[Synergistic effect of azacitidine with homoharringtonine by activating the c-MYC/DDIT3/PUMA axis in acute myeloid leukemia].

Objective: This study aimed to explore the synergistic effect and underlying mechanism of azacitidine (AZA) in combination with homoharringtonine (HHT) in acute myeloid leukemia (AML) . Methods: The synergistic effects of AZA and HHT were examined by cell proliferation, apoptosis, and colony formation assays. The synergistic effects were calculated using the combination index (CI) , and the underlying mechanisms were explored using RNA sequencing, pathway inhibitors, and gene knockdown approaches. Results: Compared with the single-drug controls, AZA and HHT combination significantly induced cell proliferation arrest and showed a synergistic effect with CI < 0.9 in AML cells. In the combination group versus the single-drug controls, colony formation was significantly decreased, whereas apoptosis was significantly increased in U937 (P<0.001) and MV4-11 (P<0.001) cells. AZA and HHT combination activated the integrated stress response (ISR) signaling pathway and induced DDIT3-PUMA-dependent apoptosis in cells. Furthermore, it remarkably downregulated the expression of c-MYC. The combination also activated c-MYC/DDIT3/PUMA-mediated ISR signaling to induce synergy on apoptosis. The synergy of AZA+HHT on apoptosis was induced by activating c-MYC/DDIT3/PUMA-mediated ISR signaling. Conclusion: The combination of AZA and HHT exerts synergistic anti-AML effects by inhibiting cellular proliferation and promoting apoptosis through activation of the ISR signaling pathway via the c-MYC/DDIT3/PUMA axis.

[Expression and clinical significance of COL1A1 and COL1A2 genes in malignant pleural mesothelioma tissues].

Objective: To investigate the expression levels and clinical significance of collagen typeⅠ α1 chain (COL1A1) and collagen type Ⅰ α2 chain (COL1A2) in malignant pleural mesothelioma (MPM) tissues. Methods: In January 2020, MPM tissues and adjacent normal pleural tissues were collected from 26 MPM patients, and the expression levels of COL1A1 and COL1A2 genes in the tissues were determined by quantitative reverse transcription PCR, and the efficacy of both levels in diagnosing MPM was assessed using receiver operating characteristic (ROC) curves. The relationship between COL1A1 and COL1A2 gene expression and clinicopathological features was analyzed by the Cancer Genome Atlas (TCGA) database, and the relationship between the expression levels of both and overall survival (OS) and disease-free progression survival (DFS) of MPM patients was dynamically analyzed by gene expression profiling, and the factors affecting the prognosis of MPM patients were explored by Cox proportional risk regression model. The TIMER 2.0 platform was used to explore the relationship between COL1A1 and COL1A2 gene expression in MPM and tumor immune infiltrative cells. Results: Compared with normal pleural tissues, the expression of COL1A1 and COL1A2 genes was significantly increased in MPM tissues (P<0.01) , and their expression was positively correlated (P<0.001) . The ROC curves showed that the area under the curve for COL1A1 and COL1A2 expression levels diagnostic of MPM was 0.900 and 0.897, respectively. The expression of COL1A1 gene was correlated with tumor type in MPM patients (P<0.05) , and COL1A2 gene expression was correlated with T stage in MPM patients (P<0.05) . Both COL1A1 and COL1A2 gene expression were associated with OS in MPM patients (Logrank P<0.05) , but there was no significant correlation with DFS (Logrank P>0.05) . Cox multivariate analysis showed that patients with high COL1A1 and COL1A2 gene expression and biphasic mixed MPM had a higher risk of death (P<0.05) . TIMER 2.0 platform analysis showed that COL1A1 and COL1A2 gene expression in MPM patients was positively correlated with macrophages, COL1A2 gene expression in MPM was negatively correlated with neutrophils (P<0.05) . Conclusion: High expression of COL1A1 and COL1A2 genes in MPM tissues is valuable for diagnosis, disease prediction and prognostic assessment of MPM, and both may jointly contribute to the development of MPM.

Effects of Mindfulness-Based Tai Chi Chuan on Physical Performance and Cognitive Function among Cognitive Frailty Older Adults: A Six-Month Follow-Up of a Randomized Controlled Trial.

OBJECTIVE: To assess the effectiveness of a mindfulness-based Tai Chi Chuan on physical performance and cognitive function among cognitive frailty older adults. DESIGN: A single-blind,three-arm randomized controlled trial. SETTING: Three communities in Daqing, China. PARTICIPANTS: The study sample comprised 93 men and women aged 65 years or older who were able to walk more than 10 m without helping tools, scored 0.5 on Clinical Dementia Rating (CDR) and absence of concurrent dementia, identified pre-frailty (scored 1-2 on Fried Frailty Criteria) and frailty older adults (scored 3-5 on Fried Frailty Criteria). INTERVENTION: Subjects were randomly allocated to three groups: Group1, which received mindfulness intervention (formal and informal mindfulness practices); Group 2, which received Tai-Chi Chuan intervention; Group 3, which received MTCC intervention. MEASUREMENTS: The primary outcomes was cognitive frailty rate(measured by Fried Frailty Criteria and Clinical Dementia Rating-CDR) , the secondary outcome were cognitive function (measured by Min-Mental State Examination-MMES) and physical level (measured by Short physical performance battery- SPPB, Timed up and Go test-TUG and the 30-second Chair test). They were all assessed at Time 1-baseline, Time 2-after the end of 6-month intervention and the follow up (Time 3-half year after the end of 6-month intervention). RESULTS: The baseline characteristics did not differ among the groups.Improvements in the cognitive function (MMES), physical performance (SPPB, TUG, 30-second Chair test) were significantly difference between time-group interaction (p<.05). The rate of CF was significantly different among groups at 6-month follow-up period (χ2=6.37, p<.05). A lower prevalence of frailty and better cognitive function and physical performance were found in the Group 3 compared with other two groups at the follow-up period (p<.05). CONCLUSIONS: MTCC seems to be effectively reverse CF, improving the cognitive and physical function among older adults, suggesting that MTCC is a preferably intervention option in community older adults with cognitive frailty.

[Prevalence of human soil-borne nematode infections in Yunnan Province: a cross-sectional study in 2015].

OBJECTIVE: To investigate the current prevalence of human soil-borne nematode infections in Yunnan province, so as to provide the scientific evidence for formulating the soil-borne nematodiasis control strategy in the province. METHODS: In 2015, a total of 20 survey sites were sampled in 10 counties (cities) of Yunnan Province using the stratified cluster random sampling method. Stool samples were collected from all local permanent residents at ages of one year and older in each survey site, and the soil-borne nematode eggs were identified using the modified Kato-Katz technique and the egg number was counted. In addition, the hookworm species was identified using the filter-paperculture method, and Enterobius vermicularis eggs were detected using the cellophane tape method in children at ages of 3 to 6 years. RESULTS: A total of 5 067 residents received stool examinations, and 950 residents were detected with soil-borne nematode infections, with an overall prevalence rate of 18.75%. The prevalence of Ascaris lumbricoides, Trichuris trichura and hookworm was 7.52%, 8.47% and 9.02%, respectively. Among 446 children detected using the cellophane tape method, 5 children were detected with E. vermicularis infections. Among the 160 residents with hookworm infections, there were 139 residents with Necator americanus infections (86.88%), 16 with A. duodenale infections (10.00%) and 5 with mixed infections (3.12%). Mild A. lumbricoides (67.98%, 259/381), T. trichura (88.58%, 380/429) and hookworm infections (94.53%, 432/457) were predominant. Among the four ecological zones, the highest prevalence of human soilborne nematode infections was found in the East Tibet-South Sichuan Ecological Zone (31.79%), and among the 10 survey counties (cities), the greatest prevalence was seen in Gongshan Derung and Nu Autonomous County (50.13%), while the lowest prevalence was found in Ninglang Yi Autonomous County (0.40%). The prevalence of human soil-borne nematode infections was 5.67% (43/759), 26.67% (610/2 287) and 14.70% (297/2 021) in high-, moderate- and low-economic-level regions, respectively. There were no significant differences in the prevalence of human soil-borne nematode infections in terms of ecological regions, survey counties (cities) or economic development levels (χ2 = 342.20, 814.60 and 201.34, all P < 0.05). There was no significantdifference in the prevalence of human soil-borne nematode infections between male (18.21%, 441/2 422) and female residents (19.24%, 509/2 645) (χ2 = 0.89, P > 0.05), and soil-borne nematode infections were detected in residents at all age groups, with the greatest prevalence found in residents at ages of 1 to 9 years (25.88%). In addition, the highest prevalence of soil-borne nematode infections was seen in residents with the Dulong Ethnic Minority (82.09%), in preschool children (25.06%) and in illiterate residents (24.80%), and there was no age-, ethnicity-, occupation- or education level-specific prevalence of soil-borne nematode infections detected (χ2 = 46.50, 1 016.96, 36.33 and 52.43, all P < 0.05). CONCLUSIONS: The prevalence of human soil-borne nematode infections remains high in Yunnan Province. The management of soil-borne nematodiasis requires to be reinforced among low-age children, farmers, old people and residents with low educations levels or ethnic groups.

Macrophage migration inhibitory factor promotes renal injury induced by ischemic reperfusion.

Macrophage migration inhibitory factor (MIF) is pleiotropic cytokine that has multiple effects in many inflammatory and immune diseases. This study reveals a potential role of MIF in acute kidney injury (AKI) in patients and in kidney ischemic reperfusion injury (IRI) mouse model in MIF wild-type (WT) and MIF knockout (KO) mice. Clinically, plasma and urinary MIF levels were largely elevated at the onset of AKI, declined to normal levels when AKI was resolved and correlated tightly with serum creatinine independent of disease causes. Experimentally, MIF levels in plasma and urine were rapidly elevated after IRI-AKI and associated with the elevation of serum creatinine and the severity of tubular necrosis, which were suppressed in MIF KO mice. It was possible that MIF may mediate AKI via CD74/TLR4-NF-κB signalling as mice lacking MIF were protected from AKI by largely suppressing CD74/TLR-4-NF-κB associated renal inflammation, including the expression of MCP-1, TNF-α, IL-1ß, IL-6, iNOS, CXCL15(IL-8 in human) and infiltration of macrophages, neutrophil, and T cells. In conclusion, our study suggests that MIF may be pathogenic in AKI and levels of plasma and urinary MIF may correlate with the progression and regression of AKI.

Oncolytic Viruses for Tumor Precision Imaging and Radiotherapy.

In 2003 in China, Peng et al. invented the recombinant adenovirus expressing p53 (Gendicine) for clinical tumor virotherapy. This was the first clinically approved gene therapy and tumor virotherapy drug in the world. An oncolytic herpes simplex virus expressing granulocyte-macrophage colony-stimulating factor (Talimogene laherparepvec) was approved for melanoma treatment in the United States in 2015. Since then, oncolytic viruses have been attracting more and more attention in the field of oncology, and may become novel significant modalities of tumor precision imaging and radiotherapy after further improvement. Oncolytic viruses carrying reporter genes can replicate and express genes of interest selectively in tumor cells, thus improving in vivo noninvasive precision molecular imaging and radiotherapy. Here, the latest developments and molecular mechanisms of tumor imaging and radiotherapy using oncolytic viruses are reviewed, and perspectives are given for further research. Various types of tumors are discussed, and special attention is paid to gastrointestinal tumors.

Symmetry breaking induced excitations of dark plasmonic modes in multilayer graphene ribbons.

Multilayer graphene can support multiple plasmon bands. If structured into graphene ribbons, they can support multiple localized plasmonic modes with interesting optical properties. However, not all such plasmonic modes can be excited directly due to the constrains of the structural symmetry. We show by numerical simulations that by breaking the symmetry all plasmonic modes can be excited. We discuss the general principles and properties of two-layer graphene ribbons and then extend to multilayer graphene ribbons. In multilayer graphene ribbons with different ribbon widths, a tunable broadband absorption can be attained due to the excitations of all plasmonic modes. Our results suggest that these symmetry-broken multilayer graphene ribbons could offer more degrees of freedom in designing photonic devices.

Measurement of serum estrogen and estrogen metabolites in pre- and postmenopausal women with osteoarthritis using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry

Although 17β-estradiol (E2) deficiency has been linked to the development of osteoarthritis (OA) in middle-aged women, there are few studies relating other estrogens and estrogen metabolites (EMs) to this condition. We developed a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method to measure the levels of six EMs (i.e., estrone, E2, estriol, 2-hydroxyestrone, 2-hydroxyestradiol, and 16a-hydroxyestrone) in healthy pre- and postmenopausal women and women with OA. This method had a precision ranging from 1.1 to 3.1% and a detection limit ranging from 10 to 15 pg. Compared to healthy women, serum-free E2 was lower in the luteal and postmenopausal phases in women with OA, and total serum E2 was lower in postmenopausal women with OA. Moreover, compared to healthy women, total serum 2-hydroxyestradiol was higher in postmenopausal women with OA and total serum 2-hydroxyestrone was lower in both the luteal and follicular phases in women with OA. In conclusion, our HPLC-ESI-MS/MS method allowed the measurement of multiple biochemical targets in a single assay, and, given its increased cost-effectiveness, simplicity, and speed relative to previous methods, this method is suitable for clinical studies.

Measurement of serum estrogen and estrogen metabolites in pre- and postmenopausal women with osteoarthritis using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.

Although 17ß-estradiol (E2) deficiency has been linked to the development of osteoarthritis (OA) in middle-aged women, there are few studies relating other estrogens and estrogen metabolites (EMs) to this condition. We developed a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method to measure the levels of six EMs (i.e., estrone, E2, estriol, 2-hydroxyestrone, 2-hydroxyestradiol, and 16a-hydroxyestrone) in healthy pre- and postmenopausal women and women with OA. This method had a precision ranging from 1.1 to 3.1% and a detection limit ranging from 10 to 15 pg. Compared to healthy women, serum-free E2 was lower in the luteal and postmenopausal phases in women with OA, and total serum E2 was lower in postmenopausal women with OA. Moreover, compared to healthy women, total serum 2-hydroxyestradiol was higher in postmenopausal women with OA and total serum 2-hydroxyestrone was lower in both the luteal and follicular phases in women with OA. In conclusion, our HPLC-ESI-MS/MS method allowed the measurement of multiple biochemical targets in a single assay, and, given its increased cost-effectiveness, simplicity, and speed relative to previous methods, this method is suitable for clinical studies.

Spontaneous emission modulation of colloidal quantum dots via efficient coupling with hybrid plasmonic photonic crystal.

The spontaneous emission of colloidal CdSe/ZnS quantum dots (CQDs) modified by the hybrid plasmonic-photonic crystal is reported in this paper. By using a spin coater, the spatial overlap between CQDs and the surface resonance modes in this quasi-2D crystal slab is achieved. In this case, the coupling efficiency of them is enhanced greatly and most excited CQDs radiate through the surface modes. Consequently, despite the low refractive index contrast of our hybrid structure, the directionality of spontaneous emission, increased radiative probability and narrowed full width at half maximum of emission peak are all clearly observed by our home-made microscopic angle-resolved spectroscopy and time-resolved photoluminescence system. Our results manifest that the quasi-2D hybrid plasmonic-photonic crystal is an ideal candidate to tailor the radiative properties of CdSe/ZnS CQDs, which might be significant for the applications of light emitting devices.

Optical response of a disordered bicontinuous macroporous structure in the longhorn beetle Sphingnotus mirabilis.

We studied the structural and optical properties of scales in the longhorn beetle Sphingnotus mirabilis. Structural characterizations revealed that the scale interior possesses a disordered bicontinuous macroporous structure, resembling a phase-separated structure obtained by spinodal decomposition. Its optical response was investigated both experimentally and theoretically. Our results show that this structure has interesting optical properties due to the existence of only short-range order and the lack of well-defined local structures.

Structural coloration and photonic pseudogap in natural random close-packing photonic structures.

Scales on the elytra of longhorn beetle Anoplophora graafi display diverse non-iridescent colors ranging from blue, green, yellow, and red to purple. By structural characterizations, optical measurements, and theoretical calculations, we found that the scale colors stem from an amorphous photonic structure possessing only short-range order: random close-packing of chitin nanoparticles. Our results showed that direction-independent photonic pseudogaps found in the photon density of states of the random close-packing photonic structure are the ultimate physical origin for non-iridescent coloration of scales. The color steering strategy of scales is ingenious, simply by varying the size of chitin nanoparticles. Revealed natural random close-packing photonic structures and the color steering strategy of scales could render valuable inspiration for the artificial fabrication and design of photonic structures and devices as well.

Dynamic modulation of cytoskeleton during in vitro maturation in human oocytes.

OBJECTIVE: To investigate the role of cytoskeleton in several important dynamic events during in vitro maturation of human oocytes. STUDY DESIGN: Human germinal vesicle stage oocytes were divided randomly into control and study groups. After cultured for 24 hours, chromatin state and position, spindle formation and migration, cortical granules, and mitochondria distribution were evaluated. RESULTS: In colchicine group, spindles did not form. Cortical granules migrated to the cortex but mitochondria maintained the peripheral distribution pattern in most of the oocytes. In cytochalasin B group, the migration of spindle and chromosomes to the cortex was prohibited. Microfilaments disruption influenced cortical granules migration but not redistribution of mitochondria. CONCLUSION: Meiosis progression could not go beyond metaphase I stage when microtubule or microfilament polymerization was prohibited in human oocytes. The migration of cortical granules to the cortex and redistribution of mitochondria to the inner cytoplasm were mediated by microfilaments and microtubules, respectively.

Structural color change in longhorn beetles Tmesisternus isabellae.

The elytra of longhorn beetles Tmesisternus isabellae show iridescent golden coloration which stems from long and flat scales imbricated densely on the elytral surface. The scales are able to change coloration from golden in the dry state to red in the wet state with water absorption. Structural characterizations revealed that the iridescent coloration of scales originates from a multilayer in the scale interior. Measurements on both water contact angle and chemical composition indicated that scales are hydrophilic. The change in scale coloration to red in the wet state is due to both the swelling of the multilayer period and water infiltration. The unraveled structural color change and its strategy may not only help us get insight into the biological functionality of structural coloration but also inspire the designs of artificial photonic devices.

Detection and distribution of rotavirus in municipal sewage treatment plants (STPs) and surface water in Beijing.

The aim of this study was to survey on the presence and distribution of rotavirus in sewage treatment plants (STPs) and surface water samples in Beijing. Also, the rotavirus removal efficacies of wastewater treatment processes in three STPs were discussed. SiO2 was used to concentrate rotavirus particles from environmental water samples. A reverse transcriptase-nested polymerase chain reaction (RT-nested PCR) method was used for detection of rotavirus. Rotavirus could be detected from almost all samples collected from STP waters (10/10 influents, 100%; 10/10 secondary effluents, 100%; 9/10 reclaimed effluents, 90%) and river waters (14/14 samples, 100%), and from some lake waters (37/45 samples, 82.2%), canal waters (7/22 samples, 31.8%), as well as wetland waters near drinking water resource (5/26 samples, 19.2%). Our results showed that rotaviruses were widely distributed in different types of waters in Beijing during sampling period. Sewage treatment processes in STPs were not efficient to eliminate rotavirus, which may lead to its spread to surface waters from August to January. This study highlights the interest to detect rotaviruses from water samples in big cities, where many gastroenteritis outbreaks occur each year in China and the results necessitate the further study on monitoring rotavirus in source drinking water.

Expression and characterization of Gag protein of HIV-1(CN) in Pichia pastoris.

To express the core protein of HIV-1 of Chinese prevalent strain (HIV-1(CN)) in Pichia pastoris, the full-length gag gene was inserted into the secretory expression vector pHILS1. Linearized recombinant plasmid pHILGAG by SalI was electrotransformed into the yeast strain GS115, and the yeast transformants were identified by PCR. To induce the interest protein to be expressed, the PCR positive transformants were inoculated in the medium of BMGY and BMMY, mRNA of the strain was detected by RT-PCR, and the expressed protein was analyzed by SDS-PAGE, Western blotting and thin layer scanning. mRNA (1.3kb) was amplified by RT-PCR. SDS-PAGE and Western blotting analysis showed that the molecular mass of the expressed protein was 55kDa, which was similar to the expected value, and the expressed protein could react with McAb to HIV-1 p24. Thin layer scanning analysis demonstrated that the whole amount of the expressed protein was approximately 13% of the soluble protein in the supernatant. The recombinant yeast had good genetic stability. The optimal expression conditions of the engineering yeast were as follows: BMMY medium, 80-90% of dissolved oxygen, 1% methanol, and 3-day-cultivation course. Gag proteins were expressed under the optimal expression condition and purified via gel filtration chromatography. The purity of the interest protein was up to 85%. After the purified proteins were inoculated into BALB/c mice, the anti-HIV-1 antibodies in the immunized mice could be detected by Western blotting.

A novel carrier molecule for high-level expression of peptide antibiotics in Escherichia coli.

Peptide antibiotics are often hard to express in engineered bacteria at high level. According to the properties of peptide antibiotics, a heterologous protein PaP3.30, encoded by ORF30 of Pseudomonas aeruginosa bacteriophage PaP3, was selected as a carrier molecule. The gene of the carrier molecule was constructed into the plasmid pQE-32 to give rise to the vector pQE-PaP30 for expression of peptide antibiotics in Escherichia coli. A his-tagged fusion protein was genetically constructed with a peptide antibiotic at its carboxy terminus. The novel carrier molecule was used for high-level expression of six peptide antibiotics with different sizes and isoelectric points in E. coli, which are hPAB-beta, MSI-78, Melletin, hBD-1, Cecropin A, and an ovine anion peptide. And further, one of six peptide antibiotics, hPAB-beta (an analog of a human peptide antibiotic), was taken as an example for studies of recovery of interesting products from the fusion partner, purification and antimicrobial activity evaluation. The results indicated that the expressed fusion protein existed as an inclusion body in the cytoplasm and the expression amounts of six peptide antibiotic fusions are all higher than 34% of the total cell protein. The expression products could be easily purified by Ni-NTA chromatography. Cyanogen bromide was used to cut at the methionine linker between the carrier and hPAB-beta peptide. hPAB-beta was recovered from the fusion partner and purified to homogeneity with High S cation-exchange and Bio-gel P6 gel chromatography. The bactericidal activities of the purified recombinant hPAB-beta against P. aeruginosa are 31-64 microg/ml, and against Staphylococcus aureus are > or = 128 microg/ml, being comparable to that of the chemical synthesis peptide. These results show that the carrier molecule can result in high-level expression of peptide antibiotics, and expression products can be easily recovered from their fusion partner and retain their bioactivity.

Changes in Hydration Properties of Silica Gel in a Process of Its Carbonization by Pyrolysis of Acetylacetone Zn (Ti) Acetylacetonates.

Changes in hydration properties of different compounds in a process of formation of a complex adsorbent comprising carbon and TiO2 or Zn2SiO4 on its surface were studied by 1H NMR spectroscopy under conditions of a liquid phase freezing. Adsorbents were synthesized on the basis of a mesoporous silica gel, the surface of which was covered with a carbon layer formed in a process of a high temperature pyrolysis of acetylacetone. Titanium oxide and zinc silicate on the surface of a parent silica gel were formed by a pyrolysis of acetylacetonates of the corresponding metals. It has been revealed that the main types of surface-active sites for the adsorbed water molecules on the carbosil surface are the systems of condensed benzene nuclei of a carbon component of the surface and hydroxyl groups of silica surface. Zn2SiO4 and TiO2 have been formed in a process of pyrolysis of the corresponding metal acetylacetonates. Water bound with the oxide component of the carbosil surface exceeds 80% of the total amount of the adsorbed water. The carbon component of the surface is localized mainly in the narrowest pores. A minimum value in the free surface energy was recorded for the carbosil sample. Copyright 1998 Academic Press.

[Determination of glycosylated hemoglobin in human erythrocytes by fast protein liquid chromatography system].

The chromatography method for analysis of glycosylated hemoglobin(HbA1c) in human erythocytes was established by using a fast protein liquid chromatography system(FPLC) and a Mono S column. The average intrabatch and interbatch coefficients of variations (n = 3) were 2.5% and 4.8%, respectively. There was a positive correlation between the results of FPLC and routine microcolumn method (r = 0.413, P < 0.02). Using FPLC method, the HbA1c levels in festing blood of 54 normal donors and 26 diabetics on admission were 4.6 +/- 1.19(%) and 10.2 +/- 3.45(%), respectively. A significant difference was found statistically between the results of two groups (t = 10.8, P < 0.01).