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1.
Molecules ; 27(15)2022 Jul 31.
Article in English | MEDLINE | ID: mdl-35956844

ABSTRACT

The effects of nanoparticles (NPs) on microbiota homeostasis and their physiological relevance are still unclear. Herein, we compared the modulation and consequent pharmacological effects of oral administration of (-)-epigallocatechin-3-gallate (EGCG)-loaded ß-cyclodextrin (ß-CD) NPs (EGCG@ß-CD NPs) and EGCG on gut microbiota. EGCG@ß-CD NPs were prepared using self-assembly and their influence on the intestinal microbiome structure was analyzed using a metagenomics approach. The "Encapsulation efficiency (EE), particle size, polydispersity index (PDI), zeta potential" of EGCG@ß-CD NPs were recorded as 98.27 ± 0.36%, 124.6 nm, 0.313 and -24.3 mV, respectively. Surface morphology of EGCG@ß-CD NPs was observed as spherical. Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and molecular docking studies confirmed that EGCG could be well encapsulated in ß-CD and formed as EGCG@ß-CD NPs. After being continuously administered EGCG@ß-CD NPs for 8 weeks, the serum cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and liver malondialdehyde (MDA) levels in the rats were significantly decreased, while the levels of catalase (CAT) and apolipoprotein-A1 (apo-A1) in the liver increased significantly in the hyperlipidemia model of rats, when compared to the high-fat-diet group. Furthermore, metagenomic analysis revealed that the ratio of Verrucomicrobia/Bacteroidetes was altered and Bacteroidetes decreased in the high-fat diet +200 mg/kg·bw EGCG@ß-CD NPs group, while the abundance of Verrucomicrobia was significantly increased, especially Akkermansia muciniphila in rat feces. EGCG@ß-CD NPs could be a promising EGCG delivery strategy to modulate the gut microbiota, enhancing its employment in the prevention of hyperlipidemia.


Subject(s)
Catechin , Gastrointestinal Microbiome , Hyperlipidemias , Nanoparticles , Animals , Catechin/analogs & derivatives , Catechin/chemistry , Cholesterol , Diet, High-Fat/adverse effects , Hyperlipidemias/drug therapy , Hyperlipidemias/etiology , Metagenomics , Molecular Docking Simulation , Nanoparticles/chemistry , Rats , Spectroscopy, Fourier Transform Infrared
2.
Article in English | MEDLINE | ID: mdl-35055780

ABSTRACT

Irregular hydrological events, according to a classic plankton ecology group (PEG) study, can generate major deviations from the standard PEG model. However, little is known about the function of hydrological factors in influencing the seasonal dynamics of plankton. We used multivariate and Partial Least Squares Path Modeling to analyze the seasonal variation in crustacean zooplankton and related environmental factors from winter 2009 to winter 2016 in Lake Poyang, the largest freshwater lake in China. We found a distinct seasonal pattern in zooplankton development, which deviated, in part, from the PEG model, as we found indications of (1) a weaker degree of food limitation in winter and spring, likely due to high concentrations of allochthonous sources caused by decomposition of seasonally flooded hygrophytes, also affecting sediment dynamics; (2) a peak in crustacean zooplankton biomass in summer when the water level was high (and predation was lower), and where horizontal transport of zooplankton from the littoral zone to the pelagic was possibleand (3) a higher predation pressure in autumn, likely due to a shrinking water volume that left the fish concentrated in less water. The majority of these differences can be attributed to the direct or indirect impacts of physical factor variation.


Subject(s)
Plankton , Zooplankton , Animals , Ecosystem , Lakes , Phytoplankton , Seasons
3.
Ecol Evol ; 11(20): 14268-14281, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34707853

ABSTRACT

Rosette-type submerged macrophytes are widely distributed across a range of water depths in shallow lakes and play a key role in maintaining ecosystem structures and functions. However, little is known about the rapid adaptive responses of such macrophytes to variations in water depth, especially at the juvenile stage. Here, we conducted a short-term in situ mesocosm experiment, in which the juveniles of Vallisneria natans were exposed to a water depth gradient ranging from 20 to 360 cm. Twenty-two leaf-related traits were examined after 4 weeks of growth in a shallow lake. Most (18) traits of V. natans generally showed high plasticity in relation to water depth. Specifically, juveniles allocated more biomass to leaves and had higher specific leaf area, leaf length-to-width ratio, chlorophyll content, and carotenoids content in deep waters, displaying trait syndrome associated with high resource acquisition. In contrast, V. natans juveniles in shallow waters had higher leaf dry matter content, leaf soluble carbohydrate content, carotenoids per unit chlorophyll, and peroxidase activity, pertaining to resource conservation. Notably, underwater light intensity was found to be the key factor explaining the trait plasticity along the water depth gradient, and 1.30 mol photons m-2 d-1 (at 270 cm) could be the optimal irradiance level based on the total biomass of V. natans juveniles. The present study highlights the significance of leaf trait plasticity for rosette-type macrophytes in response to variations in water depth and sheds new light on the differences between trade-offs in deep- and shallow-water areas.

4.
J Sci Food Agric ; 101(13): 5305-5313, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34031895

ABSTRACT

Drought stress (DS) is the most important abiotic stress affecting yield and quality of tea worldwide. DS causes oxidative stress to cells due to the accumulation of reactive oxygen species (ROS). As non-enzymatic antioxidants, tea catechins can scavenge excess ROS in response to DS. Further, catechin accumulation contributes to the formation of oxidative polymerization products (e.g. theaflavins and thearubigins) that improve the quality of black tea. However, there are no systematic reports on the response of tea catechins to DS. First, we reviewed the available literature on the response of tea plants to DS. Second, we summarized the current knowledge of ROS production in tea leaves under DS and typical antioxidant response mechanisms. Third, we conducted a detailed review of the changes in catechin levels in tea under different drought conditions. We found that the total amounts of catechin and o-quinone increased under DS conditions. We propose that the possible mechanisms underlying tea catechin accumulation under DS conditions include (i) autotrophic formation of o-quinone, (ii) polymerization of proanthocyanidins that directly scavenge excess ROS, and (iii) formation of metal ion complexes and by influencing the antioxidant systems that indirectly eliminate excess ROS. Finally, we discuss ways of potentially improving black tea quality using drought before picking in the summer/fall dry season. In summary, we mainly discuss the antioxidant mechanisms of tea catechins under DS and the possibility of using drought to improve black tea quality. Our review provides a theoretical basis for the production of high-quality black tea under DS conditions. © 2021 Society of Chemical Industry.


Subject(s)
Camellia sinensis/physiology , Catechin/metabolism , Droughts , Antioxidants/chemistry , Antioxidants/metabolism , Camellia sinensis/chemistry , Camellia sinensis/genetics , Catechin/chemistry , Oxidative Stress , Plant Leaves/genetics , Plant Leaves/metabolism , Stress, Physiological , Water/analysis , Water/metabolism
5.
BMC Complement Med Ther ; 21(1): 6, 2021 Jan 05.
Article in English | MEDLINE | ID: mdl-33402180

ABSTRACT

BACKGROUND: Germacrone (GM) is a terpenoid compound which is reported to have anti-inflammatory and anti-oxidative effects. However, its role in treating traumatic brain injury (TBI) remains largely unknown. METHODS: Male C57BL/6 mice were divided into the following groups: control group, TBI group [controlled cortical impact (CCI) model], CCI + 5 mg/kg GM group, CCI + 10 mg/kg GM group and CCI + 20 mg/kg GM group. GM was administered via intraperitoneal injection. The neurological functions (including motor coordination, spatial learning and memory abilities) and brain edema were measured. Nissl staining was used to detect the neuronal apoptosis. Colorimetric assays and enzyme linked immunosorbent assay (ELISA) kits were used to determine the expression levels of oxidative stress markers including myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD), as well as the expressions of inflammatory markers, including tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6). Additionally, protein levels of Nrf2 and p-p65 were detected by Western blot assay. RESULTS: GM significantly ameliorated motor dysfunction, spatial learning and memory deficits of the mice induced by TBI and it also reduced neuronal apoptosis and microglial activation in a dose-dependent manner. Besides, GM treatment reduced neuroinflammation and oxidative stress compared to those in the CCI group in a dose-dependent manner. Furthermore, GM up-regulated the expression of antioxidant protein Nrf2 and inhibited the expression of inflammatory response protein p-p65. CONCLUSIONS: GM is a promising drug to improve the functional recovery after TBI via repressing neuroinflammation and oxidative stress.


Subject(s)
Brain Injuries, Traumatic/drug therapy , Brain/drug effects , Nervous System Diseases/drug therapy , Plant Extracts/therapeutic use , Sesquiterpenes, Germacrane/therapeutic use , Animals , Brain/metabolism , Brain Edema/drug therapy , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/metabolism , Curcuma , Cytokines/metabolism , Disease Models, Animal , Drug Evaluation, Preclinical , Male , Memory/drug effects , Mice, Inbred C57BL , Microglia/drug effects , NF-E2-Related Factor 2/metabolism , NF-kappa B/metabolism , Nervous System Diseases/etiology , Nervous System Diseases/metabolism , Oxidative Stress/drug effects , Phytotherapy , Plant Extracts/pharmacology , Recovery of Function/drug effects , Sesquiterpenes, Germacrane/pharmacology , Spatial Learning/drug effects
6.
Environ Pollut ; 268(Pt B): 115912, 2021 Jan 01.
Article in English | MEDLINE | ID: mdl-33187844

ABSTRACT

Due to a close contact with water column, submerged macrophytes are easily disturbed by environment change in freshwater ecosystems, especially at the seedling stage. In recent decades, freshwater ecosystems have been subject to severe cadmium (Cd) pollution, which can cause toxic effects on the growth of submerged macrophytes. Moreover, the temperature rise resulting from climate warming and water level decline may further aggravate such effect, especially in shallow lakes. Here, we investigated the independent and interaction effects of Cd exposure levels (0, 0.5, 1, and 2.5 mg L-1) and temperature (15, 25, and 30 °C) on morphological and physiological traits of Myriophyllum aquaticum (Vell.) Verd. Seedlings generated from propagules and seeds. The temperature rise and Cd exposure generally resulted in a significant increase of Cd concentrations and antioxidant enzyme activities in leaves, as well as a decrease of chlorophyll a and b concentrations. The number and length of leaves generated from propagules always show a downward trend with the increase of Cd exposure, regardless of the temperature. Moreover, the lowest leaf number and length always occurred at high temperature (i.e. 30 °C) when the Cd exposure level increased to 1 and 2.5 mg L-1. For the seedlings generated from seeds, the temperature rise caused an increase of leaf emergence rate under low Cd exposure levels, but resulted in a significant decrease with the Cd exposure level. This study indicates the negative effects of Cd exposure and temperature rise on submerged macrophytes at the seedling stage, and highlights that temperature rise would enhance Cd toxicity.


Subject(s)
Cadmium , Seedlings , Cadmium/toxicity , Chlorophyll A , Ecosystem , Lakes
7.
Environ Sci Pollut Res Int ; 28(4): 4253-4261, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32939652

ABSTRACT

Submerged macrophytes, important primary producers in shallow lakes, play a crucial role in maintaining ecosystem structure and function. By altering a series of environmental factors, especially light intensity, water depth has great influences on growth of submerged macrophytes. Here, by hanging pots statically at water depths of 40, 60, 80, 100, 120, 140, 160, 180, 200, and 220 cm, respectively, we investigated effects of water depths on morphological plasticity and physiological traits of Potamogeton crispus. At 40 and 60 cm water depths versus other water depths, P. crispus showed lower plant height, larger stem diameter, thicker leaves, and smaller leaf area, leaf length, and specific leaf area. With water depth increasing, the plant height, leaf area, and leaf length gradually increased until 160 cm water depth, while the stem diameter and leaf thickness gradually decreased until 200 cm water depth. In comparison, the plant height, leaf length, and leaf number significantly decreased when the water depth further increased to 180-220 cm. The leaves contained lower concentrations of superoxide dismutase and peroxidase at 100-160 cm water depth, and lower catalase concentrations at 40-140 cm water depth, especially at 80-100 cm. In shallow waters, the concentration of chlorophyll a and b in leaves were both lower, while the ratio of chlorophyll a to b was relatively higher. As the water depth of 40-220 cm, the chlorophyll a and b concentrations increased significantly with increasing water depth, while their ratio gradually decreased. The present study provides new insights into the adaptation strategies of submerged macrophytes to the variation in water levels, and our findings are beneficial for ecosystem construction and management.


Subject(s)
Potamogetonaceae , Chlorophyll A , Ecosystem , Lakes , Water
8.
Environ Sci Pollut Res Int ; 27(4): 3908-3922, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31823258

ABSTRACT

Metal pollution has been a serious problem facing river systems worldwide, which can adversely affect human health through food chain. The goal of this study was to determine the distribution, sources, and health risk of dissolved metals (Cr, Mn, Ni, Cu, Zn, As, Cd, Pb, Al, Sb, V, Co, Mo) in major rivers located in the hilly area of southeastern China (namely, Jiulongjiang River (JL), Minjiang River (MJ), Oujiang River (OJ), Qiantangjiang River (QT), Raohe River (RR), Fuhe River (FR), Xinjiang River (XR), Ganjiang River (GR), Xiushui River (XS), Xiangjiang River (XJ), Zishui River (ZR), Yuanjiang River (YR), Lishui River (LR)) during dry and wet seasons. Results indicated that metal concentrations were spatially and temporally distinct. Metals of Mn, Ni, Cu, Cd, Sb were significantly higher in specific rivers than other metals. And metals of Cr, Ni, As, and Al concentrations were obviously higher in dry season than in wet season. The comparison with drinking water guidelines of China and other countries indicated that waterbodies were polluted higher by Al than other metals at most sites. Metals in JL and XJ may have health risk to local adults with hazard index (HI) > 1. While special attention should be paid to As, which had a potential carcinogenic risk to adults in study area with CR higher than the critical value. Source analysis with statistical method indicated that point and non-point pollutants from anthropogenic activities are the main sources of metals, with the exception of Al, Ni, V, Cr, and Mo that were mainly from natural processes. This study could be useful for the management and protection of the China's Southern hilly area river systems.


Subject(s)
Metals, Heavy , Water Pollutants, Chemical , Adult , China , Environmental Monitoring , Geologic Sediments , Humans , Metals, Heavy/analysis , Metals, Heavy/toxicity , Risk Assessment , Rivers , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/toxicity
9.
Environ Sci Pollut Res Int ; 26(3): 2270-2280, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30465241

ABSTRACT

To evaluate the possible effects of habitat type on crustacean plankton (hereafter zooplankton) biomass and body size, a 5-year study (2011 to 2015) was conducted during wet seasons in three habitats in Lake Poyang, China. The lacustrine habitat with the most stable hydrologic regime had the highest zooplankton biomass coinciding with the highest phytoplankton biomass. The riverine habitat with the lowest Secchi depth overall had the largest zooplankton body size, but high zooplankton biomass only in high water level years. The seasonally inundated floodplain habitats had the lowest zooplankton biomass and the smallest individual body size, coinciding with the lowest phytoplankton biomass and the highest predation pressure, the latter indicated by a low zooplankton: phytoplankton biomass ratio (ZB:PB). Multiple linear regression analyses indicated that pelagic zooplankton assemblages were primarily influenced by phytoplankton biomass in lacustrine habitat, by advection and turbidity in riverine regions, and by predation pressure in seasonally inundated floodplain region. We conclude that the importance of bottom-up and top-down effects on zooplankton biomass and body size varied with habitat type in Lake Poyang.


Subject(s)
Biomass , Body Size , Crustacea , Ecosystem , Lakes , Zooplankton , Animals , China , Floods , Hydrology , Phytoplankton , Plankton , Predatory Behavior , Seasons
10.
Huan Jing Ke Xue ; 37(6): 2141-2148, 2016 Jun 08.
Article in Chinese | MEDLINE | ID: mdl-29964879

ABSTRACT

As one of the few remaining lakes that are freely connected with the Yangtze River, Poyang Lake exhibits a unique aquatic ecology which is different from the disconnected lakes. In order to study the mechanism of limnological responses to water level fluctuations (WLFs), samples were collected weekly over 10 months from September 2011 to December 2012 in Xingzi and Duchang, and the effect of fluctuations in water level on nutrients and phytoplankton chlorophyll a (Chla) concentrations was investigated in Poyang Lake. Chla concentrations were strongly related to WLFs, with higher Chla concentrations in the higher water phase. The regression analysis indicated that Chla concentrations were significantly and positively correlated with water temperature (P<0.0001) and secchi depth (SD) (P<0.0001) but negatively correlated with total and inorganic nitrogen concentrations (TN,P<0.01; NOx-N,P<0.01; NH4+-N:P<0.05). SD and total and inorganic nitrogen concentrations were all significantly correlated with WLFs of Poyang Lake (SD,P<0.01; TN,P<0.0001; NOx-N:P<0.01; NH4+-N,P<0.0001). Two different water levels were identified in the lake by principal components analysis:the low water level with high nutrient values and the high water level with high water temperature, SD, and Chla values. These results supported the hypothesis that WLFs clearly exerted an overall impact on the growth of phytoplankton in Poyang Lake of the Yangtze River floodplain. WLFs affected the water transparency (expressed by SD), nutrients, and Chla concentrations of Poyang Lake, likely due to flush flood pulse, re-suspension of suspended matter, dilution effects, and human activities.


Subject(s)
Chlorophyll/analysis , Environmental Monitoring , Lakes/chemistry , Nitrogen/analysis , China , Chlorophyll A , Water
11.
Hum Immunol ; 74(12): 1636-42, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24012585

ABSTRACT

The human leukocyte antigen (HLA) allele frequencies, which differ among various ethnic populations, may result in population-specific effects on HIV-1 disease progression. No large-scale study has yet been conducted on the Chinese population. In this study, HLA class I antigen specificities were determined in a cohort including 105 long-term non-progressors (LTNPs) and 321 typical progressors (TPs), who were recruited from HIV-1-infected Northern Han Chinese, to determine the associations between certain HLA types and HIV-1 disease progression. The frequencies of HLA class I specificities and haplotypes among the two groups were compared using binary logistic stepwise regression. Results showed that HLA-A(∗)30-B(∗)13-C(∗)06 (OR = 0.387, P = 0.019) and B(∗)67 (OR = 0.134, P = 0.005) were associated with a long-term non-progressing condition, and C(∗)01 (OR = 2.539, P = 0.050) was overrepresented in TPs after adjusting for non-genetic factors (sex, age, the location of patients, HIV subtype and the route of infection). The influence of HLA homozygosity on HIV disease progression was also analyzed. However, homozygosity at HLA-A, HLA-B or HLA-C conferred no observable disadvantage in our study population (P = 0.730, 0.246 and 0.445, respectively). These findings suggest that the host's genetics make important contributions to HIV viral control and may help to develop peptide-based vaccines for this population.


Subject(s)
HIV Infections/genetics , HIV Infections/immunology , HIV-1/immunology , Haplotypes , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class I/immunology , Adult , Alleles , Asian People/genetics , China , Disease Progression , Female , Gene Frequency , HIV Infections/virology , HIV-1/genetics , Homozygote , Humans , Male , Middle Aged
12.
Zhonghua Yi Xue Za Zhi ; 92(17): 1159-64, 2012 May 08.
Article in Chinese | MEDLINE | ID: mdl-22883001

ABSTRACT

OBJECTIVE: To explore the human leukocyte antigen (HLA)-associated mutations in Gag protein of B' clade (human immunodeficiency virus-1) HIV-1 infected Han Chinese people and evaluate the impact of HLA associated Gag mutations on the disease progression of HIV infection. METHODS: A total of 95 B' clade HIV-1 infected Han Chinese cases were recruited. The gag sequences were amplified from viral RNA and sequenced directly. HLA-I genotypes were detected with the assay of polymerase chain reaction-sequence specific primer (PCR-SSP). HLA-associated mutations were identified and the relationships between HLA-associated mutations and CD4+ T cell counts or plasma viral loads analyzed. RESULTS: Forty-seven kinds of mutations at 28 sites (15, 18, 26, 30, 34, 46, 62, 67, 81, 84, 90, 102, 118, 121, 122, 125, 146, 147, 173, 176, 252, 357, 374, 376, 437, 470, 471, 478) of Gag protein were significantly associated with particular HLA class I allelotypes (P < 0.05). Among which, 9 sites (26, 30, 81, 84, 125, 146, 147, 357, 437) were located within 13 known cytotoxic T-lymphocyte (CTL) epitopes or flanking regions. The number of HLA-associated mutations was significantly associated with both CD4 T cell counts (r = -0.318, P = 0.002) and viral loads (r = 0.360, P = 0.003). CONCLUSION: HLA-associated mutations may have a significant impact on HIV disease progression in B' clade HIV-1 infected Han Chinese population.


Subject(s)
Acquired Immunodeficiency Syndrome/genetics , Acquired Immunodeficiency Syndrome/virology , Genes, MHC Class I , HIV-1/genetics , gag Gene Products, Human Immunodeficiency Virus/genetics , Adult , Aged , Alleles , Asian People/genetics , Female , Humans , Male , Middle Aged , Molecular Sequence Data , Mutation , RNA, Viral , Viral Load , Young Adult
13.
Zhonghua Yi Xue Za Zhi ; 85(11): 760-4, 2005 Mar 23.
Article in Chinese | MEDLINE | ID: mdl-15949383

ABSTRACT

OBJECTIVE: To evaluate the Virologic and Immunologic efficacy of HAART on Chinese HIV/AIDS patients and to assess the impact of of HAART on drug resistance mutations. METHODS: Three cohorts of Liaoning, Jilin and Henan province received three different regimens for 6 months respectively. Regimen of Liaoning cohort comprised Efavirenz + Indinavir (EFV + IDV), regimen of Jilin cohort comprised Stavudine + Didanosine + Efavirenz (d4T + ddI + EFV) and regimen of Henan cohort comprised Stavudine + Didanosine + Nevirapine (d4T + ddI + NVP). Viral load, CD4(+) T cell count and drug resistance genotype were detected on the three cohorts before and after treatment. Partial HIV-1 pol genes encoding protease and 1 - 220 amino acid of reverse transcriptase were amplified by RT-PCR and then automatically sequenced. All sequences were compared with the data of Stanford HIV Drug Resistance Database to assess resistance mutations against reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs). RESULTS: During observation of 6 months, viral suppression to undetectable level and Elevated CD4(+)T cell count efficacy were achieved on partial Chinese HIV/AIDS patients in each of the three different regimens, even in some patients with rather low CD4(+)T cell count baseline. Before HAART, no primary mutations against PIs and RTIs were detected on the three cohorts, except one patient in Liaoning cohort. But after HAART, drug resistance mutations against RTIs occurred on each of the three cohorts. K103N is the most common mutation against NNRTIs, which can cause high-level resistance to each of the available NNRTIs. Y181C is another common mutation occurred in Henan cohort, which causes crossing drug resistance and multi-drug resistance to NNRTIs. In addition, intermediate level and low level resistance against NRTIs caused by K65R and L74V can also be found, but less commonly. CONCLUSION: Treatment naive Chinese HIV/AIDS patients were sensitive to HAART. Expected virologic and immunologic efficacy of HAART were achieved on Chinese HIV/AIDS patients, but after the introduce of HAART, the high prevalence of drug resistance mutations against NNRTIs and NRTIs, crossing drug resistance and multi-drug resistance reminded us to pay more attention to the drug resistance mutations detection, treatment standardization, and to avoid drugs wasting and prevent the prevalence of drug resistance strains.


Subject(s)
Anti-HIV Agents/therapeutic use , Drug Resistance, Viral/genetics , HIV Infections/drug therapy , HIV-1 , Mutation , Adult , Alkynes , Antiretroviral Therapy, Highly Active , Benzoxazines , CD4 Lymphocyte Count , Cyclopropanes , Didanosine/therapeutic use , Female , Humans , Male , Middle Aged , Nevirapine/therapeutic use , Oxazines/therapeutic use , Stavudine/therapeutic use , Viral Load
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