Increasing evidence has indicated the great diagnostic and therapeutic potentials of circular RNAs (circRNAs) in human cancers. Although the biological roles of circRNAs in pancreatic ductal ...adenocarcinoma (PDAC) have been partially annotated, the potential regulatory mechanism of circRNAs in PDAC tumorigenesis remains poorly understood. Here, our study found that the novel circRNA circSLIT2 was significantly upregulated in PDAC tissues and cells. Clinically, ectopic high-expression of circSLIT2 was correlated with unfavorable prognosis of PDAC patients. Functional experiments demonstrated that circSLIT2 promoted the aerobic glycolysis and proliferation of PDAC cells in vitro, and circSLIT2 knockdown inhibited tumor growth in vivo. Mechanistically, circSLIT2 acted as miRNA sponge to target miR-510-5p/c-Myc axis. Furthermore, c-Myc bound with the promoter region of lactate dehydrogenase A (LDHA) to activate the transcription. Collectively, present findings reveal that circSLIT2/miR-510-5p/c-Myc/LDHA axis participates in the aerobic glycolysis and carcinogenesis of PDAC, and may act as a promising therapeutic target.
Treading on the heels of the spread of the coronavirus, the "loneliness virus" has been capturing territories globally. Consumers are not immune to loneliness. Although academics and the general ...public have recognized the devastating effects of loneliness, the academic attention given to consumer loneliness (CL) is scattered and fragmentary. The purpose of this article is to systematically review the antecedents (predictors and alleviators) and consequences (consumer behaviors, emotions, preferences, attitudes, and cognition) of CL in various consumption contexts. This review also presents findings on CL as a mediator and moderator in consumer studies. This work adds to the growing body of CL literature by synthesizing the existing findings and knowledge. More importantly, we present a future research agenda by linking CL to significant research lines and detailed implications for practitioners in the marketplace.
An integrated pretreatment process based on hydrothermal pretreatment (HTP) followed by alkaline pretreatment has been applied to treat Eucalyptus. The chemical composition and structure changes of ...lignin during the pretreatment were comprehensively characterized. The surface morphology of the cell walls and lignin distribution of the pretreated Eucalyptus were detected by scanning electron and confocal Raman microscopies. It was found that the chemical bonds between lignin and hemicelluloses were cleaved during the pretreatment. The results also indicated that the contents of β-O-4', β-β', and β-5' linkages were decreased with the increase of hydrothermal pretreatment temperature and the cleavage of β-O-4' linkages in lignin was accompanied with repolymerization reactions.
P NMR analysis showed that the content of aliphatic OH was reduced as the temperature increased and the total phenolic OH was elevated and then declined with the increase of temperature. Raman spectra analysis revealed that the dissolution rate of lignin in the secondary wall regions was faster than that in cell corner middle lamella regions during the pretreatment. These results will enhance the understanding of the cell wall deconstruction during the pretreatment and the mechanism of the integrated pretreatment process acting on Eucalyptus.
The U.S. with only 4% of the world's population, bears a disproportionate share of infections in the COVID-19 pandemic. To understand this puzzle, we investigate how mitigation strategies and ...compliance can work together (or in opposition) to reduce (or increase) the spread of COVID-19 infection. Building on the Oxford index, we create state-specific stringency indices tailored to U.S. conditions, to measure the degree of strictness of public mitigation measures. A modified time-varying SEIRD model, incorporating this Stringency Index as well as a Compliance Indicator is then estimated with daily data for a sample of 6 U.S. states: New York, New Hampshire, New Mexico, Colorado, Texas, and Arizona. We provide a simple visual policy tool to evaluate the various combinations of mitigation policies and compliance that can reduce the basic reproduction number to less than one, the acknowledged threshold in the epidemiological literature to control the pandemic. Understanding of this relationship by both the public and policy makers is key to controlling the pandemic. This tool has the potential to be used in a real-time, dynamic fashion for flexible policy options. Our methodology can be applied to other countries and has the potential to be extended to other epidemiological models as well. With this first step in attempting to quantify the factors that go into the "black box" of the transmission factor β, we hope that our work will stimulate further research in the dual role of mitigation policies and compliance.
Mild cognitive impairment (MCI) is a pre-clinical stage of Alzheimer's disease (AD). Understanding the transition probabilities across the disease continuum of AD, ranging from MCI to AD to Mortality ...is crucial for the economic modeling of AD and effective planning of future interventions and healthcare resource allocation decisions. This study uses the Multi-state Markov model to quantify the transition probabilities along the disease progression and specifically investigates medications as modifiable risk factors of AD associated with accelerated or decelerated transition times from MCI to AD, MCI to mortality, and AD to mortality. Individuals with MCI were identified from the National Alzheimer's Coordinating Center between September 2005 and May 2021. A three-state Markov model was postulated to model the disease progression among three states: MCI, AD, and mortality with adjustment for demographics, genetic characteristics, comorbidities and medications. Transition probabilities, the total length of stay in each state, and the hazard ratios of the use of medications for diabetes, hypertension, and hypercholesterolemia (the known modifiable risk factors of AD) were evaluated for these transitions. 3,324 individuals with MCI were identified. The probability of developing AD after one year since the initial diagnosis of MCI is 14.9%. After approximately 6 years from the initial diagnosis of MCI, the probability of transitioning to AD increases to nearly 41.7% before experiencing a subsequent decline. The expected total lengths of stay were 5.38 (95% CI: 0.002-6.03) years at MCI state and 7.61 (95%CI: 0.002-8.88) years at AD state. Patients with active use of lipid-lowering agents were associated with significantly lower hazards of transitioning from MCI to AD (HR: 0.83, 95%CI:0.71-0.96), MCI to mortality (HR: 0.51, 95%CI:0.34-0.77), and AD to mortality (HR: 0.81, 95%CI:0.66-0.99).
Osteogenic differentiation of dental pulp stem cells (DPSCs) is considered as a promising strategy in posterior maxilla tooth implantation. Information on the function and mechanisms of long ...non-coding RNAs (lncRNAs) in osteogenic differentiation of DPSCs is growing, however, the mechanism of LINC00968 and miR-3658 in regulating osteogenic differentiation of DPSCs still needs to be explored. In this study, the LINC00968 and miR-3658 expression level was upregulated and downregulated in DPSCs and peri-implantitis DPSCs (pDPSCs) treated with bone morphogenic protein (BMP)2, respectively. Moreover, the effects of LINC00968 and miR-3658 on BMP2-induced osteogenic differentiation of DPSCs in vitro using Alizarin Red S staining, alkaline phosphatase (ALP) activity, quantitative real time PCR and Western blot assays showed that overexpression of LINC00968 significantly promoted mineralized bone matrix, alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), and osterix (OSX) expression levels for osteogenic differentiation of DPSCs and pDPSCs; and overexpression of miR-3658 showed an opposite result that inhibited osteogenic differentiation of DPSCs and pDPSCs. Luciferase reporter assay showed that luciferase activities of LINC00968-WT reporter and RUNX2-WT reporter were strongly suppressed by miR-3658 overexpression. In addition, the miR-3658 upregulation interfered ectopic bone formation in vivo stimulated by LINC00968. In general, we had identified a novel molecular pathway involving LINC00968/miR-3658/RUNX2 during DPSCs and pDPSCs differentiation into osteoblasts, which might facilitate bone anabolism.
Emerging evidence indicates the critical roles of N6-methyladenosine (m6A) modification in human cancers. Herein, our work reported that a novel m6A-modified circRNA from the MYO1C gene, circMYO1C, ...upregulated in the pancreatic ductal adenocarcinoma (PDAC). Our findings demonstrated that circMYO1C is highly expressed in PDAC tissues. Functionally, circMYO1C promoted the proliferation and migration of PDAC cells in vitro and its silencing reduced the tumor growth in vivo. Mechanistically, circMYO1C cyclization was mediated by m6A methyltransferase METTL3. Moreover, methylated RNA immunoprecipitation sequencing (MeRIP-seq) unveiled the remarkable m6A modification on PD-L1 mRNA. Moreover, circMYO1C targeted the m6A site of PD-L1 mRNA to enhance its stability by cooperating with IGF2BP2, thereby accelerating PDAC immune escape. In conclusion, these findings highlight the oncogenic role of METTL3-induced circMYO1C in PDAC tumorigenesis via an m6A-dependent manner, inspiring a novel strategy to explore PDAC epigenetic therapy.
The coupling of the joint network and groundwater in rock under bias conditions has a significant impact on the deformation and failure of the surrounding rock due to tunnel excavation. This paper ...studies the deformation and failure of surrounding rock after tunnel excavation under different joint network and groundwater conditions. A finite element-based composite joint network modeling method is proposed in this paper, and the typical parameters of the surrounding rock, such as the plastic zone size, vertical displacement, and lateral displacement, are analyzed and compared through numerical calculations. According to the different stratum and hydraulic conditions considered, four numerical models under four different working conditions are established and studied. The deformation and failure laws of the surrounding rock during tunnel excavation are obtained. The results show that with a single joint network, when there is no influence of groundwater, the surrounding rock mainly undergoes shear failure at the arch crown after tunnel excavation. When the influence of groundwater is considered, there are differences in the mode of damage between the left and right sides of the tunnel. The stratum approximately 1 m from the invert breaks, and the right sidewall fails approximately 1 m from the measuring point. In rock with a composite joint network, when groundwater is not considered, two kinds of failures occur in the surrounding rock near the tunnel; however, the surrounding rock far from the tunnel is dominated by shear failure. The stratum approximately 3.5 m from the arch crown fractures and the surrounding rock within approximately 5.5 m from the measurement point on the right sidewall undergoes separation failure. Under the dual effects of joints and groundwater, soft rock deforms considerably. The total hydraulic gradient decreases from left to right before and after tunnel excavation. The total hydraulic gradient of the composite joint network strata is generally smaller than that of the single joint network. In the composite joint network strata, the total hydraulic gradient near the tunnel changes dramatically. This research can provide a reference for tunnel engineering under similar conditions.
Abstract
Determining the sustainability of antibodies targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for predicting immune response against the Coronavirus ...disease 2019 (COVID-19). To quantify the antibody decay rates among the varying levels of anti-nucleocapsid (anti-N) Immunoglobulin G (IgG) in convalescent COVID-19 patients and estimate the length of time they maintained SARS-CoV-2 specific antibodies, we have collected longitudinal blood samples from 943 patients over the course of seven months after their initial detection of SARS-CoV-2 virus by RT-PCR. Anti-N IgG levels were then quantified in these blood samples. The primary study outcome was the comparison of antibody decay rates from convalescent patients with high or low initial levels of antibodies using a mixed linear model. Additional measures include the length of time that patients maintain sustainable levels of anti-N IgG. Antibody quantification of blood samples donated by the same subject multiple times shows a gradual decrease of IgG levels to the cutoff index level of 1.4 signal/cut-off (S/C) on the Abbott Architect SARS-CoV-2 IgG test. In addition, this study shows that antibody reduction rate is dependent on initial IgG levels, and patients with initial IgG levels above 3 S/C show a significant 1.68-fold faster reduction rate compared to those with initial IgG levels below 3 S/C. For a majority of the donors naturally occurring anti-N antibodies were detected above the threshold for only four months after infection with SARS-CoV-2. This study is clinically important for the prediction of immune response capacity in COVID-19 patients.
Focusing on the safe operation of rail transit during earthquakes, the finite element method is used to construct a wheel-track-subgrade dynamics model in this study. Through spring-damper units, the ...relationship between the rail and the track slab and the connection between the track slab and the subgrade are established. A method for establishing a viscoelastic artificial boundary is proposed. Four seismic waves—the Tianjin wave, the El Centro wave, the Taft wave, and the Qian’an wave—are selected as the seismic input waveforms, and only the impact of the lateral ground motion on the wheel-track-subgrade system is considered. In this paper, the ground motion problem is transformed into a wave source problem, the seismic input is transformed into an equivalent load acting on the artificial boundary, and the wave input of the viscoelastic artificial boundary is realized. The normalization method is used to process the seismic waves, and a method that converts the input of the seismic waves into equivalent loads is proposed. The changing laws of different dynamic response indexes under the influence of the four waveforms are studied. Under the action of the Tianjin wave, the wheel-rail dynamic response is very violent near the acceleration peak, whereas, after the peak, all dynamic response indexes are within a safe range. Under the effect of the El Centro wave, the collision between the wheel and the track is relatively violent, and the train is already in a dangerous state. Under the action of the Taft wave, due to the sudden action of the peak ground motion acceleration, the displacement between the wheel and the track increases instantaneously, causing the train to derail. Under the action of the Qian’an wave, the force between the wheel and rail changes approximately linearly with respect to the frequency of the ground motion, and all dynamic response indexes are within a safe range. The vibration intensity of the four seismic waves is amplified by an intensity expansion factor. Except for the Tianjin wave, the amplified seismic wave has a greater impact on safe train operations. This paper can provide a reference for research on the running safety of trains under similar dynamic disturbance conditions.
PDF
