Apolipoprotein A-1 downregulation promotes basal-like breast cancer cell proliferation and migration associated with DNA methylation.

Apolipoprotein A-I (APOA1) performs different roles in different subtypes of breast cancer. It is hypothesized to function as a tumor suppressor in basal-like breast cancer (BLBC). However, the specific role of APOA1 in BLBC and its underlying mechanisms remain unknown. The findings of the present study demonstrated a positive correlation between the expression level of APOA1 and the overall survival of patients with BLBC. Ectopic expression of APOA1 effectively inhibits the proliferation and metastasis of BLBC cells in vitro, and these effects are closely related to DNA methylation. To the best of our knowledge, the present study is the first to report increased methylation of the promoter region and decreased methylation of the structural genes of APOA1 in BLBC cells. These alterations resulted in the downregulation of APOA1 expression and suppression of BLBC tumor growth. Collectively, the results of the present study suggested that APOA1 mRNA expression is negatively regulated by DNA methylation in BLBC. Therefore, low expression of APOA1 may be a potential risk biomarker to predict survival in patients with BLBC.

Plant size-dependent influence of foliar fungal pathogens promotes diversity through allometric growth.

The effect of pathogens on host diversity has attracted much attention in recent years, yet how the influence of pathogens on individual plants scales up to affect community-level host diversity remains unclear. Here, we assessed the effects of foliar fungal pathogens on plant growth and species richness using allometric growth theory in population-level and community-level foliar fungal pathogen exclusion experiments. We calculated growth scaling exponents of 24 species to reveal the intraspecific size-dependent effects of foliar fungal pathogens on plant growth. We also calculated the intercepts to infer the growth rates of relatively larger conspecific individuals. We found that foliar fungal pathogens inhibited the growth of small conspecific individuals more than large individuals, resulting in a positive allometric growth. After foliar fungal pathogen exclusion, species-specific growth scaling exponents and intercepts decreased, but became positively related to species' relative abundance, providing a growth advantage for individuals of abundant species with a higher growth scaling exponent and intercept compared with rare species, and thus reduced species diversity. By adopting allometric growth theory, we elucidate the size-dependent mechanisms through which pathogens regulate species diversity and provide a powerful framework to incorporate antagonistic size-dependent processes in understanding species coexistence.

m5 C regulator-mediated methylation modification patterns and tumor microenvironment infiltration characteristics in acute myeloid leukemia.

BACKGROUND: Recently, many studies have been conducted to examine immune response modification at epigenetic level, but the candidate effect of RNA 5-methylcytosine (m5 C) modification on tumor microenvironment (TME) of acute myeloid leukemia (AML) is still unknown at present. METHODS: We assessed the patterns of m5 C modification among 417 AML cases by using nine m5 C regulators. Thereafter, we associated those identified modification patterns with TME cell infiltration features. Additionally, stepwise regression and LASSO Cox regression analyses were conducted for quantifying patterns of m5 C modification among AML cases to establish the m5 C-score. Meanwhile, we validated the expression of genes in the m5C-score model by qRT-PCR. Finally, the present work analyzed the association between m5 C-score and AML clinical characteristics and prognostic outcomes. RESULTS: In total, three different patterns of m5 C modification (m5 C-clusters) were identified, and highly differentiated TME cell infiltration features were also identified. On this basis, evaluating patterns of m5 C modification in single cancer samples was important for evaluating the immune/stromal activities in TME and for predicting prognosis. In addition, the m5 C-score was established, which showed a close relation with the overall survival (OS) of test and training set samples. Moreover, multivariate Cox analysis suggested that our constructed m5 C-score served as the independent predicting factor for the prognosis of AML (hazard ratio = 1.57, 95% confidence interval = 1.38-1.79, p < 1e-5 ). CONCLUSIONS: This study shows that m5 C modification may be one of the key roles in the formation of diversity and complexity of TME. Meanwhile, assessing the patterns of m5 C modification among individual cancer samples is of great importance, which provides insights into cell infiltration features within TME, thereby helping to develop relevant immunotherapy and predict patient prognostic outcomes.

Bulk RNA-sequencing, single-cell RNA-sequencing analysis, and experimental validation reveal iron metabolism-related genes CISD2 and CYP17A1 are potential diagnostic markers for recurrent pregnancy loss.

BACKGROUND: Recurrent pregnancy loss (RPL) is associated with variable causes. Its etiology remains unexplained in about half of the cases, with no effective treatment available. Individuals with RPL have an irregular iron metabolism. In the present study, we identified key genes impacting iron metabolism that could be used for diagnosing and treating RPL. METHODS: We obtained gene expression profiles from the Gene Expression Omnibus (GEO) database. The Molecular Signatures Database was used to identify 14 gene sets related to iron metabolism, comprising 520 iron metabolism genes. Differential analysis and a weighted gene co-expression network analysis (WGCNA) of gene expression revealed two iron metabolism-related hub genes. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry were used on clinical samples to confirm our results. The receiver operating characteristic (ROC) analysis and immune infiltration analysis were conducted. In addition, we analyzed the distribution of genes and performed CellChat analysis by single-cell RNA sequencing. RESULTS: The expression of two hub genes, namely, CDGSH iron sulfur domain 2 (CISD2)and Cytochrome P450 family 17 subfamily A member 1 (CYP17A1), were reduced in RPL, as verified by both qPCR and immunohistochemistry. The Gene Ontology (GO) analysis revealed the genes predominantly engaged in autophagy and iron metabolism. The area under the curve (AUC) demonstrated better diagnostic performance for RPL using CISD2 and CYP17A1. The single-cell transcriptomic analysis of RPL demonstrated that CISD2 is expressed in the majority of cell subpopulations, whereas CYP17A1 is not. The cell cycle analysis revealed highly active natural killer (NK) cells that displayed the highest communications with other cells, including the strongest interaction with macrophages through the migratory inhibitory factor (MIF) pathway. CONCLUSIONS: Our study suggested that CISD2 and CYP17A1 genes are involved in abnormal iron metabolism, thereby contributing to RPL. These genes could be used as potential diagnostic and therapeutic markers for RPL.

Methods for improving the properties of zinc for the application of biodegradable vascular stents.

Biodegradable stents can support vessels for an extended period, maintain vascular patency, and progressively degrade once vascular remodeling is completed, thereby reducing the constraints of traditional metal stents. An ideal degradable stent must have good mechanical properties, degradation behavior, and biocompatibility. Zinc has become a new type of biodegradable metal after magnesium and iron, owing to its suitable degradation rate and good biocompatibility. However, zinc's poor strength and ductility make it unsuitable as a vascular stent material. Therefore, this paper reviewed the primary methods for improving the overall properties of zinc. By discussing the mechanical properties, degradation behavior, and biocompatibility of various improvement strategies, we found that alloying is the most common, simple, and effective method to improve mechanical properties. Deformation processing can further improve the mechanical properties by changing the microstructures of zinc alloys. Surface modification is an important means to improve the biological activity, blood compatibility and corrosion resistance of zinc alloys. Meanwhile, structural design can not only improve the mechanical properties of the vascular stents, but also endow the stents with special properties such as negative Poisson 's ratio. Manufacturing zinc alloys with excellent degradation properties, improved mechanical properties and strong biocompatibility and exploring their mechanism of interaction with the human body remain areas for future research.

Numerical Simulation of Dynamic Degradation and Fatigue Damage of Degradable Zinc Alloy Stents.

Current research on the fatigue properties of degradable zinc alloy stents has not yet considered the issue of the fatigue life changing with material properties during the dynamic degradation process. Therefore, in this paper, we established a fatigue damage algorithm to study the fatigue problem affected by the changing of material properties during the dynamic degradation process of the stent under the action of pulsating cyclic loading. Three models: the dynamic degradation model, the dynamic degradation model under pulsating cyclic loading, and the coupled model of fatigue damage and dynamic degradation, were developed to verify the effect of fatigue damage on stent life. The results show that fatigue damage leads to a deeper degree of inhomogeneous degradation of the stent, which affects the service life of the stent. Fatigue damage is a factor that cannot be ignored. Therefore, when studying the mechanical properties and lifetime of degradable stents, incorporating fatigue damage into the study can help more accurately assess the lifetime of the stents.

Exercise Mitigates Endothelial Pyroptosis and Atherosclerosis by Downregulating NEAT1 Through N6-Methyladenosine Modifications.

BACKGROUND: The benefits of exercise on the cardiovascular system are widely recognized; however, the underlying mechanisms are unknown. Here, we report the effect of the long noncoding RNA NEAT1 (nuclear paraspeckle assembly transcript 1), which is regulated by exercise, on atherosclerosis development after N6-methyladenosine (m6A) modifications. METHODS: Using clinical cohorts and NEAT1-/- mice, we determined the exercise-mediated expression and role of NEAT1 in atherosclerosis. To investigate the mechanism of epigenetic modification of NEAT1 regulated by exercise, we identified METTL14 (methyltransferase-like 14)-a key m6A modification enzyme under exercise-and found that METTL14 alters the expression and role of NEAT1 through m6A modification and elucidated the specific mechanism of METTL14 in vitro and in vivo. Finally, the NEAT1 downstream regulatory network was investigated. RESULTS: We found that NEAT1 expression was downregulated with exercise and that downregulation of NEAT1 was an important factor in the improvement of atherosclerosis with exercise. Exercise-mediated loss of function of NEAT1 can delay atherosclerosis. Mechanistically, we showed that exercise induced a significant downregulation of m6A modification and METTL14, which binds to the m6A sites of NEAT1 and promotes NEAT1 expression through subsequent YTHDC1 (YTH domain-containing 1) recognition to promote endothelial pyroptosis. Furthermore, NEAT1 induces endothelial pyroptosis by binding KLF4 (Kruppel-like factor 4) to promote the transcriptional activation of the key pyroptotic protein NLRP3 (NOD-like receptor thermal protein domain-associated protein 3), whereas exercise can attenuate NEAT1-mediated endothelial pyroptosis to improve atherosclerosis. CONCLUSIONS: Our study of NEAT1 provides new insights into the improvement of atherosclerosis by exercise. This finding demonstrates the role of exercise-mediated NEAT1 downregulation in atherosclerosis while expanding our understanding of the mechanisms by which exercise regulates long noncoding RNA function through epigenetic modifications.

Efficacy of Fufang E'jiao Jiang in the Treatment of Patients with Qi and Blood Deficiency Syndrome: A Real-World Prospective Multicenter Study with a Patient Registry.

Objective: This nationwide, multicenter prospective observational study with a patient registry was designed to evaluate the efficacy of Fufang E'jiao Jiang (FEJ) in Chinese patients with Qi and blood deficiency syndrome (QBDS). Methods: QBDS patients were consecutively recruited from 81 investigational sites in China from July, 2019, to December, 2020. Patients who met the eligibility criteria were enrolled in a prospective registry database. Baseline characteristics and changes in scores on the traditional Chinese medicine (TCM) symptom evaluation scale for Qi and blood deficiency, the clinical global impression (CGI) scale, the fatigue scale-14 (FS-14), and the Pittsburgh sleep quality index (PSQI) were analyzed to determine the clinical efficacy of FEJ. Results: A total of 3,203 patients were recruited. The average remission rate (i.e., the sum of the cure rate and improvement rate) of the 20 symptoms of QBDS was 92.49% after 4 weeks of FEJ treatment, which was higher than at baseline; the rate increased to 94.69% at 8 weeks. The CGI scale revealed that the number of total remissions at 4 and 8 weeks was 3,120 (97.41%) and 415 (100%), respectively. The total FS-14 scores decreased by 1.67 ± 4.11 (p < 0.001) at 4 weeks and 1.72 ± 3.09 (p < 0.001) at 8 weeks of treatment. The PSQI scores were 6.6 ± 4.7 and 6.52 ± 3.07 at 4 and 8 weeks, respectively, which were significantly lower than the baseline scores (p < 0.001; p = 0.0033). Both the subhealth fatigue (SF) and iron deficiency anemia (IDA) groups showed significantly improved clinical symptoms of QBDS (p < 0.01). Between-group comparisons revealed significantly greater improvements in FS-14 and PSQI scores in the SF group than in the IDA group (p < 0.05). A multivariate logistic regression analysis showed that disease course, FS-14 score at baseline, and four-week FEJ doses were independent risk factors for the degree of symptom relief in QBDS patients (p < 0.05). Conclusion: In real-world settings, FEJ has a promising effect in treating QBDS and can significantly improve the severity of its symptoms.

Recent Advances in Silver and Gold Nanoparticles-Based Colorimetric Sensors for Heavy Metal Ions Detection: A Review.

Silvetr and gold nanoparticles-based colorimetric sensors (Ag/Au-NPs-CSns) allow potential prospects for the development of efficient sensors owing to their unique shape- and size-dependent optical properties. In this review, recent (2020) advances in morphology-controllable synthesis, shape/size-dependent performance, sensing mechanism, challenges and prospects of Ag/Au-NPs-CSns for the detection of heavy metals are discussed. The size/shape-controlled synthesis of innovative Ag/Au-NPs-CSns is reviewed critically and the possible role of different parameters like temperature, time, pH, stabilizing/capping agents, reducing agents and concentration/nature of precursors are discussed. Then, we highlighted how the shape, size, optimum composition, functionalization, stabilizing/capping agents, surface structure and synergism influence the optical properties and sensing efficiency of Ag/Au-NPs-CSns. This review attempted to accentuate the efficiency of novel multimetallic Ag/AuNPs-CSns as compare to their monometallic counterparts and explained how the incorporation of multi-metals affects their performance. Besides, the sensing mechanisms of Ag/Au-NPs-CSns with special reference to recently published studies are discussed. Finally, challenges and prospects in the controllable-synthesis and practical applications of these sensors are studied. This mechanistic approach and timely review can be promisingly considered as a valuable reference and will help fuel new ideas for the development of novel colorimetric sensors. HighlightsA review of recent advances in Ag/Au-NPs-CSns for heavy metal ions detectionMorphology of Ag/Au-NPs-CSns regulate their optical properties/sensing efficiencyPromising Ag/Au-NPs-CSns can be synthesized by adjusting experimental parametersHybrid and functionalized Ag/Au-NPs-CSns have superior sensing performanceSize/shape transformation, aggregation/anti- and oxidation are sensing mechanisms.

Effect of Thermal Ablation on Growth Plates: A Study to Explore the Thermal Threshold of Rabbit Growth Plates During Microwave Ablation.

PURPOSE: To explore the temperature threshold of thermal damage to growth plates. METHODS: Nine rabbits were divided into three groups for femoral ablation, exposing the growth plate to different temperatures (T1 = 43-45 °C; T2 = 46-48 °C; T3 = 49-51 °C). After 5 weeks, the changes in the femurs were assessed by macroscopic images, micro-CT, haematoxylin and eosin staining, and immunohistochemistry of Col2a1 (type II collagen). At the cellular level, rabbit epiphyseal chondrocytes were exposed to 37 °C, 44 °C, 47 °C and 50 °C for 5 min. Then, proliferation and chondrogenic differentiation were detected. RESULTS: The rabbits in the T2 and T3 groups developed length discrepancies and axial deviations of femurs, abnormal newly formed bone in the marrow cavity, disorganized growth plates and decreased Col2a1 expression. At the cellular level, the cells exposed to 47 °C and 50 °C for 5 min showed decreased viability, increased apoptosis, decreased extracellular matrix synthesis and decreased matrix mineralization. However, the changes in rabbits in the T1 group and cells at 44 °C did not show a significant difference. CONCLUSION: The ablation of growth plates at temperatures above 45 °C for 5 min results in decreased chondrocyte viability and disorganized growth plates, leading to growth disturbances. Further studies are warranted to confirm these promising initial results.

Finite Element Analysis of the Non-Uniform Degradation of Biodegradable Vascular Stents.

Most of the studies on the finite element analysis (FEA) of biodegradable vascular stents (BVSs) during the degradation process have limited the accuracy of the simulation results due to the application of the uniform degradation model. This paper aims to establish an FEA model for the non-uniform degradation of BVSs by considering factors such as the dynamic changes of the corrosion properties and material properties of the element, as well as the pitting corrosion and stress corrosion. The results revealed that adjusting the corrosion rate according to the number of exposed surfaces of the element and reducing the stress threshold according to the corrosion status accelerates the degradation time of BVSs by 26% and 25%, respectively, compared with the uniform degradation model. The addition of the pitting model reduces the service life of the BVSs by up to 12%. The effective support of the stent to the vessel could reach at least 60% of the treatment effect before the vessel collapsed. These data indicate that the proposed non-uniform degradation model of BVSs with multiple factors produces different phenomena compared with the commonly used models and make the numerical simulation results more consistent with the real degradation scenario.

Deconstruction of the Optimal Design of Urban Road Interchange Based on the Integration of Smart Transportation and Big Data.

Urban interchange is the core hub connecting various regions, and it is of great significance for alleviating the problem of traffic congestion. In the process of urban interchange design, it is impossible to strictly control the traffic volume, interchange types, and standards by relying on traditional technologies. Smart transportation and big data are emerging technologies based on data, which can provide technical support for design and decision making. Based on this, this paper first uses smart transportation and big data technology to predict the traffic volume of Nancheng New District, so as to calculate the future development trend of the target area. Then, on the basis of traffic volume, the article uses smart transportation and big data technology to optimize the original urban interchange design scheme from the aspects of traffic capacity, safety, economic benefits, and environmental benefits. Finally, the article evaluates the optimized urban interchange scheme by means of comprehensive quantitative indicators and evaluation methods. Experiments show that the traffic capacity of the interchange on the outer ring road optimized by smart transportation and big data has increased to 72.6%, and the environmental coordination has increased from 45.2% to 55.2%. Moreover, the design aesthetics of the urban interchange after optimized design based on smart transportation and big data has increased to 65.9%. In addition, the comprehensive evaluation value of the urban interchange after optimization of smart transportation and big data reached 82.6. This fully shows that the optimal design of urban interchange based on the integration of smart transportation and big data can greatly improve the traffic capacity of urban roads.

Necroptosis-associated long noncoding RNAs can predict prognosis and differentiate between cold and hot tumors in ovarian cancer.

Objective: The mortality rate of ovarian cancer (OC) is the highest among all gynecologic cancers. To predict the prognosis and the efficacy of immunotherapy, we identified new biomarkers. Methods: The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression Project (GTEx) databases were used to extract ovarian cancer transcriptomes. By performing the co-expression analysis, we identified necroptosis-associated long noncoding RNAs (lncRNAs). We used the least absolute shrinkage and selection operator (LASSO) to build the risk model. The qRT-PCR assay was conducted to confirm the differential expression of lncRNAs in the ovarian cancer cell line SK-OV-3. Gene Set Enrichment Analysis, Kaplan-Meier analysis, and the nomogram were used to determine the lncRNAs model. Additionally, the risk model was estimated to evaluate the efficacy of immunotherapy and chemotherapy. We classified necroptosis-associated IncRNAs into two clusters to distinguish between cold and hot tumors. Results: The model was constructed using six necroptosis-associated lncRNAs. The calibration plots from the model showed good consistency with the prognostic predictions. The overall survival of one, three, and five-year areas under the ROC curve (AUC) was 0.691, 0.678, and 0.691, respectively. There were significant differences in the IC50 between the risk groups, which could serve as a guide to systemic treatment. The results of the qRT-PCR assay showed that AL928654.1, AL133371.2, AC007991.4, and LINC00996 were significantly higher in the SK-OV-3 cell line than in the Iose-80 cell line (P < 0.05). The clusters could be applied to differentiate between cold and hot tumors more accurately and assist in accurate mediation. Cluster 2 was more vulnerable to immunotherapies and was identified as the hot tumor. Conclusion: Necroptosis-associated lncRNAs are reliable predictors of prognosis and can provide a treatment strategy by screening for hot tumors.

Preparation of graphene-supported-metal-phthalocyanine and mechanistic understanding of its catalytic nature at molecular level.

The fundamental mechanistic understanding of the working principle of metal phthalocyanine (MPc) + H2O2 system, at molecular level, is in its nascent stage. In this paper, a green strategy was employed for the immobilization of sulfonated cobalt phthalocyanine (CoPc) onto reduced graphene with assistance of bio-synthesized nanocellulose, and the resulting graphene-supported-CoPc (CoPc&G) was applied for the catalytic degradation of phenol solution with H2O2 as oxidant. More than 90% of phenol can be removed within 75 min, and the existence of graphene clearly has a positive effect on the catalytic activity. Theoretical calculations were conducted to unveil the catalytic nature of CoPc&G. H2O2 was favorably chemisorbed onto CoPc&G in the form of OOH-, hydroxyl radicals were favorably formed by homolytic cleavage of OO bonds, and ΔG value for the formation of reactive species was decreased with the existence of graphene. Density of states (DOS) analysis shows that graphene could effectively boost the electronic activity, reduce HOMO-LUMO gap, and strengthen the polarizability of the catalyst, thereby lower the free energy gap for the enhanced generation of reactive species. A detailed catalytic degradation route of phenol with CoPc&G + H2O2 system was established based on the combination of theoretical calculations and experimental results.

A computational analysis of potential aortic dilation induced by the hemodynamic effects of bicuspid aortic valve phenotypes.

BACKGROUND AND OBJECTIVES: The bicuspid aortic valve (BAV) is a major risk factor for the progression of aortic dilation (AD) because of the induced abnormal blood flow environment in aorta. The differences in the development of AD induced by BAV phenotypes remains unclear. Therefore, the objective of this study was to assess the potential locations of AD induced by different phenotypes of BAV. The different effects of opening orifice area and leaflet orientation on ascending aortic hemodynamics in Type-1 BAV was investigated by means of numerical simulation. METHODS: Finite element dynamic analysis was performed on tricuspid aortic valve (TAV) and BAV models to simulate the motion of the leaflets and obtain the geometrical characteristics of AV at peak systole as a reference, which were used for aortic models. Then, four sets of aortic fluid models were designed according to the leaflet fusion types [TAV; BAV (left-right-coronary cusp fusion, LR; right-non-coronary cusp fusion, RN; left-non-coronary cusp fusion, LN)], and the computational fluid dynamics method was applied to compare the hemodynamic differences within the aorta at peak systole. RESULTS: The maximum opening area of BAV was significantly reduced, resulting in alterations in aortic hemodynamics compared with TAV. The velocity streamlines were essentially parallel to the aortic wall in TAV. The average pressure and wall shear stress in aorta tend to be stable. In contrary, the eccentricity of BAV orifice jet resulted in high-velocity flow directed toward the ascending aorta (AA) wall and aortic arch for LR and LN; RN features an asymmetrical velocity distribution toward the outer bend of the middle AA, and eccentric flow tends to impact the distal AA. As the flow angle is associated with distinct flow impingement locations, different degrees of WSS and pressure concentration occur along the aortic wall from the AA to the aortic arch in three BAV types. CONCLUSIONS: The BAV morphotype affects the aortic hemodynamics, and the abnormal blood flow associated with BAV may play a role in AD. The different BAV phenotypes determine the direction of blood flow jet and change the expression of dilation. LR is likely to cause dilation of the tubular AA; RN results in dilation of the middle AA to proximal aortic arch; and LN causes an increased incidence of the tubular AA and the proximal aortic arch.

SERS-based lateral flow immunoassay for sensitive and simultaneous detection of anti-SARS-CoV-2 IgM and IgG antibodies by using gap-enhanced Raman nanotags.

The lateral flow immunoassay (LFIA) has played a crucial role in early diagnosis during the current COVID-19 pandemic owing to its simplicity, speed and affordability for coronavirus antibody detection. However, the sensitivity of the commercially available LFIAs needs to be improved to better prevent the spread of the infection. Here, we developed an ultra-sensitive surface-enhanced Raman scattering-based lateral flow immunoassay (SERS-based LFIA) strip for simultaneous detection of anti-SARS-CoV-2 IgM and IgG by using gap-enhanced Raman nanotags (GERTs). The GERTs with a 1 nm gap between the core and shell were used to produce the "hot spots", which provided about 30-fold enhancement as compared to conventional nanotags. The COVID-19 recombinant antigens were conjugated on GERTs surfaces and replaced the traditional colloidal gold for the Raman sensitive detection of human IgM and IgG. The LODs of IgM and IgG were found to be 1 ng/mL and 0.1 ng/mL (about 100 times decrease was observed as compared to commercially available LFIA strips), respectively. Moreover, under the condition of common nano-surface antigen, precise SERS signals proved the unreliability of quantitation because of the interference effect of IgM on IgG.

Efficient Catalytic Degradation of Phenol with Phthalocyanine-Immobilized Reduced Graphene-Bacterial Cellulose Nanocomposite.

In this report, phthalocyanine (Pc)/reduced graphene (rG)/bacterial cellulose (BC) ternary nanocomposite, Pc-rGBC, was developed through the immobilization of Pc onto a reduced graphene-bacterial cellulose (rGBC) nanohybrid after the reduction of biosynthesized graphene oxide-bacterial cellulose (GOBC) with N2H4. Field emission scanning electron microscopy (FESEM) and Fourier transform infrared spectroscopy (FT-IR) were employed to monitor all of the functionalization processes. The Pc-rGBC nanocomposite was applied for the treatment of phenol wastewater. Thanks to the synergistic effect of BC and rG, Pc-rGBC had good adsorption capacity to phenol molecules, and the equilibrium adsorption data fitted well with the Freundlich model. When H2O2 was presented as an oxidant, phenol could rapidly be catalytically decomposed by the Pc-rGBC nanocomposite; the phenol degradation ratio was more than 90% within 90 min of catalytic oxidation, and the recycling experiment showed that the Pc-rGBC nanocomposite had excellent recycling performance in the consecutive treatment of phenol wastewater. The HPLC result showed that several organic acids, such as oxalic acid, maleic acid, fumaric acid, glutaric acid, and adipic acid, were formed during the reaction. The chemical oxygen demand (COD) result indicated that the formed organic acids could be further mineralized to CO2 and H2O, and the mineralization ratio was more than 80% when the catalytic reaction time was prolonged to 4 h. This work is of vital importance, in terms of both academic research and industrial practice, to the design of Pc-based functional materials and their application in environmental purification.

Efficient detection and post-surgical monitoring of colon cancer with a multi-marker DNA methylation liquid biopsy.

Multiplex assays, involving the simultaneous use of multiple circulating tumor DNA (ctDNA) markers, can improve the performance of liquid biopsies so that they are highly predictive of cancer recurrence. We have developed a single-tube methylation-specific quantitative PCR assay (mqMSP) that uses 10 different methylation markers and is capable of quantitative analysis of plasma samples with as little as 0.05% tumor DNA. In a cohort of 179 plasma samples from colorectal cancer (CRC) patients, adenoma patients, and healthy controls, the sensitivity and specificity of the mqMSP assay were 84.9% and 83.3%, respectively. In a head-to-head comparative study, the mqMSP assay also performed better for detecting early-stage (stage I and II) and premalignant polyps than a published SEPT9 assay. In an independent longitudinal cohort of 182 plasma samples (preoperative, postoperative, and follow-up) from 82 CRC patients, the mqMSP assay detected ctDNA in 73 (89.0%) of the preoperative plasma samples. Postoperative detection of ctDNA (within 2 wk of surgery) identified 11 of the 20 recurrence patients and was associated with poorer recurrence-free survival (hazard ratio, 4.20; P = 0.0005). With subsequent longitudinal monitoring, 14 patients (70%) had detectable ctDNA before recurrence, with a median lead time of 8.0 mo earlier than seen with radiologic imaging. The mqMSP assay is cost-effective and easily implementable for routine clinical monitoring of CRC recurrence, which can lead to better patient management after surgery.

Multiscale Modeling of Vascular Remodeling Induced by Wall Shear Stress.

OBJECTIVE: Hemodynamics-induced low wall shear stress (WSS) is one of the critical reasons leading to vascular remodeling. However, the coupling effects of WSS and cellular kinetics have not been clearly modeled. The aim of this study was to establish a multiscale modeling approach to reveal the vascular remodeling behavior under the interaction between the macroscale of WSS loading and the microscale of cell evolution. METHODS: Computational fluid dynamics (CFD) method and agent-based model (ABM), which have significantly different characteristics in temporal and spatial scales, were adopted to establish the multiscale model. The CFD method is for the second/organ scale, and the ABM is for the month/cell scale. The CFD method was used to simulate blood flow in a vessel and obtain the WSS in a vessel cross-section. The simulations of the smooth muscle cell (SMC) proliferation/apoptosis and extracellular matrix (ECM) generation/degradation in a vessel cross-section were performed by using ABM. During the simulation of the vascular remodeling procedure, the damage index of the SMC and ECM was defined as deviation from the obtained WSS. The damage index decreased gradually to mimic the recovery of WSS-induced vessel damage. RESULTS: (1) The significant wall thickening region was consistent with the low WSS region. (2) There was no evident change of wall thickness in the normal WSS region. (3) When the damage index approached to 0, the amount and distribution of SMCs and ECM achieved a stable state, and the vessel reached vascular homeostasis. CONCLUSION: The established multiscale model can be used to simulate the vascular remodeling behavior over time under various WSS conditions.

[Review of studies on the biomechanical modelling of the coupling effect between stent degradation and blood vessel remodeling].

The dynamic coupling of stent degradation and vessel remodeling can influence not only the structural morphology and material property of stent and vessel, but also the development of in-stent restenosis. The research achievements of biomechanical modelling and analysis of stent degradation and vessel remodeling were reviewed; several noteworthy research perspectives were addressed, a stent-vessel coupling model was developed based on stent damage function and vessel growth function, and then concepts of matching ratio and risk factor were established so as to evaluate the treatment effect of stent intervention, which may lay the scientific foundation for the structure design, mechanical analysis and clinical application of biodegradable stent.