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In the procedure of extracting hot topics and detecting emerging topic, counting term frequency is one of the most inevitable and time-consuming steps. For the purpose of text exploration, users may change the query range frequently, and the adjustment of ranges would cause recalculation of term frequency when finding hot terms, bringing unacceptable time cost. In addition, real-time update of dimensions is also a challenge. To address these problems, we first propose a novel data structure based on prefix cube to store terms and their frequencies, so that the time for counting term frequency gets a significant reduction. Based on the data structure, we propose an efficient range query algorithm that significantly decreases the number of input word lists involved in top-k queries. Considering the underlying dimension update, we also design an efficient maintenance mechanism to cope with different dimension updates. Finally, we conduct comprehensive experiments to validate the effectiveness of the proposed structure and the efficiency of the optimized query algorithm. We also prove that using the proposed data structure, the time cost of our algorithms in hot topic extraction and emerging topic detection can be reduced by about ten times compared with the previous algorithms.

In order to perform machine learning among multiple parties while protecting the privacy of raw data, privacy-preserving machine learning based on secure multi-party computation (MPL for short) has been a hot spot in recent. The configuration of MPL usually follows the peer-to-peer architecture, where each party has the same chance to reveal the output result. However, typical business scenarios often follow a hierarchical architecture where a powerful, usually privileged party, leads the tasks of machine learning. Only the privileged party can reveal the final model even if other assistant parties collude with each other. It is even required to avoid the abort of machine learning to ensure the scheduled deadlines and/or save used computing resources when part of assistant parties drop out. Motivated by the above scenarios, we propose pMPL, a robust MPL framework with a privileged part}. pMPL supports three-party training in the semi-honest setting. By setting alternate shares for the privileged party, pMPL is robust to tolerate one of the rest two parties dropping out during the training. With the above settings, we design a series of efficient protocols based on vector space secret sharing for pMPL to bridge the gap between vector space secret sharing and machine learning. Finally, the experimental results show that the performance of pMPL is promising when we compare it with the state-of-the-art MPL frameworks. Especially, in the LAN setting, pMPL is around $16\times$ and $5\times$ faster than TF-encrypted (with ABY3 as the back-end framework) for the linear regression, and logistic regression, respectively. Besides, the accuracy of trained models of linear regression, logistic regression, and BP neural networks can reach around 97%, 99%, and 96% on MNIST dataset respectively., This paper is the full version of a paper to appear in CCS 2022

The argument concerning the exact minimum number of examined lymph nodes (ELNs) has continued for a long time among various regions, and no consensus has been reached for stratified pathological T stages for data to date. Data from 4607 pN0 patients with gastric cancer were analyzed. Kaplan‐Meier analysis showed the similar overall survival (OS) outcomes among the 3 groups (ELNs ≤ 15, 16 ≤ ELNs ≤ 29 and ELNs ≥ 30, P = .171). However, the ELNs ≥ 30 group had a better disease‐free survival (DFS) outcome compared with the others (all P, The OS and DFS of the total pN0 patients in different ELNs group. (A) OS, P = .171, (B) DFS, P = .029.

Researchers proposed several data-driven methods to efficiently guess user-chosen passwords for password strength metering or password recovery in the past decades. However, these methods are usually evaluated under ad hoc scenarios with limited data sets. Thus, this motivates us to conduct a systematic and comparative investigation with a very large-scale data corpus for such state-of-the-art cracking methods. In this paper, we present the large-scale empirical study on password-cracking methods proposed by the academic community since 2005, leveraging about 220 million plaintext passwords leaked from 12 popular websites during the past decade. Specifically, we conduct our empirical evaluation in two cracking scenarios, i.e., cracking under extensive-knowledge and limited-knowledge. The evaluation concludes that no cracking method may outperform others from all aspects in these offline scenarios. The actual cracking performance is determined by multiple factors, including the underlying model principle along with dataset attributes such as length and structure characteristics. Then, we perform further evaluation by analyzing the set of cracked passwords in each targeting dataset. We get some interesting observations that make sense of many cracking behaviors and come up with some suggestions on how to choose a more effective password-cracking method under these two offline cracking scenarios.

Background Mediastinal venous aneurysm is a very rare disease and can be easily misdiagnosed. Patients are often asymptomatic while venous aneurysm of large size with adjacent structures oppressed can lead to discomfort. The surgical treatment for aneurysm of large vessels is often complex and challenging. Case presentation We reported a 52-year-old man with mediastinal mass who received operation on July 2019 in our hospital. Left innominate vein aneurysm was diagnosed during operation with superior vena cava involved. The aneurysm was resected and pericardium was taken to repair part wall of superior vena cava and reconstruct left innominate vein. The patient’s postoperative course was uneventful. Conclusions Venous aneurysm should be considered when mediastinal mass has no clear boundary with large veins or even seems to connect with them. Magnetic resonance imaging, computed tomographic angiography and invasive venography can be performed to further evaluate the mass once diagnosis of venous aneurysm was suspected. Using pericardium to repair large veins is a good choice which is safe and costless.

Rationale: Metastasis and recurrence are the primary reasons for the high mortality rate of human hepatocellular carcinoma (HCC) patients. However, the exact mechanism underlying HCC metastasis remains unclear. The Homeobox (HOX) family proteins, which are a highly conserved transcription factor superfamily, play important roles in cancer metastasis. Here, we report a novel role of HOXC10, one of the most upregulated HOX genes in human HCC tissues, in promoting HCC metastasis. Methods: The expression of HOXC10 and its functional targets was detected by immunohistochemistry in two independent human HCC cohorts. Luciferase reporter and chromatin immunoprecipitation assays were used to measure the transcriptional regulation of target genes by HOXC10. The effect of HOXC10-mediated invasion and metastasis were analyzed by Transwell assays and by an orthotopic metastasis model. Results: Elevated expression of HOXC10 was positively correlated with the loss of tumor encapsulation and with higher tumor-nodule-metastasis (TNM) stage and poor prognosis in human HCC. Overexpression of HOXC10 promoted HCC metastasis by upregulating metastasis-related genes, including 3-phosphoinositide-dependent protein kinase 1 (PDPK1) and vasodilator-stimulated phosphoprotein (VASP). Knockdown of PDPK1 and VASP inhibited HOXC10-enhanced HCC metastasis, whereas upregulation of PDPK1 and VASP rescued the decreased metastasis induced by HOXC10 knockdown. Interleukin-1β (IL-1β), which is the ligand of IL-1R1, upregulated HOXC10 expression through the c-Jun NH2-terminal kinase (JNK)/c-Jun pathway. HOXC10 knockdown significantly reduced IL-1β-mediated HCC metastasis. Furthermore, Anakinra, a specific antagonist of IL-1R1, inhibited IL-1β-induced HOXC10 upregulation and HCC metastasis. In human HCC tissues, HOXC10 expression was positively correlated with PDPK1, VASP and IL-1R1 expression, and patients with positive coexpression of HOXC10/PDPK1, HOXC10/VASP or IL-1R1/HOXC10 exhibited the poorest prognosis. Conclusions: Upregulated HOXC10 induced by IL-1β promotes HCC metastasis by transactivating PDPK1 and VASP expression. Thus, our study implicates HOXC10 as a prognostic biomarker, and targeting this pathway may be a promising therapeutic option for the clinical prevention of HCC metastasis.

Methamphetamine (METH) is one of the most highly addictive illicit drugs abused all over the world. Much evidence indicates that METH abuse leads to major toxicity, medical consequences, and even severe public health consequences. Existing studies usually focus on the pathomechanism of METH-induced toxicity; therefore, data on metabolites and elements correlating with particular toxicity remain scarce. The objective of the present study is to develop appropriate analytical procedures to identify the differential metabolic and elemental biomarkers on METH-induced hepatic injury to rats. The rats were administrated with METH (15 mg/mL/kg, two times per day) via intraperitoneal (i.p.) injections for four consecutive days. The alanine aminotransferase and aspartate aminotransferase activity levels of in the rat serum of the METH group increase significantly compared with those of the control group, suggesting obvious hepatic injury. The results are further confirmed by the histopathological microscopic observation. A total of 18 small molecular metabolites and 19 elements are selected to perform the simultaneous quantification based on the combination of liquid chromatography coupled with tandem mass spectrometry and inductively coupled plasma mass spectrometry. Sample preparation was optimized to cover all the analytes. Both methods are optimized and validated according to developed guidelines such as limits of detection, limits of quantification, linearity, precision, and recovery. All the obtained data are within the satisfactory range. The normalized data were processed according to the partial least squares discrimination analysis (PLS-DA) model. Five differential metabolic and six elemental markers are identified in rat plasma based on the variable importance in projection (VIP) ( 1) and t test results. Overall, the results obtained in this study demonstrate the developed methods are suitable for simultaneous determination of metabolic and elemental markers in the hepatic injury to rats induced by METH. Graphical abstract.

As an innovative networking paradigm in the Internet of Things, information-centric networking (ICN) has improved security than the traditional IP networks. However, it still faces a large number of security threats, especially those threats from internal attacks. The trust management technology is an effective approach for defending against internal attacks. In this paper, our contributions lie in our investigating the requirements of cybersecurity in ICN and analyzing the typical attack behaviors and defense schemes. Then, we propose a fast and efficient trust management scheme (FETMS) for defending against the on-off attack, which is an intelligent internal attack. The simulation results show that FETMS can efficiently detect and remove the malicious node in a short period of time; meanwhile, it can achieve lower latency and add its mobility.

Objectives To illustrate our workflow for lung donation and transplantation during the COVID-19 crisis and report our preliminary experience with perioperative care. Methods We retrospectively analyzed data in the China Lung Transplantation Registration from January 23rd, 2020, to March 23rd, 2020 (2020 cohort), compared to the same period in 2019 (2019 cohort). Pre- and post-lung transplantation (LTx) management strategies, including measures aiming to prevent SARS-CoV-2 infection, were applied for all recipients, including five post-COVID-19 transplants during the COVID-19 pandemic period in China. Results Twenty-eight LTx procedures were performed, including LTx for five patients with acute respiratory distress syndrome (ARDS) due to COVID-19-related pulmonary fibrosis. Compared to the 2019 cohort, more patients with urgent conditions were transplanted in 2020, with a shorter pre-LTx admission time and early mobilization post-LTx. A large proportion (60%) of lung donations were transported on high-speed trains and commercial flights or commercial flights and highways. Grafts in the preservation containers were handed over to the receiving staff at the airport for 40% (10/25) of donations, which reduced the unnecessary quarantine of transporting staff entering the city. Listed candidates were urgently transferred to other qualified centers in 17.9% (5/28) of cases, which reduced the risk of SARS-CoV-2 exposure in COVID-19 designated hospitals. The 90-day survival rate of the recipients transplanted in 2020 was 85.7%, including 3 of 5 (60%) recipients who were critically severe COVID-19 patients. Conclusion LTx and lung donation amid COVID-19 can be performed safely with coordinated efforts on medical resource sharing and medical staff protection based on stratification of the infection risk. Outcomes were not compromised during the COVID-19 outbreak. LTx can be regarded as salvage therapy for critical COVID-19 patients with a confirmed positive-turned-negative virology status., Graphical abstract

Background The effect of donor lung colonized bacteria on the prognosis of lung transplantation is not clear. We used the technique of next-generation sequencing (NGS) to detect the colonized bacteria from the lower respiratory tract and analyzed whether the colonized bacteria of donor lung could affect the outcomes of lung transplantation. Methods Seventeen patients who underwent lung transplantation from March 2018 to June 2018 at Wuxi People’s Hospital affiliated to Nanjing Medical University were included in this study. Twelve cases of donor lung were obtained, and 17 lung transplants were performed, including 12 single lung transplantation and 5 bilateral lung transplantation. The colonized bacteria in the lower lobe tissue of donor lung were detected by NGS, and the bacteria culture method was used to detect the bacteria in the airway secretion before and after the operation. The information of length of extracorporeal membrane oxygenation (ECMO) support, mechanical ventilation time, length of intensive care unit (ICU) stay, duration of fever and length of hospital stay were collected for prognostic analysis. Results Compared with bacterial culture methods, the positive rate by using NGS in the lungs were higher (52.9% vs 41.2%). Among the patients who were transplanted with donor lungs with detected bacteria by NGS before surgery, only one patient (1/9) developed the same bacteria after lung transplantation. Based on results of NGS and bacterial culture, there was no association between the colonized bacteria in donor lungs and the patients’ outcomes of immediate posttransplant period. Conclusion NGS showed more sensitive than bacterial culture for detection of bacteria. The colonized bacteria in different parts of the lung are inconsistent. There is no association between the colonized bacteria in donor lungs and short-term outcome of lung transplantation patients.

Background: The effect of donor lung pathogenic bacteria on the prognosis of lung transplantation is not clear. We used the technique of next-generation sequencing (NGS) to detect the pathogenic bacteria from the lower respiratory tract and analyzed whether the colonized bacteria of donor lung could affect the outcomes of lung transplantation.Methods: All patients who underwent lung transplantation from March 2018 to June 2018 at Wuxi People's Hospital affiliated to Nanjing Medical University were included in this study. Twelve cases of donor lung were obtained, and 17 lung transplants were performed, including 12 single lung transplantation and 5 bilateral lung transplantation. The colonized bacteria in the lower lobe tissue of donor lung were detected by NGS, and the bacteria culture method was used to detect the bacteria in the airway secretion before and after the operation. The information of length of extracorporeal membrane oxygenation (ECMO) support, mechanical ventilation time, length of intensive care unit (ICU) stay, duration of fever and length of hospital stay were collected for prognostic analysis.Results: Compared with bacterial culture methods, the positive rate by using NGS in the lungs were higher (52.9% vs 41.2%). Among the patients who had detected bacteria by NGS in donor lungs before surgery, only one patient (1/9) developed the same bacteria after lung transplantation. Based on results of NGS and bacterial culture, there is no association between the colonized bacteria in donor lungs and the patient outcomes of immediate posttransplant period. Conclusion: NGS showed more sensitive than bacterial culture for detection of bacteria. The colonized bacteria in different parts of the lung are inconsistent. There is no association between the colonized bacteria in donor lungs and short-term outcome of lung transplantation patients.

In this study, we prepared gold nanostar (GNS) composite nanoparticles containing siRNA of cyclooxygenase-2(siCOX-2) that were modified by tumor targeting ligand 2-deoxyglucose (DG) and transmembrane peptide 9-poly-D-arginine (9R) to form siCOX-2(9R/DG-GNS). Paclitaxel loaded temperature sensitive liposomes (PTX-TSL) were surface-modified to produce PTX-TSL-siCOX-2(9R/DG-GNS) displaying homogeneous star-shaped structures of suitable size (293.93 nm &plusmn, 3.21) and zeta potentials (2.47 mV &plusmn, 0.22). PTX-TSL-siCOX-2(9R/DG-GNS) had a high thermal conversion efficiency under 808 nm laser radiation and a superior transfection efficiency, which may be related to the targeting effects of DG and increased heat induced membrane permeability. COX-2 expression in HepG2/PTX cells was significantly suppressed by PTX-TSL-siCOX-2(9R/DG-GNS) in high temperatures. The co-delivery system inhibited drug-resistant cell growth rates by &ge, 77% and increased the cell apoptosis rate about 47% at elevated temperatures. PTX-TSL and siCOX-2 loaded gold nanostar particles, therefore, show promise for overcoming tumor resistance.

Currently, mobile devices often try obtaining the list of installed applications to survey the install ratio for advertisers and app owners to evaluate the market share of their applications. However, adversaries could yet infer or even directly learn the user’s interests and personal information from his/her mobile application installations. Furthermore, this investigation, which could lead to user privacy leakage, now calls for more attention than ever before. Motivated to resolve the above issue, this paper presents a scheme to investigate the install ratio of mobile applications for app owners and advertisers while at the same time preserving the users’ privacy. The scheme is executed with one round communication between a server and mobile devices. According to experiment results, the proposed scheme can balance privacy protection and publishing the application install ratio accurately. Furthermore, the proposed scheme also satisfies differential privacy. This paper has also given the curve fitting of the amount of mobile devices and a privacy budget. It may instruct users how to choose a privacy budget for a given amount of devices to investigate.

Blood vessels in the tumor periphery have high pericyte coverage and are resistant to vascular disrupting agents (VDAs). VDA treatment resistance leads to a viable peripheral tumor rim that contributes to treatment failure and disease recurrence. Here, we provide evidence to support a hypothesis that shifting the target of VDAs from tumor vessel endothelial cells to pericytes disrupts tumor peripheral vessels and the viable rim, circumventing VDA treatment resistance. Through chemical engineering, we developed Z-GP-DAVLBH (from the tubulin-binding VDA desacetylvinblastine monohydrazide [DAVLBH]) as a prodrug that can be selectively activated by fibroblast activation protein α (FAPα) in tumor pericytes. Z-GP-DAVLBH selectively destroys the cytoskeleton of FAPα-expressing tumor pericytes, disrupting blood vessels both within the core and around the periphery of tumors. As a result, Z-GP-DAVLBH treatment eradicated the otherwise VDA-resistant tumor rim and led to complete regression of tumors in multiple lines of xenografts without producing the drug-related toxicity that is associated with similar doses of DAVLBH. This study demonstrates that targeting tumor pericytes with an FAPα-activated VDA prodrug represents a potential vascular disruption strategy in overcoming tumor resistance to VDA treatments.

With the rapid development of mobile applications and online social networks, users often encounter a frustrating challenge to set privacy and security policies (i.e., permission requests) of various applications correctly. For instance, in an Android system, it is hard for users, even programmers, to identify malicious permission requests (policies) when they install a third-party application. To simplify the task of policy management, in this paper, we propose a novel policy administration method where the policy settings from users' friends will be used as a key recommendation to guide policy administration, and the security of friends' privacy will be protected. We propose to let a user invite his or her friends to help with policy setting in applications, and we call such a method socialized policy administration (SPA for short). We designed two types of SPA: basic SPA and composite SPA. Both types of SPA are equipped with a privacy preserving mechanism that enables users' friends to help users without leaking the friends' preferences. In our prototype based on Telegram, i.e., one of the most popular instant messaging applications, we utilize partially homomorphic encryption cryptosystems to implement our framework. Based on the performance evaluation, SPA is able to configure almost all types of policies of current popular Android applications with a modest performance overhead.

Many studies have indicated that the aberrant expression of long noncoding RNAs (lncRNAs) is responsible for drug resistance, which represents a substantial obstacle for cancer therapy. In the present study, we aimed to investigate the role of the lncRNA HOXA-AS3 in drug resistance and elucidate its underlying mechanisms in non-small-cell lung carcinoma (NSCLC) cells. The role of HOXA-AS3 in drug resistance was demonstrated by the cell counting kit-8 assay (CCK-8), ethynyldeoxyuridine (EDU) assay, and flow cytometry analysis. Tumor xenografts in nude mice were established to evaluate the antitumor effects of HOXA-AS3 knockdown in vivo. Western blotting and quantitative real-time PCR were used to evaluate protein and RNA expression. RNA pull-down assays, mass spectrometry, and RNA immunoprecipitation were performed to confirm the molecular mechanism of HOXA-AS3 in the cisplatin resistance of NSCLC cells. We found that HOXA-AS3 levels increased with cisplatin treatment and knockdown of HOXA-AS3 enhance the efficacy of cisplatin in vitro and in vivo. Mechanistic investigations showed that HOXA-AS3 conferred cisplatin resistance by down-regulating homeobox A3 (HOXA3) expression. Moreover, HOXA-AS3 was demonstrated to interact with both the mRNA and protein forms of HOXA3. In addition, HOXA3 knockdown increased cisplatin resistance and induced epithelial-mesenchymal transition (EMT). Taken together, our findings suggested that additional research into HOXA-AS3 might provide a better understanding of the mechanisms of drug resistance and promote the development of a novel and efficient strategy to treat NSCLC.

Objective: Reactive oxygen species (ROS) are involved in a variety of biological phenomena and serve both deleterious and beneficial roles. ROS quantification and assessment of reaction networks are desirable but difficult because of their short half-life and high reactivity. Here, we describe a pro-oxidative model in a single human lung carcinoma SPC-A-1 cell that was created by application of extracellular H(2)O(2) stimuli. Methods: Modified microfluidics and imaging techniques were used to determine O(2) (•−) levels and construct an O(2) (•−) reaction network. To elucidate the consequences of increased O(2) (•−) input, the mitochondria were given a central role in the oxidative stress mode, by manipulating mitochondria-interrelated cytosolic Ca(2+) levels, mitochondrial Ca(2+) uptake, auto-amplification of intracellular ROS and the intrinsic apoptotic pathway. Results and conclusions: Results from a modified microchip demonstrated that 1 mmol/L H(2)O(2) induced a rapid increase in cellular O(2) (•−) levels (>27 vs. >406 amol in 20 min), leading to increased cellular oxidizing power (evaluated by ROS levels) and decreased reducing power (evaluated by glutathione (GSH) levels). In addition, we examined the dynamics of cytosolic Ca(2+) and mitochondrial Ca(2+) by confocal laser scanning microscopy and confirmed that Ca(2+) stores in the endoplasmic reticulum were the primary source of H(2)O(2)-induced cytosolic Ca(2+) bursts. It is clear that mitochondria have pivotal roles in determining how exogenous oxidative stress affects cell fate. The stress response involves the transfer of Ca(2+) signals between organelles, ROS auto-amplification, mitochondrial dysfunction, and a caspase-dependent apoptotic pathway.

The sex-determining region Y (SRY)-box (SOX) family has a crucial role in carcinogenesis and cancer progression. However, the role of SOX12 and the mechanism by which it is dysregulated in colorectal cancer (CRC) remain unclear. Here we analyzed SOX12 expression patterns in two independent CRC cohorts (cohort I, n = 390; cohort II, n = 363) and found that SOX12 was significantly upregulated in CRC, indicating a poor prognosis in CRC patients. Overexpression of SOX12 promoted CRC cell proliferation and metastasis, whereas downregulation of SOX12 hampered CRC aggressiveness. Mechanistically, SOX12 facilitated asparagine synthesis by transactivating glutaminase (GLS), glutamic oxaloacetic transaminase 2 (GOT2), and asparagine synthetase (ASNS). Downregulation of GLS, GOT2, and ASNS blocked SOX12-mediated CRC cell proliferation and metastasis, whereas ectopic expression of GLS, GOT2, and ASNS attenuated the SOX12 knockdown-induced suppression of CRC progression. In addition, serial deletion, site-directed mutagenesis, luciferase reporter, and chromatin immunoprecipitation (ChIP) assays indicated that hypoxia-inducible factor 1α (HIF-1α) directly binds to the SOX12 promoter and induces SOX12 expression. Administration of l-asparaginase decreased SOX12-mediated tumor growth and metastasis. In human CRC samples, SOX12 expression positively correlated with GLS, GOT2, ASNS, and HIF-1α expression. Based on these results, SOX12 may serve as a prognostic biomarker and l-asparaginase represents a potential novel therapeutic agent for CRC.

Textual passwords are still dominating the authentication of remote file sharing and website logins, although researchers recently showed several vulnerabilities about this authentication mechanism. When a user creates or changes a password, a website usually leverages a password strength meter (PSM for short) to show the strength of the password. When the password is evaluated as a weak one, the user may replace the password with a stronger or securer one. However, the user is usually confused when the password, especially a frequently used password, is shown as a weak one. We argue that an explainable password strength meter addon, which could show the reasons of weak, may help users to more effectively create a secure password. Unfortunately, we find few sites in Alexa global top 100 showing these details. Motivated to help users with an explainable PSM, this paper proposes an addon to PSMs providing feedbacks in the form of pattern passwords explaining why a password is weak. This PSM addon can detect twelve types of patterns, which cover a very large proportion among 70 million of leaked real passwords from high-profile websites. According to our evaluation and user study, our PSM addon, which leverages textual pattern passwords, can effectively detect these popular patterns and effectively help users create securer passwords.

Influenza A virus (IAV) infection is still a major global threat for humans, especially for the risk groups: young children and the elderly. The currently licensed antiviral drugs target viral factors and are prone to viral resistance. In recent years, a few endogenous small molecules from host, such as estradiol and omega-3 polyunsaturated fatty acid (PUFA)-derived lipid mediator protection D1 (PD1), were demonstrated to be capable of inhibiting IAV infection. Chenodeoxycholic acid (CDCA), one of the main primary bile acids, is synthesized from cholesterol in the liver and classically functions in emulsification and absorption of dietary fats. Clinically, CDCA has been used in the treatment of patients with cholesterol gallstones for more than five decades. In this study, we showed that CDCA attenuated the replication of three subtypes of influenza A virus, including a highly pathogenic H5N1 strain, in A549 and MDCK cell cultures with IC50 ranging from 5.5 to 11.5 &mu, M. Mechanistically, CDCA effectively restrained the nuclear export of viral ribonucleoprotein (vRNP) complexes. In conclusion, as an endogenous physiological small molecule, CDCA can inhibit IAV replication in vitro, at least in part, by blocking vRNP nuclear export, and affords further studies for development as a potential antiviral agent against IAV infections.

Background Immunohistochemistry (IHC) for programmed cell death ligand 1 (PD-L1) displays staining diversity. We compared IHC staining of PD-L1 in gastric cancer (GC) by using three commercially available antibody clones, and analyzed the correlation with the prognosis. Methods IHC using PD-L1 antibodies (clones SP142, 28–8 and E1L3N) in 315 formalin-fixed paraffin-embedded samples was qualitatively compared at the 1, 5 and 10% cut-off by two pathologists on total, tumor and immune/stromal cells. We used computer – assisted scoring to quantitatively analyze and compare the “H-score” of PD-L1 expression in 66 samples on total cells. The antibody clone SP142 was selected to investigate the infiltration of PD-L1+CD8+ T cells using automated quantitative immunofluorescence analyses (n = 50) and the prognostic significance. The prognoses were assessed by log-rank test. Results PD-L1 clones SP142 and 28–8 displayed great concordance by qualitative (κ = 0.816, 0.810 for total cells and tumor cells at the 5% cut-off) and quantitative analyses (R2 = 0.7991, 0.8187 for positive percentage and “H-score”). PD-L1 clone SP142 showed the highest positivity in immune/stromal cells staining (18.41%) compared to 28–8 (7.62%), while clone E1L3N showed poor staining in both tumor and immune/stromal cells. Clone SP142, but not 28–8 and E1L3N, predicted a worse prognosis at the 5% cut-off (p = 0.0243). Both the clone SP142 and 28–8 had high inter-pathologist correlation for tumor staining (R2 = 0.9805 and R2 = 0.9853), but a moderate correlation for stromal/immune cell staining (R2 = 0.5653 and R2 = 0.5745). Furthermore, a higher density of PD-L1+CD8+ T cells was correlated with a shorter survival time (R2 = 0.0909, p = 0.0352). Conclusions PD-L1 antibody clone SP142 was superior in cell staining, particularly in immune/stromal cell and prognosis. These findings are important for selection of PD-L1 antibody clones in the future diagnostic test. Electronic supplementary material The online version of this article (10.1186/s13000-018-0766-0) contains supplementary material, which is available to authorized users.

Blockchain is an emerging data management technology that enables people in a collaborative network to establish trusted connections with the other participants. Recently consortium blockchains have raised interest in a broader blockchain technology discussion. Instead of a fully public, autonomous network, consortium blockchain supports a network where participants can be limited to a subset of users and data access strictly controlled. Access control policies should be defined by the respective data owner and applied throughout the network without requiring a centralized data administrator. As a result, decentralized data access control (DDAC) emerges as a fundamental challenge for such systems. However, we show from a trust model for consortium collaborative networks that current consortium blockchain systems provide limited support for DDAC. Further, the distributed, replicated nature of blockchain makes it even more challenging to control data access, especially read access, compared with traditional DBMSes. We investigate possible strategies to protect data from being read by unauthorized users in consortium blockchain systems using combinations of ledger partitioning and encryption strategies. A general framework is proposed to help inexperienced users determine appropriate strategies under different application scenarios. The framework was implemented on top of Hyperledger Fabric to evaluate feasibility. Experimental results along with a real-world case study contrasted the performance of different strategies under various conditions and the practicality of the proposed framework.

The aim of the present study was to determine whether resveratrol protects neuronal cells from inflammation and isoflurane-induced oxidative stress-associated death via attenuating apoptosis via Akt/p38 mitogen-activated protein kinase (MAPK) signaling. The PC12 rat pheochromocytoma cell line was treated with 2% isoflurane + 21% O2 + 5% CO2 for 6 h and pre-treated with resveratrol (0–1,000 µM) for 0, 24 or 48 h prior to isoflurane treatment. An MTT assay, flow cytometry and ELISA of tumor necrosis factor-α, interleukin-6, malondialdehyde and superoxide dismutase revealed that resveratrol reduced growth inhibition, restrained apoptosis and suppressed inflammation and oxidative stress induced by isoflurane in PC12 cells. Pretreatment with resveratrol effectively reduced caspase-3 activity and inducible nitric oxide synthase protein expression in isoflurane-induced PC12 cells. In addition, western blot analysis demonstrated that resveratrol treatment significantly attenuated isoflurane-induced decreases in the activated phosphorylated (p)-Akt/Akt ratio and increases in the p-p38/p38 MAPK protein ratio in PC12 cells. These findings indicated that resveratrol was able to protect neuronal cells from isoflurane-induced inflammation and oxidative stress-associated death by attenuating apoptosis via Akt/p38 MAPK signaling.

Hashtags, created by social network users, have gained a huge popularity in recent years. As a kind of metatag for organizing information, hashtags in online social networks, especially in Instagram, have greatly facilitated users' interactions. In recent years, academia starts to use hashtags to reshape our understandings on how users interact with each other. #like4like is one of the most popular hashtags in Instagram with more than 290 million photos appended with it, when a publisher uses #like4like in one photo, it means that he will like back photos of those who like this photo. Different from other hashtags, #like4like implies an interaction between a photo's publisher and a user who likes this photo, and both of them aim to attract likes in Instagram. In this paper, we study whether #like4like indeed serves the purpose it is created for, i.e., will #like4like provoke more likes? We first perform a general analysis of #like4like with 1.8 million photos collected from Instagram, and discover that its quantity has dramatically increased by 1,300 times from 2012 to 2016. Then, we study whether #like4like will attract likes for photo publishers; results show that it is not #like4like but actually photo contents attract more likes, and the lifespan of a #like4like photo is quite limited. In the end, we study whether users who like #like4like photos will receive likes from #like4like publishers. However, results show that more than 90% of the publishers do not keep their promises, i.e., they will not like back others who like their #like4like photos; and for those who keep their promises, the photos which they like back are often randomly selected.

Background Cucurbit chlorotic yellows virus (CCYV) is a recently reported bipartite crinivirus that causes chlorotic leaf spots and yellowing symptoms on the leaves of cucurbit plants. The virus–host interaction of CCYV remains to be elucidated, and the influence of criniviruses on the host gene transcriptome requires analysis. Methods We used transcriptome sequencing to analyse the differentially expressed genes (DEGs) caused by CCYV infection. Results CCYV infection resulted in 865 DEGs. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis identified 67 pathways, and the three major enrichment pathways (according to the P-values) were photosynthesis-antenna proteins (KO00196), phenylalanine metabolism (KO00360a), and phenylpropanoid biosynthesis (KO00940). Of the 13 DEGs identified in phenylalanine metabolism, 11 genes encode disease resistance-related phenylalanine ammonia-lyase (PAL) genes. Using quantitative real-time PCR, we validated the differential expression of 12 genes. Conclusions Our study based on the CCYV–cucumber interaction provides comprehensive transcriptomic information, and will improve our understanding of host–crinivirus interactions. Electronic supplementary material The online version of this article (doi:10.1186/s12985-017-0690-z) contains supplementary material, which is available to authorized users.

The aim of the study was to test the feasibility of using commercially available computer-aided design and computer-aided manufacturing (CAD/CAM) technology including 3Shape Dental System 2013 trial version, WIELAND V2.0.049 and WIELAND ZENOTEC T1 milling machine to design and fabricate complete dentures. The modeling process of full denture available in the trial version of 3Shape Dental System 2013 was used to design virtual complete dentures on the basis of 3-dimensional (3D) digital edentulous models generated from the physical models. The virtual complete dentures designed were exported to CAM software of WIELAND V2.0.049. A WIELAND ZENOTEC T1 milling machine controlled by the CAM software was used to fabricate physical dentitions and baseplates by milling acrylic resin composite plates. The physical dentitions were bonded to the corresponding baseplates to form the maxillary and mandibular complete dentures. Virtual complete dentures were successfully designed using the software through several steps including generation of 3D digital edentulous models, model analysis, arrangement of artificial teeth, trimming relief area, and occlusal adjustment. Physical dentitions and baseplates were successfully fabricated according to the designed virtual complete dentures using milling machine controlled by a CAM software. Bonding physical dentitions to the corresponding baseplates generated the final physical complete dentures. Our study demonstrated that complete dentures could be successfully designed and fabricated by using CAD/CAM.

Ten Significantly enriched pathways. (DOC 37Â kb)