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Coated microneedles (MNs) are widely used for delivering biopharmaceuticals. In this study, a novel gel encapsulated coated MNs (GEC-MNs) was developed. The water-soluble drug coating was encapsulated with sodium alginate (SA) in situ complexation gel. The manufacturing process of GEC-MNs was optimized for mass production. Compared to the water-soluble coated MNs (72.02% ± 11.49%), the drug delivery efficiency of the optimized GEC-MNs (88.42% ± 6.72%) was steadily increased, and this improvement was investigated through in vitro drug release. The sustained-release of BSA was observed in vitro permeation through the skin. The rhIFNα-1b GEC-MNs was confirmed to achieve biosafety and 6-month storage stability. Pharmacokinetics of rhIFNα-1b in GEC-MNs showed a linearly dose-dependent relationship. The AUC of rhIFNα-1b in GEC-MNs (4.51 ng/ml·h) was bioequivalent to the intradermal (ID) injection (5.36 ng/ml·h) and significantly higher than water-soluble coated MNs (3.12 ng/ml·h). The rhIFNα-1b elimination half-life of GEC-MNs, soluble coated MNs, and ID injection was 18.16, 1.44, and 2.53 h, respectively. The complexation-based GEC-MNs have proved to be more efficient, stable, and achieve the sustained-release of water-soluble drug in coating MNs, constituting a high value to biopharmaceutical., Graphical abstract In the coated microneedle produced by the layer-by-layer coating method, the water-soluble drug-containing coating is encapsulated by the complexation-based gel (GEC-MNs). After GEC-MNs are applied to the skin, the release rate of the drug is reduced by the outer layer of the gel. The pharmacokinetic results of rh-IFNα-1b showed that compared with intradermal injection and water-soluble coated microneedles, the sustained release was achieved in GEC-MNs.Image, graphical abstract

Ensuring the integrity of remote data is the prerequisite for implementing cloud-edge computing. Traditional data integrity verification schemes make users spend a lot of time regularly checking their data, which is not suitable for large-scale IoT (Internet of Things) data. On the other hand, the introduction of a third-party auditor (TPA) may bring about greater privacy and security issues. We use blockchain to address the problem of TPA. However, implementing dynamic integrity verification with blockchain is a bigger challenge due to the low throughput and poor scalability of blockchain. More importantly, whether there is a security problem with blockchain-based integrity verification is not yet known. In this paper, we propose a scalable blockchain-based integrity verification scheme that implements fully dynamic operations and blockless verification. The scheme builds scalable homomorphic verification tags based on ZSS (Zhang-Safavi-Susilo) short signatures. We exploit smart contract technology to replace TPA for integrity verification tasks, which not only eliminates the risk of privacy leakage but also resists collusion attacks. Furthermore, we formally define a blockchain-based security model and prove that our scheme is secure under the security assumption of cryptographic primitives. Finally, the mathematical analysis of our scheme shows that both the communication complexity and the communication complexity of an audit are O c , in which c is the number of challenge blocks. We compare our scheme with other schemes, and the results show that our scheme has the lowest time consumption to complete an audit.

We describe a swellable microneedle (SMN) consisting of Ca

A distributed storage system (DSS) has the ad-vantages of low price and high throughput, but it also raises serious data confidentiality and privacy issues. Fine-grained access control (AC) is important for further applications. Although attribute-based encryption (ABE) schemes can achieve fine-grained AC, almost all schemes distribute a private key to a visitor by a private key generator that may leak data. Besides, attribute revocation functions of the ABE scheme will lead to collusion attacks. Blockchain-based ABE schemes rarely consider ciphertext-based search and attribute revocation functions which lead to a large communication overhead. In this paper, we propose a secure ABE scheme in which a data owner is the only person who has the right to distribute keys. Then we combine blockchain with the proposed ABE scheme to realize fine-grained AC over a distributed storage system, which supports the attribute change function and resists collusive attacks. In addition, we build a series of smart contracts to ensure the fairness of trade between the data owner and visitor. The auxiliary information of data stored on the blockchain can realize ciphertext-based search. Finally, we prove the scheme resists collusion attacks under the computational Diffie-Hellman assumption (CDH) and conduct multiple experiments based on Ethernet test Network. The experimental results demonstrate our scheme has the running time of algorithms reached a millisecond-level and the ET H cost is acceptable.

Integrity verification of cloud data is of great importance for secure and effective cloud storage since attackers can change the data even though it is encrypted. Traditional integrity verification schemes only let the client know the integrity status of the remote data. When the data is corrupted, the system cannot hold the server accountable. Besides, almost all existing schemes assume that the users are credible. Instead, especially in a dynamic operation environment, users can deny their behaviors, and let the server bear the penalty of data loss. To address the issues above, we propose an accountable dynamic storage integrity verification (ADS-IV) scheme which provides means to detect or eliminate misbehavior of all participants. In the meanwhile, we modify the Invertible Bloom Filter (IBF) to recover the corrupted data and use the Mahalanobis distance to calculate the degree of damage. We prove that our scheme is secure under Computational Diffie-Hellman (CDH) assumption and Discrete Logarithm (DL) assumption and that the audit process is privacy-preserving. The experimental results demonstrate that the computational complexity of the audit is constant; the storage overhead is $O(\sqrt n )$, which is only 1/400 of the size of the original data; and the whole communication overhead is O(1).As a result, the proposed scheme is not only suitable for large-scale cloud data storage systems, but also for systems with sensitive data, such as banking systems, medical systems, and so on.

Cloud storage saves a lot of storage overheads for users to manage data. However, it also brings data integrity challenges. Relying only on message authentication codes (MAC) and hash functions introduces serious communication overheads. Existing integrity verification schemes usually rely on third-party auditors (TPAs) to reduce users’ audit burden. However, malicious TPAs not only extract raw data from repeated audit processes but also collude with a cloud server to launch collusive attacks. Recently, some integrity verification schemes based on blockchain are presented to solve challenges of raw data extraction and collusive attacks. These schemes cannot realize large-scale data processing on a blockchain as well as dynamic data operations. To address the above issues, we propose a blockchain-based cloud data integrity verification scheme (BCD-IV) that removes TPAs by using chain-code that solves collusive attacks. Furthermore, we construct a new homomorphic verification tag (HVT) based on the signature proposed by Zhang, Safavi, and Susilo (ZSS), which supports blockless verification. The proposed scheme realizes full dynamic operations with auxiliary information that stores on a blockchain. Mathematical analysis shows that our scheme has lower complexity in terms of communication and computation overhead, which are both O(c). Finally, we conduct experiments on Hyperledger Fabric V2.2 to demonstrate that the computation efficiency of audit is the highest compared to the state-of-the-art and the storage overhead is negligible.

Recently, optimistic fair exchange in electronic commerce (e-commerce) or mobile commerce (m-commerce) has made great progress. However, new technologies create large amounts of data and it is difficult to handle them. Fortunately, with the assistance of cloud computing and big data, optimistic fair exchange of digital items in cyber-physical systems (CPSes) can be efficiently managed. Optimistic fair exchange in cloud-assisted CPSes mainly focuses on online data exchange in e-commerce or online contracts signing. However, there exist new forms of risks in the uncertain network environment. To solve the above problems, we use a new technique called verifiably encrypted identity-based signature (VEIS) to construct optimistic fair exchange in cloud-assisted CPSes. VEIS is an encrypted signature, and we can check the validity of the underlying signature without decrypting it. We introduce a robust arbitration mechanism to guarantee fairness of the exchange, and even the trusted third party (TTP) cannot get the original signatures of the exchange parties. And the TTP in our protocol is offline, which greatly improves the efficiency. Besides, we show that our protocol is secure, fair, and practical.

Cloud storage services allow users to outsource their data remotely to save their local storage space and enable them to manage resources on demand. However, once users outsourced their data to the remote cloud platform, they lose the physical control of the data. How to ensure the integrity of outsourced data is the major concern of cloud users and also is the main challenge in the cloud service deployment. Limited by the communication and computation overheads, traditional hash-based integrity verification solutions in the stand-alone systems cannot be directly adopted in remote cloud storing environment. In this paper, we improve the previous privacy preserving model and propose an effective integrity verification scheme of cloud data based on BLS signature (EoCo), which ensures public audition and data privacy preserving. In addition, EoCo also supports batch auditing operations. We conducted theoretical analysis of our scheme, demonstrated its correctness and security properties, and evaluated the system performance as well.

It is difficult to determine the threshold of mode cell in the interval-thresholding algorithm, when it is used to denoise chaotic signals. In this paper, an adaptive denoising algorithm is proposed for chaotic signals based on improved empirical mode decomposition. First, the noisy chaotic signal is decomposed into the intrinsic mode functions (IMFs) by improved complete ensemble empirical mode decomposition. Then, the zero-crossing scale thresholding denoising algorithm is used to denoise the IMFs with different thresholds. The optimal threshold is obtained by the Durbin–Watson criterion. With the optimal threshold, the final denoised chaotic signal is obtained. The proposed algorithm effectively solves the issue mentioned above. The experimental results show the proposed algorithm can denoise noisy chaotic signals in different conditions effectively and is better than other existing algorithms.

The aim of this study was to prepare dissolving microneedles (DMNs) patches containing tranexamic acid (TA) for the treatment of melasma. Polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) were preferred as matrix materials through the compatibility experiment. In the in vitro permeation study, the transdermal amount of TA was significantly promoted through dissolving microneedles with the cumulative release was 44.43 ± 6.55%. By comparison, the release of TA solution assisted with solid microneedles (SMNs) was merely 11.31 ± 2.30% (p 0.05). Pharmacokinetics study indicated the bioavailability of dissolving microneedles was more than 1.3 times compared with oral administration. In pharmacodynamics investigation, TA dissolving microneedles obviously reduced melanin deposition in the skin of melasma guinea pigs after 8 consecutive administrations. In particular, the combination of tranexamic acid and licorice extract (LIC) dissolving microneedles worked better than tranexamic acid alone. Accelerated stress conditions including high temperature, high humidity, as well as photostability were designed to prove that TA microneedles maintained good pharmaceutical stability. In conclusion, tranexamic acid dissolving microneedles showed reliable quality and remarkable effect. Moreover, the combination of tranexamic acid and licorice extract had a synergistic therapy in melasma.

Hexapod bionic robot plays an important role in battlefield reconnaissance and battlefield rescue. However, due to the complex battlefield situation, the robot’s legs are often damaged due to attacks, electromagnetic interference and other reasons, so it cannot work normally according to the original gait planning. In this paper, the damage situation of the hexapod bionic robot gait planning study, establish a foot injury cases six-legged robot model, USES the existing six-legged robot, combined with Matlab simulation model, build six-legged robot for foot injury under the condition of six-legged robot, simulation analysis is carried out under the different gait, planning out the suitable gait of robot movement. According to the analysis, the suitable gait under the condition of different injuries was obtained. This study can be used to improve the adaptability of hexapod robot in battlefield conditions and extend the working life of hexapod robot.

Hexapod robot plays an important role in rescue and relief, battlefield rescue and other occasions. However, due to the influence of environment and other factors, the hexapod robot may be damaged to different degrees, which makes it unable to work normally. This paper studies the gait of hexapod robot under the condition of damage, analyzes the different damaged conditions of hexapod robot, establishes the hexapod robot model under different damaged conditions, studies the gait and stability of hexapod robot under the condition of single-leg damaged, and plans the stable gait suitable for the robot to continue to work. According to the simulation analysis, the four-legged and three-legged gait of the hexapod robot under the condition of single-foot damage which makes itself work normally is obtained. The research method in this paper can be applied to other multi-legged robots under different damage conditions, which has certain significance to improve the working life of these kinds of robots.

Hydrophobic drugs wrapped in poly (lactic-co-glycolic acid) (PLGA)-based microneedles (MNs) require a long time to release completely. To obtain the desired duration, it is still necessary to modulate the release of hydrophobic drugs from MNs, while the PLGA composition is unchangeable. In this work, implantable PLGA microneedles (IPMNs) composed of PLGA arrowheads encapsulating levonorgestrel (LNG) and a water-soluble supporting array were designed. We explored trehalose used as a porogen on the release of hydrophobic LNG from PLGA-based MNs. Varying the trehalose content in PLGA arrowheads could induce different rates of drug release. The highest cumulative release of LNG was 76.2 &plusmn, 3.9% for IPMNs with 33.3% trehalose during 21 days in vitro, while the cumulative release of LNG was 60.4 &plusmn, 3.5% for IPMNs without trehalose. Pharmacokinetic results in rats showed that plasma levels of LNG were sustained for 13 days for IPMNs with 33.3% trehalose and 16 days for IPMNs without trehalose. Furthermore, the PLGA arrowheads with trehalose degraded more rapidly than those without trehalose over 21 days in rats. Consequently, using trehalose as a porogen was a feasible approach to modulate the release of a hydrophobic drug from PLGA-based MNs.

Introduction Gastric cancer is the second leading cause of cancer mortality in the world. Whether the oncogene, amplified on chromosome 3q26, SOX2, a master transcriptional regulator of stemness, operate to drive strong growth phenotype in gastric cancer were unknown.

The Editor-in-Chief is retracting this article (Tian et al 2014) due to concerns regarding peer review, authorship and originality of the article.

Genistein possesses a wide variety of biological activities, and it is best known for its ability to inhibit cancer progression. Its cancer-preventive effect has been attributed to various mechanisms, including the induction of cell cycle arrest and apoptosis as well as the antioxidant functions. Nuclear factor kappa-B (NF-κB) is a signaling pathway that controls transcriptional activation of genes important for the tight regulation of many cellular processes and is aberrantly expressed in many types of cancer. Inhibitors of NF-κB pathway have shown potential anti-tumor activities. However, it is not fully elucidated in colon cancer. In the present study, we demonstrated that genistein could induce apoptosis in human colon cancer LoVo and HT-29 cells through inhibiting NF-κB pathway, as well as downregulation of Bcl-2 and upregulation of Bax, thus providing basis for clinical application of genistein in colon cancer cases.

Gastric cancer is the second leading cause of cancer mortality in the world. Whether the oncogene, amplified on chromosome 3q26, SOX2, a master transcriptional regulator of stemness, operate to drive strong growth phenotype in gastric cancer were unknown.The gene expression changes of SOX2 in human gastric cancer tissues compared with non-cancerous tissues was detected using real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohistochemistry, which identified the gene overexpression of SOX2 in gastric cancer. Moreover, we discovered that SOX2 promoted cancer cell proliferation in vitro/vivo and SOX2 expression correlated with elevated AKT phosphorylation in gastric cancer, while the AKT phosphorylation was required for SOX2's oncogenic effects. Next, our data point to the usefulness of SOX2 overexpression, as a new predictive marker for responsiveness to trastuzumab.SOX2 is a commonly activated tumor promoter that activate AKT signaling in gastric cancer and a new predictive marker for targeted therapy.