Arterial-Lymphatic-Like Endothelial Cells Appear in Hereditary Hemorrhagic Telangiectasia 2 and Contribute to Vascular Leakage and Arteriovenous Malformations.

BACKGROUND: Arteriovenous malformations (AVMs) are characteristic of hereditary hemorrhagic telangiectasia. Loss-of-function mutations in the activin receptor-like kinase 1 (Alk1) are linked to hemorrhagic telangiectasia type 2. METHODS: Endothelial-specific deletion of Alk1, endothelial lineage tracing, transcriptomics of single-cell analysis, and electron microscopy were performed to examine the vascular phenotype and characteristics of ALK1-deficient endothelial cells (ECs) after EC-specific Alk1 deletion. Ischemia assays were used to examine the cell capacity for vascular malformation. Connectivity Map with transcriptomic analysis was applied to identify chemical compounds. Specific methods for arteriovenous malformations, such as micro-computed tomography, with other molecular and cell biological tools were also performed. RESULTS: We performed endothelial-specific deletion of Alk1 in mice and found severe arteriovenous malformations and vascular leakage. The transcriptomics of single-cell analysis revealed a new distinctive cell cluster formed after Alk1 deletion where the cells coexpressed arterial and lymphatic endothelial markers. The analysis projected that these cells potentially originated from arterial ECs after Alk1 deletion. This new population was referred to as arterial-lymphatic-like ECs according to its cellular markers, and its appearance was validated in the pulmonary small arteries after Alk1 deletion. Transplantation of these cells caused vascular malformations. Endothelial lineage tracing confirmed that these new arterial-lymphatic-like ECs were derived from ALK1 depleted ECs, potentially arterial ECs. We discovered that SOX17 (SRY-box transcription factor 17) induction was responsible for the derivation of these arterial-lymphatic-like ECs. We showed that direct binding of MDM2 (mouse double minute 2) was required for Sox17 to execute this activity. Inhibition of MDM2 reduced the arteriovenous malformations in the mouse model. CONCLUSIONS: Together, our studies revealed the mechanistic underpinnings of ALK1 signaling in regulating the endothelial phenotype and provided possibilities for new therapeutic strategies in hemorrhagic telangiectasia type 2.

Tobacco toxins trigger bone marrow mesenchymal stem cells aging by inhibiting mitophagy.

Smoking disrupts bone homeostasis and serves as an independent risk factor for the development and progression of osteoporosis. Tobacco toxins inhibit the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), promote BMSCs aging and exhaustion, but the specific mechanisms are not yet fully understood. Herein, we successfully established a smoking-related osteoporosis (SROP) model in rats and mice through intraperitoneal injection of cigarette smoke extract (CSE), which significantly reduced bone density and induced aging and inhibited osteogenic differentiation of BMSCs both in vivo and in vitro. Bioinformatics analysis and in vitro experiments confirmed that CSE disrupts mitochondrial homeostasis through oxidative stress and inhibition of mitophagy. Furthermore, we discovered that CSE induced BMSCs aging by upregulating phosphorylated AKT, which in turn inhibited the expression of FOXO3a and the Pink1/Parkin pathway, leading to the suppression of mitophagy and the accumulation of damaged mitochondria. MitoQ, a mitochondrial-targeted antioxidant and mitophagy agonist, was effective in reducing CSE-induced mitochondrial oxidative stress, promoting mitophagy, significantly downregulating the expression of aging markers in BMSCs, restoring osteogenic differentiation, and alleviating bone loss and autophagy levels in CSE-exposed mice. In summary, our results suggest that BMSCs aging caused by the inhibition of mitophagy through the AKT/FOXO3a/Pink1/Parkin axis is a key mechanism in smoking-related osteoporosis.

Selectivity Modulation of Multistep Reduction Reactions by Gold Nanoclusters.

The selective synthesis of valuable azo- and azoxyaromatic chemicals via transfer coupling of nitroaromatic compounds has been achieved by fine-tuning the catalyst structure. Here, a direct method to modulate nitrobenzene reduction and selectively alter the product from azobenzene to azoxybenzene by employing the size effect of Au is reported. Au nanoclusters (NCs) with smaller sizes embedded in ZIF-8 controllably converted nitrobenzene into azoxybenzene, while supported Au nanoparticles (NPs) catalyzed nitrobenzene reduction to azobenzene. X-ray photoelectron spectroscopy (XPS) and Diffuse reflectance infrared Fourier transform spectroscopy on CO adsorption (CO-DRIFTS) of Au NC/ZIF-8 revealed a higher valence state and a lower electron density of Au than that of Au NP/ZIF-8, combined with the desorption of azoxybenzene from the Au NC and Au NP surface, suggesting that the Au NCs with lower electron density exhibit stronger adsorption. Density functional theory (DFT) calculations and charge density difference maps indicated that azoxybenzene bonded to Au NC/ZIF-8 with greater adsorption energy, resulting in more electron transfer between azoxybenzene and the generated Au sites, which inhibited further reduction of azoxybenzene and resulted in high azoxybenzene selectivity. The application of the size effect of Au particles to regulate nitrobenzene transfer coupling provided new insights into the structure-selectivity relationships.

Personalized radiomics signature to screen for KIT-11 mutation genotypes among patients with gastrointestinal stromal tumors: a retrospective multicenter study.

OBJECTIVES: Gastrointestinal stromal tumors (GISTs) carrying different KIT exon 11 (KIT-11) mutations exhibit varying prognoses and responses to Imatinib. Herein, we aimed to determine whether computed tomography (CT) radiomics can accurately stratify KIT-11 mutation genotypes to benefit Imatinib therapy and GISTs monitoring. METHODS: Overall, 1143 GISTs from 3 independent centers were separated into a training cohort (TC) or validation cohort (VC). In addition, the KIT-11 mutation genotype was classified into 4 categories: no KIT-11 mutation (K11-NM), point mutations or duplications (K11-PM/D), KIT-11 557/558 deletions (K11-557/558D), and KIT-11 deletion without codons 557/558 involvement (K11-D). Subsequently, radiomic signatures (RS) were generated based on the arterial phase of contrast CT, which were then developed as KIT-11 mutation predictors using 1408 quantitative image features and LASSO regression analysis, with further evaluation of its predictive capability. RESULTS: The TC AUCs for K11-NM, K11-PM/D, K11-557/558D, and K11-D ranged from 0.848 (95% CI 0.812-0.884), 0.759 (95% CI 0.722-0.797), 0.956 (95% CI 0.938-0.974), and 0.876 (95% CI 0.844-0.908), whereas the VC AUCs ranged from 0.723 (95% CI 0.660-0.786), 0.688 (95% CI 0.643-0.732), 0.870 (95% CI 0.824-0.918), and 0.830 (95% CI 0.780-0.878). Macro-weighted AUCs for the KIT-11 mutant genotype ranged from 0.838 (95% CI 0.820-0.855) in the TC to 0.758 (95% CI 0.758-0.784) in VC. TC had an overall accuracy of 0.694 (95%CI 0.660-0.729) for RS-based predictions of the KIT-11 mutant genotype, whereas VC had an accuracy of 0.637 (95%CI 0.595-0.679). CONCLUSIONS: CT radiomics signature exhibited good predictive performance in estimating the KIT-11 mutation genotype, especially in prediction of K11-557/558D genotype. RS-based classification of K11-NM, K11-557/558D, and K11-D patients may be an indication for choice of Imatinib therapy.

Dkk-1-TNF-α crosstalk regulates MC3T3E1 pre-osteoblast proliferation and differentiation under mechanical stress through the ERK signaling pathway.

The study aims to explore the role of the ERK signaling pathway in the crosstalk between Dkk-1 and TNF-α in MC3T3E1 pre-osteoblasts under cyclic tensile/compressive stress. A forced four-point bending system was used to apply cyclic uniaxial tensile/compressive strain (2000 µ, 0.5 Hz) to MC3T3E1 cells. Dkk-1 and TNF-α expression were upregulated in MC3T3E1 cells under compressive strain. Cell proliferation, the cell cycle, osteogenesis-related gene (Wnt5a, Runx2, Osterix) expression, ß-catenin expression, and the p-ERK/ERK ratio were significantly enhanced, whereas apoptosis, the RANKL/OPG ratio, and TNF-α expression were significantly attenuated, by Dkk-1 silencing. Dkk-1 expression increased and the effects of Dkk-1 silencing were reversed when exogenous TNF-α was added. Mechanically, TNF-α crosstalked with Dkk-1 through ERK signaling in MC3T3E1 cells. ERK signaling blockade impaired Dkk-1-induced TNF-α expression and TNF-α-mediated Dkk-1 expression. Dkk-1 and TNF-α crosstalked, partially through ERK signaling, in MC3T3E1 cells under compressive/tensile strain, synergistically modulating various biological behaviors of the cells. These findings not only provide mechanical insight into the cellular events and molecular regulation of orthodontic tooth movement (OTM), but also aid the development of novel strategies to accelerate OTM.

Imeglimin profoundly affects the circadian clock in mouse embryonic fibroblasts.

OBJECTIVE: Imeglimin is a novel antidiabetic drug structurally related to metformin. Metformin has been shown to modulate the circadian clock in rat fibroblasts. Accordingly, in the present study, we aimed to determine whether imeglimin can impact the circadian oscillator in mouse embryonic fibroblasts (MEFs). METHODS: MEFs carrying a Bmal1-Emerald luciferase (Bmal1-ELuc) reporter were exposed to imeglimin (0.1 or 1 mM), metformin (0.1 or 1 mM), a nicotinamide phosphoribosyltransferase inhibitor FK866, and/or vehicle. Subsequently, Bmal1-ELuc expression and clock gene mRNA expression levels were measured at 10-min intervals for 55 h and 4-h intervals for 32 h, respectively. RESULTS: Imeglimin significantly prolonged the period (from 26.3 to 30.0 h at 0.1 mM) and dose-dependently increased the amplitude (9.6-fold at 1 mM) of the Bmal1-ELuc expression rhythm; however, metformin exhibited minimal effects on these parameters. Moreover, imeglimin notably impacted the rhythmic mRNA expression of clock genes (Bmal1, Per1, and Cry1). The concurrent addition of FK866 partly inhibited the effects of imeglimin on both Bmal1-ELuc expression and clock gene mRNA expression. CONCLUSION: Collectively, these results reveal that imeglimin profoundly affects the circadian clock in MEFs. Further studies are needed to evaluate whether imeglimin treatment could exert similar effects in vivo.

Quercetin promotes autophagy to alleviate cigarette smoke-related periodontitis.

BACKGROUND AND OBJECTIVES: Cigarette smoking has been reported as an independent risk factor for periodontitis. Tobacco toxins affect periodontal tissue not only locally but also systemically, leading to the deterioration and recurrence of periodontitis. However, the mechanism of cigarette smoke-related periodontitis (CSRP) is unclear and thus lacks targeted treatment strategies. Quercetin, a plant-derived polyphenolic flavonoid, has been reported to have therapeutic effects on periodontitis due to its documented antioxidant activity. This study aimed to evaluate the effects of quercetin on CSRP and elucidated the underlying mechanism. METHODS: The cigarette smoke-related ligature-induced periodontitis mouse model was established by intraperitoneal injection of cigarette smoke extract (CSE) and silk ligation of bilateral maxillary second molars. Quercetin was adopted by gavage as a therapeutic strategy. Micro-computed tomography was used to evaluate the alveolar bone resorption. Immunohistochemistry detected the oxidative stress and autophagy markers in vivo. Cell viability was determined by Cell Counting Kit-8, and oxidative stress levels were tested by 2,7-dichlorodihydrofluorescein diacetate probe and lipid peroxidation malondialdehyde assay kit. Alkaline phosphatase and alizarin red staining were used to determine osteogenic differentiation. Network pharmacology analysis, molecular docking, and western blot were utilized to elucidate the underlying molecular mechanism. RESULTS: Alveolar bone resorption was exacerbated and oxidative stress products were accumulated during CSE exposure in vivo. Oxidative stress damage induced by CSE caused inhibition of osteogenic differentiation in vitro. Quercetin effectively protected the osteogenic differentiation of human periodontal ligament cells (hPDLCs) and periodontal tissue by upregulating the expression of Beclin-1 thus to promote autophagy and reduce oxidative stress damage. CONCLUSION: Our results established a role of oxidative stress damage and autophagy dysfunction in the mechanism of CSE-induced destruction of periodontal tissue and hPDLCs, and provided a potential application value of quercetin to ameliorate CSRP.

Endoscopic submucosal dissection for anastomotic lesions after colorectal surgery.

BACKGROUND: Endoscopic submucosal dissection (ESD) for anastomotic lesions is technically challenging. We aimed to characterize the clinicopathologic characteristics, feasibility, and effectiveness of ESD for anastomotic lesions of the lower gastrointestinal tract. METHOD: We retrospectively investigated 55 patients with anastomotic lesions of the lower gastrointestinal tract who underwent ESD from February 2008 to January 2021. The lesions involving one or both sides of anastomoses were classified into the unilaterally involving anastomosis (UIA) or straddling anastomosis (SA) group, respectively. We collected clinicopathological characteristics, procedure-related parameters and outcomes, and follow-up data and analyzed the impact of anastomotic involvement. RESULTS: The mean age was 62.5 years, and the median procedure duration was 30 min. The rates of en bloc resection and R0 resection were 90.9% and 85.5%, respectively. Four patients (7.3%) experienced major adverse events (AEs). During a median follow-up of 66 months (range 14-169), seven patients had local recurrence, and six patients had metastases. The 5-year disease-free survival and overall survival rates were 82.4% and 90.7%, respectively. The 5-year disease -specific survival (DSS) rate was 93.3%. Compared with the UIA group, the SA group had significantly longer procedure duration, larger specimen, lower rates of en bloc resection and R0 resection, and shorter disease-free survival (all P < 0.05). However, rates of AEs did not differ significantly between the two groups. CONCLUSIONS: The short-term and long-term outcomes of ESD for colorectal anastomotic lesions were favorable. Although with technically challenging, ESD could be performed safely and effectively for lesions at the anastomoses.

Endoscopic submucosal dissection for lesions involving the anastomosis after upper gastrointestinal surgery.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) for anastomotic lesions is technically challenging due to severe fibrosis, deformity, staples, and limited space for procedure. We aimed to characterize the clinicopathological characteristics, feasibility, and effectiveness of ESD for anastomotic lesions of the upper gastrointestinal tract. METHODS: We retrospectively investigated 43 patients with lesions involving the anastomoses of the upper GI tract who underwent ESD from April 2007 to February 2021. We collected clinicopathological characteristics, procedure­related parameters and outcomes, and follow­up data and analyzed the impact of anastomotic involvement. RESULTS: The median duration from previous upper GI surgery was 60 months and the median procedure duration was 30 min. The rate of en bloc resection and en bloc with R0 resection was 90.7% and 81.4%, respectively. Two patients (4.7%) experienced major adverse events, including delayed bleeding and febrile episode. During a median follow-up of 80 months, 3 patients had local recurrence and 4 patients had metastases. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 89.6% and 95.1%, respectively. Compared with the unilaterally involving group, the straddling anastomosis group had significantly longer procedure duration, larger specimen, lower rates of en bloc resection and en bloc with R0 resection, and shorter DFS and OS (all P < 0.05). However, rates of adverse events did not differ significantly between the two groups. CONCLUSIONS: The short­ and long-term outcomes of ESD for upper GI anastomotic lesions were favorable. Although with technically challenging, ESD could be performed safely and effectively for anastomotic lesions.

Nanotube patterning reduces macrophage inflammatory response via nuclear mechanotransduction.

The inflammatory immune environment surrounding titanium bone implants determines the formation of osseointegration, and nanopatterning on implant surfaces modulates the immune microenvironment in the implant region. Among many related mechanisms, the mechanism by which nanopatterning controls macrophage inflammatory response still needs to be elucidated. In this paper, we found that inhibition of the nuclear envelope protein lamin A/C by titania nanotubes (TNTs) reduced the macrophage inflammatory response. Knockdown of lamin A/C reduced macrophage inflammatory marker expression, while overexpression of lamin A/C significantly elevated inflammatory marker expression. We further found that suppression of lamin A/C by TNTs limited actin polymerization, thereby reducing the nuclear translocation of the actin-dependent transcriptional cofactor MRTF-A, which subsequently reduced the inflammatory response. In addition, emerin, which is a key link between lamin A/C and actin, was delocalized from the nucleus in response to mechanical stimulation by TNTs, resulting in reduced actin organization. Under inflammatory conditions, TNTs exerted favourable osteoimmunomodulatory effects on the osteogenic differentiation of mouse bone marrow-derived stem cells (mBMSCs) in vitro and osseointegration in vivo. This study shows and confirms for the first time that lamin A/C-mediated nuclear mechanotransduction controls macrophage inflammatory response, and this study provides a theoretical basis for the future design of immunomodulatory nanomorphologies on the surface of metallic bone implants.

Cox-nnet v2.0: improved neural-network-based survival prediction extended to large-scale EMR data.

SUMMARY: Cox-nnet is a neural-network-based prognosis prediction method, originally applied to genomics data. Here, we propose the version 2 of Cox-nnet, with significant improvement on efficiency and interpretability, making it suitable to predict prognosis based on large-scale population data, including those electronic medical records (EMR) datasets. We also add permutation-based feature importance scores and the direction of feature coefficients. When applied on a kidney transplantation dataset, Cox-nnet v2.0 reduces the training time of Cox-nnet up to 32-folds (n =10 000) and achieves better prediction accuracy than Cox-PH (P<0.05). It also achieves similarly superior performance on a publicly available SUPPORT data (n=8000). The high efficiency and accuracy make Cox-nnet v2.0 a desirable method for survival prediction in large-scale EMR data. AVAILABILITY AND IMPLEMENTATION: Cox-nnet v2.0 is freely available to the public at https://github.com/lanagarmire/Cox-nnet-v2.0. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Type of non-reciprocity in a fiber Sagnac interferometer induced by geometric phases.

The non-reciprocity of a Sagnac interferometer provides ultra-high sensitivity for parameter estimation and offers a wide range of applications, especially for optical fiber sensing. In this work, we study a new type of non-reciprocity existing in an optical fiber Sagnac interferometer where the polarization dependent loss is taken into consideration. In particular, this non-reciprocity is irrelevant to the physical effects that have been considered in previous studies, which originates from the geometric phases induced by a continuous-weak-measurement. Thus, it has a unique phenomenon of sudden phase transition, which may open a new way for the future design of high precision optical fiber sensors.

Luteolin attenuates glucocorticoid-induced osteoporosis by regulating ERK/Lrp-5/GSK-3ß signaling pathway in vivo and in vitro.

Glucocorticoid-induced osteoporosis (GIO) is a secondary osteoporosis with extensive use of glucocorticoids (GCs). GCs can increase bone fragility and fracture via inhibiting osteoblastic proliferation and differentiation. Luteolin (LUT), a kind of plant flavonoid, has been reported to exhibit the antioxidant activity, but the effects of LUT on GIO still remain unclear. This study aimed to investigate the effects of LUT on GIO both in vivo and in vitro and elaborate the potential molecular mechanisms. LUT increased the superoxide dismutase activity, glutathione level and decreased reactive oxygen species (ROS) level and lactate dehydrogenase release in GIO. Meanwhile, LUT decreased caspase-3, caspase-9, and Bax protein expressions and increased Bcl-2 protein expression in GIO. LUT increased the ratio of osteoprotegerin (OPG)/receptor activator of nuclear factor-κB Ligand (RANKL) messenger RNA (mRNA) expression and mRNA expression levels of osteogenic markers, including runt-related transcription factor 2, osterix, collagen type I, and osteocalcin. LUT also enhanced the extracellular signal-regulated kinases (ERK) phosphorylation, glycogen synthase kinase 3ß (GSK-3ß) phosphorylation, mRNA expression levels of lipoprotein-receptor-related protein 5 (Lrp-5) and ß-catenin. Further study revealed that Lrp-5 small interfering RNA (siRNA )and ERK-siRNA reduced the effects of LUT on GSK-3ß phosphorylation, alkaline phosphatase (ALP) activity and the ratio of OPG/RANKL mRNA expression. Moreover, ERK-siRNA decreased Lrp-5 mRNA expression in vitro. These results indicated that LUT promoted proliferation by attenuating oxidative stress and promoted osteoblastic differentiation by regulating the ERK/Lrp-5/GSK-3ß pathway in GIO. This study may bring to light the possible mechanisms involved in the action of LUT in GIO treatment, and benefit for further research on GIO.

A Nickel(II) Nitrite Based Molecular Perovskite Ferroelectric.

The X-site ion in organic-inorganic hybrid ABX3 perovskites (OHPs) varies from halide ion to bridging linkers like HCOO- , N3 - , NO2 - , and CN- . However, no nitrite-based OHP ferroelectrics have been reported so far. Now, based on non-ferroelectric [(CH3 )4 N][Ni(NO2 )3 ], through the combined methodologies of quasi-spherical shape, hydrogen bonding functionality, and H/F substitution, we have successfully synthesized an OHP ferroelectric, [FMeTP][Ni(NO2 )3 ] (FMeTP=N-fluoromethyl tropine). As an unprecedented nitrite-based OHP ferroelectric, the well-designed [FMeTP][Ni(NO2 )3 ] undergoes the ferroelectric phase transition at 400 K with an Aizu notation of 6/mmmFm, showing multiaxial ferroelectric characteristics. This work is a great step towards not only enriching the molecular ferroelectric families but also accelerating the potential practical applications.

Efficacy and safety of endoscopic submucosal dissection for submucosal tumors of the colon and rectum.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) of colorectal submucosal tumors (SMTs) is becoming increasingly common; however, there have been few large consecutive studies analyzing its therapeutic efficacy and safety. The aim of this study was to evaluate the efficacy, safety, and long-term outcomes of ESD for colorectal SMTs. METHODS: This retrospective study included 412 consecutive patients with colorectal SMTs who underwent ESD at the Zhongshan Hospital of Fudan University from January 2008 to July 2014. Tumor histopathology, completeness of resection, adverse events, tumor recurrence, and distant metastasis were analyzed. RESULTS: Complete resection was achieved for 358 lesions (86.9%). Thirteen patients had serious adverse events (3.2%) including bleeding and perforation, and 28 patients (6.8%) had post-ESD electrocoagulation syndrome (PEECS). Because more ESDs for colorectal SMTs were performed by endoscopists, the rate of complete resection increased (78.5% vs 88.5%), and the rate of serious adverse events decreased (9.2% vs 2.0%). SMTs in the colon increased the risk of incomplete resection (19.6% vs 11.3%), serious adverse events (8.7% vs 1.6%), and PEECS (16.3% vs 4.1%). SMTs originating from the muscularis propria and sized ≥20 mm increased the rate of PEECS (22.7% vs 5.9% and 31.3% vs 5.8%, respectively). CONCLUSION: ESD is effective for resection of colorectal SMTs and rarely causes serious adverse events. Tumor location and the experience of endoscopists influence the complete resection rate and the development of serious adverse events. ESD is feasible for large tumors and tumors in the muscularis propria, but this is associated with relatively high risks of adverse events.

Value of CT Density Measurements in Distinguishing Parathyroid Adenoma,Thyroid,and Lymph Node.

Objective To explore the value of multi-phase contrast-enhanced computed tomography in the differential diagnosis of parathyroid adenoma,lymph node,and thyroid. Methods The enhanced multi-slice CT (MSCT) results of 21 parathyroid adenoma patients were analyzed,and their postoperative pathological specimens were examined. During the MSCT,the plain CT scan was recorded,along with the density of thyroid adenoma,lymph nodes,and thyroid at 35 s and 65 s (D0,D35,D65) following the injection of contrast medium. Results During the D0 phase,there was significant difference in CT values between the parathyroid adenoma and thyroid parenchyma[(45?12) HU vs.(90?15)HU,P=0.007]. According to ROC curve,75 HU,with 95.2% sensitivity and specificity,was the critical value for distinguishing the density of parathyroid adenoma and that of thyroid parenchyma. At 35 s following the injection of contrast medium,there was significant difference in the enhancement degree between parathyroid adenoma and lymph node[(182?39) HU vs.(80?20)HU,P=0.004]. According to ROC curve,111 HU,with 95.2 % sensitivity and specificity,was the critical value for distinguishing the density of parathyroid adenoma and that of lymph node 35 s following the injection of contrast medium. At 35 s to 65 s following the injection of contrast medium,the parathyroid adenoma experienced a decline in density,which was dramatically different from parathyroid adenoma,however,lymph node experienced a rise in density. Conclusion Enhanced CT measurements at different time points enable the differentiation among parathyroid adenomas,lymph nodes,and thyroid.

Field and long-term demonstration of a wide area quantum key distribution network.

A wide area quantum key distribution (QKD) network deployed on communication infrastructures provided by China Mobile Ltd. is demonstrated. Three cities and two metropolitan area QKD networks were linked up to form the Hefei-Chaohu-Wuhu wide area QKD network with over 150 kilometers coverage area, in which Hefei metropolitan area QKD network was a typical full-mesh core network to offer all-to-all interconnections, and Wuhu metropolitan area QKD network was a representative quantum access network with point-to-multipoint configuration. The whole wide area QKD network ran for more than 5000 hours, from 21 December 2011 to 19 July 2012, and part of the network stopped until last December. To adapt to the complex and volatile field environment, the Faraday-Michelson QKD system with several stability measures was adopted when we designed QKD devices. Through standardized design of QKD devices, resolution of symmetry problem of QKD devices, and seamless switching in dynamic QKD network, we realized the effective integration between point-to-point QKD techniques and networking schemes.

Serum trypsin and TCR as novel markers for predicting disease activity in IgG4-related disease.

BACKGROUND: IgG4-related disease (IgG4-RD) is a novel disease named in recent years. Because of its varied clinical manifestations, like tumor but not tumor, it brings a great challenge to clinical diagnosis. Trypsin and T-cell receptor (TCR) are thought to mediate the regulation of B cell maturation, survival and antibody production. In this study, we investigated the clinical features and important novel markers of IgG4-RD. MATERIAL AND METHODS: A prospective cohort study of 22 patients with IgG4-RD was carried out from May 2009 to December 2012, and 65 cases with acute pancreatitis, 60 cases with pancreatic cancer and 120 healthy individuals were studied as controls. Serum TCR, trypsin and IgG4 levels were measured during pre- and post-treatment in the patients with IgG4-RD and their correlations with IgG4 were also assessed. RESULTS: Serum IgG4 and IgE levels in all patients were significantly increased, and tumor markers (carbohydrate antigen 19-9 and/or carbohydrate antigen 125) were also increased (12/22). Serum trypsin in patients with IgG4-RD was lower than in the ones with acute pancreatitis, pancreatic cancer, and healthy individuals. But serum TCR of IgG4-RD was significantly higher than in the pancreatic cancer group and normal controls and it was inversely correlated with the levels of IgG4 (r = -3.160, p = 0.042). CONCLUSIONS: The results indicate that serum TCR and trypsin might be useful markers for predicting disease activity in IgG4-RD.