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Purpose: The current mainstream methods for single-channel speech separation generally use a feature extraction process like the short-time Fourier transform and rely on long input sequences. Thus, they do not fully utilize the information of speech features and cause signal delays in speech separation. Methods: To achieve better performance with a lightweight model, a fully convolution end-to-end audio separation network is proposed based on the features of two domains, i.e. temporal domain channel domain. It considers not only the temporal correlation of speech signals, but also the correlation between channels in the signal feature map. At first, the end-to-end network uses a convolution process with no overlapping segments to sample and encode the speech waveform. Subsequently, it calculates the mask by convolving the encoded feature space in both time series and inter-channel dimensions. Finally, it decodes the masked feature space to restructure the waveform. Results: The proposed end-to-end speech separation method makes full use of the feature space information of speech signals. Meanwhile, the separation module introduces residual structure and dilation convolution, which improves separation accuracy and computational speed with fewer parameters. The experiments show that compared with the base Conv-TasNet, the proposed model improves the SI-SNR (scale-invariant source-to-noise ratio) metric by 3.1 dB on the WSJ0-Mix2 dataset. Conclusion: This paper proposes an improved speech separation algorithm. Compared with Conv-TasNet, the performance of speech separation is improved. At the same time, the algorithm inherits the lightweight property of Conv-TasNet. In the task of separating speech signals mixed with a random signal-to-noise ratio (SNR) between −5 and 5 dB, the proposed algorithm achieves a relatively high accuracy.

Nucleic acids play a pivotal role in the diagnosis of diseases. However, rapid, cost-efficient, and ultrasensitive identification of nucleic acid targets still represents a significant challenge. Herein, we describe an enzyme-free DNA amplification method capable of achieving accurate and ultrasensitive nucleic acid detection via DNA-templated click ligation chain reaction (DT-CLCR) catalyzed by a heterogeneous nanocatalyst made of Cu2O (hnCu2O). This hnCu2O–DT-CLCR method is built on two cross-amplifying hnCu2O-catalyzed DNA-templated azide–alkyne cycloaddition-driven DNA ligation reactions that boast a fast reaction rate and a high DNA ligation yield in minutes, enabling rapid exponential amplification of specific DNA targets. This newly developed hnCu2O–DT-CLCR-enabled DNA amplification strategy is further integrated with two signal reporting mechanisms to achieve low-cost and easy-to-use biosensors: an electrochemical sensor through the conjugation of a methylene blue redox reporter to a DNA probe used in hnCu2O–DT-CLCR and a colorimetric sensor through the incorporation of the split-to-intact G-quadruplex DNAzyme encoded into hnCu2O–DT-CLCR. Both sensors are able to achieve specific detection of the intended DNA target with a limit of detection at aM ranges, even when challenged in complex biological matrices. The combined hnCu2O–DT-CLCR and sensing strategies offer attractive universal platforms for enzyme-free and yet efficient detection of specific nucleic acid targets.

Aiming at a higher deposition rate, robotic gas tungsten arc additive manufacturing (GTA AM) always uses the front feed mode in which the wire is fed in front of the arc along the torch travel direction. However, fabricating corner structures in this mode is still a challenging issue in robotic GTA AM, since the serious hump height at corner points during torch rotation will hinder the process stability and automation of corner structures. The novelty of this study is to solve this issue by developing an in-situ monitoring and control strategy. An arc voltage sensor is designed to monitor the arc voltage that can characterize the deposition height. The arc voltage decreases first and then keeps stable at the corner points during torch rotation. It increases rapidly as the torch runs away from the corner points. An empirical mode decomposition (EMD) algorithm filters noises in sampled arc voltages. The peak arc voltage is selected to characterize the arc length since it presents fewer fluctuations than the base arc voltage. A Fuzzy-PID controller is developed for the peak arc voltage control by regulating the wire feed speed (WFS). Open-loop and closed-loop control tests of corner structures confirm that the deposition process with the fixed WFS is forced to terminate due to the serious hump height, and that with the controlled WFS can lower the hump height markedly at the corner points. This study demonstrates that the developed arc voltage sensing and control system can remove metal humps at the corner points and enhance the process automation of corner structures in robotic GTA AM.

ABSTRACTMonitoring and control of layer geometry in robotic-pulsed gas tungsten arc additive manufacturing (GTA AM) are essential and challenging issues. This study attempts to realize controllable layer width via imposing a closed-loop controller based on a composite sensing of vision and arc. A vision sensor is utilized to monitor the layer width, and an arc voltage sensor capable of characterizing the arc length is introduced to calibrate the vision sensor. The image acquisition time for layer width is determined via analyzing the features of successive molten pool images, i.e. 80 ms after the rising edge from the base current to the peak current. Image processing procedures are developed to determine the layer width. A parameter self-adjusting Fuzzy (PSA-Fuzzy) controller is designed to control the layer width by adjusting the peak current. Closed-loop tests confirm that the PSA-Fuzzy controller can significantly increase the layer width consistency in robotic pulsed GTA AM.

Ni4Mo alloys were in-situ grown on the unsaturated sulfur atoms of Sv-ZCS via interfacial Ni-S bonds. Dual IEF induced by Schottky junction and sulfur vacancies promote the separation and utilization efficiency of photoinduced carriers.

The cause for at least 50% of recurrent miscarriages is unclear, which is defined as unexplained recurrent miscarriages. The B7-H1 (PD-L1), a molecule of the B7 family, promotes tumor development by modulating immune evasion, and recent researchers have also attached importance to the role of B7-H3, another molecule of B7 family, in tumor. Based on the similarity between growth and immune response in tumors and pregnancy, we first explored the role of B7-H3 in unexplained recurrent miscarriages. We found reduced levels of B7-H3 in the villus tissue of unexplained recurrent miscarriage patients, and it was mainly expressed on the cell membrane of extravillous trophoblasts. Further, the HTR-8/SVneo and JEG-3 cells were selected to explore the role of B7-H3 in proliferation, apoptosis, tube formation, migration, and invasion. We found that B7-H3 regulated trophoblast migration and invasion via RhoA/ROCK2 signaling pathway. Inflammatory cytokines were detected through enzyme-linked immunosorbent assay after co-culturing with decidual natural killer cells and B7-H3-knockout JEG-3. Results showed that B7-H3 inhibited IL-8 and IP-10 secretion from the decidual natural killer cells. In a CBA/J × DBA/2 abortion-prone mice model, treatment with B7-H3-Fc protein successfully reduced the rate of embryo resorption. In conclusion, our results revealed a possible mechanism by which decreased B7-H3 on trophoblasts of unexplained recurrent miscarriages inhibited trophoblast migration and invasion and increased IL-8 and IP-10 secretion from the decidual natural killer cells. Furthermore, B7-H3 may be a promising new therapeutic target in unexplained recurrent miscarriage patients.Decreased B7-H3 participates in unexplained recurrent miscarriage by inhibiting trophoblast migration and invasion via RhoA/ROCK2 pathway and regulating decidual NK secretion.

Purpose: The accuracy of real-time sound source localization is an important issue in acoustics. The steered sample algorithm (SSA), an algorithm developed based on the reciprocity of wave propagation, has a higher spatial resolution than the steered response power – phase transform (SRP-PHAT) algorithm. The algorithm can also render an accurate sound source localization under limited array elements and low signal-to-noise ratio. However, the actual implementation of the algorithm is usually based on an expensive grid search process, which makes the computational cost a serious problem. Methods: An improved implementing algorithm based on beetle swarm optimization (BSO) is proposed for SSA, which can effectively reduce the computational cost. The modified algorithm has a good convergence speed as the SSA algorithm has fewer local extremums. Results: Experimental results demonstrate that compared with steered sample algorithm (SSA), the proposed algorithm has almost the same localization performance and robustness with lower computational cost. Conclusion: This paper proposes an improved algorithm about SSA algorithm. Compared with SRC algorithm, the amount of computation is reduced more than twice. Meanwhile, the proposed algorithm inherits the anti-noise performance of SSA. Under the condition of low SNR, the positioning success rate and RMSE performance are excellent. Under the condition of high reverberation, the improved algorithm needs more particles to ensure the positioning performance. When the number of particles is not less than 70, the localization success rate of the proposed algorithm is highly consistent with the conventional SSA, and the RMSE is slightly less than the conventional SSA. Compared with SRC algorithm, the proposed algorithm better inherits the robustness of original SSA and improves the positioning accuracy.

Cr(VI)-based compounds pollution have attracted global concern due to serious harm to humans and environment. Hence, it is crucial to exploit an effective technique to eliminate Cr(VI) in water. Herein, we in-situ grown BiOI on graphitic carbon nitride to prepare the BiOI/g-C3N4(BCN) direct Z-scheme heterojunction by solid phase engineering method at room temperature. Experimental result shown the photocatalytic activity of pure BiOI were obviously enhanced by constructing Z-scheme BCN heterostructure, and BCN-3 heterostructure exhibited the optimal photocatalytic degradation of RhB with 98% yield for 2.5 h and reduction of Cr(VI) with more than 99% yield for 1.5 h at pH = 2. Stability test shows BCN-3 still kept more than 98% reduction efficiency after 6 cycles. In addition, we also studied the reduction mechanism that shown the ·O2−radicals essentially helped to reduce the Cr(VI) in aqueous solution under illumination, verified the direct Z-scheme charge transfer path by X-ray photoelectron spectroscopy (XPS) and the free radical trapping experiment. The work open a new way for rationally designing photocatalyst heterostructure to reduce Cr(VI) to Cr(III).

Developing low-cost and earth-abundant electrocatalysts with high performance for electrochemical water splitting is a challenging issue. Herein, we report a facile and effective way to fabricate three-dimension (3D) ordered mesoporous Co1−xFexP (x=0, 0.25, 0.5, 0.75) electrocatalyst. Benefiting from 3D ordered mesoporous pore channels and composition optimization, the Co0.75Fe0.25P exhibits excellent electrocatalytic activities with low overpotentials of 270 and 209 mV at 10 mA cm−2for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER), respectively, in the alkaline electrolyte along with a durable electrochemical stability. In addition, as both the cathode and anode, the Co0.75Fe0.25P also exhibits superior electrolysis water splitting performance with only an applied voltage of 1.63 V to attain a current density of 10 mA cm−2without obvious decay for 18 h, indicating that the Co0.75Fe0.25P is an efficient electrocatalyst for overall water splitting.

DNA-templated reactions have found wide applications in sensing and drug discovery. However, this strategy has been limited to the use of nucleic acids as templating elements to direct the proximity effect. Herein, we describe a versatile protein-templated split aptamer click ligation reaction (PT-SpA-CLR) in which the protein template-induced covalent proximity ligation of split aptamer elements enables translating protein/aptamer binding events into the output of ligated DNA products. A ligation yield of >80% is observed for three model protein templates, including VEGF165, PDGF-BB, and SARS-CoV-2 S1. The ligation reaction compensates for the weakness of reduced binding affinity resulting from splitting the aptamer, as evidenced by an approximately 2-fold lower dissociation constant than the non-ligated system. This newly developed PT-SpA-CLR strategy is further integrated with colorimetric or fluorescent reporting mechanisms to achieve easy-to-use and low-cost biosensors utilizing ligation to produce a fully active G-quadruplex or an RNA-cleaving DNAzyme to report protein binding. Both assays can achieve specific detection of an intended protein target with a limit of detection at the picomolar level even when challenged in biological samples. The combined PT-SpA-CLR and versatile sensing strategies offer attractive universal platforms for efficient detection of protein biomarkers.

As an ideal drug carrier, it should possess high drug loading and encapsulation efficiency and precise drug targeting release. Herein, we utilized a template-guided self-weaving technology of phase-separated silk fibroin (SF) in reverse microemulsion (RME) to fabricate a kind of hyaluronic acid (HA) coated SF nanocage (HA-gNCs) for drug delivery of cancer immunotherapy. Due to the hollow structure, HA-gNCs were capable of simultaneous encapsulation of the anti-inflammatory drug betamethasone phosphate (BetP) and the immune checkpoint blockade (ICB) agent PD-L1 antibody (αPD-L1) efficiently. Another point worth noting was that the thiocarbonate cross-linkers used to strengthen the SF shell of HA-gNCs could be quickly broken by overexpressed glutathione (GSH) to reach responsive drug release inside tumor tissues accompanied by hydrogen sulfide (H2S) production in one step. The synergistic effect of released BetP and generated H2S guaranteed chronological modulation of the immunosuppressive tumor microenvironment (ITME) to amplify the therapeutic effect of αPD-L1 for the growth, metastasis, and recurrence of tumors. This study highlighted the exceptional prospect of HA-gNCs as a self-assistance platform for cancer drug delivery.

A hybrid co-catalysts system comprising Au nanoparticles (NPs) and PtSAs with different functions was constructed on the polymeric carbon nitride (PCN) surface by double-solvent method.For the dual co-catalysts, the Au NPs absorb relatively long-wavelength light to produce plasmonic hot-electrons, and the adjacent Pt single atoms (PtSAs) can trap the plasmonic hot-electrons effectively for H2evolution.The PtSAs–Au2.5/PCN exhibits excellent broad-spectrum photocatalytic H2evolution activity with the H2evolution rate of 8.8 mmol g−1h−1at 420 nm and 264 μmol g−1h−1at 550 nm, respectively.

We report a new strategy of controlling catalytic activity and selectivity of Cu nanoparticles (NPs) for the ammonia borane initiated hydrogenation reaction. Cu NPs are active and selective for chemoselective reduction of nitrostyrene to vinylaniline under ambient conditions. Their activity, selectivity, and more importantly, stability are greatly enhanced by their anchoring on WO2.72nanorods, providing a room-temperature full conversion of nitrostyrene selectively to vinylaniline (>99% yield). Compared with all other catalysts developed thus far, our new Cu/WO2.72catalyst shows much enhanced hydrogenation selectivity and stability without the use of pressured hydrogen. The synthetic approach demonstrated here can be extended to prepare various M/WO2.72catalysts (M = Fe, Co, Ni), with M being stabilized for many chemical reactions.

L10-FePt nanoparticles (NPs) have great potential in areas of advanced magnetic and catalytic applications. Here, we present a facile control route for synthesis of hard magnetic L10-FePt NPs in which halide ions (Cl–, Br–, or I–) were added to the synthetic process to promote the phase transformation. It is confirmed that the strong ionic binding force between halide ions and Fe3+or Pt2+ions could facilitate the formation of L10-FePt phase due to favoring growth of FePt NPs in a more thermodynamically stable way, which enables the formation of an ordered structure. L10-FePt NPs with the highest coercivity of 8.64 kOe and saturation magnetization of 64.21 emu/g at room temperature can be directly obtained by controlling the amount of the halide ions. In comparison with conventional solution phase reduction methods, the halide ion-assisted method shows enhanced capability to tune the growth of hard magnetic bimetallic NPs, particularly Pt-based bimetallic NPs.

In this paper, hierarchical mesoporous Co3O4@ZnCo2O4hybrid nanowire arrays (NWAs) on Ni foam were prepared through a two-step hydrothermal process associated with successive annealing treatment. The Co3O4@ZnCo2O4hybrid NWAs exhibited excellent electrochemical performances with a high specific capacity of 1240.5 C g−1at a current density of 2 mA cm−2, with rate capability of 59.0% shifting from 2 to 30 mA cm−2, and only a 9.1% loss of its capacity even after 3,000 cycles at a consistent current density of 10 mA cm−2. An asymmetric supercapacitor (Co3O4@ZnCo2O4NWAs||activated carbon) was fabricated and exhibited a high specific capacity of 168 C g−1at a current density of 1 A g−1. And a preferable energy density of 37.3Wh kg−1at a power density of 800 W kg−1was obtained. The excellent electrochemical performances indicate the promising potential application of the hierarchical mesoporous Co3O4@ZnCo2O4hybrid NWAs in energy storage field. 本文采用两步水热法和连续的退火处理过程, 制备了分层介孔Co3O4@ZnCo2O4复合纳米线阵列. 所制备的Co3O4@ZnCo2O4复合纳米线阵列具有优异的电化学性能, 在2 mA cm−2的电流密度下具有高达1240.5 C g−1的比容量. 当电流密度升高至30 mA cm−2时, 比容量保持率为59.0%, 甚至在10 mA cm−2的电流密度下循环3000圈, 比容量仅下降9.1%. 将其与活性炭组装成非对称超级电容器, 可以在1 A g−1的电流密度下表现出168 C g−1的比容量. 当功率密度为800 W kg−1时, 能量密度为37.3 W h kg−1. Co3O4@ZnCo2O4复合纳米阵列在储能领域具有广阔的应用前景.

ABSTRACTDendritic cells (DCs) play a predominant role in initiating cell immune responses. Here we generated a DC-targeting lentiviral vector (LVDC-UbHBcAg-LIGHT) and evaluated its capacity to elicit HBV-specific cytotoxic T lymphocyte (CTL) responses. DC-SIGN-mediated specific transduction using this construct was confirmed in DC-SIGN-expressing 293T cells and ex vivo-cultured bone marrow cells. LVDC-UbHBcAg-LIGHT-loaded DCs were highly effective in inducing HBV-specific CTLs. Mechanistic studies demonstrated autophagy blocking led to a significant increase in apoptosis and obvious inhibition of CD8 + T cells entry into S-phase, correspondingly attenuated LVDC-UbHBcAg-LIGHT-loaded DC-induced T cell responses. This observation was supported by accumulation of pro-apoptotic proteins and the main negative cell cycle regulator-CDKN1B that otherwise would be degraded in activated T cells where autophagy preferentially occured. Our findings revealed an important role of autophagy in the activation of T cells and suggested LVDC-UbHBcAg-LIGHT may potentially be used as a therapeutic strategy to combat persistent HBV infection with higher security.

Targeted covalent inhibitors of protein–protein interactions differ from reversible inhibitors in that the former bind and covalently bond the target protein at a specific site of the target. The site specificity is the result of the proximity of two reactive groups at the bound state, for example, one mild electrophile in the inhibitor and a natural cysteine in the target close to the ligand binding site. Only a few pharmaceutically relevant proteins have this structural feature. Grb2, a key adaptor protein in maintaining the ERK activity via binding Sos1 to activated RTKs, is one: the N-terminal SH3 domain of Grb2 (Grb2N-SH3) carries a unique solvent-accessible cysteine Cys32close to its Sos1-binding site. Here we report the design of a peptide-based antagonist (a reactive peptide) that specifically binds to Grb2N-SH3and subsequently undergoes a nucleophilic reaction with Cys32to form a covalent bond thioether, to block Grb2–Sos1 interaction. Through rounds of optimization, we eventually obtained a dimeric reaction reactive peptide that can form a covalent adduct with endogenous Grb2 protein inside the cytosol of SK-BR-3 human breast cancer cells with pronounced inhibitory effect on cell mobility and viability. This work showcases a rational design of Grb2-targeted site-specific covalent inhibitor and its pronounced anticancer effect by targeting Grb2–Sos1 interaction.

AbstractThe municipal solid waste in China is increasing at an unprecedented pace due to the upgrading urbanization and improving living standard. The waste-to-energy (WTE) incineration technology offers a viable and potentially profitable technical solution to this booming phenomenon. The highly complex and systematic nature of WTE technologies have led to the emergence of WTE innovation network in the past decade. This study applies complex network theory as well as social network analysis to investigate the social network structure evolution of WTE technologies in terms of global network properties, major actors’ centrality and collaboration relationships. Based on the data-set covering joint filing patents pertaining to waste heat over the period 2006–2015, this study finds that the overall WTE innovation network exhibits the properties of scale-free network with minority organizations linking to abundant organizations. A large fraction of major actors represent the first-movers in the WTE research and still control the technological trajectories. The collaboration relationships have moved toward higher level of multidisciplinary and larger technological distance. Overall, the evolution of WTE innovation network features a young state of industry with high regime dependence. Finally, some suggestions are proposed to shed light on benign development of WTE innovation network.

Reinforcing the charge separation and transfer in layered polymeric carbon nitride (PCN) is the key issue to enhance its photocatalytic activity but still remains very challenging. Herein, for the first time, the synergetic Pd single atoms (PdSAs) and carbon-supported Pd nanoparticles (NPs) are introduced into the interlayer and surface of layered PCN respectively to address this challenge. The PdSAs are in intimate contact with the adjacent PCN layers and serve as interlayer charge transfer channels, while the carbon-supported Pd NPs contribute to multistep PCN-carbon-Pd NPs Schottky junctions on PCN surface. Experiments and theoretical calculations demonstrate that such unique architectures provide intrinsic driving force to extract the electrons from PCN to outermost Pd NPs with high migration rate via vertical PdSAs channels. This directional charge transfer in PCN greatly expedite the separation of charge carriers in both inner and surface of PCN and simultaneously yield electron-rich Pd NPs active sites with optimized H2adsorption energy, thus leading to improved intrinsic H2evolution reaction kinetics. Consequently, the Pd/PCN2performs ultrahigh photocatalytic H2evolution rate of 83.34 mmol g−1h−1in the dispersed particulate system and 100.4 mmol h−1m−2in the film form under simulated sunlight. This work provides a new promising approach to engineer the spatial charge transfer behaviors for high-performance PCN-based photocatalysts.

Specific and dynamic biological interactions pave the blueprint of signal networks in cell. For example, a great variety of specific protein-ligand interactions define how intracellular signals flow. Taking advantage of the specificity of these interactions, we postulate an “affinity-guided covalent conjugation” strategy to lock binding ligands through covalent reactions between the ligand and the receptor protein. The presence of a nucleophile close to the ligand binding site of a protein is sine qua noneof this reaction. Specific noncovalent interaction of a ligand derivative (which contains an electrophile at a designed position) to the ligand binding site of the protein brings the electrophile to the close proximity of the nucleophile. Subsequently, a conjugation reaction spontaneously takes place between the nucleophile and the electrophile, and leads to an intermolecular covalent linkage. This strategy was first showcased in coiled coil peptides which include a cysteine mutation at a selected position. The short peptide sequence was used for covalent labeling of cell surface receptors. The same strategy was then used to guide the design of a set of protein Lego bricks for covalent assembly of protein complexes of unnatural geometry. We finally made “reactive peptides” for natural adaptor proteins that play significant roles in signal transduction. The peptides were designed to react with a single domain of the multidomain adaptor protein, delivered into the cytosol of neurons, and re-directed the intracellular signal of neuronal migration. The trilogy of protein labeling, assembly, and inhibition of intracellular signals, all through a specific covalent bond, fully demonstrated the generality and versatility of “affinity-guided covalent conjugation” in various applications.

Intracellular reactions on nonenzymatic proteins that activate cellular signals are rarely found. We report one example here that a designed peptide derivative undergoes a nucleophilic reaction specifically with a cytosolic PDZ protein inside cells. This reaction led to the activation of ephrin-B reverse signaling, which subsequently inhibited SDF-1 induced neuronal chemotaxis of human neuroblastoma cells and mouse cerebellar granule neurons. Our work provides direct evidence that PDZ-RGS3 bridges ephrin-B reverse signaling and SDF-1 induced G protein signaling for the first time.

Objective To determine whether polymorphisms in IL-6 and IL-12 contribute to the etiology of coal workers’ pneumoconiosis (CWP) in a Chinese Hui population, and to evaluate the efficacy and safety of high frequency oscillatory ventilation (HFOV) in the treatment of CWP.Introduction Genes and the environments interplay in the development of CWP, and the association between the potential functional polymorphisms in many genes and CWP have been reported.Methods We genotyped the IL-6-634C/G (rs1800796) and IL-12B-1188A/C (rs3212227) polymorphisms in a case-control study including 160 CWP patients and 150 dust-exposed control subjects of Chinese Hui population, and analyzed the associations between these genetic variants and CWP risk. We also evaluated the efficacy and safety of HFOV for whole lung lavage (WLL) in the treatment of CWP.Results Carrying the C allele of IL-6-634C/G (rs1800796) was associated with decreased risk of CWP (p< 0.05). No significant differences in allele or genotype frequencies of IL-12B-1188A/C was found between the CWP cases and control subjects (p> 0.05). Compared with CWP patients with routine WLL, CWP patients received HFOV showed better pulmonary functions. HFOV treatment also yield a significant higher efficient rate (97.50%) than WLL treatment (81.25%, p= 0.001). CWP patients receiving HFOV and WLL treatment both showed significantly increased serum contents of Clara cell protein 16 (CC16) and superoxide dismutase (SOD), and decreased serum contents of serum malonaldehyde (MDA). While the increasing of CC16 and SOD, and decreasing of MDA in patients receiving HFOV was more noticeable than patients receiving WLL.Conclusions Taking together, the −634C/G polymorphisms in IL-6 play a role in the etiology of CWP. HFOV, when applied in CWP patients, significant improves their pulmonary functions.

Covariance tracking has achieved impressive successes owing to its competent region covariance–based feature descriptor. However, the brute–force search strategy in covariance tracking is inefficient and it possibly leads to inconsecutive tracking trajectory and distraction. In this work, a hybrid search strategy for optimisation on covariance tracking is proposed. The hybrid strategy contains the integral region computation, the coarse–to–fine and circular search, and mean shift optimisation. The integral region is much faster than integral image and adaptive to the tracking target and tracking condition. The other three dramatically speed up the convergence of the search. The proposed approach yields much better efficiency, robustness of distraction, and stable trajectory by local search in normal steady state. Our approach shows excellent target representation ability, faster speed, and more robustness, which has been verified on some video sequences.

Phase change materials (PCMs) are considered the most promising cooling technology due to their high latent heat, good reversibility, and low cost. However, in practical applications, PCMs encounter problems such as a sharp temperature increase after full melting and low thermal conductivity. To solve these problems, a new double helix-type liquid cooling plate is developed and coupled with a hydrated salt composite PCM (CPCM) for battery pack cooling. The modified CPCM has a high latent heat (249 J/g), suitable phase change temperature (35 °C), improved thermal conductivity to 1.86 W/(m·K), and reduced subcooling to 1.9 °C. The design of the liquid cooling plate structure can make the average water temperature on both sides of each cell approximate, thereby ensuring the temperature uniformity for the battery pack. A battery module system test rig is constructed and the heat dissipation effect for the battery module is compared with four cooling methods. The results reveal that the CPCM/liquid coupled cooling method is the most effective for cooling the battery pack. At a low coolant flow rate of 0.5 L/min, the maximum temperature difference for the coupled battery module is retained at 1.88 °C, and the average temperature is found to increase by only 9.6 °C. In addition, different coolant flow rates and control strategies of the coupled heat sink system are tested and compared. An optimal strategy is selected for the cyclic charge/discharge test of the coupled cooling module. The system is found to maintain good cooling performance and temperature uniformity after four charge/discharge cycles, and the highest temperature peak for the battery pack is only 40.3 °C, which is within the normal operating temperature range.

Bifunctional magnetic/fluorescent core-shell silica nanospheres (MNPs) encapsulated with the magnetic Fe3O4core and a derivate of 8-amimoquinoline (N-(quinolin-8-yl)-2-(3-(triethoxysilyl) propylamino) acetamide) (QTEPA) into the shell were synthesized. These functional MNPs were prepared with a modified stöber method and the formed Fe3O4@SiO2-QTEPA core-shell nanocomposites are biocompatible, water-dispersible, and stable. These prepared nanoparticles were characterized by X-ray power diffraction (XRD), transmission electron microscopy (TEM), thermoelectric plasma Quad II inductively coupled plasma mass spectrometry (ICP-MS), superconducting quantum interference device (SQUID), TG/DTA thermal analyzer (TGA) and Fourier transform infrared spectroscopy (FTIR). Further application of the nanoparticles in detecting Zn2+was confirmed by the fluorescence experiment: the nanosensor shows high selectivity and sensitivity to Zn2+with a 22-fold fluorescence emission enhancement in the presence of 10 μM Zn2+. Moreover, the transverse relaxivity measurements show that the core-shell MNPs have T2 relaxivity (r2) of 155.05 mM−1S−1based on Fe concentration on the 3.0 T scanner, suggesting that the compound can be used as a negative contrast agent for MRI. Further in vivoexperiments showed that these MNPs could be used as MRI contrast agent. Therefore, the new nanosensor provides the dual modality of magnetic resonance imaging and optical imaging.

Bacterial Vaginosis (BV) is the most common vaginal infection. A large amount of evidence shows that the anatomical scope of BV's pathogenic effect is far beyond the lower reproductive tract. BV is closely related to adverse reproductive outcomes, which may be due to the infection of the vaginal flora ascending to the upper genital tract. In addition, the incidence of BV is relatively high in infertile women. The vaginal microbiome also plays an important role in women's health and diseases. For most women, the normal vaginal microbiota is dominated by Lactobacillus, which can maintain a healthy vaginal environment by producing lactic acid, H2O2and bacteriocin, etc. BV is characterized by the imbalanced vaginal flora. It changes the acidic environment that is normally dominated by Lactobacillus, and causes an overgrowth of anaerobic and facultative anaerobic bacteria such as Gardnerella vaginalis and Atopobium vaginae. Studies have shown that bacterial infections in the vagina can spread to upper genital tract and cause adverse fertility outcome. Therefore, early diagnosis and therapeutics of symptomatic BV is helpful to improve the outcome of poor fertility.

Conventional antibody-based targeted cancer therapy is one of the most promising avenues of successful cancer treatment, with the potential to reduce toxic side effects to healthy cells surrounding tumor cells. However, the full potential of antibodies is severely limited due to their large size, low stability, slow clearance, and high immunogenicity. Alternatively, recently discovered nanobodies, which are the smallest naturally occurring antigen-binding format, have shown great potential for addressing these limitations. Bioconjugation of nanobodies to functional groups such as toxins, enzymes, radionucleotides, and fluorophores can improve the efficacy and potency of nanobodies, enhance their in vivopharmacokinetics, and expand the range of potential applications. Herein, we review the superior characteristics of nanobodies in comparison to conventional antibodies and provide insight into recent developments in nanobody conjugates for targeted cancer therapy and imaging.

Although Epirubicin (EPI) is a commonly used anthracycline for the treatment of breast cancer in clinic, the serious side effects limit its long-term administration including myelosuppression and cardiomyopathy. Nanomedicines have been widely utilized as drug delivery vehicles to achieve precise targeting of breast cancer cells. Herein, we prepared a DSPE-PEG nanocarrier conjugated a peptide, which targeted the breast cancer overexpression protein Na+/K+ ATPase α1 (NKA-α1). The nanocarrier encapsulated the EPI and grafted with the NKA-α1 targeting peptide through the click reaction between maleimide and thiol groups. The EPI was slowly released from the nanocarrier after entering the breast cancer cells with the guidance of the targeting NKA-α1 peptide. The precise and controllable delivery and release of the EPI into the breast cancer cells dramatically inhibited the cells proliferation and migration in vitroand suppressed the tumor volume in vivo. These results demonstrate significant prospects for this nanocarrier as a promising platform for numerous chemotherapy drugs.

Psoriasis is a chronic inflammatory skin disease characterized by an active dynamic interplay between immune cells and keratinocytes (KCs). STING is a universal receptor that recognizes cytosolic DNA and triggers innate immune activation. This study aims to elucidate the role of STING in the inflammation in psoriasis. STING deficiency alleviated psoriatic symptoms and inflammation in mouse models of psoriasis. Stimulation of macrophages with double-stranded DNA induced STING-dependent release of TNF-α and hydrogen peroxide in vitro. Furthermore, incubation of KCs with TNF-α or hydrogen peroxide increased oxidative DNA damage, induced nuclear DNA release into the cytosol, and inhibited double-stranded DNA‒induced degradation of STING protein. More importantly, transfection of KCs with double-stranded DNA synergized with TNF-α or hydrogen peroxide to induce STING-dependent activation of NF-κB and subsequent expression of Il1b, Ccl20, and Cxcl10. Finally, exposure to 5,6-dimethylxanthenone-4-acetic acid (a STING agonist) aggravated psoriatic symptoms and inflammation in wild-type mice but not in STING-deficient mice. Collectively, STING functioned as a self-DNA sensor in macrophages and KCs of psoriatic skin. Cytosolic DNA–induced activation of STING in immune cells and KCs acted synergistically and contributed to the inflammation in psoriasis.