Gene delivery to breast cancer by incorporated EpCAM targeted DARPins into AAV2.

OBJECTIVE: The aim of this study is to evaluate an AAV vector that can selectively target breast cancer cells and to investigate its specificity and anti-tumor effects on breast cancer cells both in vitro and in vivo, offering a new therapeutic approach for the treatment of EpCAM-positive breast cancer. METHODS: In this study, a modified AAV2 viral vector was used, in which EpCAM-specific DARPin EC1 was fused to the VP2 protein of AAV2, creating a viral vector that can target breast cancer cells. The targeting ability and anti-tumor effects of this viral vector were evaluated through in vitro and in vivo experiments. RESULTS: The experimental results showed that the AAV2MEC1 virus could specifically infect EpCAM-positive breast cancer cells and accurately deliver the suicide gene HSV-TK to tumor tissue in mice, significantly inhibiting tumor growth. Compared to the traditional AAV2 viral vector, the AAV2MEC1 virus exhibited reduced accumulation in liver tissue and had no impact on tumor growth. CONCLUSION: This study demonstrates that AAV2MEC1 is a gene delivery vector capable of targeting breast cancer cells and achieving selective targeting in mice. The findings offer a potential gene delivery system and strategies for gene therapy targeting EpCAM-positive breast cancer and other tumor types.

[Testing Effectiveness of Localized Cognitive Stimulation Training With Musical Rhythm Courses Among Older People in Day Care Centers: A Pilot Study].

BACKGROUND: Staff caregivers of day care centers provide many activities for older people. However, there is a lack of a systematic curriculum based on Taiwanese culture to improve cognitive function, self-care ability, and depressive mood status in these individuals. PURPOSE: This study was designed to test the effectiveness of a series of localized cognitive stimulation training courses implemented by direct caregivers and aimed at improving cognitive function, self-care ability, and depressive mood in older people at day care centers. METHODS: This cluster-randomized controlled trial research was conducted over a four-month period. The participants were randomly assigned to the experimental, comparison, or control groups based on their day care center affiliation. The experimental group received a series of localized cognitive stimulation training sessions with musical rhythm courses from day care center direct caregivers. The cognitive function, self-care ability, and depression mood state of the three groups were then tested. RESULTS: The experimental group reported statistically significant changes in average scores for attention, feeding, and depressive mood. After controlling for time and degree of participation in activities, the comparison group reported a lower average score for cognitive function at timepoint 3. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The results of this study support caregivers at day care centers implementing a series of localized cognitive stimulation training course interventions to prevent declines in activities of daily living and cognitive function and ameliorate depressive mood in older adults. In the future, a larger sample size should be used to improve the effectiveness of the intervention.

[Differential transcription of mating-type genes during sexual reproduction of natural Cordyceps sinensis].

Natural Cordyceps sinensis as an insect-fungal complex, which is developed after Ophiocordyceps sinensis infects a larva of Hepialidae family. Seventeen genotypes of O. sinensis have been identified in natural C. sinensis. This paper summarized the literature reports and GenBank database regarding occurrence and transcription of the mating-type genes of MAT1-1 and MAT1-2 idiomorphs in natural C. sinensis, in Hirsutella sinensis(GC-biased Genotype #1 of O. sinensis), to infer the mating pattern of O. sinensis in the lifecycle of natural C. sinensis. The mating-type genes and transcripts of MAT1-1 and MAT1-2 idiomorphs were identified in the metagenomes and metatranscriptomes of natural C. sinensis. However, their fungal sources are unclear because of co-colonization of several genotypes of O. sinensis and multiple fungal species in natural C. sinensis. The mating-type genes of MAT1-1 and MAT1-2 idiomorphs were differentially present in 237 H. sinensis strains, constituting the genetic control of the O. sinensis reproduction. Transcriptional control of the O. sinensis reproduction includes: differential transcription or silencing of the mating-type genes of MAT1-1 and MAT1-2 idiomorphs, and the MAT1-2-1 transcript with unspliced intron I that contains 3 stop codons. Research on the H. sinensis transcriptome demonstrated differential and complementary transcriptions of the mating-type genes of MAT1-1 and MAT1-2 idiomorphs in Strains L0106 and 1229, which may become mating partners to accomplish physiological heterothallism. The differential occurrence and transcription of the mating-type genes in H. sinensis are inconsistent with the self-fertilization hypothesis under homothallism or pseudohomothallism, but instead indicate the need of mating partners of the same H. sinensis species, either monoecious or dioecious, for physiological heterothallism, or heterospecific species for hybridization. Multiple GC-and AT-biased genotypes of O. sinensis were identified in the stroma, stromal fertile portion(densely covered with numerous ascocarps) and ascospores of natural C. sinensis. It needs to be further explored if the genome-independent O. sinensis genotypes could become mating partners to accomplish sexual reproduction. S. hepiali Strain FENG experienced differential transcription of the mating-type genes with a pattern complementary to that of H. sinensis Strain L0106. Additional evidence is needed to explore a hybridization possibility between S. hepiali and H. sinensis, whether they are able to break the interspecific reproductive isolation. Genotypes #13～14 of O. sinensis feature large DNA segment reciprocal substitutions and genetic material recombination between 2 heterospecific parental fungi, H. sinensis and an AB067719-type fungus, indicating a possibility of hybridization or parasexuality. Our analysis provides important information at the genetic and transcriptional levels regarding the mating-type gene expression and reproduction physiology of O. sinensis in the sexual life of natural C. sinensis and offers crucial reproductive physiology evidence, to assist in the design of the artificial cultivation of C. sinensis to supplement the increasing scarcity of natural resource.

Exposure to ambient air pollutants with kidney function decline in chronic kidney disease patients.

Chronic kidney disease (CKD) has been a global public health problem with many adverse outcomes, but data are lacking regarding the relationship between air pollutants and risk of renal progression in patients with CKD. This study was to investigate whether 1-year average exposure to ambient air pollutants -CO, NO, NO2, SO2, O3, PM2.5, and PM10-is related to renal function deterioration among patients with CKD. A total of 5301 CKD patients were included in this study between October 2008 and February 2016. To estimate each patient's exposure to ambient air pollution, we used the 24-h ambient air pollution concentration monitoring data collected one year prior to renal progression or their last renal function assessment. Renal progression was considered when estimated glomerular filtration rate (eGFR) decreased more than 25% from the baseline eGFR. Cox proportional hazard regression was performed to calculate hazard ratios (HRs). Among 5301 patients with CKD, 1813 (34.20%) developed renal progression during the 30.48 ± 14.99-month follow-up. Patients with the highest quartile exposure to CO [HR = 1.53 (95% CI: 1.24, 1.88)], NO [HR = 1.38 (95% CI: 1.11, 1.71)], NO2 [HR = 1.63 (95% CI: 1.36, 1.97)], SO2 [HR = 2.27 (95% CI: 1.83, 2.82)], PM2.5 [HR = 7.58 (95% CI: 5.97, 9.62)], and PM10 [HR = 3.68 (95% CI: 2.84, 4.78)] had a significantly higher risk of renal progression than those with the lowest quartile exposure. In the multipollutant model, the analyses yielded to similar results. These results reinforce the importance of measures to mitigate air pollution and strategies to prevent worsening of kidney function in patients with CKD. One-year high exposure to ambient CO, NO, NO2, SO2, PM2.5, and PM10 is significantly associated with deteriorated kidney function in patients with CKD among Taiwanese adults.

Molecular chaperone heat shock protein 70 inhibitors suppress conditioned place preference induced by morphine exposure in male rats.

Previous studies have indicated a role for molecular chaperone heat shock protein 70 (Hsp70) in the development of behavioural sensitization to morphine in rodents, suggesting that Hsp70 expression following morphine exposure is involved in molecular changes that may underlie addiction vulnerability. The current study was carried out to investigate the role of Hsp70 in the positive reinforcing properties of morphine using conditioned place preference (CPP) in male rats. An unbiased CPP procedure of three phases (pre-conditioning: d1-d3; conditioning: d4-d6; and testing: d7) was used. During the conditioning phase, morphine injections (5 mg/kg, subcutaneously) were administered to induce significant place preference. To explore the effect of Hsp70 on the development and expression of morphine CPP, Hsp70 inhibitors (PES, KNK437 and methylene blue) were administered into the lateral ventricle prior to either morphine conditioning sessions or a morphine challenge on the test day. Furthermore, Hsp70 expression within the mesocorticolimbic system was measured after the treatment with KNK437, a transcriptional inhibitor. We found that PES and KNK437, respectively, injected intracerebroventricularly dose-dependently attenuated both the development and expression of morphine CPP. Methylene blue treatment demonstrated an attenuation of the development, but had no effect on the expression of morphine CPP. Following KNK437 treatment, Hsp70 expression was significantly inhibited in the shell of nucleus accumbens (NAc) during both the development and expression of morphine CPP. The findings suggest that Hsp70 in the NAc shell plays an important role in the reinforcing effects of morphine and may be involved in the development of morphine dependence.

Mu-opioid receptors in septum mediate the development of behavioural sensitization to a single morphine exposure in male rats.

Behavioural sensitization (BS) is characterized by enhanced psychomotor responses to a dose of substance of abuse after prior repeated exposure. We previously reported that BS can be induced by a single injection of morphine in rats, whereas septal nuclei are specifically involved in the development phase of BS. Here, we demonstrated that intra-LS or intra-MS microinjections also incubated BS to a systemic morphine injection in a cross-sensitization fashion, whereas inactivation of either subdivision of septal nuclei (LS: lateral septum; MS: medial septum) can negate this ability of morphine. Then, non-selective (naloxone) and selective (µ-, δ- and κ-)opioid receptor antagonists were directly delivered into LS or MS, respectively, ahead of a morphine microinjection, whereas only µ-opioid receptors in both LS and MS play indispensable roles in mediating the BS development. Finally, there was a pronounced elevation in the levels of the monoamines (i.e. dopamine, homovanillic acid, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid) in the septum, 8 h after a morphine injection detected with a HPLC-ECD method, suggesting that dopaminergi and serotoninergic systems are implicated in the BS formation. Our studies demonstrated that septal nuclei critically participate in the BS development. Essentially, µ- instead of δ- or κ-opioid receptors in LS and MS mediate sensitization to opiates.

Chiral Analysis of Lactate during Direct Contact Coculture by Single-Cell On-Probe Enzymatic Dehydrogenation Derivatization: Unraveling Metabolic Changes Caused by d-Lactate.

In vitro noncontact cell-based coculture models are frequently employed to study cell-to-cell communication. However, these models cannot accurately represent the complexity of in vivo signaling. d-Lactate is an unusual metabolite produced and released by cancer cells. The characterization of d-lactate is challenging as it shares the same mass but has much lower amounts compared with l-lactate. Herein, d-α-hydroxy acids were specifically recognized and dehydrogenated by d-α-hydroxy acid dehydrogenase. The dehydrogenation products were rapidly quaternized for enhancement of mass signals. An on-probe enzymatic dehydrogenation-derivatization method was proposed for chiral analysis of α-hydroxy acids at the single-cell level. It is a promising amplification methodology and affords over 3 orders of magnitude signal enhancement. Furthermore, direct contact coculture models were used to precisely mimic the tumor microenvironment and explore the communication between cancer and normal cells. Single-cell mass spectrometry (SCMS) was further applied to easily sample cell extracts and study the differences of the aspects of small molecule metabolism in cocultured cells. On the basis of direct contact coculture SCMS, several differential small molecule metabolites and differences of oxidative stress between cocultured and monocultured normal cells were successfully detected. Additionally, d-lactate was discovered as a valuable differential metabolite with application of the two developed methods. It may account for the cancer-associated metabolic behavior of normal cells. These changes could be relieved after d-lactate metabolism-related drug treatment. This discovery may promote the investigation of d-lactate metabolism, which may provide a novel direction for cancer therapy.

Long-term exposure to ozone and sulfur dioxide increases the incidence of type 2 diabetes mellitus among aged 30 to 50 adult population.

AIMS/HYPOTHESIS: Worldwide, the information regarding the associations between long-term exposure to ozone (O3) and sulfur dioxide (SO2) and the development of type 2 diabetes remains scarce, especially in Asia. This study aimed to investigate the long-term effects of exposure to ambient O3 and SO2 on the incidence of type 2 diabetes with consideration of other air pollutants in Taiwanese adults aged 30 to 50 years. METHODS: A total of 6,426,802 non-diabetic participants aged between 30 and 50 years old were obtained from the National Health Insurance Research Database between 2005 and 2016. Incident type 2 diabetes was the main diagnosis at medical visits. Air quality data were provided by the Taiwan Environmental Protection Administration. The air pollutant concentrations for each participant were estimated using the ordinary kriging method to interpolate daily concentrations of O3, SO2, carbon monoxide (CO), nitrogen dioxide (NO2), suspended fine particles (with an aerodynamic diameter less than 2.5 µm; PM2.5), and suspended particles (with an aerodynamic diameter less than 10 µm; PM10) in residential districts across Taiwan. Six-year average concentrations of pollutants were calculated from January 1, 2005 to December 31, 2010, and data were categorized into quartiles. We performed Cox regression models to analyze the long-term effects of exposure to O3 and SO2 on the incidence of type 2 diabetes. RESULTS: The hazard ratio (HR) for the incidence of diabetes per each interquartile range (IQR) increase in ozone exposure (3.30 ppb) was 1.058 (95% confidence interval (CI): 1.053, 1.064) and 1.011 (95% CI: 1.007, 1.015) for SO2 exposure (1.77 ppb) after adjusting for age, sex, socioeconomic status, urbanization level, temperature, humidity, and chronic comorbidities (Model 3). Furthermore, for every 3.30 ppb increase of O3, the HR for incident type 2 diabetes was 1.093 (95% CI: 1.087, 1.100) after controlling factors shown in Model 3 plus SO2 and PM2.5. On the other hand, for every 1.77 ppb increase of SO2, the HR for incident type 2 diabetes was 1.073 (95% CI: 1.068, 1.079) after controlling factors shown in Model 3 plus NO2 and PM2.5. CONCLUSIONS: Long-term exposure to ambient O3 and SO2 was associated with a higher risk of developing type 2 diabetes for Taiwanese population. Exposure to O3 and SO2 may play a role in the adult early-onset type 2 diabetes.

L-Type Amino Acid Transporter 1 Regulates Cancer Stemness and the Expression of Programmed Cell Death 1 Ligand 1 in Lung Cancer Cells.

The l-type amino acid transporter 1 (LAT1) is a membranous transporter that transports neutral amino acids for cells and is dysregulated in various types of cancer. Here, we first observed increased LAT1 expression in pemetrexed-resistant non-small cell lung cancer (NSCLC) cells with high cancer stem cell (CSC) activity, and its mRNA expression level was associated with shorter overall survival in the lung adenocarcinoma dataset of the Cancer Genome Atlas database. The inhibition of LAT1 by a small molecule inhibitor, JPH203, or by RNA interference led to a significant reduction in tumorsphere formation and the downregulation of several cancer stemness genes in NSCLC cells through decreased AKT serine/threonine kinase (AKT)/mammalian target of rapamycin (mTOR) activation. The treatment of the cell-permeable leucine derivative promoted AKT/mTOR phosphorylation and reversed the inhibitory effect of JPH203 in the reduction of CSC activity in pemetrexed-resistant lung cancer cells. Furthermore, we observed that LAT1 silencing caused the downregulation of programmed cell death 1 ligand 1 (PD-L1) on lung cancer cells. The PD-L1+/LAT1+ subpopulation of NSCLC cells displayed great CSC activity with increased expression of several cancer stemness genes. These data suggest that LAT1 inhibitors can serve as anti-CSC agents and could be used in combination with immune checkpoint inhibitors in lung cancer therapy.

Mass Spectrometry-Based Discovery of New Chemical Scaffold Rearrangement Ions: Aza-biphenylene as a Novel Potent Biradical Agent in Cancer Chemotherapy.

Discovery of a new drug is time-consuming, laborious, and expensive. Herein, a novel integrative strategy for discovering potential new lead compounds has been developed, which was based on the characteristics of mass spectrometry (MS). MS was used to predict the potential forced degradation products (DPs) and metabolites of drugs by electrospray ionization and collision-induced dissociation (CID). Special rearrangement ions representing unique predicted DPs and metabolites were identified. The consistency between the predicted and the measured results was proven by in vitro metabolism and forced degradation of a commercial drug, respectively. From this, new chemical scaffold rearrangement ions named (aza)-biphenylenes, as potent anticancer agents, were discovered. As a representative aza-biphenylene analogue, 2-azabiphenylene was proven in vitro to induce apoptosis and inhibit the growth of various human cancer cells in a dose-dependent manner. Surprisingly, 2-azabiphenylene exhibited the best comparable bioactivity with the positive control sorafenib, but showed significantly lower in vitro cytotoxicity than sorafenib (at least a 5-fold decrease in cytotoxicity) because it could be targeted to the tumor microenvironment at low pH. A biradical mechanism accompanied by a mitochondrion-dependent oxidative stress mechanism was proposed to explore its anticancer mechanism. The highly reactive intermediate aza-biphenylenediyl worked as an active pharmaceutical ingredient and induced apoptosis of cancer cells. This provided the basis for the potential applications of CID-induced special rearrangement ions in developing new lead compounds.

Brucine N-Oxide Reduces Ethanol Intake and Preference in Alcohol-Preferring Male Fawn-Hooded Rats.

BACKGROUND: Alcohol use disorder places a heavy burden on global public health systems and thus is in urgent need of improved pharmacotherapies. Previously, our group has demonstrated that 30 mg/kg of the indole alkaloid brucine significantly attenuates alcohol-drinking behavior; however, the high toxicity, poor water solubility, short half-life, and limited therapeutic window of brucine restrain its clinical application as an antialcoholism medication. We subsequently hypothesized that the oxide of brucine (brucine N-oxide) would produce a similar behavioral effect without the risk profile associated with brucine. METHODS: Male Fawn-Hooded rats with high innate alcohol preference underwent 2-bottle choice procedures (Experiments 1 to 3). Experiment 1 examined the effects of 7 daily BNO injections of 0, 30, 50, or 70 mg/kg (s.c.) on voluntary alcohol consumption (n = 9/group). Experiment 2 evaluated the impact of a single dose of 0 or 70 mg/kg BNO on the increased alcohol intake induced by a 4-day alcohol deprivation (n = 8/group). Experiment 3 tested the effect of 7 daily BNO injections of 0 or 70 mg/kg (s.c.) on sucrose preference (n = 6/group). Experiment 4 measured the median lethal dose (LD50) values of BNO and brucine to compare their acute toxicity in rats. Experiment 5 tested whether BNO (0, 30, 50, and 70 mg/kg, s.c.) affected locomotor activity using an open-field paradigm (n = 8/group). Finally, Experiment 6 evaluated the possible conditioned rewarding effects of 0, 30, 50, and 70 mg/kg BNO using the conditioned place preference paradigm (n = 6/group). RESULTS: BNO administration dose-dependently attenuated alcohol consumption without affecting food intake, total fluid consumption, or the natural preference for a sucrose solution, with 70 mg/kg BNO reducing consumption by 22.8%. A single dose of 70 mg/kg BNO significantly inhibited the alcohol deprivation effect. The LD50 values of BNO and brucine in rats were determined to be 1,103.5 ± 177.0 mg/kg and 264.6 ± 17.7 mg/kg, respectively. Finally, BNO administration did not affect spontaneous locomotor activity or induce a place preference. CONCLUSIONS: BNO may help to control excessive alcohol use and should be considered a treatment strategy for future study and development.

Cervical epidural hematoma after spinal manipulation therapy: a case report.

BACKGROUND: Cervical spinal manipulation therapy is a common non-invasive treatment for neck pain and stiffness, and has been widely used in the population. However, most people do not pay attention to the potential risks of neck manipulation, such as ligament damage, fractures, and spinal cord injuries. Epidural hematoma is a disease in which blood accumulates in the epidural space of the vertebral body. This disease is usually caused by trauma or iatrogenic surgery, and may be associated with blood coagulopathies, neoplasms, or degenerative spinal disease. Reports of epidural hematoma caused by cervical spinal manipulation are rare. CASE PRESENTATION: We present the case of a patient with tetraplegia and spinal shock after neck manipulation. A physical examination of the patient on admission found tenderness in the neck and increased muscle tension in both upper limbs. The superficial sensation of the upper limb disappeared, but the deep sensation still remained. The lower extremity had 0/5 power on both sides. The sensation below the T2 level completely disappeared. A cervical magnetic resonance imaging scan showed an acute posterior epidural hematoma from the C3-T3 vertebrae. Ultimately, the patient underwent emergency hematoma removal and showed partial improvement in symptoms of paralysis during follow-up. CONCLUSIONS: Although spinal manipulation is simple and neck pain is common and recurrent in the general population, the basic condition and disease history of patients should be determined before manipulation. For high-risk patients, caution should be applied for cervical spinal manipulation or it should be prohibited. For a suspected hematoma, MRI should be used at an early stage to diagnose and locate the hematoma.

[Influence of genetic and environment factors on aggressive behavior in twin children].

OBJECTIVE: To investigate the influence of genetic and environmental factors on aggressive behavior in twin children, and to provide clues for further exploring the causal relationship between such factors and aggressive behavior. METHODS: A questionnaire was used to investigate aggressive behavior, temperament type and parenting style among 261 twin children aged 4-12.8 years. The Holzinger method and the maximum likelihood method were used to construct a structural equation model for the estimation of heritability. Binary logistic regression analysis, multivariate linear regression analysis and general linear model analysis were used to analyze the association between aggressive behavior and environmental factors in twin children. RESULTS: The heritability of aggressive behavior was 44.4% in twin children and the score of aggressive behavior showed moderate heritability (60.9% in boys and 65.6% in girls). The multivariate analysis showed that the score of aggressive behavior in twin children was affected by the mother's emotional warmth/understanding, the mother's punishment/severity and the father's overprotection (P<0.05). There was an interaction between the mother's emotional warmth/understanding and the father's overprotection (P<0.05). CONCLUSIONS: Both genetic and environmental factors have influence on children's aggressive behavior, and parenting style is the main environmental factor affecting the aggressive behavior of twin children.

Case Control Study of Impulsivity, Aggression, Pesticide Exposure and Suicide Attempts Using Pesticides among Farmers.

A case-control study was conducted to investigate associations between organophosphate pesticide (OP) exposure, aggression, impulsivity, and attempted suicide. Questionnaires were used to collect information; impulsivity and aggression were measured by the Barratt Impulsivity Scale (BIS) and the Aggression Inventory (AI). A greater number of OP symptoms was associated with an increased odds of a suicide attempt after adjusting for marital status and income (OR = 1.45; CI 1.14-1.86). Attempted suicide was significantly associated with high impulsivity scores (means: 72.4 vs. 60.6, P < 0.0001) and high aggression scores (means: 38.5 vs. 26.1, P < 0.0001). Suicide attempters had a higher number of OP exposure symptoms than controls and scored higher on scales of impulsivity and aggression.

[Association between dopamine D4 receptor gene exon III 48bp VNTR polymorphism and temperament in school-aged children].

OBJECTIVE: To investigate the association between dopamine D4 receptor gene DRD4 exon III 48bp variable number of tandem repeat (VNTR) polymorphism and temperament in school-aged children. METHODS: Randomized cluster sampling was used to select 350 healthy children aged 8-12 years, and a questionnaire survey was performed. Oral epithelial samples were collected from half of these children. The complete questionnaire data of 164 children with a high level of DNA in oral epithelial samples were included in this study. PCR was used for the typing of DRD4 exon III 48bp VNTR, and the effect of this gene and its interaction with the environment on temperament was analyzed. RESULTS: Compared with the children with S-DRD4 genotype, the children with L-DRD4 genotype had significantly lower scores on the four dimensions of activity level, reaction intensity, emotion essence, and persistence (P<0.05). The main effects of mother's rejection/denial (OR=2.281, P<0.05) and sex (OR=2.766, P<0.05) and the interaction between sex and DRD4 exon III 48bp VNTR (OR=0.582, P<0.05) had an influence on activity level. The main effect of DRD4 exon III 48bp VNTR (OR=0.314, P<0.01) and the interaction between this gene and mother's rejection/denial (OR=1.872, P<0.01) had an influence on reaction intensity. The main effect of DRD4 exon III 48bp VNTR (OR=0.420, P<0.05) and mother's rejection/denial (OR=2.236, P<0.05) had an influence on persistence. CONCLUSIONS: DRD4 exon III 48bp VNTR and its interaction with other factors may affect the activity level and reaction intensity of school-aged children.

Multifunctional Metal-Organic Frameworks with Fluorescent Sensing and Selective Adsorption Properties.

Metal-organic frameworks (MOFs) have attracted great attention in the past years due to their diverse structures as well as interesting properties. However, MOFs with multifunctionality are still challenging. Under solvothermal conditions, reactions of 1,3,5-tris(1-imidazolyl)benzene (tib) and 4,4',4″-benzene-1,3,5-triyl-tribenzoic acid (H3BTB) with Cd(II) salt give rise to two novel MOFs [Cd3(tib)2(BTB)2]·3DEF·4.5H2O (1) and [Cd3(tib)2(BTB)2(DMA)2(H2O)2]·2DMA·8H2O (2) (DEF = N,N-diethylformamide, DMA = N,N-dimethylacetamide) with three-dimensional framework structures. It is fascinating that 1 and 2 not only show unique selectivity for detection of acetone through fluorescence quenching mechanism but also exhibit selective adsorption of gas (CO2 over N2 at 298 K) and dye (methyl orange) molecules.

EphB4/ephrinB2 Contributes to Imatinib Resistance in Chronic Myeloid Leukemia Involved in Cytoskeletal Proteins.

INTRODUCTION: The mechanism of EphB4/ephrinB2 in the resistance of chronic myelogenous leukemia to imatinib keeps unknown. METHODS: The imatinib resistant chronic myelogenous leukemia cell line-K562-R, was established. EphB4 receptor expression was detected in patients and resistant cells. Cell migration and drug sensitivity were tested in the EphB4 knockdown cells and mouse models. RESULTS: The EphB4 receptor was over-expressed in blast crisis patients compared to chronic phase patients. The level of EphB4 receptor expression was associated with a complete cytogenetic response within 12 months. Enhanced expression of the EphB4 receptor was detected in the K562-R cells. EphB4 knockdown inhibited cell migration ability and restored sensitivity to imatinib in vitro and in vivo. Restored sensitivity to imatinib was observed in K562-R cells, along with increased levels of phospho-EphB4 and decreased phosphorylation levels of RhoA, Rac1, and Cdc42. CONCLUSION: Our study illustrates that aberrant activation of EphB4/ephrinB2 may mediate chronic myeloid leukemia resistance involved in cytoskeletal proteins.

[Effects of rs4274224 polymorphisms in the DRD2 gene and family factors on the regularity based on the temperament in school-age children].

OBJECTIVE: To study the effects of rs4274224 polymorphisms in the DRD2 gene, family factors and their interaction on the regularity in school-age children. METHODS: The rs4274224 polymorphisms were genotyped using Sequenom Mass Array. The regularity was assessed based on the Middle Childhood Temperament Questionnaire (MCTQ). The parental rearing pattern was assessed with Egna Minnen av Bardnodnauppforstran (EMBU). The family function was assessed using Family Cohesion and Adaptability Scale (FACES II-CV). RESULTS: The regularity score in children with AA genotype of rs4274224 in the DRD2 gene was significantly lower than in those with GA/GG genotype (2.9±0.6 vs 3.1±0.7; P<0.05). The results of multiple regression analysis showed that the regularity was related to child gender, father's education level and family adaptability. The results of logistic regression analysis showed that the main factors influencing the regularity were family adaptability and its interaction with rs4274224 polymorphisms. The regularity was better in children with high family adaptability than in those with low family adaptability (OR=0.112, P<0.01). The children with AA genotype and low family adaptability were tend to be associated with low regularity (OR=21.554, P<0.01). CONCLUSIONS: The regularity based the temperament for school-age children might be influenced by family adaptability and its interaction with rs4274224 polymorphisms.

[Association between anxiety-depression and 5-HTTLPR gene polymorphism in school-aged twins].

OBJECTIVE: To investigate the association between anxiety-depression and 5-HTTLPR gene polymorphism in school-aged twins. METHODS: A total of 147 pairs of twins (47 pairs of monozygotic twins, 100 pairs of dizygotic twins) aged 8-12 years from Baotou and Hohhot were selected as respondents. The Achenbach Child Behavior Checklist (CBCL) was used to calculate the scores of anxiety-depression factors in school-aged twins. The DNA was extracted from oral epithelial cells, and polymerase chain reaction was applied for 5-HTTLPR genotyping. The generalized estimating equation (GEE) was used to analyze the effect of 5-HTTLPR polymorphism and family environment on anxiety-depression in school-aged twins. RESULTS: The children with LS and SS genotypes had significantly higher scores of anxiety-depression factors than those with LL genotype (χ2=3.938, P<0.05). The interaction of 5-HTTLPR genotype with family cohesion and family rearing patterns had a significant impact on the scores of anxiety-depression factors in twins (χ2=6.129 and 7.665, both P<0.05). CONCLUSIONS: 5-HTTLPR genotype is significantly correlated with the scores of anxiety-depression factors in school-aged twins. In the family with high cohesion and an autocratic family rearing pattern, S allele may increase the possibility of anxiety-depression in twin children.