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Biomedical subjects

Li Huang

Publications and source records attributed to Li Huang.

At least 19 recordsLinked to original sources

Age as a core disease modifier: Distinct clinical, molecular and prognostic landscapes of essential thrombocythaemia in adolescents and young adults.

Essential thrombocythaemia (ET) in adolescents and young adults (AYA, 15-39 years) is a distinct entity with an incompletely defined prognosis. In this multicentre retrospective study, 1728 ET patients from 29 centres across China were stratified into AYA (n = 328) and non-AYA (≥40 years, n = 1400) cohorts. We compared their clinical profiles, genomic landscapes, long-term outcomes and risk factors for progression to post-ET myelofibrosis (MF). AYA patients had fewer cardiovascular risks and lower thrombosis rates, but higher rates of extreme thrombocytosis. Molecularly, AYA patients were enriched for calreticulin (CALR) mutations, whereas Janus kinase 2 (JAK2) predominated in older patients. The burden of non-driver mutations (tet methylcytosine dioxygenase 2 [TET2], DNA methyltransferase 3A [DNMT3A], ASXL transcriptional regulator 1 [ASXL1], SH2‑B adaptor protein 3 [SH2B3]) was lower in AYA patients. Consequently, AYA patients achieved superior long-term outcomes across all key survival endpoints, including overall, myelofibrosis-free and leukaemia-free survival. Analysis of post-ET MF progression risks identified age-specific patterns: CALR mutations are enriched in younger patients and show an age-specific association with MF progression. AYA-ET constitutes a unique clinicomolecular subtype with a favourable prognosis, supporting age-stratified management. The enrichment of CALR mutations and their specific link to MF progression in young patients underscore the urgent need for targeted therapies against CALR-mutant clones.

adolescents and young adults (AYA)↗

Deficiency of Bim in dendritic cells contributes to overactivation of lymphocytes and autoimmunity.

Apoptosis in dendritic cells (DCs) can potentially regulate DC homeostasis and immune responses. We have previously observed that inhibition of the Fas signaling pathway in DCs results in spontaneous T-cell activation and the development of systemic autoimmunity in transgenic mice. However, the role for different apoptosis pathways in DCs in regulating DC homeostasis and immune tolerance remains to be determined. Bim, a BH3-only protein of the Bcl-2 family, was expressed at low levels in DCs and was significantly up-regulated by signaling from CD40 or toll-like receptors (TLRs). Because Bim(-/-) mice develop spontaneous systemic autoimmunity, we investigated whether Bim(-/-) DCs contributed to lymphoproliferation and autoimmunity in these mice. Bim(-/-) DCs showed decreased spontaneous cell death, and induced more robust T-cell activation in vitro and in vivo. Moreover, Bim(-/-) DCs induced autoantibody production after adoptive transfer. Our data suggest that Bim is important for regulating spontaneous cell death in DCs, and Bim-deficient DCs may contribute to the development of autoimmune diseases in Bim(-/-) mice.

Animals↗

Photochemistry in the mixed aqueous solution of nitrobenzene and nitrous acid as initiated by the 355 nm UV light.

The 355 nm photon-initiated microscopic reaction mechanisms of the mixed aqueous solution of nitrobenzene and nitrous acid in the presence or absence of O(2) were studied by the laser flash photolysis technique. The main transient absorption peaks in the recorded spectra were assigned and the growth/decay trends of several transient species were investigated. It was found that the OH radical formed from the photolysis of nitrous acid triggered most of the subsequent radical reactions. The rate constant of the reaction between OH radical and nitrobenzene was measured to be (3.4 +/- 0.1) x 10(9) l mol(-1) s(-1). The product from this reaction, namely C(6)H(5)NO(2)-OH adduct, was found to react with O(2) to yield C(6)H(5)NO(2)-OHO(2) adduct with a rate constant of (1.6 +/- 0.2) x 10(9) l mol(-1) s(-1). Final steady-state products were identified by GC/MS analysis and were in accordance with the transient spectroscopic results. The possible reaction pathways were proposed.

Gas Chromatography-Mass Spectrometry↗

Interplay between primase and replication factor C in the hyperthermophilic archaeon Sulfolobus solfataricus.

The heterodimeric primase from the hyperthermophilic archaeon Sulfolobus solfataricus synthesizes long RNA and DNA products in vitro. How primer synthesis by primase is coupled to primer extension by DNA polymerase in this organism is unclear. Here we show that the small subunit of the clamp loader replication factor C (RFC) of S. solfataricus interacted with both the catalytic and non-catalytic subunits of the primase by yeast two-hybrid and co-immunoprecipitation assays. Further, the primase-RFC interaction was also identified in the cell extract of S. solfataricus. Deletion analysis indicated that the small subunit of RFC interacted strongly with the N-terminal domain of the catalytic subunit of the primase. RFC stimulated dinucleotide formation but decreased the amount of primers synthesized by the primase. The inhibition of primer synthesis is consistent with the observation that RFC reduced the affinity of the primase for DNA templates. On the other hand, primase stimulated the ATPase activity of RFC. These findings suggest that the primase-RFC interaction modulates the activities of both enzymes and therefore may be involved in the regulation of primer synthesis and the transfer of primers to DNA polymerase in Archaea.

Adenosine Triphosphatases↗

Refractive error and visual impairment in school children in rural southern China.

PURPOSE: To assess the prevalence of refractive error and visual impairment in school children in a rural area of southern China. DESIGN: Prospective cross-sectional survey. PARTICIPANTS: Two thousand four hundred children from junior high schools in Yangxi County. METHODS: Random selection of classes from the 3 junior high school grade levels was used to identify the study sample. Children from 36 classes in 13 schools were examined in April 2005. The examination included visual acuity (VA) testing; ocular motility evaluation; cycloplegic autorefraction; and examination of the external eye, anterior segment, media, and fundus. MAIN OUTCOME MEASURES: Distance VA and cycloplegic refraction. RESULTS: Among 2515 enumerated children, 2454 (97.6%) were examined. The study population consisted of the 2400 children between 13 and 17 years old. Prevalences of uncorrected, presenting, and best-corrected VA < or = 20/40 in the better eye were 27.0%, 16.6%, and 0.46%, respectively. Sixty percent of those who could achieve acuity > or =20/32 in at least one eye with best correction were without the necessary spectacles. Refractive error was the cause in 97.1% of eyes with reduced vision; amblyopia, 0.81%; other causes, 0.67%; and unexplained causes, 1.4%. Myopia (spherical equivalent, -0.50 diopters [D] or more in either eye) affected 36.8% of 13-year-olds, increasing to 53.9% of 17-year-olds. Myopia was associated with higher grade level, female gender, schooling in the county urban center, and higher parental education. Hyperopia (+2.00 D or more) affected approximately 1.0% in all age groups. Astigmatism (> or =0.75 D) was present in 25.3% of all children. CONCLUSIONS: Reduced vision because of uncorrected myopia is a public health problem among school-age children in rural China. Effective VA screening strategies are needed to eliminate this easily treated cause of visual impairment.

Adolescent↗

Anti-AIDS agents 69. Moronic acid and other triterpene derivatives as novel potent anti-HIV agents.

In a continuing structure-activity relationship study of potent anti-HIV agents, seven new triterpene derivatives were designed, synthesized, and evaluated for in vitro antiviral activity. Among them, moronic acid derivatives 19, 20, and 21 showed significant activity in HIV-1 infected H9 lymphocytes. Compounds 19 and 20 were also evaluated against HIV-1 NL4-3 and drug resistant strains in the MT-4 cell line. Compounds 19 and 20 showed better antiviral profiles than the betulinic acid analogue 8 (PA-457), which has successfully completed a Phase IIa clinical trial. Compound 20 showed potent anti-HIV activity with EC50 values of 0.0085 microM against NL4-3, 0.021 microM against PI-R (a multiple protease inhibitor resistant strain), and 0.13 microM against FHR-2 (an HIV strain resistant to 8). Promising compound 20 has become a new lead for modification, and further development of 20-related compounds as clinical trial candidates is warranted.

Anti-HIV Agents↗

Production and characterization of single chain Fv directed against beta2-agonist clenbuterol.

The single chain Fv (scFv) directed against beta2-agonist clenbuterol (CBL) was produced by using phage display technology. The heavy chain and light chain variable region genes (VH) VL) were amplified by the polymerase chain reaction (PCR) from CBL specific hybridoma cell lines 5D1 and assembled as a single chain Fv (scFv) fragment with linker peptide (Gly4Ser)3. Then the scFv DNA fragment was cloned into M13 phagemid vector pCANTAB5E and the anti-CBL antibody libraries were constructed. Phages displaying scFv were enriched by panning with CBL-ovalbumin (CBL-OVA) conjugate. After only one round of panning, antigen-positive recombinant phage clones were successfully selected by ELISA. The positive phage was used to infect Escherichia coli HB2151, and the expression of soluble scFv was then induced by IPTG. The scFv showed an improved sensitivity (with IC50 of 0.78 +/- 0.005 ng/mL (n = 4)) when compared with the parent monoclonal antibody (MAb) (with IC50 of 1.34 +/- 0.006 ng/mL (n = 4)) in competitive indirect ELISA (CI-ELISA). Cross-reactivity studies showed that the specificity of scFv was similar to that of MAb. The recombinant scFv prepared in this study could be potentially used instead of conventional antisera or MAb for development of a rapid and affordable immunoassay for the detection of residual CBL in biological matrices.

Adrenergic beta-Agonists↗

A novel ZnII-sensitive fluorescent chemosensor assembled within aminopropyl-functionalized mesoporous SBA-15.

A novel Zn2+-sensitive fluorescent chemosensor SC/SBA-15 has been obtained by the self-assembly of 4-chloroaniline-N-salicylidene (SC), a Schiff base ligand, within the channel of silylation-modified SBA-15 without destroying its hexagonally ordered mesoporous structure. The remarkable 200-fold fluorescence enhancement with a large Stokes shift of 180 nm in luminescence emission upon the addition of Zn2+ is attributed to the formation of a coordinate complex of a large rigid conjugate system and Zn2+ ions.

Amination↗

EGF signaling overcomes a uterine cell death associated with temporal mis-coordination of organogenesis within the C. elegans egg-laying apparatus.

We isolated cog-3(ku212) as a C. elegans egg-laying defective mutant that is associated with a connection-of-gonad defective phenotype. cog-3(ku212) mutants appear to have no connection between the vulval and the uterine lumens at the appropriate stage because the uterine lumen develops with a temporal delay relative to the vulva and, thus, is not present when the connection normally forms. The lack of temporal synchronization between the vulva and the uterus is not due to precocious or accelerated vulval development. Instead, global gonadogenesis is mildly delayed relative to development of extra-gonadal tissue. cog-3(ku212) mutants also have a specific uterine fate defect. Normally, four cells of the uterine pi lineage respond via their LET-23 epidermal growth factor-like receptors to a vulval-derived LIN-3 EGF signal and adopt the uterine vulval 1 (uv1) fate. In cog-3(ku212) mutants, these four pi progeny cells are set aside as a pre-uv1 population but undergo necrosis prior to full differentiation. A gain-of-function mutation in LET-23 EGF receptor and ectopic expression of LIN-3 EGF within the proper temporal constraints can rescue the uv1 defect, suggesting that a signaling defect, perhaps due to the temporal delay, is at fault. In support of this model, we demonstrate that lack of vulval-uterine coordination due to precocious vulval development also leads to uv1 cell differentiation defects.

Animals↗

Oxidation-induced changes in human lens epithelial cells. 1. Phospholipids.

Lipid compositional changes in lens epithelial cells (HLE B-3) grown in a hyperoxic atmosphere were studied to determine if oxidation could cause changes in the amount and type of phospholipid similar to those found in vivo with age and cataract. The phosphatidylcholines in HLE B-3 cells were 8 times more unsaturated than the sphingomyelins. Cell viability was the same for cells grown for up to 48 h in a normoxic or hyperoxic atmosphere. Lipid oxidation was about three times higher after growth in a hyperoxic atmosphere compared with cells grown in a normoxic atmosphere. The lack of change in the relative amount of sphingomyelin and the decrease in phosphatidylcholine coupled with the increase in lysophosphatidylcholine support the idea that similar mechanisms may be responsible for the lipid compositional changes in both lens epithelial and fiber cells. It is postulated that lipases eliminate oxidized unsaturated glycerolipids, leaving a membrane increasingly composed of more ordered and more saturated sphingolipids. Oxidative stress leads to changes in membrane composition that are consistent with those seen with age in human epithelial cells. Oxidation-induced epithelial phospholipid change is an area of research that has gone virtually unexplored in the human lens and could be relevant to all cell types and may be important to lens clarity.

Aging↗

Investigation of a new approach to decompose two potent greenhouse gases: photoreduction of SF(6) and SF(5)CF(3) in the presence of acetone.

In this paper, we addressed the utilization of photochemical method as an innovative technology for the destruction and removal of two potent greenhouse gases, SF(6) and SF(5)CF(3). The destruction and removal efficiency (DRE) of the process was determined as a function of excitation wavelength, irradiation time, initial ratio of acetone to SF(5)X (X represented F or CF(3)), initial SF(5)X concentration, additive oxygen and water vapor concentration. A complete removal was achieved by a radiation period of 55min and 120min for SF(6)-CH(3)COCH(3) system and SF(5)CF(3)-CH(3)COCH(3) system respectively under 184.9nm irradiation. Extra addition of water vapor can enhance DRE by approximately 6% points in both systems. Further studies with GC/MS and FT-IR proved that no hazardous products such as S(2)F(10), SO(2)F(2), SOF(2), SOF(4) were generated in this process.

Acetone↗

Risky sexual behaviors, alcohol use, and drug use: a comparison of Eastern and Western European adolescents.

PURPOSE: The current study examined to what extent cultural context moderated developmental processes, namely the patterns of association between low self-control, family processes and three indicators of health-compromising behaviors (risky sexual behaviors, alcohol and drug use) in two Eastern European and two Western European adolescent samples. METHODS: School-based questionnaire data were collected from n = 7291 middle and late adolescents in Hungary, Slovenia, The Netherlands, and Switzerland. Students rated measures of self-control, family processes (closeness, support, and monitoring), and health-compromising behaviors. The data were analyzed by a series of set hierarchical regression analyses as well as follow-up z-tests for comparisons of individual regression coefficients. RESULTS: Findings provided evidence that low self-control was positively associated with all three measures of health-compromising behaviors in a largely invariant fashion across countries. Differences were found in developmental processes, where low self-control was more weakly associated with risky sexual behaviors in samples of both Eastern European countries as compared with Western European ones, thus providing some evidence of idiosyncratic cultural norms. Results also provided evidence of mostly direct effects by family processes on measures of health-compromising behaviors. With two exceptions, no differences were observed in these effects across the four samples. CONCLUSION: Low self-control explains variability in health-compromising behaviors, especially in alcohol and drug use. The observed differences in the link between low self-control and risky sexual behaviors may provide some evidence of distinct norms and values among Eastern European youth in comparison with Western European adolescents related to these behaviors.

Adolescent↗

Oxidation-induced changes in human lens epithelial cells 2. Mitochondria and the generation of reactive oxygen species.

The relationships among reactive oxygen species (ROS) generation, lipid compositional changes, antioxidant power, and mitochondrial membrane potential were determined in a human lens epithelial cell line, HLE-B3. Cells grown in a hyperoxic atmosphere grew linearly for about 3 days, and then progressively died. Total antioxidant power and ROS generation increased by 50 and 43%, respectively, in cells grown in a hyperoxic atmosphere compared to those cultured in a normoxic atmosphere. By specifically uncoupling the mitochondrial proton gradient, we determined that the mitochondria are most likely the major source of ROS generation. ROS generation correlated inversely with mitochondrial membrane potential and the amount of cardiolipin, factors likely to contribute to loss of cell viability. Our results support the idea that hyperoxic damage to HLE-B3 cells derives from enhanced generation of ROS from the mitochondrial electron transport chain resulting in the oxidation of cardiolipin. With extended hyperoxic insult, the oxidants overwhelm the antioxidant defense system and eventually cell death ensues.

Carbonyl Cyanide m-Chlorophenyl Hydrazone↗

Design, synthesis, and biological evaluation of semicarbazide-sensitive amine oxidase (SSAO) inhibitors with anti-inflammatory activity.

In an attempt to examine the effect of inhibition of semicarbazide-sensitive amine oxidase (SSAO; EC 1.4.3.6, also known as VAP-1) as a novel anti-inflammatory target, the structure/mechanism based design and synthesis of a series of novel hydrazino-containing small molecules are described. The in vitro biological results show that compounds 4a,c are highly potent SSAO inhibitors with notable selectivity toward SSAO over monoamine oxidases A and B (MAO-A and MAO-B). SAR studies based on compound 4c were performed, and the results are discussed. The most potent and selective compound, 4a (IC(50) = 2 nM), is an orally active, competitive, and apparently irreversible inhibitor of SSAO that is effective at reducing disease incidence and severity in an in vivo animal disease model of multiple sclerosis.

Acute Disease↗

Dendritic cell apoptosis in the maintenance of immune tolerance.

Apoptosis in the immune system is critical for maintaining self-tolerance and preventing autoimmunity. Nevertheless, inhibiting apoptosis in lymphocytes is not alone sufficient to break self-tolerance, suggesting the involvement of other cell types. We investigated whether apoptosis in dendritic cells (DCs) helps regulate self-tolerance by generating transgenic mice expressing the baculoviral caspase inhibitor, p35, in DCs (DC-p35). DC-p35 mice displayed defective DC apoptosis, resulting in their accumulation and, in turn, chronic lymphocyte activation and systemic autoimmune manifestations. The observation that a defect in DC apoptosis can independently lead to autoimmunity is consistent with a central role for these cells in maintaining immune self-tolerance.

Adoptive Transfer↗

Structural variation and evolution of a defense-gene cluster in natural populations of Aegilops tauschii.

Genetic mapping and sequencing of plant genomes have been useful for investigating eukaryotic chromosome structural organization. In many cases, analyses have been limited in the number of representatives sampled from specific groups. The degree of intraspecific genome diversity remains in question. The possibility exists that a single model genome may have limited utility for identifying genes in related members of the species or genus. Crop improvement programs have particular interests in disease resistance genes that are harbored by wild relatives of modern cultivated crops. These genes are evolutionarily dynamic and under selective pressure by a broad range of pathogenic organisms. Using resistance gene analogs as models for gene evolution, intraspecific genome comparisons were made among populations of wild diploid wheat (Aegilops tauschii). We observed that deletion haplotypes are occurring frequently and independently in the genome. Haplotypes are geographically correlated and maintenance of gene complements in localized populations indicates selective advantage. Furthermore, deletion haplotypes are not detrimental to plant health, since genes without adaptive value in alternate environments are eliminated from the genome. Deletion haplotypes appear to be a common form of allelic variation in plants, and we address the consequences on genome restructuring and gene evolution.

Chromosomes, Plant↗

Surface mobility difference between Si and Ge and its effect on growth of SiGe alloy films and islands.

Based on first-principles calculations of surface diffusion barriers, we show that on a compressive Ge(001) surface the diffusivity of Ge is 10(2)-10(3) times higher than that of Si in the temperature range of 300 to 900 K, while on a tensile surface, the two diffusivities are comparable. Consequently, the growth of a compressive SiGe film is rather different from that of a tensile film. The diffusion disparity between Si and Ge is also greatly enhanced on the strained Ge islands compared to that on the Ge wetting layer on Si(001), explaining the experimental observation of Si enrichment in the wetting layer relative to that in the islands.

Journal Article↗