Multifunctional Roles of Clathrate Hydrate Nanoreactors for CO2 Reduction.

In this study, we explore a possible platform for the CO2 reduction (CO2 R) in one of water's solid phases, namely clathrate hydrates (CHs), by ab initio molecular dynamics and well-tempered metadynamics simulations with periodic boundary conditions. We found that the stacked H2 O nanocages in CHs help to initialize CO2 R by increasing the electron-binding ability of CO2 . The substantial CO2 R processes are further influenced by the hydrogen bond networks in CHs. The first intermediate CO2 - in this process can be stabilized through cage structure reorganization into the H-bonded [CO2 - ⋅⋅⋅H-OHcage ] complex. Further cooperative structural dynamics enables the complex to convert into a vital transient [CO2 2- ⋅⋅⋅H-OHcage ] intermediate in a low-barrier disproportionation-like process. Such a highly reactive intermediate spontaneously triggers subsequent double proton transfer along its tethering H-bonds, finally converting it into HCOOH. These hydrogen-bonded nanoreactors feature multiple functions in facilitating CO2 R such as confining, tethering, H-bond catalyzing and proton pumping. Our findings have a general interest and extend the knowledge of CO2 R into porous aqueous systems.

Hydrated electrons as nodes in porous clathrate hydrates.

We investigate the structures of hydrated electrons (e- aq) in one of water's solid phases, namely, clathrate hydrates (CHs). Using density functional theory (DFT) calculations, DFT-based ab initio molecular dynamics (AIMD), and path-integral AIMD simulations with periodic boundary conditions, we find that the structure of the e- aq@node model is in good agreement with the experiment, suggesting that an e- aq could form a node in CHs. The node is a H2O defect in CHs that is supposed to be composed of four unsaturated hydrogen bonds. Since CHs are porous crystals that possess cavities that can accommodate small guest molecules, we expect that these guest molecules can be used to tailor the electronic structure of the e- aq@node, and it leads to experimentally observed optical absorption spectra of CHs. Our findings have a general interest and extend the knowledge of e- aq into porous aqueous systems.

Optical image conversion and encryption based on structured light illumination and a diffractive neural network.

In this paper, an optical image encryption method is proposed based on structured light illumination and a diffractive neural network (DNN), which can realize conversion between different images. With the use of the structured phase mask (SPM) in the iterative phase retrieval algorithm, a plaintext image is encoded into a DNN composed of multiple phase-only masks (POMs) and ciphertext. It is worth noting that ciphertext is a visible image such that the conversion of one image to another is achieved, leading to high concealment of the proposed optical image encryption method. In addition, the wavelength of the illuminating light, all Fresnel diffraction distances, the optical parameters of the adopted SPM such as focal length and topological charge number, as well as all POMs in the DNN are all considered as security keys in the decryption process, contributing to a large key space and high level of security. Numerical simulations are performed to demonstrate the feasibility of the proposed method, and simulation results show that it exhibits high feasibility and safety as well as strong robustness.

Differences in susceptibility of HT-29 and A549 cells to statin-induced toxicity: An investigation using high content screening.

Statins are a group of hydroxymethylglutaryl coenzyme A reductase inhibitors that are used in the treatment of cardiovascular diseases. However, statins have been found to be cytotoxic, and many unexpected side effects have been reported in clinical applications. The susceptibilities of different cell lines toward statins are diverse, and the mechanisms of cytotoxicity remain unknown. Therefore, the present study aimed to investigate differences in the susceptibility to and mechanisms of statin-induced cytotoxicity in two cell lines, HT-29 and A549, using a high content screening-based multiparametric toxicity assay panel. We found that the two cell types exhibited differing susceptibilities to the cytotoxic effects of the different statins. Additionally, the cytotoxicity was inconsistent between different statins in the two cell lines. Four statins with strong cytotoxicity decreased the viability of HT-29 cells via the mitochondrial pathway, as evidenced by decreased mitochondrial membrane potential, and elevated mitochondrial mass, calcium release and cell apoptosis, and reactive oxygen species. In contrast, these four statins only induced a decrease in the mitochondrial membrane potential in A549 cells. The above results provide an objective reason for future evaluations of cytotoxic differences in cell types and the underlying mechanisms of cytotoxicity in different statins, and provide a good scientific basis for further research on countermeasures against statin-induced cell injuries.

General Dual-Switched Dynamic Singlet Fission Channels in Solvents Governed Jointly by Chromophore Structural Dynamics and Solvent Impact: Singlet Prefission Energetics Analyses.

The singlet fission (SF) channels in many systems are controlled by the thermodynamic driving force (Switch-1) and kinetic barrier (Switch-2), both of which could be modulated by chromophore structure dynamics and solvent properties. Using ab initio molecular dynamics (AIMD), we here simulate how the structural dynamics and solvent jointly govern singlet prefission energetics, taking a covalent BODIPY dimer (di-BODIPY) in solvents as an example. We report a general dual-switched dynamic channel for intramolecular SF in solvents and suggest an effective AIMD sampling method to characterize the joint effect of chromophore structure dynamics and the solvent impact on SFs. Results reveal that the joint effect not only provides di-BODIPY more chances for meeting the SF thermodynamic requirement (Switch-1 ON) but also tunes the charge-transfer state toward removing the kinetic barrier (Switch-2 ON). Two factors jointly govern each switch in the dual-switched SF channel, and any one does not open the channel alone. We suggest a general principle for dynamically dual-switching the SF channel in solvents by utilizing the joint effect to tune the pre-SF energetics for photoexcitation and the opening of the subsequent channel. AIMD sampling is used for the first time to discover explicit solvent-solute interaction and dynamics information and thus their effect on excitation energetics. This work also shows the statistical information for an ensemble of SF chromophores in solvents, which can undergo different photoexcitations and possible SFs. The high agreement of the findings here with the experiments justifies our AIMD sampling-based pre-SF energetic prediction as a reliable way for exploring novel SF systems and their controllability.

Construction and application of a high-content analysis for identifying human carboxylesterase 2 inhibitors in living cell system.

Human carboxylesterase 2 (hCE2), one of the most principal drug-metabolizing enzymes, catalyzes the hydrolysis of a variety of endogenous esters, anticancer agents, and environmental toxicants. The significant roles of hCE2 in both endobiotic and xenobiotic metabolism sparked great interest in the discovery and development of efficacious and selective inhibitors. However, the safe and effective inhibitors of hCE2 are scarce, due to the lack of efficient screening and evaluation systems for complex biological systems. To offer a solution to this problem, a high-content analysis (HCA)-based cell imaging and multiparametric assay method was constructed for evaluating the inhibitory effect and safety of hCE2 inhibitors in living cell system. In this study, we first established a cell imaging-based method for identifying hCE2 inhibitors at the living cell level with hCE2 fluorescent probe NCEN. Meanwhile, two nuclear probes, Hoechst 33342 and PI, were integrated to evaluate the potential cytotoxicity of compounds simultaneously. Then, the accuracy of the HCA-based method was verified by the LC-FD-based method with a positive inhibitor BNPP, and the results showed that the HCA-based method exhibited excellent precision, robustness, and reliability. Finally, the newly established HCA-based multiparametric assay panel was successfully applied to re-evaluate a series of reported hCE2 inhibitors in living cells. In summary, the HCA-based multiparametric method could serve as an efficient tool for the accuracy measurement inhibitory effect and cytotoxicity of compounds against hCE2 in living cell system. Graphical abstract.

Vaginal delivery outcomes of pregnancies following ultrasound-guided high-intensity focused ultrasound ablation treatment for uterine fibroids.

OBJECTIVE: To evaluate the feasibility and safety of vaginal delivery after ultrasound-guided high-intensity focused ultrasound (HIFU) ablation treatment for women with uterine fibroids of child-bearing ages. METHODS: A prospective study was conducted on women who underwent ultrasound-guided HIFU therapy for uterine fibroids at the Chinese PLA General Hospital from January 2008 to December 2014. Patients were interviewed yearly to assess their fertility outcomes, including conception method, delivery mode, neonatal outcomes and complications during pregnancy, labor, and delivery. RESULTS: A total of 174 patients with plans for future pregnancy were included, and 88 pregnancies in 81 women occurred. The pregnancy rate was 46.6% (81/174), and the median follow-up time was 76 months. The rate of pregnancies that ended in miscarriages was 10% (9/88), the rate of elective pregnancy termination was 6% (5/88), and 84% (74/88) of the pregnancies resulted in deliveries, with 3 of the 71 women having two deliveries. A cesarean section was requested by 50% (37/74) of the women, and 50% (37/74) opted for a vaginal delivery. Eleven of the 37 pregnancies were scheduled for elective cesarean sections, owing to pregnancy complications; the remaining 26 pregnancies were scheduled for vaginal delivery, and 21 (80.8%) were successful. None of the patients with a vaginal delivery experienced any complications during pregnancy and labor. CONCLUSIONS: Ultrasound-guided HIFU ablation could be considered a promising clinical treatment for women with uterine fibroids and plans for future pregnancy, and vaginal delivery after ultrasound-guided HIFU ablation treatment appear to be feasible and safe.

Integrated network pharmacology and serum metabonomics analysis to explore the potential mechanism of Anemarrhena asphodeloides Bunge-Phellodendron chinense Schneid herb pair in the treatment of benign prostatic hyperplasia.

Anemarrhena asphodeloides Bunge-Phellodendron chinense Schneid (AAPC) is one of the most widely accepted herb pairs in Chinese medicine prescription for treating benign prostatic hyperplasia (BPH). However, the mechanisms underlying the combination of the two herbs for anti-BPH are still not completely clear. To uncover the potential mechanism of the AAPC herb pair in the treatment of BPH, chemical profiling, network pharmacology, serum metabonomics and experimental validation were integrated. UHPLC-Q-Exactive Orbitrap-MS was performed to characterize the chemical profiling of the herb pair extract, and network pharmacology was employed to forecast the potential effective components, core targets and key signaling pathways. Then, western blot and RT-PCR experiments were conducted to verify the PI3K/Akt/NF-κB signaling pathway predicted by network pharmacology. Finally, the serum differential metabolites and metabolic pathways were analyzed by serum non-targeted metabonomics, and these results were jointly analyzed by MetScape. 51 chemical components of the AAPC herb pair extract were identified, including phellodendrine, magnoflorine, berberine, mangiferin, anemarsaponin BIII, etc. In network pharmacology, the predicted core targets of these components include AKT1, TNF, EGFR, PTGS2, PIK3CA, etc. The KEGG pathway enrichment analysis indicated that PI3K-Akt, Rap1 and MAPK signaling pathways may play a key role in the AAPC herb pair for the treatment of BPH, and the results of animal experiments demonstrated that the herb pair could significantly inhibit the activation and expression of p-PI3K/PI3K, p-Akt/Akt, p-NF-κB/NF-κB in protein and mRNA levels. Furthermore, 31 serum differential metabolites and three main metabolic pathways were obtained by serum non-targeted metabonomics. And the crucial metabolic pathway of arachidonic acid (AA) was obtained by integrated analysis of network pharmacology and metabonomics results. In conclusion, the AAPC herb pair can improve BPH through inhibiting the activation and expression of the PI3K/Akt/NF-κB signaling pathway and AA metabolism.

Combining untargeted and targeted metabolomics to reveal the mechanisms of herb pair Anemarrhena asphodeloides Bunge and Phellodendron chinense C. K. Schneid on benign prostatic hyperplasia.

ETHNOPHARMACOLOGICAL RELEVANCE: Anemarrhena asphodeloides Bunge (Ane) and Phellodendron chinense C. K. Schneid (Phe) is classical herb pair in traditional Chinese medicine, commonly used to ameliorate the symptoms of Benign Prostatic Hyperplasia (BPH). However, the mechanisms underlying this effect are remained indistinct. AIM OF THE STUDY: This study aimed to clarify potential therapeutic mechanisms of herb pair on BPH from a metabolic perspective. MATERIALS AND METHODS: Testosterone propionate-induced BPH rat model was established, prostatic parameters, histopathology and the levels of serum dihydrotestosterone (DHT) and testosterone (T) were used to evaluate the pharmacological effect of the herb pair on BPH. Subsequently, untargeted metabolomics of prostate tissues samples was performed by UHPLC-Q-Exactive-Orbitrap-MS, followed by multivariate statistical analysis. Targeted metabolomics by UHPLC-QQQ-MS was further utilized to verify and supplement the results of lipids and amino acids found by untargeted metabolomics, clarifying the relationship between disease, herbal pair and metabolism pathway. RESULTS: The study found that Ane-Phe could relieve the progression of BPH and regulate metabolic imbalances. The levels of 13 metabolites decreased and 11 increased in prostatic tissues including glycerolphospholipid, arachidonic acid, citric acid and so on, these altered metabolites were primarily associated with TCA cycle, arachidonic acid metabolism, lipid metabolism and amino acid metabolism. Furthermore, targeted metabolomics was fulfilled to further analyze the lipid metabolism disorders, the levels of 5 lipids in serum and 21 in prostatic tissues were changed in the herb pair group compared to the model group, which closely related to glycerophospholipid, sphingolipid and glycerolipid metabolism. Besides, amino acid metabolism may be regulated by activating arginine metabolism pathway. CONCLUSIONS: In this study, the combination of untargeted metabolomics and targeted metabolomics was applied to explore therapeutic mechanisms of Ane-Phe on BPH. In summary, Ane-Phe could improve the levels of endogenous metabolites by regulating multiple metabolic pathways and plays a role in energy supply, anti-inflammation and oxidative stress in BPH treatment.

The regulation of GSH/GPX4-mediated lipid accumulation confirms that schisandra polysaccharides should be valued equally as lignans.

ETHNOPHARMACOLOGICAL RELEVANCE: Acetaminophen (APAP) induced liver injury (AILI) is a common cause of clinical hepatic damage and even acute liver failure. Our previous research has shown that Schisandra chinensis lignan extract (SLE) can exert a hepatoprotective effect by regulating lipid metabolism. Although polysaccharides from Schisandra chinensis (S. chinensis), like lignans, are important components of S. chinensis, their pharmacological activity and target effects on AILI have not yet been explored. AIM OF THE STUDY: This study aims to quantitatively reveal the role of SCP in the pharmacological activity of S. chinensis, and further explore the pharmacological components, potential action targets and mechanisms of S. chinensis in treating AILI. MATERIALS AND METHODS: The therapeutic effect of SCP on AILI was systematically determined via comparing the efficacy of SCP and SLE on in vitro and in vivo models. Network pharmacology, molecular docking and multi-omics techniques were then used to screen and verify the action targets of S. chinensis against AILI. RESULTS: SCP intervention could significantly improve AILI, and the therapeutic effect was comparable to that of SLE. Notably, the combination of SCP and SLE did not produce mutual antagonistic effects. Subsequently, we found that both SCP and SLE could significantly reverse the down-regulation of GPX4 caused by the APAP modeling, and then further improving lipid metabolism abnormalities. CONCLUSIONS: Hepatoprotective effects of SCP and SLE is most correlated with their regulation of GSH/GPX4-mediated lipid accumulation. This is the first exploration of the hepatoprotective effect and potential mechanism of SCP in treating AILI, which is crucial for fully utilizing S. chinensis and developing promising AILI therapeutic agents.

Symmetry-Breaking Manipulated Channel Ergodicity in Intramolecular Singlet Fission Uncovered Statistically by Molecular Dynamics Samplings.

Persistent structure dynamics of chromophores in a solvent has a pivotal influence on singlet fission (SF) phenomena through breaking structure symmetry and tuning electronic properties. However, clarifying how the dynamic factors manipulate the SF dynamics faces major challenges. Here, we for the first time propose a dynamic symmetry-breaking strategy for manipulating intramolecular SF and unveil channel-ergodic characters by constructing transient configuration space of an individual solvated monomer in a chromophore-in-solvent ensemble by sampling its dynamics trajectory. Dynamic symmetry-breaking leads an SF ensemble to find possible SF channels (i.e., subensembles), characterized by a broad energy population of a charge-transfer state and its coupling with a locally excited state, and the populated multichannels featuring distinct probability distributions determine the dominant SF mechanism and also reveal channel conversion and ergodic behavior, agreeing highly with experimental observations. This work emphasizes the vital role of the inherent structure dynamics of a chromophore in solvent in manipulating such photophysics characteristics by evaluating their symmetry-breaking properties statistically.

Clinical characteristics of bloodstream infections in adult patients with solid tumours and a nomogram for mortality prediction: a 5-year case-controlled retrospective study in a tertiary-level hospital.

Background: Bloodstream infections (BSIs) are one of the leading causes of death in cancer patients. Nevertheless, the risk factors of BSIs in solid tumors have rarely been ascertained adequately. Methods: We conducted a single-center case-controlled retrospective study from 2017 to 2021 among adults with solid tumors in a tertiary-level hospital. The BSIs and control group were matched by the propensity score matching method. We found independent risk factors of occurrence and death of BSIs using univariate and multivariate regression analysis. Additionally, a nomogram was constructed to predict the risk of mortality in BSIs. Results: Of 602 patients with solid tumors in the study period, 186 had BSIs and 416 had non-BSIs. The incidence of BSIs was 2.0/1,000 admissions (206/102,704), and the 30-day mortality rate was 18.8% (35/186). Compared to the control group, the BSIs had longer hospital stays (24.5 days vs. 20.0 days), and higher frequency complicating with organ failure (10.5% vs. 2.4%), nephropathy (19.6% vs. 3.8%), comorbidities≥3 (35.5% vs. 20.0%), and liver-biliary-pancreatic infections (15.6% vs. 5.3%) (all P<0.001). Among the 186 patients with BSIs, 35 died within 30 days after BSIs. Gram-negative bacteria were the most frequent microorganisms (124/192, 64.6%). Liver cancer, organ failure, a high level of lactate dehydrogenase and septic shock were the independent hazardous factors for death of BSIs. What's more, a nomogram was constructed to predict the 30-day survival rate of BSIs, which was proved to have good accuracy (AUC: 0.854; 95% confidence interval: 0.785~0923) and consistency. Conclusion: Being aware of the risk factors of BSIs redounds to take preventive measures to reduce the incidence and death of BSIs.

Schisandra lignans ameliorate nonalcoholic steatohepatitis by regulating aberrant metabolism of phosphatidylethanolamines.

Nonalcoholic steatohepatitis (NASH) is a spectrum of chronic liver disease characterized by hepatic lipid metabolism disorder. Recent reports emphasized the contribution of triglyceride and diglyceride accumulation to NASH, while the other lipids associated with the NASH pathogenesis remained unexplored. The specific purpose of our study was to explore a novel pathogenesis and treatment strategy of NASH via profiling the metabolic characteristics of lipids. Herein, multi-omics techniques based on LC-Q-TOF/MS, LC-MS/MS and MS imaging were developed and used to screen the action targets related to NASH progress and treatment. A methionine and choline deficient (MCD) diet-induced mouse model of NASH was then constructed, and Schisandra lignans extract (SLE) was applied to alleviate hepatic damage by regulating the lipid metabolism-related enzymes CES2A and CYP4A14. Hepatic lipidomics indicated that MCD-diet led to aberrant accumulation of phosphatidylethanolamines (PEs), and SLE could significantly reduce the accumulation of intrahepatic PEs. Notably, exogenous PE (18:0/18:1) was proved to significantly aggravate the mitochondrial damage and hepatocyte apoptosis. Supplementing PE (18:0/18:1) also deteriorated the NASH progress by up regulating intrahepatic proinflammatory and fibrotic factors, while PE synthase inhibitor exerted a prominent hepatoprotective role. The current work provides new insights into the relationship between PE metabolism and the pathogenesis of NASH.

Retraction: A solid ultrasonic coupling membrane for superficial vascular ultrasonography.

Retraction of 'A solid ultrasonic coupling membrane for superficial vascular ultrasonography' by Di Sun et al., Nanoscale, 2022, 14, 3545-3553, https://doi.org/10.1039/D1NR05353A.

A solid ultrasonic coupling membrane for superficial vascular ultrasonography.

Superficial thrombophlebitis is one of the most significant complications of superficial vein thrombosis. Rapid imaging and mapping with high resolution is particularly important for accurate diagnosis so as to carry out treatment as soon as possible. Ultrasound imaging technology has been used extensively because of the low-cost, minimal invasiveness, and convenient application in clinical practice. And the ultrasonic couplant is an essential component in ultrasound examination. However, when imaging superficial structures, traditional liquid ultrasonic couplants often produce inadequate results. In this study, we investigate whether a hydrogel membrane can be used to improve the imaging of superficial vessels. To this end, we generated a polyacrylamide-bacterial nanocellulose hydrogel membrane (PAM-BC) that efficiently forms at 60 °C in only 10 min by redox polymerization. With PAM-BC-2.5, it was possible to acquire high resolution intravascular ultrasound images to assess superficial vessels in humans and the superficial vasculature in rats and miniature pigs using various brands of ultrasound instruments. The PAM-BCs represent a new, solid ultrasonic membrane which is suitable for diagnosing disease in superficial vessels.

Design, synthesis and biological evaluation of indanone-chalcone hybrids as potent and selective hCES2A inhibitors.

Human carboxylesterase 2 (hCES2A), one of the major serine hydrolases distributed in the small intestine, plays a crucial role in hydrolysis of ester-bearing drugs. Accumulating evidence has indicated that hCES2A inhibitor therapy can modulate the pharmacokinetic and toxicological profiles of some important hCES2A-substrate drugs, such as the anticancer agent CPT-11. Herein, a series of indanone-chalcone hybrids are designed and synthesized to find potent and highly selective hCES2A inhibitors. Inhibition assays demonstrated that most indanone-chalcone hybrids displayed strong to moderate hCES2A inhibition activities. Structure-hCES2A inhibition activity relationship studies showed that introduction of a hydroxyl at the C4' site and introduction of an N-alkyl group at the C6 site were beneficial for hCES2A inhibition. Particularly, B7 (an N-alkylated 1-indanone-chalcone hybrid) exhibited the most potent inhibition on hCES2A and excellent specificity (this agent could not inhibit other human esterases including hCES1A and butyrylcholinesterase). Inhibition kinetic analyses demonstrated that B7 potently inhibited hCES2A-mediated FD hydrolysis in a mixed inhibition manner, with a calculated Ki value of 0.068 µM. Furthermore, B7 was capable of inhibiting intracellular hCES2A in living cells and displayed good metabolic stability. Collectively, our findings show that indanone-chalcone hybrids are good choices for the development of hCES2A inhibitors, while B7 is a promising candidate for the development of novel anti-diarrhea agents to ameliorate irinotecan-induced intestinal toxicity.

Influence of the Length of the Donor-Acceptor Bridge on Thermally Activated Delayed Fluorescence.

Small singlet-triplet energy splitting is a dominant condition for efficient thermally activated delayed fluorescence (TADF), which could be obtained by increasing the length of the connecting bridge between the donor (D) and the acceptor (A) units in molecules. However, the long connecting bridge could also give rise to a small radiative decay rate, which is harmful for the overall luminescent efficiency of TADF. Herein, we calculate the singlet-triplet energy splitting and the radiative decay rate and discuss the bridge length effect on the TADF efficiency. The results indicate that there is an optimal value of the D-A bridge length at which the delayed fluorescence efficiency and internal quantum efficiency reach their maxima. The optimal value depends on the size of the donor or acceptor unit. Furthermore, molecules with larger unit size have larger optimal TADF efficiency. Our findings shed new light on the design strategies of high-efficiency TADF molecules.

Kidney injury molecule-1 expression is closely associated with renal allograft damage.

The aim of our study was to investigate the expression of kidney injury molecule-1 (KIM-1) in renal allograft biopsy samples and assess the clinical significance of its use as a biomarker for tissue damage. A total of 69 renal allograft biopsy samples from 17 patients with normal serum creatinine and 52 cases of increased serum creatinine were collected. They were divided into different groups according to the Banff 2007 diagnostic criteria. KIM-1 expression was detected by immunohistochemical methods and the association of KIM-1 and blood biochemical indexes was analyzed. KIM-1 expression increased as Banff 2007 classification grade increased and was positively correlated with tubular inflammation severity in the acute T-cell rejection group. Moreover, KIM-1 expression was strongly positive in the chronic active antibody-mediated rejection group. Interestingly, KIM-1 was weakly positive in the normal group without obvious acute rejection and injury of immunosuppressant toxicity. In this group, 27.3% (3/11) of the cases with normal serum creatinine level showed weakly positive KIM-1 expression in their renal tissues. KIM-1 expression level is positively correlated with renal allograft damage and tubular cell injury. KIM-1 is expressed in tubular epithelial cells before blood biochemical indexes become elevated and morphological changes occur. KIM-1 expression is an early, sensitive, and specific biomarker to determine renal tubular epithelial cell injury in renal allograft tissue.

Chronic humoral rejection of human kidney allografts associates with broad autoantibody responses.

BACKGROUND: Chronic humoral rejection (CHR) is a major complication after kidney transplantation. The cause of CHR is currently unknown. Autoantibodies have often been reported in kidney transplant recipients alongside antidonor human leukocyte antigen antibodies. Yet, the lack of comprehensive studies has limited our understanding of this autoimmune component in the pathophysiology of CHR. METHODS: By using a series of ELISA and immunocytochemistry assays, we assessed the development of autoantibodies in 25 kidney transplant recipients with CHR and 25 patients with stable graft function. We also compared the reactivity of five CHR and five non-CHR patient sera with 8027 recombinant human proteins using protein microarrays. RESULTS: We observed that a majority of CHR patients, but not non-CHR control patients, had developed antibody responses to one or several autoantigens at the time of rejection. Protein microarray assays revealed a burst of autoimmunity at the time of CHR. Remarkably, microarray analysis showed minimal overlap between profiles, indicating that each CHR patient had developed autoantibodies to a unique set of antigenic targets. CONCLUSION: The breadth of autoantibody responses, together with the absence of consensual targets, suggests that these antibody responses result from systemic B-cell deregulation.

[The effect of newcastle disease virus on the biological behavior of tumor cells].

AIM: To investigate the anti-tumor effect of newcastle disease virus (NDV). METHODS: Plaque formation test was used to investigate the effect of NDV on chicken embryofibroblasts(CEF). Cell suppression test, agarose gel electrophoresis, cytoskeleton staining, fluorescence staining, TUNEL staining, and sialic acid content determination were used to observe the influence of NDV on several human tumor cells. RESULTS: The Plaque formation was observed in chicken embryo fibroblasts.NDV could lead to the apparent cytopathy of BHK, Hela and Hep-2 tumor cells, but has no apparent effect on Wish cells. The strong suppressive effect of NDV on the growth of these tumor cells was found without dose dependence. The optimal dose of NDV could induce the death of tumor cells which was mainly apoptosis, as showed by the classical DNA ladder in DNA gel electrophoresis. NDV also resulted in the changes of cytoskeleton and decreased the level of sialic acid contents on tumor cells. CONCLUSION: NDV may be a potential anti-tumor agent.