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DNA in eukaryotic genomes is under constant assault from both exogenous and endogenous sources, leading to DNA damage, which is considered a major molecular driver of ageing. Fortunately, the genome and the central exome are safeguarded against these attacks by abundant peripheral non-coding DNA. Non-coding DNA codes for small non-coding RNAs that inactivate foreign nucleic acids in the cytoplasm and physically blocks these attacks in the nucleus. Damage to non-coding DNA produced during such blockage is removed in the form of extrachromosomal circular DNA (eccDNA) through nucleic pore complexes. Consequently, non-coding DNA serves as a line of defence for the exome against DNA damage. The total amount of non-coding DNA/heterochromatin declines with age, resulting in a decrease in both physical blockage and eccDNA exclusion, and thus an increase in the accumulation of DNA damage in the nucleus during ageing and in age-related diseases. Here, we summarize recent evidence supporting a protective role of non-coding DNA in healthy and pathological states and argue that DNA damage is the proximate cause of ageing and age-related genetic diseases. Strategies aimed at strengthening the protective role of non-coding DNA/heterochromatin could potentially offer better systematic protection for the dynamic genome and the exome against diverse assaults, reduce the burden of DNA damage to the exome, and thus slow ageing, counteract age-related genetic diseases and promote a healthier life for individuals., (© 2024 Cambridge Philosophical Society.)

G protein-coupled receptors (GPCRs) are essential contributors to tumor growth and metastasis due to their roles in immune cell regulation. Therefore, GPCRs are potential targets for cancer immunotherapy. Here, we discuss the current understanding of the roles of GPCRs and their signaling pathways in tumor progression from an immunocellular perspective. Additionally, we focus on the roles of GPCRs in regulating immune checkpoint proteins involved in immune evasion. Finally, we review the progress of clinical trials of GPCR-targeted drugs for cancer treatment, which may be combined with immunotherapy to improve treatment efficacy. This expanded understanding of the role of GPCRs may shed light on the mechanisms underlying tumor progression and provide a novel perspective on cancer immunotherapy., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

The commercialization of lithium-sulfur (Li-S) batteries has been hindered by the shuttle effect and sluggish redox kinetics of lithium polysulfides (LiPSs). Herein, we reported a viologen-based ionic conjugated mesoporous polymer (TpV-Cl), which acts as the cathode host for modifying Li-S batteries. The viologen component serves as a reversible electron conveyer, leading to a comprehensive enhancement in the adsorption of polysulfides and improved conversion rate of polysulfides during the electrochemical process. As a result, the S@TpV-PS cathode exhibits outstanding cycling performance, achieving 300 cycles at 2.0 C (1 C = 1675 mA g - 1 ) with low decay rate of 0.032% per cycle. Even at a high sulfur loading of 4.0 mg cm - 2 , S@TpV-PS shows excellent cycling stability with a Coulombic efficiency of up to 98%. These results highlight the significant potential of S@TpV-PS in developing high-performance Li-S batteries., (Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved.)

Immune-related adverse events (irAEs) pose a significant challenge for the widespread adoption of immuno-oncology therapies, but their symptoms can vary widely. In particular, the relationship between irAEs and pleural effusion (PE) in patients with advanced non-small cell lung cancer (NSCLC) remains unclear. In this report, we present the case of an advanced NSCLC patient who developed persistent PE despite receiving camrelizumab (an anti-programmed death receptor 1 [PD-1] antibody) and chemotherapy as first-line treatment. While the patient's tumor biomarkers decreased after multiple cycles of treatment, the PE persisted despite negative findings on cytology and pleural biopsy. Additionally, the use of anti-angiogenic drugs failed to alleviate the PE. Screening for rheumatic connective tissue markers and tuberculosis yielded negative results, but intrathoracic dexamethasone injections in two doses resulted in a significant reduction of the PE. This case suggests that PE may represent a rare type of irAE that should be monitored for during prolonged immuno-oncology therapy.

In this paper, a novel, to the best of our knowledge, polymer-based negative curvature ring-core fiber (NC-RCF) is proposed and investigated. The hollow-core NC-RCF is composed of TOPAS as background material. The inner and outer negative curvature structure layers are connected to the annular area, and the orbital angular momentum (OAM) modes can propagate in the annular core. In the frequency region of 1.0-1.5 THz, the designed NC-RCF can stably transmit 82 OAM modes. Investigation results indicate that the effective refractive index differences between the corresponding HE and EH modes are above 10 -4 . The confinement losses of EH or HE modes are smaller than 10 -8 d B / m , and the dispersion variations are lower than 0.31 ps/THz/cm. Effective mode areas are larger than 5.14 m m 2 . Additionally, the highest mode purity of all vector modes is 99.78%. In addition, modal birefringence, also known as the walk-off length, has also been discussed. All these operation performances indicate that the designed NC-RCF make contributions to the optical communication systems.

In pattern classification, we may have a few labeled data points in the target domain, but a number of labeled samples are available in another related domain (called the source domain). Transfer learning can solve such classification problems via the knowledge transfer from source to target domains. The source and target domains can be represented by heterogeneous features. There may exist uncertainty in domain transformation, and such uncertainty is not good for classification. The effective management of uncertainty is important for improving classification accuracy. So, a new belief-based bidirectional transfer classification (BDTC) method is proposed. In BDTC, the intraclass transformation matrix is estimated at first for mapping the patterns from source to target domains, and this matrix can be learned using the labeled patterns of the same class represented by heterogeneous domains (features). The labeled patterns in the source domain are transferred to the target domain by the corresponding transformation matrix. Then, we learn a classifier using all the labeled patterns in the target domain to classify the objects. In order to take full advantage of the complementary knowledge of different domains, we transfer the query patterns from target to source domains using the K-NN technique and do the classification task in the source domain. Thus, two pieces of classification results can be obtained for each query pattern in the source and target domains, but the classification results may have different reliabilities/weights. A weighted combination rule is developed to combine the two classification results based on the belief functions theory, which is an expert at dealing with uncertain information. We can efficiently reduce the uncertainty of transfer classification via the combination strategy. Experiments on some domain adaptation benchmarks show that our method can effectively improve classification accuracy compared with other related methods.

A multifunctional design based on vanadium dioxide (VO 2 ) metamaterial structure is proposed. Broadband absorption, linear-to-linear (LTL) polarization conversion, linear-to-circular (LTC) polarization conversion, and total reflection can be achieved based on the insulator-to-metal transition (IMT) of VO 2 . When the VO 2 is in the metallic state, the multifunctional structure can be used as a broadband absorber. The results show that the absorption rate exceeds 90% in the frequency band of 2.17 - 4.94 THz, and the bandwidth ratio is 77.8%. When VO 2 is in the insulator state, for the incident terahertz waves with a polarization angle of 45°, the structure works as a polarization converter. In this case, LTC polarization conversion can be obtained in the frequency band of 0.1 - 3.5 THz, and LTL polarization conversion also can be obtained in the frequency band of 3.5 - 6 THz, especially in the 3.755 - 4.856 THz band that the polarization conversion rate is over 90%. For the incident terahertz waves with a polarization angle of 0°, the metamaterial structure can be used as a total reflector. Additionally, impacts of geometrical parameters, incidence angle and polarization angle on the operating characteristics have also been investigated. The designed switchable multifunctional metasurfaces are promising for a wide range of applications in advanced terahertz research and smart applications.

Extrachromosomal circular DNA (eccDNA) accumulates within the nucleus of eukaryotic cells during physiological aging and in age-related diseases (ARDs) and the accumulation could be caused by the declined exclusion of nuclear eccDNA in these states. This review focuses on the formation of eccDNA and the roles of some main factors, such as nuclear pore complexes (NPCs), nucleoplasmic reticulum (NR), and nuclear actin, in eccDNA exclusion. eccDNAs are mostly formed from non-coding DNA during DNA damage repair. They move to NPCs along nuclear actin and are excluded out of the nucleus through functional NPCs in young and healthy cells. However, it has been demonstrated that defective NPCs, abnormal NPC components and nuclear actin rods are increased in aged cells, various cancers and certain other ARDs such as cardiovascular diseases, premature aging, neurodegenerative diseases and myopathies. Therefore, mainly resulting from the increase of dysfunctional NPCs, the exclusion of nuclear eccDNAs may be reduced and eccDNAs thus accumulate within the nucleus in aging and the aforementioned ARDs. In addition, the protective function of non-coding DNA in tumorigenesis is further discussed., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: A growing number of studies have suggested that microRNAs exert an essential role in the development and occurrence of multiple tumours and act as crucial regulators in various biological processes. However, the expression and function of miRNA-140 in hepatocellular carcinoma (HCC) cells are not yet adequately identified and manifested., Methods: The expression of miRNA-140 was determined in HCC tissues and adjacent nontumour tissues by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier survival analysis and Cox regression analysis were performed to explore the correlation between miRNA-140 expression level and the survival rate of patients with HCC. Additionally, overexpression experiments were conducted to investigate the biological role of miRNA-140 in HCC cells. Bioinformatics was used to predict the related target genes and pathways of miRNA-140., Results: QRT-PCR results signified that the expression level of miRNA-140 in HCC was lower than that of adjacent normal tissues ( P < 0.0001). Compared with the control group, the SMMC-7721 HCC cells in the miRNA-140 mimic group had a decrease in proliferation, migration, and invasion ( P < 0.05), whereas those in the miRNA-140 inhibitor group had an increase in proliferation, migration, and invasion ( P < 0.05). Cell cycle arrest occurred in the G0/1 phase. Prognosis analysis showed that the expression level of miRNA-140 was not related to the prognosis of HCC. Furthermore, the Kaplan-Meier test revealed that patients with lower miRNA-140 expression levels in liver cancer tissue had significantly shorter disease-free survival (DFS, P = 0.004) and overall survival (OS) times ( P = 0.010) after hepatectomy. Cox regression analysis further indicated that miRNA-140 was an independent risk factor that may affect the DFS ( P = 0.004) and OS times ( P = 0.014) of patients after hepatectomy. Our results suggested that miRNA-140 might be a crucial regulator involved in the HCC progression and is thus considered a potential prognostic biomarker and therapeutic target for HCC., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Cun-qing Kong et al.)

This publisher's note contains corrections to Opt. Lett.46, 290 (2021)OPLEDP0146-959210.1364/OL.412229.

Aging is a progressive decline of physiological function in tissue and organ accompanying both accumulation of DNA damage and reduction of non-coding DNA. Peripheral non-coding DNA/heterochromatin has been proposed to protect the genome and centrally-located protein-coding sequences in soma and male germ cells against radiation and the invasion of exogenous nucleic acids. Therefore, this review summarizes the reduction of non-coding DNA/heterochromatin (including telomeric DNA and rDNA) and DNA damage accumulation during normal physiological aging and in various aging-related diseases. Based on analysis of data, it is found that DNA damage accumulation is roughly negatively correlated with the reduction of non-coding DNA and therefore speculated that DNA damage accumulation is likely due to the reduction of non-coding DNA protection in genome defense during aging. Therefore, it is proposed here that means to increase the total amount of non-coding DNA and/or heterochromatin prior to the onset of these diseases could potentially better protect the genome and protein-coding DNA, reduce the incidence of aging-related diseases, and thus lead to better health during aging.

In this work, agricultural waste edible fungus slag derived nitrogen-doped hierarchical porous carbon (EFS-NPC) was prepared by a simple carbonization and activation process. Owing to the biodegradation and infiltrability of hyphae, this EFS-NPC possessed an ultra-high specific surface area (3342 m 2 /g), large pore volume (1.84 cm 3 /g) and abundant micropores and mesopores. The obtained EFS-NPC could effectively adsorb bisphenol A (BPA) with the maximal adsorption capacity of 1249 mg/g and the removal process reached 89.9% of the equilibrium uptake in the first 0.5 h. Besides, the EFS-NPC showed much better removal performance towards 2,4-dichlorophenol (2,4-DCP) and methylene blue (MB) than commercial activated carbons (Norit RO 0.8 and DARCO granular activated carbon). Furthermore, adsorption isotherms, thermodynamics and kinetics researches indicated that the adsorption process of BPA was monolayer, exothermic and spontaneous. This research has given evidence that the low-cost EFS-NPC can serve as a high-efficient adsorbent for removing organic contaminants from water., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Angiopoietin-like protein 3 (ANGPTL3) belongs to a multifunctional secreted protein that mainly expresses in the liver, and is regulated by numerous post-translational modifications, including multiple cleavage and glycosylation. Accumulating evidences have revealed that ANGPTL3 plays a critical role in both biological processes, such as lipid metabolism, angiogenesis and haematopoietic function and pathological changes, including atherosclerosis, carcinogenesis, nephrotic syndrome, diabetes, liver diseases and so on. Thus, ANGPTL3 may serve as a potential biomarker in these diseases. Furthermore, ANGPTL3 signalling pathways including LXR/ANGPTL3, thyroid hormone/ANGPTL3, insulin/ANGPTL3 and leptin/ANGPTL3 are also involved in physiological and pathological processes. Some biological ANGPTL3 inhibitors, chemical drugs and traditional Chinese medicine exert beneficial effects by targeting ANGPTL3 directly or indirectly. Therefore, elucidating the effects and underlying mechanisms of ANGPTL3 is essential to develop promising strategies in the diagnosis and treatment of related diseases.

The tumor suppressor DLEC1 has been shown to promote cell proliferation when AP-2α2 is down-regulated in HCT116 stable clones, suggesting its pro-survival nature. However, the pro-survival function of DLEC1 has not been confirmed in other cells and its underlying mechanisms remain elusive. Therefore, we knocked down DLEC1 in a panel of cell lines and found that DLEC1 depletion caused various extents of cell death through intrinsic pathway. DLEC1 overexpression promoted cell survival and reduced cell death in cancer cells after 5-FU treatment, while DLEC1 down-regulation sensitized cancer cells to 5-FU. Further studies demonstrated that DLEC1 attenuated the increase in cleaved PARP, caspase-3 and caspase-7, the activity of caspase-9 and the diffusion of cytosolic cytochrome c from mitochondria. Our data also showed that BCL-XL was up-regulated by DLEC1 in stable clones after 5-FU treatment. Altogether, these results indicated that DLEC1 protects cells against cell death induced by 5-FU through the attenuation of active proteins in caspase cascade and the up-regulation of BCL-XL. Therefore, DLEC1 can be a pro-survival protein under certain circumstances and a potential therapeutic target for increasing sensitivity of cancer cells to 5-FU.

From a three-dimensional (3D) metal-organic framework (MOF) of {[Cu(Cmdcp)(phen)(H 2 O)] 2 ·9H 2 O} n (1, H 3 CmdcpBr = N-carboxymethyl-(3,5-dicarboxyl)pyridinium bromide, phen = phenanthroline), a sensitive and selective fluorescence sensor has been developed for the simultaneous detection of ebolavirus conserved RNA sequences and ebolavirus-encoded microRNA-like (miRNA-like) fragment. The results from molecular dynamics simulation confirmed that MOF 1 absorbs carboxyfluorescein (FAM)-tagged and 5(6)-carboxyrhodamine, triethylammonium salt (ROX)-tagged probe ss-DNA (probe DNA, P-DNA) by π … π stacking and hydrogen bonding, as well as additional electrostatic interactions to form a sensing platform of P-DNAs@1 with quenched FAM and ROX fluorescence. In the presence of targeted ebolavirus conserved RNA sequences or ebolavirus-encoded miRNA-like fragment, the fluorophore-labeled P-DNA hybridizes with the analyte to give a P-DNA@RNA duplex and released from MOF 1, triggering a fluorescence recovery. Simultaneous detection of two target RNAs has also been realized by single and synchronous fluorescence analysis. The formed sensing platform shows high sensitivity for ebolavirus conserved RNA sequences and ebolavirus-encoded miRNA-like fragment with detection limits at the picomolar level and high selectivity without cross-reaction between the two probes. MOF 1 thus shows the potential as an effective fluorescent sensing platform for the synchronous detection of two ebolavirus-related sequences, and offer improved diagnostic accuracy of Ebola virus disease., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Peripheral and abundant noncoding DNA has been hypothesized to protect the genome and the central protein-coding sequences against DNA damage in somatic genome. In the cytosol, invading exogenous nucleic acids may first be deactivated by small RNAs encoded by noncoding DNA via mechanisms similar to the prokaryotic CRISPR-Cas system. In the nucleus, the radicals generated by radiation in the cytosol, radiation energy and invading exogenous nucleic acids are absorbed, blocked and/or reduced by peripheral heterochromatin, and damaged DNA in heterochromatin is removed and excluded from the nucleus to the cytoplasm through nuclear pore complexes. To further strengthen the hypothesis, this review summarizes the experimental evidence supporting the protective function of noncoding DNA in the genome of male germ cells. Based on these data, this review provides evidence supporting the protective role of noncoding DNA in the genome defense of sperm genome through similar mechanisms to those of the somatic genome.

We report herein five sensing platforms for the detection of five gastric cancer associated microRNAs (miRNAs). The sensing platforms are hybrids formed from a water-stable metal organic framework (MOF) {[Cu(dcbb) 2 (H 2 O) 2 ]·10H 2 O} n (1, H 2 dcbbBr=1-(3,5-dicarboxybenzyl)-4,4'-bipyridinium bromide), respectively with five carboxyfluorescein (FAM) labeled probe single-stranded DNA (probe ss-DNA, denoted as P-DNA). Within the hybrid, MOF 1 tightly interacts with the P-DNA through electrostatic and/or π-stacking interactions and results in fluorescence quenching of FAM via a photo-induced electron transfer (PET) process. In the presence of the complementary target miRNAs miR-185, miR-20a, miR-92b, miR-25 and miR-210, which are expressed abnormally in the plasma of gastric carcinoma patients, P-DNA is released from the surface of MOF 1 ascribed to the stronger base pair matching, leading to the FAM fluorescence recovery. Each P-DNA@1 system is effective and reliable for the detection of its complementary target miRNA with the detection limits from 91 to 559pM, and is not interfered by other four miRNA sequences., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Traditionally, the genome has been described as the 'book of life'. However, the metaphor of a book may not reflect the dynamic nature of the structure and function of the genome. In the eukaryotic genome, the number of centrally located protein-coding sequences is relatively constant across species, but the amount of noncoding DNA increases considerably with the increase of organismal evolutional complexity. Therefore, it has been hypothesized that the abundant peripheral noncoding DNA protects the genome and the central protein-coding sequences in the eukaryotic genome. Upon comparison with the habitation, sociality and defense mechanisms of a social insect colony, it is found that the genome is similar to a social insect colony in various aspects. A social insect colony may thus be a better metaphor than a book to describe the spatial organization and physical functions of the genome. The potential implications of the metaphor are also discussed.

Haemophilus parasuis (H. parasuis) is the etiological agent of swine Glässer's disease, which leads to significant economic loss in swine industry over the world. Subunit vaccine based on outer membrane protein is one of the promising choices to protect pigs against H. parasuis infection despite low immunity efficiency. In this paper, outer membrane protein 16 (Omp16) of H. parasuis encapsulated by alginate-chitosan microspheres as antigen carriers was explored for the first time in a mouse model. Our results showed that the microspheres with Omp16 induced significant higher H. parasuis-specific antibodies, and higher titers of IL-2, IL-4, and IFN-γ than those by Omp16-FIA in treated mice (p<0.05). Moreover, H. parasuis load in the tissues from liver, spleen, and lung of mice immunized with microspheres containing Omp16 was significantly decreased (p<0.05) than that in the same counterpart tissues of control groups. In addition, 80% mice treated with Omp16 and 70% mice with Omp16-FIA were survived after challenged with H. parasuis virulent strain LY02 (serovar 5). Therefore, Omp16-based microsphere vaccine induces both humoral and cellular immune responses and provides promising protection against H. parasuis infection in mice., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Coordination reaction of a known three-dimensional (3D) polymer precursor {Na3[Na9(Cbdcp)6(H2O)18]}n (A, Cbdcp = N-(4-carboxybenzyl)-(3,5-dicarboxyl)pyridinium) with Zn(NO3)2·6H2O in H2O or H2O/DMF at 100 °C and in the presence of aspirin, 5-fluorouracil (5-FU) as modulators, trans-1,2-bis(4-pyridyl)ethylene (bpe) or 1,2-bis(4-pyridyl)ethane (bpea) as ancillary ligands afforded six novel Zn(II)-based metal-organic frameworks (MOFs), that is, {[Zn(Cbdcp)(H2O)3]·H2O}n (1, 1D zigzag chain), {[Zn(HCbdcp)2]·H2O}n (2, 2D sheet), {[Zn(Cbdcp)(bpe)1/2]·2H2O}n (3, 3D polymer), {[Zn(Cbdcp)(bpe)1/2]·2H2O}n (4, 2D network), {[Zn(Cbdcp)(bpea)1/2]·2H2O}n (5, 3D polymer) and {[Zn(Cbdcp)(bpea)1/2]·2H2O}n (6, 2D network). Among them, compound 2 contains aromatic rings, positively charged pyridinium, Zn(2+) cation centers and carboxylic acid groups lined up on the 2D sheet structure with a certain extended surface exposure. The unique structure of 2 facilitates effective association with carboxyfluorescein (FAM) labeled probe single stranded DNA (probe ss-DNA, delineates as P-DNA) to yield a P-DNA@2 system, and leads to fluorescence quenching of FAM via a photoinduced electron transfer process. The P-DNA@2 system is effective and reliable for the detection of human immunodeficiency virus 1 ds-DNA (HIV ds-DNA) sequences and capable of distinguishing complementary HIV ds-DNA from mismatched target sequences with the detection limit as low as 10 pM (S/N = 3)., (Copyright © 2016. Published by Elsevier B.V.)

As one of the manganese oxides, which are easily generated and widely distributed in supergene environment, manganite participates in the oxidation of dissolvable sulfide (S²⁻), and affects the migration, transformation, and the fate of sulfides. In the present work, the redox mechanism was studied by determining the intermediates, and the influence of initial pH and oxygen atmosphere on the processes were studied. The chemical composition, crystal structures and micromorphologies were characterized by XRD, FTIR and TEM. The concentration of S²⁻ and its oxidation products were analyzed using spectrophotometer, high performance liquid chromatograph and ion chromatograph. The results indicated that elemental sulfur was formed as the major oxidation product of S²⁻ oxidation, and decreased pH could accelerate the oxidation rate of S²⁻ in the initial stage, however, there was no significant influence on final products. Elemental S could be further oxidized to S₂O₃²⁻ when the reaction system was bubbled with oxygen, and manganite exhibited excellent catalytic performance and chemical stability during the oxidation of dissolvable sulfide by oxygen. After reaction of more than 10 h, the crystal structure of manganite remained stable.

Polymorphic compounds {[Cu(dcbb)2(H2O)2]·10H2O}n (2, 1D chain), [Cu(dcbb)2]n (3, 2D layer) and their co-crystal {[Cu(dcbb)2(H2O)][Cu(dcbb)2]2}n (4) have been prepared from the coordination reaction of a 2D polymer [Na(dcbb)(H2O)]n (1, H2dcbbBr = 1-(3,5-dicarboxybenzyl)-4,4'-bipyridinium bromide) with Cu(NO3)2·3H2O at different temperatures in water. Compounds 2-4 have an identical metal-to-ligand stoichiometric ratio of 1 : 2, but absolutely differ in structure. Compound 3 features a 2D layer structure with aromatic rings, positively charged pyridinium and free carboxylates on its surface, promoting electrostatic, π-stacking and/or hydrogen-bonding interactions with the carboxyfluorescein (FAM) labeled probe single-stranded DNA (probe ss-DNA, delineates as P-DNA). The resultant P-DNA@3 system facilitated fluorescence quenching of FAM via a photoinduced electron transfer process. The P-DNA@3 system functions as an efficient fluorescent sensor selective for HIV double-stranded DNA (HIV ds-DNA) due to the formation of a rigid triplex structure with the recovery of FAM fluorescence. The system reported herein also distinguishes complementary HIV ds-DNA from mismatched target DNA sequences with the detection limit of 1.42 nM.

To investigate the Terahertz's application prospect, corn, wheat husk and reed were used to detect their Terahertz Time Domain Spectroscopy, and be compared with that of cellulose powder. The experimental results show that all of their absorption peaks exist at 1.75, 1.62, 1.1, and 0.7 THz. Absorption intensity of cellulose powder, corn, wheat husk and reed were compared in some frequencies points. It finds that corn, wheat husk and reed have higher absorption intensity than cellulose powder in early frequency domain. However, absorption intensity of cellulose powder is the strongest at 1.62 THz. Cellulose content in corn, wheat husk and reed were detected by using the method of chemical analysis. The peaks of absorption coefficient are related to their cellulose content at this frequency. It shows that plant cellulose occur lattice vibration in the frequency. Deformation, bending, flexing, and other changes appear to their functional keys. Quantum chemical calculation was carried out by using density functional theory to cellulose and the structure diagram of cellulose molecular formula was obtained. It also finds some absorption peaks exist at 0.7, 1.1, and 1.75 THz. Characterization of cellulose clusters mainly includes CH2, OH, CH, and so on. Glucose hydroxyl radical on the ring is active in the cellulose chain. Where hydroxyl related chemical reaction can occur, Hydroxyl can also be integrated into the intermolecular and intramolecular hydrogen bond. Terahertz wave can promote hydrogen bond vibration. This kind of vibration is weak in the intermolecular interaction. The vibration and rotating happen in dipole transition. The crystal lattice rotates and is absorptive in low frequency, and large molecular skeleton vibrates. All of them can show different intensity and position of the absorption peak in the terahertz band. Corn and cellulose were analyzed by infrared spectrum. The reverse and vibration mode of cellulose was discussed. The absorption peak is basically in line with its theoretical calculating result. It is feasible that Terahertz Time Domain Spectroscopy can detect cellulose, and it provides a new method for the detection and judgement of cellulose in plants.

We herein report a water-stable 3D dysprosium-based metal-organic framework (MOF) that can non-covalently interact with probe ss-DNA. The formed system can serve as an effective fluorescence sensing platform for the detection of complementary Ebolavirus RNA sequences with the detection limit of 160 pM.

In this review, the protective function of the abundant non-coding DNA in the eukaryotic genome is discussed from the perspective of genome defense against exogenous nucleic acids. Peripheral non-coding DNA has been proposed to act as a bodyguard that protects the genome and the central protein-coding sequences from ionizing radiation-induced DNA damage. In the proposed mechanism of protection, the radicals generated by water radiolysis in the cytosol and IR energy are absorbed, blocked and/or reduced by peripheral heterochromatin; then, the DNA damage sites in the heterochromatin are removed and expelled from the nucleus to the cytoplasm through nuclear pore complexes, most likely through the formation of extrachromosomal circular DNA. To strengthen this hypothesis, this review summarizes the experimental evidence supporting the protective function of non-coding DNA against exogenous nucleic acids. Based on these data, I hypothesize herein about the presence of an additional line of defense formed by small RNAs in the cytosol in addition to their bodyguard protection mechanism in the nucleus. Therefore, exogenous nucleic acids may be initially inactivated in the cytosol by small RNAs generated from non-coding DNA via mechanisms similar to the prokaryotic CRISPR-Cas system. Exogenous nucleic acids may enter the nucleus, where some are absorbed and/or blocked by heterochromatin and others integrate into chromosomes. The integrated fragments and the sites of DNA damage are removed by repetitive non-coding DNA elements in the heterochromatin and excluded from the nucleus. Therefore, the normal eukaryotic genome and the central protein-coding sequences are triply protected by non-coding DNA against invasion by exogenous nucleic acids. This review provides evidence supporting the protective role of non-coding DNA in genome defense., (Copyright © 2016 Elsevier B.V. All rights reserved.)

We herein report a water-stable three-dimensional Cu-based metal-organic framework (MOF) 1 supported by a tritopic quaternized carboxylate and 4,4'-dipyridyl sulfide as an ancillary ligand. This MOF exhibits unique pore shapes with aromatic rings, positively charged pyridinium and unsaturated Cu(II) cation centers, free carboxylates, tessellating H2O, and coordinating SO4(2-) on the pore surface. Compound 1 can interact with two carboxyfluorescein (FAM)-labeled single-stranded DNA sequences (probe ss-DNA, delineated as P-DNA) through electrostatic, π-stacking, and/or hydrogen-bonding interactions to form two P-DNA@1 systems, and thus quench the fluorescence of FAM via a photoinduced electron-transfer process. These P-DNA@1 systems can be used as effective fluorescent sensors for human immunodeficiency virus 1 double-stranded DNA and Sudan virus RNA sequences, respectively, with detection limits of 196 and 73 pM, respectively.

Background: The molecular mechanisms of tumor suppressor gene DLEC1 are largely unknown., Objectives: In this study, we established DLEC1 over-expression stable clones to study the cellular function of DLEC1 in the colorectal cancer cell line, HCT116., Materials and Methods: Stable clones with DLEC1 over-expression were first established by the transfection of DLEC1 expression construct pcDNA31DLEC1 in HCT116. On G418 selection, positive stable clones were screened for DLEC1 expression level by conventional reverse transcription-polymerase chain reaction (RT-PCR), and verified by real-time RT-PCR and Western blotting. Subsequently, these stable clones were subjected to colony formation and cell cycle analyses and identification of factors involved in G1 arrest. Lastly, three stable clones, DLEC1-7 (highest DLEC1 expression), DLEC1-3 (lowest expression) and pcDNA31 vector control, were employed to analyze cell proliferation and cell cycle after AP-2α2 knockdown by siRNAs., Results: The DLEC1 over-expression was found to reduce the number of colonies in colony formation and to induce G1 arrest in seven clones, and apoptosis in one clone in the cell cycle analysis. Furthermore, regardless of the different cell cycle defects in all eight stable clones, the expression level of transcriptional factor AP-2α2 was found to be elevated. More interestingly, we found that when AP-2α2 was knocked down, DLEC1 over-expression neither suppressed cancer cell growth nor induced G1 arrest, yet, instead promoted cell growth and decreased cells in the G1 fraction. This promotion of cell proliferation and release of G1 cells also seemed to be proportional to DLEC1 expression levels in DLEC1 stable clones., Conclusions: DLEC1 suppresses tumor cell growth the presence of AP-2α2 and stimulates cell proliferation in the down-regulation of AP-2α2 in DLEC1 over-expression stable clones of HTC116.

Non-coding DNA comprises a very large proportion of the total genomic content in higher organisms, but its function remains largely unclear. Non-coding DNA sequences constitute the majority of peripheral heterochromatin, which has been hypothesized to be the genome's 'bodyguard' against DNA damage from chemicals and radiation for almost four decades. The bodyguard protective function of peripheral heterochromatin in genome defense has been strengthened by the results from numerous recent studies, which are summarized in this review. These data have suggested that cells and/or organisms with a higher level of heterochromatin and more non-coding DNA sequences, including longer telomeric DNA and rDNAs, exhibit a lower frequency of DNA damage, higher radioresistance and longer lifespan after IR exposure. In addition, the majority of heterochromatin is peripherally located in the three-dimensional structure of genome organization. Therefore, the peripheral heterochromatin with non-coding DNA could play a protective role in genome defense against DNA damage from ionizing radiation by both absorbing the radicals from water radiolysis in the cytosol and reducing the energy of IR. However, the bodyguard protection by heterochromatin has been challenged by the observation that DNA damage is less frequently detected in peripheral heterochromatin than in euchromatin, which is inconsistent with the expectation and simulation results. Previous studies have also shown that the DNA damage in peripheral heterochromatin is rarely repaired and moves more quickly, broadly and outwardly to approach the nuclear pore complex (NPC). Additionally, it has been shown that extrachromosomal circular DNAs (eccDNAs) are formed in the nucleus, highly detectable in the cytoplasm (particularly under stress conditions) and shuttle between the nucleus and the cytoplasm. Based on these studies, this review speculates that the sites of DNA damage in peripheral heterochromatin could occur more frequently and may be removed by repetitive elements in non-coding DNA through the formation of eccDNAs and expelled out of the nucleus to the cytoplasm via the NPC. Therefore, this review proposes that the genome and central protein-coding sequences are doubly protected by non-coding DNA in peripheral heterochromatin against DNA damage from radiation, which may be a novel protective role of non-coding DNA in genome defense., (Copyright © 2015 Elsevier B.V. All rights reserved.)

As cellular models for in vitro liver cancer and toxicity studies, HepG2 and Hep3B are the two most frequently used liver cancer cell lines. Because of their similarities they are often treated as the same in experimental studies. However, there are many differences that have been largely over-sighted or ignored between them. In this review, we summarize the differences between HepG2 and Hep3B cell lines that can be found in the literature based on PubMed search. We particularly focus on the differential gene expression, differential drug responses (chemosensitivity, cell cycle and growth inhibition, and gene induction), signaling pathways associated with these differences, as well as the factors in governing these differences between HepG2 and Hep3B cell lines. Based on our analyses of the available data, we suggest that neither HBx nor p53 may be the crucial factor to determine the differences between HepG2 and Hep3B cell lines although HBx regulates the expression of the majority of genes that are differentially expressed between HepG2 and Hep3B. Instead, the different maturation stages in cancer development of the original specimen between HepG2 and Hep3B may be responsible for the differences between them. This review provides insight into the molecular mechanisms underlying the differences between HepG2 and Hep3B and help investigators especially the beginners in the areas of liver cancer research and drug metabolism to fully understand, and thus better use and interpret the data from these two cell lines in their studies.

Objective: A retrospective study was conducted to investigate the clinical features and prognostic factors of 73 cases of severe hepatitis., Methods: To summarize clinical features of 73 cases of severe hepatitis, grouping by etiology and pathogenesis. A retrospective analysis was performed to evaluate the relationship between biochemical characteristics (liver function, renal function, electrolytes, PTA, etc) and complications (hepatic encephalopathy, upper gastrointestinal bleeding, hepatorenal syndrome, ascites, abdominal infections, etc) and prognosis., Results: (1) HBV infection alone accounted for 65.75%. Alcoholic liver disease, drug-induced liver injury, hepatitis E, autoimmune hepatitis, overlapping causes and other factors were five cases (6.85%), six cases (8.22%), two cases (2.74%), two cases (2.74%), seven cases (9.59%) and three cases (4.11%) respectively. According to the incidence rate, severity and underlying liver condition, subacute hepatitis, cases based on chronic hepatitis and on cirrhosis were 12 cases (16.43%), 11 cases (15.07%), 50 cases (68.49%) respectively. Clinical manifestations with or without hepatic encephalopathy accounted for 58.90% or 41.10%. (2) The highest mortality of severe hepatitis was alcoholic liver disease and patients on the basis of overlapping factors (66.67%), followed by autoimmune liver disease (50%). The mortality of HBV-related hepatitis was 18.75%. Overall mortality of 73 cases of severe hepatitis was 28.77%, of which cirrhosis group was higher than non-cirrhotic group (40% vs 4.3%, P = 0.002). The difference was statistically significant. Patients without hepatic encephalopathy had lower mortality than with hepatic encephalopathy (3.33% vs 46.51%). The mortality of patients with hepatic encephalopathy Stage III and IV was 72.73%. (3) Independent samples t test filtered nine factors associated with death, namely cirrhosis, upper gastrointestinal bleeding, hepatic encephalopathy, hepatorenal syndrome, serum creatinine, total bilirubin (TBIL), direct bilirubin (DBIL), albumin (ALB) and serum sodium. The results of multivariate conditional logistic regression analysis indicated that hepatic encephalopathy, serum creatinine levels were risk factors for death, whereas ALB as a protective factor., Conclusion: Hepatic encephalopathy, serum creatinine levels were risk factors for severe hepatitis death, But ALB was protective factor. Nucleotide analogs using was the main reason why the mortality of hepatitis B was as low as 18.75%.

Objective: To explore the etiology of acute hepatitis hospitalized patients in Beijing Ditan Hospital from 2002 to 2011., Methods: We summed up the changes in the characteristics of the etiology of acute hepatitis of patients mentioned above, and preliminarily analyze the causes., Results: From 2002 to 2011, 6235 patients with acute hepatitis were admitted to Ditan Hospital, aged between 12 and 78 years old, Of which 4309 were male and 1926 female. Acute viral hepatitis accounted for 70.44%-85.07%, while CMV, EBV, drug-induced liver injury accounted less than 5%, and acute hepatitis D and acute hepatitis C less than 1.10%. From year to year, the incidence and constitution of acute hepatitis changed significantly. The proportion of patients with acute hepatitis in total hospitalized patients was from 20. 38% to 2.05%. In 10 years, the percentage of acute hepatitis A decreased most obviously, about 99.11%, while 45.07% decline in incidence of acute hepatitis B and 62. 28% of acute hepatitis E. The constituent ratio of acute hepatitis also changed significantly. The proportion of acute hepatitis A declined from 31.31% in 2002, to less than 1% in 2011. The proportion of acute hepatitis B increased from 26.47% in 2002 to 45.88% in 2011, an increase of about 2 folds in 10 years. The proportion of acute hepatitis E increased from 26.73% in 2002 to 32.05% in 2010, a rise of 1.20 times in 10 years., Conclusions: The proportion of patients with acute hepatitis in total hospitalized patients decreased from 20. 38% in 2002 to 2. 05% in 2011 in Beijing Ditan Hospital. The constituent ratio of acute hepatitis changed, too.

Objective: To explore the effect of intensive treatment for refractory chronic hepatitis C, and to improve the sustained viral response (SVR) rate of treatment with interferon plus ribavirin by optimizing therapeutic dose and course., Methods: Patients who did not acquire response or partial response by standard therapy (PEG-IFN alpha subcutaneous injection weekly plus Ribavirin 10.5 mg/kg) every day were enrolled and retreated with intensive treatment of 10 MU interferon every other day or 360 microg pegylated interferon alpha-2a weekly according to patients' wishes, and ribavirin 15 mg/kg every day. Serum HCV RNA was detected at baseline,treatment week 4, 12 and every 12 weeks succedent and 24 weeks after treatment end. Course of treatment was 72 to 96 weeks according to viral response. SVR was the mark of therapeutic effect., Results: 18 patients completed whole range therapy and follow-up, in which 12 patients acquired SVR, 5 patients treatment failure and 1 relapse. 3 patients acquired rapid viral response (RVR), and they all got complete Early Viral Response (cEVR) and SVR. RVR Patients' viral loads were significantly lower than that of patients who did not acquire RVR (t = 4. 687, P < 0.001). In 15 patients who did not acquire RVR, 8 patients acquired cEVR, and 9 acquired SVR. SVR rate of patients who were administered PEG-IFN alpha-2a was 4/5, 11 patients who acquired cEVR all acquired SVR, while in 7 patients who did not acquire cEVR, only 1 patient acquired SVR., Conclusions: High percent patients, who did not acquire response or partial response by previous standard antiviral therapy, could gain SVR by intensive dose interferon plus Ribavirin. In intensive treatment procedure, adjusting and prolonging course according to viral response after HCV RNA turned negative were important measures to improve refractory Chronic Hepatitis C SVR rate.

Objective: To explore the retreatment of CHC patients with initial treatment failure and how to achieve SVR., Methods: 54 patients who had experienced treatment failure were enrolled and retreated with standard treatment of pegylated interferon and ribavirin or intensive treatment, respectively. Their SVR rates were statistically compared, to decide two therapies' application., Results: 54 patients had been retreated, and total SVR rate was up to 75.92%, with 88.46% in relapsed patients and 64.29% in non-responders. After retreatment with pegylated interferon and ribavirin, SVR rate was 95.45% in patients with prior interferon monotherapy, and 64.71% in patients with prior interferon and ribavirin, and 60% in patients with prior pegylated interferon alpha-2a monotherapy. SVR rate of relapsed patients was significantly higher than that of non-responders., Conclusions: In CHC patients with treatment failure, SVR rate of retreatment with standard treatment or intensive treatment still can be up to 60%-90%. Retreatment with standard therapy can be applied to patients who had received interferon monotherapy or interferon plus ribavirin. Three types of patients who need intensive retreatment were as following: patients nonresponsive to interferon plus ribavirin or pegylated interferon alpha-2a monotherapy, and patients with treatment failure who had received prior standard treatment.

Adsorption characteristics of mineral surface for heavy metal ions are largely determined by the type and amount of surface adsorption sites. However, the effects of substructure variance in manganese oxide on the adsorption sites and adsorption characteristics remain unclear. Adsorption experiments and powder X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) were combined to examine the adsorption characteristics of Pb2+, Cu2+, Zn2+ and Cd2+ sequestration by birnessites with different Mn average oxidation state (AOS), and the Mn AOS dependent adsorption sites and adsorption characteristics. The results show that the maximum adsorption capacity of Pb2+, Cu2+, Zn2+ and Cd2+ increased with increasing birnessite Mn AOS. The adsorption capacity followed the order of Pb2+ > Cu2+ > Zn2+ > Cd2+. The observations suggest that there exist two sites on the surface of birnessite, i. e., high-binding-energy site (HBE site) and low-binding-energy site (LBE site). With the increase of Mn AOS for birnessites, the amount of HBE sites for heavy metal ions adsorption remarkably increased. On the other hand, variation in the amount of LBE sites was insignificant. The amount of LBE sites is much more than those of HBE sites on the surface of birnessite with low Mn AOS. Nevertheless, both amounts on the surface of birnessite with high Mn AOS are very close to each other. Therefore, the heavy metal ions adsorption capacity on birnessite is largely determined by the amount of HBE sites. On birnessite surface, adsorption of Cu2+, Zn2+, and Cd2+ mostly occurred at HBE sites. In comparison with Zn2+ and Cd2+, more Cu2+ adsorbed on the LBW sites. Pb2+ adsorption maybe occupy at both LBE sites and HBE sites simultaneously.

Nonviral vectors present considerable advantages over viral counterparts in gene transfer. However, the poor expression efficiency of the transfected genes poses a challenge for their use in gene therapy, primarily due to the inability of these vectors to overcome various barriers, including the biological barriers. Here, we report that ZNF511-PRAP1 may be involved in the recognition and inactivation of transfected plasmids. ZNF511-PRAP1 is induced by transfection of plasmid DNA and suppresses the transcription of transfected plasmids. It binds directly to the p21 promoter in transfected plasmids but not the endogenous counterpart. Similarly, ZNF511-PRAP1 suppresses the expression of the green fluorescent protein reporter gene on transiently transfected plasmids but not an integrated red fluorescence reporter gene with the same cytomegalovirus (CMV) promoter. Therefore, ZNF511-PRAP1 is able to differentiate between exogenous/nonintegrated and endogenous/integrated DNA. The suppression by ZNF511-PRAP1 is independent of DNA methylation and can be abolished by trichostatin A (TSA) treatment and knockdown of HDAC2 and/or ZNF511-PRAP1. Furthermore, ZNF511-PRAP1 interacts directly with HDAC2. Our results revealed that transfected plasmids are recognized by ZNF511-PRAP1 and suppressed by a repressor complex comprising ZNF511-PRAP1 and HDAC2 and suggest that ZNF511-PRAP1 could play a role as a potential molecular barrier in nonviral transgene expression.

Objective: To study the clinical features, outcomes and treatments of viral hepatitis combined with aplastic anemia., Methods: 25 cases diagnosed as viral hepatits combined with aplastic anemia in Beijing Ditan Hsopital between April 2004 and September 2009 were retrospectively analyzed. In this group of patients aplastic anemia was finally diagnosed by bone marrow aspiration. We collected clinical data of these patients, including a history of liver disease, drug allergies, hospital medication history, laboratory data, and then performed descriptive analysis., Results: 25 patients with viral hepatitis were diagnosed as complicated with aplastic anemia by histopathological data. Among these patients, 17 were male and 8 were women. Viral hepatitis included: chronic hepatitis B (12 cases), chronic hepatitis C (4 cases), acute hepatits E (1 case), hepatitis caused by CMV infection (1 case), and unclassified hepatitis (7 cases). Among these patients, 7 were diagnosed as severe hepatits. Considering previous history, only 3 patients had history of short term interferon therapy before hospitalization, and the remaining patients did not use drug that affects blood system. Treatments were as followings: using colony stimulating factor in 6 patients, gamma globulin in 9 patients, glucocorticoids in 3 patients, erythropoietin in 1 patient, only oral drug to raise erythrocytes in 2 patients, red blood cells transfusion in 6 patients, platelets transfusion in 2 patients. As for clinical outcomes, 20 patients acquired improved condition and were dicharged, 3 patients were discharged voluntarily and 2 patients died of severe hepatits combined with other complications., Conclusion: Main treatments of viral hepatitis combined with aplastic anemia were to treat primary hepatopathy and nucleoside analogue-based antiviral therapy, to provide symptomatic and supportive treatment for blood diseases. Blood diseases would recover simultaneously while liver disease was improved, and the prognosis was good.

As one of the common manganese oxide minerals in supergene environment, cryptomelane affects the migration, transformation and environmental fate of sulfur in soil. In this work, oxidation process of sodium sulfide solution by cryptomelane was investigated without oxygen gas. The species and concentration of oxidation products of sulfide in solution were determined by spectrophotometry and ion chromatography, and the crystal structures and micro-morphologies of solid oxidation products of sulfide were characterized by XRD and SEM. The influence of solution temperature, pH value of solution, manganese average oxidation state (AOS) and the amount of added cryptomelane on the initial oxidation rate of S2- was studied. It was observed that the oxidation products of sulfide were S2O3(2-), SO3(2-), SO4(2-) and S, and S was the main one for that the total transformation rate of S2- to S2O3(2-), SO3(2-) and SO4(2-) was below 13.4%. The initial oxidation rate of S2- follows a pseudo-first-order law. Oxidation rate increased with elevating reaction temperature, decreasing pH value of solution and the increase of the amount of added mineral. The oxidation capacity of cryptomelane increased with the increase of Mn(III) content, and the initial oxidation rate constants (K(obs)) of S2- were 0.220 3 min(-1) and 0.1729 min(-1) when cryptomelane was applied with AOS about 3.81 and 3.98, respectively. During the redox process, cryptomelane was reduced to Mn(OH)2, which could be oxidized into Mn3O4, by O2 in air, and Mn3O4 was further transformed into MnOOH likely due to the reaction of surface-adsorbed water on manganese oxide and O2 and Mn3O4.

In order to study the effects of transition metal ions on the physic-chemical properties of manganese dioxides as environmental friendly materials, three-dimensional nano-microsphere cobalt-doped birnessite was synthesized by reduction of potassium permanganate by mixtures of concentrated hydrochloride and cobalt (II) chloride. Powder X-ray diffraction, chemical analysis, N2 physical adsorption, field emission scanning electron microscopy (FE-SEM) and X-ray photoelectron spectra (XPS) were used to characterize the crystal structure, chemical composition and micro-morphologies of products. In the range of molar ratios from 0.05 to 0.20, birnessite was fabricated exclusively. It was observed that cobalt incorporated into the layers of birnessite and had little effect on the crystal structure and micromorpholgy, but crystallinity decreased after cobalt doping. Both chemical analysis and XPS results showed that manganese average oxidation state decreased after cobalt doping, and the percentage of Mn3+ increased. Co(III) OOH existed mainly in the structure. With the increase of cobalt, hydroxide oxygen percentage in molar increased from 12.79% for undoped birnessite to 13.05%, 17.69% and 17.79% for doped samples respectively. Adsorption capacity for lead and oxidation of arsenite of birnessite were enhanced by cobalt doping. The maximum capacity of Pb2+ adsorption increased in the order HB (2 538 mmol/kg) < CoB5 (2798 mmol/kg) < CoB10 (2932 mmol/kg) < CoB20 (3 146 mmol/kg). Oxidation percentage of arsenite in simulated waste water by undoped birnessite was 76.5%, those of doped ones increased by 2.0%, 12.8% and 18.9% respectively. Partial of Co3+ substitution for Mn4+ results in the increase of negative charge of the layer and the content of hydroxyl group, which could account for the improved adsorption capacity of Pb2+. After substitution of manganese by cobalt, oxidation capacity of arsenite by birnessite increases likely due to the higher standard redox potential of Co3+/Co2+ than those of Mn4+/Mn3+/Mn2+. Therefore, Co-doped birnessite is more applicable for the remediation of water polluted with heavy metal ions, implying new methods of modification of manganese dioxides in practice.

Objective: HBsAg loss and seroconversion in patients with chronic hepatitis B leads to long-lasting good clinical outcomes. The aim of this paper was to investigate to improve the rate of HBsAg loss and seroconversion in chronic hepatitis B patients by prolonged treatment of PEG-IFNa-2a. 217 cases of HBeAg-positive or negative patients were collected from inpatient and outpatient in Beijing Ditan Hospital from May 2005 to October 2009 and subcutaneous injection of 135 ug or 180 ug PEGASYS were given once a week according to body weights. The drug doses were adjusted according to the neutrophilic granulocyte and platelet counts during treatment course. Quantitative HBV DNA test was conducted using a commercially available real-time fluorescence quantitative PCR kit. The serum HBsAg/anti-HBs and HBeAg/anti-HBe were quantitatively detected by Abbott i 2000 chemiluminescent kit before and during treatment every three months. Patients with HBsAg steadily decreased and reached serum HBsAg level below 200 IU/ml after 48 weeks of treatment would receive prolonged treatment. Patients with more than 12 weeks of treatment entered into analysis. Main efficacy of prolonged treatment was evaluated by the incidences of HBsAg loss and seroconversion., Results: The treatment courses of the 217 patients ranged from 12.0 to 197.6 weeks with an average of 53.1+/-33.4 weeks, 118 cases took more than 48 weeks and another 89 cases less than 48 weeks. 13.4% (29/217) of patients achieved HBsAg loss or HBsAg seroconversion with treatment courses from 17.6 to 197.6 weeks (average 75.4+/-42.8 weeks). Among these 29 patients 24 (82.8%) received more than 48 weeks of treatment, but the treatment courses of HBV DNA reached undetectable level were 20.8+/-8.9 weeks. In this study, 9.5% (14/148) of HBeAg-positive patients achieved HBsAg loss or seroconversion, all of them treated more than 48 weeks, from 48 to 194 weeks, average 81.32+/-39.36 weeks. 21.7% (15/69) of HBeAg-negative patients achieved HBsAg loss or seroconversion, significantly higher than that of HBeAg-positive patients (9.5%) (x2 = 6.129, P = 0.013). The average treatment course for HBeAg-negative patients with HBsAg loss was 70.2+/-48.0 weeks, shorter than that of HBeAg-positive patients with HBsAg loss (81.3+/-39.4 weeks), but no significant difference (t = -0.522, P = 0.602) found between., Conclusion: Higher rate of HBsAg loss and seroconversion could be obtained by individual extended treatment courses in patients with rapid HBV DNA and HBsAg response to PEG-IFNa-2a treatment and the HBeAg-negative patients could got higher rate of HBsAg loss than HBeAg-positive patients.

Objective: To investigate the relation of serum HBsAg, HBeAg contents and HBV-DNA load changes in HBeAg-positive chronic hepatitis B during IFN-alpha treatment., Methods: After enrolled, the patients were treated with 3MU-5MU IFN subcutaneous injection every two days, and their serum was collected before treatment and every 3 months during the treatment course. The serum HBV-DNA load was determined by real-time fluorescence quantitative PCR method kit (lower detection limit 500 copies/ml, Piji company, Shenzhen city, China,) according to production instruction, and HBeAg and HBsAg contents were detected by ARCHITECH I 2000.chemiluminescent kit. The relation of serum HBV-DNA, HBeAg and HBsAg content was analyzed by SPSS statistic software., Results: There were 228 patients enrolled into this group, male 162 cases, female 66 cases, aged 14-60 years, average 30.94 years old. After IFN treatment the HBV-DNA, HBeAg and HBsAg levels were all gradually decreased. But there was no relation of HBsAg content to HBV DNA and HBeAg content before and during treatment course(P > 0.05). However the serum HBeAg content was related to HBV-DNA content significantly (P < 0.05) and their changes was correspondence., Conclusion: Before and during treatment of interferon, HBeAg and HBV-DNA content changes are closely related, while there is no significant correlation between HBsAg and HBeAg and HBV-DNA content. During interferon therapy, HBsAg, HBeAg, HBV-DNA contents should be detected together.

Cr(III) could be oxidized only by manganese oxide minerals as natural inorganic oxidants in nature, and so the rate and mechanism of interaction between manganese oxide minerals and Cr(III) were widely concerned. The effects of Mn(III) in birnessites, the most common Mn oxide mineral in the environment, on the rate of Cr(III) oxidation with birnessites and the kinetic characteristics were investigated through batch kinetic technique. The results show that Cr(III) oxidation rate follows a pseudo-first-order reaction, and the apparent rate constant K(obs), is 0.031 3 min(-1) when the average oxidation state (AOS) of Mn is about 3.50 in birnessite. When the birnessite is pretreated with Na4P2O7 solution, and the Mn(III) can be complexed out from the solid oxides. Therefore the content of Mn(III) in the birnessites decreases and the AOS of manganese increases. The AOSs of Mn for the pretreated birnessites increase from 3.50 to 3.63, 3.73 and 3.78 when the concentrations of Na4P2O7 are about 10, 20 and 50 mmol/L respectively. The Mn(III) content does not affect the initial oxidation rate of Cr(III) markedly, although oxidation amount of Cr(III) increases with the AOS of Mn. The apparent rate constants for the corresponding pretreated birnessites are 0.035 1, 0.032 5 and 0.0309 min(-1) respectively. The oxidation rate of Cr( III) is markedly influenced by the amount of Mn(III) produced in the transformation process of Mn(VN) --> Mn(III). The newly formed Mn(III) is complexed by Na4P2O7 and the oxidation rate decreases to 45%-88%. The lower content of Mn(III) in birnessites, the more Mn(III) newly formed from the transformation of Mn(IV) is complexed out from the minerals, and the greater amplitude in the decrease of Cr(III) oxidation rate. Thus the newly formed Mn(III) is highly active and possesses fast rate of electron transfer, however the rate of electron transfer in the transformation process of Mn(IV) --> Mn(III) is relatively slow. It could be deduced that the controlling step of initial oxidation rate of Cr(III) with birnessites may be the electron transfer process of Mn(IV) --> Mn(III).

Objective: To evaluate whether the rapid viral response (RVR) to combinational therapy with interferon and rabavirin can be used to predict the sustained viral response (SVR) in chronic hepatitis C patients., Methods: According to their clinical characteristics, all patients in this study were given pegylated or conventional interferon injection and different dose of ribavirin according to their weight. Patients were injected Pegasys (pegierferon alpha-2a) 180 microg or 135 microg once a week, or pegyintron 50-80 microg once a week, or conventional interferon 3-5 MU every two days, in combination with a dose of 600-1500 mg/d ribavirin. The serum HCV RNA load was determined at 0, 4, 12 week, and then every 12 weeks. After the viral response obtained, the patients were treated for another 24-72 weeks and followed up 24 weeks. The main parameter to evaluate the efficacy was SVR rate. The influence factors associated with rapid viral response were investigated., Results: RVR was obtained at week 4 in 84.2% of the 120 patients. The HCV RNA baseline of RVR group was (5.883+/-1.246) lg copies/ml, which was significantly lower than that of the group without RVR [(6.502+/-0.693) lg copies/ml, t=2.15, P=0.034]. 97 patients with RVR who finished treatment and follow-up, 90.7% of these patients obtained SVR, but the SVR rate in patients (82.4%) without RVR was lower than that in patients with RVR (x2=0.371, P=0.543). In this study, RVR rate was not associated with HCV genotype and the dose of interferon used. In the naive patients, the RVR to pegylated interferon was 87.8%, which was significantly higher than that in retreat patients (x2=4.651, P=0.031)., Conclusion: High RVR rate could be obtained in chronic hepatitis C patients treated combined with interferon and ribavirin. RVR rate is associated with the HCV RNA baseline load in both naive and retreat patients but not correlated to HCV genotype. RVR could predict the SVR.

Promoter CpG methylation of tumour suppressor genes (TSGs) is an epigenetic biomarker for TSG identification and molecular diagnosis. We screened genome wide for novel methylated genes through methylation subtraction of a genetic demethylation model of colon cancer (double knockout of DNMT1 and DNMT3B in HCT116) and identified DLEC1 (Deleted in lung and oesophageal cancer 1), a major 3p22.3 TSG, as one of the methylated targets. We further found that DLEC1 was downregulated or silenced in most colorectal and gastric cell lines due to promoter methylation, whereas broadly expressed in normal tissues including colon and stomach, and unmethylated in expressing cell lines and immortalised normal colon epithelial cells. DLEC1 expression was reactivated through pharmacologic or genetic demethylation, indicating a DNMT1/DNMT3B-mediated methylation silencing. Aberrant methylation was further detected in primary colorectal (10 out of 34, 29%) and gastric tumours (30 out of 89, 34%), but seldom in paired normal colon (0 out of 17) and gastric (1 out of 20, 5%) samples. No correlation between DLEC1 methylation and clinical parameters of gastric cancers was found. Ectopic expression of DLEC1 in silenced HCT116 and MKN45 cells strongly inhibited their clonogenicity. Thus, DLEC1 is a functional tumour suppressor, being frequently silenced by epigenetic mechanism in gastrointestinal tumours.