Distinct neuronal types contribute to hybrid temporal encoding strategies in primate auditory cortex.

Studies of the encoding of sensory stimuli by the brain often consider recorded neurons as a pool of identical units. Here, we report divergence in stimulus-encoding properties between subpopulations of cortical neurons that are classified based on spike timing and waveform features. Neurons in auditory cortex of the awake marmoset (Callithrix jacchus) encode temporal information with either stimulus-synchronized or nonsynchronized responses. When we classified single-unit recordings using either a criteria-based or an unsupervised classification method into regular-spiking, fast-spiking, and bursting units, a subset of intrinsically bursting neurons formed the most highly synchronized group, with strong phase-locking to sinusoidal amplitude modulation (SAM) that extended well above 20 Hz. In contrast with other unit types, these bursting neurons fired primarily on the rising phase of SAM or the onset of unmodulated stimuli, and preferred rapid stimulus onset rates. Such differentiating behavior has been previously reported in bursting neuron models and may reflect specializations for detection of acoustic edges. These units responded to natural stimuli (vocalizations) with brief and precise spiking at particular time points that could be decoded with high temporal stringency. Regular-spiking units better reflected the shape of slow modulations and responded more selectively to vocalizations with overall firing rate increases. Population decoding using time-binned neural activity found that decoding behavior differed substantially between regular-spiking and bursting units. A relatively small pool of bursting units was sufficient to identify the stimulus with high accuracy in a manner that relied on the temporal pattern of responses. These unit type differences may contribute to parallel and complementary neural codes.

Male vitellogenin regulates gametogenesis through a testis-enriched big protein in Chrysopa pallens.

In insects, vitellogenin (Vg) is generally viewed as a female-specific protein. Its primary function is to supply nutrition to developing embryos. Here, we reported Vg from the male adults of a natural predator, Chrysopa pallens. The male Vg was depleted by RNAi. Mating with Vg-deficient male downregulated female Vg expression, suppressed ovarian development and decreased reproductive output. Whole-organism transcriptome analysis after male Vg knockdown showed no differential expression of the known spermatogenesis-related regulators and seminal fluid protein genes, but a sharp downregulation of an unknown gene, which encodes a testis-enriched big protein (Vcsoo). Separate knockdown of male Vg and Vcsoo disturbed the assembly of spermatid cytoplasmic organelles in males and suppressed the expansion of ovary germarium in mated females. These results demonstrated that C. pallens male Vg signals through the downstream Vcsoo and regulates male and female reproduction.

Spatiotemporal Acoustic Vortex Beams with Transverse Orbital Angular Momentum.

Recently, the discovery of optical spatiotemporal (ST) vortex beams with transverse orbital angular momentum (OAM) has attracted increasing attention and is expected to extend the research scope and open new opportunities for practical applications of OAM states. The ST vortex beams are also applicable to other physical fields that involve wave phenomena, and here we develop the ST vortex concept in the field of acoustics and report the generation of Bessel-type ST acoustic vortex beams. The ST vortex beams are fully characterized using the scalar approach for the pressure field and the vector approach for the velocity field. We further investigate the transverse spreading effect and construct ST vortex beams with an ellipse-shaped spectrum to reduce the spreading effect. We also experimentally demonstrated the orthogonality relations between ST vortex beams with different charges. Our study successfully demonstrates the versatility of the acoustic system for exploring and discovering spatiotemporally structured waves, inspiring further investigation of exotic wave physics.

NAPSB as a predictive marker for prognosis and therapy associated with an immuno-hot tumor microenvironment in hepatocellular carcinoma.

BACKGROUND: Napsin B Aspartic Peptidase, Pseudogene (NAPSB) was associated with CD4 + T cell infiltration in pancreatic ductal adenocarcinoma. However, the biological role of NAPSB in hepatocellular carcinoma (HCC) remains to be determined. METHODS: The expression of NAPSB in HCC as well as its clinicopathological association were analyzed using data from several public datasets. qRT-PCR was used to verify the relative expression of NAPSB in patients with HCC using the Zhongnan cohort. Kaplan-Meier analyses, and univariate and multivariate Cox regression were conducted to determine the prognosis value of NAPSB on patients with HCC. Then enrichment analyses were performed to identify the possible biological functions of NAPSB. Subsequently, the immunological characteristics of NAPSB in the HCC tumor microenvironment (TME) were demonstrated comprehensively. The role of NAPSB in predicting hot tumors and its impact on immunotherapy and chemotherapy responses was also analyzed by bioinformatics methods. RESULTS: NAPSB was downregulated in patients with HCC and high NAPSB expression showed an improved survival outcome. Enrichment analyses showed that NAPSB was related to immune activation. NAPSB was positively correlated with immunomodulators, tumor-infiltrating immune cells, T cell inflamed score and cancer-immunity cycle, and highly expressed in immuno-hot tumors. High expression of NAPSB was sensitive to immunotherapy and chemotherapy, possibly due to its association with pyroptosis, apoptosis and necrosis. CONCLUSIONS: NAPSB was correlated with an immuno-hot and inflamed TME, and tumor cell death. It can be utilized as a promising predictive marker for prognosis and therapy in HCC.

[Prediction of anti-liver fibrosis effect of Piperis Longi Fructus based on network pharmacology].

Network pharmacology and liver fibrosis(LF) model in vitro were used to analyze the underly mechanism of anti-liver fibrosis effect that induced by Piperis Longi Fructus and its major active compounds. TCMSP and TCMIP were used to search for the chemical constituents of Piperis Longi Fructus, as well as the oral bioavailability(OB), drug-likeness(DL), intercellular permeability of intestinal epithelial cells(Caco-2) and Drug-likeness grading were set as limiting conditions. The related target genes of Piperis Longi Fructus were queried by TCMSP database, while related targets of LF were screened by GeneCards databases. Interaction network was constructed using Cytoscape 3.7.1. These above data were imported into STRING database for PPI network analysis. Enrichment of gene ontology(GO) and pathway analysis(KEGG) within Bioconductor database were utilized to note functions of related targets of Piperis Longi Fructus. Finally, the core targets and pathways were preliminarily verified by in vitro experiments. The effects of piperlongumine(PL), the major active component of Piperis Longi Fructus, on proliferation of rat liver stellate cells(HSC-T6) and expression of α smooth muscle actin(α-SMA) and collagen Ⅰ were investigated. The major factors TNF-α of tumor necrosis factor(TNF) pathway and NF-κB p65, IL-6 protein expressions of LF process were examined. A total of 12 active compounds such as PL were obtained by analyzing the bioavailability and drug-like properties, which inferred to 48 targets. The functional enrichment analysis of GO obtained 1 240 GO items, mainly involving in process of biology and molecular function. A total of 99 signaling pathways were enriched in the KEGG pathway enrichment analysis, including TNF signaling pathway, cGMP-PKG signaling pathway, calcium signaling pathways. CCK-8 assay showed that PL inhibited proliferation of HSC-T6 induced by transforming growth factor-ß1(TGF-ß1). Western blot analysis found that treated with PL suppressed the protein expressions of α-SMA, collagen Ⅰ, TNF-α and p65 in HSC-T6. Enzyme linked immunosorbent assay(ELISA) showed that PL inhibited the expressions of TNF-α and IL-6 in the cluture supertant of HSC-T6 cells. In conclusion, PL could play an anti-liver fibrosis role by regulating TNF/NF-κB signaling pathway. This study provided the mechanism basis of anti-LF effects induced by Piperis Longi Fructus and its major active compounds, which might help for the further study of the mechanism and key targets of Piperis Longi Fructus.

To construct a ceRNA regulatory network as prognostic biomarkers for bladder cancer.

Emerging evidence demonstrates that competing endogenous RNA (ceRNA) hypothesis has played a role in molecular biological mechanisms of cancer occurrence and development. But the effect of ceRNA network in bladder cancer (BC), especially lncRNA-miRNA-mRNA regulatory network of BC, was not completely expounded. By means of The Cancer Genome Atlas (TCGA) database, we compared the expression of RNA sequencing (RNA-Seq) data between 19 normal bladder tissue and 414 primary bladder tumours. Then, weighted gene co-expression network analysis (WGCNA) was conducted to analyse the correlation between two sets of genes with traits. Interactions between miRNAs, lncRNAs and target mRNAs were predicted by MiRcode, miRDB, starBase, miRTarBase and TargetScan. Next, by univariate Cox regression and LASSO regression analysis, the 86 mRNAs obtained by prediction were used to construct a prognostic model which contained 4 mRNAs (ACTC1 + FAM129A + OSBPL10 + EPHA2). Then, by the 4 mRNAs in the prognostic model, a ceRNA regulatory network with 48 lncRNAs, 14 miRNAs and 4 mRNAs was constructed. To sum up, the ceRNA network can further explore gene regulation and predict the prognosis of BC patients.

Strong Correlation between the Expression of CHEK1 and Clinicopathological Features of Patients with Multiple Myeloma.

Multiple myeloma (MM) is one of the most common malignancies, and the clinical outcome of patients with MM remains poor. Our objective is to screen biomarkers correlated with clinicopathological features and survival of patients with MM. A gene co-expression network was constructed to screen hub genes related to the three stages in the International Staging System (ISS) of MM. Functional analysis and protein-protein interaction analysis of the hub genes was performed. CHEK1, a gene most related to the ISS stages of MM, was selected for further clinical validation. A total of 780 hub genes correlated with ISS stages of MM were identified. Functional enrichment analysis of hub genes suggested that these genes were mostly enriched in several gene ontology (GO) terms and pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) that were involved in cell proliferation and immune response. Expression of the gene for the protein checkpoint kinase I (CHEK1) was increased in MM cells from newly diagnosed patients (P = 0.0304) and relapsed patients (P = 0.0002) as compared to normal plasma cells. Meanwhile, CHEK1 was increased more in MM patients with stage II disease (P = 0.0321) and stage III disease (P = 0.0076) than in those with stage I disease. Survival analysis indicated that MM patients in the group characterized by low CHEK1 expression were associated with better clinical outcomes in terms of time to progression, event-free survival, and overall survival. High expression of CHEK1 predicted poor clinical characteristics of MM patient, and our results indicate that it can be considered a biomarker for the diagnosis of MM.

Design, synthesis, and biological evaluation of a novel indoleamine 2,3-dioxigenase 1 (IDO1) and thioredoxin reductase (TrxR) dual inhibitor.

Targeting the Trp-Kyn pathway is an attractive approach for cancer immunotherapy. Thioredoxin reductase (TrxR) enzymes are reactive oxygen species (ROS) modulators that are involved in the tumor cell growth and survival processes. The 4-phenylimidazole scaffold is well-established as useful for indoleamine 2,3-dioxygenase 1 (IDO1) inhibition, while piperlongumine (PL) and its derivatives have been reported to be inhibitors of TrxR. To take advantage of both immunotherapy and TrxR inhibition, we designed a first-generation dual IDO1 and TrxR inhibitor (ZC0101) using the structural combination of 4-phenylimidazole and PL scaffolds. ZC0101 exhibited better dual inhibition against IDO1 and TrxR in vitro and in cell enzyme assays than the uncombined forms of 4-phenylimidazole and PL. It also showed antiproliferative activity in various cancer cell lines, and a selective killing effect between normal and cancer cells. Furthermore, ZC0101 effectively induced apoptosis and ROS accumulation in cancer cells. Knockdown of TrxR1 and IDO1 expression induced cellular enzyme inhibition and ROS accumulation effects during ZC0101 treatment, but only reduced TrxR1 expression was able to improve ZC0101's antiproliferation effect. This proof-of-concept study provides a novel strategy for cancer treatment. ZC0101 represents a promising lead compound for the development of novel antitumor agents that can also be used as a valuable probe to clarify the relationships and mechanisms of cancer immunotherapy and ROS modulators.

Genome-wide analysis reveals alcohol dehydrogenase 1C and secreted phosphoprotein 1 for prognostic biomarkers in lung adenocarcinoma.

To seek out novel promising biomarkers for predicting lung adenocarcinoma (LUAD) prognosis, we conducted this study. First, 279 upregulated and 37 downregulated differentially expressed genes were obtained from LUAD and para-carcinoma tissues by the Affymetrix GeneChip Human Transcriptome Array. Then, we randomly classified samples of LUAD data set GSE31210 as training and testing sets in a 1:1 ratio. Alcohol dehydrogenase 1C (ADH1C) and secreted phosphoprotein 1 (SPP1) were finally identified correlating with the LUAD survival through least absolute shrinkage and selection operator penalized Cox proportion hazards regression model, and applied to build a 2-gene signature related to prognosis in training set. Univariate and multivariable survival analyses suggested that overall survival (OS) and relapse-free survival (RFS) in the 2-gene signature low-risk group were better than the high-risk group. Kaplan-Meier curves proved that elevated ADH1C expression and reduced SPP1 expression were related to better OS and RFS. Besides, the SPP1 expressed higher in LUAD than para-carcinoma tissues using quantitative reverse transcription polymerase chain reaction assay. Finally, the association between the two genes and clinicopathological parameters in 80 LUAD were analyzed, it is suggested that SPP1 was relevant to epidermal growth factor receptor mutation. These findings indicated that ADH1C and SPP1 might be novel promising biomarkers for predicting LUAD prognosis.

Four novel biomarkers for bladder cancer identified by weighted gene coexpression network analysis.

Bladder cancer (BC) is one of the most malignancies in terms of incidence and recurrence worldwide. The aim of this study is to find out novel and prognostic biomarkers for patients with BC. First, we identified 258 differentially expressed genes by using GSE19915 from Gene Expression Omnibus database. Second, a total of 33 modules were identified by constructing a coexpression network by using weighted gene coexpression network analysis and yellow module was regarded as the key module. Furthermore, by constructing protein-protein interaction networks, we preliminarily picked out 13 genes. Among them, four hub genes (CCNB1, KIF4A, TPX2, and TRIP13) were eventually identified by using five different methods (survival analysis, one-way analysis of variance, the Spearman correlation analysis, receiver operating characteristic curve, and expression value comparison), which were significantly correlated with the prognosis of BC. The validation of transcriptional and translational levels made sense (based on Oncomine and The Human Protein Atlas database). Moreover, functional enrichment analysis suggested that all the hub genes played crucial roles in chromosome segregation, sister chromatid segregation, nuclear chromosome segregation, mitotic nuclear division, nuclear division, and organelle fission during cell mitosis. In addition, three of the hub genes (KIF4A, TPX2, and TRIP13) might be potential targets of cancer drugs according to the results of the genetical alteration. In conclusion, this study indicates that four hub genes have great predictive value for the prognosis of BC, and may contribute to the exploration of the further and more in-depth research of BC.

Shape-based virtual screen for the discovery of novel CDK8 inhibitor chemotypes.

With the aim of discovering novel cyclin-dependent kinase 8 (CDK8) inhibitors, a combined similarity search and molecular docking approach was employed, which led to 32 hits. Biological tests led to the discovery of several novel submicromolar inhibitors. In particular, compound C768-0769 (ZC0201) showed good CDK8 inhibitory activity, and compound ZC0201 effectively suppressed HCT-116 colorectal cancer cell proliferation by inducing G1/S transition arrest. Furthermore, modulation of phosphorylated signal transducer and activator of transcription 1 (Ser 727) (STAT1SER727), a pharmacodynamic biomarker of CDK8 activity, demonstrated that ZC0201 may cause G1/S transition arrest through CDK8 activity inhibition. Due to its good cellular activity, ZC0201 may be an ideal lead compound for further modification as a potential cancer therapeutic agent.

Coil Embolization for Persistent Thoracic False Lumen of Type B Aortic Dissection after Thoracic Endovascular Aortic Repair.

BACKGROUND: The natural history of the thoracic false lumen after coil embolization for type B aortic dissection (TBAD) treated by previous thoracic endovascular aortic repair (TEVAR) remains a matter of debate. The aim of this study is to assess the efficacy of coil embolization in promoting thoracic aortic remodeling of TBAD with persistent thoracic false lumen after TEVAR. METHODS: Between January 2015 and December 2016, 7 consecutive TBAD patients with persistent thoracic false lumen post-TEVAR underwent coil embolization, either isolated (3 with maximum thoracic aortic diameter <55 mm) or combined with adjunctive procedure(s) specifically for distal re-entry tears (4 with thoracic aneurysmal aortic dissection ≥55 mm in diameter). Pre- and postcoiling computer tomography angiography (CTA) images were used to evaluate aortic remodeling via false lumen thrombosis status and maximum thoracic aorta diameter. RESULTS: Procedures were performed successfully in all patients, without intraoperative complications or 30-day mortality. Two dissection-related deaths occurred after hospital discharge, yielding a 6-month mortality of 28.6%. Six patients had surveillance CTA images available for analyses at median 11.2 months (range 5.6-23.5) of follow-up. Thoracic aortic shrinkage and completely thrombosed thoracic false lumen were seen in 1 patient (16.7%); thoracic aortic stabilization albeit with persistent blood flow along the false lumen below or even more proximal to the embolization in 4 patients (66.7%); and continued thoracic aortic growth and aortoesophageal fistula proximal to the embolized false lumen in 1 patient. CONCLUSIONS: In this retrospective single center experience, the efficacy of coil embolization in promoting thoracic aortic remodeling of TBAD with persistent thoracic false lumen post-TEVAR appears to be limited, especially in patients with thoracic aneurysmal aortic dissection. Further studies are warranted to inform the optimal treatment strategy.

Photonic topological insulator with broken time-reversal symmetry.

A topological insulator is a material with an insulating interior but time-reversal symmetry-protected conducting edge states. Since its prediction and discovery almost a decade ago, such a symmetry-protected topological phase has been explored beyond electronic systems in the realm of photonics. Electrons are spin-1/2 particles, whereas photons are spin-1 particles. The distinct spin difference between these two kinds of particles means that their corresponding symmetry is fundamentally different. It is well understood that an electronic topological insulator is protected by the electron's spin-1/2 (fermionic) time-reversal symmetry [Formula: see text] However, the same protection does not exist under normal circumstances for a photonic topological insulator, due to photon's spin-1 (bosonic) time-reversal symmetry [Formula: see text] In this work, we report a design of photonic topological insulator using the Tellegen magnetoelectric coupling as the photonic pseudospin orbit interaction for left and right circularly polarized helical spin states. The Tellegen magnetoelectric coupling breaks bosonic time-reversal symmetry but instead gives rise to a conserved artificial fermionic-like-pseudo time-reversal symmetry, Tp ([Formula: see text]), due to the electromagnetic duality. Surprisingly, we find that, in this system, the helical edge states are, in fact, protected by this fermionic-like pseudo time-reversal symmetry Tp rather than by the bosonic time-reversal symmetry Tb This remarkable finding is expected to pave a new path to understanding the symmetry protection mechanism for topological phases of other fundamental particles and to searching for novel implementations for topological insulators.

Simple Chip Electrophoresis Titration of Neutralization Boundary with EDTA Photocatalysis for Distance-Based Sensing of Melamine in Dairy Products.

Melamine was sometimes adulterated to dairy products for false protein content increase in developing countries. However, a portable sensor has not been developed for on-spot determination of melamine in dairy products yet. Herein, a distance-based sensor was advanced for the quantification of melamine in dairy products based on chip electrophoretic titration (ET) of moving neutralization boundary (NB) and EDTA photocatalysis. In the chip sensor, EDTA, H2O2, and leucomalachite green (LMG) were added in the anode well. Under UV light, EDTA photocatalyzes H2O2 and colorless LMG as H2O and color malachite green (MG) with one positive charge. When applying an electric field, the MG in the anode well migrated into the channel and was neutralized with the base in the channel, resulting in colorless MG-OH and NB. If the melamine-content dairy sample was added into the EDTA-H2O2-LMG system, H2O2 reacts with melamine, leading to the decrease of MG. Thus, the higher the melamine content in dairy products, the shorter the distance of NB migration under the given time, implying a distance-based sensor of melamine. A series of experiments manifested the validity of ET-NB sensor for detection of melamine. Moreover, the results revealed the numerous merits of ET-NB sensor, such as good selectivity, high sensitivity (LOD down to 0.20 µM for milk and 0.10 µM for infant formula vs the FDA safety limits of 20 µM for milk and 8.0 µM for infant formula), good repeatability and recoveries (87-108% for milk, 90-107% for formula). Particularly, the cell phone-like sensor was portable, simple (no any pretreatment), rapid (within 15 min), as well as low cost, to evaluate the quality of dairy products. The developed sensor has great potential in on-spot detection of melamine in dairy products as well as other analytes, at which we are testing in our lab.

Z2 topological edge state in honeycomb lattice of coupled resonant optical waveguides with a flat band.

Two-dimensional (2D) coupled resonant optical waveguide (CROW), exhibiting topological edge states, provides an efficient platform for designing integrated topological photonic devices. In this paper, we propose an experimentally feasible design of 2D honeycomb CROW photonic structure. The characteristic optical system possesses two-fold and three-fold Dirac points at different positions in the Brillouin zone. The effective gauge fields implemented by the intrinsic pseudo-spin-orbit interaction open up topologically nontrivial bandgaps through the Dirac points. Spatial lattice geometries allow destructive wave interference, leading to a dispersionless, near-flat energy band in the vicinity of the three-fold Dirac point in the telecommunication frequency regime. This nontrivial structure with a near-flat band yields topologically protected edge states. These characteristics underpin the fundamental importance as well as the potential applications in various optical devices. Based on the honeycomb CROW lattice, we design the shape-independent topological cavity and the beam splitter, which demonstrate the relevance for a wide range of photonic applications.

High performance ultra-compact SOI waveguide crossing.

Waveguide crossing is an important integrated photonic component that will be routinely used for high-density and large-scale photonic integrated circuits, such as optical switches and routers. Several techniques have been reported in achieving high performance waveguide crossings on a silicon-on-insulator photonic platform, i.e., low-loss and low-crosstalk waveguide crossings based on multimode interference, bi-layer tapering, optical transformation, metamaterials, and subwavelength gratings. Until recently, not much attention has been given to the reduction of the footprint of waveguide crossings. Here we experimentally demonstrate an ultra-compact waveguide crossing on silicon photonic platform with a footprint only ~1 × 1 µm2. Our simulations show that it has a low insertion loss (< 0.175 dB) and low crosstalk (< -37dB) across the whole C-band, while the fabricated one has an insertion loss < 0.28 dB and crosstalk around -30 dB for the C-band.

Baicalein Inhibits Proliferation of Myeloma U266 Cells by Downregulating IKZF1 and IKZF3.

BACKGROUND Baicalein can suppress the growth of multiple tumors, including multiple myeloma (MM), but the exact mechanisms remains elusive. Here, we investigated the exact mechanisms of the anti-myeloma activity of baicalein. MATERIAL AND METHODS Proliferation and rates of apoptosis of myeloma U266 cells exposed to baicalein were detected. Microarray, polymerase chain reaction (PCR) assay, and Western blot analysis were applied to evaluate the mRNA and protein levels of associated molecules. Survival analysis of IKZF1 and IKZF3 was conducted as well. RESULTS Baicalein suppressed the growth and stimulated apoptosis of myeloma U266 cells in a dose- and time-dependent way. Baicalein increased mRNA level of CRBN, and further studies suggested that baicalein downregulated IKZF1 and IKZF3 on a post-transcriptional level. Although the differences did not reach statistical significance, IKZF1 and IKZF3 were associated with poor overall survival. CONCLUSIONS Our results suggest that baicalein suppresses the growth and promotes apoptosis of myeloma U266 cells through downregulating IKZF1 and IKZF3. Baicalein increased the expression of CRBN, which might exert a reversion effect on resistance of IMiDs. MM patients in IKZF1 and IKZF3 low-expression groups had better overall survival than those in IKZF1 and IKZF3 high-expression groups. Thus, the present results indicate that baicalein might be a therapeutic choice for targeting IKZF1 and IKZF3.

The Clinical Relevance of Fragile Histidine Triad Protein (FHIT) in Patients with Bladder Cancer.

BACKGROUND The present study aimed to investigate the clinical relevance of fragile histidine triad protein (FHIT) in patients with bladder cancer (BC). MATERIAL AND METHODS Three independent BC microarray studies were collected and reanalyzed. The expression of FHIT was evaluated between BC samples and normal bladder tissues. The correlation between the expression of FHIT and clinicopathological features was analyzed using the chi-square test. Log-rank based survival analysis was conducted to detect the survival significance of FHIT in patients with BC. Gene set enrichment analysis (GSEA) was performed to identify the mechanisms. RESULTS FHIT was significantly downregulated in BC cells (p=0.0044). BC patients in the FHIT high expression group had better clinical characteristics (including invasiveness, tumor grade, disease progression, and T staging) than those in the FHIT low expression group (p<0.0001, p<0.0001, p=0.031, p<0.0001, and p=0.056, respectively). Patients in the FHIT high expression group had better cancer-specific survival (p<0.0001) and overall survival (p=0.0008) than those in the FHIT low expression. GSEA results indicated that BC samples in the FHIT low expression group were enriched in interferon alpha response, apoptosis, androgen response, interferon gamma response, heme metabolism, and transforming growth facto r(TGF) beta signaling. CONCLUSIONS FHIT predicts better clinical relevance for patients with BC, which may be a promising therapeutic target.

Novel Morphological Features for Prediction of Distal Thoracic Aortic Enlargement after Thoracic Endovascular Aortic Repair of DeBakey IIIb Aortic Dissection.

BACKGROUND: Identifying the risk factors predisposing to aortic enlargement after thoracic endovascular aortic repair (TEVAR) is needed for DeBakey IIIb aortic dissection. The aim of the study is to assess the novel morphological features for DeBakey IIIb aortic dissection in predicting distal thoracic aortic enlargement after TEVAR. METHODS: Sixty-seven patients who underwent TEVAR for DeBakey IIIb aortic dissection between January 2011 and December 2013 at our center were divided based on preoperative computer tomography angiography (CTA) features into 3 groups: I (n = 27) and III (n = 9), with true and false lumen, respectively, coursing closely along thoracic vertebral bodies and II, spiral configuration (n = 31). Distal thoracic aortic enlargement was determined using preoperative and postoperative CTA images. RESULTS: At median 12.2 (interquartile range, 4.3-26.6) months, 12 patients developed distal thoracic aortic enlargement, with estimated cumulative incidence tending to increase from categories I to III (P for trend < 0.01). Categories II and III versus I had more frequently concave location of primary entry tear (P < 0.01), larger dissection length and height index (L/Hi) (P = 0.05), and greater number of abdominal small branches involved preoperatively (P = 0.03), with otherwise similar baseline characteristics; and significantly greater total aortic diameter increase and lower false lumen regression up to 24 months, and lower true lumen expansion up to 12 months. In multivariable regression analysis, categories II and III were independently associated with distal thoracic aortic enlargement (hazard ratio, 19.95 [95% confidence interval, 2.14-186.09]; 41.23 [3.61-470.22], respectively) after adjustment for Society of Vascular Surgery score, preoperative maximum total aortic diameter, L/Hi, and number of abdominal small branches involved preoperatively. CONCLUSIONS: The CTA-based morphological features described in this study might improve preoperative risk stratification of DeBakey IIIb aortic dissection, with categories II and III having higher risk of distal thoracic aortic enlargement after TEVAR.

Complement C5a induces mesenchymal stem cell apoptosis during the progression of chronic diabetic complications.

AIMS/HYPOTHESIS: Regeneration and repair mediated by mesenchymal stem cells (MSCs) are key self-protection mechanisms against diabetic complications, a reflection of diabetes-related cell/tissue damage and dysfunction. MSC abnormalities have been reported during the progression of diabetic complications, but little is known about whether a deficiency in these cells plays a role in the pathogenesis of this disease. In addition to MSC resident sites, peripheral circulation is a major source of MSCs that participate in the regeneration and repair of damaged tissue. Therefore, we investigated whether there is a deficiency of circulating MSC-like cells in people with diabetes and explored the underlying mechanisms. METHODS: The abundance of MSC-like cells in peripheral blood was evaluated by FACS. Selected diabetic and non-diabetic serum (DS and NDS, respectively) samples were used to mimic diabetic and non-diabetic microenvironments, respectively. The proliferation and survival of MSCs under different serum conditions were analysed using several detection methods. The survival of MSCs in diabetic microenvironments was also investigated in vivo using leptin receptor mutant (Lepr db/db ) mice. RESULTS: Our data showed a significant decrease in the abundance of circulating MSC-like cells, which was correlated with complications in individuals with type 2 diabetes. DS strongly impaired the proliferation and survival of culture-expanded MSCs through the complement system but not through exposure to high glucose levels. DS-induced MSC apoptosis was mediated, at least in part, by the complement C5a-dependent upregulation of Fas-associated protein with death domain (FADD) and the Bcl-2-associated X protein (BAX)/B cell lymphoma 2 (Bcl-2) ratio, which was significantly inhibited by neutralising C5a or by the pharmacological or genetic inhibition of the C5a receptor (C5aR) on MSCs. Moreover, blockade of the C5a/C5aR pathway significantly inhibited the apoptosis of transplanted MSCs in Lepr db/db recipient mice. CONCLUSIONS/INTERPRETATION: C5a-dependent apoptotic death is probably involved in MSC deficiency and in the progression of complications in individuals with type 2 diabetes. Therefore, anticomplement therapy may be a novel intervention for diabetic complications.