Research Progress of DNA Methylation in Thyroid Cancer

We have summarized increasing data from all kinds of experiment results of papers in recent years, which are associated with tumor suppressor genes, oncogenes, and thyroid-specific genes and attempt to elucidate the importance of epigenetic modifications and the mechanisms of aberrant DNA methylation in thyroid cancer in this review. The results showed that current articles have revealed the importance of epigenetic modifications and the different types of mechanisms in thyroid cancer. The mechanisms of DNA methylation related to thyroid cancer demonstrate that acquired epigenetic abnormalities together with genetic changes play an important role in alteration of gene expression patterns. Aberrant DNA methylation has been well known in the CpG regions. Among the genes identified, we have shown the status of DNA promoter methylation in papillary, follicular, medullary, and anaplastic thyroid cancer. It suggested that thyroid cancer subtypes present differential promoter methylation signatures, which will encourage potential thyroid cancer detection in its early stages, assessment of prognosis, and targeted cancer treatment

Expectation Modulates Human Brain Responses to Acute Cocaine: A Functional Magnetic Resonance Imaging Study

Background Human expectation of psychoactive drugs significantly alters drug effects and behavioral responses. However, their neurophysiological mechanisms are not clear. This study investigates how cocaine expectation modulates human brain responses to acute cocaine administration. Methods Twenty-six right-handed non–treatment-seeking regular cocaine abusers participated in this study. Changes in blood oxygenation level-dependent (BOLD) signals were measured, and online behavioral ratings during cocaine expectation and acute cocaine administration were recorded. Results Distinct regional characteristics in BOLD responses to expected and unexpected cocaine infusions were observed in the medial orbitofrontal gyrus (Brodmann area [BA] 11), frontal pole (BA 10), and anterior cingulate gyrus regions. Active engagement in the amygdala and the lateral orbitofrontal cortex (OFC; BA 47) by unexpected but not expected cocaine infusion was discovered. Cocaine expectation did not change BOLD responses to acute cocaine administration in a set of subcortical substrates, the nucleus accumbens, ventral putamen, ventral tegmental area, and thalamus. Conclusions These results suggest that cocaine expectation modulates neural-sensitivity adaptation between the expected events and the actual outcomes but did not modulate the pharmacological characteristics of cocaine. In addition, the amygdala–lateral OFC circuitry plays an important role in mediating stimulus-outcome relations and contextual factors of drug abuse

Cardiovascular risk burden, dementia risk and brain structural imaging markers:a study from UK Biobank

Background:Cardiovascular risk burden is associated with dementia risk and neurodegeneration-related brain structure, while the role of genetics and incident cardiovascular disease (CVD) remains unclear. Aims:To examine the association of overall cardiovascular risk burden with the risk of major dementia subtypes and volumes of related brain regions in a large sample, and to explore the role of genetics and CVD onset. Methods:A prospective study among 354 654 participants free of CVD and dementia (2006–2010, mean age 56.4 years) was conducted within the UK Biobank, with brain magnetic resonance imaging (MRI) measurement available for 15 104 participants since 2014. CVD risk burden was evaluated by the Framingham General Cardiovascular Risk Score (FGCRS). Dementia diagnosis was ascertained from inpatient and death register data. Results:Over a median 12.0-year follow-up, 3998 all-cause dementia cases were identified. Higher FGCRS was associated with increased all-cause dementia risk after adjusting for demographic, major lifestyle, clinical factors and the polygenic risk score (PRS) of Alzheimer’s disease. Comparing the high versus low tertile of FGCRS, the odds ratios (ORs) and 95% confidence intervals (CIs) were 1.26 (1.12 to 1.41) for all-cause dementia, 1.67 (1.33 to 2.09) for Alzheimer’s disease and 1.53 (1.07 to 2.16) for vascular dementia (all ptrend&lt;0.05). Incident stroke and coronary heart disease accounted for 14% (95% CI: 9% to 21%) of the association between FGCRS and all-cause dementia. Interactions were not detected for FGCRS and PRS on the risk of any dementia subtype. We observed an 83% (95% CI: 47% to 128%) higher all-cause dementia risk comparing the high–high versus low–low FGCRS–PRS category. For brain volumes, higher FGCRS was associated with greater log-transformed white matter hyperintensities, smaller cortical volume and smaller grey matter volume. Conclusions:Our findings suggest that the positive association of cardiovascular risk burden with dementia risk also applies to major dementia subtypes. The association of cardiovascular risk burden with all-cause dementia is largely independent of CVD onset and genetic predisposition to dementia.</p

Cardiovascular risk burden, dementia risk and brain structural imaging markers:a study from UK Biobank

Background:Cardiovascular risk burden is associated with dementia risk and neurodegeneration-related brain structure, while the role of genetics and incident cardiovascular disease (CVD) remains unclear. Aims:To examine the association of overall cardiovascular risk burden with the risk of major dementia subtypes and volumes of related brain regions in a large sample, and to explore the role of genetics and CVD onset. Methods:A prospective study among 354 654 participants free of CVD and dementia (2006–2010, mean age 56.4 years) was conducted within the UK Biobank, with brain magnetic resonance imaging (MRI) measurement available for 15 104 participants since 2014. CVD risk burden was evaluated by the Framingham General Cardiovascular Risk Score (FGCRS). Dementia diagnosis was ascertained from inpatient and death register data. Results:Over a median 12.0-year follow-up, 3998 all-cause dementia cases were identified. Higher FGCRS was associated with increased all-cause dementia risk after adjusting for demographic, major lifestyle, clinical factors and the polygenic risk score (PRS) of Alzheimer’s disease. Comparing the high versus low tertile of FGCRS, the odds ratios (ORs) and 95% confidence intervals (CIs) were 1.26 (1.12 to 1.41) for all-cause dementia, 1.67 (1.33 to 2.09) for Alzheimer’s disease and 1.53 (1.07 to 2.16) for vascular dementia (all ptrend&lt;0.05). Incident stroke and coronary heart disease accounted for 14% (95% CI: 9% to 21%) of the association between FGCRS and all-cause dementia. Interactions were not detected for FGCRS and PRS on the risk of any dementia subtype. We observed an 83% (95% CI: 47% to 128%) higher all-cause dementia risk comparing the high–high versus low–low FGCRS–PRS category. For brain volumes, higher FGCRS was associated with greater log-transformed white matter hyperintensities, smaller cortical volume and smaller grey matter volume. Conclusions:Our findings suggest that the positive association of cardiovascular risk burden with dementia risk also applies to major dementia subtypes. The association of cardiovascular risk burden with all-cause dementia is largely independent of CVD onset and genetic predisposition to dementia.</p

Flavokawain A alleviates the progression of mouse osteoarthritis: An in vitro and in vivo study

Osteoarthritis (OA) is one of the most prevalent chronic degenerative joint diseases affecting adults in their middle or later years. It is characterized by symptoms such as joint pain, difficulty in movement, disability, and even loss of motion. Moreover, the onset and progression of inflammation are directly associated with OA. In this research, we evaluated the impact of Flavokawain A (FKA) on osteoarthritis. In-vitro effects of FKA on murine chondrocytes have been examined using cell counting kit-8 (CCK-8), safranin o staining, western blot, immunofluorescence staining, senescence β-galactosidase staining, flow cytometry analysis, and mRFP-GFP-LC3 adenovirus infection. An in-vivo model of destabilization of the medial meniscus (DMM) was employed to investigate FKA’s effect on OA mouse. An analysis of bioinformatics was performed on FKA and its potential role in OA. It was observed that FKA blocked interleukin (IL)-1β-induced expression of inflammatory factors, i.e., cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (iNOS) in chondrocytes. In addition, FKA also downregulated the catabolic enzyme expression, i.e., aggrecanase-2 (ADAMTS5) and matrix metalloproteinases (MMPs), and helped in the upregulation of the anabolic protein expression, i.e., type II collagen (Col2), Aggrecan, and sry-box transcription factor 9 (SOX9). Moreover, FKA ameliorated IL-1β-triggered autophagy in chondrocytes, and it was observed that the FKA causes anti-inflammatory effects by the mitogen-activated protein kinase (MAPK) and phosphoinositide-3-kinase/Akt/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathways inhibition. The results of immunohistochemical analysis and microcomputed tomography from the in vivo OA mouse model confirmed the therapeutic effect of FKA. Finally, we assessed the anti-arthritic impacts of FKA by conducting in vivo and in vitro analyses. We concluded that FKA can be employed as a useful therapeutic agent for OA therapy, but the findings require needs further clinical investigation

Modeling and IAHA Solution for Task Scheduling Problem of Processing Crowdsourcing in the Context of Social Manufacturing

The paper addresses the discrete characteristics of the processing crowdsourcing task scheduling problem in the context of social manufacturing, divides it into two subproblems of social manufacturing unit selecting and subtask sorting, establishes its mixed-integer programming with the objective of minimizing the maximum completion time, and proposes an improved artificial hummingbird algorithm (IAHA) for solving it. The IAHA uses initialization rules of global selection, local selection, and random selection to improve the quality of the initial population, the Levy flight to improve guided foraging and territorial foraging, the simplex search strategy to improve migration foraging to enhance the merit-seeking ability, and the greedy decoding method to improve the quality of the solution and reduce solution time. For the IAHA, orthogonal tests are designed to obtain the optimal combination of parameters, and comparative tests are made with variants of the AHA and other algorithms on the benchmark case and a simulated crowdsourcing case. The experimental results show that the IAHA can obtain superior solutions in many cases with economy and effectiveness

Bone Transport for Treatment of Traumatic Composite Tibial Bone and Soft Tissue Defects: Any Specific Needs besides the Ilizarov Technique?

Objective. To evaluate the surgical efficacy of bone transport (Ilizarov technique) plus “shortening-lengthening,” “flap surgery,” and “open bone transport” as individualized treatments for traumatic composite tibial bone and soft tissue defects. Methods. We retrospectively analyzed sixty-eight cases (mean age: 35.69 years, (range, 16–65)) treated from July 2014 to June 2017, including 29 middle, 18 distal, and 21 proximal tibial bone defects (4–18 cm, mean: 7.97 cm) with soft tissue defects (2.5 cm × 4.0 cm to 30.0 cm × 35.0 cm after debridement). We adopted the bone transport external fixator to fix the fracture after debriding the defect parts. In the meantime, we adopted the “shortening-lengthening technique,” “flap surgery,” and “open bone transport” as individualized treatment based on the location, range, and severity of the composite tibial bone and soft tissue defects. Postoperative follow-up was carried out. Surgical efficacy was assessed based on (1) wound healing; (2) bone defect healing rate; (3) external fixation time and index; (4) incidence/recurrence of deep infection; (5) postoperative complications; and (6) Association for the Study and Application of the Methods of Ilizarov (ASAMI) score. Results. The mean duration from injury to reconstruction was 22 days (4–80 d), and the mean postoperative follow-up period was 30.8 months (18–54 m). After the repair and reconstruction, 2 open bone transport patients required infected bone removal first before continuing the bone transport treatment. No deep infection (osteomyelitis) occurred or recurred in the remaining patients, and no secondary debridement was required. Some patients had complications after surgery. All the postoperative complications, including flap venous crisis, nail channel reaction, bone nonunion, mechanical axis deviation, and refracture, were improved or alleviated. External fixation time was 12.5 ± 3.41 months, and the index was 1.63 ± 0.44. According to the ASAMI score, 76.47% of the outcomes were good/excellent. Conclusion. The Ilizarov technique yields satisfactory efficacy for composite tibial bone and soft tissue defects when combined with “shortening-lengthening technique,” “flap surgery,” and “open bone transport” with appropriate individualized treatment strategies

Preventive Effect of Bifidobacterium Supplementation on Neonatal Cholestasis in Preterm Neonates with Very Low Birth Weight

Background. Cholestasis is a common but serious clinical condition in preterm neonates. The current management for preterm neonatal cholestasis has limitations. The aim of this study was to determine effects of Bifidobacterium supplementation on the prevention and alleviation of cholestasis in preterm infants with very low birth weight. Methods. Preterm neonates with very low birth weight were enrolled in the Children’s Hospital of Soochow University between December 2012 and December 2017. The patients were randomly assigned into Bifidobacterium and control groups, and effects of Bifidobacterium supplementation on the outcomes were compared between the two groups. Results. There was no significant difference in the baseline characteristics in the two groups. Notably, the proportion of cases with neonatal cholestasis was significantly lower, with fewer neonatal cholestasis-associated complications in the Bifidobacterium group compared with the control group (6% versus 22%, P<0.01). Furthermore, the Bifidobacterium group exhibited less severe cholestasis and better improvement of the liver function than the control group as evidenced by the biochemical tests (P<0.05). Finally, comparison of the other outcomes revealed that significant shorter duration of hospitalization (14.45±2.13 versus 16.12±2.22 days, P<0.01), fewer days to reach the full enteral feeding (9.2±2.11 versus 12±5.67 days, P<0.01), shorter duration of meconium passage (5.0±3.6 versus 6.6±3.38 days, P<0.05), lower proportion of cases on fasting and duration of fasting (0.8% versus 5.6%, P<0.05 and 3.0±1.6 versus 5.6±2.38 days, P<0.01, respectively), and shorter duration of weight gain to normal (4.77±2.49 versus 6.87±2.71 days, P<0.01) in the Bifidobacterium group versus the control group. Conclusions. Bifidobacterium supplementation has significantly preventive and other beneficial effects on the management of cholestasis in preterm infants with very low birth weight. Its long-term safety and effectiveness will need further investigation. This trial is registered with the Chinese Clinical Trial Registry (Registration No. ChiCTR1900022296)

Promoting Effect of the Core-Shell Structure of MnO2@TiO2 Nanorods on SO2 Resistance in Hg0 Removal Process

Sorbent of &alpha;MnO2 nanorods coating TiO2 shell (denoted as &alpha;MnO2-NR@TiO2) was prepared to investigate the elemental mercury (Hg0) removal performance in the presence of SO2. Due the core-shell structure, &alpha;MnO2-NR@TiO2 has a better SO2 resistance when compared to &alpha;MnO2 nanorods (denoted as &alpha;MnO2-NR). Kinetic studies have shown that both the sorption rates of &alpha;MnO2-NR and &alpha;MnO2-NR@TiO2, which can be described by pseudo second-order models and SO2 treatment, did not change the kinetic models for both the two catalysts. In contrast, X-ray photoelectron spectroscopy (XPS) results showed that, after reaction in the presence of SO2, S concentration on &alpha;MnO2-NR@TiO2 surface is lower than on &alpha;MnO2-NR surface, which demonstrated that TiO2 shell could effectively inhibit the SO2 diffusion onto MnO2 surface. Thermogravimetry-differential thermosgravimetry (TG-DTG) results further pointed that SO2 mainly react with TiO2 forming Ti(SO4)O in &alpha;MnO2-NR@TiO2, which will protect Mn from being deactivated by SO2. These results were the reason for the better SO2 resistance of &alpha;MnO2-NR@TiO2