Artificial Intelligence-Assisted Prescription Determination for Orthokeratology Lens Fitting: From Algorithm to Clinical Practice.

OBJECTIVES: To explore the potential of artificial intelligence (AI) to assist prescription determination for orthokeratology (OK) lenses. METHODS: Artificial intelligence algorithm development followed by a real-world trial. A total of 11,502 OK lenses fitting records collected from seven clinical environments covering major brands. Records were randomly divided in a three-way data split. Cross-validation was used to identify the most accurate algorithm, followed by an evaluation using an independent test data set. An online AI-assisted system was implemented and assessed in a real-world trial involving four junior and three senior clinicians. RESULTS: The primary outcome measure was the algorithm's accuracy (ACC). The ACC of the best performance of algorithms to predict the targeted reduction amplitude, lens diameter, and alignment curve of the prescription was 0.80, 0.82, and 0.83, respectively. With the assistance of the AI system, the number of trials required to determine the final prescription significantly decreased for six of the seven participating clinicians (all P <0.01). This reduction was more significant among junior clinicians compared with consultants (0.76±0.60 vs. 0.32±0.60, P <0.001). Junior clinicians achieved clinical outcomes comparable to their seniors, as 93.96% (140/149) and 94.44% (119/126), respectively, of the eyes fitted achieved unaided visual acuity no worse than 0.8 ( P =0.864). CONCLUSIONS: AI can improve prescription efficiency and reduce discrepancies in clinical outcomes among clinicians with differing levels of experience. Embedment of AI in practice should ultimately help lessen the medical burden and improve service quality for myopia boom emerging worldwide.

Influence of pulling direction on knot security: A laboratory research.

BACKGROUND: When tying knots, some surgeons do not pay particular attention to the direction in which they pull to lay down throws. We examine to what extent does pulling direction influence on knot security. METHODS: A total of 368 residents were instructed to tie knots with from 2 to 7 throws using silk braided suture in 3-0 gauge. The direction in which they pulled to lay down throws was recorded. Only the knots tied either by pulling in alternate directions (Group A) or in constant direction (Group C) from the first throw to the last were involved in statistical analysis. Tensile strength and untying rate of the knots were then measured for comparative analysis. RESULTS: For knots with from 2 to 7 throws, the tensile strength of the ones from Group A was significantly higher than that of the ones from Group C (p < 0.05), respectively. For knots with from 5 to 7 throws, the untying rate of the ones from Group A was significantly lower than that of the ones from Group C (p < 0.05), respectively. For the unraveled knots with from 2 to 7 throws (except for the ones with 5 throws), the tensile strength of the ones from Group A was significantly higher than that of the ones from Group C (p < 0.05), respectively. CONCLUSION: Pulling in constant direction results in inferior knot security. Surgeons must ascertain the influence of pulling direction on knot security, and try to achieve superior security with fewer throws to ensure patient safety.

Case report: One case of umbilical vein thrombosis in the second trimester with associated portal vein thrombosis after childbirth.

Background: Umbilical vein thrombosis is a rare pregnancy complication, that is difficult to detect prenatally but can lead to poor fetal outcomes. Case presentation: We described a 33-year-old primiparae who was identified as having umbilical vein thrombosis by ultrasound at 21 weeks gestation, and the neonate was found to have a portal vein thrombus after delivery. Following enoxaparin anticoagulant therapy, the thrombus disappeared within 4 weeks. No thrombus formation occured during the 10-month follow-up, and the baby was in excellent clinical condition. Conclusion: Owing to the poor fetal outcomes related to umbilical thrombosis, pay attention to abnormal clinical signs during prenatal ultrasound, fetal heart monitoring and counting fetal movements can help in the early identification of umbilical cord thrombosis.The findings highlight the importance of regular prenatal ultrasound evaluation, enabling early detection and monitoring of any anomalies or vascular abnormalities related to the fetal umbilical vein. Further research is warranted to explore the clinical implications and long-term outcomes associated with these findings.

Characterization of a Novel Polysaccharide Derived from Rhizospheric Paecilomyces vaniformisi and Its Mechanism for Enhancing Salinity Resistance in Rice Seedlings.

Soil salinity is an important limiting factor in agricultural production. Rhizospheric fungi can potentially enhance crop salinity tolerance, but the precise role of signaling substances is still to be systematically elucidated. A rhizospheric fungus identified as Paecilomyces vaniformisi was found to enhance the salinity tolerance of rice seedlings. In this study, a novel polysaccharide (PPL2b) was isolated from P. vaniformisi and identified as consisting of Manp, Glcp, GalpA, and Galp. In a further study, PPL2b showed significant activity in alleviating salinity stress-induced growth inhibition in rice seedlings. The results indicated that under salinity stress, PPL2b enhances seed germination, plant growth (height and biomass), and biochemical parameters (soluble sugar and protein contents). Additionally, PPL2b regulates genes such as SOS1 and SKOR to decrease K+ efflux and increase Na+ efflux. PPL2b increased the expression and activity of genes related to antioxidant enzymes and nonenzyme substances in salinity-induced oxidative stress. Further study indicated that PPL2b plays a crucial role in regulating osmotic substances, such as proline and betaine, in maintaining the osmotic balance. It also modulates plant hormones to promote rice seedling growth and enhance their tolerance to soil salinity. The variables interacted and were divided into two groups (PC1 77.39% and PC2 18.77%) based on their relative values. Therefore, these findings indicate that PPL2b from P. vaniformisi can alleviate the inhibitory effects of salinity stress on root development, osmotic adjustment, ion balance, oxidative stress balance, and growth of rice seedlings. Furthermore, it suggests that polysaccharides produced by rhizospheric fungi could be utilized to enhance crop tolerance to salinity.

Evaluation of negative effect of Naphthenic acids (NAs) on physiological metabolism and polycyclic aromatic hydrocarbons adsorption of Phragmites australis.

Toxic substances in the environment disturb the adsorption of pollutants in plants but little is known about the underlying mechanisms of these processes. This study evaluated the PAH adsorption by Phragmites australis under NAs stress. Results showed that Naphthenic acids (NAs) significantly decreased the adsorption of PAHs and had higher selectivity for type and structure. P. australis root cell growth and mitosis were significantly affected by NAs, which was accompanied by serious disturbances in mitochondrial function. The physiological evaluation showed the NAs could increase Reactive Oxygen Species (ROS) accumulation by around 16-fold and cause damage to the root cell normal redox equilibrium. The levels of three key related antioxidants, PLA, CAT and POD, decreased significantly to 35-50% under NAs stress and were dependent upon NAs concentration. Furthermore, NAs could significantly change the concentration and species of root exudates of P. ausralis. Autotoxic substances, including alcohol and amines, increased by 28.63% and 23.96, respectively. Sixteen compounds were identified and assumed as potential biomarkers. Galactonic, glyceric, and octadecanoic acid had the general effect of activating PAH in soil. The global view of the metabolic pathway suggests that NAs influenced the citric acid cycle, fatty acid synthesis, amino acid metabolism and the phenylpropanoid pathway. Detection data results indicated that the energy products cause hypoxia and oxidative stress, which are the main processes under the NAs. Furthermore, verification of these processes was fulfilled through gene expression and biomarkers quantification. Our results provide novel metabolic insights into the mechanisms of PAHs adsorption by P. australis under NAs disturbance, suggesting that monitoring NAs in phytoremediation applications is necessary.

Evaluation of Physiological Coping Strategies and Quality Substances in Purple SweetPotato under Different Salinity Levels.

Although salinity stress is one of the principal abiotic stresses affecting crop yield, a suitable concentration of NaCl has proven to be useful for increasing crop quality. This study used low salinity (34 mmol/L NaCl) and high salinity (85 mmol/L) to cultivate purple sweetpotato. Using transcriptomics and metabolomics to profile the pathway indicated that glycometabolism, secondary metabolite biosynthesis and the starch catabolic process were the significant pathways under the salinity stress. Further research showed that purple sweetpotato could regulate genes related to the regulation of the cellular Na+, K+, and other ions concentration in response to the low salinity tolerance, but loses this ability under high salinity. Meanwhile, under low salinity, the activity of antioxidant enzymes and their related gene expression are maintained at a high level. The low salinity influences the monosaccharide composition as well as the content and regulation of genes related to starch synthesis. Quality analysis showed that the low salinity could increase the starch content and influence the amylopectin biosynthesis. It suggested that low salinity promotes substance accumulation. High salinity could increase the anthocyanins biosynthesis and low salinity had a significant impact on phenolic acid and flavonol. Finally, the gene expression levels also prove the low salinity could change the composition and content level of the purple sweetpotato. This study showed that an appropriate concentration of NaCl can be used as an elicitor for application in purple sweetpotato planting.

Efficacy of the herbal pair, Radix Achyranthis Bidentatae and Eucommiae Cortex, in preventing glucocorticoid-induced osteoporosis in the zebrafish model.

OBJECTIVE: In traditional Chinese medicine, the herbal pair, Radix Achyranthis Bidentatae (RAB) and Eucommiae Cortex (EC), is widely used to treat osteoporosis. Herein, we determined whether this herbal pair can be used to ameliorate glucocorticoid (GC)-induced osteoporosis (GIOP) and find its optimal dosage in zebrafish. METHODS: The characteristics of the aqueous extract of RAB and EC were separately characterized using high-performance liquid chromatography. Osteoporosis was induced in 5-day post-fertilization zebrafish larvae by exposing them to 10 µmol/L dexamethasone (Dex) for 96 h. Seven combinations of different ratios of RAB and EC were co-administered. Treatment efficacy was determined by calculating zebrafish vertebral area and sum brightness, via alizarin red staining, and by detecting alkaline phosphatase (ALP) activity. Multiple regression analysis was conducted to test the optimal dosage ratio. RESULTS: According to the Chinese Pharmacopoeia (2015), ß-ecdysone (ß-Ecd) is a major bioactive marker in RAB extract, while pinoresinol diglucoside (PDG) is the major marker in EC extract. Both of ß-Ecd and PDG content values aligned with the Chinese Pharmacopoeia standards. Treatment with 10 µmol/L Dex reduced zebrafish vertebral area, sum brightness, and ALP activity, but RAB and EC attenuated these effects. Combining 50 µg/mL RAB and 50 µg/mL EC was optimal for preventing GIOP in zebrafish. Reverse transcription-quantitative polymerase chain reaction was used to evaluate the mRNA expression of osteogenesis-related genes. A treatment of 10 µmol/L Dex decreased runt-related transcription factor 2 (Runx2), osteogenic protein-1 (OP-1), bone γ-carboxyglutamic acid-containing protein (BGLAP), and ß-catenin levels. This effect was counteracted by RAB and EC co-treatment (P < 0.05). Additionally, the effect of using the two herbal extracts together was better than single-herb treatments separately. These results demonstrated that RAB and EC preserve osteoblast function in the presence of GC. The best mass ratio was 1:1. CONCLUSION: RAB and EC herbal pair could ameliorate GC-induced effects in zebrafish, with 1:1 as the optimal dosage ratio.

Experimental composable security decoy-state quantum key distribution using time-phase encoding.

Quantum key distribution (QKD) promises provably secure communications. In order to improve the secret key rate, combining a biased basis choice with the decoy-state method is proposed. Concomitantly, there is a basis-independent detection efficiency condition, which usually cannot be satisfied in a practical system, such as the time-phase encoding. Fortunately, this flaw has been recently removed theoretically and experimentally in the four-intensity decoy-state BB84 QKD protocol using the fact that the expected yields of single-photon states prepared in two bases stay the same for a given measurement basis. However, the security proofs do not fully consider the finite-key effects for general attacks. In this work, we provide the rigorous finite-key security bounds in the universally composable framework for the four-intensity decoy-state BB84 QKD protocol. We build a time-phase encoding system with 200 MHz clock to implement this protocol, in which the real-time secret key rate is more than 60 kbps over 50 km single-mode fiber.

Beta-Ecdysone Protects Mouse Osteoblasts from Glucocorticoid-Induced Apoptosis In Vitro.

Glucocorticoid-induced osteoporosis is a common form of secondary osteoporosis. Glucocorticoids affect both bone formation and resorption, and prolonged glucocorticoid exposure can suppress osteoblast activities. beta-Ecdysone, found in many plants, is involved in protein synthesis, carbohydrate and lipid metabolism, and immunologic modulation. Here, we evaluated the effects of beta-ecdysone on osteoblast viability by assessing apoptosis following treatment with excess glucocorticoids. Mouse bone marrow stromal cells were induced to differentiate and grow into osteoblasts, and then treated with 10 µM glucocorticoid and 10, 1, or 0.1 µM beta-ecdysone. The expression levels of osteoblast growth and differentiation factors (runt-related transcription factor 2, osteogenic protein-1, and alkaline phosphatase), apoptosis-related genes (transformation-related protein 53, ataxia telangiectasia mutated protein, caspase-3, and caspase-8), and Akt1 and phospho-Akt (Thr308) were then assessed via alkaline phosphatase staining, acridine orange-propidium iodide staining, annexin V/PI apoptosis assay, real-time RT-PCR, and Western blot analyses. Notably, treatment with 10 µM glucocorticoid resulted in reduced osteoblast viability and the specific activity of alkaline phosphatase as well as reduced runt-related transcription factor 2, osteogenic protein-1, and alkaline phosphatase mRNA expression in vitro, indicating that glucocorticoid inhibited osteogenic differentiation. Moreover, glucocorticoid treatment yielded increased transformation-related protein 53, ataxia telangiectasia mutated protein, caspase-3, and caspase-8 expression and decreased Akt1 and phospho-Akt levels, indicating glucocorticoid-induced apoptosis. Meanwhile, beta-ecdysone inhibited glucocorticoid function, preserving the expression of Akt1 and phospho-Akt and reducing the expression of transformation-related protein 53, ataxia telangiectasia mutated protein, caspase-3, and caspase-8. Thus, beta-ecdysone prevented glucocorticoid-induced osteoblast apoptosis in vitro. These data highlight the potential for beta-ecdysone as a treatment for preventing the effects of glucocorticoid on bone growth.

A simply prepared small-diameter artificial blood vessel that promotes in situ endothelialization.

Synthetic grafts are of limited use in small-diameter vessels (Φ<6mm) due to the poor patency rate. The inability of such grafts to achieve early endothelialization together with the compliance mismatch between the grafts and the native vessels promote thrombosis, which eventually leads to graft occlusion. In the current study, stromal cell-derived factor (SDF)-1α/vascular endothelial growth factor (VEGF)-loaded polyurethane (PU) conduits were simply prepared via electrospinning. The mechanical property, drug release behavior and cytocompatibility of the conduits were investigated. The effects of the conduits on endothelial progenitor cell (EPC) mobilization and differentiation were examined in vitro. Then, the conduits were implanted as canine femoral artery interposition grafts. The results revealed that SDF-1α and VEGF were quickly released shortly after implantation, and the conduits exhibited slow and sustained release thereafter. The cytokines had definite effects on EPC mobilization and differentiation in vitro and promoted conduit endothelialization in vivo. The conduits had good tissue compatibility and favorable compliance. All of these features inhibited the conduits from being occluded, thereby improving their long-term patency rate. At 6th month postoperatively, 5 of the 8 grafts were patent while all the 8 grafts without the cytokines were occluded. These findings provide a simple and effective method for the construction of small-diameter artificial blood vessels with the aim of facilitating early endothelialization and improving long-term patency. STATEMENT OF SIGNIFICANCE: (1) SDF-1α/VEGF loaded PU conduits were simply prepared by electrospinning. The cytokines with definite and potent effects on angiogenesis were used to avoid complicated mechanism researches. Compared with most of the current vascular grafts which are of poor strength or elasticity, the conduits have favorable mechanical property. All of these inhibit the conduits from occlusion, and thus improve their long-term patency rate. (2) For the in vivo tests, the dogs did not receive any anticoagulant medication in the follow-up period to expose the grafts to the strictest conditions. In vivo endothelialization of the conduits was thoroughly investigated by Sonography, HE staining, SEM and LSCM. The study will be helpful for the construction of small-diameter artificial blood vessels.

[Responses of the natural abundance of carbon and nitrogen isotopes of Quercus mongolica leaf and soil to elevated CO2]. / è’™å¤æ Žå¶ç‰‡åŠå ¶åœŸå£¤ç¢³ã€æ°®åŒä½ç´ è‡ªç„¶ä¸°åº¦å¯¹å¤§æ°”CO2浓度升高的响应.

The rising atmospheric CO2 concentration significantly changed soil nitrogen (N) cycling which is important for us to predict the carbon (C) sequestration potential of terrestrial ecosystems. The natural abundance of N isotope as an integrative indicator of ecosystem N cycling processes can effectively indicate the effect of elevated CO2 on soil N cycling processes. Here, we used an open top chamber experiment to examine the effects of elevated CO2for ten years on the natural abundance of Quercus mongolica, soil and microbial biomass C and N isotopes in northeastern China. Our results showed that elevated CO2 significantly changed soil N cycling processes, resulting in the increase of microbial and leaf δ15N; stimulated the decomposition of 13C-enriched soil organic C, and offset the effect of more 13C-depleted plant photosynthetic C inputs, resulting in unchanged δ13C of soil dissolved organic C and microbes under elevated CO2. These results indicated that elevated CO2 likely increased the mineralization of soil organic matter, and the system is getting more N-limited.

Improving endothelialization by the combined application of polyethylene glycol coated cerium oxide nanoparticles and VEGF in electrospun polyurethane scaffolds.

Synthetic small-diameter vascular grafts are of limited use mainly due to the lack of endothelial cells (ECs), which inhibit intraluminal thrombosis and intimal hyperplasia. Grafts loaded with homing factors for circulating endothelial progenitor cells (EPCs) have the potential to achieve in situ endothelialization. In view of the important role that EPCs play in the construction of small-diameter artificial blood vessels, antioxidant therapy aiming to inhibit oxidative stress-induced EPC apoptosis should be the focus of clinical interest. In this study, polyethylene glycol coated cerium oxide nanoparticles (CNPs-PEG) with antioxidant properties were successfully synthesized and characterized. The effects of CNPs-PEG on EPC viability and EPC apoptosis induced by oxidative stress were examined. Then, CNPs-PEG together with a potent angiogenesis cytokine vascular endothelial growth factor (VEGF) were encapsulated into polyurethane (PU) scaffolds via electrospinning. The morphology, mechanical properties and CNPs-PEG/VEGF release profiles of the scaffolds were investigated. The growth of EPCs on the scaffolds, and the effects of the released CNPs-PEG and VEGF on anti-EPC apoptosis and endothelialization in vitro were studied. The results showed that CNPs-PEG had favorable stability and cytocompatibility. They could effectively inhibit H2O2-induced EPC apoptosis. The scaffolds showed sustained release behavior of CNPs-PEG/VEGF and favorable cytocompatibility. The released CNPs-PEG retained the anti-apoptosis properties and, moreover, enhanced the effects of VEGF on the mobilization and differentiation of EPCs. It is concluded that the combined application of CNPs-PEG and VEGF in electrospun PU scaffolds facilitated endothelialization in vitro, and thus should be promising for the construction of small-diameter artificial blood vessels.

Prediction of antiviral efficacy in patients with chronic hepatitis C by changes in forkhead box protein 3 levels.

The aim of the present study was to investigate the distribution of CD4+CD25+ regulatory T cells (Tregs) in the peripheral blood of patients with chronic hepatitis C; in addition to identifying whether the distribution of CD4+CD25+ Tregs predicts the efficacy of antiviral therapy for HCV. The expression of CD4+CD25+ forkhead box protein (FOXP) 3+ Tregs within a CD4+ T cell population was detected in the peripheral blood obtained from patients with chronic hepatitis C and from healthy control subjects using flow cytometry. The hepatitis C virus (HCV)-RNA load was measured using quantitative-fluorescence polymerase chain reaction. CD4+CD25+FOXP3+ Tregs accounted for 14.24±1.33% of the CD4+ T cells in the peripheral blood of patients with chronic hepatitis C, which was higher than that of the healthy control subjects (5.62±1.21%; P<0.001). Furthermore, the frequency of CD4+CD25+FOXP3+ Tregs in CD4+ T cells of the peripheral blood positively correlated with the HCV-RNA load (r=0.73; P=0.032). Therefore, the results of the present study indicated that the expression of CD4+CD25+FOXP3+ Tregs increased in patients that were chronically infected with HCV and positively correlated with the HCV-RNA load.

[The crosstalking between aging and autophagy].

Aging is the syndrome caused by the functional decline and physiological disorder during the organism deterioration. Autophagy is the way that cells use to deliver cytoplasmic protein and organelle to lysosomes for degradation. Constitutive autophagy has a housekeeping role and is essential for survival, development and metabolic regulation. Recent studies from model organisms demonstrate that there is close relationship between aging and autophagy. Normal aging and phathological aging are often associated with a reduced autophagic potential. This paper reviewed the cross-talk between aging and autophagy, and possible molecular mechanisms as well.

[Design and experiment of micro biochemical detector based on micro spectrometer].

According to the requirements of rapid detection of important life parameters for the sick and wounded, a new micro bio-chemical detection configuration was proposed utilizing continuous spectroscopy analysis, which was founded on MOEMS and embedded technology. The configuration was developed as so much research work was carried out on the detecting objects and methods. Important parameters such as stray light, absorbance linearity, absorbance ratability, stability and temperature accuracy of the instrument were tested, which are all in good agreement with the design requirements. Clinic tests show that it can detect multiple life parameters quickly (Na+, GLU, Hb eg.).

[Effect of acupuncture on contents of beta-endorphin in the plasma and hypothalamus in rats with stress-induced gastric mucosal injury].

OBJECTIVE: To explore the mechanism of acupuncture in preventing and treating stress-induced gastric mucosal injury from the view of brain-gut axis. METHODS: Forty male Wister rats were randomly divided into normal control, model 1, treatment, model 2 and prevention groups (n=8). Gastric mucosa injury model was established by intragastric perfusion of dehydrated alcohol (1.0 mL/rat). Rats of the treatment group were treated with acupuncture after modeling, while those of the prevention group treated first, followed by modeling. The time of modeling in model 1 group and model 2 group was simultaneous with that of the treatment group and prevention group respectively. Acupuncture was applied to "Zusanli"(ST 36), "Zhongwan" (CV 12) and "Neiguan" (PC 6) for 20 min, once daily for 5 days. Before sampling the tissues, 10% charcoal suspension was intragastric perfused 1 h for analyzing the rate of gastrointestinal propulsion(distance from the upper end of the charcoal powder to the cardia/total length of the cardia to the anus x 100%). Gastric mucosal ulcer index was measured by using Guth's method. The contents of beta-endorphin(beta-EP)in plasma and hypothalamus were determined by enzyme-linked immunosorbent assay. RESULTS: Compared with the normal control group, the gastrointestinal propulsion rates were decreased considerably in the two model groups (P < 0.05), while the gastric mucosal ulcer indexes and the contents of beta-EP in both plasma and hypothalamus were increased significantly in the model groups (P < 0.05, P < 0.01). Compared with the corresponding model groups, the gastrointestinal propulsion rate was increased remarkably in the prevention group (P < 0.05), and the gastric mucosal ulcer indexes and the contents of plasma beta-EP level were decreased obviously in both treatment and prevention groups (P < 0.05, P < 0.01). The contents of hypothalamic beta-EP were increased further in the later two groups (P < 0.01). CONCLUSION: Acupuncture of ST 36, CV 12 and PC 6 can promote the repair of gastric mucosal injury and improve gastrointestinal function, which may be related to its effects in reducing plasma beta-EP and upregulating hypothalamic beta-EP level. Acupuncture also has a better effect in preventing gastric mucosal injury.

Dysregulated chemokine receptor expression and chemokine-mediated cell trafficking in pediatric patients with ESRD.

BACKGROUND AND OBJECTIVES: Children and adolescents with ESRD on dialysis are susceptible to serious bacterial infections (SBI). Chemokines and chemokine receptors play a critical role in modulating macrophage and neutrophil function. This study examined the hypothesis that expression and/or function of these molecules is dysregulated in patients with ESRD, contributing to leukocyte dysfunction. Design setting, participants, & measurements: Pediatric patients, age 6 mo to 18 yr, with ESRD treated with either hemodialysis or peritoneal dialysis were enrolled in this prospective, nontherapeutic study. Blood was collected for plasma chemokine levels, chemokine receptor profiling by flow cytometry, and functional chemotaxis studies on neutrophils and mononuclear cells. RESULTS: ESRD in children was associated with reduced expression of the chemokine receptors CXCR1 and chemokine (C-C motif) receptor 2 (CCR2) on circulating neutrophils and monocytes, respectively. When ESRD patients were divided into two subgroups, those who were infection-free and those who had three or more SBI in the preceding year, the differences in chemokine receptor expression were statistically significant compared with control subjects only in those with recurrent infection. In addition to the effects of ESRD on baseline chemokine receptor expression, the hemodialysis procedure itself acutely lowered neutrophil CXCR1 and monocyte CCR2 expression. Furthermore, neutrophil and monocyte responsiveness to chemokine-mediated trafficking signals was impaired in all ESRD patients studied. This abnormality was independent of the level of chemokine receptor expression on the leukocytes. CONCLUSIONS: The data presented in this study suggest that chemokine receptor dysregulation contributes to leukocyte dysfunction in patients with ESRD. This alteration is especially prominent in ESRD patients with recurrent infection.

Redox regulation of cyclophilin A by glutathionylation.

Using redox proteomics techniques to characterize the thiol status of proteins in human T lymphocytes, we identified cyclophilin A (CypA) as a specifically oxidized protein early after mitogen activation. CypA is an abundantly expressed cytosolic protein, target of the immunosuppressive drug cyclosporin A (CsA), for which a variety of functions has been described. In this study, we could identify CypA as a protein undergoing glutathionylation in vivo. Using MALDI-MS we identified Cys52 and Cys62 as targets of glutathionylation in T lymphocytes, and, using bioinformatic tools, we defined the reasons for the susceptibility of these residues to the modification. In addition, we found by circular dichroism spectroscopy that glutathionylation has an important impact on the secondary structure of CypA. Finally, we suggest that glutathionylation of CypA may have biological implications and that CypA may play a key role in redox regulation of immunity.