHa activity. The activity of LacHa was enhanced 1.5-fold by chloride at concentrations lower than 500 mM, and 57.6% of its initial activity remained in the reaction system containing 1000 mM. NaCl. Furthermore, LacHa showed decolorization rates ranging from 90.28 to 100% for indigo carmine and two azo dyes without mediators, with wide pH (5.0–9.0) and temperature (25–65 °C) ranges. Conclusions In this study, LacHa was expressed and showed unusual properties, indicating its great application potential in textile industries or environmental fields.

BackgroundCOVID-19 is a highly infectious respiratory disease that can manifest in various clinical presentations. Although many studies have reported the lipidomic signature of COVID-19, the molecular changes in asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals remain elusive.MethodsThis study combined a comprehensive lipidomic analysis of 220 plasma samples from 166 subjects: 62 healthy controls, 16 asymptomatic infections, and 88 COVID-19 patients. We quantified 732 lipids separately in this cohort. We performed a difference analysis, validated with machine learning models, and also performed GO and KEGG pathway enrichment analysis using differential lipids from different control groups.ResultsWe found 175 differentially expressed lipids associated with SASR-CoV-2 infection, disease severity, and viral persistence in patients with COVID-19. PC (O-20:1/20:1), PC (O-20:1/20:0), and PC (O-18:0/18:1) better distinguished asymptomatic infected individuals from normal individuals. Furthermore, some patients tested positive for SARS-CoV-2 nucleic acid by RT-PCR but did not become negative for a longer period of time (≥60 days, designated here as long-term nucleic acid test positive, LTNP), whereas other patients became negative for viral nucleic acid in a shorter period of time (≤45 days, designated as short-term nucleic acid test positive, STNP). We have found that TG (14:1/14:1/18:2) and FFA (4:0) were differentially expressed in LTNP and STNP.ConclusionIn summary, the integration of lipid information can help us discover novel biomarkers to identify asymptomatic individuals and further deepen our understanding of the molecular pathogenesis of COVID-19.

Abstract The barium ferrite BaTi x Fe12−x O19 (x = 0.2, 0.4, 0.6, 0.8) (BFTO-x) ceramics doped by Ti4+ were synthesized by a modified sol—gel method. The crystal structure and magnetic structure of the samples were determined by neutron diffraction, and confirm that the BFTO-x ceramics were high quality single phase with sheet microstructure. With x increasing from 0.2 to 0.8, the saturation magnetization (M s) decreases gradually but the change trend of coercivity (H c) is complex under the synergy of the changed grain size and the magnetic crystal anisotropy field. Relying on the high valence of Ti4+, double resonance peaks are obtained in the curves of the imaginary part of magnetic conductivity (μ″) and the resonance peaks could move toward the low frequency with the increase of x, which facilitate the samples perform an excellent wideband modulation microwave absorption property. In the x = 0.2 sample, the maximum reflection loss (RL) can reach −44.9 dB at the thickness of only 1.8 mm, and the bandwidth could reach 5.28 GHz at 2 mm when RL is less than −10 dB. All the BFTO-x ceramics show excellent frequency modulation ability varying from 18 (x = 0.8) to 4 GHz (x = 0.4), which covers 81% of the investigated frequency in microwave absorption field. This work not only implements the tunable of electromagnetic parameters but also broadens the application of high-performance microwave absorption devices.

PurposeFinding a better treatment position (prone or supine) for whole-breast irradiation for Chinese female patients diagnosed with breast cancer by identify the associations between predictive somatotype parameters and dosimetric gains.Materials and methodsTwo volumetric-modulated arc therapy (VMAT) plans were deployed for whole-breast irradiation in supine and prone position with a total dose of 50 Gy in 25 fractions. Dose-volume parameters were compared and analysed both in the target volume and organs at risk, and equivalent uniform dose-based figure-of-merit (fEUD) models were further used to quantitatively evaluate the overall merits of the two plans. Body shape parameters, including body mass index (BMI), body surface area (BSA), breast shape, cup size, bust size and chest size, were collected. Anatomic features such as the central heart distance (CHD) were measured on supine CT. Spearman’s correlation analysis, receiver operating characteristic (ROC) curve analysis, and the linear regression models were conducted.ResultsDoses to the heart and left anterior descending coronary artery (LADCA) are greater in left-sided breast cancer (BC) patients in the prone position than in the supine position, and the opposite was true for right-sided BC patients (p

Reuterin can be produced from glycerol dehydration catalyzed by glycerol dehydratase (GDHt) in Lactobacillus reuteri and has broad application prospects in industry, agriculture, food, and other fields as it is active against prokaryotic and eukaryotic organisms and is resistant to proteases and lipases. However, high concentrations of glycerin inhibit reuterin production, and the mechanism behind this phenomenon is not clear. To elucidate the inhibitory mechanism of glycerol on reuterin synthesis in L. reuteri and provide reference data for constructing an L. reuteri culture system for highly effective 3-hydroxypropionaldehyde synthesis, we used transcriptome-sequencing technology to compare the morphologies and transcriptomes of L. reuteri cultured in a medium with or without 600 mM of glycerol. Our results showed that after the addition of 600 mM of glycerol to the culture medium and incubation for 10 h at 37 °C, the culture medium of L. reuteri LR301 exhibited the best bacteriostatic effect, and the morphology of L. reuteri cells had significantly changed. The addition of 600 mM of glycerol to the culture medium significantly altered the transcriptome and significantly downregulated the transcription of genes involved in glycol metabolism, such as gldA, dhaT, glpK, plsX, and plsY, but significantly upregulated the transcription of genes related to D-glucose synthesis.

Abstract A precise estimation of the heavy metal concentrations in soils using multispectral remote sensing technology is challenging. Herein, Landsat8 imagery, a digital elevation model, and geochemical data derived from soil samples are integrated to improve the accuracy of estimating the Cu, Pb, and As concentrations in topsoil, using the Daxigou mining area in Shaanxi Province, China, as a case study. The relationships between the three heavy metals and soil environmental factors were investigated. The optimal combination of factors associated with the elevated concentrations of each heavy metal was determined combining correlation analysis with collinearity tests. A back propagation network optimised using a genetic algorithm was trained with 80% of the data for samples and subsequently employed to estimate the heavy metal concentrations in the area. The validation results show that the RMSE of the proposed model is lower than those of the existing linear model and rule-based M5 model tree. From the spatial distribution map of the three metals concentrations using the proposed method, there are findings that high concentrations of the heavy metals studied occur in the mining area, across the slag storage area, on the sides of the road used for transporting ore materials, and along the base of slopes in the area. These findings are consistent with the survey results in the field. The validation and findings validate the effectiveness of the proposed method.

Background: The role of peripheral blood lymphocyte (pBL) in breast cancer has long been studied. However, the predictive role of pBL in advanced breast cancer (ABC) is poorly understood. Methods: A total of 303 patients with ABC were consecutively recruited at our center between January 2015 and September 2019. At baseline, pBL subtypes were detected in all patients with 229 blood samples available for circulating tumor DNA (ctDNA) detection. pBL was analyzed through flow cytometry. ctDNA-based gene mutations were detected using next generation sequencing. The cutoff value of pCTL was estimated by X-tile software. Progression free survival (PFS) was estimated by Kaplan-Meier curve and Cox hazard proportion regression model, with difference detection by log-rank test. Results: Median follow-up time of the study was 21.0 months. The median age of diagnosis was 52.0 years. Among the pBL subtypes, only pCTL level was found predictive for PFS in the HER2+ patients whom received anti-HER2 therapy (13.1 vs. 5.6 months, P = 0.001). However, the predictive role of pCTL was not found in HR-positive (P = 0.716) and TNBC (P = 0.202). pCTL high associated with suppressive immune indictors including lower CD4/CD8 ratio (P = 0.004) and high level of Treg cell (P = 0.004). High occurrence of FGFR1 amplification which has been reported as immune suppressor was also found in HER2+ patients with pCTL high (22.2% vs. 4.3%, P = 0.048). Conclusions: Higher pCTLs level associated with shorter PFS and FGFR1 mutation in HER2+ ABC patients.

Background: The immune checkpoint blockade (ICB) with anti-programmed cell death protein 1(PD-1) on HNSCC is not as effective as on other tumors. In this study, we try to find out the key factors in the heterogeneous tumor-associated monocyte/macrophage (TAMM) that could regulate immune responses and predict the validity of ICB on HNSCC.Experimental Design: To explore the correlation of the TAMM heterogeneity with the immune properties and prognosis of HNSCC, we established the differentiation trajectory of TAMM by analyzing the single-cell RNA-seq data of HNSCC, by which the HNSCC patients were divided into different sub-populations. Then, we exploited the topology of the network to screen out the genes critical for immune hot phenotype of HNSCC, as well as their roles in TAMM differentiation, tumor immune cycle, and progression. Finally, these key genes were used to construct a neural net model via deep-learning framework to predict the validity of treatment with anti-PD-1/PDL-1Results: According to the differentiation trajectory, the genes involved in TAMM differentiation were categorized into early and later groups. Then, the early group genes divided the HNSCC patients into sub-populations with more detailed immune properties. Through network topology, CXCL9, 10, 11, and CLL5 related to TAMM differentiation in the TME were identified as the key genes initiating and maintaining the immune hot phenotype in HNSCC by remarkably strengthening immune responses and infiltration. Genome wide, CASP8 mutations were found to be key to triggering immune responses in the immune hot phenotype. On the other hand, in the immune cold phenotype, the evident changes in CNV resulted in immune evasion by disrupting immune balance. Finally, based on the framework of CXCL9-11, CLL5, CD8+, CD4+ T cells, and Macrophage M1, the neural network model could predict the validity of PD-1/PDL-1 therapy with 75% of AUC in the test cohort.Conclusion: We concluded that the CXCL9, 10,11, and CCL5 mediated TAMM differentiation and constructed immune hot phenotype of HNSCC. Since they positively regulated immune cells and immune cycle in HNSCC, the CXCL9-11 and CCL5 could be used to predict the effects of anti-PD-1/PDL-1 therapy on HNSCC.

Summary: MicroRNAs (miRNAs) have been shown to play important roles in viral infections, but their associations with SARS-CoV-2 infection remain poorly understood. Here, we detected 85 differentially expressed miRNAs (DE-miRNAs) from 2,336 known and 361 novel miRNAs that were identified in 233 plasma samples from 61 healthy controls and 116 patients with COVID-19 using the high-throughput sequencing and computational analysis. These DE-miRNAs were associated with SASR-CoV-2 infection, disease severity, and viral persistence in the patients with COVID-19, respectively. Gene ontology and KEGG pathway analyses of the DE-miRNAs revealed their connections to viral infections, immune responses, and lung diseases. Finally, we established a machine learning model using the DE-miRNAs between various groups for classification of COVID-19 cases with different clinical presentations. Our findings may help understand the contribution of miRNAs to the pathogenesis of COVID-19 and identify potential biomarkers and molecular targets for diagnosis and treatment of SARS-CoV-2 infection.

Abstract Multiferroic BiFeO3-based ceramics were synthesized using the rapid liquid-phase sintering method. The rare-earth ion (Sm3+, Gd3+, Y3+) doping causes structural distortion without changing the intrinsic rhombohedral perovskite structure. Raman analysis shows that the effect of doping on E modes is greater than A1 modes, and the microstructure of FeO6 octahedron can be regulated by ion doping. A-site trivalent ion doped ceramics exhibit improved magnetism compared with pure BiFeO3 ceramic, which originated from the suppressed spiral spin structure of Fe ions. The tilt of FeO6 octahedron as a typical structure instability causes the anomalous change of the imaginary part of permittivity at high frequency, and doped ceramics exhibit natural resonance around 16–17 GHz.

Abstract Objective To explore the efficacy and sensitivity of 3D gamma analysis and bio-mathematical model for cervical cancer in detecting dose changes caused by dose-calculation-grid-size (DCGS). Methods 17 patients’ plans for cervical cancer were enrolled (Pinnacle TPS, VMAT), and the DCGS was changed from 2.0 mm to 5.0 mm to calculate the planned dose respectively. The dose distribution calculated by DCGS = 2.0 mm as the “reference” data set (RDS), the dose distribution calculated by the rest DCGS as the“measurement”data set (MDS), the 3D gamma passing rates and the (N) TCPs of the all structures under different DCGS were obtained, and then analyze the ability of 3D gamma analysis and (N) TCP model in detecting dose changes and what factors affect this ability. Results The effect of DCGS on planned dose was obvious. When the gamma standard was 1.0 mm, 1.0 and 10.0%, the difference of the results of the DCGS on dose-effect could be detected by 3D gamma analysis (all p value 0.05 accounted for the majority. With DCGS = 2.0 mm being RDS, ∆gamma-passing-rate presented the same trend with ∆(N) TCPs of all structures except for the femurs only when the 1.0 mm, 1.0 and 10.0% standards were adopted for the 3D gamma analysis. Conclusions The 3D gamma analysis and bio-mathematical model can be used to analyze the effect of DCGS on the planned dose. For comparison, the former’s detection ability has a lot to do with the designed standard, and the latter’s capability is related to the parameters and calculated accuracy instrinsically.

Abstract Bismuth ferrite (BiFeO3)-based materials are multiferroic materials widely studied. This study reports that strong ferroelectricity and enhanced magnetic performance are simultaneously obtained in the quenched (1−x)BiFeO3−x BaTiO3 (BFBT100x, x = 0.2 and 0.3) ceramics. Quenching treatment can reduce the amount of defects and Fe2+ ions and make the defect dipole in a random state, which is conducive to improving the ferroelectricity and magnetism. Compared with the conventional sintered samples, the quenched ceramics have higher remnant and saturation polarization. As for magnetism, the coercive field (H c) of the quenched ceramics is smaller and the quenching treatment can increase the maximum magnetization by up to 15%.

Abstract Objective The prevalence of hepatitis C virus (HCV) infection is typically evaluated based on the current rate of positivity of anti-HCV antibody; however, HCV RNA positivity is considered the main criterion for antiviral treatment of HCV infection in the clinical setting. In this study, we evaluated the prevalence of HCV infection based on anti-HCV and HCV RNA detection in the population of Liaoning Province, and investigated the correlation between serum HCV RNA positivity and anti-HCV levels. Methods A total of 192,202 patients who underwent serum anti-HCV examination at Shengjing Hospital in 2018 were enrolled in the study. Anti-HCV production was tested using a chemiluminescence assay, and serum HCV RNA detection was performed with Roche COBAS TaqMan (CTM) Analyzer. Results The prevalence of anti-HCV was 1.21 and 0.93% among male and female patients in Liaoning Province, respectively. The positive rates of anti-HCV and serum anti-HCV levels were both age-related, in which patients over 40 years of age had a significantly higher anti-HCV positive rate than those younger than 40 years. Among the anti-HCV-positive patients, the average HCV RNA positive rate was 51.66 and 35.93% in males and females, respectively. Spearman rank analysis showed a significantly positive correlation between serum HCV RNA positivity and the level of anti-HCV. The best cut-off value using serum anti-HCV levels to predict the positivity of HCV RNA was determined to be 9.19 signal-to-cut-off ratio (s/co) in males and 10.18 s/co in females. Conclusion The prevalence of anti-HCV in the general population of Liaoning Province was around 1.04%, which was higher than that previously reported from a national survey of HCV infection in China. Approximately 42.9% of the anti-HCV-positive patients also tested positive for HCV RNA. However, the positive correlation between the serum anti-HCV and HCV RNA levels suggests that the positivity of serum HCV RNA can be predicted according to the anti-HCV level in anti-HCV-positive patients, which can improve screening and facilitate timely intervention to prevent the spread of infection.

The cell-mediated protective and pathogenic immune responses to SARS-CoV-2 infection remain largely elusive. Here we identified 76 distinct cell subsets in the PBMC samples that were associated with various clinical presentations of COVID-19 using scRNA-seq technology coupled with a deep and comprehensive analysis of unique cell surface markers and differentially expressed genes. We revealed that (TRAV1-2+CD8+)MAIT cells and (NCAM1hiCD160+)NK cells significantly enriched in the asymptomatic subjects whereas (LAG3+CD160+CD8+)NKT cells increased in the symptomatic patients. We also observed that (CD68-CSF1R-IL1BhiCD14+)classical monocytes were positively correlated with the disease severity. Moreover, (CD33-HLA-DMA-CD14+)classical monocytes and (CLEC10A-S100A9lo)pDC were associated with the viral persistence. The GO and KEGG analyses identified enriched pathways related to immune responses, inflammation, and apoptosis. These findings may enhance our understanding of the immunopathogenesis of COVID-19 and help develop novel strategies against SARS-CoV-2 infection.

Purpose: This study aimed to evaluate (1) the performance of the Auto-Planning module embedded in the Pinnacle treatment planning system (TPS) with 30 left-side breast cancer plans and (2) the dose-distance correlations between dose-based patients and overlap volume histogram-based (OVH) patients. Method: A total of 30 patients with left-side breast cancer after breast-conserving surgery were enrolled in this study. The clinical manual-planning (MP) and the Auto-Planning (AP) plans were generated by Monaco and by the Auto-Planning module in Pinnacle respectively. The geometric information between organ at risk (OAR) and planning target volume (PTV) of each patient was described by the OVH. The AP and MP plans were ranked to compare with the geometry-based patients from OVH. The Pearson product-moment correlation coefficient (R) was used to describe the correlations between dose-based patients (APs and MPs) and geometry-based patients (OVH). Dosimetric differences between MP and AP plans were evaluated with statistical analysis. Result: The correlation coefficient (mean R = 0.71) indicated that the AP plans have a high correlation with geometry-based patients from OVH, whereas the correlation coefficient (mean R = 0.48) shows a weak correlation between MP plans and geometry-based patients. The dosimetric comparison revealed a statistically significant improvement in the ipsilateral lung V 5Gy and V 10Gy, and in the heart V 5Gy of AP plans compared to MP plans, while statistical reduction was seen in PTV V 107% for MP plans compared to AP plans. Conclusion: The overall results of AP plans were superior to MP plans. The dose distribution in AP plans was more consistent with the distance-dose relationship described by OVH. After eliminating the interference of human factors, the AP was able to provide more stable and objective plans for radiotherapy patients.

Purpose: The purpose of the present study was to evaluate the feasibility of using 4-dimensional computed tomography (4DCT)-ventilation-weighted dose analysis to predict radiation-induced pneumonia probability (RIPP). Methods and Materials: The study population for this retrospective analysis included 16 patients with stage III lung cancer. Each patient’s 4DCT images, including end-inhale and end-exhale sequences, were used for the deformable image registration, and the Hounsfield units (HU) density-change was used to calculate the ventilation. A previously established equation was used to convert the original dose (OD) D 0, i in the lungs in the original plan (OP) to the weighted-dose (WD) D w, i in the weighted plan (WP). The patients were divided into 2 groups, one with radiation-induced pneumonia (RIP), and one without. The Spearman correlation analysis was used to analyze the correlation of RIP with ΔV 20 (ΔV x = V w, x in the WP – V 0, x in the OP), ΔMLD (ΔMLD = mean lung dose (MLD) in the WP – MLD in the OP), and ΔV 5 . Results: The results showed that 5 of the 16 patients were suffering from acute RIP, 4 of which had higher ΔV 20 and ΔMLD values than the rest of the patients. The results of the Spearman correlation analysis for those 4 patients were as follows: RIP vs. ΔV 20 , r = 0.5123; RIP vs. ΔMLD, r = 0.5119; RIP vs. ΔV 5 , r = 0.1904. Conclusions: The 4DCT-ventilation-based weighted-dose analysis showed some correlation between RIPP and both ΔV 20 and ΔMLD, when comparing the weighted-dose and the conventional dose-volume histogram (DVH) analyses.

With the massive use of computers, the growth and explosion of data has greatly promoted the development of artificial intelligence (AI). The rise of deep learning (DL) algorithms, such as convolutional neural networks (CNN), has provided radiation oncologists with many promising tools that can simplify the complex radiotherapy process in the clinical work of radiation oncology, improve the accuracy and objectivity of diagnosis, and reduce the workload, thus enabling clinicians to spend more time on advanced decision-making tasks. As the development of DL gets closer to clinical practice, radiation oncologists will need to be more familiar with its principles to properly evaluate and use this powerful tool. In this paper, we explain the development and basic concepts of AI and discuss its application in radiation oncology based on different task categories of DL algorithms. This work clarifies the possibility of further development of DL in radiation oncology.

Metabolic changes, especially in glucose metabolism, are widely established during the occurrence and development of tumors and regarded as biological markers of pan-cancer. The well-known ‘Warburg effect’ demonstrates that cancer cells prefer aerobic glycolysis even if there is sufficient ambient oxygen. Accumulating evidence suggests that aerobic glycolysis plays a pivotal role in colorectal cancer (CRC) development. However, few studies have examined the relationship of glycolytic gene clusters with prognosis of CRC patients. Here, our aim is to build a glycolysis-associated gene signature as a biomarker for colorectal cancer. The mRNA sequencing and corresponding clinical data were downloaded from TCGA and GEO databases. Gene set enrichment analysis (GSEA) was performed, indicating that four gene clusters were significantly enriched, which revealed the inextricable relationship of CRC with glycolysis. By comparing gene expression of cancer and adjacent samples, 236 genes were identified. Univariate, multivariate, and LASSO Cox regression analyses screened out five prognostic-related genes (ENO3, GPC1, P4HA1, SPAG4, and STC2). Kaplan–Meier curves and receiver operating characteristic curves (ROC, AUC = 0.766) showed that the risk model could become an effective prognostic indicator (P < 0.001). Multivariate Cox analysis also revealed that this risk model is independent of age and TNM stages. We further validated this risk model in external cohorts (GES38832 and GSE39582), showing these five glycolytic genes could emerge as reliable predictors for CRC patients’ outcomes. Lastly, based on five genes and risk score, we construct a nomogram model assessed by C-index (0.7905) and calibration plot. In conclusion, we highlighted the clinical significance of glycolysis in CRC and constructed a glycolysis-related prognostic model, providing a promising target for glycolysis regulation in CRC.

Objectives: To test the effectiveness of quantitative linear-quadratic-based (qLQB) model on evaluating irradiation-induced liver injury (ILI) and establish the relation between the damaged ratio/percent (DRP) in qLQB model and normal tissue complication probility (NTCP). Materials and Methods: We established the qLQB model to calculate the ratio/percent (RP) between damaged cell/functional subunit (FSU) and entire cell/FSU of liver for radiation dose response, tested the qLQB against the Lyman-Kutcher-Burman (LKB) model, and established relation between the RP and NTCP through analyzing the dose of 32 patients with cancer of abdominal cavity who were treated with radiation therapy at our department. Based on varied α/β and varied parameters for NTCP, we put the calculated results into varied arrays for the next analysis. We named the 2 groups of RPs: RP1 (α/β = 3.0, α = 0.03) and RP2 (α/β = 8.0, α = 0.26), and named the 2 groups of NTCPs: NTCP1 (n = 0.32, m = 0.15, TD50(1) = 4000 cGy) and NTCP2 (n = 1.10, m = 0.28, TD50(1) = 4050 cGy). Results: Spearman correlation analysis was used to analyze the correlations among the groups, the results were as follows: RP1 vs NTCP1, rs = 0.83827, p < 0.0001; RP1 vs NTCP2, rs = 0.83827, p < 0.0001; RP2 vs NTCP2, rs = 0.79289, p < 0.0001; and RP2 vs NTCP1, rs = 0.79289, p < 0.0001. Conclusions: There is a significant correlation between RP value and NTCP for evaluating ILI, and there is no difference between qLQB model and LKB model on evaluating ILI.

Salivary gland tumor (SGT) is a rare tumor type, which exhibits broad-spectrum phenotypic, biological, and clinical heterogeneity. Currently, the molecular mechanisms that cause SGT pathogenesis remain poorly understood. A lack of animal models that faithfully recapitulate the naturally occurring process of human SGTs has hampered research progress on this field. In this report, we developed an inducible keratin 5-driven conditional knockout mouse model to delete gene(s) of interest in murine salivary gland upon local RU486 delivery. We have deleted two major tumor suppressors, Pten, a negative regulator of the PI3K pathway, and Smad4, the central signaling mediator of TGFβ pathway, in the murine salivary gland. Our results have shown that deletion of either Pten or Smad4 in murine salivary gland resulted in pleomorphic adenomas, the most common tumor in human SGT patients. Deletion of both Pten and Smad4 in murine salivary gland developed several malignancies, with salivary adenoid cystic carcinoma (SACC) being the most frequently seen. Molecular characterization showed that SACC exhibited mTOR activation and TGFβ1 overexpression. Examination of human SGT clinical samples revealed that loss of Pten and Smad4 is common in human SACC samples, particularly in the most aggressive solid form, and is correlated with survival of SACC patients, highlighting the human relevance of the murine models. In summary, our results offer significant insight into synergistic role of Pten and Smad4 in SGT, providing a rationale for targeting mTOR and/or TGFβ signaling to control SGT formation and progression.

It is known that, by taking advantage of heteroatom doping, the electronic states and transition channels in carbon nano-dots (CNDs) can be effectively modulated. Thus, the photoluminescence (PL) properties of CNDs can be changed. For potential applications of CNDs as advanced materials for optoelectronic devices, it is important and significant to develop the practical techniques for doping heteroatoms into CNDs. In this work, we synthesize the multi-color fluorescent by using a fast and effective microwave method where the CNDs are nitrogen-doped. We examine the influence of different ratios of the raw materials on the structure and optical properties of N-CNDs. The results show that the prepared N-CNDs can generate blue (445 nm), green (546 nm), and orange (617 nm) fluorescence or PL with the mass ratio of the raw materials at 1:1, 1:2 and 1:3, respectively. We find that the N content in N-CNDs leads to different surface/edge states in n−π∗ domain. Thus, the wavelength of the PL emission from N-CNDs can be tuned via controlling the N concentration doped into the CNDs. Moreover, it is shown that the intensity of the PL from N-CNDs is mainly positively related to the content of C-O groups attached on the surface/edges of the N-CNDs. This study provides an effective experimental method and technical way to improve the fluorescent emission, and to modulate the color of the PL emission from CNDs.

Abstract Background We previously reported that Wnt5a/CaMKIIδ (calcium/calmodulin-dependent protein kinase II delta) pathway was involved in the embryonic tongue deformity induced by excess retinoic acid (RA). Our latest study found that the expression of miR-31-5p, which was predicted to target the 3′UTR of CamkIIδ, was raised in the RA-treated embryonic tongue. Thus, we hypothesized that the excess RA regulated Wnt5a/CaMKIIδ pathway through miR-31-5p in embryonic tongue. Methods C2C12 myoblast line was employed as an in vitro model to examine the suppression of miR-31-5p on CamkIIδ expression, through which RA impaired the myoblast proliferation and differentiation in embryonic tongue. Results RA stimulated the expression of miR-31-5p in both embryonic tongue and C2C12 myoblasts. Luciferase reporter assay confirmed that the 3′UTR of CamkIIδ was a target of miR-31-5p. MiR-31-5p mimics disrupted CamkIIδ expression, C2C12 proliferation and differentiation as excess RA did, while miR-31-5p inhibitor partially rescued these defects in the presence of RA. Conclusions Excess RA can stimulate miR-31-5p expression to suppress CamkIIδ, which represses the proliferation and differentiation of tongue myoblasts.

Geometric design consistency refers to the conformance of a proposed or existing freeway’s geometry with the driver’s expectancy. Considerable efforts have been undertaken to develop potential quantitative consistency measures and models to estimate them. However, little work has been focused on the facts of freeways in China, especially in mountainous areas. The primary objective of this study is to examine and quantify the design consistency of a freeway, using an interactive driving simulator, so as to identify any inconsistency on the roadway geometry and improve its overall safety performance. More specifically, the techniques to evaluate the consistency of a geometric design depend on three criteria: design consistency, operating speed consistency, and consistency in driving dynamics, as well as three levels of consistency: good, acceptable and poor. In the case of Taigan Freeway, a part of G45 Daguang Freeway in Jiangxi, China, a 21km long segment has been divided into 38 sections including 22 curves and 16 tangents, and transferred into the graphics models in the simulator system. There were 42 drivers required to take part in the simulation experiment and the speed, location of vehicle, and other real time data were recorded as well. The findings have shown that these proposed measures and standards can identify a geometric inconsistency more effectively when there is a large rate of change in the alignment elements for a successive roadway segment.

There is a need to evaluate the safety performance of road intersections in a vehicle platoon environment. For this purpose, this study attempts to quantify intersection related accidents and develop countermeasures to reduce injuries resulting from such accidents, using the selected data of 3520 casualties over the period 1992–2007 in Harbin. Then the distribution characteristics of accident number and rate via a half experience model are statisticed and find that proportionately 89.15% of total records occurred at unsignalized intersections and the injuries and fatalities account for approximately 62.35% at irregular ones. Using techniques of linear regression, several different explanatory models are constructed to identify the factors associated with annual average daily traffic, junction numbers and volume/capacity and thus 3 stages are classified in response to diverse risk level. Moreover, we developed a pedestrian risk factor to quantity the crossing risk around intersection locations, due to pedestrian are more likely to be at-fault in accidents, and 8 roads in Harbin, including Hongqi Str., Nanzhi Rd., etc., are consequently detected with higher crosswalk risk. For safety enhancement approaches, effective measures are proposed to be a combination of facilities improvement, intelligent transportation system application, enforcement and educational programs implemented for both drivers, pedestrians and other users to reduce the overall number of crashes and provide a safer traffic environment.

To promote the development of anode materials for rechargeable batteries, we investigated the relationships between the structure characteristics and the electronic, mechanical, adsorption, diffusion and electrochemical properties of the designed Ti3N2T2/VS2 (T = F, O, OH) heterostructures for lithium/sodium/magnesium-ion batteries using density functional theory calculations. Three optimal heterostructures with different terminations, Ti3N2F2/VS2, Ti3N2O2/VS2 and Ti3N2(OH)2/VS2, were selected, and the mechanisms of charge transfer and ion diffusion were expounded clearly. These heterostructures can be used as novel anode materials based on excellent thermal stability, metallicity, mechanical stability, adsorption and diffusion performance. The results indicate that the main contributors to the metallicity are the d-orbital electronic states derived from Ti and V. The intrinsic nature of metallicity guarantees a good electrical conductivity that enables rapid charge migration and accelerates the redox process. The ion insertion not only affects the density of states distributions of the heterostructures, but also enhances their Fermi levels. The amount of charge transfer from a metal ion to VS2 is more than that to Ti3N2T2 at the respective interlayers of Ti3N2F2/VS2 and Ti3N2(OH)2/VS2, while the opposite trend appears for Ti3N2O2/VS2. The monolayer that gains more charges from the ion corresponds to the charge acceptor in the pristine heterostructure without ion adsorption. The most favorable ion-diffusion path between two optimal adsorption sites inevitably passes through the second optimal adsorption site with the second smallest adsorption energy. Considering the structural integrity, strong adsorption abilities, low diffusion energy barriers, high capacities and suitable open-circuit voltages, Ti3N2F2/VS2 and Ti3N2(OH)2/VS2 are proposed to be promising high-performance anode materials for SIBs and LIBs/MIBs, respectively, and Ti3N2O2/VS2 is an ideal anode material for LIBs/SIBs/MIBs. [ABSTRACT FROM AUTHOR]