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By dividing encryption as online and offline stages, the online/offline encryption schemes are very suitable to lightweight equipment. For the offline stage, high-performance equipment is used for complex preprocessing calculation, and the online stage the lightweight devices only make some simple calculations. In addition, side channel attacks can disclose some secret information of the cryptosystem, which leads to the destruction of the security of the cryptography schemes. Most of the online/offline identity-based encryption schemes cannot resist side channel attacks. The paper proposes a concrete hierarchical identity-based and online/offline encryption scheme that can resist continuous leakage of secret key. By the dual system encryption technology, we prove that the given scheme is fully secure. Through key updation technology, our proposed scheme resists continual leakage of private key. The relative leakage rate of the private key can reach 1/3. In addition, the presented scheme has the hierarchical function which effectively solves the problem of heavy load in a single key generation center. The given scheme is suitable for applications in distributed environment. &nbsp

Vascular smooth muscle cell (VSMC) plasticity is tightly associated with the pathological process of vasculopathy. Blood vessel epicardial substance (Bves) has emerged as an important regulator of intracardiac vasculogenesis and organ homeostasis. However, the involvement and role of Bves in VSMC plasticity and neointimal lesion development remain unclear.We used an in vivo rat model of graft arteriosclerosis and in vitro PDGF-treated VSMCs and identified the novel VSMC contractile phenotype-related gene Bves using a transcriptomic analysis and literature search. In vitro knockdown and overexpression approaches were used to investigate the mechanisms underlying VSMC phenotypic plasticity. In vivo, VSMC-specific Bves overexpression in rat aortic grafts was generated to assess the physiological function of Bves in neointimal lesion development.Here, we found that Bves expression was negatively regulated in aortic allografts in vivo and PDGF-treated VSMCs in vitro. The genetic knockdown of Bves dramatically inhibited, whereas Bves overexpression markedly promoted, the VSMC contractile phenotype. Furthermore, RNA sequencing unraveled a positive correlation between Bves and dual-specificity protein phosphatase 1 (Dusp1) expression in VSMCs. We found that Bves knockdown restrained Dusp1 expression, but enhanced p38MAPK and ERK1/2 activation, resulting in the loss of the VSMC contractile phenotype. In vivo, an analysis of a rat graft model confirmed that VSMC-specific Bves and Dusp1 overexpression in aortic allografts significantly attenuated neointimal lesion formation.Bves maintains the VSMC contractile phenotype through Dusp1-dependent p38MAPK and ERK1/2 signaling, and protects against neointimal formation, underscoring the important role of Bves in preventing transplant vasculopathy.

The proliferation and migration of vascular smooth muscle cells (VSMCs) are fundamental hallmarks of vasculopathy. Transforming growth factor β-activated kinase-1 (TAK1) plays a crucial role in mediating cellular functions, including autophagy, which has been recently linked to the regulation of VSMC functions and the development of vasculopathy. This study aims to better dissect how TAK1 controls VSMC proliferation and migration.A rat model of graft arteriosclerosis was employed to explore the influence of TAK1 signaling activation on VSMC proliferation, migration, autophagy, and neointima formation in vivo. Knockdown and pharmacological inhibition of TAK1 were utilized in cultured VSMCs to investigate the mechanisms underlying the progression of VSMC proliferation and migration.Increased phosphorylation of TAK1 (Thr-184/Thr-187) was examined in SMα-actin positive cells in the medial and neointimal lesions of aortic allografts. Lentivirus-mediated Tak1 shRNA transfection of aortic allografts robustly suppressed neointimal formation and lumen stenosis, as well as autophagy and cell proliferative responses. In cultured PDGF-BB-incubated VSMCs, genetic and pharmacological inhibition of TAK1 markedly attenuated autophagy activation, and blocked the progression of cell cycle, proliferation, and migration responses.Activation of TAK1 in VSMCs in the setting of aortic transplantation is an early and critical event in VSMC proliferation and migration, as well as neointima formation, because it controls autophagy activation, constituting a potential molecular mechanism and target for preventing transplant vasculopathy.

Sonic hedgehog (SHH) signaling pathway and glioma-associated oncogene homolog 1 (GLI1) play important roles in the initiation and progression of pancreatic ductal adenocarcinoma (PDAC). GS homeobox 2 (GSX2, formerly GSH2) is a downstream target of SHH signaling, but its role in pancreatic cancer remains unclear. This study evaluates the role of GSH2 in the development and drug resistance of pancreatic cancer. Both cell culture and xenograft mouse model were used. Immunohistochemistry, Western blotting and quantitative RT-PCR were used to examine the expression of GSH2 and other related molecules. CCK8 assay was used to test the cell proliferation, and flow cytometry used to examine cell apoptosis upon gemcitabine treatment. It was found that GSH2 is overexpressed in human pancreatic cancer tissues and cells. The expression of SHH and GLI1 was reversely correlated with GSH2 in pancreatic cancer cells. SHH and GLI1 have protein-protein interactions with GSH2. GSH2 silencing in pancreatic cancer cells inhibited cell proliferation, migration and invasion, increased cell apoptosis and sensitized pancreatic cancer cells to gemcitabine treatment. Furthermore, in vivo study demonstrated that silencing GSH2 increased the efficacy of gemcitabine-based treatment. Our results indicate that GSH2 is overexpressed in pancreatic cancer. GSH2 silencing in pancreatic cancer alleviates gemcitabine resistance by activating SHH/GLI1 pathway. Thus, targeting GSH2 in PDAC could be a novel cancer therapeutic strategy.

Recent studies indicate that host immune responses are dysregulated with either myeloid cell compartment or lymphocyte composition being disturbed in COVID-19. This study aimed to assess the impact of SARS-CoV-2 viral infection on the composition of circulating immune cells in severe COVID-19 patients. In this retrospective single-center cohort, 71 out of 87 COVID-19 patients admitted to the intense care unit for oxygen treatment were included in this study. Demographics, clinical features, comorbidities, and laboratory findings were collected on admission. Out of the 71 patients, 5 died from COVID-19. Compared with survived patients, deceased patients showed higher blood cell counts of neutrophils and monocytes but lower cell counts of lymphocytes. Intriguingly, the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and basophil-to-lymphocyte ratio (BLR) were markedly higher in deceased patients compared to survived patients. Furthermore, the lymphocyte counts were negatively correlated with D-dimer levels, while the ratios between myeloid cells and lymphocyte (NLR, MLR, and BLR) were positively correlated with D-dimer levels. Our findings revealed that the ratios between myeloid cells and lymphocytes were highly correlated with coagulation status and patient mortality in severe COVID-19.

The adversary is able to obtain some secret information from side channel attacks, which further damages the security for the system. To resolve this issue, we provide a hierarchical identity-based online/offline encryption scheme which resists side channel attacks. In our scheme, most encryption operations are preprocessed in the offline stage and only a small amount of lightweight calculation needs to be performed in the online stage for generating ciphertext. The presented scheme greatly reduces the workload of online encryption and is suitable for the resource-constrained device. The security of the proposed scheme is proved by the dual system technique. The leakage performance analysis shows that the presented scheme is resilient to leakage for almost the whole symmetric key.

With the progress of precision medicine treatment in pancreatic ductal adenocarcinoma (PDAC), individualized cancer-related examination and prediction is of great importance in this high malignant tumor, and antibody-dependent cell phagocytosis (ADCP) with changed pathways highly enrolled in the carcinogenesis of PDAC. High-throughput data of pancreatic ductal adenocarcinoma were downloaded and 160 differentially expressed ADCP-related genes (ARGs) were obtained. Secondly, GO and KEGG enrichment analyses show that ADCP is a pivotal biologic process in pancreatic carcinogenesis. Next, CALB2, NLGN2, NCAPG and SERTAD2 are identified through multivariate Cox regression. These 4 genes are confirmed with significant prognostic value in PDAC. Then, a risk score formula is constructed and tested in PDAC samples. Finally, the correlation between these 4 genes and M2 macrophage polarization was screened. Some pivotal differentially expressed ADCP-related genes and biologic processes, four pivotal subgroup was among identified in the protein-protein network, and hub genes was found in these sub group. Then, an ADCP-related formula was set: CALB2* 0.355526 + NLGN2* -0.86862 + NCAPG* 0.932348 + SERTAD2* 1.153568. Additionally, the significant correlation between M2 macrophage-infiltration and the expression of each genes in PDAC samples was identified. Finally, the somatic mutation landscape and sensitive chemotherapy drug between high risk group and low risk group was explored. This study provides a potential prognostic signature for predicting prognosis of PDAC patients and molecular insights of ADCP in PDAC, and the formula focusing on the prognosis of PDAC can be effective. These findings will contribute to the precision medicine of pancreatic ductal adenocarcinoma treatment.

Multiple proinflammatory conditions, including chemotherapy, radiotherapy, transplant rejection, and microbial infections, have been identified to induce involution of the thymus. However, the underlying cellular and molecular mechanisms of these inflammatory conditions inducing apoptosis of thymic epithelial cells (TECs), the main components of the thymus, remain largely unknown. In the circulation, mature dendritic cells (mDCs), the predominant initiator of innate and adaptive immune response, can migrate into the thymus. Herein, we demonstrated that mDCs were able to directly inhibit TECs proliferation and induce their apoptosis by activating the Jagged1/Notch3 signaling pathway. Intrathymic injection of either mDCs or recombinant mouse Jagged1-human Fc fusion protein (rmJagged1-hFc) into mice resulted in acute atrophy of the thymus. Furthermore, DAPT, a γ-secretase inhibitor, reversed the effects induced by mDC or rmJagged1-hFc. These findings suggest that acute or aging-related thymus degeneration can be induced either by mass migration of circulating mDCs in a short period of time or by a few but constantly homing mDCs.

Hypoxia-inducible gene domain family member 1A (Higd1a) has recently been reported to protect cells from hypoxia by helping to maintain normal mitochondrial function. The potential induction of Higd1a under high-fat exposure and whether it could protect cells from oxidative stress attracted our attention. Initially, 0.4 mM oleic acid and 0.2 mM palmitate were added to the growth media of HepG2 and LO2 cells for 72 hours. We discovered increased Higd1a expression, and knocking down Higd1a impaired mitochondrial transmembrane potential and induced cell apoptosis. We then identified that elevated reactive oxygen species (ROS) is responsible for increased Higd1a expression. Furthermore, we found that ROS promoted Higd1a expression by upregulating HIF-1a and PGC-1a expressions, and these two proteins could exert synergistic effects in inducing Higd1a expression. Taken together, these data suggest that Higd1a plays positive roles in protecting cells from oxidative stress, and ROS could induce Higd1a expression by upregulating PGC-1a and HIF-1a expressions.

Attribute-based encryption mechanism can achieve very flexible access control, so it has a wide range of applications in the distributed environment, such as fine-grained access control, audit log applications, cloud storage systems. Key-policy attribute-based encryption (KP-ABE) scheme is especially suitable for video on demand, pay TV, etc. Most of the existing KP-ABE schemes do not consider the side channel attacks which probably leak some secret information about the cryptosystems. In the paper, we present the formal definition and security model of key-policy attribute-based encryption scheme which is resilient to continual auxiliary input (CAI) leakage. What is more, we present a concrete KP-ABE scheme. The proposed scheme is proved secure under the static assumptions.

Background Liver cancer is one of the most common malignancies worldwide. HCC (hepatocellular carcinoma) is the predominant pathological type of liver cancer, accounting for approximately 75–85 % of all liver cancers. Lipid metabolic reprogramming has emerged as an important feature of HCC. However, the influence of lipid metabolism-related gene expression in HCC patient prognosis remains unknown. In this study, we performed a comprehensive analysis of HCC gene expression data from TCGA (The Cancer Genome Atlas) to acquire further insight into the role of lipid metabolism-related genes in HCC patient prognosis. Methods We analyzed the mRNA expression profiles of 424 HCC patients from the TCGA database. GSEA(Gene Set Enrichment Analysis) was performed to identify lipid metabolism-related gene sets associated with HCC. We performed univariate Cox regression and LASSO(least absolute shrinkage and selection operator) regression analyses to identify genes with prognostic value and develop a prognostic model, which was tested in a validation cohort. We performed Kaplan-Meier survival and ROC (receiver operating characteristic) analyses to evaluate the performance of the model. Results We identified three lipid metabolism-related genes (ME1, MED10, MED22) with prognostic value in HCC and used them to calculate a risk score for each HCC patient. High-risk HCC patients exhibited a significantly lower survival rate than low-risk patients. Multivariate Cox regression analysis revealed that the 3-gene signature was an independent prognostic factor in HCC. Furthermore, the signature provided a highly accurate prediction of HCC patient prognosis. Conclusions We identified three lipid-metabolism-related genes that are upregulated in HCC tissues and established a 3-gene signature-based risk model that can accurately predict HCC patient prognosis. Our findings support the strong links between lipid metabolism and HCC and may facilitate the development of new metabolism-targeted treatment approaches for HCC.

Background At present, serum Aspergillus IgG and IgM antibody detection is mainly used in the diagnosis of chronic pulmonary aspergillosis (CPA), but its value in the diagnosis of invasive pulmonary aspergillosis (IPA) in non-agranulocytic patients is still unclear. IgM can be used as a marker of acute infection to help diagnose acute infection-related diseases. IgG is a marker of long-term infection and is used to assist in the diagnosis of pre-existing or chronic infection-related diseases. The aim of this study was to investigate and compare the value of serum Aspergillus IgG and IgM antibody detection in the diagnosis of IPA and CPA in non-agranulocytic patients. Methods Fifty-eight cases of pulmonary aspergillosis (37 IPA and 21 CPA cases), 15 cases of community-acquired bacterial pneumonia and 50 cases in the healthy control group were collected. The serum (1,3)-β-D-glucan test (G test) was performed with a chromogenic method, and the galactomannan test (GM test) and Aspergillus IgG and IgM antibody detection were performed by commercial enzyme-linked immunosorbent assay (ELISA) in all patients. The sensitivity and specificity, cut-off value and area under the curve (AUC) of Aspergillus IgG and IgM antibodies were further obtained by receiver operating characteristic (ROC) curves. Results The positive rate of the G test, Aspergillus IgG antibody detection and the GM test also showed notable differences among the IPA, CPA, community-acquired bacterial pneumonia and healthy groups (P = 0.006, P P = 0.217, respectively). Only the positive rate of the GM test showed a significant difference between the IPA and CPA groups (P = 0.04). ROC curves indicated that Aspergillus IgG antibody detection had a higher specificity in the IPA group than in the CPA group (0.952). The detection of Aspergillus IgG antibody can preferably distinguish IPA from community-acquired bacterial pneumonia and healthy controls (sensitivity = 0.923, specificity = 0.459, cut-off value = 134.46, AUC = 0.727). It can also distinguish CPA from community-acquired bacterial pneumonia and healthy controls (sensitivity = 0.952, specificity = 0.692, cut-off value = 75.46, AUC = 0.873). Conclusions Serum Aspergillus IgG antibody detection may have certain clinical value in the diagnosis of IPA and CPA in non-agranulocytic patients.

Background: At present, serum Aspergillus IgG and IgM antibody detection is mainly used in the diagnosis of chronic pulmonary aspergillosis (CPA), but its value in the diagnosis of invasive pulmonary aspergillosis (IPA) in non-agranulocytic patients is still unclear. IgG is a marker of long-term infection and is used to assist in the diagnosis of pre-existing or chronic infection-related diseases. The aim of this study was to investigate and compare the value of serum Aspergillus IgG and IgM antibody detection in the diagnosis of IPA and CPA in non-agranulocytic patients. Methods: Fifty-eight cases of pulmonary aspergillosis (37 IPA and 21 CPA cases), 15 cases of community-acquired bacterial pneumonia and 50 cases in the healthy control group were collected. The serum (1,3)-β-D-glucan test (G test) was performed with a chromogenic method, and the galactomannan test (GM test) and Aspergillus IgG and IgM antibody detection were performed by commercial enzyme-linked immunosorbent assay (ELISA) in all patients. The sensitivity and specificity, cut-off value and area under the curve (AUC) of Aspergillus IgG and IgM antibodies were further obtained by receiver operating characteristic (ROC) curves. Results: The positive rate of the G test, Aspergillus IgG antibody detection and the GM test also showed notable differences among the IPA, CPA, community-acquired bacterial pneumonia and healthy groups ( P = 0.006, P < 0.001 and P = 0.217, respectively). Only the positive rate of the GM test showed a significant difference between the IPA and CPA groups ( P = 0.04). ROC curves indicated that Aspergillus IgG antibody detection had a higher specificity in the IPA group than in the CPA group (0.952). The detection of Aspergillus IgG antibody can preferably distinguish IPA from community-acquired bacterial pneumonia and healthy controls (sensitivity = 0.923, specificity = 0.459, cut-off value = 134.46, AUC = 0.727). It can also distinguish CPA from community-acquired bacterial pneumonia and healthy controls (sensitivity = 0.952, specificity = 0.692, cut-off value = 75.46, AUC = 0.873). Conclusions: Serum Aspergillus IgG antibody detection may have certain clinical value in the diagnosis of IPA and CPA in non-agranulocytic patients.

Additional file 1: Table S1. The results of ROC analysis of Aspergillus IgG antibody in different groups

Forkhead box P3 (FOXP3), which is a transcription factor, has a primary role in the development and function of regulatory T cells, and thus contributes to homeostasis of the immune system. A previous study generated a cell-permeable fusion protein of mouse FOXP3 conjugated to a protein transduction domain (PTD-mFOXP3) that successfully blocked differentiation of type 17 T helper cells in vitro and alleviated experimental arthritis in mice. In the present study, the role of PTD-mFOXP3 in type 1 T helper (Th1) cell-mediated immunity was investigated and the possible mechanisms for its effects were explored. Under Th1 polarization conditions, cluster of differentiation 4+ T cells were treated with PTD-mFOXP3 and analyzed by flow cytometry in vitro, which revealed that PTD-mFOXP3 blocked Th1 differentiation in vitro. Mice models of delayed type hypersensitivity (DTH) reactions were generated by subcutaneous sensitization and challenge with ovalbumin (OVA) to the ears of mice. PTD-mFOXP3, which was administered via local subcutaneous injection, significantly reduced DTH-induced inflammation, including ear swelling (ear swelling, P

The phenotypic modulation of VSMCs is a key cellular event driving neointimal formation and vascular remodeling. As a multifaceted cytokine of cell-mediated immunity, IFN-γ has been shown to play a critical role in the pathogenesis of vascular proliferative diseases. Although the important function of IFN-γ on regulating VSMC activation is well established, the molecular mechanisms by which elicits VSMC responses are poorly defined. Recent studies have identified HMGB1 as a principal effector to mediate IFN-γ-dependent biological functions in multiple cell types. Moreover, SIRT1 has emerged as a critical regulator of cellular processes through deacetylating multiple substrates, including HMGB1. Thus, we examined the role of IFN-γ on HMGB1 release, SIRT1 expression, and VSMC phenotypic modulation as well as the underlying molecular mechanisms. We show that IFN-γ dose-dependently induces HMGB1 cytoplasmic accumulation and its active release from VSMCs, resulting in enhanced HMGB1 in the medium. Conversely, IFN-γ treatment led to a dramatic decrease in SIRT1 expression. Additionally, pretreatment with resveratrol, a selective SIRT1 activator, abrogated IFN-γ-induced HMGB1 translocation and its release. Moreover, IFN-γ stimulates VSMC phenotypic modulation to an activated synthetic state characterized by the repression of SMC differentiation markers such as SM22α and calponin and the increase in cell motility. In contrast, blocking HMGB1 release or activity by resveratrol and HMGB1-neutralizing antibody prevents IFN-γ-induced phenotypic modulation of VSMCs. Overall, this study provides the first evidence showing that HMGB1 plays a critical role in regulating VSMC phenotypic modulation, suggesting that HMGB1 may be a potential therapeutic target to prevent vascular occlusive diseases. J. Cell. Biochem. 118: 518-529, 2017. © 2016 Wiley Periodicals, Inc.

Background: At present, serum Aspergillus IgG and IgM antibodies are mainly used in the diagnosis of chronic pulmonary aspergillosis (CPA), but the diagnostic value in invasive pulmonary aspergillosis (IPA) in non-agranulocytic patients is still unclear. The aim of this study was to investigate the diagnostic value of serum Aspergillus IgG and IgM antibody detection for pulmonary aspergillosis in non-agranulocytic patients.. Methods: 58 cases of pulmonary aspergillosis (37 IPA and 21 CPA cases), 15 cases of bacterial pneumonia and 50 cases of healthy control group were collected. Serum G test and GM test were performed, and Aspergillus IgG and IgM antibody were detected in all patients. The sensitivity and specificity, cut off value and AUC of Aspergillus IgG and IgM antibodies were further obtained by the ROC curves. Results: The positive rates of G test and Aspergillus IgG antibody in pulmonary aspergillosis group were significantly higher compared with bacterial pneumonia group or healthy group (P = 0.015 and P < 0.0001, respectively). Aspergillus IgG antibody can preferably distinguish CPA from bacterial pneumonia and healthy controls (sensitivity = 0.952, specificity = 0.692, cut off value = 75.46, AUC = 0.873). However, the performance of it was poor in distinguishing IPA from CPA, healthy group and pneumonia group (AUC < 0.7). Conclusions: Serum Aspergillus IgG has certain clinical value in the diagnosis of pulmonary aspergillosis in non-agranulocytic patients.

Background: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder without obvious structural abnormalities or consistent associated biomarkers, making its diagnosis difficult. In the present study, we used a urine-based metabolomics approach to identify IBS biomarkers. Methods: We used an ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) on urine samples from patients suffering from IBS and healthy controls. Data were coupled for multivariate statistical analysis methods. Results: We selected 30 differential metabolites associated with IBS and found steroid hormone biosynthesis and histidine metabolism alterations in patients with IBS that may be involved in the pathogenesis of the disease. In addition, we identified a panel of five metabolite markers composed of cortisone, citric acid, tiglylcarnitine, N6,-N6,-N6-trimethyl-L-lysine and L-histidine that could be used to discriminate between patients and healthy controls and may be appropriate as IBS diagnosis biomarkers. Conclusion: Our findings indicate that metabolomics combined with pattern recognition can be useful to identify disease diagnostic IBS markers. Clinical trial registration: ChiCTR1800020072

Background Conventionally, disconnected pancreatic duct syndrome is treated surgically. Endoscopic management is associated with lesser morbidity and mortality than that observed with surgery and shows similar success rates. However, limited data are available in this context. We evaluated the efficacy of endotherapeutic management for this syndrome. Methods We prospectively obtained data of patients with disconnected pancreatic duct syndrome between September 2008 and January 2016. Demographic and clinical data were assessed, and factors affecting clinical outcomes were statistically analyzed. Results Thirty-one patients underwent 40 endoscopic transpapillary procedures, and 1 patient developed an infection after prosthesis insertion. Etiological contributors to disconnected pancreatic duct syndrome were abdominal trauma (52%) and acute necrotizing pancreatitis (48%). The median interval between the appearance of pancreatic leaks and disconnected pancreatic duct syndrome was 6.6 months (range 0.5–84 months). The median follow-up after the last treatment procedure was 38 months (range 17–99 months). Patients with complete main pancreatic duct disruption in the body/tail showed a low risk of pancreatic atrophy (P = 0.009). This study highlighted the significant correlation between endoscopic transpapillary drainage and clinical success (P = 0.014). Conclusions Disconnected pancreatic duct syndrome is not an uncommon sequel of pancreatic injury, and much of the delayed diagnosis is attributable to a lack of knowledge regarding this disease. Endoscopic transpapillary intervention with ductal stenting is an effective and safe treatment for this condition.

Objective— Vascular smooth muscle cells (VSMCs) phenotype modulation is critical for the resolution of vascular injury. Genetic and pharmacological inhibition of PI3Kγ (phosphoinositide 3-kinase γ) exerts anti-inflammatory and protective effects in multiple cardiovascular diseases. This study investigated the role of PI3Kγ and its downstream effector molecules in the regulation of VSMC phenotypic modulation and neointimal formation in response to vascular injury. Approach and Results— Increased expression of PI3Kγ was found in injured vessel wall as well in cultured, serum-activated wild-type VSMCs, accompanied by a reduction in the expression of calponin and SM22α, 2 differentiation markers of VSMCs. However, the injury-induced downregulation of calponin and SM22α was profoundly attenuated in PI3Kγ −/− mice. Pharmacological inhibition and short hairpin RNA knockdown of PI3Kγ (PI3Kγ-KD) markedly attenuated YAP (Yes-associated protein) expression and CREB (cyclic AMP-response element binding protein) activation but improved the downregulation of differentiation genes in cultured VSMCs accompanied by reduced cell proliferation and migration. Mechanistically, activated CREB upregulated YAP transcriptional expression through binding to its promoter. Ectopic expression of YAP strikingly repressed the expression of differentiation genes even in PI3Kγ-KD VSMCs. Moreover, established carotid artery ligation and chimeric mice models demonstrate that deletion of PI3Kγ in naïve PI3Kγ −/− mice as well as in chimeric mice lacking PI3Kγ either in bone marrow or vascular wall significantly reduced neointimal formation after injury. Conclusions— PI3Kγ controls phenotypic modulation of VSMCs by regulating transcription factor CREB activation and YAP expression. Modulating PI3Kγ signaling on local vascular wall may represent a new therapeutic approach to treat proliferative vascular disease.

Photosensitizer (PS) serves as the central element of photodynamic therapy (PDT). The use of common nanoparticles (NPs) for PDT has typically been rendered less effective by the undesirable aggregation-caused quenching (ACQ) effect, resulting in quenched fluorescence and reduced reactive oxygen species (ROS) generation that diminish the imaging quality and PDT efficacy. To overcome the ACQ effect and to enhance the overall efficacy of PDT, herein, integrin ανβ3-targeted organic nanodots for image-guided PDT were designed and synthesized based on a red emissive aggregation-induced emission (AIE) PS. Methods: The TPETS nanodots were prepared by nano-precipitation method and further conjugated with thiolated cRGD (cRGD-SH) through a click reaction to yield the targeted TPETS nanodots (T-TPETS nanodots). Nanodots were characterized for encapsulation efficiency, conjugation rate, particle size, absorption and emission spectra and ROS production. The targeted fluorescence imaging and antitumor efficacy of T-TPETS nanodot were evaluated both in vitro and in vivo. The mechanism of cell apoptosis induced by T-TPETS nanodot mediated-PDT was explored. The biocompatibility and toxicity of the nanodots was examined using cytotoxicity test, hemolysis assay, blood biochemistry test and histological staining. Results: The obtained nanodots show bright red fluorescence and highly effective 1O2 generation in aggregate state. Both in vitro and in vivo experiments demonstrate that the nanodots exhibit excellent tumor-targeted imaging performance, which facilitates image-guided PDT for tumor ablation in a hepatocellular carcinoma model. Detailed analysis reveals that the nanodot-mediated PDT is able to induce time- and concentration-dependent cell death. The use of PDT at a high PDT intensity leads to direct cell necrosis, while cell apoptosis via the mitochondria-mediated pathway is achieved under low PDT intensity. Conclusion: Our results suggest that well-designed AIE nanodots are promising for image-guided PDT applications.

Encryption schemes are generally considered to be secure in an ideal environment, where the adversary cannot obtain the secret internal state of schemes. However, in the realistic environment, the adversary can gain partial information about decryption private key through various types of side channel attacks. In order to capture these attacks, it is crucial to design encryption schemes which are resilient to leakage. In this article, we first formalize a continuous leakage-resilient security model of certificate-based encryption. In the model, the adversary continuously obtains partial information about the secret states through the continuous leakage attacks. Furthermore, we construct a continuous leakage-resilient certificate-based encryption (CLR-CBE) scheme which is resilient to continuous leakage, and it is secure against adaptive chosen ciphertext attacks under the bilinear Diffie-Hellman inversion (BDHI) hardness assumption. Lastly, we show the bound on leakage and make comparison between proposed and existing schemes in terms of security properties and efficiency.

Certificate-based encryption (CBE) is an important class of public key encryption but the existing schemes are secure only under the premise that the decryption key (or private key) and master secret key are absolutely secret. In fact, a lot of side channel attacks and cold boot attacks can leak secret information of a cryptographic system. In this case, the security of the cryptographic system is destroyed, so a new model called leakage-resilient (LR) cryptography is introduced to solve this problem. While some traditional public key encryption and identity-based encryption with resilient-leakage schemes have been constructed, as far as we know, there is no leakage-resilient scheme in certificate-based cryptosystems. This paper puts forward the first certificate-based encryption scheme which can resist not only the decryption key leakage but also the master secret key leakage. Based on composite order bilinear group assumption, the security of the scheme is proved by using dual system encryption. The relative leakage rate of key is close to 1/3. We put forward the formal definition and security model of LR-CBE.We present first certificate-based encryption scheme with leakage resilience.The security of the scheme is reduced to composite order bilinear group assumption.The relative leakage rate of key is close to 1/3.

Identity-based encryption (IBE) has many appealing applications. However, some traditional IBE schemes may not be secure in the real world due to the side-channel attacks. Leakage-resilient cryptography can capture these attacks by modeling information leakage that adversary can access. In this paper, we apply a hash proof technique in the existing CCA-secure variant of the Gentry's IBE scheme to construct a new leakage-resilient IBE scheme in the bounded-leakage model. The proposed scheme is more computationally efficient than the original Alwen et al.'s leakage-resilient IBE scheme. It enjoys a shorter key (public/secret key) length, and a higher relative key leakage ratio. The new leakage-resilient scheme is proved semantically secure against adaptive chosen ciphertext attack in the standard model under the truncated augmented bilinear Diffie-Hellman exponent ( $q$ -TABDHE) assumption.

The situation for post-challenge continuous auxiliary input leakage has not been considered in the cryptography schemes for previous literature. We present a semantic-security model with post-challenge continuous auxiliary inputs for identity-based encryption. In this model, the adversary is permitted to obtain some information of the private keys constantly and to query more information after seeing the challenge ciphertext through the side-channel attacks. Furthermore, we present an identity-based encryption scheme resilient to leakage under composite order groups. Our scheme is secure against post-challenge continuous auxiliary input, adaptive chosen-identity, and adaptive chosen plaintext attacks under three static assumptions in the standard model. Compared with existing identity-based encryption schemes under security properties and performance, our scheme is practical. Copyright © 2015 John Wiley & Sons, Ltd.

The purpose of this study was to understand the incidence, clinical characteristics and related factors of bronchiectasis in chronic obstructive pulmonary disease (COPD) patients. From January 2015 to January 2017, 133 patients with moderate to severe COPD admitted to our hospital were enrolled in the study. Bronchiectasis analysis was performed by high resolution CT of the chest, the clinical data of all patients were collected including increasing state of COPD, peripheral blood samples, pulmonary function, blood gas. And sputum samples were collected for detection of microorganisms. the patients were aged 70.18 ± 8.31 years, and 62.4% of the patients were male. FEV1 accounted for an estimated value of 37.91 ± 10.68%, and 104 (78.2%) were severe COPD, and 43 (32.3%) had bronchiectasis. Bronchiectasis is mainly bilateral, multiple and columnar bronchiectasis. The most easily involved sites are the left lower lobe, left lingual lobe and right middle lobe. Bronchiectasis is associated with history of disease (P = .027), at least one hospitalization exacerbated by COPD in the past year (P = .025), and the separation of potential pathogenic microorganisms from sputum (P = .022). The most commonly isolated pathogen was Pseudomonas aeruginosa (P