Biomedical subjects

Liang Xu

Publications and source records attributed to Liang Xu.

At least 19 recordsLinked to original sources

PubMed2026

Driver genomic lesions in MDM2, CDK4, and JUN co-opt targetable super-enhancer networks to impose liposarcomagenic core regulatory circuitry.

INTRODUCTION: Amplification of chromosome 12q13-15 spanning MDM2 and CDK4 genes serves as a molecular diagnostic hallmark of dedifferentiated liposarcoma (DDLPS), an aggressive soft-tissue sarcoma. Epigenetic activation of master transcription factors (RUNX proteins, FOSL2, and MYC) establishes a self-reinforcing oncogenic transcriptional circuitry in DDLPS. Nevertheless, the collaborative interplay between genomic alterations and epigenetic dysregulation in defining DDLPS cell identity remains elusive. OBJECTIVES: This work aimed to elucidate the primary genetic drivers and mechanistic basis of DDLPS-specific core transcriptional regulatory circuitry. METHODS: We performed integrative chromatin profiling analysis of DDLPS clinical specimens and cell lines to map cis-regulatory landscapes. Cistromes of MDM2, JUN, and E2F1 were delineated through chromatin immunoprecipitation sequencing in two DDLPS models. Essential driver functions and transcriptional regulatory effects of key regulators were assessed via various genetic manipulation approaches. Synergistic interactions between BET-targeting agents and MDM2/p53 or CDK4 inhibitors were quantified by cell viability assays. In vivo xenograft assays evaluated the oncogenic potential of key regulators and the therapeutic efficacy of novel strategies. RESULTS: Co-amplification of MDM2, CDK4, and JUN during sarcomagenesis converges with BET protein-dependent chromatin remodeling to fuel feed-forward transcriptional circuits among master transcription factors. Mechanistically, excessively expressed MDM2 stabilizes the core regulatory circuitry by forming chromatin-bound complexes with JUN/FOSL2 at cis-regulatory elements, especially super-enhancers across DDLPS genome. Concurrently, CDK4 maintains expression of E2F1 which further fosters transcriptional output of master transcription factors in DDLPS cells. Leveraging DDLPS-selective overexpression of MDM2 and its E3 ligase activity, targeted degradation of BET proteins by MDM2-recruiting proteolysis targeting chimera selectively disrupted the core regulatory circuitry, suppressing DDLPS growth and exhibiting strong synergy with CDK4 inhibitor. CONCLUSION: DDLPS-associated genomic lesions collaborate with BET-dependent chromatin regulation to establish disease-sustaining transcriptional circuitry. Our findings also provide a mechanistic rationale for harnessing MDM2's E3 ligase activity to therapeutically degrade oncoproteins in MDM2-amplified malignancies.

Core transcriptional regulatory circuitry↗

PubMed2026

Marine air promotes structural compaction and coating growth of soot aerosols after long-range transport from East Asia.

Soot aerosol, a key global warming contributor, undergoes morphological and chemical transformations during atmospheric transport, particularly in humidified marine environments. This study investigates morphology, mixing state, and aging mechanisms of soot particles collected in the Bohai Sea and Yellow Sea. Transmission electron microscopy analyses reveal that coated soot particles dominate the marine atmosphere, accounting for over 98 % of soot-containing particles, with a mean mixing state index (χ) of 0.83. The fractal dimension (Df) of soot particles is 1.84 ± 0.05 in the Northern Yellow Sea, 1.90 ± 0.08 in the Bohai Sea, and 1.96 ± 0.07 in the Southern Yellow Sea, indicating structural compaction during long-range transport. Correspondingly, the average Dp/Dcore ratios (particle to core size ratio) are 5.3 in the Bohai Sea, 4.2 in the Northern Yellow Sea, and 3.9 in the Southern Yellow Sea. Notably, those ratios are higher in marine environments compared to those observed during continental regional transport from northern to southern China (3.54), suggesting enhanced coating growth in humid marine air. The results highlight the important role of marine atmospheres in accelerating soot aging, which in turn leads to significantly stronger light absorption compared to soot in continental air. Our results highlight the necessity of incorporating compact morphologies, uniform mixing states, and thick coatings into optical models for accurate radiative forcing simulations.

Aerosols↗

PubMed2025

Redistribution of super-enhancers promotes malignancy in human hepatocellular carcinoma.

INTRODUCTION: Super-enhancers (SEs) are defined as the regulatory region where intensive transcriptional cofactors bind. Dysregulation of SEs is related to multiple diseases, however, its role in hepatocellular carcinoma (HCC) remains elusive. OBJECTIVES: This work aimed to reveal the dysregulation of SEs in HCC and the therapeutic potential for HCC treatment. METHODS: Fifteen HCC and twelve paracancerous samples underwent chromatin immunoprecipitation (ChIP) sequencing targeting H3K27ac, and subsequently the SEs were identified by the Rank Ordering of Super-Enhancers algorithm. Differential SEs featured by tumor or paracancerous tissues were identified, and cross-referenced with the differential expression genes and prognosis-related genes in 2 independent public or in-house HCC cohorts. The SE region of HSPA4 was deleted in the genome of HCCLM3 cell by CRISPR-Cas9, named HSPA4-SE-KO cells. The potential druggable transcriptional factors were identified by CRCmapper, GeneMANIA and Drug Gene Interaction Database (DGID). RESULTS: Five targets, including CDKN2C, HSPA4, GGH, PDGFA, and CAP2, were identified as HCC-gain SEs with oncogenic potential, which were further validated experimentally by SE inhibitors and ChIP targeting H3K27ac and BRD4. Cell proliferation and migration assays further confirmed that silencing of these HCC-gain SEs significantly suppressed the malignant phenotype of HCC cell lines. HSPA4 appeared strongest oncogenic functions among these targets, which was further verified by HCC mouse xenograft models and clinical sample investigation. Moreover, HSPA4-SE-KO cells obtained significantly suppressed HSPA4 expression and retarded tumorigenic capability. Finally, dysregulation of transcriptional factors engaged in the oncogenic role of SEs, and Danthron that targeting RXRA were identified from DGID for HCC treatment. CONCLUSION: The dysregulated SE landscape of HCC promoted the malignancy phenotype by the upregulation of oncogenes, and SE-regulatory network might be potential drug targets for HCC treatment. Our study deepened the insight of epigenetic dysregulation in HCC, offering the groundwork for SEs as potential therapeutic targets of HCC treatment.

Humans↗

PubMed2006

Synthesis of CdSnO(3).3H(2)O nanocubes via ion exchange and their thermal decompositions to cadmium stannate.

Uniform crystalline CdSnO3.3H2O nanocubes with a 28-35 nm edge length have been obtained via the ion-exchange reaction of Na2Sn(OH)6 in a CdSO4 aqueous solution, assisted by ultrasonic treatment. Precursor Na2Sn(OH)6 crystals were prepared via hydrothermal treatment in an ethanol/water solution. The formation of CdSnO3.3H2O nanocubes resulted from the strain during the ion-exchange process. The influences of reaction conditions, such as ion-exchange (ultrasonic treatment) duration, solvent constitutes, surfactant, and pH on the formation of CdSnO3.3H2O crystals were described. Crystalline CdSnO3 and Cd2SnO4 have been obtained by thermal treatment at 300 and 500 degrees C, respectively, for 5 h under an inert-gas protecting condition using CdSnO3.3H2O nanocubes as the precursor. The cube shape of CdSnO3.3H2O was sustained after thermal decomposition to CdSnO3.

Journal Article↗

PubMed2006

CD5-CK2 binding/activation-deficient mice are resistant to experimental autoimmune encephalomyelitis: protection is associated with diminished populations of IL-17-expressing T cells in the central nervous system.

Regulating the differentiation and persistence of encephalitogenic T cells is critical for the development of experimental autoimmune encephalomyelitis (EAE). We reported recently that CD5 has an engagement-dependent prosurvival activity in T cells that played a direct role in the induction and progression EAE. We predicted that CD5 regulates T cell apoptosis/survival through the activation of CK2, a prosurvival serine/threonine kinase that associates with the receptor. To test this hypothesis, we generated mice expressing CD5 with the inability to bind and activate CK2 and assessed their susceptibility to EAE. We found mice deficient in CD5-CK2 signaling pathway were mostly resistant to the development of EAE. Resistance to EAE was associated with a dramatic decrease in a population of effector infiltrating Th cells that coexpress IFN-gamma and IL-17 and, to a lesser extent, cells that express IFN-gamma or IL-17 in draining lymph nodes and spinal cords. We further show that T cells deficient in CD5-CK2 signaling hyperproliferate following primary stimulation; however, following restimulation, they rapidly develop nonresponsiveness and exhibit elevated activation-induced cell death. Our results provide a direct role for CD5-CK2 pathway in T cell activation and persistence of effector T cells in neuroinflammatory disease. This study predicts that targeting of IFN-gamma(+)/IL-17(+) infiltrating Th cells will be useful for the treatment of multiple sclerosis and other systemic autoimmune diseases.

Animals↗

PubMed2006

High myopia and glaucoma susceptibility the Beijing Eye Study.

OBJECTIVE: To evaluate whether marked myopia, compared with moderate myopia and low myopia, is associated with a higher prevalence of glaucomatous optic nerve damage. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Four thousand four hundred thirty-nine of 5324 subjects 40 years or older were invited to participate (response rate, 83.4%). The group was stratified according to refractive error into high myopia (myopia > -8 diopters [D]), marked myopia (<-6 to -8 D), moderate myopia (<-3 to -6 D), low myopia (<-0.5 to -3 D), emmetropia (-0.5 to + <2 D), and hyperopia (>+ 2 D) subgroups. METHODS: Morphologic assessment of optic disc monoscopic photographs. MAIN OUTCOME MEASURES: Morphologic optic disc parameters and intraocular pressure (IOP). RESULTS: For 4319 (97.3%) subjects (8484 eyes), optic disc photographs were evaluated. Prevalence of glaucomatous optic nerve atrophy as defined by the glaucomatous optic nerve head appearance did not vary significantly (P = 0.77; odds ratio [OR], 1.2; 95% confidence interval [CI], 0.38-3.81) between the highly myopic group and the group with marked myopia. In both refractive groups combined, glaucoma frequency seemed to be higher (P = 0.075; OR, 2.28; 95% CI, 0.99-5.25) higher than in the group with moderate myopia; it was significantly (P = 0.001; OR, 3.5; 95% CI, 1.71-7.25) higher than in the group with low myopia; significantly (P<0.001; OR, 7.56; 95% CI, 3.98-14.35) higher than in the group with emmetropia; and significantly (P = 0.005; OR, 4.23; 95% CI, 1.57-11.45) higher than in the group with hyperopia. Glaucoma frequency did not vary significantly between the hyperopic group and the emmetropic group (P = 0.17), the group with low myopia (P = 0.83), and the group with moderate myopia (P = 0.32). Intraocular pressure did not vary significantly (P>0.10) between any of the subgroups. Similar results were obtained for the frequency of glaucoma defined as glaucomatous optic disc appearance and visual field defects. In binary logistic regression analysis, presence of glaucoma was significantly associated with the myopic refractive error (P<0.001), age (P<0.001), and IOP (P<0.001). CONCLUSIONS: Marked to high myopia with a myopic refractive error exceeding -6 D may be a risk factor associated with glaucomatous optic neuropathy.

Adult↗

PubMed2006

Characteristics of highly myopic eyes: the Beijing Eye Study.

OBJECTIVE: To evaluate factors associated with high myopia (defined as a myopic refractive error exceeding -8 diopters) in a population-based study. DESIGN: Population-based prevalence study. PARTICIPANTS: The Beijing Eye Study included 4439 participants from among 5324 individuals from a rural area and an urban region of Greater Beijing, > or =40 years old and invited to participate (response rate, 83.4%). METHODS: Interview and detailed ophthalmic examination. MAIN OUTCOME MEASURES: Refractive error, microvascular retinal abnormalities, optic disc morphometry, amount of cataract, and age-related macular changes. RESULTS: Fundus photographs and data for refractive error were available for 4319 participants (97.3%; 8484 eyes). In binary logistic regression analysis, prevalence of high myopia was significantly associated with low best-corrected visual acuity (P<0.001; 95% confidence interval [CI], 0.15-0.40), large optic disc size (P<0.001; 95% CI, 1.64-2.25), large size of beta zone (P = 0.31; 95% CI, 1.45-1.75) and alpha zone of peripapillary atrophy (P<0.001; 95% CI, 1.20-1.58), and lower macular drusen count (P = 0.020; 95% CI, 0.81-0.98). The highly myopic group had a smaller mean size of macular drusen (P = 0.03; 95% CI, 0.02-0.26) and a smaller area covered by drusen (P = 0.01; 95% CI, 0.03-0.22). In the highly myopic group, the predominant drusen type was significantly (P = 0.01; 95% CI, 0.05-0.41) more often the hard distinct drusen type than the soft drusen type, and visual field defects were significantly more common (P<0.001; odds ratio [OR], 24.0; 95% CI, 13.9-41.4) and larger (P<0.001; 95% CI, -1.67 to -1.13). The frequencies of early macular degeneration (P = 0.03; OR, 3.0; 95% CI, 1.21-7.51) and late macular degeneration (P<0.001; OR, 6.33) were significantly lower in the highly myopic group than in the non-highly myopic group. High myopia was not significantly associated with gender (P = 0.18; 95% CI, 0.76-1.05), focal arteriolar thinning (P>0.35), arteriolar sheathing (P>0.45), arteriovenous crossing abnormalities (P>0.20), self-reported diagnosis of diabetes mellitus (P = 0.54; OR, 1.36; 95% CI, 0.48-3.80), or arterial hypertension (P = 0.34; OR, 0.66; 95% CI, 0.32-1.34). CONCLUSIONS: In the adult Chinese population, high myopia is associated with a lower number, smaller, size and less advanced type of macular drusen, a larger optic nerve head, and decreased best-corrected visual acuity. The risk of early and late macular degeneration was lower for highly myopic participants than for non-highly myopic participants.

Adult↗

PubMed2006

COPASI--a COmplex PAthway SImulator.

MOTIVATION: Simulation and modeling is becoming a standard approach to understand complex biochemical processes. Therefore, there is a big need for software tools that allow access to diverse simulation and modeling methods as well as support for the usage of these methods. RESULTS: Here, we present COPASI, a platform-independent and user-friendly biochemical simulator that offers several unique features. We discuss numerical issues with these features; in particular, the criteria to switch between stochastic and deterministic simulation methods, hybrid deterministic-stochastic methods, and the importance of random number generator numerical resolution in stochastic simulation. AVAILABILITY: The complete software is available in binary (executable) for MS Windows, OS X, Linux (Intel) and Sun Solaris (SPARC), as well as the full source code under an open source license from http://www.copasi.org.

Algorithms↗

PubMed2006

Prevalence of age-related maculopathy in the adult population in China: the Beijing eye study.

OBJECTIVE: To evaluate the prevalence of age-related maculopathy (ARM) in adult Chinese living in rural or urban regions of mainland China. DESIGN: Population-based prevalence study. METHODS: The study included 4439 subjects (aged 40 or more years) out of 5324 subjects invited to participate (response rate 83.4%). It was held in rural and urban regions of Greater Beijing. The participants underwent a detailed ophthalmic examination including fundus photography. All fundus photographs were graded by the Wisconsin Age-Related Maculopathy Grading System. RESULTS: Fundus photographs were available for 4376 (98.6%) subjects. Early ARM was present in 122 (1.4%) of 8655 (95% confidence interval [CI] 1.16% to 1.66%) eyes or 63 (1.4%) of 4376 (95% CI 1.09% to 1.79%) subjects, late ARM in 12 (0.14%) of 8655 (95% CI 0.06% to 0.22%) eyes or seven (0.2%) of 4376 (95% CI 0.04% to 0.28%) subjects, and exudative ARM as part of late ARM in seven (0.1%) of 8655 (95% CI 0.02% to 0.14%) eyes or six (0.1%) of 4376 (95% CI 0.03% to 0.25%) subjects. The prevalence of early ARM, late ARM, and exudative ARM, respectively, increased from 0.61%, 0.07%, and 0.07% in the 40-to-44-year age group, to 1.66%, 0.26%, and 0.26% in the 55-to-59-year group, and to 2.99%, 0.90%, and 0.60% in the group aged 75 years and older. ARM was causative for visual impairment (best-corrected visual acuity in the better eye, <20/60 and > or =20/400) or blindness (visual acuity <20/400) in one subject (0.023%). CONCLUSIONS: Visual impairment due to ARM was relatively uncommon in the adult Chinese population in rural and urban regions.

Adult↗

PubMed2006

How does single oxygen atom addition affect the properties of an Fe-nitrile hydratase analogue? The compensatory role of the unmodified thiolate.

Nitrile hydratase (NHase) is one of a growing number of enzymes shown to contain post-translationally modified cysteine sulfenic acids (Cys-SOH). Cysteine sulfenic acids have been shown to play diverse roles in cellular processes, including transcriptional regulation, signal transduction, and the regulation of oxygen metabolism and oxidative stress responses. The function of the cysteine sulfenic acid coordinated to the iron active site of NHase is unknown. Herein we report the first example of a sulfenate-ligated iron complex, [Fe(III)(ADIT)(ADIT-O)](+) (5), and compare its electronic and magnetic properties with those of structurally related complexes in which the sulfur oxidation state and protonation state have been systematically altered. Oxygen atom addition was found to decrease the unmodified thiolate Fe-S bond length and blue-shift the ligand-to-metal charge-transfer band (without loss of intensity). S K-edge X-ray absorption spectroscopy and density functional theory calculations show that, although the modified RS-O(-) fragment is incapable of forming a pi bond with the Fe(III) center, the unmodified thiolate compensates for this loss of pi bonding by increasing its covalent bond strength. The redox potential shifts only slightly (75 mV), and the magnetic properties are not affected (the S = (1)/(2) spin state is maintained). The coordinated sulfenate S-O bond is activated and fairly polarized (S(+)-O(-)). Addition of strong acids at low temperatures results in the reversible protonation of sulfenate-ligated 5. An X-ray structure demonstrates that Zn(2+) binds to the sulfenate oxygen to afford [Fe(III)(ADIT)(ADIT-O-ZnCl(3))] (6). The coordination of ZnCl(3)(-) to the RS-O(-) unit causes the covalent overlap with the unmodified thiolate to increase further. A possible catalytic role for the unmodified NHase thiolate, involving its ability to "tune" the electronics in response to protonation of the sulfenate (RS-O(-)) oxygen and/or substrate binding, is discussed.

Hydro-Lyases↗

PubMed2006

Synthesis and in vivo evaluation of non-hepatotoxic acetaminophen analogs.

A series of acetaminophen (APAP) analogs, 2-(1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)-N-(4-hydroxyphenyl)alkanecarboxamides, bearing a heterocyclic moiety linked to the p-acylaminophenol fragment, were prepared in a general project to develop APAP analogs with modulated pharmacokinetic profiles. Unexpectedly, the products described maintained the in vivo analgesic profile, while the characteristic hepatotoxicity of APAP was consistently reduced. One of the products, 5a, was studied in vivo in comparison with APAP. Compound 5a displayed an analgesic efficacy comparable to that of APAP. A relatively high acute oral dose of 5a (6 mmol/kg) produced no measurable toxicity, whereas the equimolar dose of APAP increased transaminase activity, depleted hepatic and renal glutathione, and resulted in mortality. In human hepatocytes (HEPG-2) and in human primary cultures of normal liver cells, APAP, but not 5a, was associated with apoptotic cell death, Fas-ligand up-regulation, and CAR (constitutive androstane receptor) activation, contributing to a favorable safety profile of 5a as an orally delivered analgesic.

Acetaminophen↗

PubMed2006

Synthesis of dopamine transporter selective 3-diarylmethoxymethyl-8-arylalkyl-8-azabicyclo[3.2.1]octane derivatives.

A series of diarylmethoxymethyltropane-GBR hybrid analogues with all three possible stereochemical orientations at C3 were synthesized and evaluated at dopamine and serotonin transporters. The 3alpha derivatives were found to be the most potent compounds with the 3alpha-di(4-fluorophenyl)methoxymethyl-8-(3-phenylpropyl)-8-azabicyclo[3.2.1]octane 15b (Ki = 5 nM) being the most potent compound of the series. The corresponding 3-di(4-fluorophenyl)-methoxymethyl-8-(3-phenylpropyl)-8-azabicyclo[3.2.1]oct-2-ene 12b (Ki = 12 nM) was slightly less potent than the 3alpha-analogue, while the 3beta-di(4-fluorophenyl)methoxymethyl-8-(3-phenylpropyl)-8-azabicyclo[3.2.1]octane 23b (Ki = 78 nM) exhibited only modest affinity for the dopamine transporter. Only the 3alpha-analogue 15b (SERT/DAT = 48) exhibited higher SERT/DAT selectivity than GBR 12909. These results indicate that the dopamine transporter can tolerate some variability in proximity of the benzhydryl ether to the basic nitrogen atom of the tropane without loss in potency. In addition, the structure-activity data for these tropane-GBR 12909 hybrid analogues support previous findings that the stereochemical and conformational effects imparted by unsaturation at C3 are important for dopamine transporter selectivity over the serotonin transporter.

Bridged Bicyclo Compounds, Heterocyclic↗

PubMed2006

Retinal vascular abnormalities in adult Chinese in rural and urban Beijing: the Beijing Eye Study.

OBJECTIVE: To assess retinal vascular abnormalities, including focal and generalized arteriolar narrowing, arteriovenous nicking, and arteriolar sheathing, in adult Chinese in rural and urban Beijing, and their associations with self-reported diagnosis of cardiovascular and cerebrovascular diseases. DESIGN: Population-based cross-sectional cohort study. PARTICIPANTS: The study included 4439 subjects out of 5324 subjects invited to participate (response rate, 83.4%) with an age of > or =40 years. It was divided into a rural part (n = 1973 [44.4%]) and an urban part (n = 2466 [55.6%]). Mean age was 56.2+/-10.6 years (range, 40-101 years). METHODS: Color optic disc photographs were morphometrically examined. One eye of each participant was randomly selected. Generalized and focal arteriolar narrowing, arteriovenous nicking (arteriovenous crossing abnormalities), and arteriolar sheathing were assessed. Self-reported histories of cardiovascular and cerebrovascular diseases and habits of smoking and alcohol drinking were obtained from questionnaires. MAIN OUTCOME MEASURES: Frequency of generalized and focal arteriolar narrowing, arteriovenous nicking, and arteriolar sheathing. RESULTS: Optic disc photographs were available for 4228 (95.2%) subjects. Focal arteriolar narrowing was found in 6.3%, arteriovenous nicking in 6.6%, arteriolar sheathing in 4.8%, and generalized narrowing in 4.3% of the subjects. Abnormalities were more common in the temporal quadrant; they were rare in the inferior nasal quadrant. Frequencies and severities of all retinal microvascular abnormalities examined increased with age (P<0.05). The microvascular abnormalities were detected more frequently in the rural population than in the urban population (P<0.05). After controlling for age, gender, area, and habit of drinking alcohol, generalized arteriolar narrowing (odds ratio [OR], 2.63; 95% confidence interval [CI], 1.64, 4.22), focal arteriolar narrowing (OR, 1.51; 95% CI, 1.00, 2.29), and arteriolar sheathing (OR, 1.71; 95% CI, 1.08, 2.71) were significantly associated with the self-reported diagnosis of arterial hypertension. The microvascular abnormalities were not significantly associated with the self-reported diagnosis of coronary heart disease or stroke. CONCLUSIONS: Retinal vascular abnormalities in adult Chinese increase with age and are more commonly found in people living in rural areas. Retinal vascular abnormalities are associated with the self-reported diagnosis of arterial hypertension, and are not related to self-reported diagnosis of coronary heart disease or previous cerebrovascular events such as stroke.

Adult↗

PubMed2006

Causes of blindness and visual impairment in urban and rural areas in Beijing: the Beijing Eye Study.

OBJECTIVE: To evaluate the causes of visual impairment and blindness in adult Chinese in an urban and rural region of Beijing, China. DESIGN: Population-based prevalence survey. PARTICIPANTS: From a rural region and an urban region of Greater Beijing, 4439 of 5324 > or=40-year-old invited subjects participated in the study (response rate, 83.4%). Using the World Health Organization (WHO) standard and the United States standard, blindness was defined as best-corrected visual acuity (BCVA) in the better-seeing eye of <20/400 and of <2/20, respectively, and visual impairment was defined as best-corrected vision of <20/60 and > or =20/400, and of <20/40 and > or =2/20, respectively. METHODS: Determination of BCVA, pneumotonometry, frequency doubling perimetry, evaluation of photographs of the fundus and lens, and clinical examination. MAIN OUTCOME MEASURE: Causes of visual impairment and blindness. RESULTS: Visual acuity measurements were available for 8816 eyes of 4409 subjects (99.3%). Using the WHO standard and the U.S. standard, 49 (1.1%) subjects and 95 (2.2%) subjects, respectively, had low vision, and 13 (0.3%) subjects and 15 (0.3%) subjects, respectively, were blind by definition. Taking the whole study population, the most frequent cause of low vision/blindness was cataract (36.7%/38.5%), followed by degenerative myopia (32.7%/7.7%), glaucoma (14.3%/7.7%), corneal opacity (6.1%/15.4%), and other optic nerve damage (2.0%/7.7%). Age-related macular degeneration (AMD) (2.0%/7.7%) and diabetic retinopathy (0%/7.7%) were responsible for a minority of cases. In subjects 40 to 49 years old, the most frequent cause of low vision and blindness was degenerative myopia. In the 50- to 59-year age group, the most frequent cause was cataract, followed by degenerative myopia. In the 60- to 69-year-old subjects and the > or =70-year group, the most frequent cause of low vision and blindness was cataract, followed by degenerative myopia and glaucoma. CONCLUSIONS: The most frequent cause of low vision and blindness in adult Chinese is cataract, followed by degenerative myopia and glaucomatous optic neuropathy, with degenerative myopia dominating in younger groups and cataract dominating in elder groups. In contrast to studies in Western countries, AMD and diabetic retinopathy appear to play a minor role as a cause of visual impairment in elderly Chinese.

Adult↗

PubMed2006

Synthesis and characterization of indium-doped ZnO nanowires with periodical single-twin structures.

In-doped ZnO (IZO) nanowires have been synthesized by a thermal evaporation method. The morphology and microstructure of the IZO nanowires have been extensively investigated using scanning electron microscopy (SEM), X-ray diffraction (XRD), and high-resolution transmission electron microscopy (HRTEM). The products in general contain several kinds of nanowires. In this work, a remarkable type of IZO zigzag nanowire with a periodical twinning structure has been investigated by transmission electron microscopy (TEM). HRTEM observation reveals that this type of IZO nanowire has an uncommonly observed zinc blend crystal structure. These nanowires, with a diameter about 100 nm, grow along the [111] direction with a well-defined twinning relationship and a well-coherent lattice across the boundary. In addition, an IZO nanodendrite structure was also observed in our work. A growth model based on the vapor-liquid-solid mechanism is proposed for interpreting the growth of zigzag nanowires in our work. Due to the heavy doping of In, the emission peak in photoluminescence spectra has red-shifted as well as broadened seriously.

Journal Article↗

PubMed2006

[The prevalence of disc hemorrhage and papillary atrophy in Beijing Eye Study].

OBJECTIVE: To evaluate the prevalence of disc hemorrhage and papillary atrophy in Beijing defined area. METHODS: To review 4163 right eyes consecutive plain color fundus photographs of 4163 subjects (male/female = 1832/2331) who attended the eye screening. RESULTS: The prevalence of glaucoma is 3.0% (135/4439). Disc hemorrhage was found in 42 eyes of 42 subjects (1.0%), and more frequently in women. The prevalences of papillary atrophy (alpha zone and beta zone) were 70.98% (2955/4163) and 20.95% (872/4163), respectively. The prevalence of beta zone was greater in glaucoma group than in non-glaucomatous group (Fisher's test, P < 0.01). CONCLUSION: The prevalence of disc hemorrhage is low in whole population and women are easier to have disc hemorrhage with aging. Disc hemorrhage and papillary atrophy have different prevalences in defined-population study and might have close association on the early onset of glaucoma.

Adult↗

PubMed2006

Polymorphisms in DNA damage binding protein 2 (DDB2) and susceptibility of primary lung cancer in the Chinese: a case-control study.

DNA damage binding protein 2 (DDB2) is one of the major DNA repair proteins involved in the nucleotide excision repair (NER) pathway. Mutations in the DDB2 gene can cause a repair-deficiency syndrome xeroderma pigmentosum group E. Because tobacco carcinogens can cause DNA damage that is repaired by NER and suboptimal NER capacity is reported to be associated with lung cancer risk, we hypothesized that common variants in the DDB2 gene are associated with lung cancer risk. To test this hypothesis, we conducted a case-control study of 1010 patients with incident lung cancer and 1011 cancer-free controls and genotyped two DDB2 single nucleotide polymorphisms (SNPs) (rs830083 and rs3781620) that are in linkage disequilibrium with other untyped SNPs. We found that compared with the rs830083CC, subjects carrying the heterozygous rs830083CG genotype had a significantly 1.31-fold increased risk of lung cancer [95% confidence interval (CI) 1.08-1.60] and those carrying the homozygous rs830083GG genotype had a non-significantly 1.22-fold elevated risk (95% CI 0.89-1.67). In addition, effects of the combined rs830083CG/GG variant genotypes were more evident in young subjects, heavy smokers and subjects with a positive family history of cancer. These findings indicate, for the first time, that the DDB2 rs830083 polymorphism may contribute to the etiology of lung cancer. Further functional studies on this SNP and/or related variants are warranted to elucidate the underlying molecular mechanisms of the association.

Aged↗

PubMed2006

Linkage disequilibrium sharing and haplotype-tagged SNP portability between populations.

The discovery of the block-like structure of linkage disequilibrium (LD) in human populations holds the promise of delineating the etiology of common diseases. However, understanding the magnitude, mechanism, and utility of between-population LD sharing is critical for future genome-wide association studies. In this study, substantial LD sharing between six non-African populations was observed, although much less between African-American and non-African, based on 20,000 SNPs of chromosome 21. We also demonstrated the respective roles of recombination and demographic events in shaping LD sharing. Furthermore, we showed that the haplotype-tagged SNPs chosen from one population are portable to the others in East Asia. Therefore, we concluded that the magnitude of LD sharing between human populations justifies the use of representative populations for selecting haplotype-tagged SNPs in genome-wide association studies of complex diseases.

Africa↗