•MiR-424-5p expression is reduced in basal-like breast cancer.•MiR-424-5p low-expression is associated with malignant status of basal-like breast cancer patient.•MiR-424-5p inhibits basal-like breast ...cancer cell proliferation and motility.•DCLK1 is a functional target of miR-424-5p to regulate basal-like breast cancer cell proliferation and motility.
Our previous study has showed doublecortin like kinase 1 (DCLK1) serves as an oncogene to regulate basal-like breast cancer cell proliferation, migration and invasion, and is associated with malignant status and poor prognosis. The aim of this study is to identify microRNAs (miRNAs), which target DCLK1 to regulate basal-like breast cancer cell proliferation, migration and invasion. In our results, we observed that miR-424-5p expression was decreased in basal-like breast cancer tissues and cell lines. Furthermore, we found 3’-UTR of DCLK1 had binding site of miR-424-5p based on microRNA target databases, and there was an inverse correlation between miR-424-5p and DCLK1 in basal-like breast cancer tissues. Moreover, we confirmed miR-424-5p directly targeted to 3’-UTR of DCLK1 through luciferase reporter assay, and miR-424-5p negatively regulated DCLK1 mRNA and protein expressions through qRT-PCR and western blot. The gain-of-function studies showed that miR-424-5p suppressed basal-like breast cancer cell proliferation, migration and invasion. The rescued-function studies suggested up-regulation of DCLK1 could rescue inhibition of miR-424-5p mimics in the regulation of basal-like breast cancer cell proliferation, migration and invasion. Finally, low-expression of miR-424-5p was associated with advanced clinical stage, large tumor size, more metastatic lymph nodes, present distant metastasis and poor histological grade in basal-like breast cancer patients. In conclusion, miR-424-5p is a tumor suppressive microRNA to regulate tumor cell proliferation, migration and invasion via binding to the functional target DCLK1, and associated with malignant status in basal-like breast cancer.
The high attrition rate in drug development and the deteriorated drug ability as a result of the shifted chemical space of new therapeutic target for unmet medical needs have posed drastic challenges ...in current drug discovery. It has triggered the strategic transition in the past decade into parallel assessment of efficacy and comprehensive ADMET (absorption, distribution, metabolism, elimination and toxicity) properties of new chemical entities (NCEs) in the lead selection and optimization stages, to convert chemically a problematic NCE to an "all-around" candidate. This review summarizes multiple in silico, in vitro and in vivo ADMET filters developed and implemented in various stages of drug discovery to flag potential ADMET issues in the clinic. The full awareness of the benefits and limitations of each tool assures right questions to be answered using right tools at right time. The integrated ADMET risk assessment will allow project teams to have a clear vision in terms of the competitive position of own NCEs against comparable marketed drugs.
Late-preterm birth (34-36 weeks' gestation) has been associated with a risk for long-term cognitive and socioemotional problems. However, many studies have not incorporated measures of important ...contributors to these outcomes, and it is unclear whether effects attributed to gestational age are separate from fetal growth or its proxy, birth weight for gestational age.
Data came from a study of low- and normal-weight births sampled from urban and suburban settings between 1983 and 1985 (low birth weight, n = 473; normal birth weight; n = 350). Random sampling was used to pair singletons born late-preterm with a term counterpart whose birth weight z score was within 0.1 SD of his or her match (n = 168 pairs). With random-effects models, we evaluated whether pairs differed in their IQ scores and teacher-reported behavioral problems at the age of 6 years.
In adjusted models, late-preterm birth was associated with an increased risk of full-scale (adjusted odds ratio aOR: 2.35 95% confidence interval (CI): 1.20-4.61) and performance (aOR: 2.04 95% CI: 1.09-3.82) IQ scores below 85. Late-preterm birth was associated with higher levels of internalizing and attention problems, findings that were replicated in models that used thresholds marking borderline or clinically significant problems (aOR: 2.35 95% CI: 1.28-4.32 and 1.76 95% CI: 1.04-3.0, respectively).
Late-preterm birth is associated with behavioral problems and lower IQ at the age of 6, independent of maternal IQ, residential setting, and sociodemographics. Future research is needed to investigate whether these findings result from a reduction in gestational length, in utero (eg, obstetric complications) or ex-utero (eg, neonatal complications) factors marked by late-preterm birth, or some combination of these factors.
Molybdenum is a trace dietary element necessary for the survival of humans. Some molybdenum-bearing enzymes are involved in key metabolic activities in the human body (such as xanthine oxidase, ...aldehyde oxidase and sulfite oxidase). Many molybdenum-based compounds have been widely used in biomedical research. Especially, MoS2-nanomaterials have attracted more attention in cancer diagnosis and treatment recently because of their unique physical and chemical properties. MoS2 can adsorb various biomolecules and drug molecules via covalent or non-covalent interactions because it is easy to modify and possess a high specific surface area, improving its tumor targeting and colloidal stability, as well as accuracy and sensitivity for detecting specific biomarkers. At the same time, in the near-infrared (NIR) window, MoS2 has excellent optical absorption and prominent photothermal conversion efficiency, which can achieve NIR-based phototherapy and NIR-responsive controlled drug-release. Significantly, the modified MoS2-nanocomposite can specifically respond to the tumor microenvironment, leading to drug accumulation in the tumor site increased, reducing its side effects on non-cancerous tissues, and improved therapeutic effect. In this review, we introduced the latest developments of MoS2-nanocomposites in cancer diagnosis and therapy, mainly focusing on biosensors, bioimaging, chemotherapy, phototherapy, microwave hyperthermia, and combination therapy. Furthermore, we also discuss the current challenges and prospects of MoS2-nanocomposites in cancer treatment.
Display omitted
•MoS2 with a large specific surface area can combine a variety of molecules to form a multifunctional nano-platform.•MoS2 with excellent optical absorption and photothermal conversion efficiency can be used in cancer therapy and bioimaging.•MoS2-nanocomposite can specifically respond to the tumor microenvironment and reduce side effects on non-cancerous tissues.
Asphalt pavement recycling technology with high reclaimed asphalt pavement (RAP) content has always been limited by unsatisfactory pavement performance and the rising cost of pavement materials. To ...address these challenges, polyurethane-prepolymer-modified bitumen (PPB) was proposed to be utilized as the asphalt binder of fully reclaimed asphalt pavement (FRAP) in this study. The proper formula of the PPB binder was determined based on a range of tests. The rheological behavior and tensile properties of the PPB binder were then investigated, and the economic cost of materials was discussed as well. Results revealed that the PPB system can be obtained through chemical synthesis using readily available raw materials. The reaction of polyurethane prepolymer and chain extender provides PPB with significant improvement in temperature susceptibility, rutting resistance, and tensile properties. It is also demonstrated in this study that the PPB mixture containing 100% RAP, on the whole, takes advantage of cost-saving especially compared to the epoxy asphalt mixture. Therefore, the PPB binder exhibits a favorable application prospect in FRAP.
The recent discovery by Ibata et al. of a vast thin disc of satellites (VTDS) around M31 offers a new challenge for the understanding of the Local Group properties. This comes in addition to the ...unexpected proximity of the Magellanic Clouds (MCs) to the Milky Way (MW), and to another vast polar structure (VPOS), which is almost perpendicular to our Galaxy disc. We find that the VTDS plane is coinciding with several stellar, tidally induced streams in the outskirts of M31, and, that its velocity distribution is consistent with that of the giant stream (GS). This is suggestive of a common physical mechanism, likely linked to merger tidal interactions, knowing that a similar argument may apply to the VPOS at the MW location. Furthermore, the VTDS is pointing towards the MW, being almost perpendicular to the MW disc, as the VPOS is.
We compare these properties to the modelling of M31 as an ancient, gas-rich major merger, which has been successfully used to predict the M31 substructures and the GS origin. We find that without fine tuning, the induced tidal tails are lying in the VTDS plane, providing a single and common origin for many stellar streams and for the vast stellar structures surrounding both the MW and M31. The model also reproduces quite accurately positions and velocities of the VTDS spheroidal dwarfs. Our conjecture leads to a novel interpretation of the Local Group past history, as a gigantic tidal tail due to the M31 ancient merger is expected to send material towards the MW, including the MCs. Such a link between M31 and the MW is expected to be quite exceptional, though it may be in qualitative agreement with the reported rareness of MW-MCs systems in nearby galaxies.
Pakistan is the world’s most susceptible country to extreme climatic events, such as floods and droughts. This study aims to investigate the risks related to climate variability and the adaptation ...measures utilized by farm households in their farms to cope with the adverse shocks of climatic disasters. A dataset of 600 respondents was collected using structured questionnaire from four districts namely Charsadda, Mardan, Nowshera and Peshawar of Khyber Pakhtunkhwa province of Pakistan. Findings of the research showed that soil fertility loss, water scarcity, changes in crop yields and crop diseases were the main determinants of climate variability. Further study participants were also utilizing several adaptation techniques such as change in crop type and variety, change fertilizer, seed quality, pesticide, plant shade trees; water storage and farm diversification. Results of our study further showed that in the study area, study participants were facing various constraints in adoption of certain adaptation measures to deal with climate variability, such as shortage of labor, insecure land tenure system, lack of market access, poverty, land of governmental support, lack of access to assets, lack of water sources, lack of credit sources and lack of knowledge and information were the main constraints faced by the farm households. Findings of this research provide useful insights to the responsible authorities for policy implementation. Our study further suggests that the government should provide proper support to the farmers in the shape of access to farm inputs, access to information and extension services on climate variability and adaptation.
To evaluate the possibility of judging the degree of bone healing by wall thickness analysis provide reference for quantitative analysis of bone healing. Patients with lower limb fracture from April ...2014 to October 2019 were recruited and divided into bone healing (group A), poor bone healing (group B), and nonunion (group C). Models were built in Mimics 20.0 with DICOM 3.0 data obtained from patient's CT. Three-dimensional geometric models of unaffected limb and affected limb after simulated removal of internal fixation were established, corresponding to basic phase and simulated phase, respectively. Wall thickness analysis was performed to obtain median wall thickness after meshing. R2 (median wall thickness ratio), R4 (CT value ratio), and R5 (healing index ratio) were obtained by calculating the ratio of each value in simulated phase to that in basic phase. Receiver operating characteristic curve analysis was used to evaluate the ability of Wall Thickness Analysis to indicate fracture healing. 112 CT scans of 79 patients were included in the study. The frequency of categorization in groups A, B, and C was 49, 37 and 26, respectively. The median R2 in groups A, B, and C was 0.91, 0.80, and 0.67, respectively (group A > group B > group C, all P < 0.05). The best cutoff point for R2 in predicting bone healing was 0.84, and predicting bone nonunion was 0.74. The Wall Thickness Analysis can be used to quantitatively evaluate fracture healing state, with median wall thickness ratio as a more intuitive and reliable judgment index.
The incidence of periodontitis is very high, and up to 45-50% of people are suffering from periodontitis. Periodontitis is caused by pathogens that invade teeth-supporting tissues such as gingiva, ...periodontal ligament, and alveolar bone. Pathogens trigger host immune responses characterized by the overproduction of reactive oxygen species (ROS). The development of effective ROS scavengers through nanotechnology has been emerging as a promising strategy for the treatment of periodontitis. Nanomaterial-based antioxidants can effectively scavenge ROS, prevent ROS-mediated tissue damage, and relieve inflammation in periodontitis. This mini-review focuses on the generation of ROS in periodontitis and its molecular mechanism of destroying periodontal tissue. Meanwhile, we summarize the research progress of ROS-scavenging nanomaterials in the treatment of periodontitis and discuss the challenges and prospects of its application.
Objectives
To explore the value of multiple metabolic and heterogeneity parameters of 2-deoxy-2-fluorine-18 fluoro-D-glucose positron emission tomography/computed tomography (
18
F-FDG PET/CT) in ...predicting epidermal growth factor receptor gene (EGFR) mutations in non-small cell lung cancer (NSCLC).
Materials and methods
A retrospective analysis was performed by reviewing 98 patients with NSCLC who underwent EGFR mutation testing and
18
F-FDG PET/CT examination in our hospital between March 2016 and March 2021. Patients were divided into an EGFR-mutant group and a wild-type group. A multivariate logistic regression analysis was performed to screen and construct a prediction model. The diagnostic performance of the model was evaluated using a receiver-operating characteristic (ROC) curve.
Results
The study found that EGFR mutations were more likely to occur in women, non-smokers, and patients with peripheral lesions, shorter maximum tumor diameter, adenocarcinoma, and T1 stage cancer. Low maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume, total lesion glycolysis, and high coefficient of variation (COV) were significantly correlated with EGFR mutations, and the area under the ROC curve (AUC) was 0.622, 0.638, 0.679, 0.687, and 0.672, respectively. Multivariate logistic regression analysis indicated that non-smokers (odds ratio (OR) = 0.109,
P
= 0.014), peripheral lesions (OR = 6.917,
P
= 0.022), low SUVmax (≤ 7.85, OR = 5.471,
P
= 0.001), SUVmean (≤ 5.34, OR = 0.044,
P
= 0.000), and high COV (≥ 106.08, OR = 0.996,
P
= 0.045) were independent predictors of EGFR mutations. The AUC of the prediction model established by combining the above factors was 0.926; the diagnostic efficiency was significantly higher than that of a single parameter.
Conclusion
Among the metabolic and heterogeneity parameters of
18
F-FDG PET/CT, low SUVmax, SUVmean, and high COV were significantly associated with EGFR mutations, and the predictive value of EGFR mutations could be enhanced when combined with clinicopathological features.
PDF
