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Biomedical subjects

Shu Chen

Publications and source records attributed to Shu Chen.

At least 19 recordsLinked to original sources

The chromosome-level genome of Stylosanthes guianensis provides insights into genome evolution and environmental adaptation.

Stylosanthes guianensis is a leguminous forage crop of significant economic importance, primarily distributed in tropical and subtropical regions. It exhibits strong adaptability to various stresses, yet the genetic basis underlying this trait remains unclear. In this study, we constructed the first chromosome-scale reference genome of S. guianensis using a combination of Nanopore and Hi-C sequencing technologies. The assembled genome size is 1254 Mb, with 10 pseudochromosomes. Using Nanopore full-length transcriptome data, we generated high-quality transcript-level gene annotations, identifying 36 585 gene models and 110 601 transcripts. The repetitive sequences in S. guianensis account for 79.16% of the genome, with the extensive expansion of Gypsy elements in long terminal repeats contributing to its genome size enlargement. Comparative genomic and transcriptomic analyses revealed that flavonoid metabolism plays a pivotal role in stress adaptation, providing new insights into the genetic basis of stress tolerance. Additionally, we generated whole-genome methylation profiles under cold treatment and control conditions, offering valuable data for future epigenomic research. These findings provide essential molecular resources for understanding stress resilience in S. guianensis and advancing its molecular breeding.

Genome, Plant↗

Effect of acid on the aggregation of poly(ethylene xide)-poly(propylene oxide)-poly(ethylene oxide) block copolymers.

The acid effect on the aggregation of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymers EO(20)PO(70)EO(20) has been investigated by transmission electron microscopy (TEM), particle size analyzer (PSA), Fourier transformed infrared, and fluorescence spectroscopy. The critical micellization temperature for Pluronic P123 in different HCl aqueous solutions increases with the increase of acid concentration. Additionally, the hydrolysis degradation of PEO blocks is observed in strong acid concentrations at higher temperatures. When the acid concentration is low, TEM and PSA show the increase of the micelle mean diameter and the decrease of the micelle polydispersity at room temperature, which demonstrate the extension of EO corona and tendency of uniform micelle size because of the charge repulsion. When under strong acid conditions, the aggregation of micelles through the protonated water bridges was observed.

Epoxy Compounds↗

A rice gene activation/knockout mutant resource for high throughput functional genomics.

Using transfer DNA (T-DNA) with functions of gene trap and gene knockout and activation tagging, a mutant population containing 55,000 lines was generated. Approximately 81% of this population carries 1-2 T-DNA copies per line, and the retrotransposon Tos17 was mostly inactive in this population during tissue culture. A total of 11,992 flanking sequence tags (FSTs) have been obtained and assigned to the rice genome. T-DNA was preferentially ( approximately 80%) integrated into genic regions. A total of 19,000 FSTs pooled from this and another T-DNA tagged population were analyzed and compared with 18,000 FSTs from a Tos17 tagged population. There was difference in preference for integrations into genic, coding, and flanking regions, as well as repetitive sequences and centromeric regions, between T-DNA and Tos17; however, T-DNA integration was more evenly distributed in the rice genome than Tos17. Our T-DNA contains an enhancer octamer next to the left border, expression of genes within genetics distances of 12.5 kb was enhanced. For example, the normal height of a severe dwarf mutant, with its gibberellin 2-oxidase (GA2ox) gene being activated by T-DNA, was restored upon GA treatment, indicating GA2ox was one of the key enzymes regulating the endogenous level of GA. Our T-DNA also contains a promoterless GUS gene next to the right border. GUS activity screening facilitated identification of genes responsive to various stresses and those regulated temporally and spatially in large scale with high frequency. Our mutant population offers a highly valuable resource for high throughput rice functional analyses using both forward and reverse genetic approaches.

Base Sequence↗

Effect of hydrophobicity inside PEO-PPO-PEO block copolymer micelles on the stabilization of gold nanoparticles: experiments.

In this paper we present the effect of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymer micelles and their hydrophobicity on the stabilization of gold nanoparticles. Gold nanoparticles were prepared by a method developed by Sakai et al. (Sakai, T.; Alexandridis, P. Langmuir 2004, 20, 8426). An absorption centered at 300-400 nm in time-dependent UV spectra provided evidence that the very first step of the synthesis was to form primary gold clusters. Then the gold clusters grew in size and were stabilized by block copolymer micelles. The stabilization capacities of the micelles were modulated by tuning the block copolymer concentration and composition and by adding salts. With good stabilization, gold particles were spherical and uniform in size with a diameter of 5-10 nm. Otherwise they were aggregates with irregular shapes such as triangular, hexagonal, and rodlike. The presence of a small amount of NaF significantly increased the stabilization capacity of the micelles and consequently modified the quality of the gold particles. Using FTIR and 1H NMR spectroscopy, micellization of the block copolymers and hydrophobicity of the micelles were proven very important for the stabilization. A higher hydrophobicity of the micelle cores was expected to favor the entrapment of primary gold clusters and the stabilization of gold nanoparticles.

Colloids↗

[Formation of platelets from cord blood CD34+ cells-derived megakaryocytes induced by S-nitrosoglutathione].

To investigate the effect of S-nitrosoglutathione (GSNO), a nitric oxide donor, on platelet production from megakaryocytes differentiated from cord blood CD34(+) cells in vitro, the CD34 (+) cells from eight fresh umbilical cord blood samples by a high-gradient magnetic cell sorting (MACS) system were cultured in serum-free medium for 14 d with thrombopoietin (TPO) 50 ng/ml, IL-3 10 ng/ml, stem cell factor (SCF) 50 ng/ml and rHuGM-CSF 20 ng/ml. Then, CD61 (+) cells were purified by MACS system from these CD34 (+) cells, and were cultured in serum-free medium supplemented with TPO 50 ng/ml, IL-3 10 ng/ml and SCF 50 ng/ml in the presence (treatment group) and absence (control group) of GSNO for 30 min or 2 h. Platelet-sized particles were counted by flow cytometry; megakaryocyte structure was detected by scanning electron microscope. Aggregation of the thrombin-induced platelet particle was observed under inversion microscope. cGMP was assessed by commercial ELISA kit. The results showed that, compared with the control group, the number of platelet-sized particles significantly increased (P<0.05) in the treatment group, in which megakaryocytes presented significant pseudopod formation and extensive membrane blebbing. The platelet particle aggregation could be observed under microscope after thrombin induction. cGMP activity was significantly increased after treatment with GSNO (P<0.05). These results propose that GSNO can facilitate platelet production from megakaryocyte, and it may be partly through cGMP pathway.

Antigens, CD34↗

Quantitative trait loci modulate vertebral morphology and mechanical properties in a population of 18-month-old genetically heterogeneous mice.

The aim of this study was to examine effects of polymorphic genes on vertebral bone morphology and mechanical properties. Genotypes from 525 18-month-old female mice were compared to geometric traits obtained from micro-computed tomography and mechanical properties from compression testing. Genetic markers were associated with traits on at least 13 different chromosomes, demonstrating the complexity of genetic control over vertebral form, function and aging.

Aging↗

Quantitative analysis of HIV-1 variants with the K103N resistance mutation after single-dose nevirapine in women with HIV-1 subtypes A, C, and D.

INTRODUCTION: We used a sensitive point mutation assay, LigAmp, to detect and quantify K103N-containing variants in African women who received single-dose nevirapine (NVP) to prevent mother-to-child HIV-1 transmission. METHODS: Plasma for testing was collected 6 to 8 weeks postpartum from 301 women (144 subtype A, 63 subtype C, and 94 subtype D). RESULTS: The portion of women with 0.5% or more K103N-containing variants was lowest for subtype A (60/144, 41.7%) and highest for subtype C (44/63, 69.8%; P < 0.0001). K103N was rarely detected in pre-NVP samples. In a multivariate model, K103N detection was associated with HIV-1 subtype (C > A), after adjusting for log10 delivery viral load, the number of days between NVP dosing and sample collection, age, and parity. Among women with K103N detected: (1) the median %K103N was lower for subtype A (2.2%) than C (11.7%, P = 0.0001) or D (5.5%, P = 0.04), and (2) in a multivariate linear model, higher log10 (%K103N) was associated with HIV subtype (C > A, P = 0.0001; D > A, P = 0.01; and C vs D, no difference), but not other factors. CONCLUSIONS: After administration of single-dose NVP, K103N was detected more frequently and at higher levels in women with subtypes C and D than A. Further studies are needed to evaluate the clinical significance of NVP-resistant variants in this setting.

Amino Acid Substitution↗

[Hepatic safety of itraconazole intravenous solution in treatment of invasive fungal infection].

OBJECTIVE: To investigate the hepatic safety of itraconazole intravenous solution in the treatment of invasive fungal infection. METHODS: Forty-nine patients with invasive fungal infection, such as pneumonia, meningitis, endocarditis, and blood stream infection, caused by Aspergillus spp. Cryptococcus neoformans, Candida spp. Penicillium marneffei, and Prototheca wickerhamii, 50 of which had underlying diseases, including hepatic diseases, such as hepatitis, cirrhosis, fatty liver etc. were treated with intravenous itraconazole for 12.6 days (2 - 42 days). Liver function test was conducted before and after the treatment. The relationship between liver adverse reaction and itraconazole treatment was evaluated. RESULTS: Liver function test was abnormal in 20 patients. The patients with liver enzyme abnormalities before itraconazole treatment were easier to suffer from hepatic damage during itraconazole treatment (chi(2) = 11.54, P = 0.001). However, only in 2 patients with mild liver function test abnormality the liver adverse reaction could be associated with itraconazole treatment. CONCLUSION: Itraconazole treatment for invasive fungal infection is rather safe, even in the patients with underlying hepatic diseases. Liver function test is recommended for all patients suggestive of liver dysfunction and protective therapy for liver is needed.

Adolescent↗

Oleate-induced decrease in hepatocyte insulin binding is mediated by PKC-delta.

We have previously shown that free fatty acids (FFA) impair hepatic insulin extraction in vivo and thus generate hyperinsulinemia, a suspected risk factor for atherosclerosis and cancer. Hepatic insulin extraction is a receptor-mediated event, which is initiated by hepatocyte insulin binding. In the present study, we investigated the effect of FFA on insulin binding in freshly isolated rat hepatocytes maintained at 10 mM glucose. Hepatocyte insulin binding decreased after 1 h exposure to oleate in a concentration-dependent manner reaching a maximum (35-40%) at 125 microM. Inhibition of FFA oxidation by >90% with the carnitine palmitoyltransferase I (CPT-I) inhibitor methylpalmoxirate (MP, 30 microM) did not prevent the effect of oleate. However, when hepatocytes were treated with the PKC inhibitor bisindolylmaleimide (BIM, 1 microM) the effect of oleate was abolished. Subcellular fractionation and immunoblotting of specific PKC isoforms revealed that oleate-induced hepatic PKC-delta membrane translocation, but did not translocate-epsilon, -theta, -alpha, -betaI and -betaII. These results indicate that PKC-delta activation mediated the FFA-induced decrease in hepatocyte insulin binding under our conditions, and thus provides a mechanistic basis for FFA-induced hyperinsulinemia.

Animals↗

Association between the replication capacity and mother-to-child transmission of HIV-1, in antiretroviral drug-naive Malawian women.

Replication capacity and transmission of human immunodeficiency virus (HIV)-1 in antiretroviral drug-naive Malawian women who had subtype C infection were investigated. Infant children of these women received either 1 dose of nevirapine or 1 dose of nevirapine plus 1 week of daily doses of zidovudine. PhenoSense HIV was used to determine replication capacity in 49 women whose infants were infected with HIV-1 and in 47 women whose infants were uninfected by 6-8 weeks of age. Mean replication capacity was higher in transmitters than in nontransmitters (P=.01). In a multivariate model, higher replication capacity was associated with transmission (odds ratio, 1.45 for each 10% increase in replication capacity [95% confidence interval, 1.11-1.90]; P = .0063), after adjustment for maternal HIV-1 load and other factors.

Adult↗

Estimated risk for developing autoimmune Addison's disease in patients with adrenal cortex autoantibodies.

CONTEXT: Patients with adrenal cortex autoantibodies (ACA) without overt autoimmune Addison's disease (AAD) are at risk of adrenal failure. DESIGN: To assess the contribution of different clinical, immunological, genetic, and functional factors in the progression to AAD, we followed up 100 ACA-positive and 63 ACA-negative patients without AAD for a maximum of 21 yr (mean 6.0 yr, median 4.8). ACA were measured by immunofluorescence and 21-OH autoantibodies (Abs) by RIA. Adrenal function was assessed by measuring basal levels of cortisol, aldosterone, ACTH, renin activity, and cortisol response to ACTH. The risk of developing AAD was calculated using survival and multivariate analyses. RESULTS: AAD developed in 31 ACA-positive patients and one ACA-negative patient. The cumulative risk of disease in ACA-positive patients was 48.5% [95% confidence interval (CI) 40.8-56.1]. The cumulative risk was higher in children than adults (100 vs. 31.9%; P < 0.0001), males than females (68.6 vs. 42.7%; P = 0.006), patients with subclinical rather than normal adrenal function at entry (87.4 vs. 30.1%; P < 0.0001), patients with hypoparathyroidism and/or candidiasis than patients with other autoimmune or nonautoimmune diseases (100 vs. 29.7%; P < 0.0001), and patients with high rather than low-medium ACA titers (62.8 vs. 41.2%; P = 0.12). The presence of human leukocyte antigen (HLA)-DRB1 did not appear to contribute to the prediction of AAD. Adjusted hazard ratios by Cox model for the development of AAD were 3.37 for males (CI 1.38-8.24), 5.23 for hypoparathyroidism and/or candidiasis (CI 1.53-17.92), 3.33 for high antibody titers (CI 1.43-7.78), and 6.15 for impaired adrenal function at entry (CI 2.79-13.57). CONCLUSIONS: These results were used to construct a risk algorithm for estimating the probability of developing AAD from the combination of gender, age, adrenal function, antibody titer, and associated autoimmune disorders at entry. The values of estimated risk could be used to decide appropriate follow-up intervals and future immunointervention strategies.

Addison Disease↗

Microenvironmental and conformational structure of triblock copolymers in aqueous solution by 1H and 13C NMR spectroscopy.

1H and 13C nuclear magnetic resonance (NMR) spectra of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymers in D2O solutions have been systematically investigated. The detailed assignments of various 1H and 13C NMR signals are presented. The hyperfine structure of PO -CH2- protons was clearly assigned, the arising reason of this hyperfine structure was attributed to the influence of the chiral center of -CHCH3- groups and the direct coupling between the PO -CH2- and -CH3 protons. The external standard 2,2-dimethyl-2-silapentane-5-sulfonate sodium salt (DSS) was firstly applied in this system. Accurate chemical shift values referenced to the external standard DSS were obtained. 1H NMR chemical shift of PO -CH2- and -CH3 signals shows a larger decrease in ppm values than that of EO -CH2- signal with the increase of PPO/PEO ratio or temperature indicating that PO segments exist in a more hydrophobic microenvironment. A new resonance signal assigned to the PO -CH2- protons appeared when the temperature is above the CMT, which is attributed to the breakdown of the intra-molecular (C-H)...O hydrogen bond between the PO -CH2- protons and the ester oxygens. The breakdown of this intra-molecular hydrogen bond may result in a decrease of gauche conformers of the PPO chain. The increase of 13C NMR chemical shift of block copolymers validates this conformational change assumption. It can be inferred that the amount of gauche conformers decreases whereas that of trans conformers increases in both PO and EO chains when elevating the PPO/PEO ratio or temperature. The observed 13C NMR chemical shifts of PO segments show a bigger increase than those of EO segments, supporting the formation of a nonpolar microenvironment around PO segments.

Journal Article↗

Development of nevirapine resistance in infants is reduced by use of infant-only single-dose nevirapine plus zidovudine postexposure prophylaxis for the prevention of mother-to-child transmission of HIV-1.

We analyzed the development of nevirapine (NVP) resistance in human immunodeficiency virus type 1 (HIV-1)-infected Malawian infants who received regimens containing single-dose NVP (SD-NVP) for the prevention of mother-to-child transmission (MTCT) of HIV-1. All infants received SD-NVP, and some randomly received zidovudine (ZDV) as well. Mothers did or did not receive SD-NVP on the basis of when they arrived at the hospital for delivery. In infants 6-8 weeks of age, NVP resistance was less frequent when infants had received SD-NVP plus ZDV and mothers had not received SD-NVP than when infants had received SD-NVP alone and mothers had received SD-NVP (4/15 [27%] vs. 20/23 [87%]; P < .001). The risk of MTCT of HIV-1 was comparable with these regimens. Infant-only prophylaxis also eliminates the development of NVP resistance in mothers.

Anti-Retroviral Agents↗

Dynamic balance and stepping versus tai chi training to improve balance and stepping in at-risk older adults.

OBJECTIVES: To compare the effect of two 10-week balance training programs, Combined Balance and Step Training (CBST) versus tai chi (TC), on balance and stepping measures. DESIGN: Prospective intervention trial. SETTING: Local senior centers and congregate housing facilities. PARTICIPANTS: Aged 65 and older with at least mild impairment in the ability to perform unipedal stance and tandem walk. INTERVENTION: Participants were allocated to TC (n = 107, mean age 78) or CBST, an intervention focused on improving dynamic balance and stepping (n = 106, mean age 78). MEASUREMENTS: At baseline and 10 weeks, participants were tested in their static balance (Unipedal Stance and Tandem Stance (TS)), stepping (Maximum Step Length, Rapid Step Test), and Timed Up and Go (TUG). RESULTS: Performance improved more with CBST than TC, ranging from 5% to 10% for the stepping tests (Maximum Step Length and Rapid Step Test) and 9% for TUG. The improvement in TUG represented an improvement of more than 1 second. Greater improvements were also seen in static balance ability (in TS) with CBST than TC. CONCLUSION: Of the two training programs, in which variants of each program have been proven to reduce falls, CBST results in modest improvements in balance, stepping, and functional mobility versus TC over a 10-week period. Future research should include a prospective comparison of fall rates in response to these two balance training programs.

Aged↗

Sensitivity of the ViroSeq HIV-1 genotyping system for detection of the K103N resistance mutation in HIV-1 subtypes A, C, and D.

The US Food and Drug Administration-cleared ViroSeq HIV-1 Genotyping System (ViroSeq) and other population sequencing-based human immunodeficiency virus type 1 (HIV-1) genotyping methods detect antiretroviral drug resistance mutations present in the major viral population of a test sample. These assays also detect some mutations in viral variants that are present as mixtures. We compared detection of the K103N nevirapine resistance mutation using ViroSeq and a sensitive, quantitative point mutation assay, LigAmp. The LigAmp assay measured the percentage of K103N-containing variants in the viral population (percentage of K103N). We analyzed 305 samples with HIV-1 subtypes A, C, and D collected from African women after nevirapine administration. ViroSeq detected K103N in 100% of samples with >20% K103N, 77.8% of samples with 10 to 20% K103N, 71.4% of samples with 5 to 10% K103N, and 16.9% of samples with 1 to 5% K103N. The sensitivity of ViroSeq for detection of K103N was similar for subtypes A, C, and D. These data indicate that the ViroSeq system reliably detects the K103N mutation at levels above 20% and frequently detects the mutation at lower levels. Further studies are needed to compare the sensitivity of different assays for detection of HIV-1 drug resistance mutations and to determine the clinical relevance of HIV-1 minority variants.

Anti-HIV Agents↗

The impact of breastfeeding on the health of HIV-positive mothers and their children in sub-Saharan Africa.

OBJECTIVE: We assessed the impact of breastfeeding by women infected with human immunodeficiency virus (HIV)-1 on their morbidity and risk of mortality and on the mortality of their children. METHODS: We analysed longitudinal data from two previous randomized clinical trials of mother-to-child transmission of HIV conducted between April 2000 and March 2003 in the Republic of Malawi, Africa. Mothers infected with HIV, and their newborns, were enrolled at the time of their child's birth; they then returned for follow-up visits when the child was aged 1 week, 6-8 weeks and then 3, 6, 9, 15, 18, 21 and 24 months. Patterns of breastfeeding (classified as exclusive, mixed or no breastfeeding), maternal morbidity and mortality, and mortality among their children were assessed at each visit. Descriptive and multivariate analyses were performed to determine the association between breastfeeding and maternal and infant outcomes. FINDINGS: A total of 2000 women infected with HIV were enrolled in the original studies. During the 2 years after birth, 44 (2.2%) mothers and 310 (15.5%) children died. (Multiple births were excluded.) The median duration of breastfeeding was 18 months (interquartile range (IQR)=9.0-22.5), exclusive breastfeeding 2 months (IQR=2-3) and mixed feeding 12 months (IQR=6-18). Breastfeeding patterns were not significantly associated with maternal mortality or morbidity after adjusting for maternal viral load and other covariates. Breastfeeding was associated with reduced mortality among infants and children: the adjusted hazard ratio for overall breastfeeding was 0.44 (95% confidence interval (CI)=0.28-0.70), for mixed feeding 0.45 (95% CI=0.28-0.71) and for exclusive breastfeeding 0.40 (95% CI=0.22-0.72). These protective effects were seen both in infants who were infected with HIV and those who were not. CONCLUSION: Breastfeeding by women infected with HIV was not associated with mortality or morbidity; it was associated with highly significant reductions in mortality among their children.

Adult↗

[Advances in diabetic erectile dysfunction].

Erectile dysfunction is common complication of diabetes mellitus. The incidence of diabetes mellitus induced erectile dysfunction (DMED) is 20% - 75%. DMED appears to be due to vascular-neuropathic and corpus cavernosum smooth muscular damage. To control blood glucose, blood pressure and blood lipids is the basis of DMED therapy. In 50% of the patients with DMED, the phosphodiesterase 5 inhibitors is effective, while intracavernous pharmacotherapy is effective for more than 90%. Penile prosthesis implantation continues to be the treatment of choice in case of other therapy failure.

Animals↗