Report of IRF2BP1 as a novel partner of RARA in variant acute promyelocytic leukemia.

IRF2BP1 breaked in the middle of exon 1 at the c.322 position and fused with RARA intron 2 which is located at 3717 bp upstream of its exon 3. The fusion produced a new intron by forming a paired splicing donor GT at 9 bp downstream of RARA breakpoint and acceptor AG at the 5' end of RARA exon 3. The IRF2BP1::RARA fusion gene leads a fusion transcript involving IRF2BP1 exon 1 and RARA exon 3, linked by a 9-bp fragment derived from RARA intron 2. The patient with IRF2BP1::RARA has same clinical features of APL.

Research progress of chlorogenic acid in improving inflammatory diseases. / ç»¿åŽŸé ¸æ”¹å–„ç‚Žç—‡æ€§ç–¾ç— çš„ç ”ç©¶è¿›å±•.

Long-term inflammation will develop into chronic inflammation and become inflammatory diseases. Antibiotics are commonly used in clinical practice to treat inflammatory diseases. But patients are prone to drug resistance. So we need to find new treatment. Chlorogenic acid is an organic compound extracted from honeysuckle and other plants. Its anti-inflammatory activity is strong, and it has a significant anti-inflammatory effect on inflammatory diseases in various systems. It has been shown that chlorogenic acid can regulate inflammation-related signaling pathways, such as nuclear factor κB (NF-κB) canonical signaling pathway, NF-κB atypical signaling pathway, nuclear factor-erythroid 2-related factor 2 (Nrf2) canonical signaling pathway, and Nrf2 atypical signaling pathway, etc. It can up-regulate the expression of anti-inflammatory cytokines such as interleukin (IL)-4, IL-10, IL-13 and down-regulate the expression of pro-inflammatory cytokine such as IL-1ß, IL-6, and IL-8. Although chlorogenic acid has a strong anti-inflammatory effect, but clinical trials and application still face many difficulties. In the future, the anti-inflammatory molecular mechanism of chlorogenic acid should be further studied to explore its clinical application value and improve new ideas for the treatment of inflammatory diseases.

Electric field induced intra-molecular self-redox: superalkali Li3N3Mg as a candidate for NLO molecular switches.

A novel intra-molecular self-redox switch, Li3N3Mg, is constructed theoretically. Our investigation showed that a suitably oriented external electric field (OEEF) can drive a long-range excess electron transfer from Mg atoms to Li3 rings. And subsequently, an interesting intra-molecular self-redox from Li32+N33-Mg+ to Li3+N33-Mg2+ accompanying the large different electronic static first hyperpolarizability (ß) is exhibited. The increase of the ß value constitutes an order of magnitude improvement from Li32+N33-Mg+ (34 986 a.u.) to Li3+N33-Mg2+ (101 225 a.u.), which indicates that Li3N3Mg is a good candidate for a self-redox NLO molecular switch.

Differential Metabolic Pathways and Metabolites in a C57BL/6J Mouse Model of Alcoholic Liver Disease.

BACKGROUND Alcoholic liver disease (ALD), an important cause of acute or chronic liver injury, results from binge drinking or long-term alcohol consumption. To date, there is no well-established mouse model with a comprehensive metabolic profile that mimics ALD in humans. This study aimed to explore the differential metabolic pathways and related differential metabolites in the liver of an ALD mouse model. MATERIAL AND METHODS A C57BL/6J mouse model of ALD was induced by alcohol feeding for 10 days plus binge alcohol feeding. The metabolomic profiles in the liver of the ALD mouse model was detected through ultra-high-pressure liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC/Q-TOF-MS). RESULTS A total 35 metabolites were significantly altered during the development of ALD. These metabolites were correlated to multiple metabolic pathways, including purine metabolism, the pentose phosphate pathway, cysteine and methionine metabolism, D-glutamine and D-glutamate metabolism, pyrimidine metabolism, and vitamin B6 metabolism. CONCLUSIONS The findings of the present study reveal potential biomarkers of ALD, and provide further insights into the pathogenesis of ALD.

LincRNA Cox-2 Regulates Lipopolysaccharide-Induced Inflammatory Response of Human Peritoneal Mesothelial Cells via Modulating miR-21/NF-κB Axis.

Postoperative peritoneal adhesion (PPA) is a common postoperative complication caused by any peritoneal inflammatory process. This study aimed to identify the biological function of large intergenic non-coding RNAs (lincRNAs) Cox-2 in the inflammation reaction of adhesion formation. The Cox-2 expression in peritoneal adhesion tissues and normal tissues was detected. The human peritoneal mesothelium cells (HPMCs) were treated with lipopolysaccharide (LPS) to induce inflammatory injury. The effect of Cox-2 suppression on cell viability, apoptosis and inflammatory factors of LPS induced HPMCs injury were explored. The regulatory correlation between Cox-2 and miR-21, as well as the targeted genes of miR-21 were identified. Meanwhile, the regulatory mechanism of Cox-2/miR-21 axis on NF-κB pathway was explored. It indicated that Cox-2 was highly expressed in peritoneal adhesion tissues compared with that in normal tissues. Suppression of Cox-2 ameliorated LPS induced HMPCs injury as cell viability was promoted, and cell apoptosis and the production of inflammatory factors were inhibited. And suppression of Cox-2 reversed the LPS induced HPMCs injury by regulation of miR-21 negatively. miR-21 was negatively correlated with TLR4, and TLR4 was predicted as target gene of miR-21. Furthermore, the suppression of miR-21 on LPS induced HPMCs injury was reversed by knockdown of TLR4, which could inhibited the activation of NF-κB pathway axis. It suggested that the effect of Cox-2 on LPS induced HPMCs injury was achieved by negatively regulation of miR-21 and targeted TLR4 through NF-κB pathway axis. The findings may provide a new insight into preventing postoperative peritoneal adhesion.

Silencing of Long Non-Coding RNA MALAT1 Promotes Apoptosis of Glioma Cells.

The metastasis-associated lung adenocarcinoma transcription 1 (MALAT1) is a highly conserved long non-coding RNA (lncRNA) gene. However, little is known about the pathological role of lncRNA MALAT1 in glioma. In the present study, we explored the expression level of lncRNA MALAT1 in primary glioma tissues as well as in U87 and U251 glioma cell lines. Using qRT-PCR, we found that the expression of lncRNA MALAT1 was significantly increased in glioma tissues compared with that of paracancerous tissues. Meanwhile, the expression of MALAT1 was highly expressed in U98 and U251 cells. In order to explore the function of MALAT1, the expression of MALAT1 was greatly reduced in U87 and U251 cells transfected with siRNA specifically targeting MALAT1. Consequently, cell viability of U87 and U251 cells were drastically decreased after the knockdown of MALAT1. Concomitantly, the apoptosis rate of the two cell lines was dramatically increased. Furthermore, the expression levels of some tumor markers were reduced after the knockdown of MALAT1, such as CCND1 and MYC. In summary, the current study indicated a promoting role of MALAT1 in the development of glioma cell.

The methylation of the PcMYB10 promoter is associated with green-skinned sport in Max Red Bartlett pear.

Varieties of the European pear (Pyrus communis) can produce trees with both red- and green-skinned fruits, such as the Max Red Bartlett (MRB) variety, although little is known about the mechanism behind this differential pigmentation. In this study, we investigated the pigmentation of MRB and its green-skinned sport (MRB-G). The results suggest that a reduction in anthocyanin concentration causes the MRB-G sport. Transcript levels of PcUFGT (for UDP-glucose:flavonoid 3-O-glucosyltransferase), the key structural gene in anthocyanin biosynthesis, paralleled the change of anthocyanin concentration in both MRB and MRB-G fruit. We cloned the PcMYB10 gene, a transcription factor associated with the promoter of PcUFGT. An investigation of the 2-kb region upstream of the ATG translation start site of PcMYB10 showed the regions -604 to -911 bp and -1,218 to -1,649 bp to be highly methylated. A comparison of the PcMYB10 promoter methylation level between the MRB and MRB-G forms indicated a correlation between hypermethylation and the green-skin phenotype. An Agrobacterium tumefaciens infiltration assay was conducted on young MRB fruits by using a plasmid constructed to silence endogenous PcMYB10 via DNA methylation. The infiltrated fruits showed blocked anthocyanin biosynthesis, higher methylation of the PcMYB10 promoter, and lower expression of PcMYB10 and PcUFGT. We suggest that the methylation level of PcMYB10 is associated with the formation of the green-skinned sport in the MRB pear. The potential mechanism behind the regulation of anthocyanin biosynthesis is discussed.

Disclosure of same-sex behavior by young Chinese migrant men: context and correlates.

The purpose of the study is to explore the disclosure of same-sex behavior by men who have sex with men (MSM) to different groups of people (i.e. family, friends, coworkers, and doctors) and the associated sociodemographic, behavioral, and psychosocial factors. A self-administered survey was conducted among 307 migrant MSM, aged 18-30, in Beijing in 2009. Most MSM disclosed their same-sex behavior to friends (69%), followed by family (25%), coworkers (25%), and doctors (24%). Factors associated with disclosure to friends included higher levels of perceived stigma, social capital and acculturation in Beijing, and suspecting partner to have a sexually transmitted disease (STD). Factors associated with disclosure to family included lower levels of internalized stigma, higher levels of acculturation in Beijing, and both risk and protective behavioral factors. MSM who disclosed to coworkers reported having worked in more cities, living with coworkers, and lower levels of social capital in Beijing. Disclosure to doctors was related to STD infection, sex partner, and sociodemographic factors. Results indicated that selective disclosure by MSM was situational and context-based. Future HIV/STD intervention needs to take into account factors relevant to their selective disclosure to different audiences.

The Correlation between Serum Vitamin D and Total IgE Levels and Chronic Spontaneous Urticaria among Chinese Population: A Retrospective Study.

Objective: This study aims to investigate the relationship between serum vitamin D, total IgE levels and chronic spontaneous urticaria (CSU). Methods: We collected data from 101 patients with chronic spontaneous urticaria (experimental group) and 115 healthy normal subjects (control group) in the same period of physical examination. Results: The results showed that the number of deficient and absolute deficient 25-hydroxyvitamin D in the experimental group was significantly lower than in the control group (P < 0.05). Pearson correlation analysis showed that the activity score of CSU patients was negatively correlated with serum vitamin D (r = -0.2278, P = 0.0220) and positively correlated with IgE (r = 0.2078, P = 0.0380). It was observed that serum vitamin D in CSU patients was negatively correlated with their activity (r = -0.2278, P = 0.0220) and positively correlated with age (r = 0.2675, P = 0.0069). The Point-biserial correlation analysis revealed that gender was positively correlated with serum vitamin D (Pearson correlation coefficient = 0.286, P = 0.004) and UAS score (Pearson correlation coefficient = 0.273, P = 0.006). Ordinal logistic regression analysis showed that only serum vitamin D was correlated to activity scores (P = 0.008). In addition to activity scores, age (P = 0.005) and gender (P = 0.04) were correlated to serum vitamin D. Conclusion: The activity score of CSU patients was negatively correlated with serum vitamin D and positively correlated with IgE. Serum vitamin D in CSU patients was negatively correlated with activity score and disease duration and positively correlated with age and gender.

Pyrosequencing analysis of bacterial community changes in dental unit waterlines after chlorogenic acid treatment.

Introduction: The contamination of dental unit waterlines (DUWLs) poses a significant risk of cross-infection in dentistry. Although chemical disinfectants have been effective in reducing number of bacteria, they do have limitations. Methods: This study aimed to investigate the potential of chlorogenic acid, a natural substance with broadspectrum antibacterial properties, for treating DUWLs. Over a period of three months, we analyzed the microbial communities in 149 DUWLs samples collected from 5 dental units using high-throughput pyrophosphate sequencing. Results: The results revealed that chlorogenic acid treatment had a significant impact on the microbial community profile in the DUWLs, with the most significant changes occurring within the first 15 days and stabilization observed in the last 30 days. The predominant genera detected in the samples were Bacteroides, Lactobacillus, Streptococcus, Methylobacterium, and Phreatobacter. Additionally, the relative abundance of certain beneficial bacteria, such as Alloprevotella, Roseburia, and Blautia, increased, while the presence of opportunistic pathogens like Mycobacteria significantly decreased. The functional prediction analysis using the KEGG database indicated a decrease in the pathogenicity of the bacterial community in the DUWLs following chlorogenic acid treatment. Discussion: This study introduces a novel approach for the prevention and treatment of infections associated with dental care.

Socio-demographic and behavioral correlates for HIV and syphilis infections among migrant men who have sex with men in Beijing, China.

Migrant men who have sex with men (MSM) may be particularly vulnerable to sexually transmitted infections (STIs) including HIV. This study examines the rates of HIV and syphilis infections and associated socio-demographic and behavioral factors among migrant MSM in China. Data from 307 migrant MSM were collected in Beijing, China. Blood specimens were collected to test for HIV and syphilis infections. HIV and syphilis rates were 5.9% and 20.2%, respectively. Multivariate logistic regression analyses showed that having ever been married, living a longer period in Beijing, having more sexual partners, and having a foreign MSM friend were significantly associated with HIV infection. Migrating from a rural area, experiencing one's sexual debut at an older age, having a male as first sexual partner, having more sexual partners, and being recruited from peer outreach and social network were associated with syphilis infection. Migrant MSM in China are at high risk for HIV and syphilis infections. HIV prevention programs targeting rural migrant MSM who have been married are needed.

Sex-Specific Association between Antioxidant Defense System and Therapeutic Response to Risperidone in Schizophrenia: A Prospective Longitudinal Study.

BACKGROUND: There are various differences in response to different antipsychotics and antioxidant defense systems (ADS) by sex. Previous studies have shown that several ADS enzymes are closely related to the treatment response of patients with antipsychotics-naïve first-episode (ANFE) schizophrenia. OBJECTIVE: Therefore, the main goal of this study was to assess the sex difference in the relationship between changes in ADS enzyme activities and risperidone response. METHODS: The plasma activities of glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and total antioxidant status (TAS) were measured in 218 patients and 125 healthy controls. Patients were treated with risperidone for 3 months, and we measured PANSS for psychopathological symptoms and ADS biomarkers at baseline and at the end of 3 months of treatment. We compared sex-specific group differences between 50 non-responders and 168 responders at baseline and at the end of the three months of treatment. RESULTS: We found that female patients responded better to risperidone treatment than male patients. At baseline and 3-month follow-up, there were no significant sex differences in TAS levels and three ADS enzyme activities. Interestingly, only in female patients, after 12 weeks of risperidone treatment, the GPx activity of responders was higher than that of non-responders. CONCLUSION: These results indicate that after treatment with risperidone, changes in GPx activity were associated with treatment response, suggesting that changes in GPx may be a predictor of response to risperidone treatment in female patients with ANFE schizophrenia.

A comparison of four sampling methods among men having sex with men in China: implications for HIV/STD surveillance and prevention.

Sample representativeness remains one of the challenges in effective HIV/STD surveillance and prevention targeting men who have sex with men (MSM) worldwide. Although convenience samples are widely used in studies of MSM, previous studies suggested that these samples might not be representative of the broader MSM population. This issue becomes even more critical in many developing countries where needed resources for conducting probability sampling are limited. We examined variations in HIV and Syphilis infections and sociodemographic and behavioral factors among 307 young migrant MSM recruited using four different convenience sampling methods (peer outreach, informal social network, Internet, and venue-based) in Beijing, China in 2009. The participants completed a self-administered survey and provided blood specimens for HIV/STD testing. Among the four MSM samples using different recruitment methods, rates of HIV infections were 5.1%, 5.8%, 7.8%, and 3.4%; rates of Syphilis infection were 21.8%, 36.2%, 11.8%, and 13.8%; and rates of inconsistent condom use were 57%, 52%, 58%, and 38%. Significant differences were found in various sociodemographic characteristics (e.g., age, migration history, education, income, and places of employment) and risk behaviors (e.g., age at first sex, number of sex partners, involvement in commercial sex, and substance use) among samples recruited by different sampling methods. The results confirmed the challenges of obtaining representative MSM samples and underscored the importance of using multiple sampling methods to reach MSM from diverse backgrounds and in different social segments and to improve the representativeness of the MSM samples when the use of probability sampling approach is not feasible.

A Comparative Transcriptome Between Anti-drug Sensitive and Resistant Candida auris in China.

Candida auris emerged as a pathogenic species of fungus that causes severe and invasive outbreaks worldwide. The fungus exhibits high intrinsic resistance rates to various first-line antifungals, and the underlying molecular mechanism responsible for its multidrug resistance is still unclear. In this study, a transcriptomic analysis was performed between two C. auris isolates that exhibited different anti-drug patterns by RNA-sequencing, namely, CX1 (anti-drug sensitive) and CX2 (resistant). Transcriptomic analysis results revealed 541 upregulated and 453 downregulated genes in the resistant C. auris strain compared with the susceptible strain. In addition, our findings highlight the presence of potential differentially expressed genes (DEGs), which may play a role in drug resistance, including genes involved in ergosterol and efflux pump biosynthesis such as SNQ2, CDR4, ARB1, MDR1, MRR1, and ERG genes. We also found that Hsp related genes were upregulated for expression in the anti-drug-resistant strain. Biofilm formation and growth conditions were also compared between the two isolates. Our study provides novel clues for future studies in terms of understanding multidrug resistance mechanisms of C. auris strains.

Absence of MHC class â ¡ molecules promotes natural killer cells activation in mice.

The development and immune recognition of natural killer (NK) cell are regulated critically by major histocompatibility complex (MHC) class I molecules. However, it remains unclear whether the function of NK cells is regulated by MHC class II molecules. To test this, we monitored the development, phenotype and function of NK cells by using MHC class II deficient (H2-/-) mice. The numbers and development of NK cells keep unaltered in H2-/- mice, compared with those in wide type (H2+/+) mice. A part of Ly49 family receptors on NK cells are down-regulated both in mRNA and protein expression in absence of MHC class II molecules. Furthermore, NK cells obtained from H2-/- mice exhibit more expression of CD69 and IFN-γ after cross-linking with NK1.1. Also, the cytotoxicity against tumor cell lines of NK cells from H2-/- mice was increased significantly. Taken together, our study indicates that the absence of MHC class II molecules promotes the activation and function of NK cells in mice.

A 14 nucleotide deletion mutation in the coding region of the PpBBX24 gene is associated with the red skin of "Zaosu Red" pear (Pyrus pyrifolia White Pear Group): a deletion in the PpBBX24 gene is associated with the red skin of pear.

Red skin is an important quality trait for pear fruits and is determined by the concentration and composition of anthocyanins. The regulatory mechanism underlying anthocyanin accumulation is a popular topic in fruit research. Red mutants are ideal materials for studying the molecular mechanism of color diversity in pear. Although several red pear mutants have been cultivated and are in production, no exact locus containing the responsible genetic mutation has been identified. In this study, by combining the bulked segregant analysis with whole-genome sequencing, we identified a 14 nucleotide deletion mutation in the coding region of the PpBBX24 gene from the red pear mutant "Zaosu Red". We further verified that the deletion was present only in the red mutant of "Zaosu" and in its red offspring, which was different from that which occurred in other red pear fruits. This deletion results in a coding frame shift such that there is an early termination of the PpBBX24 gene and loss of key NLS and VP domains from PpBBX24. The lost domains may reduce or alter the normal function of PpBBX24. In addition, we found that the transcript levels of the PpMYB10 and PpHY5 genes in red samples were significantly higher than those in green samples, whereas the results for the normal-type PpBBX24 gene were the opposite. We ultimately revealed that the 14 nucleotide deletion mutation in the coding region of the PpBBX24 gene is associated with the red skin of the "Zaosu Red" pear. This finding of somatic mutational events will be helpful for breeding new red pear cultivars and for understanding the regulatory mechanisms involved in pear skin pigmentation.

NK cells contribute to hepatic CD8+ T cell failure in hepatitis B virus-carrier mice after alcohol consumption.

Despite the fact that both Hepatitis B virus (HBV) infection and excessive alcohol consumption represent health problems worldwide, the mechanism by which alcohol affected the progression of HBV-associated liver disease are not completely understood. Therefore, we studied how alcohol affects the development of HBV infection and the role of T cells and NK cells in the antiviral response. Mononuclear cells (MNCs) derived from HBV-carrier mice and wild type (WT) mice were characterized for phenotype by flow cytometry, HBV antigen and gene expression were detected by Radio Immunoassay (RIA), immunohistochemistry and quantitative real-time (qRT)-PCR. Metabolomics changes were detected in mice liver tissue based on ultra high performance liquid tandem chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOFMS). The mice after ethanol consumption shows higher levels of HBV surface Ag (HBsAg), HBV core antigen (HBcAg) and HBV 3.5 kb RNA expression, and a lower level of CD8+ T cells during HBV persistence, with an increased lymphocyte activation gene-3 (LAG-3) expression on CD8+ T cell. In addition, the energy metabolism was downregulated and the oxidative stress was upregulated in the liver tissue. Furthermore, NK cells depletion results in a lower levels of HBV surface Ag (HBsAg) and HBV 3.5 kb RNA expression, and a higher level of CD8+ T cells with reduced expression of LAG-3. In conclusion, alcohol abuse induces CD8+ T cells failure after acute HBV infection, but depletion of NK cells could retore CD8+ T cell activity. Moreover, downregulation of energy metabolism and upregulation of oxidative stress may also contribute to CD8+ T cell failure.

A de novo genome assembly of the dwarfing pear rootstock Zhongai 1.

'Zhongai 1' [(Pyrus ussuriensis × communis) × spp.] is an excellent pear dwarfing rootstock common in China. It is dwarf itself and has high dwarfing efficiency on most of main Pyrus cultivated species when used as inter-stock. Here we describe the draft genome sequences of 'Zhongai 1' which was assembled using PacBio long reads, Illumina short reads and Hi-C technology. We estimated the genome size is approximately 511.33 Mb by K-mer analysis and obtained a final genome of 510.59 Mb with a contig N50 size of 1.28 Mb. Next, 506.31 Mb (99.16%) of contigs were clustered into 17 chromosomes with a scaffold N50 size of 23.45 Mb. We further predicted 309.86 Mb (60.68%) of repetitive sequences and 43,120 protein-coding genes. The assembled genome will be a valuable resource and reference for future pear breeding, genetic improvement, and comparative genomics among related species. Moreover, it will help identify genes involved in dwarfism, early flowering, stress tolerance, and commercially desirable fruit characteristics.

Aged human cells rejuvenated by cytokine enhancement of biomaterials for surgical ventricular restoration.

OBJECTIVES: This study investigated whether cytokine enhancement of a biodegradable patch could restore cardiac function after surgical ventricular restoration (SVR) even when seeded with cells from old donors. BACKGROUND: SVR can partially restore heart size and improve function late after an extensive anterior myocardial infarction. However, 2 limitations include the stiff synthetic patch used and the limited healing of the infarct scar in aged patients. METHODS: We covalently immobilized 2 proangiogenic cytokines (vascular endothelial growth factor and basic fibroblast growth factor) onto porous collagen scaffolds. We seeded human mesenchymal stromal cells from young (50.0 ± 8.0 years, N = 4) or old (74.5 ± 7.4 years, N = 4) donors into the scaffolds, with or without growth factors. The patches were characterized and used for SVR in a rat model of myocardial infarction. Cardiac function was assessed. RESULTS: In vitro results showed that cells from old donors grew slower in the scaffolds. However, the presence of cytokines modulated the aging-related p16 gene and enhanced cell proliferation, converting the old cell phenotype to a young phenotype. In vivo studies showed that 28 days after SVR, patches seeded with cells from old donors did not induce functional recovery as well as patches seeded with young cells. However, cytokine-enhanced patches seeded with old cells exhibited preserved patch area, prolonged cell survival, and augmented angiogenesis, and rats implanted with these patches had better cardiac function. The patch became an elastic tissue, and the old cells were rejuvenated. CONCLUSIONS: This sustained-release, cytokine-conjugated system provides a promising platform for engineering myocardial tissue for aged patients with heart failure.