Dysregulation of long non-coding RNAs has been found in many human cancers, including colorectal cancer that is still the third most prevalent cancer worldwide and related to poor prognosis; along ...with this, robust testimony has identified that long non-coding RNAs can take charge of tumor suppressor genes or oncogenes. This review summarizes nowadays research achievements on the character of long non-coding RNAs in the prognosis and diagnosis of colorectal cancer. On the basis of the results acquired in the last decade, some long non-coding RNAs are rising as biomarkers of colorectal cancer for prognosis, diagnosis, even prediction of therapeutic result, and have crucial effects in the regulation of colorectal cancer cell functions such as proliferation, invasion, apoptosis, metastasis, and drug resistant ability. Also, long non-coding RNAs, circulating in body fluids, could act as novel, affordable, lightly accessible, non-invasive detection tools for the personal health management of patients with colorectal cancer. Especially, circulating long non-coding RNA profiles may be demonstrating preferable prognostic and diagnostic capability and better accuracy than respective long non-coding RNAs in colorectal cancer.
The uniformity of membrane pore sizes, which is essentially determined by the membrane synthesis conditions, significantly affects the rejection performance of nanofiltration (NF) membranes. In this ...study, we applied two modeling methods, i.e., the DSPM (Donnan Steric Pore Model) and the log-normal distribution methods, for the determination of the average membrane pore size and pore size uniformity of lab-made NF membranes. The synthesis conditions included concentration of monomers (e.g., piperazine and trimesoyl chloride), (thermal) curing temperature and time, and activation solvent type and duration. Results showed that both high piperazine (PIP) concentration (≥0.5 wt%) and curing temperature (≥40 °C) could enhance the membrane pore size uniformity. Although the average membrane pore size calculated by the DSPM method was higher than that by the log-normal distribution method, they significantly correlated. It appears that the log-normal distribution method could more directly characterize membrane pore size uniformity. Obviously, the pore uniformity of NF membranes affected the rejection of small molecules, such as trace organic compounds. These insights provided a theoretical foundation for the characterization of membrane pore size distribution with more accuracy and the fabrication of membranes with higher pore size uniformity.
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•Two different modeling methods were used to characterize membrane pore size uniformity.•Thermal curing could improve membrane pore size uniformity while solvent activation generally not.•The average pore radius determined by the two methods significantly correlated, but pore size uniformity not.•Membrane pore size non-uniformity substantially decreased the TrOCs rejection performance.
To achieve the goals of carbon peaking and carbon neutrality under the backgrounds of poor resource endowments, weak theoretical basis and other factors, the development of the coalbed methane ...industry of China faces many bottlenecks and challenges. This paper systematically analyzes the coalbed methane resources, key technologies and progress, exploration effect and production performance in China and abroad. The main problems are summarized as low exploration degree, low technical adaptability, low return on investment and small development scale. This study suggests that the coalbed methane industry in China should follow the “two-step” (short-term and long-term) development strategy. The short-term action before 2030, can be divided into two stages: (1) From the present to 2025, to achieve new breakthroughs in theory and technology, and accomplish the target of annual production of 10 billion cubic meters; (2) From 2025 to 2030, to form the technologies suitable for most geological conditions, further expand the industry scale, and achieve an annual output of 30 billion cubic meters, improving the proportion of coalbed methane in the total natural gas production. The long-term action after 2030 is to gradually realize an annual production of 100 billion cubic meters. The strategic countermeasure to achieve the above goals is to adhere to “technology+management dual wheel drive”, realize the synchronous progress of technology and management, and promote the high-quality development of the coalbed methane industry. Technically, the efforts will focus on fine and effective development of coalbed methane in the medium to shallow layers of mature fields, effective development of coalbed methane in new fields, extensive and beneficial development of deep coalbed methane, three-dimensional comingled development of coalbed methane, applying new technologies such as coalbed methane displacement by carbon dioxide, microwave heating and stimulation technology, ultrasonic stimulation, high-temperature heat injection stimulation, rock breaking by high-energy laser. In terms of management, the efforts will focus on coordinative innovation of resource, technology, talent, policy and investment, with technological innovation as the core, to realize an all-round and integrated management and promote the development of coalbed methane industry at a high level.
The aim of the present study is to design and characterize quercetin-loaded solid lipid nanoparticles (QT-SLNs), clarify the absorption mechanism of QT-SLNs and to evaluate the potential of using ...solid lipid nanoparticles (SLNs) as an oral delivery carrier for poorly water soluble drugs. QT-SLNs were prepared by an emulsification and low-temperature solidification method. The QT-SLNs presented as spherically shaped under transmission electron microscopy, with an average diameter of 155.3 nm. The average drug entrapment efficiency, drug loading and zeta potential were 91.1%, 13.2% and −
32.2 mV, respectively. Drug release from QT-SLNs was fitted to a double phase kinetics model and the equation was as follows: 100
−
Q
=
98.87e
−
0.1042t
+
42.45e
−
0.0258t
. The absorption of QT-SLNs in the gastrointestinal (GI) tract was studied using an
in situ perfusion method in rats. It was found that the absorption percent in the stomach for 2 h was only 6.20%
, the absorption process of intestine was first-process with passive diffusion mechanism, and the main absorptive segments were ileum and colon. A pharmacokinetic study was conducted in rats after oral administration of quercetin at 50 mg/kg in the form of either QT-SLNs or suspension. The plasma concentration-time curves were both fitted to a one-compartment model. The relative bioavailability of QT-SLNs to quercetin suspension was 571.4%. The T
max and MRT for quercetin in plasma were both delayed. Our studies provide evidence that SLNs are valuable as an oral delivery carrier to enhance the absorption of a poorly water soluble drug, quercetin.
Background Bilateral breast cancer (BBC), as well as ovarian cancer, are significantly associated with germline deleterious variants in BRCA1/2, while BRCA1/2 germline deleterious variants carriers ...can exquisitely benefit from poly (ADP-ribose) polymerase (PARP) inhibitors. However, formal genetic testing could not be carried out for all patients due to extensive use of healthcare resources, which in turn results in high medical costs. To date, existing BRCA1/2 deleterious variants prediction models have been developed in women of European or other descent who are quite genetically different from Asian population. Therefore, there is an urgent clinical need for tools to predict the frequency of BRCA1/2 deleterious variants in Asian BBC patients balancing the increased demand for and cost of cancer genetics services. Methods The entire coding region of BRCA1/2 was screened for the presence of germline deleterious variants by the next generation sequencing in 123 Chinese BBC patients. Chi-square test, univariate and multivariate logistic regression were used to assess the relationship between BRCA1/2 germline deleterious variants and clinicopathological characteristics. The R software was utilized to develop artificial neural network (ANN) and nomogram modeling for BRCA1/2 germline deleterious variants prediction. Results Among 123 BBC patients, we identified a total of 20 deleterious variants in BRCA1 (8; 6.5%) and BRCA2 (12; 9.8%). c.5485del in BRCA1 is novel frameshift deleterious variant. Deleterious variants carriers were younger at first diagnosis (P = 0.0003), with longer interval between two tumors (P = 0.015), at least one medullary carcinoma (P = 0.001), and more likely to be hormone receptor negative (P = 0.006) and HER2 negative (P = 0.001). Area under the receiver operating characteristic curve was 0.903 in ANN and 0.828 in nomogram modeling individually (P = 0.02). Conclusion This study shows the spectrum of the BRCA1/2 germline deleterious variants in Chinese BBC patients and indicates that the ANN can accurately predict BRCA deleterious variants than conventional statistical linear approach, which confirms the BRCA1/2 deleterious variants carriers at the lowest costs without adding any additional examinations. Keywords: Bilateral breast cancer, BRCA1, BRCA2, Germline deleterious variant, Artificial neural network
Cyber Physical Systems (CPS) has been a popular research area in the last decade. The dependability of CPS is still a critical issue, and few surveys have been published in this domain. CPS is a ...dynamic complex system, which involves various multidisciplinary technologies. To avoid human errors and to simplify management, self-management CPS (SCPS) is a wise choice. To achieve dependable self-management, systematic solutions are necessary to verify the design and to guarantee the safety of self-adaptation decisions, as well as to maintain the health of SCPS. This survey first recalls the concepts of dependability, and proposes a generic environment-in-loop processing flow of self-management CPS, and then analyzes the error sources and challenges of self-management through the formal feedback flow. Focusing on reducing the complexity, we first survey the self-adaptive architecture approaches and applied dependability means, then we introduce a hybrid multi-role self-adaptive architecture, and discuss the supporting technologies for dependable self-management at the architecture level. Focus on dependable environment-centered adaptation, we investigate the verification and validation (V&V) methods for making safe self-adaptation decision and the solutions for processing decision dependably. For system-centered adaptation, the comprehensive self-healing methods are summarized. Finally, we analyze the missing pieces of the technology puzzle and the future directions. In this survey, the technical trends for dependable CPS design and maintenance are discussed, an all-in-one solution is proposed to integrate these technologies and build a dependable organic SCPS. To the best of our knowledge, this is the first comprehensive survey on dependable SCPS building and evaluation.
Background
Bile duct leaks (BDLs) are serious complications that occurs after hepatobiliary surgery and trauma, leading to rapid clinical deterioration. Endoscopic retrograde cholangiopancreatography ...(ERCP) is the first-line treatment for BDLs, but it is not clear which patients will respond to this therapy and which patients will require additional surgical intervention. The aim of our study was to explore the predictors of successful ERCP for BDLs.
Methods
A retrospective analysis was conducted using data from six centers' databases. All consecutive patients who were clinically confirmed as BDLs were included in the study. Collected data were demographics, disease severity, and ERCP procedure characteristics. Univariate and multivariate analysis were used to select independent predictive factors that affect the outcome of ERCP for BDLs, and a nomogram was established. Calibration and ROC curves were used to evaluate the models.
Results
Four hundred and forty-eight consecutive patients were clinically confirmed as BDLs and 347 were excluded. In the 101 patients included patients, clinical success was achieved in 78 patients (77.2%). In logistic multivariable regression, two independent factors were negatively associated with the success of ERCP: SIRS (OR, 0.183; 95% CI 0.039–0.864;
P
= 0.032) and high-grade leak (OR 0.073; 95% CI 0.010–0.539;
P
= 0.010). Two independent factors were positively associated with the success of ERCP: leak-bridging drainage (OR 4.792; 95% CI 1.08–21.21;
P
= 0.039) and cystic duct leak (OR 6.193; 95% CI 1.03–37.17;
P
= 0.046). The prediction model with these four factors was evaluated using a receiver-operating characteristic (ROC) curve, which demonstrated an area under the curve of 0.9351. The calibration curve showed that the model had good predictive accuracy.
Conclusion
Leak-bridging drainage and cystic duct leak are positive predictors for the success of ERCP, while SIRS and high-grade leak are negative predictors. This prediction model with nomogram has good predictive ability and practical clinical value, and may be helpful in clinical decision-making and prognostication.
Graphical abstract
Schwann cell (SC) transplantation is a promising approach for the treatment of spinal cord injury (SCI); however, SC grafts show a low migratory capacity within the astrocytic environment, which ...inevitably hampers their therapeutic efficacy. The purpose of this study was to explore mechanisms to modify the characteristics of SCs and astrocytes (ASs), as well as to adjust the SC-AS interface to break the SC-AS boundary, thus improving the benefits of SCI treatment. We observed that the expression levels of miR-124 in SCs and astrocytes were significantly lower than those in the normal spinal cord. Furthermore, overexpressing miR-124 in SCs (miR-124-SCs) significantly inhibited gene and protein expression levels of SC-specific markers, such as GFAP and Krox20. The expression of neurotrophic factors, Bdnf and Nt-3, was up-regulated in miR-124-SCs without affecting their proliferation. Further, the boundary assay showed an increased number of miR-124-SCs that had actively migrated and entered the astrocytic region to intermingle with astrocytes, compared with normal SCs. In addition, although Krox20 protein expression was down-regulated in miR-124-SCs, the luciferase assay showed that Krox20 is not a direct target of miR-124. RNA sequencing of miR-124-SCs revealed seven upregulated and eleven downregulated genes involved in cell migration and motility. Based on KEGG pathway and KOG functional analyses, changes in these genes corresponded to the activation of Hippo, FoxO, and TGF-beta signaling pathways, cytokine-cytokine receptor interactions, and the cell cycle. Finally, co-culturing of miR-124-SCs and astrocytes in a transwell system revealed that GFAP and p-STAT3 protein expression in astrocytes was significantly reduced. Collectively, these results show that overexpression of miR-124 in SCs promotes SC-AS integration in vitro and may attenuate the capacity of astrocytes to form glial scars. Thus, this study provides novel insights into modifying SCs by overexpressing miR-124 to improve their therapeutic potential in SCI.
Objective: Delayed neurological deficit was often observed in patients underwent craniectomy, which could be improved by cranioplasty. Little is known about hemodynamic improvement before and after ...cranioplasty.
Methods: Cerebral blood perfusion, tympanic membrane temperature (TMT), neuropsychological and cognitive function were assessed in eleven craniectomy patients before and after cranioplasty.
Results: Before cranioplasty, the cerebral blood volume (CBV) on the decompressed side was significantly lower than that of the contralateral side. The cranioplasty led to instant improvement (7 days after cranioplasty) of cerebral perfusion at the cranioplasty side in the frontal lobe, parietal lobe, temporal lobe, mesencephalon, basal ganglia and thalamus, but not the occipital lobe and epencephalon. Interestingly, CBV of the thalamus and basal ganglia gradually decreased to pre-surgical status 6 months later while the frontal lobe, parietal lobe, temporal lobe, mesencephalon remained well perfused. Meanwhile, the TMT changes acquired positive correlation with the perfusion of temporal lobe and mesencephalon as well as the GCS and MMSE score.
Conclusion: The cranioplasty remarkably improves neurological and cognitive function by ameliorating cerebral perfusion in certain regions. The TMT could be used as a non-invasive method to monitor the cerebral perfusion improvement after the cranioplasty.
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