Metagenomic analysis of the gut virome in patients with irritable bowel syndrome.

Irritable bowel syndrome (IBS), a chronic functional gastrointestinal disorder, is recognized for its association with alterations in the gut microbiome and metabolome. This study delves into the largely unexplored domain of the gut virome in IBS patients. We conducted a comprehensive analysis of the fecal metagenomic data set from 277 IBS patients and 84 healthy controls to characterize the gut viral community. Our findings revealed a distinct gut virome in IBS patients compared to healthy individuals, marked by significant variances in between-sample diversity and altered abundances of 127 viral operational taxonomic units (vOTUs). Specifically, 111 vOTUs, predominantly belonging to crAss-like, Siphoviridae, Myoviridae, and Quimbyviridae families, were more abundant in IBS patients, whereas the healthy control group exhibited enrichment of 16 vOTUs from multiple families. We also investigated the interplay between the gut virome and bacteriome, identifying a correlation between IBS-enriched bacteria like Klebsiella pneumoniae, Fusobacterium varium, and Ruminococcus gnavus, and the IBS-associated vOTUs. Furthermore, we assessed the potential of gut viral signatures in predicting IBS, achieving a notable area under the receiver operator characteristic curve (AUC) of 0.834. These findings highlight significant shifts in the viral diversity, taxonomic distribution, and functional composition of the gut virome in IBS patients, suggesting the potential role of the gut virome in IBS pathogenesis and opening new avenues for diagnostic and therapeutic strategies targeting the gut virome in IBS management.

Metagenomic analysis reveals altered gut virome and diagnostic potential in pancreatic cancer.

Pancreatic cancer (PC) is a highly aggressive malignancy with a poor prognosis, making early diagnosis crucial for improving patient outcomes. While the gut microbiome, including bacteria and viruses, is believed to be essential in cancer pathogenicity, the potential contribution of the gut virome to PC remains largely unexplored. In this study, we conducted a comparative analysis of the gut viral compositional and functional profiles between PC patients and healthy controls, based on fecal metagenomes from two publicly available data sets comprising a total of 101 patients and 82 healthy controls. Our results revealed a decreasing trend in the gut virome diversity of PC patients with disease severity. We identified significant alterations in the overall viral structure of PC patients, with a meta-analysis revealing 219 viral operational taxonomic units (vOTUs) showing significant differences in relative abundance between patients and healthy controls. Among these, 65 vOTUs were enriched in PC patients, and 154 were reduced. Host prediction revealed that PC-enriched vOTUs preferentially infected bacterial members of Veillonellaceae, Enterobacteriaceae, Fusobacteriaceae, and Streptococcaceae, while PC-reduced vOTUs were more likely to infect Ruminococcaceae, Lachnospiraceae, Clostridiaceae, Oscillospiraceae, and Peptostreptococcaceae. Furthermore, we constructed random forest models based on the PC-associated vOTUs, achieving an optimal average area under the curve (AUC) of up to 0.879 for distinguishing patients from controls. Through additional 10 public cohorts, we demonstrated the reproducibility and high specificity of these viral signatures. Our study suggests that the gut virome may play a role in PC development and could serve as a promising target for PC diagnosis and therapeutic intervention. Future studies should further explore the underlying mechanisms of gut virus-bacteria interactions and validate the diagnostic models in larger and more diverse populations.

The Active Fraction of Polyrhachis vicina Roger (AFPR) activates ERK to cause necroptosis in colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Polyrhachis vicina Roger (P. vicina), a traditional Chinese medicinal animal, has been used to treat rheumatoid arthritis, hepatitis, cancer, and other conditions. Due to its anti-inflammatory properties, our previous pharmacological investigations have demonstrated that it is effective against cancer, depression, and hyperuricemia. Nevertheless, the key active components and targets of P. vicina in cancers are still unexplored. AIM OF THE STUDY: The study aimed to evaluate the pharmacological treatment mechanism of the active fraction of P. vicina (AFPR) in treating colorectal cancer (CRC) and to further reveal its active ingredients and key targets. METHODS: To examine the inhibitory impact of AFPR on CRC growth, tumorigenesis assays, cck-8 assays, colony formation assays, and MMP detection were utilized. The primary components of AFPR were identified by GC-MS analysis. The network pharmacology, molecular docking, qRT-PCR, western blotting, CCK-8 assays, colony formation assay, Hoechst staining, Annexin V-FITC/PI double staining, and MMP detection were performed to pick out the active ingredients and potential key targets of AFPR. The function of Elaidic acid on necroptosis was investigated through siRNA interference and the utilization of inhibitors. Elaidic acid's effectiveness to suppress CRC growth in vivo was assessed using a tumorigenesis experiment. RESULTS: Studies confirmed that AFPR prevented CRC from growing and evoked cell death. Elaidic acid was the main bioactive ingredient in AFPR that targeted ERK. Elaidic acid greatly affected the ability of SW116 cells to form colonies, produce MMP, and undergo necroptosis. Additionally, Elaidic acid promoted necroptosis predominantly by activating ERK/RIPK1/RIPK3/MLKL. CONCLUSION: According to our findings, Elaidic acid is the main active component of AFPR, which induced necroptosis in CRC through the activation of ERK. It represents a promising alternative therapeutic option for CRC. This work provided experimental support for the therapeutic application of P. vicina Roger in the treatment of CRC.

[Characteristics, Ozone Formation Potential, and Source Apportionment of VOCs During the COVID-19 Epidemic in Xiong'an].

Many restrictive measures were implemented in China from January-February 2020 to control the rapid spread of COVID-19. Many studies reported that the COVID-19 lockdown impacted PM2.5, SO2, volatile organic compounds (VOCs), etc. VOCs play important roles in the production of ozone and PM2.5. Ambient VOCs in Xiong'an were measured from December 25, 2019 to January 24, 2020 (prior to epidemic prevention, P1) and from January 25, 2020 to February 24, 2020 (during epidemic prevention, P2) through a VOCs online instrument. In the study, VOCs characteristics and ozone generation potential (OFP) of ambient VOCs were analyzed, and source apportionment of VOCs were analyzed by using Positive Matrix Factorization (PMF). The results showed that φ(TVOCs) during epidemic prevention and control was 45.1×10-9, which was approximately half of that before epidemic prevention and control (90.5×10-9). The chemical composition of VOCs showed significant changes after epidemic prevention and control, the contribution rate of alkanes increased from 37.6% to 53.8%, and the contribution rate of aromatic hydrocarbons and halogenated hydrocarbons decreased from 13.3% and 12.0% to 7.5% and 7.8%, respectively. Aromatic hydrocarbons, halogenated hydrocarbons, and OVOCs decreased by more than 60%. Seven types of the top ten species were the same before and during the epidemic prevention and control, mainly low-carbon alkanes, olefins, aldehydes, and ketones. Dichloromethane, trichloromethane, and BTEXs decreased significantly. The OPP was 566 µg·m-3 and 231 µg·m-3 in P1 and P2, respectively. The OPP of VOCs decreased by more than 30%. The proportion of OFP contribution of aromatic hydrocarbons decreased significantly after the epidemic prevention and control, and the proportion of OFP contribution of alkanes and alkynes increased significantly. Positive matrix factorization (PMF) was then applied for VOCs sources apportionment. Six sources were identified, including background sources, oil-gas volatile sources, combustion sources, industrial sources, solvent use sources, and vehicle exhaust sources. The results showed that after the epidemic prevention and control, the contribution rate of solvent use sources to TVOCs decreased from 24% to 9%. The contribution rates of background sources, oil-gas volatile sources, and combustion sources increased from 13%, 34%, and 24% to 6%, 14%, and 13%, respectively. The relative contributions of vehicle exhaust sources before and after epidemic prevention and control were 21% and 18%, respectively. The observation points were affected by the emission of VOCs from paroxysmal industrial sources before the epidemic prevention and control. The emission was stopped after the epidemic prevention and control, and its contribution rate was reduced from 22% before the epidemic prevention and control to 1%. The concentrations of industrial sources, solvent sources, motor vehicle tail gas sources, and combustion sources decreased by 97%, 82%, 61%, and 15%, respectively, after the epidemic prevention and control. The concentration of background sources remained stable, and the concentration of oil and gas volatile sources increased by 7%. The control of production and traffic activities cannot reduce the emission of VOCs from oil and gas volatile sources, which is the focus of VOCs control in Xiong'an.

Relative Density-Based Intuitionistic Fuzzy SVM for Class Imbalance Learning.

The support vector machine (SVM) has been combined with the intuitionistic fuzzy set to suppress the negative impact of noises and outliers in classification. However, it has some inherent defects, resulting in the inaccurate prior distribution estimation for datasets, especially the imbalanced datasets with non-normally distributed data, further reducing the performance of the classification model for imbalance learning. To solve these problems, we propose a novel relative density-based intuitionistic fuzzy support vector machine (RIFSVM) algorithm for imbalanced learning in the presence of noise and outliers. In our proposed algorithm, the relative density, which is estimated by adopting the k-nearest-neighbor distances, is used to calculate the intuitionistic fuzzy numbers. The fuzzy values of the majority class instances are designed by multiplying the score function of the intuitionistic fuzzy number by the imbalance ratio, and the fuzzy values of minority class instances are assigned the intuitionistic fuzzy membership degree. With the help of the strong capture ability of the relative density to prior information and the strong recognition ability of the intuitionistic fuzzy score function to noises and outliers, the proposed RIFSVM not only reduces the influence of class imbalance but also suppresses the impact of noises and outliers, and further improves the classification performance. Experiments on the synthetic and public imbalanced datasets show that our approach has better performance in terms of G-Means, F-Measures, and AUC than the other class imbalance classification algorithms.

Mechanisms of Defect Correction by Reversible Chemistries in Covalent Organic Frameworks.

Reversible chemistries have been extensively explored to construct highly crystalline covalent organic frameworks (COFs) via defect correction. However, the mechanisms of defect correction that can explain the formation of products as single crystals, polycrystal/crystallites, or amorphous solids remain unknown. Herein, we employed molecular dynamics simulations combined with a polymerization model to investigate the growth kinetics of two-dimensional COFs. By virtue of the Arrhenius two-state model describing reversible reactions, we figured out the conditions in terms of active energy and binding energy for different products. Specifically, the ultraslow growth of COFs under high reversibility of reactions corresponding to low binding energies resulted in a single crystal by inhibiting the emergence of nuclei as well as correcting defects through continually dropping small defective fragments off at crystal boundaries. High bonding energies responsible for the high nucleation rate and rapid growth that incorporated defects in crystals and caused the division of crystals through defect correcting processes led to small crystallites or polycrystals. The insights into the mechanisms help us to understand and further control the growth kinetics by exploiting reversible conditions to synthesize COFs of higher quality.

A controlling parameter of topological defects in two-dimensional covalent organic frameworks.

Synthesis of covalent organic frameworks with long-range molecular ordering is an outstanding challenge due to the fact that defects against predesigned topological symmetries are prone to form and break crystallization. The physical origins and controlling parameters of topological defects remain scarcely understood. By virtue of molecular dynamics simulations, we found that pentagons for combination [C4 + C4] and [C4 + C2] and heptagons for [C3 + C3] and [C3 + C2] were initial defects for growth dynamics with both uncontrolled and suppressed nucleation, further inducing more complex defects. The defects can be significantly reduced by achieving the growth with monomers added to a single nucleus, agreeing well with previous simulations and experiments. To understand the nature of defects, we proposed a parameter φ to describe the range of biased rotational angle between two monomers, within which chemical reactions are allowed. The parameter φ shows a monotonic relationship with defect population, which is demonstrated to be highly computable by using density functional theory calculations. When φ < 20, we can even observe defect-free growth for the four combinations, irrespective of growth dynamics. The results are essential for screening and designing condensation reactions for the synthesis of single crystals of high quality.

Heterozygous SOD2 deletion deteriorated chronic intermittent hypoxia-induced lung inflammation and vascular remodeling through mtROS-NLRP3 signaling pathway.

Oxidative stress caused by chronic intermittent hypoxia (CIH) is the hallmark of obstructive sleep apnea (OSA). Among the first line of defense against oxidative stress is the dismutation of superoxide radicals, which in the mitochondria is carried out by manganese superoxide dismutase (SOD2). In this study, wild-type (WT) and SOD2-heterozygous knockout (SOD2+/-) mice were exposed to CIH or normoxic (Nor) conditions. After 4 weeks, pulmonary artery pressure was measured, and the mice were processed to harvest either serum for cytokine assays or lungs for flow cytometry and histopathological studies. Herein, we showed that heterozygous deletion of SOD2 markedly deteriorated pulmonary remodeling and increased the oxidative stress, especially promoted the infiltration of macrophages in the lungs of CIH mouse. Moreover, in the intermittent hypoxia (IH)-treated RAW264.7 cells, SOD2 knockdown increased the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation accompanied with the IL-1ß elevation and caspase-1 activity. Additionally, mitochondrial ROS (mtROS) scavenger mito-TEMPO abolished NLRP3 inflammasome activation in IH-treated RAW264.7 cells. Collectively, our results supported that SOD2 contributed to the pathogenesis of CIH-induced lung remodeling. Meanwhile, SOD2 knockdown exacerbates oxidative damage through assembly and activation of NLRP3 inflammasome in macrophages. SOD2 may be a novel therapeutic target for CIH-induced pulmonary inflammation and arteriole remodeling.

Building Block Design for Minimizing Defects in the Construction of Two-Dimensional Covalent Organic Frameworks.

Polymerization of monomers into two-dimensional covalent organic frameworks with precise porous structures exhibits desired catalytic, gas separation, and optoelectronic properties. However, the defects arising from covalent bonding in a polymerization process always result in amorphous films with small crystalline domains or polycrystalline powders. It is still a tremendous challenge to synthesize high-quality crystalline products, even single crystals with a large size over the micrometer scale. In this work, we propose a general strategy of building block design to reduce the defects during growth of two-dimensional covalent organic frameworks. We demonstrate that the building block with a hexagonal pore unit, i.e., a hexamer, could greatly decrease defects by directional uniform growth in polymerization, while monomer, dimer, and trimer building blocks form more defects due to linear growth. Our work provides a new strategy to construct superlarge single crystals in practical applications by combining building block design and growing dynamics control.

Isolation, identification and character analysis of Streptococcus dysgalactiae from Megalobrama terminalis.

Pure bacterial cultures were isolated from different tissues of moribund Megalobrama terminalis from a high mortality event that occurred at a farm in Foshan, China. Two isolates (F2 and F3) were identified as Streptococcus dysgalactiae subsp. dysgalactiae based on morphological and biochemical detection as well as molecular analysis. In brain heart infusion broth, the best growth conditions of isolate F3 were 35ºC, salinity 5‰ and pH 7. Furthermore, infection with isolate F3 (1.2 × 106  CFU/fish) led to the death of M. terminalis and zebrafish (Danio rerio). However, isolate F3 had no obvious pathogenicity to tilapia (GIFT, Oreochromis niloticus). When the water temperature was 29ºC, the corresponding mortality rates for zebrafish infected by isolate F3 were higher than those at 23ºC. Culture for 24 and 72 hr with isolate F3 resulted in the same mortality rates for zebrafish. The antimicrobial susceptibility assay revealed that isolate F3 was susceptible to ampicillin, florfenicol and several other antibiotics but resistant to nalidixic acid, streptomycin, sulfamethoxazole/trimethoprim, neomycin and amikacin. To our knowledge, this is the first report that S. dysgalactiae infected the subtropical freshwater fish M. terminalis, which indicates that this bacterium is a potential threat to subtropical freshwater fish.

Heterogeneous dynamics of unentangled chains in polymer nanocomposites.

We present a systematic investigation on the effect of adding nanoparticles on the dynamics of polymer chains by using coarse-grained molecular dynamics simulation. The dynamics is characterized by three aspects: molecular motion, relaxation at different length scales, and dynamical heterogeneity. It is found that the motion of polymer chains slows down and the deviation from Gaussian distribution becomes more pronounced with increasing nanoparticle volume fractions. For polymer nanocomposites with R ≤ Rg, the relaxation at the wave vector q = 7.0 displays multistep decay, consistent with the previous reports in strongly interacting polymer nanocomposites. Moreover, a qualitatively universal law is established that dynamic heterogeneity at whole chain's scale follows a nonmonotonic increase with increasing nanoparticle loadings, where the volume fraction of the maximum dynamic heterogeneity corresponds to the particle loading when the average distance between nanoparticles is equal to the Kuhn length of polymer chains. We show that the decoupling between whole chain's dynamics and segment dynamics is responsible for the nonmonotonic behavior of dynamic heterogeneity of whole chains.

Pharmacological modulation of the voltage-gated neuronal Kv7/KCNQ/M-channel alters the intrinsic excitability and synaptic responses of pyramidal neurons in rat prefrontal cortex slices.

The prefrontal cortex (PFC) critical for higher cognition is implicated in neuropsychiatric diseases, such as Alzheimer's disease, depression and schizophrenia. The voltage-activated Kv7/KCNQ/M-channel or M-current modulates the neuronal excitability that defines the fundamental mechanism of brain function. However, whether M-current functions to regulate the excitability of PFC neurons remains elusive. In this study, we recorded the native M-current from PFC layer V pyramidal neurons in rat brain slices and showed that it modulated the intrinsic excitability and synaptic responses of PFC pyramidal neurons. Application of a specific M-channel blocker XE991 (40 µmol/L) or opener retigabine (10 µmol/L) resulted in inhibition or activation of M-current, respectively. In the current-clamp recordings, inhibition of M-current was evidenced by the increased average spike frequency and the reduced first inter-spike interval (ISI), spike onset latency and fast afterhyperpolarization (fAHP), whereas activation of M-current caused opposite responses. Furthermore, inhibition of M-current significantly increased the amplitude of excitatory postsynaptic potentials (EPSPs) and depolarized the resting membrane potential (RMP) without affecting the miniature EPSC (mEPSC) frequency. These data demonstrate that voltage-gated neuronal Kv7/KCNQ/M-current modulates the excitability and synaptic transmission of PFC neurons, suggesting that pharmacological modulation of M-current in the PFC may exert beneficial effects on cognitive deficits implicated in the pathophysiology of neuropsychiatric disorders.

Mineralized Collagen Regulates Macrophage Polarization During Bone Regeneration.

The host immune response to bone biomaterials is vital in determining the fate of scaffolds and also the outcomes of bone regeneration. Mineralized collagen is an ideal tissue-engineering scaffold for bone repair; however, little is known about its immunomodulatory properties after implantation. In this study, extrafibrillarly-mineralized collagen (EMC) and intrafibrillarly-mineralized collagen (IMC) scaffolds with different nanostructures were fabricated and their immunomodulatory properties via macrophage polarization during bone regeneration were investigated. Micro-CT findings showed that the IMC scaffold yielded more new bone formation than the EMC scaffold. In the defect area, more CD68 + CD163 + M2-like macrophages were observed in the IMC group, while M1-like macrophages positive for CD68 and inducible nitric oxide synthase (iNOS) increased dramatically in the EMC group. We further demonstrated, from the protein and RNA levels, that M2-associated anti-inflammatory cytokines interleukin (IL)-10 and arginase-1 were highly expressed in the macrophages seeded on the IMC scaffold, while those seeded on the EMC scaffold expressed more M1-related genes iNOS and IL-6. Moreover, the macrophage polarization in response to the nanostructure of mineralized collagen scaffolds influenced the osteogenesis of human bone marrow stromal cells. These findings suggest that the nanostructure of mineralized collagen scaffolds affects macrophage functional polarization during bone regeneration. The immunomodulatory properties of biomaterial scaffolds can be a dictator of bone regeneration outcomes.

[Effect of moxibustion of "dachangshu" (BL 25) area on pain reaction and TRPV 1 mRNA expression of bone marrow cells in visceral hyperalgesia rats].

OBJECTIVE: To observe the effect of moxibustion of "Dachangshu" (BL 25) on pain reaction and expression of transient receptor potential vanilloid 1 (TRPV 1) of bone marrow cells in visceral hyperalgesia (VHA) rats so as to explore its mechanism underlying visceral pain-relief. METHODS: Twenty-eight male SD rats were divided into control group, control+moxibustion group, VHA model and VHA+moxibustion group (n = 7/group). The VHA model was made by giving colorectal distension (CRD, 60 mmHg) to the newborn rats for 1 min (repeated once again in 30 min) from postnatal day 8 on, once daily for a week. Moxibustion was applied to ipsilateral "Dachangshu"(BL 25) area for 40 min from the 8th week on after birth. Abdominal withdrawal reflex (AWR) and pain threshold during CRD were measured before and after moxibustion. The TRPV 1 mRNA expressio of bone marrow cells was detected by real time-POR. RESULTS: (1) The AWR score of the model group was significantly higher than that of the control group, but the pain threshold of the model group was significantly lower than that of the control group (P < 0.01), suggesting a VHA in model rats. (2) After moxibustion, the AWR scores were significantly lower in the VHA+moxibustion group than in the model group (P < 0.05, P < 0.01), and the pain threshold was remarkably higher in the former group than in the latter group (P < 0.01). Similar results were found in the control+moxibustion group compared to the control group: the decreased AWR scores (CRD 40 mmHg, 60 mmHg and 80 mmHg, P < 0.01) and the increased pain threshold (P < 0.05). (3) The TRPV 1 mRNA expression level of bone marrow cells was significantly lower in the VHA + moxibustion group than in the model group (P < 0.01). No significant difference was found between the control and moxibustion+control groups in TRPV 1 mRNA expression level (P > 0.05). CONCLUSION: Moxibustion of "Dachangshu" (BL 25) can reduce visceral hyperalgesia and down-regulate TRPV 1 mRNA expression of bone marrow cells in VHA rats, suggesting an involvement of TRPV 1 mRNA of bone marrow cells in CRD-induced visceral pain development.

[Effects of soil moisture before sowing and nitrogen fertilization on winter wheat yield and water use on Weibei Plain of Loess Plateau].

A five-year site-specific experiment was carried out on the Weibei Plain of Loess Plateau in Shaanxi Province of northwestern China to study the effects of soil moisture regime before sowing (SMBS) and nitrogen fertilization on the grain yield and water use of winter wheat. On the basis of applying 100 kg x hm(-2) of P2O5, five nitrogen fertilization levels (0, 80, 160, 240, and 320 kg N x hm(-2)) were installed, and took the precipitation in the five years into consideration. In the study area, there was a linear correlation between the precipitation in summer (from July to September) and the SMBS, with an increment of 0.6 mm SMBS per 1 mm precipitation. For a stable or high wheat yield, the SMBS should be kept around 550 mm, and the precipitation in summer should be around 370-390 mm. In the years with adequate precipitation (> 386 mm) in summer, the SMBS in present winter wheat growth season less decreased by the increase of the nitrogen fertilization rate in previous growth season. However, in the years with less precipitation in summer (< 350 mm), the SMBS in present winter wheat growth season decreased significantly by 9-17 mm when the nitrogen fertilization rate in previous growth season was increased by each 100 kg N x hm(-2). In addition to SMBS, adequate precipitation in key growth stages was another important factor to ensure the wheat yield in dryland area because 1 mm SMBS could produce 10.6-11.4 kg x hm(-2) of wheat grain, and 1 mm precipitation occurred in the key growth stages could lead to more grain yield as high as 30.6-33.1 kg x hm(-2). Variation analysis showed that nitrogen fertilization rate affected the utilization degree of SMBS by winter wheat, while SMBS controlled the allocation and transportation of dry matter from vegetative parts to grain.

Relationship between structural gel and mechanical gel for ABA triblock copolymer in solutions: a molecular dynamics simulation.

Polymer gel exists ubiquitously in our daily life, as in food, cosmetics, drugs, and so on. From the structural point of view, the 3D network can be found in a structural gel. In most experimental work, the gel is identified by the sharp increase in modules; that is, the gel should have similar properties as those of a solid, which is named as mechanical gel. However, not all structural gels have strong mechanical responses. Therefore, studying the relationship between structural gel and mechanical gel is very important. In this work, we investigate the structure and mechanical properties of symmetric ABA copolymers with solvophobic end blocks during the sol-gel transition. Three typical systems with weak, middle, and strong solvophobicities are simulated. It is found that the gelation concentration, gel structure, and mechanical response of structural gel are strongly affected by the solvophobicity of ABA block copolymer. We also find that only the gel formed in strong solvophobic systems has a strong mechanical response. Furthermore, the influence of solvophobicity of A-block on the static and dynamic properties of ABA block copolymers in solutions is also studied to give a molecular understanding of physical gelation.

Monte Carlo simulation of a single ring among linear chains: structural and dynamic heterogeneity.

We perform lattice Monte Carlo simulation using the bond-fluctuation model to examine the conformation and dynamic properties of a single small flexible ring polymer in the matrix of linear chains as functions of the degree of polymerization of the linear chains. The average conformation properties as gauged by the mean-square radius of gyration and asphericity parameter are insensitive to the chain length for all the chain lengths examined (30, 100, 300, and 1000). However, in the longer chain (300 and 1000) samples, there is an increased spread in the distribution of the value of these quantities, suggesting structural heterogeneity. The center-of-mass diffusion of the ring shows a rapid decrease with increasing chain length followed by a more gradual change for the two longer chain systems. In these longer chain systems, a wide spread in the value of the apparent self-diffusion coefficient is also observed, as well as qualitatively different square displacement trajectories among the different samples, suggesting heterogeneity in the dynamics. A primitive path analysis reveals that in these long chain systems, the ring can exist in topologically distinct states with respect to threading by the linear chains. Threading by the linear chain can dramatically slow down and in some cases stall the diffusive motion of the ring. We argue that the life times for these topological conformers can be longer than the disentanglement time of the linear chain matrix, so that the ring exhibits nonergodic behavior on time scales less or comparable to the life time of these conformers. Our results suggest a picture of the ring diffusion as one where the diffusion path consists of distinctive segments, each corresponding to a different conformer, with slow interconversion between the different conformers.

[Comparison of peripheral blood hematopoietic progenitor cells among patients with paroxysmal, permanent atrial fibrillation or sinus rhythm].

OBJECTIVE: To compare peripheral blood hematopoietic progenitor cells (HPCs), plasma atrial natriuretic peptide (ANP) and stromal cell-derived factor-1alpha (SDF-1alpha) among patients with paroxysmal, permanent atrial fibrillation (AF) or sinus rhythm. METHODS: Peripheral blood concentration of CD34+HPCs were quantified by flow cytometric analysis (FCM), plasma ANP levels were measured by radioimmunoassay (RIA) method, plasma levels of SDF-1alpha were determined by enzyme linked immunosorbent assay (ELISA) in 30 patients with permanent AF, 28 patients with paroxysmal AF, and 30 patients with sinus rhythm (SR). HPCs were separated, cultured and stained for ANP by the use of alkaline phosphatase-anti-alkaline phosphatase technique (APAAP) in 30 patients (10 from each group). RESULTS: (1) The number of CD34+HPCs in permanent AF group [(5.31 +/- 1.67) x 10(6)/L] were significantly higher comparing to paroxysmal AF group [(2.33 +/- 1.29) x 10(6)/L] (P < 0.05) and SR group [(2.03 +/- 0.64) x 10(6)/L] (P < 0.05) while CD34+HPCs was similar between paroxysmal AF group and SR group (P > 0.05). (2) Plasma levels of ANP (0.312 +/- 0.121) microg/L and SDF-1alpha (3210.2 +/- 1234.7) ng/L were also significantly higher in permanent AF group than paroxysmal AF group and SR group (all P < 0.05) and were similar in paroxysmal AF group and SR group (all P > 0.05). (3) The plasma levels of ANP and SDF-1alpha were both positive correlated with peripheral blood concentration of CD34+HPCs (r = 0.783, P < 0.01; r = 0.427, P < 0.01). (4) After 3 days of culture, ANP was weakly expressed in HPCs from patients with permanent AF but not from patients with paroxysmal AF and SR. CONCLUSIONS: Peripheral blood HPCs together with plasma ANP and SDF-1alpha were significantly increased in patients with permanent AF. CD34+HPCs were positive correlated with the plasma levels of ANP and SDF-1alpha.