Biomedical subjects
Publications and source records attributed to Wei Lu.
Self-assembly of positively charged and charge-neutral tridentate cyclometalated platinum(II) complexes leads to nanowires and the drop-cast film containing these nanowires behaves as a n-type semiconductor.
A series of novel benzimidazole derivatives was synthesized and evaluated for their anti-hepatitis B virus (HBV) activity and cytotoxicity in vitro. Strong activity against HBV replication and low cytotoxicity were generally observed in these benzimidazoles. The most promising compounds were 12a and 12b, with similar high antiviral potency (IC50 = 0.9 and 0.7 microM, respectively) and remarkable selectivity indices (>1111 and 714, respectively). They were selected for further evaluation as novel HBV inhibitors.
We have demonstrated that the strong and far-field focusing of a point source and a plane wave in a two-dimensional photonic-crystal-based concave lens by the use of the standard finite-difference time-domain simulations. The effect of the distance between the point source and the lens on the focusing is discussed. The far-field focus of a plane wave is shown. In addition, a plane wave is formed with placing the source at the focus point. According to the calculation, the strong and good quality far-field focusing of the transmitted wave, explicitly following the well-known wave beam negative refraction law, can be realized. Moreover, the spatial frequencies information of the Bloch mode in multiple Brillouin zones is investigated in order to indicate the wave propagation in two different regions.
A series of monocyclic thiazepine inhibitors of interleukin-1beta converting enzyme (ICE) were synthesized in eight steps from commercially available intermediates. In vitro biological evaluation showed the thiazepines to be moderately potent ICE inhibitors, with the most active compound exhibiting an IC50 value of 30 nM in an enzyme inhibition assay. Compounds of this class possessed good selectivity against the related enzymes caspase-3 and caspase-8.
BACKGROUND: Being diagnosed with breast cancer is a very stressful event that has a profound impact on multiple aspects of a patient's daily life. Little is known about the quality of life (QOL) of Chinese women with newly diagnosed breast cancer. METHODS: The authors evaluated QOL in 2,236 Chinese women with newly diagnosed breast cancer who were recruited into the Shanghai Breast Cancer Survival Study between April 1, 2002 and March 31, 2004. Patients' QOL was assessed after cancer diagnosis (median time 6.4 months; range 3.6-11.1 months) by using the General Quality of Life Inventory. Multiple linear regression models were used to analyze the associations of QOL outcomes with medical and socio-demographic factors. RESULTS: Patients showed significantly worse overall QOL and perceived health status than healthy women, reflected mainly by lower QOL scores in physical and psychological well-being domains. Completion of radiotherapy, ever use of tamoxifen, being underweight, having an increased number of chronic diseases, and low household income were significantly associated with lower overall QOL scores after adjusting for other factors. Age at diagnosis was inversely associated with physical well-being, positively associated with material well-being, and had minimal influence on overall QOL. Stage of disease, chemotherapy, and education were only associated with certain domains, but had no influence on overall QOL. Estrogen receptor/progesterone receptor status and type of surgery or immunotherapy did not appear to be associated with QOL. CONCLUSIONS: The findings of the present study provide important information on QOL and their correlates among Chinese women with newly diagnosed breast cancer and are helpful in developing treatment strategies accordingly.
OBJECTIVE: To investigate the transdifferentiation of pulmonary artery endothelial cells (PAECs) into smooth muscle-like cells under hypoxia and the role of myocardin therein. METHODS: Recombinant plasmid psimyocardin (pSi), capable of silencing the expression of myocardin gene, was constructed by RNAi to be used to transfect the PAECs. Endothelial cells of adult pig pulmonary small arteries were purified by immunomagnetic purification technique, and divided into 4 groups: normoxia group (to be cultured in normoxic cell culture box containing 21% O(2), 5% CO2, and 74% N(2)), normoxia + pSi group, hypoxia group (to be cultured in cell box containing 1% O(2), 5% CO2, and 74% N(2)), and hypoxia + pSi group to be cultured for 1, 4, and 7 days respectively. Indirect fluorescence technique and morphological examination were used to identify the smooth muscle (SM) -like cells and the alpha-SM-actin positive cell ratio. RT-PCR was used to detect the mRNA expression of myocardin. RESULTS: Alpha-SM-actin positive cell could not be seen in the normoxia group and hypoxia 1 d group. The alpha-SM-actin positive cell rate of the hypoxia 7 days group was 2.07% +/- 0.06%, significantly higher than that of the hypoxia 4 d group (0.96% +/- 0.08%, P < 0.01). mRNA expression of myocardin gene could not be seen in the normoxia, normoxia + pSi, hypoxia 1 days, and hypoxia + pSi 1 days groups. The mRNA expression of myocardin gene of the hypoxia 7 days group was 0.23 +/- 0.03, significantly higher than that of the hypoxia 4 days group (0.14 +/- 0.01, P < 0.01). The mRNA expression levels of myocardin gene of the hypoxia + pSi 4 days and 7 days groups 0.03 +/- 0.02 and 0.05 +/- 0.01, both significantly lower than those of the hypoxia 4 days and 7 days groups respectively (0.14 +/- 0.01 and 0.23 +/- 0.03, both P < 0.01). The SM-like cell transdifferentiation rates of the hypoxia + pSi 4 days and 7 days groups were 0.19% +/- 0.07% and 0.21% +/- 0.04% respectively, both significantly lower than those of the corresponding hypoxia groups (0.96% +/- 0.08 and 2.07% +/- 0.06% respectively, both P < 0.01). CONCLUSION: Some PAECs have the potential to transdifferentiate into SM-like cells and may be one of the resources of muscularization of peripheral small vessels. Hypoxia remarkably promotes this transdifferentiation and myocardin may play an important role in this process.
We study the kinetics of migration-driven aggregate growth on completely connected scale-free networks. A reversible migration system is considered with the size-dependent rate kernel K(k; l/i;j) approximately k(u)i(v)(lj)(v), at which an i-mer aggregate located on the node with j links gains one monomer from a k-mer aggregate on the node with l links. The results show that the evolution behavior of the aggregate size distribution is drastically different from that for the corresponding same system in normal space. This model can be used to mimic some phenomena such as the distribution of city populations. Moreover, we verify our analytic results in good agreement with the data of the population distributions of all U.S. counties.
NC-1900, an active fragment analog of arginine vasopressin [arginine vasopressin-(4-9)], has proved to be capable of improving the spatial memory deficits and the impairments in passive avoidance test. In this study, a novel drug carrier for brain delivery, cationic bovine serum albumin conjugated pegylated nanoparticles (CBSA-NPs) holding NC-1900, was developed and its improvement on scopolamine-induced memory deficits was investigated in mice using the platform-jumping avoidance test. CBSA-NPs loaded with NC-1900 in spherical shape and uniform size below 100 nm were prepared by the double emulsion/solvent evaporation procedure, and the zeta potential of CBSA-NPs was about -8mV with the loading capacity of NC-1900 around 0.46%. The in vitro study showed that approximately 10% NC-1900 was released from CBSA-NPs in pH 7.4 phosphate buffer saline (PBS) during 56 h incubation with about 15% NC-1900 released in pH 4.0 PBS during 7 days, indicating the sustained release of this carrier. Furthermore, the half-life of NC-1900 loaded in CBSA-NPs in plasma was about 78 h, which was 4-fold longer than that of free NC-1900 (19 h). The active avoidance behavioral results showed that the s.c. administration of NC-1900 tended to improve memory deficits, but the difference did not present any statistical significance, whereas this peptide failed to produce any positive effects by i.v. administration. However, the i.v. injection of CBSA-NPs loaded with NC-1900 greatly improved memory impairments to a normal level, but the efficacy was slight if the loaded nanoparticles (NPs) were exclusive of the conjugation of CBSA, indicating that CBSA-NP was a promising brain delivery carrier for NC-1900 with CBSA as a potent brain targetor. It was concluded that CBSA-NP loaded with NC-1900 was potentially efficacious in the treatment of memory deficits via i.v. administration.
By an extended plane-wave-based transfer-matrix method, the photonic band structure and the corresponding transmission spectrum have been calculated for a two-dimensional photonic crystal composed of negative-phase-velocity-medium (NPVM) cylindrical rods. Dispersionless anticrossing bands in the two-dimensional NPVM periodic structure are generated by the couplings among surface polaritons localized in the NPVM rods. In part of the negative-phase-velocity frequency region, the photonic band structures of the NPVM photonic crystal are characterized by a topographical continuous dispersion relationship accompanied by many anticrossing bands. The effect of the filling fraction of the NPVM rods on the optical properties of photonic crystals has also been studied.
OBJECTIVE: To investigate the prevalence of type 2 diabetes and impaired glucose regulation among the permanent urban and rural inhabitants in Shanghai. METHODS: Questionnaire survey, physical examination, and laboratory testing were conducted among 14401 urban and rural inhabitants aged 15 - 74 in Shanghai selected by multistage cluster random sampling. The data about the prevalence of type 2 diabetes and impaired glucose regulation were collected and analyzed. RESULTS: The respondent rate of this investigation was 80.5% (11,589/14,401). The prevalence rates of type 2 diabetes, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) were 8.6% (1000/11,589), 6.9% (802/11,589), and 1.0% (120/11,589) respectively (the standardized rates were 6.2%, 5.1% and 0.8%). The prevalence rates of type 2 diabetes, IGT, and IFG were significantly higher in those with overweight, obesity, central obesity, and hypertension. The prevalence rates of type 2 diabetes, IGT, and IFG in men were 8.9% (412/4621), 6.4% (296/4621), and 1.0% (47/4621) respectively, all not significantly different from those of the women, i.e. e., 8.4% (588/6968), 7.3% (506/6968), and 1.0% (73/6968) respectively (all P > 0.05). The prevalence rates of type 2 diabetes and IGT in the urban area were 11.2% (730/6500) and 6.4% (419/6500) respectively, both significantly higher than those in the rural area, i.e., 5.3% (270/5089) and 7.5% (383/5089) respectively (both P < 0.05). The prevalence rate of IFG in the urban area was 1.2% (77/6500), not significantly different from that in the rural area (0.8%, 43/5039, P > 0.05). The prevalence of type 2 diabetes, IGT, and IFG increased apparently with age, body mass index, waist hip ratio, and waist circumference. The ratios of undiagnosed type 2 diabetes in the urban area and rural area were 39.6% (289/730) and 69.3% (187/270) respectively (chi(2) = 74.07, P < 0.01). CONCLUSION: The prevalence rate of type 2 diabetes in Shanghai is higher than the mean national level and shows an increasing tendency. Screening of type 2 diabetes in rich rural areas should be emphasized.
Although the complete picture for alopecia areata (AA) pathogenesis has yet to be determined, recent research has made much progress in our understanding of the disease mechanism. Numerous circumstantial evidence supports the notion that AA is fundamentally a disease mediated by inflammatory cells and may be autoimmune in nature. Recent research has shown the hair-loss phenotype is precipitated predominantly by CD8+ lymphocytes, but the disease mechanism is driven by CD4+ lymphocytes. Although genetic susceptibility is a key contributor to disease development, disease onset and phenotypic presentation are probably modified by complex environmental interplay. On the basis of our current understanding of AA disease pathogenesis, several experimental and theoretical therapeutic approaches might be possible. However, the pathogenetic disease mechanism is particularly robust and the development of a cure for AA will be a significant challenge.
Novel 1-(2-acylhydrazinocarbonyl)cycloalkyl carboxamides were designed as peptidomimetic inhibitors of interleukin-1beta converting enzyme (ICE). A short synthesis was developed and moderately potent ICE inhibitors were identified (IC(50) values <100 nM). Most of the synthesized examples were selective for ICE versus the related cysteine proteases caspase-3 and caspase-8, although several dual-acting inhibitors of ICE and caspase-8 were identified. Several of the more potent ICE inhibitors were also shown to inhibit IL-1beta production in a whole cell assay (IC(50) < 500 nM).
BACKGROUND: Fifteen human tissue kallikrein (KLK) genes have been identified as a cluster on chromosome 19. KLK expression is associated with various human diseases including cancers. Noncoding RNAs such as PCA3/DD3 and PCGEM1 have been identified in prostate cancer cells. METHODS: Using massively parallel signature sequencing (MPSS) technology, RT-PCR, and 5' rapid amplification of cDNA ends (RACE), we identified and cloned a novel gene that maps to the KLK locus. RESULTS: We have characterized this gene, named as KLK31P by the HUGO Gene Nomenclature Committee, as an unprocessed KLK pseudogene. It contains five exons, two of which are KLK-derived while the rest are "exonized" interspersed repeats. KLK31P is expressed abundantly in prostate tissues and is androgen regulated. KLK31P is expressed at lower levels in localized and metastatic prostate cancer cells than in normal prostate cells. CONCLUSIONS: KLK31P is a novel androgen regulated and transcribed pseudogene of kallikreins that may play a role in prostate carcinogenesis or maintenance.
An effective elongation method has been developed to study electronic structures and electron transport properties of nanoelectronic and bioelectronic devices at a hybrid density functional theory level. It enables to treat finite nanostructures consisting of as many as 28 000 electrons and has been successfully applied to sub-120-nm-long conjugated polymers, sub-60-nm-long single-walled carbon nanotubes, and 30 base-pair DNA molecules. The calculated current-voltage characteristics of different systems are found to be in good agreement with the experiments. Some unexpected behaviors of these nanosized devices have been discovered.
Semiconducting carbon nanotubes and nanowires are potential alternatives to planar metal-oxide-semiconductor field-effect transistors (MOSFETs) owing, for example, to their unique electronic structure and reduced carrier scattering caused by one-dimensional quantum confinement effects. Studies have demonstrated long carrier mean free paths at room temperature in both carbon nanotubes and Ge/Si core/shell nanowires. In the case of carbon nanotube FETs, devices have been fabricated that work close to the ballistic limit. Applications of high-performance carbon nanotube FETs have been hindered, however, by difficulties in producing uniform semiconducting nanotubes, a factor not limiting nanowires, which have been prepared with reproducible electronic properties in high yield as required for large-scale integrated systems. Yet whether nanowire field-effect transistors (NWFETs) can indeed outperform their planar counterparts is still unclear. Here we report studies on Ge/Si core/shell nanowire heterostructures configured as FETs using high-kappa dielectrics in a top-gate geometry. The clean one-dimensional hole-gas in the Ge/Si nanowire heterostructures and enhanced gate coupling with high-kappa dielectrics give high-performance FETs values of the scaled transconductance (3.3 mS microm(-1)) and on-current (2.1 mA microm(-1)) that are three to four times greater than state-of-the-art MOSFETs and are the highest obtained on NWFETs. Furthermore, comparison of the intrinsic switching delay, tau = CV/I, which represents a key metric for device applications, shows that the performance of Ge/Si NWFETs is comparable to similar length carbon nanotube FETs and substantially exceeds the length-dependent scaling of planar silicon MOSFETs.
In this study, we examined the expression and functions of related to testes-specific, vespid, and pathogenesis protein 1 (RTVP-1) in glioma cells. RTVP-1 was expressed in high levels in glioblastomas, whereas its expression in low-grade astrocytomas and normal brains was very low. Transfection of glioma cells with small interfering RNAs targeting RTVP-1 decreased cell proliferation in all the cell lines examined and induced cell apoptosis in some of them. Overexpression of RTVP-1 increased astrocyte and glioma cell proliferation and the anchorage-independent growth of the cells. In addition, overexpression of RTVP-1 rendered glioma cells more resistant to the apoptotic effect of tumor necrosis factor-related apoptosis-inducing ligand and serum deprivation. To delineate the molecular mechanisms involved in the survival effects of RTVP-1, we examined the expression and phosphorylation of various apoptosis-related proteins. We found that overexpression of RTVP-1 decreased the phosphorylation of c-Jun-NH2-kinase and increased the expression of Bcl2 and that the protective effect of RTVP-1 was partially mediated by Bcl2. Finally, we found that RTVP-1 regulated the invasion of glioma cells as was evident by their enhanced migration through Matrigel and by their increased invasion in a spheroid confrontation assay. The increased invasive potential of the RTVP-1 overexpressors was also shown by the increased activity of matrix metalloproteinase 2 in these cells. Our results suggest that the expression of RTVP-1 is correlated with the degree of malignancy of astrocytic tumors and that RTVP-1 is involved in the regulation of the growth, survival, and invasion of glioma cells. Collectively, these findings suggest that RTVP-1 is a potential therapeutic target in gliomas.
OBJECTIVE: To study the features of postprandial glucose state in individuals with normal glucose regulation (NGR) and type 2 diabetes (T2DM) and the relations between hemoglobin A1c (HbA1c) and postprandial glucose in T2DM. METHODS: 41 NGR individuals and 60 newly diagnosed T2DM patients without previous management in Shanghai were measured by continuous glucose monitoring system for 3 days. The postprandial glucose spike (PGS), time to PGS (Deltat), postprandial glucose excursion (PPGE), duration of postprandial glucose (DUR) and incremental area under the curve of postprandial glucose (IAUC) were calculated in each individual. RESULTS: (1) The levels of PGS and Deltat in the T2DM group were significantly higher than those of the NGR group (all P < 0.01). The levels of PPGE, DUR and IAUC of the T2DM group were 5.87 mmol/L +/- 0.19 mmol/L, 14.1 h +/- 0.3 h and 2.04 mmol.L(-1).d +/- 0.09 mmol.L(-1).d respectively, all significantly higher than those of the NGR group (2.10 mmol/L +/- 0.12 mmol/L, 8.3 h +/- 0.4 h and 0.43 mmol.L(-1).d +/- 0.03 mmol.L(-1).d respectively, all P < 0.01). The breakfast had higher PGS and lower Deltat than those of lunch and dinner in the T2DM group (both P < 0.01). The PPGE was arranged from high to low in the order of breakfast, dinner and lunch. The highest IAUC appeared during dinner. (2) There was a significantly correlation between PPGE and IAUC (r = 0.93, P < 0.01) in the T2DM group. After being adjusted by preprandial glucose, the partial correlation of HbA1c and IAUC disappeared (before r = 0.29, P = 0.03, after P = 0.05). (3) The relative contribution of postprandial glucose to overall glucose levels in the T2DM group was significantly higher than that of the NGR group (18.1% +/- 0.8% vs 8.0% +/- 0.7%, P < 0.01), but both were significantly lower than those of preprandial glucose. (4) Relative contribution of postprandial hyperglycemia to overall diurnal hyperglycemia decreased progressively from the lowest to the highest quarter of HbA1c. By contrast, the relative contribution of preprandial hyperglycemia showed a significant increase with increasing levels of HbA1c. Postprandial hyperglycemia played a major role when the HbA1c level below 7.5% (P < 0.05). CONCLUSION: (1) The features of postprandial glucose state in T2DM is representative in the delay of PGS and excessive glucose excursion for a long time after the ingestion of a meal. (2) HbA1c can't reflect postprandial glucose excursions. PPGE can be used as a simple clinic index to evaluate the amplitude of postprandial glucose excursions. (3) Postprandial glucose excursions play a major role in T2DM suffering from mild or moderate hyperglycemia. The present results suggest that postprandial hyperglycemia is an important target for intervention when T2DM patients are approaching the ideal glycemic control.
BACKGROUND: Loss of heterozygosity (LOH) at 13q is one of the most common chromosomal alterations in high-stage prostate cancer, yet little is known about genetic changes in earlier-stage prostate cancer. METHODS: We used five microsatellite markers at 13q14, 21, and 33 to compare LOH frequencies in 51 lesions of high-grade prostatic intraepithelial neoplasia (HGPIN), 21 cases of incidental prostate cancers (IPCs), 31 cases of latent prostate cancers (LPCs), and 102 cases of clinical prostate cancers (CPCs). RESULTS: The frequency of LOH at 13q with at least 1 marker was 0%, 38%, 56%, and 49% in HGPIN, IPCs, LPCs, and CPCs, respectively. No statistically significant difference was found between the types of prostate cancer. Allelic loss at 13q14 was significantly more frequent in pT4 tumors than in earlier-stage tumors (P=0.011). CONCLUSIONS: Allelic loss at 13q is not only an important event in the metastasis of prostate cancer, but also associated with the initiation of the tumor.