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Abstract Multi-cloud computing provides services by used different clouds simultaneously multi-signature can be used as the interactive technology between multi-cloud and users. However, the limited resources of some terminal devices make multi-signature, which based on bilinear map, is not suitable for multi-cloud computing environment. In addition, the signers are disclosure in multi-signature so there is the risk of attack. To solve this issues, this paper proposes a certificateless designated verifier multi-signature scheme based on multivariable public key cryptography (MPKC). Firstly, the formalized definition and security model of the proposed scheme are given. Secondly, it is proved that the proposed scheme is against adaptive chosen-message attacks. Finally, the analysis shows that the proposed scheme is more efficiency and suitable for multi-cloud. Moreover, the proposed scheme can hidding signature source to achieve privacy protection.

BackgroundMobile health (mHealth) technology has the potential to support shared decision-making (SDM) and improve hypertension control. However, our understanding of the variations in individuals’ involvement in SDM and mHealth usage across different racial and ethnic groups in the United States is still limited. ObjectiveThis study aimed to investigate the extent of involvement in SDM and the usage of mHealth technology in health-related activities among US adults with hypertension from diverse racial and ethnic backgrounds and to examine whether the mHealth usage differed by individuals’ level of engagement in SDM. MethodsThis study used cross-sectional data from the 2017 to 2020 Health Information National Trends Survey, which was conducted on US adults with self-reported hypertension, and race and ethnicity data were included. The exposure of interest was race and ethnicity. The outcomes were SDM and mHealth usage. SDM was assessed using an item: “In the past 12 months, how often did your health professional: involve you in decisions about your healthcare as much as you wanted?” mHealth usage was defined as using a smartphone or tablet to engage in (1) making health decisions, (2) discussing health decisions with health providers, (3) tracking health progress, and (4) sharing health information. Weighted multivariable logistic regression models were used to examine the association between race and ethnicity and SDM or mHealth usage adjusted for covariates and stratified by the level of engagement in SDM. ResultsThis study included 4893 adults with hypertension, and the mean age was 61 (SD 13) years. The sample was 53% female, 61% (n=3006) non-Hispanic White, 19% (n=907) non-Hispanic Black or African American, 12% (n=605) Hispanic, 4% (n=193) non-Hispanic Asian, and 4% (n=182) non-Hispanic other. Compared to the non-Hispanic White adults, non-Hispanic Black adults were more likely to use mHealth to make health decisions (adjusted odds ratio [aOR] 1.70, 95% CI 1.23-2.34), share health information (aOR 1.46, 95% CI 1.02-2.08), and discuss health decisions with health providers (aOR 1.38, 95% CI 1.02-1.87). Significant associations were observed specifically among those who were always involved in SDM. Asian adults were less likely to be involved in SDM (aOR 0.51, 95% CI 0.26-0.99) and were more likely to use mHealth to track progress on a health-related goal (aOR 2.07, 95% CI 1.28-3.34) than non-Hispanic White adults. Hispanic adults were less likely to use mHealth to share health information (aOR 0.47, 95% CI 0.33-0.67) and discuss health decisions with health providers (aOR 0.65, 95% CI 0.46-0.94) compared to non-Hispanic White adults. ConclusionsThis study observed racial and ethnic disparities in SDM and mHealth usage among US adults with hypertension. These findings emphasize the significance of comprehending the involvement of SDM and the usage of mHealth technology within racially and ethnically diverse populations.

ABSTRACT Increasing evidence shows that protein lysine acetylation is involved in almost every aspect of cellular physiology in bacteria. Yersinia pestis is a flea-borne pathogen responsible for millions of human deaths in three global pandemics. However, the functional role of lysine acetylation in this pathogen remains unclear. Here, we found more acetylated proteins and a higher degree of acetylation in Y. pestis grown under mammalian host (Mh) conditions than under flea vector (Fv) conditions, suggesting that protein acetylation could significantly change during fleabite transmission. Comparative acetylome analysis of mutants of YfiQ and CobB, the major acetyltransferase and deacetylase of Y. pestis, respectively, identified 23 YfiQ-dependent and 315 CobB-dependent acetylated proteins. Further results demonstrated that acetylation of Lys73 of the SlyA protein, a MarR-family transcriptional regulator, inhibits its binding to the promoter of target genes, including hmsT that encodes diguanylate cyclase responsible for the synthesis of c-di-GMP, and significantly enhances biofilm formation of Y. pestis. Our study presents the first extensive acetylome data of Y. pestis and a critical resource for the functional study of lysine acetylation in this pathogen. IMPORTANCE Yersinia pestis is the etiological agent of plague, historically responsible for three global pandemics. The 2017 plague epidemic in Madagascar was a reminder that Y. pestis remains a real threat in many parts of the world. Plague is a zoonotic disease that primarily infects rodents via fleabite, and transmission of Y. pestis from infected fleas to mammals requires rapid adaptive responses to adverse host environments to establish infection. Our study provides the first global profiling of lysine acetylation derived from mass spectrometry analysis in Y. pestis. Our data set can serve as a critical resource for the functional study of lysine acetylation in Y. pestis and provides new molecular insight into the physiological role of lysine acetylation in proteins. More importantly, we found that acetylation of Lys73 of SlyA significantly promotes biofilm formation of Y. pestis, indicating that bacteria can use lysine acetylation to fine-tune the expression of genes to improve adaptation.

Clear cell renal cell carcinoma (ccRCC) is a frequently occurring renal cancer. The Von Hippel-Lindau disease tumor suppressor VHL, a known tumor suppressor gene, is frequently mutated in about 50% of patients with ccRCC. However, it is unclear whether VHL influences the progression of ccRCC tumors expressing wild-type VHL. In the present study, we found that higher expression of VHL was correlated with the better disease-free survival (DFS) in ccRCC patients using The Cancer Genome Atlas (TCGA) datasets. We revealed that VHL overexpression in ccRCC cells inhibited epithelial-mesenchymal transition (EMT), sterol regulatory element-binding protein 1 (SREBP1)-regulated triglyceride synthesis, and cell proliferation. Proteomic analysis provided us a global view that VHL regulated four biological processes, including metabolism, immune regulation, apoptosis, and cell movement. Importantly, we found that VHL overexpression led to up-regulated expression of proteins associated with antigen processing and interferon-responsive proteins, thus rendering ccRCC cells more sensitive to interferon treatment. We defined an interferon-responsive signature (IRS) composed of ten interferon-responsive proteins, whose mRNA expression levels were positively correlated with DFS in ccRCC patients. Taken together, our results propose that the subset of ccRCC patients with high VHL expression benefit from immunotherapy.

Cilia project from cells to serve sensory functions, and ciliary disruption can result in multiple disorders known as ciliopathies. Here the authors show that the ciliopathy gene TCTN1 functions to regulate the ciliary transition zone and ectosome formation.

MicroRNAs (miRNAs) in oral squamous cell carcinoma (OSCC)-derived small extracellular vesicles (sEVs) play a pivotal role in modulating intercellular communications between tumor cells and other cells in the microenvironment, thereby influencing tumor progression and the efficacy of therapeutic interventions. However, a comprehensive inventory of these secretory miRNAs in sEVs and their biological and clinical implications remains elusive. This study aims to profile the miRNA content of OSCC cell line sEVs and computationally elucidate their biological and clinical relevance. We conducted miRNA sequencing to compare the miRNA profiles of OSCC cells and their corresponding sEVs. Our motif enrichment analysis identified specific sorting motifs that are implicated in either cellular retention or preferential sEV secretion. Target cell analysis suggested that the sEV miRNAs potentially interact with various immune cell types, including natural killer cells and dendritic cells. Additionally, we explored the clinical relevance of these miRNAs by correlating their expression levels with TNM stages and patient survival outcomes. Intriguingly, our findings revealed that a distinct sEV miRNA signature is associated with lymph node metastasis and poorer survival in patients in TCGA-HNSC dataset. Collectively, this research furthers our understanding of the miRNA sorting mechanisms in OSCC and underscores their clinical implications.

Abstract Fe3O4 magnetic nanoparticles (MNPs) are biomedical materials that have been approved by the FDA. To date, MNPs have been developed rapidly in nanomedicine and are of great significance. Stem cells and secretory vesicles can be used for tissue regeneration and repair. In cell therapy, MNPs which interact with external magnetic field are introduced to achieve the purpose of cell directional enrichment, while MRI to monitor cell distribution and drug delivery. This paper reviews the size optimization, response in external magnetic field and biomedical application of MNPs in cell therapy and provides a comprehensive view.

Four deep eutectic solvents were used to produce plasticized thermoplastic starch films by a solution casting method. The mechanical properties of thin films, the stability of these properties over time, and the effects of humidity were investigated with the quartz crystal microbalance. The crystallinity, glass transition temperature, modulus and elongation at break for thicker films was measured using a combination of x-ray diffraction, differential scanning calorimetry and tensile testing. The films had very low glass transition temperatures (-50 ∘C or lower), with mechanical properties determined by the crystallinity of the films. The crystallinity did not change significantly over a period of one week, giving materials with a stable mechanical response. Deep eutectic solvents containing ammonium acetate, glycerol, and urea produced films with a crystalline structure that was much more stable at high humidity values than films plasticized only with glycerol or a traditional ionic liquid. These effects are attributed to the complex hydrogen bonding interactions between the different components of the deep eutectic solvents, and between these components and the starch polymer.

BackgroundSmoking is a leading cause of premature death globally. Quitting smoking reduces the risk of all-cause mortality by 11%-34%. Smartphone app–based smoking cessation (SASC) interventions have been developed and are widely used. However, the evidence for the effectiveness of smartphone-based interventions for smoking cessation is currently equivocal. ObjectiveThe purpose of this study was to synthesize the evidence for the effectiveness of smartphone app–based interventions for smoking cessation. MethodsWe conducted a systematic review and meta-analysis of the effectiveness of smartphone interventions for smoking cessation based on the Cochrane methodology. An electronic literature search was performed using the Cochrane Library, Web of Science, PubMed, Embase, PsycINFO, China National Knowledge Infrastructure, and Wanfang databases to identify published papers in English or Chinese (there was no time limit regarding the publication date). The outcome was the smoking abstinence rate, which was either a 7-day point prevalence abstinence rate or a continuous abstinence rate. ResultsA total of 9 randomized controlled trials involving 12,967 adults were selected for the final analysis. The selected studies from 6 countries (the United States, Spain, France, Switzerland, Canada, and Japan) were included in the meta-analysis between 2018 and 2022. Pooled effect sizes (across all follow-up time points) revealed no difference between the smartphone app group and the comparators (standard care, SMS text messaging intervention, web-based intervention, smoking cessation counseling, or apps as placebos without real function; odds ratio [OR] 1.25, 95% CI 0.99-1.56, P=.06, I2=73.6%). Based on the subanalyses, 6 trials comparing smartphone app interventions to comparator interventions reported no significant differences in effectiveness (OR 1.03, 95% CI 0.85-1.26, P=.74, I2=57.1%). However, the 3 trials that evaluated the combination of smartphone interventions combined with pharmacotherapy compared to pharmacotherapy alone found higher smoking abstinence rates in the combined intervention (OR 1.79, 95% CI 1.38-2.33, P=.74, I2=7.4%). All SASC interventions with higher levels of adherence were significantly more effective (OR 1.48, 95% CI 1.20-1.84, P

Abstract Acyl-CoA oxidase 2 (Acox2) is an enzyme involved in peroxisomal bile acid synthesis and branched-chain fatty acid degradation. Acox2 knockout (−/−) mice spontaneously developed liver cancer with marked lymphocytic infiltrate. Tandem-affinity purification coupled with mass spectrometry analysis revealed that Acox2 interacted with methylcrotonoyl-CoA carboxylase followed by co-immunoprecipitation confirmation. Here we reported that non-histone lysine crotonylation (Kcr) levels were downregulated in Acox2 −/− mice livers. Interestingly, Kcr signals were concentrated in the nucleus of tumor cells but mostly located in the cytoplasm of adjacent normal liver cells of Acox2 −/− mice. Quantitative analysis of the global crotonylome further revealed that 54% (27/50) of downregulated non-histone Kcr sites were located in mitochondrial (11/50) and peroxisomal (17/50) enzymes including Ehhadh, Scp2, Hsd17b4, Crot, Etfa, Cpt1a, Eci1/2, Hadha, Etfdh, and Idh2. Subsequent site-directed mutagenesis and transcriptome analysis revealed that Ehhadh K572cr might have site-specific regulatory roles by downregulating TOP3B expression that lead to increased DNA damage in vitro. Our findings suggested Acox2 is a regulator of Kcr that might play critical role on hepatic metabolic homeostasis.

Abstract Background A specific feature of the autoimmune response in rheumatoid arthritis (RA) is the presence of anti‐citrullinated protein antibodies (ACPAs) in patient sera. These antibodies can appear several years before disease onset and are involved in the development of RA. Objective We performed proteomic analysis by mass spectroscopy to identify novel citrullinated antigens and autoantibodies in RA patients. Methods Polypeptides isolated from the sera of RA patients were identified by Orbitrap high‐precision mass spectrometry and then citrulline‐containing proteins were selected. The levels of ACPAs against these newly identified citrullinated autoantigens in sera of 100 RA patients and 50 healthy controls were determined by enzyme‐linked immunosorbent assays. Results A total of 135 proteins were identified in RA patients and the protein profile included 11 citrulline‐containing antigens. Three of the 11 citrullinated proteins had been reported in previous studies. ACPAs against the novel citrullinated epitopes from these proteins were increased in sera from the RA patients compared with those from healthy controls. Autoantibodies against one of the citrullinated antigens, lipopolysaccharide‐binding protein (LBP), was significantly increased in RA patients and associated with disease activities. The titer of anti‐citrullinated LBP antibodies (anti‐cLBP) was closely related to the infection incidence in RA patients. Conclusion Serum protein analysis by high‐precision proteomic technology is a feasible method to identify novel citrullinated epitopes in RA patients. Anti‐cLBP antibodies are associated with disease severity and infection in RA patients.

Abstract K-anonymity has been gaining widespread attention as one of the most widely used technologies to protect location privacy. Nevertheless, there are still some threats such as behavior deception and service swing, since utilizing distributed k-anonymity technology to construct an anonymous domain. More specifically, the coordinate of the honest node will be a leak if the malicious nodes submit wrong locations coordinate to take part in the domain construction process. Worse still, owing to service swing, the attacker increases the reputation illegally to deceive honest nodes again. To overcome those drawbacks, we propose a trusted de-swinging k-anonymity scheme for location privacy protection. Primarily, we introduce a de-swinging reputation evaluation method (DREM), which designs a penalty factor to curb swinging behavior. This method calculates the reputation from entity honesty degree, location information entropy, and service swing degree. Besides, based on our proposed DREM, a credible cloaking area is constructed to protect the location privacy of the requester. In the area, nodes can choose some nodes with a high reputation for completing the construction process of the anonymous domain. Finally, we design reputation contracts to calculate credit automatically based on smart contracts. The security analysis and simulation results indicate that our proposed scheme effectively resists malicious attacks, curbs the service swing, and encourages nodes to participate honestly in the construction of cloaking areas.

ObjectiveTo evaluate safety and efficacy of dietary polyphenols in the treatment of rheumatoid arthritis (RA).MethodsCNKI, Pubmed, Cochrane library, Embase were searched to collect randomized controlled trials (RCTs) of dietary polyphenols in the treatment of RA. The databases were searched from the time of their establishment to November 8nd, 2022. After 2 reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies, Meta-analysis was performed using RevMan5.4 software.ResultsA total of 49 records (47 RCTs) were finally included, involving 3852 participants and 15 types of dietary polyphenols (Cinnamon extract, Cranberry extract, Crocus sativus L. extract, Curcumin, Garlic extract, Ginger extract, Hesperidin, Olive oil, Pomegranate extract, Puerarin, Quercetin, Resveratrol, Sesamin, Tea polyphenols, Total glucosides of paeony). Pomegranate extract, Resveratrol, Garlic extract, Puerarin, Hesperidin, Ginger extract, Cinnamon extract, Sesamin only involve in 1 RCT. Cranberry extract, Crocus sativus L. extract, Olive oil, Quercetin, Tea polyphenols involve in 2 RCTs. Total glucosides of paeony and Curcumin involve in more than 3 RCTs. These RCTs showed that these dietary polyphenols could improve disease activity score for 28 joints (DAS28), inflammation levels or oxidative stress levels in RA. The addition of dietary polyphenols did not increase adverse events.ConclusionDietary polyphenols may improve DAS28, reduce C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and improve oxidative stress, etc. However, more RCTs are needed to verify or modify the efficacy and safety of dietary polyphenols.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022315645.

Accurate information concerning crown profile is critical in analyzing biological processes and providing a more accurate estimate of carbon balance, which is conducive to sustainable forest management and planning. The similarities between the types of data addressed with LSTM algorithms and crown profile data make a compelling argument for the integration of deep learning into the crown profile modeling. Thus, the aim was to study the application of deep learning method LSTM and its variant algorithms in the crown profile modeling, using the crown profile database from Pinus yunnanensis secondary forests in Yunnan province, in southwest China. Furthermore, the SHAP (SHapley Additive exPlanations) was used to interpret the predictions of ensemble or deep learning models. The results showed that LSTM’s variant algorithms was competitive with traditional Vanila LSTM, but substantially outperformed ensemble learning model LightGBM. Specifically, the proposed Hybrid LSTM-LightGBM and Integrated LSTM-LightGBM have achieved a best forecasting performance on training set and testing set respectively. Furthermore, the feature importance analysis of LightGBM and Vanila LSTM presented that there were more factors that contribute significantly to Vanila LSTM model compared to LightGBM model. This phenomenon can explain why deep learning outperforms ensemble learning when there are more interrelated features.

The emerging cloud storage technology has significantly improved efficiency and productivity in the traditional electronic healthcare field. However, it has also brought about many security concerns. Ciphertext policy attribute-based encryption (CP-ABE) holds immense potential in achieving fine-grained access control, providing robust security for electronic healthcare data in the cloud. However, current CP-ABE schemes still face issues such as inflexible attribute revocation, relatively lower computational capabilities, and key management. To address these issues, this paper introduces a revocable and traceable undeniable ciphertext policy attribute-based encryption scheme (MA-RUABE). MA-RUABE not only enables fast and accurate data traceability, effectively preventing malicious user key leakage, but also includes a direct revocation feature, significantly enhancing computational efficiency. Furthermore, the introduction of a multi-permission mechanism resolves the issue of centralization of power caused by single-attribute permissions. Furthermore, a security analysis demonstrates that our system ensures resilience against chosen plaintext attacks. Experimental results demonstrate that MA-RUABE incurs lower computational overhead, effectively enhancing system performance and ensuring data-sharing security in cloud-based electronic healthcare systems.

Abstract Background Out-of-hospital cardiac arrest (OHCA), a global health problem with a survival rate ranging from 2 to 22% across different countries, has been a leading cause of premature death for decades. The aim of this study was to evaluate the trends of survival after OHCA over time and its relationship with bystander cardiopulmonary resuscitation (CPR), initial shockable rhythm, return of spontaneous circulation (ROSC), and survived event. Methods In this prospective observational study, data of OHCA patients were collected following the “Utstein style” by the Beijing, China, Emergency Medical Service (EMS) from January 2011 (data from February to June in 2011 was not collected) to October 2016. Patients who had a cardiac arrest and for whom an ambulance was dispatched were included in this study. All cases were followed up to determine hospital discharge or death. The trend of OHCA survival was analyzed using the Chi-square test. The relationship among bystander CPR, initial shockable rhythm, ROSC, survived event, and OHCA survival rate was analyzed using multivariate path analyses with maximum standard likelihood estimation. Results A total of 25,421 cases were transferred by the Beijing EMS; among them, 5042 (19.8%) were OHCA (median age: 78 years, interquartile range: 63–85, 60.1% male), and 484 (9.6%) received bystander CPR. The survival rate was 0.6%, which did not improve from 2012 to 2015 (P = 0.569). Overall, bystander CPR was indirectly associated with an 8.0% (β = 0.080, 95% confidence interval [CI] = 0.064–0.095, P = 0.002) increase in survival rate. The indirect effect of bystander CPR on survival rate through survived event was 6.6% (β = 0.066, 95% CI = 0.051–0.081, P = 0.002), which accounted for 82.5% (0.066 of 0.080) of the total indirect effect. With every 1 increase in survived event, the possibility of survival rate will directly increase by 53.5% (β = 0.535, 95% CI = 0.512–0.554, P = 0.003). Conclusions The survival rate after OHCA was low in Beijing which has not improved between 2012 and 2015. The effect of bystander CPR on survival rate was mainly mediated by survived event. Trial registration Chinese Clinical Trial Registry: ChiCTR-TRC-12002149 (2 May, 2012, retrospectively registered). http://www.chictr.org.cn/showproj.aspx?proj=7400

Abstract With the rapid development of wearable and intelligent flexible electronic devices (FEDs), the demand for flexible energy storage/conversion devices (ESCDs) has also increased. Rechargeable flexible metal‐air batteries (MABs) are expected to be one of the most ideal ESCDs due to their high theoretical energy density, cost advantage, and strong deformation adaptability. With the improvement of the device design, material assemblies, and manufacturing technology, the research on the electrochemical performance of flexible MABs has made significant progress. However, achieving the high mechanical flexibility, high safety, and wearable comfortability required by FEDs while maintaining the high performance of flexible MABs are still a daunting challenge. In this review, flexible Zn‐air and Li‐air batteries are mainly exemplified to describe the most recent progress and challenges of flexible MABs. We start with an overview of the structure and configuration of the flexible MABs and discuss their impact on battery performance and function. Then it focuses on the research progress of flexible metal anodes, gel polymer electrolytes, and air cathodes. Finally, the main challenges and future research perspectives involving flexible MABs for FEDs are proposed.

Abstract Blockchain technology has the characteristics of decentralization and tamper resistance, which can store data safely and reduce the cost of trust effectively. However, the existing blockchain system has weak performance in data management, and only supports traversal queries with transaction hashes as keywords. The query method based on the account transaction trace chain (ATTC) improves the query efficiency of historical transactions of the account. However, the efficiency of querying accounts with longer transaction chains has not been effectively improved. Given the inefficiency and single method of the ATTC index in the query, we propose a subchain-based account transaction chain (SCATC) index structure. First, the account transaction chain is divided into subchains, and the last block of each subchain is connected by a hash pointer. The block-by-block query mode in ATTC is converted to the subchain-by-subchain query mode, which shortens the query path. Multiple transactions of the same account in the same block are merged and stored, which simplifies the construction cost of the index and saves storage resources. then, the construction algorithm and query algorithm is given for the SCATC index structure. Simulation analysis shows that the SCATC index structure significantly improves query efficiency.

Background: An association between inflammatory bowel disease (IBD) [which includes ulcerative colitis (UC) and Crohn’s disease (CD)] and IgA nephropathy (IgAN) has been discovered in observational studies, but the causal relationship is still unknown. The aim of this study was to clarify the causal link between IBD (which includes UC and CD) and IgAN via a two-sample Mendelian randomization (MR) analysis.Methods: Eligible single-nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) for analyses and were obtained from the publicly available genome-wide association study (GWAS) summary statistics. Inverse-variance weighting (IVW), Mendelian randomization–Egger (MR-Egger) regression, the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test, and the weighted median were utilized to obtain the results. The MR-PRESSO test and MR-Egger regression were also performed to detect and correct horizontal pleiotropy. The Cochran’s Q test and “leave-one-out” analysis were also conducted to assess the stability and reliability of the MR results.Results: This study found that IBD, UC, and CD all had significant positive causal effects on IgAN risk (IBD: OR = 1.58, 95% CI 1.15–2.16, p = 4.53 × 10–3; UC: OR = 1.55, 95% CI 1.14–2.11, p = 4.88 × 10–3; CD: OR = 1.57, 95% CI 1.21–2.03, p = 5.97 × 10–4). No significant horizontal pleiotropic effect was found for the causal association between IBD, UC, CD, and the risk of IgAN. Cochran’s Q test identified no evidence of heterogeneity for the IV estimates. The “leave-one-out” sensitivity analysis also revealed that the MR results were robust.Conclusion: The results of this two-sample MR analysis supported that IBD, UC, and CD were causally associated with the risk of IgAN, while there was no sufficient evidence for the causal effect of IgAN on IBD, UC, or CD. Our findings provide theoretical support and a new perspective for the diagnosis and treatment of these two diseases.

Abstract The delegating computation has become an irreversible trend, together comes the pressing need for fairness and efficiency issues. To solve this problem, we leverage game theory to propose a smart contract-based solution. First, according to the behavioral preferences of the participants, we design an incentive contract to describe the motivation of the participants. Next, to satisfy the fairness of the rational delegating computation, we propose a rational delegating computation protocol based on reputation and smart contract. More specifically, rational participants are to gain the maximum utility and reach the Nash equilibrium in the protocol. Besides, we design a reputation mechanism with a reputation certificate, which measures the reputation from multiple dimensions. The reputation is used to assure the client’s trust in the computing party to improve the efficiency of the protocol. Then, we conduct a comprehensive experiment to evaluate the proposed protocol. The simulation and analysis results show that the proposed protocol solves the complex traditional verification problem. We also conduct a feasibility study that involves implementing the contracts in Solidity and running them on the official Ethereum network. Meanwhile, we prove the fairness and correctness of the protocol.

Abstract Background Mobile health-based individualized interventions have shown potential effects in managing cardiovascular risk factors. This study aims to assess whether or not mHealth based individualized interventions delivered by an Individualized Cardiovascular Application system for Risk Elimination (iCARE) could reduce the incidence of major cardiovascular events in individuals with coronary heart disease. Methods This study is a large-scale, multi-center, parallel-group, open-label, randomized controlled clinical trial. This study will be conducted from September 2019 to December 2025. A total of 2820 patients with coronary heart disease will be recruited from two clinical sites and equally randomized into three groups: the intervention group and two control groups. All participants will be informed of six-time points (at 1, 3, 6, 12, 24, and 36 months after discharge) for follow-up visits. Over a course of 36 months, patients who are randomized to the intervention arm will receive individualized interventions delivered by a fully functional iCARE that using various visualization methods such as comics, videos, pictures, text to provide individualized interventions in addition to standard care. Patients randomized to control group 1 will receive interventions delivered by a modified iCARE that only presented in text in addition to routine care. Control group 2 will only receive routine care. The primary outcome is the incidence of major cardiovascular events within 3 years of discharge. Main secondary outcomes include changes in health behaviors, medication adherence, and cardiovascular health score. Discussion If the iCARE trial indeed demonstrates positive effects on patients with coronary heart disease, it will provide empirical evidence for supporting secondary preventive care in this population. Results will inform the design of future research focused on mHealth-based, theory-driven, intelligent, and individualized interventions for cardiovascular risk management. Trial registration Trial registered 24th December 2016 with the Chinese Clinical Trial Registry (ChiCTR-INR-16010242). URL: http://www.chictr.org.cn/showproj.aspx?proj=17398 .

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor with poor prognosis. Temozolomide (TMZ) is the standard chemotherapy for glioblastoma treatment, but TMZ resistance significantly compromises its efficacy. In the present study, we generated a TMZ-resistant cell line and identified that mitochondrial dysfunction was a novel factor contributing to TMZ resistance though multi-omics analyses and energy metabolism analysis. Furthermore, we found that rotenone treatment induced TMZ resistance to a certain level in glioblastoma cells. Notably, we further demonstrated that elevated Ca2+ levels and JNK–STAT3 pathway activation contributed to TMZ resistance and that inhibiting JNK or STAT3 increases susceptibility to TMZ. Taken together, our results indicate that co-administering TMZ with a JNK or STAT3 inhibitor holds promise as a potentially effective treatment for glioblastoma.

Pumping stations play an important role in China’s South-to-North Water Diversion, agricultural irrigation, and municipal drainage. Some pumping station units have been put into operation for long periods with improper operation and require maintenance. Moreover, the surfaces of the flow components have been worn and corroded, leading to an increase in the relative roughness and a decrease in the hydraulic performance efficiencies of pumping station units. In this work, we performed field measurements and numerical simulations to study the influence of the wall roughness on the hydraulic performance of slanted axial-flow pump devices under multiple working conditions. The effects of the wall roughness of the impeller chamber on the hydraulic performance of the pump, the guide vane chamber, and the inlet and outlet flow channel were investigated. Wall roughness had the largest influence on the hydraulic performance of the pump and the smallest influence on the inlet and outlet flow channels. For devices with different roughness values on the impeller chamber wall under different flow rate conditions, the performance of the pump device worsened under the large-flow-rate condition, and the device performance was better under the small-flow-rate and designed flow conditions. The efficiency of the slanted axial-flow pump device decreased significantly as the flow rate increased. Under the same flow rate condition, the performance of the device with Ra = 5 μm was similar to that with a smooth wall, where Ra is the roughness of the wall. With the increase in the roughness, the uniformity of the axial velocity distribution coefficient decreased, and the velocity-weighted average drift angle increased. External characteristic parameters, such as the torque and the static pressure, on the blade pressure surface gradually decreased with the increase in the wall roughness. A large roughness could induce instability of the wall flow and enhance the turbulent kinetic energy near the blade surface.

Cellular metabolism modulates effector functions in human CD4+ T (Th) cells by providing energy and building blocks. Conversely, cellular metabolic responses are modulated by various influences, e.g., age. Thus, we hypothesized that metabolic reprogramming in human Th cells during aging modulates effector functions and contributes to “inflammaging”, an aging-related, chronic, sterile, low-grade inflammatory state characterized by specific proinflammatory cytokines. Analyzing the metabolic response of human naive and memory Th cells from young and aged individuals, we observed that memory Th cells exhibit higher glycolytic and mitochondrial fluxes than naive Th cells. In contrast, the metabolism of the latter was not affected by donor age. Memory Th cells from aged donors showed a higher respiratory capacity, mitochondrial content, and intracellular ROS production than those from young donors without altering glucose uptake and cellular ATP levels, which finally resulted in higher secreted amounts of proinflammatory cytokines, e.g., IFN-γ, IP-10 from memory Th cells taken from aged donors after TCR-stimulation which were sensitive to ROS inhibition. These findings suggest that metabolic reprogramming in human memory Th cells during aging results in an increased expression of proinflammatory cytokines through enhanced ROS production, which may contribute to the pathogenesis of inflammaging.

Abstract The constitutive activation of B-cell receptor (BCR) signaling, together with the overexpression of the Bcl-2 family anti-apoptotic proteins, represents two hallmarks of chronic lymphocytic leukemia (CLL) that drive leukemia cell proliferation and sustain their survival. TG02 is a small molecule multi-kinase inhibitor that simultaneously targets both of these facets of CLL pathogenesis. First, its inhibition of cyclin-dependent kinase 9 blocked the activation of RNA polymerase II and transcription. This led to the depletion of Mcl-1 and rapid induction of apoptosis in the primary CLL cells. This mechanism of apoptosis was independent of CLL prognostic factors or prior treatment history, but dependent on the expression of BAX and BAK. Second, TG02, which inhibits the members of the BCR signaling pathway such as Lck and Fyn, blocked BCR-crosslinking-induced activation of NF-κB and Akt, indicating abrogation of BCR signaling. Finally, the combination of TG02 and ibrutinib demonstrated moderate synergy, suggesting a future combination of TG02 with ibrutinib, or use in patients that are refractory to the BCR antagonists. Thus, the dual inhibitory activity on both the CLL survival pathway and BCR signaling identifies TG02 as a unique compound for clinical development in CLL and possibly other B cell malignancies.

Circular RNA (circRNA) is a newly discovered class of noncoding RNAs that plays key regulatory role in pathological development, including the regulation of several solid tumors. However, the effects of circRNA expression on oral squamous cell carcinoma (OSCC) remain unclear. With the use of high-throughput RNA sequencing data on eight paired oral cancer and adjacent healthy tissues, we observed that circRNA derived from the gene encoding pleckstrin homology domain-interacting protein (circPHIP) was highly expressed in OSCC. Additionally, circPHIP was highly expressed in other OSCC-related cell lines and was associated with tumor metastasis, TNM stage, and human papilloma virus infection status. The inhibition of circPHIP expression reduced OSCC cell migration, invasion, and proliferation. We found that circPHIP could adsorb microRNA (miR)-142-5p and upregulate the expression of PHIP and alpha-actinin 4 (ACTN4), both of which are potential oncogenes closely related to OSCC prognosis. The inhibition of miR-142-5p or overexpressing PHIP or ACTN4 reversed the circPHIP depletion-induced attenuation of OSCC malignancy. In conclusion, circPHIP is overexpressed in OSCC and enhances its malignancy via an miR-142-5p/PHIP-ACTN4/AKT serine/threonine kinase 1 signaling axis. Therefore, circPHIP may represent a novel target for treating OSCC.

Objectives: The novel long non-coding RNA (lncRNA) LINC01094 is often upregulated in renal cell carcinoma and glioma; however, its role in gastric cancer remains unclear. Here, we aim to demonstrate the relationship between LINC01094 and gastric cancer. Method: The gene expression (RNASeq) data of 375 patients with localized, locally advanced, and metastatic gastric cancer were extracted from The Cancer Genome Atlas. The Kruskal–Wallis test, Wilcoxon signed-rank test, and logistic regression were used to analyze the relationship between the clinicopathological characteristics and LINC01094 expression. Cox regression analysis and the Kaplan–Meier method were used to assess prognostic factors of gastric cancer. A nomogram based on Cox multivariate analysis was used to predict the impact of LINC01094 on gastric cancer prognosis. Gene set enrichment analysis (GSEA) was used to identify key LINC01094-associated signaling pathways. Fluorescence in situ hybridization (FISH) was performed to detect the location of LINC01094 in the tissue, and a competing endogenous (ce)RNA network was constructed to identify LINC01094-related genes. Spearman's rank correlation was used to elucidate the association between LINC01094 expression level and immune cell infiltration level. Result: LINC01094 expression was upregulated in gastric cancer tissues and strongly associated with overall survival using univariate Cox regression (hazard ratio [HR] = 1.476, 95% CI = 1.060-2.054, P = .021) and multivariate Cox regression analysis (HR = 1.535, 95% CI = 1.021-2.308, P = .039). The area under the receiver operating characteristic curve of LINC01094 was 0.910. GSEA showed a strong relationship between LINC01094 and the epithelial-mesenchymal transition pathway. RNA-FISH demonstrated that LINC01094 localized in the cytoplasm. It was closely related to the epithelial-mesenchymal transition (EMT) marker SNAI2 , according to ceRNA ( R = 0.61, P

Microplastics (MPs) have been found in nearly half of the fish samples collected from the field worldwide. There are feeding behavior differences caused by animal personality among fish individuals. However, how personality affects the exposure of fish to microplastics is unclear. In this study, adult zebrafish were used as a model to study the effects of fish personality (boldness) on MPs exposure. Experiment showed that zebrafish captured MPs actively when MPs were added to the system but spit part of the MPs out after capturing. Bold zebrafish had higher feeding activities, captured MPs more frequently and swallowed more MPs than shy zebrafish. Zebrafish ingested brine shrimp preferentially when both brine shrimp and MPs were provided at the same time, and less MPs were swallowed in co-ingestion situation. Spearman correlation analysis indicated that there is a significantly positive correlation between boldness and feeding MPs frequency. Results of this work demonstrate that zebrafish mistake MPs as food and capture them actively but can discriminate MPs as inedible substances after ingestion and spit part of the MPs out. Bold zebrafish have a higher MP exposure burden than shy zebrafish due to their difference in feeding behaviors. The influence of fish personality needs to be considered for future toxicity studies and risk assessment of fish exposed to MPs.

The adversarial attack is crucial to improving the robustness of deep learning models; they help improve the interpretability of deep learning and also increase the security of the models in real-world applications. However, existing attack algorithms mainly focus on image classification tasks, and they lack research targeting object detection. Adversarial attacks against image classification are global-based with no focus on the intrinsic features of the image. In other words, they generate perturbations that cover the whole image, and each added perturbation is quantitative and undifferentiated. In contrast, we propose a global-to-local adversarial attack based on object detection, which destroys important perceptual features of the object. More specifically, we differentially extract gradient features as a proportion of perturbation additions to generate adversarial samples, as the magnitude of the gradient is highly correlated with the model’s point of interest. In addition, we reduce unnecessary perturbations by dynamically suppressing excessive perturbations to generate high-quality adversarial samples. After that, we improve the effectiveness of the attack using the high-frequency feature gradient as a motivation to guide the next gradient attack. Numerous experiments and evaluations have demonstrated the effectiveness and superior performance of our from global to Local gradient attacks with high-frequency momentum guidance (GLH), which is more effective than previous attacks. Our generated adversarial samples also have excellent black-box attack ability.

Public key encryption with keyword search (PEKS) allows users to perform keyword searches of ciphertext on untrusted cloud storage servers, protecting data privacy while sharing data. However, it faces several security problems in practical applications. First, an attacker can launch a keyword guessing attack to obtain keywords of interest to users, causing the leakage of their sensitive information. Second, untrusted cloud servers may return incorrect or incomplete results. In addition, with the continuous development of quantum computers, existing PEKS schemes face the problem of quantum attacks. Since cloud servers are mostly untrusted, verifiable search has become a hot research topic among scholars. However, most of the current schemes are based on bilinear pairing constructions, which are vulnerable to quantum attacks. To solve these problems, we propose a new ciphertext retrieval scheme based on fully homomorphic encryption (FHE), called VR-PEKS. This scheme implements verifiable search and is able to solve the problems of keyword guessing attacks and quantum attacks. We propose to improve the security of the scheme by using the oblivious pseudorandom function to randomize keywords and then encrypt them using FHE. An encrypted verified index structure is constructed and exposed by the data owner, enabling the data recipient to achieve verification of the correctness and integrity of the retrieved results without relying on a trusted third party. We demonstrate the security of the proposed scheme in a stochastic prediction model, and prove that our scheme satisfies keyword ciphertext indistinguishability and keyword trapdoor indistinguishability under adaptive keyword selection attacks. The comparison shows that our scheme is secure and feasible.

Advances in information technology have made data accessible anytime and anywhere. Currently, data confirmation is a popular area of research. Many current approaches to data confirmation rely on submitting certificates of ownership, embedding digital watermarks, or using blockchain. However, none of these approaches can avoid exposing source data to third parties that are not fully trusted. To address this issue, this paper proposes a new data confirmation method based on ciphertext policy attribute-based encryption (CP-ABE), which is widely used in cloud storage environments. The unique identifier of the data owner is encrypted by Paillier encryption and embedded into the ciphertext, so that the ownership corresponding to the plaintext is converted to the ownership corresponding to the ciphertext. During the entire confirmation process, third-party organizations cannot access the source data, reducing the risk of source data leakage. Finally, the feasibility of the scheme is proved by security proof and experiment comparison.

Federated Learning (FL) is an emerging distributed framework that enables clients to conduct distributed learning and globally share models without requiring data to leave the local. In the FL process, participants are required to contribute data resources and computing resources for model training. However, the traditional FL lacks security guarantees and is vulnerable to attacks and damages by malicious adversaries. In addition, the existing incentive methods lack fairness to participants. Therefore, accurately identifying and preventing malicious nodes from doing evil, while effectively selecting and incentivizing participants, plays a vital role in improving the security and performance of FL. In this paper, we propose a Robust Federated Learning Based on Malicious Detection and Incentives (MDIFL). Specifically, MDIFL first uses a gradient similarity to calculate reputation, thereby maintaining the reputation of participants and identifying malicious opponents, and then designs an effective incentive mechanism based on contract theory to achieve collaborative fairness. Extensive experimental results demonstrate that the proposed MDIFL can not only preferentially select and effectively motivate high-quality participants, but also correctly identify malicious adversaries, achieve fairness, and improve model performance.

BackgroundDeath and disability from coronary heart disease (CHD) can be largely reduced by improving risk factor management. However, adhering to evidence-based recommendations is challenging and requires interventions at the level of the patient, provider, and health system. ObjectiveThe aim of this study was to develop an Intelligent Individualized Cardiovascular App for Risk Elimination (iCARE) to facilitate adherence to health behaviors and preventive medications, and to test the usability of iCARE. MethodsWe developed iCARE based on a user-centered design approach, which included 4 phases: (1) function design, (2) iterative design, (3) expert inspections and walkthroughs of the prototypes, and (4) usability testing with end users. The usability testing of iCARE included 2 stages: stage I, which included a task analysis and a usability evaluation (January to March 2019) of the iCARE patient app using the modified Health Information Technology Usability Survey (Health-ITUES); and stage II (June 2020), which used the Health-ITUES among end users who used the app for 6 months. The end users were individuals with a confirmed diagnosis of CHD from 2 university-affiliated hospitals in Beijing, China. ResultsiCARE consists of a patient app, a care provider app, and a cloud platform. It has a set of algorithms that trigger tailored feedback and can send individualized interventions based on data from initial assessment and health monitoring via manual entry or wearable devices. For stage I usability testing, 88 hospitalized patients (72% [63/88] male; mean age 60 [SD 9.9] years) with CHD were included in the study. The mean score of the usability testing was 90.1 (interquartile range 83.3-99.0). Among enrolled participants, 90% (79/88) were satisfied with iCARE; 94% (83/88) and 82% (72/88) reported that iCARE was useful and easy to use, respectively. For stage II usability testing, 61 individuals with CHD (85% [52/61] male; mean age 53 [SD 8.2] years) who were from an intervention arm and used iCARE for at least six months were included. The mean total score on usability testing based on the questionnaire was 89.0 (interquartile distance: 77.0-99.5). Among enrolled participants, 89% (54/61) were satisfied with the use of iCARE, 93% (57/61) perceived it as useful, and 70% (43/61) as easy to use. ConclusionsThis study developed an intelligent, individualized, evidence-based, and theory-driven app (iCARE) to improve patients’ adherence to health behaviors and medication management. iCARE was identified to be highly acceptable, useful, and easy to use among individuals with a diagnosis of CHD. Trial RegistrationChinese Clinical Trial Registry ChiCTR-INR-16010242; https://tinyurl.com/2p8bkrew

At sites of inflammation, monocytes carry out specific immune functions while facing challenging metabolic restrictions. Here, we investigated the potential of human monocytes to adapt to conditions of gradually inhibited oxidative phosphorylation (OXPHOS) under glucose free conditions. We used myxothiazol, an inhibitor of mitochondrial respiration, to adjust two different levels of decreased mitochondrial ATP production. At these levels, and compared to uninhibited OXPHOS, we assessed phagocytosis, production of reactive oxygen species (ROS) through NADPH oxidase (NOX), expression of surface activation markers CD16, CD80, CD11b, HLA-DR, and production of the inflammatory cytokines IL-1β, IL-6 and TNF-α in human monocytes. We found phagocytosis and the production of IL-6 to be least sensitive to metabolic restrictions while surface expression of CD11b, HLA-DR, production of TNF-α, IL-1β and production of ROS through NOX were most compromised by inhibition of OXPHOS in the absence of glucose. Our data demonstrate a short-term hierarchy of immune functions in human monocytes, which represents novel knowledge potentially leading to the development of new therapeutics in monocyte-mediated inflammatory diseases.

Because social networks exemplify the phenomenon of homogeneity in complex networks, researchers generally believe that a user's privacy disclosure is closely related to that of the users around them, but we find that the related users studied in previous methods were not correct. That is, the analyzed user groups may have had nothing to do with the privacy disclosure of the target users. Since private information is time-sensitive, information held by users who are no longer in the same environment as the target user may no longer be true and have lost its value. For example, considering students and members of the working class, transfers to another school for further studies or job changes entail dramatic changes to most of their information. This lack of timeliness has an overarching impact on the effectiveness of social network analysis and privacy protection, but this problem has not been addressed by researchers. Therefore, we study and characterize this problem, add the user's behavior trace to solve this problem and measure the user's privacy status more accurately.

Streaming media has been largely used by millions of users every day. The number of customers and programs, e.g., TV series, movies, and various shows, are still growing fast. However, the demand for video transcoding for various personal terminal devices results in the shortage of computing resources and the prolongation of processing delay in centralized video transcoding systems. To solve this issue, we propose a blockchain, especially, smart contract based scheme that can achieve decentralized and on-demand crowdsourcing for video transcoding, which remarkably mitigates the transcoding overhead. Specifically, our scheme consists of four key components such as employers, workers, task allocation, and payment. An employer initializes the smart contract, releases the task, and initiates the smart contract. Workers bid for the task, and the successful bidder will obtain the task and execute the task. The task allocation mechanism and the payment mechanism can guarantee the profits of both and encourage both as well. Moreover, the smart contract consists of the bidding contract and the task execution contract. The extensive analysis of our proposed scheme justified the feasibility, security for defending against typical threats, applicability in realistic situations, and portability for most multimedia such as videos and audios.

With the gradually opening of energy markets and popularization of Electric Vehicles (EVs), EVs can transmit, dispatch and recharge energy in different markets and domains dynamically. However, in Vehicular Energy Network, EVs may randomly enter and leave a market, it imposes a difficult problem in that how to schedule and distribute energy effectively. Additionally, the location of EV owners usually includes sensitive information such as home addresses, company names, hospital traces, and so on, which may be collected by attackers and may result in the privacy leakage about EV owners. In this article, we propose a decentralized blockchain-enabled energy trading scheme that can trade cross over various domains efficiently, which enables reliable transactions between EVs and energy nodes within short processing delay. It can also preserve the privacy of EV owners, by adopting the k-anonymity method in constructing a united request to hide the location information and creating a clocking area based on undirected graphs. Even though the server is maliciously attacked, the attacker cannot distinguish among EV owners, which breaks the linkage between real locations and identities to preserve EV owners’ privacy. Finally, we conduct a comprehensive experimental evaluation to evaluate the trading performance and location privacy protection performance. The simulation results show that our proposed architecture outperforms over most state-of-the-art schemes in terms of processing delay and location privacy awareness.

Abstract Background The mortality of coronary heart disease can be largely reduced by modifying unhealthy lifestyles. However, the long-term effectiveness of interventions for modifying unhealthy diet and physical inactivity of patients with coronary heart disease remain unsatisfactory worldwide. This study aims to systematically design a set of theory-based and evidence-based, individualized, and intelligent interventions for promoting the adoption and maintenance of a healthy diet and physical activity level in patients with coronary heart disease. Methods The interventions will be delivered by a mobile health care system called Individualized, Intelligent and Integrated Cardiovascular Application for Risk Elimination. Three steps of the intervention mapping framework were used to systematically develop the interventions. Step 1: needs assessment, which was carried out by a literature review, in-depth interviews and focus group discussions. Step 2: development of objective matrix for diet and physical activity changes, based on the intersection of objectives and determinants from the Contemplation-Action-Maintenance behavior change model. Step 3: formulation of evidence-based methods and strategies, and practical applications, through a systematic review of existing literature, research team discussions, and consultation with multidisciplinary expert panels. Results Three needs relevant to content of the intervention, one need relevant to presentation modes of the intervention, and four needs relevant to functional features of the application were identified. The objective matrix includes three performance objectives, and 24 proximal performance objectives. The evidence-based and theory-based interventions include 31 strategies, 61 evidence-based methods, and 393 practical applications. Conclusions This article describes the development of theory-based and evidence-based interventions of the mobile health care system for promoting the adoption and maintenance of a healthy diet and physical activity level in a structured format. The results will provide a theoretical and methodological basis to explore the application of intervention mapping in developing effective behavioral mobile health interventions for patients with coronary heart disease. Trial registration Chinese Clinical Trial Registry: ChiCTR-INR-16010242. Registered 24 December 2016. http://www.chictr.org.cn/index.aspx

Macrophage activation is an important process in controlling infection, but persistent macrophage activation leads to chronic inflammation and diseases, such as tumor progression, insulin resistance and atherosclerosis. Characterizing metabolic signatures of macrophage activation is important for developing new approaches for macrophage inactivation. Herein, we performed metabolomic analysis on lipopolysaccharide (LPS)-activated macrophages and identified the associated changes in metabolites. Notably, the cellular Nicotinamide adenine dinucleotide+ levels were decreased while NADPH was increased, proposing that NAD+ restoration can inhibit macrophage activation. Indeed, supplementation of nicotinamide mononucleotide (NMN) increased cellular NAD+ levels and decreased cytokine productions in LPS-activated cells. Quantitative proteomics identified that nicotinamide mononucleotide downregulated the expressions of LPS-responsive proteins, in which cyclooxygenase-2 (COX-2) expression was significantly decreased in NMN-treated cells. Consequently, the cellular levels of prostaglandin E2 (PGE2) was also decreased, indicating that NMN inactivated macrophages via COX-2-PGE2 pathway, which was validated in activated THP-1 cells and mouse peritoneal macrophages. In conclusion, the present study identified the metabolic characteristics of activated macrophages and revealed that NMN replenishment is an efficient approach for controlling macrophage activation.

Summary: Mitogen-activated protein kinases (MAPKs) are inactivated by dual-specificity phosphatases (DUSPs), the activities of which are tightly regulated during cell differentiation. Using knockdown screening and single-cell transcriptional analysis, we demonstrate that DUSP4 is the phosphatase that specifically inactivates p38 kinase to promote megakaryocyte (Mk) differentiation. Mechanistically, PRMT1-mediated methylation of DUSP4 triggers its ubiquitinylation by an E3 ligase HUWE1. Interestingly, the mechanistic axis of the DUSP4 degradation and p38 activation is also associated with a transcriptional signature of immune activation in Mk cells. In the context of thrombocytopenia observed in myelodysplastic syndrome (MDS), we demonstrate that high levels of p38 MAPK and PRMT1 are associated with low platelet counts and adverse prognosis, while pharmacological inhibition of p38 MAPK or PRMT1 stimulates megakaryopoiesis. These findings provide mechanistic insights into the role of the PRMT1-DUSP4-p38 axis on Mk differentiation and present a strategy for treatment of thrombocytopenia associated with MDS.

A numerical study is conducted for converging stepped spillways with various spillway slopes, sidewall convergence and flow discharges to understand the influences of converging sidewalls on skimming flows. Compared with the traditional uniform-width stepped spillway, the converging sidewall changes the skimming flow features by generating standing waves on the free-surface, curving the mainstream streamlines and squeezing and distorting the bottom rotations. For free-surface, mainstream and bottom rotations, the width of disturbed regions by the converging sidewall varies, with that for bottom rotations being 1.5 times that for mainstream and 3 times that for free-surface. The variation rules of disturbed region widths along the spillway are obtained, and the maximum widths increase as the convergence angle and incoming flow discharge increase, and the spillway slope decreases. Three equations are established for predicting the maximum widths of disturbed regions for free-surface, mainstream and bottom rotations of skimming flow. Since the disturbed region of skimming flow generated by the converging sidewall is characterized by strong standing waves, high flow velocity and low air concentration, appropriate engineering measurements should be taken for the disturbed region to meet the challenges to overtopping, energy dissipation and cavitation control.

In Location-Based Social Networks (LBSNs), registered users submit their reviews for visited point-of-interests (POIs) to the system providers (SPs). The SPs anonymously publish submitted reviews to build reputations for POIs. Unfortunately, the user profile and trajectory contained in reviews can be easily obtained by adversaries who SPs has compromised with. Even worse, existing techniques, such as cryptography and generalization, etc., are infeasible due to the necessity of public publication of reviews and the facticity of reviews. Inspired by pseudonym techniques, we propose an approach to exchanging reviews before users submit reviews to SPs. In our approach, we introduce two attacks, namely review-based location correlation attack (RLCA) and semantic-based long-term statistical attack (SLSA). RLCA can be exploited to link the real user by reconstructing the trajectory, and SLSA can be launched to establish a connection between locations and users through the difference of semantic frequency. To resist RLCA, we design a method named User Selection to Resist RLCA (USR-RLCA) to exchange reviews. We propose a metric to measure the correlation between a user and a trajectory. Based on the metric, USR-RLCA can select reviews resisting RLCA to exchange by suppressing the number of locations on each reconstructed trajectory below the correlation. However, USR-RLCA fails to resist SLSA because of ignoring the essential semantics. Hence, we design an enhanced USR-RLCA named User Selection to Resist SLSA (USR-SLSA). We first propose a metric to measure the indistinguishability of locations concerning the difference of semantic frequency in a long term. Then, USR-SLSA can select reviews resisting SLSA to exchange by allowing two reviews whose indistinguishability is below the probability difference after the exchange to be exchanged. Evaluation results verify the effectiveness of our approach in terms of privacy and utility.

Today, data is exploding. A large amount of data needs to be processed in a timely and an efficient manner. Aggregate signatures are an efficient and secure way to handle large numbers of digital signatures. In an aggregate signature scheme, n signatures on n messages from n users can be combined into a single signature, which can make anyone believes that the n messages were indeed signed by the n corresponding users. In the recent decade, numerous certificateless aggregate signature (CLAS) schemes have been introduced. In most CLAS schemes currently known, the number of hash-to-point operations and the size of signature increase linearly with the number of signers, so they are not suitable for computing restricted devices, such as mobile devices. In this paper, a new CLAS scheme is constructed, which requires only two pairing operations and the signature contains only one point and state information. It is more efficient than the previous ones and suit for the mobile devices.

The Internet of Things (IoT) is also known as the Internet of everything. As an important part of the new generation of intelligent information technology, the IoT has attracted the attention both of researchers and engineers all over the world. Considering the limited capacity of smart products, the IoT mainly uses cloud computing to expand computing and storage resources. The massive data collected by the sensor are stored in the cloud storage server, also the cloud vulnerability will directly threaten the security and reliability of the IoT. In order to ensure data integrity and availability in the cloud and IoT storage system, users need to verify the integrity of remote data. However, the existing remote data integrity verification schemes are mostly based on the RSA and BLS signature mechanisms. The RSA-based scheme has too much computational overhead. The BLS signature-based scheme needs to adopt a specific hash function, and the batch signature efficiency in the big data environment is low. Therefore, for the computational overhead and signature efficiency issues of these two signature mechanisms, we propose a scheme of data integrity verification based on a short signature algorithm (ZSS signature), which supports privacy protection and public auditing by introducing a trusted third party (TPA). The computational overhead is effectively reduced by reducing hash function overhead in the signature process. Under the assumption of CDH difficult problem, it can resist adaptive chosen-message attacks. The analysis shows that the scheme has a higher efficiency and safety.

Trajectory k-anonymity is a prevalent technique for protecting trajectory privacy. However, the existing techniques for generating fake trajectories can be easily broken by an adversary because of the failure to capture the probabilistic features and geographic features of the trajectories. They also reduce data availability. Thus, this paper proposes a location recombination mechanism (LRM) for achieving trajectory k-anonymity privacy protection. First, we propose a metric that measures the location pair similarity between location pairs. Based on this metric, we select sampling locations and divide locations into different equivalent probability classes. Locations in one equivalent probability class have the same probability as one corresponding base location. Then, we also introduce two metrics that measure the probabilistic similarity and geographic similarity between locations. Based on these metrics, we design algorithms to generate fake trajectories. These algorithms can recombine locations sampled from each equivalent probability class into trajectories. All of these trajectories meet the privacy protection requirements for both base trajectories and sampling trajectories. Finally, we evaluate our scheme thoroughly with real-world data. The results show that our method can protect the privacy of base trajectories and sampling trajectories and achieve a better performance of service provider utility and data availability than other schemes.

Local business service systems (LBSS), as an essential role of location-based service (LBS), have been gaining tremendous popularity in our daily life. Individuals' reviews in these systems are very important as they not only contribute to building reputations for businesses but also play a guiding role for consumers. However, users' privacy disclosure and the effectiveness of reviews are the urgent problems to be solved for the further development of LBSS. This paper proposes a mechanism to improve effectiveness and privacy preservation for review publication. In users' privacy protection, the mechanism firstly formalizes the model of attackers, then focuses on the identification or inference attack caused by reviews. For improving the effectiveness of reviews, the mechanism introduces users' reputation scores to rank the reviews. We evaluate our mechanism thoroughly by extensive experiments, and the results validate that our mechanism can achieve a better performance.

Smart card is indispensable part in our daily life, which brings us many conveniences including e-commerce and m-commerce service. However, because of the limited computation resource, the remote authentication between smart card and server is vulnerable to be attacked over insecure communication channel. Until now, many authentication schemes are proposed with their own pros and cons. Note that most of them are based on Elliptic curve cryptography, which are vulnerable to the card lose attack and desynchronization attack, where some schemes add a random number in verifier-value to resist the card lose attack and store both the old and new pseudo-identities between authenticator and the corresponding authenticated party to withstand desynchronization attack. However, the random number stored in card memory can be extracted and the new conversation may be blindly blocked by adversary. Hence, in this paper, we propose a novel authentication protocol that can utilize physical unclonable function (PUF) and elliptic curve cryptography (ECC) to protect the random number and support offline updating if online updating is blocked, which can be proven safe in formal security analysis. Meanwhile, we also introduce the robust PUF to prevent the modification of help data. Finally, our scheme is efficient by comparing with other related schemes in computation and communication overhead.