Quantum Phase Transition in Magnetic Nanographenes on a Lead Superconductor.

Quantum spins, also known as spin operators that preserve SU(2) symmetry, lack a specific orientation in space and are hypothesized to display unique interactions with superconductivity. However, spin-orbit coupling and crystal field typically cause a significant magnetic anisotropy in d/f shell spins on surfaces. Here, we fabricate atomically precise S = 1/2 magnetic nanographenes on Pb(111) through engineering sublattice imbalance in the graphene honeycomb lattice. Through tuning the magnetic exchange strength between the unpaired spin and Cooper pairs, a quantum phase transition from the singlet to the doublet state has been observed, consistent with the quantum spin models. From our calculations, the particle-hole asymmetry is induced by the Coulomb scattering potential and gives a transition point about kBTk ≈ 1.6Δ. Our work demonstrates that delocalized π electron magnetism hosts highly tunable magnetic bound states, which can be further developed to study the Majorana bound states and other rich quantum phases of low-dimensional quantum spins on superconductors.

RAB6A functions as a critical modulator of the stem-like subsets in cholangiocarcinoma.

RAB6A is a member of RAB GTPase family and plays an important role in the targeted transport of neurotrophic receptors and inflammatory cytokines. RAB6A-mediated secretory pathway is involved in many physiological and pathological processes. Defects in RAB6A-mediated secretory pathway may lead to the development of many diseases, including cancer. However, its role in cholangiocarcinoma (CCA) has not yet been revealed. We explored the regulatory role of RAB6A in the stem-like subsets of CCA. We showed that RAB6A knockdown (KD) impedes cancer stem cells (CSCs) properties and epithelial-mesenchymal transition in vitro and that suppression of RAB6A inhibits tumor growth in vivo. We screened target cargos of RAB6A in CCA cells and identified a extracellular matrix component as the target cargo. RAB6A binds directly to OPN, and RAB6A KD suppressed OPN secretion and inhibited the interaction between OPN and αV integrin receptor. Moreover, RAB6A KD inhibited the AKT signaling pathway, which is a downstream effector of the integrin receptor signaling. In addition, shRNA targeting OPN blocked endogenous expression of OPN and consequently weakened CSCs properties in RAB6A-formed spheres. Similarly, inhibitor of AKT signaling, MK2206 also impedes oncogenic function of RAB6A in the stem-like subsets of CCA cells. In conclusion, our findings showed that RAB6A sustains CSCs phenotype maintenance by modulating the secretion of OPN and consequentially activating the downstream AKT signaling pathway. Targeting the RAB6A/OPN axis may be an effective strategy for CCA therapy.

National survey on the availability of oncology palliative care services at tertiary general and cancer hospitals in China.

BACKGROUND: This nationwide survey studied the level of palliative care (PC) access for Chinese patients with cancer among cancer care providers either in tertiary general hospitals or cancer hospitals in China. METHODS: Using a probability-proportionate-to-size method, we identified local tertiary general hospitals with oncology departments to match cancer hospitals at the same geographic area. A PC program leader or a designee at each hospital reported available PC services, including staffing, inpatient and outpatient services, education, and research, with most questions adapted from a previous national survey on PC. The primary outcome was availability of a PC service. RESULTS: Most responders reported that some type of PC service (possibly called "comprehensive cancer care," "pain and symptom management," or "supportive care") was available at their institution (84.3% of tertiary general hospitals, 82.8% of cancer hospitals). However, cancer hospitals were significantly more likely than tertiary general hospitals to have a PC department or specialist (34.1% vs. 15.5%, p < 0.001). The most popular services were pain consultation (> 92%), symptom management (> 77%), comprehensive care plans (~ 60%), obtaining advanced directives and do-not-resuscitate orders (~ 45%), referrals to hospice (> 32%), and psychiatric assessment (> 25%). Cancer hospitals were also more likely than tertiary general hospitals to report having inpatient beds for PC (46.3% vs. 30.5%; p = 0.010), outpatient PC clinics (28.0% vs. 16.8%; p = 0.029), educational programs (18.2% vs. 9.0%, p = 0.014), and research programs (17.2% vs. 9.3%, p < 0.001). CONCLUSIONS: Cancer hospitals are more likely to offer PC than are tertiary general hospitals in China. Our findings highlight opportunities to further increase the PC capacity in Chinese hospitals.

Quantifying the direct effects of long-term dynamic land use intensity on vegetation change and its interacted effects with economic development and climate change in jiangsu, China.

Vegetation change reflects sensitive responses of ecosystem environment to global climate change as well as land use. It is well known that land use type and its transformation affect vegetation change. However, how the changes in land use intensity (LUI) within different land use types impact vegetation and the interactions with other drivers remain poorly understood. We measured the LUI of Jiangsu Province, China, within the main land use types in 1995, 2000, 2005, 2010, 2015 and 2018 by combining remote sensing-based land use data with representative county scale economic and social indicators. Structural equation models (SEMs) were built to quantify the influences of long term LUI on vegetation change interacting with economic development, climate change and topographical conditions in transformed land, cropland, rural settlements and urbanized land, respectively. Seventy percent of significant vegetation change existed in non-transformed land use types. Although the area with a vegetation greening trend is larger than that with a vegetation browning trend, the vegetation browning areas is prominent in urbanized lands and some croplands in south basins. The constructed SEMs suggested the dominant negative effect of fast economic development regardless of land use types, while LUI played important and different direct and indirect effects on affecting vegetation change significantly interacting with economic development and climate change in different land use types. The LUI increasing led a vegetation greening in cropland, and stronger than climate warming with both positive direct and indirect effects for influencing climate change. The LUI change took negative effects on vegetation change in rural and urban areas, while a positive indirect effect of LUI increasing in urbanized land signaled the positive results of human managements. We then provided some land use-specific suggestions on basin scale for land management in Jiangsu. Our results highlight the necessity of long-term LUI quantification and promote the understanding of its effects on vegetation change interacted with other drivers within different land use types. This can be very helpful for sustainable land use and managements in regions with fast economic development.

Higher pH is associated with enhanced co-occurrence network complexity, stability and nutrient cycling functions in the rice rhizosphere microbiome.

The rice rhizosphere microbiota is crucial for crop yields and nutrient use efficiency. However, little is known about how co-occurrence patterns, keystone taxa and functional gene assemblages relate to soil pH in the rice rhizosphere soils. Using shotgun metagenome analysis, the rice rhizosphere microbiome was investigated across 28 rice fields in east-central China. At higher pH sites, the taxonomic co-occurrence network of rhizosphere soils was more complex and compact, as defined by higher average degree, graph density and complexity. Network stability was greatest at medium pH (6.5 < pH < 7.5), followed by high pH (7.5 < pH). Keystone taxa were more abundant at higher pH and correlated significantly with key ecosystem functions. Overall functional genes involved in C, N, P and S cycling were at a higher relative abundance in higher pH rhizosphere soils, excepting C degradation genes (e.g. key genes involved in starch, cellulose, chitin and lignin degradation). Our results suggest that the rice rhizosphere soil microbial network is more complex and stable at higher pH, possibly indicating increased efficiency of nutrient cycling. These observations may indicate routes towards more efficient soil management and understanding of the potential effects of soil acidification on the rice rhizosphere system.

Coexistence of Ferroelectriclike Polarization and Dirac-like Surface State in TaNiTe_{5}.

By combining angle-resolved photoemission spectroscopy, scanning tunneling microscopy, atomic force microscope based piezoresponse force microscopy and first-principles calculations, we have studied the low-energy band structure, atomic structure, and charge polarization on the surface of a topological semimetal candidate TaNiTe_{5}. Dirac-like surface states were observed on the (010) surface by angle-resolved photoemission spectroscopy, consistent with the first-principles calculations. On the other hand, piezoresponse force microscopy reveals a switchable ferroelectriclike polarization on the same surface. We propose that the noncentrosymmetric surface relaxation observed by scanning tunneling microscopy could be the origin of the observed ferroelectriclike state in this novel material. Our findings provide a new platform with the coexistence of a ferroelectriclike surface charge distribution and novel surface states.

FBXO31 sensitizes cancer stem cells-like cells to cisplatin by promoting ferroptosis and facilitating proteasomal degradation of GPX4 in cholangiocarcinoma.

BACKGROUND & AIMS: Cholangiocarcinoma (CCA) is a malignant tumour originating from the biliary epithelium that easily infiltrates, metastasizes and recurs. The deficiency of FBXO31 facilitates the initiation and progression of several types of cancer. However, the involvement of FBXO31 in CCA progression has remained unclear. METHODS: qRT-PCR was used to detect the expression of FBXO31 in CCA. The biological functions of FBXO31 were confirmed in vivo and in vitro. Sphere formation and flow cytometry were used to identify the stem cell properties of CCA. RESULTS: FBXO31 is downregulated in CCA and that deficiency of FBXO31 is associated with the TNM stage of CCA. Functional studies showed FBXO31 inhibits cell growth, migration, invasion, cancer stem cell (CSC) properties and epithelial-mesenchymal transition (EMT) in vitro and impedes tumour growth in vivo. In addition, overexpression of FBXO31 increases the cisplatin (CDDP) sensitivity of CCA cells. RNA-sequencing analysis revealed that FBXO31 is involved in redox biology and metal ion metabolism in CCA cells during CDDP treatment. Further studies revealed that FBXO31 enhances ferroptosis induced by CDDP in CCA and CSC-like cells. FBXO31 enhances ubiquitination of glutathione peroxidase 4 (GPX4), which leads to proteasomal degradation of GPX4. Moreover, overexpression of GPX4 compromises the promoting effects of FBXO31 on CDDP-induced ferroptosis in CCA and CSC-like cells. CONCLUSIONS: Our studies indicate that FBXO31 functions as a tumour suppressor in CCA and sensitizes CSC-like cells to CDDP by promoting ferroptosis and facilitating the proteasomal degradation of GPX4.

Sierpinski Structure and Electronic Topology in Bi Thin Films on InSb(111)B Surfaces.

Deposition of Bi on InSb(111)B reveals a striking Sierpinski-triangle (ST)-like structure in Bi thin films. Such a fractal geometric topology is further shown to turn off the intrinsic electronic topology in a thin film. Relaxation of a huge misfit strain of about 30% to 40% between Bi adlayer and substrate is revealed to drive the ST-like island formation. A Frenkel-Kontrova model is developed to illustrate the enhanced strain relief in the ST islands offsetting the additional step energy cost. Besides a sufficiently large tensile strain, forming ST-like structures also requires larger adlayer-substrate and intra-adlayer elastic stiffnesses, and weaker intra-adlayer interatomic interactions.

FBXO31 modulates activation of hepatic stellate cells and liver fibrogenesis by promoting ubiquitination of Smad7.

Liver fibrosis is a critical pathological process in the early stage of many liver diseases, including hepatic cirrhosis and liver cancer. However, the molecular mechanism is not fully revealed. In this study, we investigated the role of F-box protein 31 (FBXO31) in liver fibrosis. We found FBXO31 upregulated in carbon tetrachloride (CCl4 ) induced liver fibrosis and in activated hepatic stellate cells, induced by transforming growth factor-ß (TGF-ß). The enforced expression of FBXO31 caused enhanced proliferation and increased expression of α-smooth muscle actin (α-SMA) and Col-1 in HSC-T6 cells. Conversely, suppression of FBXO31 resulted in inhibition of proliferation and decreased accumulation of α-SMA and Col-1 in HSC-T6 cells. In addition, upregulation of FBXO31 in HSC-T6 cells decreased accumulation of Smad7, the negative regulator of the TGF-ß/smad signaling pathway, and suppression of the FBXO31 increased accumulation of Smad7. Immunofluorescence staining showed FBXO31 colocalized with Smad7 in HSC-T6 cells and in liver tissues of BALB/c mice treated with CCl4 . Immunoprecipitation demonstrated FBXO31 interacted with Smad7. Moreover, FBXO31 enhanced ubiquitination of Smad7. In conclusion, FBXO31 modulates activation of HSCs and liver fibrogenesis by promoting ubiquitination of Smad7.

miR-486-3p Influences the Neurotoxicity of a-Synuclein by Targeting the SIRT2 Gene and the Polymorphisms at Target Sites Contributing to Parkinson's Disease.

BACKGROUND/AIMS: Increasing evidence suggests the important role of sirtuin 2 (SIRT2) in the pathology of Parkinson's disease (PD). However, the association between potential functional polymorphisms in the SIRT2 gene and PD still needs to be identified. Exploring the molecular mechanism underlying this potential association could also provide novel insights into the pathogenesis of this disorder. METHODS: Bioinformatics analysis and screening were first performed to find potential microRNAs (miRNAs) that could target the SIRT2 gene, and molecular biology experiments were carried out to further identify the regulation between miRNA and SIRT2 and characterize the pivotal role of miRNA in PD models. Moreover, a clinical case-control study was performed with 304 PD patients and 312 healthy controls from the Chinese Han population to identify the possible association of single nucleotide polymorphisms (SNPs) within the miRNA binding sites of SIRT2 with the risk of PD. RESULTS: Here, we demonstrate that miR-486-3p binds to the 3' UTR of SIRT2 and influences the translation of SIRT2. MiR-486-3p mimics can decrease the level of SIRT2 and reduce a-synuclein (α-syn)-induced aggregation and toxicity, which may contribute to the progression of PD. Interestingly, we find that a SNP, rs2241703, may disrupt miR-486-3p binding sites in the 3' UTR of SIRT2, subsequently influencing the translation of SIRT2. Through the clinical case-control study, we further verify that rs2241703 is associated with PD risk in the Chinese Han population. CONCLUSION: The present study confirms that the rs2241703 polymorphism in the SIRT2 gene is associated with PD in the Chinese Han population, provides the potential mechanism of the susceptibility locus in determining PD risk and reveals a potential target of miRNA for the treatment and prevention of PD.

MiR-4673 Modulates Paclitaxel-Induced Oxidative Stress and Loss of Mitochondrial Membrane Potential by Targeting 8-Oxoguanine-DNA Glycosylase-1.

BACKGROUND: Our previous study identified a novel microRNA, miR-4673, which is upregulated in A549 cells exposed to paclitaxel (PTX). In this study, we investigated the role of miR-4673 in PTX-induced cytotoxicity. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, apoptosis assay, 5,5',6,6'-Tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide (JC-1) staining and 2',7'-Dichlorofluorescein (DCFH) staining were used to evaluate cell viability, apoptosis, mitochondrial membrane potential (MMP) loss and reactive oxygen species (ROS) generation in A549 and H1299 cells. Bioinformatics analysis and Luciferase reporter assay were used to explore whether 8-oxoguanine-DNA glycosylase-1 (OGG1) is a target gene of miR-4673. RESULTS: Enforced expression of miR-4673 decreased cell viability and increased PTX-induced apoptosis, MMP loss and reactive oxygen species (ROS) generation in A549 and H1299 cells. Bioinformatics analysis, which was used to identify potential target of miR-4673, revealed a binding site of miR-4673 in 3'UTR of OGG1. Luciferase reporters assays showed that miR-4673 specifically binds to 'CUGUUGA' in 3'UTR of OGG1. Enforced expression of miR-4673 decreased accumulation of OGG1. In addition, silencing OGG1 enhanced inhibitory effects of PTX on apoptosis, MMP loss and ROS generation, which is similar to effects of miR-4673. Moreover, enforced expression of OGG1 compromised promoting effects of miR-4673 on PTX-induced apoptosis, MMP loss and ROS generation. CONCLUSION: miR-4673 modulates PTX-induced apoptosis, MMP loss and ROS generation by targeting OGG1.

Abnormal nonlocal scale effect on static bending of single-layer MoS2.

The nonlocal scale parameter of nonlocal Euler-Bernoulli beam theory is evaluated for the static bending of single-layer molybdenum disulfide (SLMoS2) without predetermined bending rigidity. The evaluation is performed by matching the fitted curve between the maximum deflection and the beam length obtained from molecular mechanics simulations. It was observed that the fitted curves have an abnormal sign in the second-order term of the maximum deflection for SLMoS2, opposite to that for graphene and regardless of the interatomic interaction potentials used. Based on the nature of 'nonlocal' and the phenomenological point of view, a modified nonlocal constitutive relation with a positive sign in front of the higher-order term is suggested for SLMoS2. The nonlocal parameter and the bending rigidity of SLMoS2 are finally extracted, and the effect of the nonlocal scale parameter on the bending response for SLMoS2 is found to be significant for beam length less than a critical length, depending on both the interatomic interaction potentials and the boundary conditions. Our new perspective should be useful for researchers who are interested in the engineering application of graphene-like quasi-two-dimensional nanostructures using nonlocal beam theories.

Mir-152 inhibits cell proliferation and colony formation of CD133(+) liver cancer stem cells by targeting KIT.

miR152 is involved in diverse biological functions and development of disease. This study investigates the role of mir-152 in cell proliferation and colony formation of liver cancer stem cells. We show that exogenous overexpression of mir-152 suppresses cell proliferation and colony formation in CD133(+) hep3B cells. We also show that KIT is a direct target of miR-152 and miR-152 downregulates protein expression of KIT by directly binding to 3' untranslated region of KIT. Downregulation of KIT by specific siRNAs inhibits proliferation and colony formation of CD133(+) hep3B cells, which is similar to inhibitory effects of miR-152. Moreover, exogenous expression of KIT compromises inhibitory effects of miR-152 on cell proliferation and colony formation. Our findings suggest that mir-152 inhibits cell proliferation and colony formation of CD133(+) hep3B cells by targeting KIT.

Mitochondrial OGG1 protects against PM2.5-induced oxidative DNA damage in BEAS-2B cells.

The enzyme 8-oxoguanine glycosylase 1 (OGG1) has been shown to be involved in the repair of oxidative DNA damage. However, the effect of OGG1 on oxidative DNA damage caused by particulate matter 2.5 (PM2.5) is unknown. Herein, we demonstrated that OGG1 could inhibit the generation of ROS and alleviate mitochondrial dysfunction and increased the expression of IL-1ß caused by PM2.5. The dichlorodihydrofluorescein diacetate (DCFH-DA) staining and 5,5',6,6'-tetrachloro-1,1',3,3'-. tetraethylbenzi-midazolylcarbocyanine iodide (JC-1) staining using flow cytometry showed that PM2.5 induces the generation of ROS and leads to a reduction in mitochondrial membrane potential (MMP) in BEAS-2B cells. Overexpression of OGG1 inhibited the generation of ROS and the decline in MMP. Knockdown of OGG1 by RNA interference (RNAi) increased the generation of ROS and reduced the MMP. Real-time quantitative PCR (RT-qPCR) for the mitochondrial DNA copy number (mtDNAcn) and flow cytometry for apoptosis revealed that OGG1 inhibits the apoptosis and decreases mtDNAcn induced by PM2.5. Additionally, the results of the comet assay showed that OGG1 had a significant repair effect on DNA strand breaks caused by PM2.5. Overexpression of OGG1 also significantly suppressed the expression of IL-1ß caused by PM2.5. Together, these data suggest that PM2.5 leads to mitochondrial dysfunction and the up-regulation of IL-1ß could be reversed by overexpression of OGG1. The mitochondrial dysfunction caused by PM2.5 could be relieved by OGG1. Thus, the base excision repair enzyme OGG1 may alleviate mitochondrial dysfunction caused by PM2.5 involved in the expression of IL-1ß.

Circulating microRNA Signatures Associated with Childhood Asthma.

BACKGROUND: MicroRNAs (miRNAs) exist stably and reproducibly in plasma and may be used as biomarkers for various diseases. Little is known about circulating miRNAs in the peripheral blood of juvenile patients with asthma. METHODS: In this study, we used hybridization arrays to compare the miRNA expression profiles among 6 juvenile patients with or without asthma. Using quantitative PCR (qPCR), we verified the expression levels of these miRNAs in plasma from patients with asthma (n = 40) and healthy subjects (n = 14). RESULTS: Our results showed that the levels of plasma miR-Let7C, miR-486, and miR-1260a in childhood asthma patients were significantly higher than in healthy controls (p < 0.01). Additionally, miR-1260a is correlated with the treatment schedule of these patients and patients with long treatment times had higher expression of miR-1260a than short treatment times; miR494 was significantly associated with challenge, and miR-3162-3p was significantly associated with MEF25 in asthma patients suggesting a potential correlation of miRNA levels with clinical disease parameters. Receiver operator characteristic analysis confirmed that the levels of miR-3162-3p could be used to discriminate childhood asthma patients from healthy subjects (area under the curve of 0.821), suggesting it may be a potential diagnostic biomarker. CONCLUSIONS: These results indicate that circulating miR-3162-3p and miR-1260a should be further evaluated as potential non-invasive biomarkers in diagnosis and treatment for childhood asthma.

Prevalence and associated factors for temporomandibular disorders in Chinese civilian pilots.

PURPOSE: Piloting is a special profession with prolonged stress, which could induce the occurrence of TMD. This sample is useful to reduce the effect of confounders in the analyses. Based on this, the present study aims to determine the prevalence and associated factors for TMD in civilian pilots of China. METHODS: A cross-sectional epidemiological survey was carried out in 616 male subjects (aged 23-52 years). The questionnaire included general information, chewing preference (bilateral or unilateral), and Trait Anxiety section of Spielberger State-Trait Anxiety Inventory (STAI-T). The clinical examination contained TMD screening per research diagnostic criteria for TMD and diagnosis of sleep bruxism per American Academy of Sleep Medicine standards. The level of statistical significance was set at P ≤ 0.05. RESULTS: The program was conducted from June 2012 to April 2013, in which period, and the percentage of TMD in the samples we examined was 33.3 % (=205/616). Only high anxiety (OR 2.48; 95 % CI 1.25-4.90) and unilateral chewing preference (OR 12.67; 95 % CI 7.77-20.65) were the most significant associated factors with TMD. Also, salivary cortisol and the STAI-T score had a significant correlation (r = 0.47, P < 0.001). CONCLUSIONS: It was more reliable to study the associated factors on TMD with the exclusion of the possible confounding factors, and only unilateral chewing preference and psychological stress had a significant association with TMD. In addition, the salivary cortisol levels might assist to assess psychological stress in epidemiological research.

Effect of human umbilical cord blood mesenchymal stem cell transplantation on neuronal metabolites in ischemic rabbits.

BACKGROUND: Because there is little research on the effects of transplanted stem cells on neuronal metabolites in infarct areas, we transplanted human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) into cerebral ischemic rabbits and examined the neuronal metabolites. RESULTS: Rabbits (n = 40) were equally divided into sham, middle cerebral artery occlusion (MCAO), hUCB-MSC, and saline groups. The rabbit ischemic model was established by MCAO. The effects of hUCB-MSC transplantation were assessed by proton magnetic resonance spectroscopy (1H-MRS), neurological severity scores (NSSs), infarct area volume, neuronal density, and optical density (OD) of microtubule-associated protein 2 (MAP2)-positive cells. We also evaluated complete blood cell counts(CBCs) and serum biochemical parameters. NSSs in the hUCB-MSC group at 7 and 14 days after reperfusion were lower than in MCAO and saline groups (p < 0.05). Compared with MCAO and saline groups at 2 weeks after MCAO, the infarction volume in the hUCB-MSC group had decreased remarkably (p < 0.05). Significant neuronal metabolic changes occurred in the infarct area at 24 h and 2 weeks after MCAO. 1H-MRS revealed an elevation in the lactate (Lac)/creatine including phosphocreatine (Cr) ratio and a decrease in the N-acetylaspartate (NAA)/Cr and choline-containing phospholipids (Cho)/Cr ratios at 24 h after MCAO in the MCAO group (p < 0.01). Compared with saline and MCAO groups at 24 h and 2 weeks after MCAO, NAA/Cr and Cho/Cr ratios had increased significantly, whereas the Lac/Cr ratio had decreased significantly in the hUCB-MSC group (p < 0.01). Neuronal density and OD of MAP2-positive cells in the MCAO group were significantly lower than those in the sham group, whereas the neuronal density and OD of MAP2-positive cells in the hUCB-MSC group were higher than those in MCAO and saline groups (p < 0.05). CBCs and biochemical parameters were unchanged in the MCAO group at 24 h and 2 weeks after hUCB-MSC transplantation. CONCLUSIONS: Transplanted hUCB-MSCs might ameliorate ischemic damage by influencing neuronal metabolites in the infarct area, providing additional evidence for neuroprotection by stem cells. No significant changes were observed in CBCs or serum biochemical parameters, suggesting that intravenous infusion of hUCB-MSCs is safe for rabbits in the short-term.

CHD5 a tumour suppressor is epigenetically silenced in hepatocellular carcinoma.

BACKGROUND: Chromodomain helicase DNA binding protein 5 (CHD5) has recently been identified as a potent tumour suppressor by acting as a master regulator of a tumour-suppressive network. Its inactivation resulted from aberrant methylation in the promoter occurs in several types of human malignancy and is associated with malignant tumour behaviour. In human hepatocellular carcinoma (HCC), CHD5 gene expression, methylation status and tumour-suppressive function have not been elucidated. AIMS: In this study, we focused on the epigenetic modification and tumour-suppressive mechanism of CHD5 gene in HCC. METHODS: CHD5 expression in nine HCC cell lines and 30 pairs of HCC specimens and adjacent non-cancerous tissues were analysed by quantitative reverse transcription PCR and Western blotting. Methylation-specific sequencing and methylation-specific PCR were performed to examine DNA methylation status of the CHD5 promoter in HCC cell lines and samples. The effect of CHD5 restoration on proliferation, colony formation, senescence, apoptosis and tumourigenicity were examined. RESULTS: CHD5 expression was sinificantly down-regulated in HCC cell lines and tissues examined, and the -841 to -470 region of CHD5 promoter was hypermethylated in these samples. Treatment with DNA methyltransferase inhibitor 5-aza-2-deoxycytidine resulted in a striking regional demethylation of the -841 to -470 region of CHD5 promoter and an increase in CHD5 expression. The restoration of CHD5 expression inhibited tumour cell proliferation, colony formation and tumourigenicity and caused cellular senescence. CONCLUSIONS: Our findings demonstrate that CHD5 is a potential tumour suppressor gene epigenetically silenced in HCC.

Human umbilical cord blood mesenchymal stem cell transplantation suppresses inflammatory responses and neuronal apoptosis during early stage of focal cerebral ischemia in rabbits.

AIM: Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) have been shown to ameliorate cerebral ischemia in animal models. In this study we investigated the effects of hUCB-MSCs on inflammatory responses and neuronal apoptosis during the early stage of focal cerebral ischemia in rabbits. METHODS: Focal cerebral ischemia was induced in male New Zealand rabbits by occlusion of MCA for 2 h. The blood samples were collected at different time points prior and during MCAO-reperfusion. The animals were euthanized 3 d after MCAO, and the protein levels of IL-1ß, IL-6, IL-10 and TNF-α in the serum and peri-ischemic brain tissues were detected using Western blot and ELISA, respectively. Inflammatory cell infiltration, neuronal apoptosis and neuronal density were measured morphologically. hUCB-MSCs (5 × 10(6)) were iv injected a few minutes after MCAO. RESULTS: The serum levels of IL-1ß, IL-6 and TNF-α were rapidly increased, and peaked at 2 h after the start of MCAO. hUCB-MSC transplantation markedly and progressively suppressed the ischemia-induced increases of serum IL-1ß, IL-6 and TNF-α levels within 6 h MCAO-reperfusion. Focal cerebral ischemia decreased the serum level of IL-10, which was prevented by hUCB-MSC transplantation. The expression of IL-1ß, IL-6, IL-10 and TNF-α in the peri-ischemic brain tissues showed similar changes as in the serum. hUCB-MSC transplantation markedly suppressed the infiltration of inflammatory cells, and increased the neuronal density around the ischemic region. Furthermore, hUCB-MSC transplantation significantly decreased the percentage of apoptosis around the ischemic region. CONCLUSION: hUCB-MSCs transplantation suppresses inflammatory responses and neuronal apoptosis during the early stage focal cerebral ischemia in rabbits.

Parental health penalty on adult children's employment: Gender differences and long-term consequences.

This study examines the gender-specific and enduring impacts of parental health shocks on adult children's employment in China, where both formal care and health insurance are limited. Using an event-study approach, we establish a causal link between parental health shocks and a notable decline in female employment, which persists for at least six years following the shock. Male employment, however, exhibits minimal change on average, although this conceals an increase among poor families, indicating a channel beyond heightened informal care. Our findings underscore the consequences of "growing old before getting rich" for developing countries.