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Biomedical subjects

Hong Cao

Publications and source records attributed to Hong Cao.

At least 19 recordsLinked to original sources

Genome-wide association study reveals that TaODORANT1 negatively contributes to thousand grain weight by affecting starch synthesis in wheat.

Thousand grain weight (TGW) is one of the most important factors that control grain weight and crop yield. To date, dozens of wheat genes related to TGW have been isolated; however, the underlying molecular mechanisms governing grain development in wheat (Triticum aestivum) remain largely unknown. Benefiting from whole-genome resequencing and genome-wide association study, we identified an R2R3-type myeloblastosis (MYB) transcription factor, TaODORANT1, which was tightly associated with TGW. TaODORANT1 was specifically and highly expressed during the wheat grain developing stage. Knockout of TaODORANT1 led to an increase in TGW and starch content, as well as affected the expression of starch synthesis-related genes. Loss of function of TaODORANT1 altered the molecular structure and physiochemical properties of grain starch. Haplotype analysis showed that favorable Hap IV of TaODORANT1-A and favorable Hap I of TaODORANT1-B were significantly associated with the production of larger grains and higher TGW, respectively. Moreover, TaODORANT1 was a crucial targeted gene continuously selected in wheat domestication and breeding, and its orthologous genes might have retained similar functions in response to grain development. Our results highlight the importance of TaODORANT1 in affecting TGW, presenting potential targets for improving yield in wheat.

Triticum↗

Discovery of HIV-1 protease inhibitors with picomolar affinities incorporating N-aryl-oxazolidinone-5-carboxamides as novel P2 ligands.

Here, we describe the design, synthesis, and biological evaluation of novel HIV-1 protease inhibitors incorporating N-phenyloxazolidinone-5-carboxamides into the (hydroxyethylamino)sulfonamide scaffold as P2 ligands. Series of inhibitors with variations at the P2 phenyloxazolidinone and the P2' phenylsulfonamide moieties were synthesized. Compounds with the (S)-enantiomer of substituted phenyloxazolidinones at P2 show highly potent inhibitory activities against HIV-1 protease. The inhibitors possessing 3-acetyl, 4-acetyl, and 3-trifluoromethyl groups at the phenyl ring of the oxazolidinone fragment are the most potent in each series, with K(i) values in the low picomolar (pM) range. The electron-donating groups 4-methoxy and 1,3-dioxolane are preferred at P2' phenyl ring, as compounds with other substitutions show lower binding affinities. Attempts to replace the isobutyl group at P1' with small cyclic moieties caused significant loss of affinities in the resulting compounds. Crystal structure analysis of the two most potent inhibitors in complex with the HIV-1 protease provided valuable information on the interactions between the inhibitor and the protease enzyme. In both inhibitor - enzyme complexes, the carbonyl group of the oxazolidinone ring makes hydrogenbond interactions with relatively conserved Asp29 residue of the protease. Potent inhibitors from each series incorporating various phenyloxazolidinone based P2 ligands were selected and their activities against a panel of multidrug-resistant (MDR) protease variants were determined. Interestingly, the most potent protease inhibitor starts out with extremely tight affinity for the wild-type enzyme (K(i) = 0.8 pM), and even against the MDR variants it retains picomolar to low nanomolar K(i), which is highly comparable with the best FDA-approved protease inhibitors.

Amides↗

New evidence for the involvement of spinal fractalkine receptor in pain facilitation and spinal glial activation in rat model of monoarthritis.

Fractalkine, a chemokine binding to only one known receptor CX3CR1, has recently been proposed to be a neuron-to-glia signal in the spinal cord leading to microglial activation and glially dependent pain facilitation. The previous studies explored that blockade of endogenous fractalkine, using anti-CX3CR1 neutralizing antibody, dose-dependently attenuated neuropathic pain. The present study examined the role of endogenous fractalkine in inflammatory pain. Intra-articular injection of complete Freund's adjuvant (CFA)-induced rat ankle joint monoarthritis (MA) model was used. Western blot analysis revealed that CX3CR1 expression in the spinal cord was significantly increased following CFA-induced MA. Intrathecal injection of anti-CX3CR1 neutralizing antibody both delayed the development of mechanical allodynia and thermal hyperalgesia, and reversed established pain facilitation. Furthermore, blockade of CX3CR1 significantly suppressed activation of spinal glia, especially microglia, evoked by MA. These data provided new evidence for the contribution of endogenous fractalkine to the initiation and early maintenance of inflammatory pain facilitation via activating spinal microglia.

Analysis of Variance↗

The microfauna communities and operational monitoring of an activated sludge plant in China.

The composition of the microfauna community in aeration tanks at the Baoding Sewage Treatment Plant in China was analysed each week from July 2002 to July 2003. The community composition of these microfauna populations was compared with effluent quality data recorded on the same days. A total of 94 species of ciliates, 40 species of amoebae and 13 species of large flagellates were identified in the 50 samples analysed. Numbers of metazoa including rotifers, nematodes, gastrotrichs and oligochaeta were also recorded. Although, Aspidisca cicada showed the highest mean abundance and was present in 98% of the samples, factor analysis revealed, among other things, that high Vorticella convallaria and Arcella hemisphaerica populations correlated with good performance of the treatment plant, while high numbers of Litonotus obtusus indicated poor conditions for settlement of sludge. These results show some agreement with an earlier study of sewage plants in Beijing, but analysis of more plants having a diversity of input components working under a range of different operating conditions should be performed to gain a general understanding of the value of indicator species for predicting the efficiency of activated sludge plants in China.

Animals↗

Hemagglutinin (HA) proteins from H1 and H3 serotypes of influenza A viruses require different antigen designs for the induction of optimal protective antibody responses as studied by codon-optimized HA DNA vaccines.

Effective antibody responses provide crucial immunity against influenza virus infection. The hemagglutinin (HA) protein is the major target of protective antibody responses induced by viral infection and by vaccination with both inactivated and live-attenuated flu vaccines, but knowledge about the optimal designs of protective HA antigens from different flu serotypes is still limited. In this study, we have significantly improved the immunogenicity of HA-expressing DNA vaccines by using codon-optimized HA sequences for either an H1 serotype (A/NewCal/20/99) or an H3 serotype (A/Panama/2007/99) human influenza A virus and then used these constructs as model antigens to identify the optimal HA antigen designs to elicit high-level protective antibody responses. Two forms of HA antigen, a wild-type, full-length HA and a secreted form with transmembrane (TM) domain-truncated HA, were produced. Both forms of HA DNA vaccines, from either H1 or H3 serotypes, were able to elicit high levels of HA-specific immunoglobulin G responses in immunized rabbits as measured by enzyme-linked immunosorbent assay. Interestingly, the abilities of H1 HA and H3 HA antigens to elicit hemagglutination inhibition (HI) and neutralizing antibody (NAb) responses differ. For the H1 HA antigens, the full-length HA induced significantly higher HI and NAb responses than did the TM-truncated HA. For the H3 HA antigen, both the full-length HA and TM-truncated HA induced high levels of HI and NAb responses. These data indicate that H1 and H3 antigens have different expression requirements for the induction of an optimal protective antibody response and that the structure integrity of HA antigens is critical for eliciting type-specific protective antibody responses. Our findings will have an important impact on future subunit-based flu vaccine development.

Animals↗

Light chain editing generates polyreactive antibodies in chronic graft-versus-host reaction.

The chronic graft-versus-host (cGvH) reaction is a model of induced lupus caused by alloreactive CD4(+) T cells from a Bm-12 mouse in a C57BL/6 recipient. We used this cGvH reaction in C57BL/6 anti-DNA H chain transgenic mice, 56R/B6, to understand the structure, specificity, and origin of the induced autoantibodies (auto-Abs). We found anti-DNA Abs that reacted to several different antigens, such as phosphatidylserine, myelin basic protein, thyroglobulin, histone, insulin, cytochrome C, and beta-galactosidase. This polyreactivity was found for Abs from B cells that expressed the 56R H chain transgene with "editor" L chains that did not completely veto autoreactivity. We suggest that such incomplete editing results in polyreactivity and that incompletely edited polyreactive B cells influence the subsequent expression of pathogenic auto-Abs in disease. We also found B cells that coexpress kappa and lambda L chain. These B cells contributed to the autoimmune response and are possibly in the marginal zone of the spleen.

Animals↗

Effect of cytochromes P450 chemical inhibitors and monoclonal antibodies on human liver microsomal esterase activity.

Selective and nonselective cytochromes P450 (P450) chemical inhibitors and monoclonal antibodies (mAbs) are routinely used to determine the contribution of P450 enzymes involved in the biotransformation of a drug. A fluorometric assay has been established using fluorescein diacetate as a model substrate to determine the effect of some commonly used P450 inhibitors and mAbs on human liver microsomal esterase activity. Of those inhibitors studied, only alpha-naphthoflavone, clotrimazole, ketoconazole, miconazole, nicardipine, and verapamil significantly inhibited human liver microsomal esterase activity, with apparent IC50 values of 18.0, 20.5, 6.5, 15.0, 19.4, and 5.4 microM, respectively. All of these showed > or =20% inhibition of human liver microsomal esterase activity at concentrations typically used for P450 reaction phenotyping studies, with clotrimazole, miconazole, nicardipine, and verapamil showing >60% inhibition. Unlike the chemical inhibitors, no inhibition of human liver microsomal esterase activity was observed in the presence of mAb to CYP1A2, 2C8, 2C9, 2C19, 2D6, and 3A4. These results suggest that P450 chemical inhibitors are capable of inhibiting human liver microsomal esterase activity and should not be used to assess the role of P450 enzymes in the biotransformation of esters. The lack of inhibition of human liver microsomal esterase activity by P450-specific monoclonal antibodies suggests that they may be used to assess the role of P450 enzymes in the biotransformation of esters. Additional experiments to assess the contribution of oxidative enzymes in the metabolism of esters may include incubations in the presence and absence of beta-nicotinamide adenine dinucleotide 2'-phosphate reduced.

Antibodies, Monoclonal↗

Is endogenous D-serine in the rostral anterior cingulate cortex necessary for pain-related negative affect?

Functional activation of NMDA receptors requires co-activation of glutamate- and glycine-binding sites. D-serine is considered to be an endogenous ligand for the glycine site of NMDA receptors. Using a combination of a rat formalin-induced conditioned place avoidance (F-CPA) behavioral model and whole-cell patch-clamp recording in rostral anterior cingulate cortex (rACC) slices, we examined the effects of d-amino acid oxidase (DAAO), an endogenous D-serine-degrading enzyme, and 7-chlorokynurenate (7Cl-KYNA), an antagonist of the glycine site of NMDA receptors, on pain-related aversion. Degradation of endogenous D-serine with DAAO, or selective blockade of the glycine site of NMDA receptors by 7Cl-KYNA, effectively inhibited NMDA-evoked currents in rACC slices. Intra-rACC injection of DAAO (0.1 U) and 7Cl-KYNA (2 and 0.2 mM, 0.6 microL per side) 20 min before F-CPA conditioning greatly attenuated F-CPA scores, but did not affect formalin-induced acute nociceptive behaviors and electric foot shock-induced conditioned place avoidance. This study reveals for the first time that endogenous D-serine plays a critical role in pain-related aversion by activating the glycine site of NMDA receptors in the rACC. Furthermore, these results extend our hypothesis that activation of NMDA receptors in the rACC is necessary for the acquisition of specific pain-related negative emotion. Thus a new and promising strategy for the prevention of chronic pain-induced emotional disturbance might be raised.

Animals↗

Isolation and characterization of a pseudomonas oleovorans degrading the chloroacetamide herbicide acetochlor.

To date, no pure bacterial cultures that could degrade acetochlor have been described. In this study, one strain of microorganism capable of degrading acetochlor, designated as LCa2, was isolated from acetochlor-contaminated soil. The strain LCa2 is Pseudomonas oleovorans according to the criteria of Bergey's manual of determinative bacteriology and sequence analysis of the partial 16S rRNA gene. Optimum growth temperature and pH were 35 degrees C and 8.0, respectively. The strain could degrade 98.03% of acetochlor treated at a concentration of 7.6 mg l(-1) after 7 days of incubation and could tolerate 200 mg l(-1) of acetochlor. When the acetochlor concentration became higher, the degradation cycle became longer. The acetochlor biodegradation products were identified by GC-MS based on mass spectral data and fragmentation patterns. The main plausible degradative pathways involved dechlorination, hydroxylation, N-dealkylation, C-dealkylation and dehydrogenation.

Herbicides↗

Effects of an organophosphorous insecticide on survival, fecundity, and development of Hylyphantes graminicola (Sundevall) (Araneae: Linyphiidae).

Abstract-The effects of an organophosphorous insecticide, methamidophos, on fecundity and development of the spider Hylyphantes graminicola (Sundevall) (Araneae: Linyphiidae) were assessed under laboratory conditions. Susceptibility of adults of both sexes to the insecticide and its influence on fecundity of females and development of offspring were investigated. At 48 h after topical application in adults, the median lethal dose (LD50) and 10% lethal dose (LD10) were 0.35 and 0.12 microg/spider, respectively, for males and 0.52 and 0.16 microg/spider, respectively, for females. Methamidophos had detrimental effects on fecundity of females; number of eggs per clutch, total egg mass, and clutch size decreased significantly. The hatching rate of eggs from LD10-treated females was slightly higher than the rate in the controls, but the hatching rate of eggs from LD50-treated females was lower than the rate in the controls. However, no significant differences were observed in hatching time and development time across treatments. Development time of spiderlings from LD50-treated females was significantly longer than the time in the controls, and body sizes of the first spiderlings from insecticide-treated females were larger than those in the controls. However, matured offspring were smaller than those in the controls. It was concluded that methamidophos has long-term effects on H. graminicola, and that this may affect the development of spider populations in the field.

Animals↗

[Construction and identification of genomic cDNA subclones of dengue 2 virus NGC strain].

OBJECTIVE: To construct the cDNA subclones spanning the entire genome of dengue 2 virus NGC strain for further construction of full-length infectious viral cDNA clone. METHODS: Two pairs of primers were designed according to the restriction endonuclease sites in the viral genome of dengue 2 virus NGC strain. After viral RNA extraction from the brain of infected new-born mice, two parts of full-length viral cDNA were amplified by long RT-PCR and cloned into the vector pCR-XL-TOPO. The partial sequence of the recombinant plasmid was determined. RESULTS AND CONCLUSION: Sequence analysis and digestion with restriction enzymes demonstrated that the two cDNA subclones were specific for dengue 2 virus NGC strain, suggesting the successful construction of the two cDNA subclones of dengue 2 virus NGC strain.

Animals↗

[Studies on phenolic compounds from Polygonum aviculane].

OBJECTIVE: To study the chemical constituents from the aerial parts of Polygomun aviculane. METHOD: The chemical constituents were isolated by silica gel column chromatography and preparative silica thin layer chromatography, and their structures were elucidated on the basis of physico-chemical evidences and spectroscopic analysis (IR, MS, 1H and 13C-NMR). RESULT: Seven phenolic compounds were identified as rosmarinic acid (1), gallic acid (2), gentisic acid 5-O-(6'-O-galloyl)-beta-D-glucopyranoside (3), caffeic acid (4), p-coumaric acid (5), ethyl caffeate (6) and acteoside (7), respectively. CONCLUSION: Compounds 1, 3, 6 and 7 were isolated from this plant for the first time. These results provided theoretical evidences for the further bioactive investigation on this plant.

Caffeic Acids↗

A novel biosensor for sterigmatocystin constructed by multi-walled carbon nanotubes (MWNT) modified with aflatoxin-detoxifizyme (ADTZ).

Sterigmatocystin, ST, is carcinogenic mycotoxin with toxicity second to aflatoxins, contaminated in foods- and feeds-stuff widely. A three-electrode system was employed to examine the response character of the covalently united ADTZ-MWNTs electrode to ST, and the results indicated that an oxidation peak of ST was observed at about +400 mv, the linear detection range of ST was from 4.16 x 10(-5) mg/ml (0.13 microM) to 1.33 x 10(-3) mg/ml (4.29 microM) with the detection limit at 0.13 microM. Compared to the corresponding results obtained from the MWNTs modified electrode that ADTZ was directly sediment (adsorbed) on it, the sensitivity of ours had been improved by two orders of magnitude, which could provide some important data to further research.

Adsorption↗

Effects of magnolol and honokiol derived from traditional Chinese herbal remedies on gastrointestinal movement.

AIM: To study the effects of magnolol and honokiol on isolated smooth muscle of gastrointestinal tract and their relationship with Ca2+, and on the gastric emptying and the intestinal propulsive activity in mice. METHODS: Routine experimental methods using isolated gastric fundus strips of rats and isolated ileum segments of guinea pigs were adopted to measure the smooth muscle tension. The effects of magnolol 10(-3), 10(-4), 10(-5) mol/L, and honokiol 10(-4), 10(-5), 10(-6) mol/L on the contractility of gastric fundus strips of rats and ileum of guinea pigs induced by acetylcholine (Ach) and 5-hydroxytryptamine (5-HT) was assessed respectively. The method using nuclein and pigment methylene blue was adopted to measure the gastric retention rate of nuclein and the intestinal propulsive ratio of a nutritional semi-solid meal for assessing the effect of magnolol and honokiol (0.5, 2, 20 mg/kg) on gastric emptying and intestinal propulsion. RESULTS: Magnolol and honokiol significantly inhibited the contractility of isolated gastric fundus strips of rats treated with Ach or 5-HT and isolated ileum guinea pigs treated with Ach or CaCl2, and both of them behaved as non-competitive muscarinic antagonists. Magnolol and honokiol inhibited the contraction induced by Ach in Ca2+-free medium and extracellular Ca2+-dependent contraction induced by Ach. Each group of magnolol and honokiol experiments significantly decreased the residual rate of nuclein in the stomach and increased the intestinal propulsive ratio in mice. CONCLUSION: The inhibitory effect of magnolol and honokiol on contractility of the smooth muscles of isolated gastric fundus strips of rats and isolated ileum of guinea pigs is associated with a calcium-antagonistic effect. Magnolol and honokiol can improve the gastric emptying of a semi-solid meal and intestinal propulsive activity in mice.

Animals↗

High-Throughput GoMiner, an 'industrial-strength' integrative gene ontology tool for interpretation of multiple-microarray experiments, with application to studies of Common Variable Immune Deficiency (CVID).

BACKGROUND: We previously developed GoMiner, an application that organizes lists of 'interesting' genes (for example, under-and overexpressed genes from a microarray experiment) for biological interpretation in the context of the Gene Ontology. The original version of GoMiner was oriented toward visualization and interpretation of the results from a single microarray (or other high-throughput experimental platform), using a graphical user interface. Although that version can be used to examine the results from a number of microarrays one at a time, that is a rather tedious task, and original GoMiner includes no apparatus for obtaining a global picture of results from an experiment that consists of multiple microarrays. We wanted to provide a computational resource that automates the analysis of multiple microarrays and then integrates the results across all of them in useful exportable output files and visualizations. RESULTS: We now introduce a new tool, High-Throughput GoMiner, that has those capabilities and a number of others: It (i) efficiently performs the computationally-intensive task of automated batch processing of an arbitrary number of microarrays, (ii) produces a human-or computer-readable report that rank-orders the multiple microarray results according to the number of significant GO categories, (iii) integrates the multiple microarray results by providing organized, global clustered image map visualizations of the relationships of significant GO categories, (iv) provides a fast form of 'false discovery rate' multiple comparisons calculation, and (v) provides annotations and visualizations for relating transcription factor binding sites to genes and GO categories. CONCLUSION: High-Throughput GoMiner achieves the desired goal of providing a computational resource that automates the analysis of multiple microarrays and integrates results across all of the microarrays. For illustration, we show an application of this new tool to the interpretation of altered gene expression patterns in Common Variable Immune Deficiency (CVID). High-Throughput GoMiner will be useful in a wide range of applications, including the study of time-courses, evaluation of multiple drug treatments, comparison of multiple gene knock-outs or knock-downs, and screening of large numbers of chemical derivatives generated from a promising lead compound.

Binding Sites↗

Use of PFU protozoan community structural and functional characteristics in assessment of water quality in a large, highly polluted freshwater lake in China.

Structural and functional parameters of protozoan communities colonizing on PFU (polyurethane foam unit) artificial substrate were assessed as indicators of water quality in the Chaohu Lake, a large, shallow and highly polluted freshwater lake in China. Protozoan communities were sampled 1, 3, 6, 9 and 14 days after exposure of PFU artificial substrate in the lake during October 2003. Four study stations with the different water quality gradient changes along the lake were distinguishable in terms of differences in the community's structural (species richness, individual abundance, etc.) and functional parameters (protozoan colonization rates on PFU). The concentrations of TP, TN, COD and BOD as the main chemical indicators of pollution at the four sampling sites were also obtained each year during 2002-2003 for comparison with biological parameters. The results showed that the species richness and PFU colonization rate decreased as pollution intensity increased and that the Margalef diversity index values calculated at four sampling sites also related to water quality. The three functional parameters based on the PFU colonization process, that is, S(eq), G and T90%, were strongly related to the pollution status of the water. The number of protozoan species colonizing on PFU after exposure of 1 to 3 days was found to give a clear comparative indication of the water quality at the four sampling stations. The research provides further evidence that the protozoan community may be utilized effectively in the assessment of water quality and that the PFU method furnishes rapid, cost-effective and reliable information that may be useful for measuring responses to pollution stress in aquatic ecosystems.

Animals↗

Wavelength tuning in optically mode-locked semiconductor fiber ring lasers with linearly chirped fiber Bragg gratings.

We demonstrate wavelength tuning in single-wavelength and multiwavelength semiconductor fiber ring lasers that are mode locked with an optically injected control signal. A semiconductor optical amplifier is used to provide gain as well as to function as an optically controlled mode-locking element. Linearly chirped fiber Bragg gratings--single or superimposed--are used to define the lasing wavelengths as well as to provide wavelength tunability and allow for multiwavelength operation. We obtain pulses of tens of picoseconds in duration when we inject a sinusoidal optical control signal into the laser cavity, and we can tune the lasing wavelength(s) over the reflection bandwidth(s) of the grating(s) by simply changing the frequency of the injected control signal.

Journal Article↗