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An accurate and efficient automatic brain tumor segmentation algorithm is important for clinical practice. In recent years, there has been much interest in automatic segmentation algorithms that use convolutional neural networks. In this paper, we propose a novel hierarchical multi-scale segmentation network (HMNet), which contains a high-resolution branch and parallel multi-resolution branches. The high-resolution branch can keep track of the brain tumor’s spatial details, and the multi-resolution feature exchange and fusion allow the network’s receptive fields to adapt to brain tumors of different shapes and sizes. In particular, to overcome the large computational overhead caused by expensive 3D convolution, we propose a lightweight conditional channel weighting block to reduce GPU memory and improve the efficiency of HMNet. We also propose a lightweight multi-resolution feature fusion (LMRF) module to further reduce model complexity and reduce the redundancy of the feature maps. We run tests on the BraTS 2020 dataset to determine how well the proposed network would work. The dice similarity coefficients of HMNet for ET, WT, and TC are 0.781, 0.901, and 0.823, respectively. Many comparative experiments on the BraTS 2020 dataset and other two datasets show that our proposed HMNet has achieved satisfactory performance compared with the SOTA approaches.

Rationally engineering three dimensional (3D) architrctures of transition-metal oxides (TMOs) is of great concern for the effective enhancement of electrochemical capacity, nevertheless, it is still challenging to selectively construct well-defined 3D architectured electrode materials in planar-configuration supercapacitors (SCs). Herein, we demonstrated a novel 3D nanotube-structured Ni@MnO2 electrode with interdigital configuration for high-performance planar supercapacitors. By combining transfer printing, alloying-dealloying and electrodeposition methods, 3D architecture of nanotube-structured Ni@MnO2 was subtly built on flexible Kapton substrate. The highly conductive Ni nanotubes embedded in MnO2 nanoflakes offer efficient electron collection paths, endowing the 3D electrodes with low internal resistance. Simultaneously, this 3D nanotube architecture provides multiple channels for electrolyte penetration and large active surface for Faradaic reactions. For these reasons, 3D SCs deliver remarkably enhanced areal capacitance of 10.75 mF cm−2, 2.4 times of the pristine SCs without 3D architecture. Moreover, 3D SCs exhibit desirable flexibility under different bending conditions, which indicates the potential feasibility of planar-configuration SCs as energy-storage components for wearable electronics.

A carefully designed energy storage smart window (ESSW) was successfully demonstrated with transparent-to-dark electrochromic behavior and improved pseudocapacitive performance that constructed by Mo-doped WO3 film electrode and MnO2 nanoflake film electrode. These two electrodes were all synthesized by facile electrodeposition method which is simple, economic and easy-to-production. The proposed ESSW could change its color between transparent and dark with over 60% optical modulations in all visible bands (420–800 nm), which is satisfactory to the applications toward energy saving. Also, the areal capacitance of the ESSW reaches 19.1 mF cm−2 with working voltage window of 2.0 V so that just one single ESSW could power an LED bulb for more than 90 s. The complementary electrochromic behavior of the two electrodes guarantees the commendable electrochromic performance of the proposed ESSW, and the well-matched working potentials and areal capacitances of the asymmetric electrodes improve the pseudocapacitive performance. Such ESSW could have widely future applications toward energy saving and storing fields.

High-quality perovskite (111) BaTiO3 (BTO) ferroelectric thin films were epitaxially grown on wurtzite (0002) GaN substrates with the rationally designed SrTiO3 (STO)/TiN buffer layers by pulsed laser deposition. Particularly, TiN thin films with excellent conductivity could also be served as the bottom electrodes. The epitaxial relationship of the BTO/STO/TiN/GaN heterostructures was proved to be (111)[1 $$\bar{1}$$ 0] BTO//(111)[1 $$\bar{1}$$ 0] STO//(111)[1 $$\bar{1}$$ 0] TiN//(0002)[11 $$\bar{2}$$ 0] GaN by reflection high-energy electron diffraction and high resolution X-ray diffraction. Furthermore, the detailed interface structure and epitaxial relationship of the BTO/STO/TiN/GaN heterostructures were identified on atomic scale by high resolution transmission electron microscopy. The epitaxial (111) BTO ferroelectric thin films on GaN substrates exhibited the favorable ferroelectric properties with the remnant polarization of 12.97 μC cm−2. The high-quality epitaxial integration of perovskite BTO thin films on wurtzite GaN substrates could promote the potential applications in the advanced GaN-based integrated ferroelectric devices.

In attribute-based searchable encryption (ABSE) scheme, data owners can encrypt their data with access policy for security consideration, and encrypt keywords to obtain keyword index for privacy keyword search, and data users can search interesting keyword on keyword indexes by keyword search trapdoor. However, many existing searchable encryption schemes only support single keyword search and most of the existing attribute-based encryption (ABE) schemes have high computational costs at user client. These problems significantly limit the application of attribute-based searchable encryption schemes in practice. In this paper, we propose a verifiable and multi-keyword searchable attribute-based encryption (VMKS-ABE) scheme for cloud storage, in our new scheme, multi-keyword can be searched and the search privacy is protected. That is, the cloud server can search the multi-keyword with keyword search trapdoor but it does not know any information about the keywords searched. In the proposed scheme, many computing tasks are outsourced to the cloud proxy server, which greatly reduces the computing burden at the user client. Besides, the scheme also supports the verification of the correctness of the outsourced private key. The proposed scheme is proved secure that the keyword index is indistinguishable under the adaptive keyword attacks in the general group model, and the ciphertext is selective secure under selective plaintext attacks in the random oracle model. The security and experimental results show that our scheme is suitable for practicability.

Epitaxial integration of SrTiO3 (STO) with GaN plays a key role in exploring monolithic and multifunctional GaN-based devices. Herein, high quality perovskite (1 1 1) STO thin films were epitaxially grown on wurtzite (0 0 0 2) GaN substrates with novel designed single unit-cell TiN buffer layers by pulsed laser deposition. Epitaxial relationship model is proposed to be (1 1 1) [1 1 ¯ 0] STO//(1 1 1)[1 1 ¯ 0] TiN//(0 0 0 2)[1 1 2 ¯ 0] GaN. Furthermore, interfacial structure and epitaxial relationship of STO/TiN/GaN heterostructure is directly confirmed on atomic scale by high-resolution transmission electron microscopy. With the insertion of TiN, lattice mismatch between (1 1 1) STO and (0 0 0 2) GaN is reduced tremendously from 13.3% to 7.9%. More significantly, relaxation process and N atom vacancies in surface atom layer of single unit-cell (1 1 1) TiN could further release lattice mismatch strain between STO and GaN, and thus enormously facilitates epitaxial growth of STO. Moreover, the formation mechanism of twin domain structures and tilted twin grain-boundaries in STO is also discussed to clarify the epitaxial growth process of perovskite (1 1 1) STO on wurtzite (0 0 0 2) GaN.

Point-of-care testing (POCT) with the advantages of speed, simplicity, and low cost, as well as no need for instrumentation, is critical for the measurement of analytes in a variety of environments lacking access to laboratory infrastructure. In the present study, a hydrogel pressure-based assay for quantitative POCT was developed by integrating a target-responsive hydrogel with pressuremeter readout. The target-responsive hydrogels were constructed with DNA grafted linear polyacrylamide and the cross-linking DNA for selective target recognition. The hydrogel response to the target substance allows release of the preloaded Pt nanoparticles, which have good stability and excellent catalytic ability for decomposing H2O2 to O2. Then, the generated O2 in a sealed environment leads to significant pressure increase, which can be easily read out by a handheld pressuremeter. Using this target-responsive hydrogel pressure-based assay, portable and highly sensitive detection of cocaine, ochratoxin A, and lead ion w...

Curcumin, a commonly used natural product for antitumor therapy, is unable to achieve full potential due to poor bioavailability. Based on our previous report of a novel delivery system for curcumin using functionalized single-walled carbon nanotubes by phosphatidylcholine and polyvinylpyrrolidone (SWCNT-Cur), we further evaluated SWCNT-Cur’s performance in vivo and characteristics in vitro. SWCNT-Cur significantly increased the blood concentration of curcumin, up to 18-fold, in mice. And in a murine S180 tumor model, SWCNT-Cur exhibited significantly higher inhibition efficacy on tumor growth and no obvious toxicity in main organs. Moreover, photothermal therapy induced by SWCNT under near-infrared radiation further facilitated SWCNT-Cur to inhibit the tumor growth in vivo. In addition, solvent residue is negligible in SWCNT-Cur formulation, and hydrogen bonding was formed between void carriers and curcumin, as demonstrated by GC chromatograph and IR spectra. Furthermore, experiments of confocal microscopy and spectrofluorometer showed that SWCNT-Cur gave a six-fold higher uptake for curcumin compared to native curcumin in human prostate cancer PC-3 cells. In conclusion, curcumin delivery with functionalized SWCNT is a promising strategy to enhance anticancer activity in vivo by enhancing cell uptake and blood concentration, changing physicochemical properties of curcumin and combining phototherapeutic with chemotherapeutic effects.

Immunocytological technologies, molecular technologies, and functional assays are widely used for detecting circulating tumor cells (CTCs) after enrichment from patients' blood sample. Unfortunately, accessibility to these technologies is limited due to the need for sophisticated instrumentation and skilled operators. Portable microfluidic devices have become attractive tools for expanding the access and efficiency of detection beyond hospitals to sites near the patient. Herein, a volumetric bar chart chip (V-Chip) is developed as a portable platform for CTC detection. The target CTCs are labeled with aptamer-conjugated nanoparticles (ACNPs) and analyzed by V-Chip through quantifying the byproduct (oxygen) of the catalytic reaction between ACNPs and hydrogen peroxide, which results in the movement of an ink bar to a concentration-dependent distance for visual quantitative readout. Thus, the CTC number is decoded into visually quantifiable information and a linear correlation can be found between the distance moved by the ink and number of cells in the sample. This method is sensitive enough that a single cell can be detected. Furthermore, the clinical capabilities of this system are demonstrated for quantitative CTC detection in the presence of a high leukocyte background. This portable detection method shows great potential for quantification of rare cells with single-cell sensitivity for various applications.

R6G spectra on AuNP assembled area, and relative intensity of SERS signal as a function of the concentration of OTA.

We describe a facile and low-cost approach for a flexibly integrated surface-enhanced Raman scattering (SERS) substrate in microfluidic chips. Briefly, a SERS substrate was fabricated by the electrostatic assembling of gold nanoparticles, and shaped into designed patterns by subsequent lift-up soft lithography. The SERS micro-pattern could be further integrated within microfluidic channels conveniently. The resulting microfluidic SERS chip allowed ultrasensitive in situ SERS monitoring from the transparent glass window. With its advantages in simplicity, functionality and cost-effectiveness, this method could be readily expanded into optical microfluidic fabrication for biochemical applications.

A versatile point-of-care assay platform was developed for simultaneous detection of multiple targets based on a microfluidic paper-based analytic device (μPAD) using a target-responsive hydrogel to mediate fluidic flow and signal readout. An aptamer-cross-linked hydrogel was used as a target-responsive flow regulator in the μPAD. In the absence of a target, the hydrogel is formed in the flow channel, stopping the flow in the μPAD and preventing the colored indicator from traveling to the final observation spot, thus yielding a "signal off" readout. In contrast, in the presence of a target, no hydrogel is formed because of the preferential interaction of target and aptamer. This allows free fluidic flow in the μPAD, carrying the indicator to the observation spot and producing a "signal on" readout. The device is inexpensive to fabricate, easy to use, and disposable after detection. Testing results can be obtained within 6 min by the naked eye via a simple loading operation without the need for any auxiliary equipment. Multiple targets, including cocaine, adenosine, and Pb(2+), can be detected simultaneously, even in complex biological matrices such as urine. The reported method offers simple, low cost, rapid, user-friendly, point-of-care testing, which will be useful in many applications.

A target-responsive aptamer-cross-linked hydrogel was designed and synthesized for portable and visual quantitative detection of the toxin Ochratoxin A (OTA), which occurs in food and beverages. The hydrogel network forms by hybridization between one designed DNA strand containing the OTA aptamer and two complementary DNA strands grafting on linear polyacrylamide chains. Upon the introduction of OTA, the aptamer binds with OTA, leading to the dissociation of the hydrogel, followed by release of the preloaded gold nanoparticles (AuNPs), which can be observed by the naked eye. To enable sensitive visual and quantitative detection, we encapsulated Au@Pt core-shell nanoparticles (Au@PtNPs) in the hydrogel to generate quantitative readout in a volumetric bar-chart chip (V-Chip). In the V-Chip, Au@PtNPs catalyzes the oxidation of H2O2 to generate O2, which induces movement of an ink bar to a concentration-dependent distance for visual quantitative readout. Furthermore, to improve the detection limit in complex real samples, we introduced an immunoaffinity column (IAC) of OTA to enrich OTA from beer. After the enrichment, as low as 1.27 nM (0.51 ppb) OTA can be detected by the V-Chip, which satisfies the test requirement (2.0 ppb) by the European Commission. The integration of a target-responsive hydrogel with portable enrichment by IAC, as well as signal amplification and quantitative readout by a simple microfluidic device, offers a new method for portable detection of food safety hazard toxin OTA.

With a fully classical ensemble model, we investigate the nonsequential double ionization (NSDI) of Xe by linearly polarized (LP) and elliptically polarized (EP) ultra-short laser pulses respectively. For these two cases, the momentum distributions of correlated electron in the direction of parallel to the laser field (for LP) and along the long axis of the laser polarization plane (for EP) show significant difference, but along perpendicular to the laser field (for LP) and the short axis of the laser polarization plane (for EP), the momentum distributions often emit into the opposite hemisphere. By back analyzing the classical trajectories of NSDI, it shows that the recollision is still the underlying mechanism. For LP, the recollision often occurs at the first returning of tunneled electron, but for EP, all of the successful NSDI come from the “exit collision” [PRA 81, 023409 (2010)] which is responsible for the momentum distribution of correlated electron. Moreover, for LP, we divide the trajectories of NSDI into four cases based on the time delay between singly ionization and recollision, and find the ionization mechanism is different for them, so the momentum distribution of correlated electron exhibits a strongly distinction.

Structure and optical properties of GaInP epilayer with the ultrathin interfacial layers grown on germanium by metal–organic vapor-phase epitaxy (MOVPE) were characterized by high resolution transmission electron microscopy (HRTEM), photoluminescence (PL), Raman as well as surface morphology measurement. A five angstroms (5 A) AlAs interfacial layer results in the decrease of PL intensity arising from the emission of [Ge (Ga,In) − V (Ga,In) ] complex. With the incorporation of AlAs interfacial layer, an increased ordered degree of GaInP epilayer is observed. On the basis of the combination of step–terrace-reconstruction (STR) mode with the dimer-induced-stress model, a CuPt-B type ordering of GaInP which is related to AlAs reconstruction with 2× periodicity process is proposed to explain this effect. Long range order occurs as a consequence of the minimization of the strain energy with increased interfacial layer thickness from 5 A to 5 nm.

Attaching thiolated DNA on gold nanoparticles (AuNPs) has been extremely important in nanobiotechnology because DNA-AuNPs combine the programmability and molecular recognition properties of the biopolymers with the optical, thermal, and catalytic properties of the inorganic nanomaterials. However, current standard protocols to attach thiolated DNA on AuNPs involve time-consuming, tedious steps and do not perform well for large AuNPs, thereby greatly restricting applications of DNA-AuNPs. Here we demonstrate a rapid and facile strategy to attach thiolated DNA on AuNPs based on the excellent stabilization effect of mPEG-SH on AuNPs. AuNPs are first protected by mPEG-SH in the presence of Tween 20, which results in excellent stability of AuNPs in high ionic strength environments and extreme pHs. A high concentration of NaCl can be applied to the mixture of DNA and AuNP directly, allowing highly efficient DNA attachment to the AuNP surface by minimizing electrostatic repulsion. The entire DNA loading process can be completed in 1.5 h with only a few simple steps. DNA-loaded AuNPs are stable for more than 2 weeks at room temperature, and they can precisely hybridize with the complementary sequence, which was applied to prepare core-satellite nanostructures. Moreover, cytotoxicity assay confirmed that the DNA-AuNPs synthesized by this method exhibit lower cytotoxicity than those prepared by current standard methods. The proposed method provides a new way to stabilize AuNPs for rapid and facile loading thiolated DNA on AuNPs and will find wide applications in many areas requiring DNA-AuNPs, including diagnosis, therapy, and imaging.

Accurate sensing of the extracellular pH is a very important yet challenging task in biological and clinical applications. This paper describes the development of an amphiphilic lipid-DNA molecule as a simple yet useful cell-surface-anchored ratiometric fluorescent probe for extracellular pH sensing. The lipid-DNA probe, which consists of a hydrophobic diacyllipid tail and a hydrophilic DNA strand, is modified with two fluorescent dyes; one is pH-sensitive as pH indicator and the other is pH-insensitive as an internal reference. The lipid-DNA probe showed sensitive and reversible response to pH change in the range of 6.0-8.0, which is suitable for most extracellular studies. In addition, based on simple hydrophobic interactions with the cell membrane, the lipid-DNA probe can be easily anchored on the cell surface with negligible cytotoxicity, excellent stability, and unique ratiometric readout, thus ensuring its accurate sensing of extracellular pH. Finally, this lipid-DNA-based ratiometric pH indicator was successfully used for extracellular pH sensing of cells in 3D culture environment, demonstrating the potential applications of the sensor in biological and medical studies.

A disposable, equipment-free, versatile point-of-care testing platform, microfluidic distance readout sweet hydrogel integrated paper-based analytical device (μDiSH-PAD), was developed for portable quantitative detection of different types of targets. The platform relies on a target-responsive aptamer cross-linked hydrogel for target recognition, cascade enzymatic reactions for signal amplification, and microfluidic paper-based analytic devices (μPADs) for visual distance-based quantitative readout. A "sweet" hydrogel with trapped glucoamylase (GA) was synthesized using an aptamer as a cross-linker. When target is present in the sample, the "sweet" hydrogel collapses and releases enzyme GA into the sample, generating glucose by amylolysis. A hydrophilic channel on the μPADs is modified with glucose oxidase (GOx) and colorless 3,3'-diaminobenzidine (DAB) as the substrate. When glucose travels along the channel by capillary action, it is converted to H2O2 by GOx. In addition, DAB is converted into brown insoluble poly-3,3'-diaminobenzidine [poly(DAB)] by horseradish peroxidase, producing a visible brown bar, whose length is positively correlated to the concentration of targets. The distance-based visual quantitative platform can detect cocaine in urine with high selectivity, sensitivity, and accuracy. Because the target-induced cascade reaction is triggered by aptamer/target recognition, this method is widely suitable for different kinds of targets. With the advantages of low cost, ease of operation, general applicability, and disposability with quantitative readout, the μDiSH-PAD holds great potential for portable detection of trace targets in environmental monitoring, security inspection, personalized healthcare, and clinical diagnostics.

Context: Functionalized single-walled carbon nanotubes (SWNT) with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) were used as novel and more convenient carriers of small interfering RNA (siRNA). Objective: To utilize the unique capability of SWNT to be easily modified by functional groups and readily internalized by mammalian cells to bind, condense, stabilize siRNA and enhance its transfection efficiency. Methods: After SWNT were non-covalently functionalized by cationic DOTAP (SWNT–DOTAP), siRNA interacted with SWNT–DOTAP via static electricity (SWNT–DOTAP/siRNA). Subsequently, the size, zeta potential and morphology of SWNT–DOTAP/siRNA were analyzed. The optimal compression ratio and stability of siRNA were assessed by agarose gel electrophoresis. Furthermore, in prostate carcinoma PC-3 cells, RT-PCR, flow cytometry and sulforhodamine B assays were used to evaluate the silencing activity, transfection efficiency and cell proliferation, respectively. Results and discussion: The characteristics of SWNT–DOTAP, i.e. an average size of 194.49 nm, a zeta potential of 45.16 mV and lower cytotoxicity than Lipofectamine 2000, indicated that this vector was suitable for siRNA delivery. Moreover, after interaction with SWNT–DOTAP, siRNA of human telomerase reverse transcriptase was bound, condensed and stabilized. In PC-3 cells, SWNT–DOTAP/siRNA exhibited 82.6% silencing activity and 92% transfection efficiency. Furthermore, the complexes inhibited cell proliferation by 42.1%. Conclusion: SWNT–DOTAP may be a promising siRNA delivery vector for gene-based therapeutic applications in cancer.

Paper based microfluidics (µPADs) with advantages of portability, low cost, and ease of use have attracted extensive attention. Here we describe a novel method that integrates glucoamylase-trapped aptamer-crosslinked hydrogel for molecular recognition with cascaded enzymatic reactions for signal amplification and a µPAD for portable readout. Upon target introduction, the hydrogel decomposes to release glucoamylase, which catalyzes the hydrolysis of amylose to produce a large amount of glucose. With a simple folding of the µPAD, the sample solution containing glucose product wicks and diffuses in parallel to each test-zone to carry out homogeneous assays, where glucose is used to produce I2 for brown color visualization through multiple enzymatic and chemical cascade reactions. Through color gradient changes based on different concentrations of the target, a semiquantitative assay is achieved by the naked eye, and quantitation can be obtained by handheld devices. Detection of cocaine in buffer and urine was performed to demonstrate the utility of the hydrogel–µPAD system. More importantly, the hydrogel–µPAD system can be extended to the detection of various targets by incorporating the corresponding aptamer into the hydrogel. The hydrogel–µPAD system reported here provides a new platform for portable, disposable and visual detection of a wide range of targets.

DNA conjugated gold nanorods (AuNRs) are widely applied for nanostructure assembly, gene therapy, biosensing, and drug delivery. However, it is still a great challenge to attach thiolated DNA on AuNRs, because the positively charged AuNRs readily aggregate in the presence of negatively charged DNA. This article reports an mPEG-SH/Tween 20-assisted method to load thiolated DNA on AuNRs in 1 h. Tween 20 and mPEG-SH are used to synergistically displace CTAB on the surface of AuNRs by repeated centrifugation and resuspension, and thiolated DNA are attached to AuNRs in the presence of 1 M NaCl, 100 mM MgCl2, or 100 mM citrate. AuNRs with different sizes and aspect ratios can be functionalized with DNA by this method. The number of DNA loaded on each AuNR can be easily controlled by the concentrations of mPEG-SH and Tween 20 or the ratio between DNA and AuNR. Functionalized AuNRs were used for nanoparticle assembly and cancer cell imaging to confirm that DNA anchored on the surface of AuNRs retains its hybridization and molecular recognition capability. The new method is easy, rapid, and robust for the preparation of DNA functionalized AuNRs for a variety of applications such as cancer therapy, drug delivery, self-assembly, and imaging.

Herein, we demonstrate that a very familiar, yet underutilized, physical parameter—gas pressure—can serve as signal readout for highly sensitive bioanalysis. Integration of a catalyzed gas-generation reaction with a molecular recognition component leads to significant pressure changes, which can be measured with high sensitivity using a low-cost and portable pressure meter. This new signaling strategy opens up a new way for simple, portable, yet highly sensitive biomedical analysis in a variety of settings.

Point-of-care testing (POCT) with the advantages of speed, simplicity, portability, and low cost is critical for the measurement of analytes in a variety of environments where access to laboratory infrastructure is lacking. While qualitative POCTs are widely available, quantitative POCTs present significant challenges. Here we describe a novel method that integrates an Au core/Pt shell nanoparticle (Au@PtNP) encapsulated target-responsive hydrogel with a volumetric bar-chart chip (V-Chip) for quantitative POCT. Upon target introduction, the hydrogel immediately dissolves and releases Au@PtNPs, which can efficiently catalyze the decomposition of H2 O2 to generate a large volume of O2 to move of an ink bar in the V-Chip. The concentration of the target introduced can be visually quantified by reading the traveling distance of the ink bar. This method has the potential to be used for portable and quantitative detection of a wide range of targets without any external instrument.

With their advantages as molecular recognition elements, aptamers have been extensively studied and used for bioanalytical and biomedical applications. However, the process of enrichment and screening of aptamers remains a bottleneck for aptamer development. Recently, microfluidic methods have been increasingly used for rapid and efficient aptamer selection, showing their remarkable advantages over conventional methods. This review briefly introduces aptamers and their advantages. The conventional process of generating aptamers is discussed, followed by the analysis of the key obstacles to efficient aptamer selection. Microfluidic methods for highly efficient enrichment and screening of aptamers are reviewed in detail.