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Self-assembly of biomolecules is critical for the realization of biological functions. Thus, the precise control of self-assembly has great significance in the design of biochips and biomedical agents. In this report, we design a Y-shaped funnel on a two-dimensional (2D) heterostructure, called 2D funnel, based on monolayered polyaniline carbon nitride (C

Ground military target recognition plays a crucial role in unmanned equipment and grasping the battlefield dynamics for military applications, but is disturbed by low-resolution and noisy-representation. In this paper, a recognition method, involving a novel visual attention mechanism-based Gabor region proposal sub-network (Gabor RPN) and improved refinement generative adversarial sub-network (GAN), is proposed. Novel central–peripheral rivalry 3D color Gabor filters are proposed to simulate retinal structures and taken as feature extraction convolutional kernels in low-level layer to improve the recognition accuracy and framework training efficiency in Gabor RPN. Improved refinement GAN is used to solve the problem of blurry target classification, involving a generator to directly generate large high-resolution images from small blurry ones and a discriminator to distinguish not only real images vs. fake images but also the class of targets. A special recognition dataset for ground military target, named Ground Military Target Dataset (GMTD), is constructed. Experiments performed on the GMTD dataset effectively demonstrate that our method can achieve better energy-saving and recognition results when low-resolution and noisy-representation targets are involved, thus ensuring this algorithm a good engineering application prospect.

PDF file - 119KB, Characteristics of patient who received CIK cell treatment.

Purpose: Triple-negative breast cancer (TNBC) is a high risk form of this disease, even after surgery, due to the absence of targets for hormone treatment and anti–Her-2 therapy. Chemotherapy is the main therapeutic strategy for such patients with breast cancer, although the outcome is often unsatisfactory. Thus, the development of combination adjuvant therapies is essential for improved prognosis in patients with TNBC. In this study, we investigated the efficacy of a sequential combination of cytokine-induced killer cell (CIK) infusion and chemotherapy for patients with post-mastectomy TNBC.Experimental Design: From 2008 to 2012, 90 patients with post-mastectomy TNBC were included in this retrospective study: 45 cases received chemotherapy alone or with sequential radiotherapy; a further 45 cases received chemotherapy with/without radiotherapy and sequential CIK infusion.Results: Survival analysis showed significantly higher disease-free survival (DFS) and overall survival (OS) rates in the CIK treatment group compared with the control group (P = 0.0382, P = 0.0046, respectively; log-rank test). Multivariate survival analysis showed that CIK adjuvant treatment was an independent prognostic factor for OS of patients with TNBC. In subgroup analyses, CIK adjuvant treatment significantly increased the DFS rate of patients with pathologic grade 3, and significantly increased the OS rate of patients in N1, N2, N3, IIB, III TNM (tumor–node–metastasis) stages, and with pathologic grade 3.Conclusions: These data indicate that adjuvant CIK treatment combined with chemotherapy is an effective therapeutic strategy to prevent disease recurrence and prolong survival of patients with TNBC, particularly those with lymph node metastasis, advanced TNM stage, and poor pathologic grade. Clin Cancer Res; 20(11); 3003–11. ©2014 AACR.

PDF file - 108KB, CIK cell treatment protocol.

The r-N-GDY filter can be switched between a high-flux “open” state (up to 81.8 L per cm2 per day per MPa) and a “closed” state (4% along the ZZ-direction) by applying tensile strain along different directions, yielding a highly tunable nanopore interface.

Background Treatment options for refractory metastatic colorectal cancer (mCRC) were limited. Anlotinib is a novel multitarget tyrosine kinase inhibitor. ALTER0703 study was conducted to assess efficacy and safety of anlotinib for patients with refractory mCRC. Materials and Methods This was a multicenter, double-blinded, placebo-controlled, randomized phase III trial involving 33 hospitals in China. Patients had taken at least two lines of therapies were 2:1 randomized to receive oral anlotinib (12 mg/day; days 1–14; 21 days per cycle) or placebo, plus best supportive care. Randomization was stratified by previous VEGF-targeting treatments and time from diagnosis to metastases. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL), and safety. Results A total of 419 patients (anlotinib: 282; placebo: 137) were treated from December 2014 to August 2016. The median PFS was improved in anlotinib group (4.1 months; 95% confidence interval [CI], 3.4–4.5) over placebo group (1.5 months; 95% CI, 1.4–1.5), with a hazard ratio (HR) of 0.34 (95% CI, 0.27–0.43; p < .0001). However, median OS was similar between two groups (8.6 months; 95% CI, 7.8–9.7 vs. 7.2 months; 95% CI, 6.2–8.8; HR, 1.02; p = .870). Improvements of ORR and DCR were observed in anlotinib over placebo. The most common grade ≥ 3 anlotinib related adverse events were hypertension (20.92%), increased γ-GT (7.09%), and hand-foot skin reaction (6.38%). Conclusion Anlotinib was tolerated in Chinese patients with refractory mCRC. Although OS did not reach significant difference, anlotinib still provided clinical benefits by substantially prolonged PFS in these patients. Implications for Practice In this randomized clinical trial that included 419 patients with refractory metastatic colorectal cancer, substantial prolonged in progression-free survival was noted in patients who received anlotinib compared with those given placebo. Improvements on objective response rate and disease control rate was also observed in anlotinib group. However, overall survival was similar between the two groups. In a word, in third-line or above treatment of Chinese patients with refractory metastatic colorectal cancer, anlotinib provided clinical benefit by significantly prolonged progression-free survival.

Several works have shown that graphene materials can effectively regulate the double-stranded DNA (dsDNA) structures and are used to remove antibiotic resistance genes in the environment, during which the morphology of the graphene surface plays a key role. However, the mechanism of how different graphene surfaces interact with dsDNA is poorly documented. Here, the interactions of dsDNA with defective graphene (D-Gra) and pristine graphene (P-Gra) have been explored by molecular dynamics simulations. Our data clearly showed that both D-Gra and P-Gra were able to attract dsDNA to form stable bindings. However, the structure evolutions of dsDNA are distinctly different. In detail, D-Gra can initiate quick unwinding of dsDNA and cause significant structural disruption. While for P-Gra, it demonstrated a much weaker capability to disrupt the dsDNA structure. This difference is due to the strong electrostatic interaction between defects and DNA nucleotides. Nucleotides can be highly restricted by the defect while the other parts of dsDNA could move along the transverse directions of D-Gra. This effectively introduces a "pulling force" from the defect that causes the breaking of the hydrogen bonds between dsDNA base pairs. Such force finally leads to the serious unwinding of dsDNA. Our present findings could help us to better understand the molecular mechanism of how the dsDNA canonical B-form was lost upon adsorption to graphene. The findings of the key roles of defects on graphene are beneficial for the design of functional graphenic materials for biological and medical applications through nanostructure engineering.

Nanozymes, a type of nanomaterials that function similarly to natural enzymes, receive extensive attention in biomedical fields. However, the widespread applications of nanozymes are greatly plagued by their unsatisfactory enzyme-mimicking activity. Localized surface plasmon resonance (LSPR), a nanoscale physical phenomenon described as the collective oscillation of surface free electrons in plasmonic nanoparticles under light irradiation, offers a robust universal paradigm to boost the catalytic performance of nanozymes. Plasmonic nanozymes (PNzymes) with elevated enzyme-mimicking activity by leveraging LSPR, emerge and provide unprecedented opportunities for biocatalysis. In this review, the physical mechanisms behind PNzymes are thoroughly revealed including near-field enhancement, hot carriers, and the photothermal effect. The rational design and applications of PNzymes in biosensing, cancer therapy, and bacterial infections elimination are systematically introduced. Current challenges and further perspectives of PNzymes are also summarized and discussed to stimulate their clinical translation. It is hoped that this review can attract more researchers to further advance the promising field of PNzymes and open up a new avenue for optimizing the enzyme-mimicking activity of nanozymes to create superior nanocatalysts for biomedical applications.

Sepsis is a life-threatening organ dysfunction characterized by severe systemic inflammatory response to infection. Effective treatment of bacterial sepsis remains a paramount clinical challenge, due to its astonishingly rapid progression and the prevalence of bacterial drug resistance. Here, we present a decoy nanozyme-enabled intervention strategy for multitarget blockade of proinflammatory cascades to treat multi-drug-resistant (MDR) bacterial sepsis. The decoy nanozymes (named MCeC@M Φ ) consist mesoporous silica nanoparticle cores loaded with CeO 2 nanocatalyst and Ce6 photosensitizer and biomimetic shells of macrophage membrane. By acting as macrophage decoys, MCeC@M Φ allow targeted photodynamic eradication of MDR bacteria and realize simultaneous endotoxin/proinflammatory cytokine neutralization. Meanwhile, MCeC@M Φ possess intriguing superoxide dismutase and catalase-like activities as well as hydroxyl radical antioxidant capacity and enable catalytic scavenging of multiple reactive oxygen species (ROS). These unique capabilities make MCeC@M Φ to collaboratively address the issues of bacterial infection, endotoxin/proinflammatory cytokine secretion, and ROS burst, fully cutting off the path of proinflammatory cascades to reverse the progression of bacterial sepsis. In vivo experiments demonstrate that MCeC@M Φ considerably attenuate systemic hyperinflammation and rapidly rescue organ damage within 1 day to confer higher survival rates (>75%) to mice with progressive MDR Escherichia coli bacteremia. The proposed decoy nanozyme-enabled multitarget collaborative intervention strategy offers a powerful modality for bacterial sepsis management and opens up possibilities for the treatment of cytokine storm in the COVID-19 pandemic and immune-mediated inflammation diseases.

Staphylococcus aureus (S. aureus) related staphylococcal infection is one of the most common types of hospital-acquired infections, which requires selective and effective treatment in clinical practice. Considering gelatinase as a characteristic feature of S. aureus, gelatinase-responsive release of the antibiotic reagent thereby can target the pathogenic S. aureus while sparing beneficial bacteria in the microflora. In this work, we design a hybrid antibacterial photodynamic peptide (APP, Ce6-GKRWWKWWRRPLGVRGC) based on the polycationic antimicrobial peptide GKRWWKWWRR by introducing a photosensitizer chlorin e6 (Ce6) at the N-terminus, a cysteine residue at the C-terminus, and a gelatinase cleavage site (PLGVRG) inserted between the C-terminal cysteine and the polycationic peptide. This multi-motif peptide assembles with gold nanoclusters (AuNc) via Au–thiol bonding and affords a gelatinase-responsive antibacterial photodynamic nanocomposite (GRAPN). In vitro results show that the gelatinase secreted by S. aureus can cleave and release APP from AuNc, thereby resulting in preferential killing of S. aureus over E. coli. In a mouse model of staphylococcal skin wound infection, by integrating gelatinase-responsive drug release and the synergistic effect of a photodynamic agent and APP, GRAPN exhibits a marked photodynamic antibacterial activity, effectively eradicates S. aureus infection, and promotes rapid healing of the infected wounds.

Quantum dense coding properties between two identical and spatially separated atoms in free space with different initial states is investigated. It shows that dense coding capacity χ experienced a sharp decline firstly and then gradually increased to be one steady value 1 with increasing Γt. The realization of dense coding capacity χ is found to be strongly dependent on the initial states. It is worth noting that the initial pure state |ee〉 is not useful for dense coding in this system, due to the dense coding capacity χ is always less than 1(a valid dense coding capacity satisfies χ > 1). Otherwise, for the initial entangled state and mixed state, one can obtain the valid dense coding capacity, the results show that one threshold value of tc is exists, and when t < tc the dense coding capacity is valid. Tuning the atomic distance between the two atoms slightly broaden the valid dense coding region and improve the value of tc. Decreasing the purity a of initial states not only broaden the region but also prolong the effective time where one can carry out the valid dense coding successfully.

Optimal dense coding of a two-qubit anisotropic Heisenberg XXZ model under decoherence is investigated with the Werner state as the initial state. With the time evolution, the dense coding capacity χ oscillates firstly, and then reaches a stable value 1 in the long time limit, whatever the values of other parameters are. Our results imply that the purity r of the initial state have a strong influence on the initial value of the optimal dense coding capacity. When the purity r of the initial state increase, the initial value of dense coding capacity increase. Besides, the coupling coefficient and Dzyaloshinski-Moriya(DM) both have strong influence on the frequency of the oscillation and the area of t that the optimal dense coding is feasible(tf). Interestingly, the decoherence rate γ can strongly affect the dense coding capacity. With the decreasing of γ, the area of tf(which will make the dense coding capacity greater than 1) becomes more wider. When γ = 0, it will still allows a valid dense coding. So we can adjust the parameters to get a optimal dense coding.

The preparation of tetragonal zirconia nanopowders by sol–gel method using zirconium oxychloride as raw material, ammonia water and sodium hydroxide solution as precipitant, and calcium oxide or magnesium oxide powders as stabilizing agents is described. After suction filtration, drying, and calcination, tetragonal zirconia nanopowders with different particle size and tetragonal phase content were obtained. The particle size and phase composition of the powders are characterized by using a laser particle size analyzer and an X-ray diffractometer, and the tetragonal phase content and grain size are calculated from the crystal plane formula and Scherrer formula. The analysis of the relationship between the tetragonal phase content and the particle size of the zirconia nanopowders stabilized by calcium oxide and magnesium oxide at room temperature reveals the inhibitory effect of the stabilizing agents on the growth of zirconia grains. The stabilized zirconia nanopowder is finer than unstabilized zirconia nanopowder, and the particle distribution is more uniform in the former. The stabilizing effect of calcium oxide is superior to that of magnesium oxide; the critical transformation size of the zirconia grains stabilized by calcium oxide is the largest, and that of unstabilized zirconia is the smallest. The critical transformation size of calcium oxide-stabilized, magnesium oxide-stabilized, and unstabilized zirconia nanopowders is 18–22.6 nm, 24–28 nm, and 26–33.6 nm, respectively. Under the same calcination condition, the calcium oxide-stabilized zirconia nanopowder retains the highest tetragonal phase content at room temperature.

The COVID-19 pandemic caused by SARS-CoV-2 has been declared a global health crisis. The development of anti-SARS-CoV-2 drugs heavily depends on the systematic study of the critical biological processes of key proteins of coronavirus among which the main proteinase (M

The emergence of bacterial resistance due to the evolution of microbes under antibiotic selection pressure, and their ability to form biofilm, has necessitated the development of alternative antimicrobial therapeutics. Physical stimulation, as a powerful antimicrobial method to disrupt microbial structure, has been widely used in food and industrial sterilization. With advances in nanotechnology, nanophysical antimicrobial strategies (NPAS) have provided unprecedented opportunities to treat antibiotic-resistant infections, via a combination of nanomaterials and physical stimulations. In this review, NPAS are categorized according to the modes of their physical stimulation, which include mechanical, optical, magnetic, acoustic, and electrical signals. The biomedical applications of NPAS in combating bacterial infections are systematically introduced, with a focus on their design and antimicrobial mechanisms. Current challenges and further perspectives of NPAS in the clinical treatment of bacterial infections are also summarized and discussed to highlight their potential use in clinical settings. The authors hope that this review will attract more researchers to further advance the promising field of NPAS, and provide new insights for designing powerful strategies to combat bacterial resistance.

Cable’s fundamental frequency (CFF) is an important characteristic of the working state of long-span cable-stayed bridges. The change in the bridge’s temperature field will influence CFF by altering the cable’s tension and the cables’ sags. An accurate regression model between the temperature-induced variation of CFF and the real-time changing temperature field should be established. Then, the reference value of the temperature-induced variation of CFF can be obtained after inputting the real-time temperature data. In this study, an intelligent real-time prediction model for CFF is proposed based on the full-bridge temperature field, including the average temperature of the main beam, the vertical temperature difference of the main beam, and the temperature of the cable tower. Besides, a machine learning method named the long short-term memory (LSTM) network is exploited to ensure the nonlinear fitting performance of the model, and a paradigm for optimal hyperparameter selection and training strategy selection is provided. To verify the superiority of the LSTM-based model, the output accuracy of the linear regression, BP network, and LSTM network was tested and compared using the monitoring data collected from cable sensors in the main span and side span, which provides an important basis for the intelligent maintenance and sustainable operation of the bridge cables.

Insect carboxylesterases are major enzymes involved in metabolism of xenobiotics including insecticides. Two carboxylesterase genes, CarE001A and CarE001H, were cloned from the destructive agricultural pest Helicoverpa armigera. Quantitative real-time polymerase chain reaction showed that CarE001A and CarE001H were predominantly expressed in fat body and midgut, respectively; developmental expression analyses found that the expression levels of both CarEs were significantly higher in fifth-instar larvae than in other life stages. Recombinant CarE001A and CarE001H expressed in the Escherichia coli exhibited high enzymatic activity toward α-naphthyl acetate. Inhibition assays showed that organophosphates had strong inhibition on CarEs activity compared to pyrethroids. Metabolism assays indicated that CarE001A and CarE001H were able to metabolize β-cypermethrin and λ-cyhalothrin. Homology modeling and molecular docking analyses demonstrated that β-cypermethrin could fit nicely into the active pocket of both carboxylesterases. These results suggested that CarE001A and CarE001H could play important roles in the detoxification of pyrehtroids in H. armigera.

Adjuvant cytokine-induced killer (CIK) cell immunotherapy has shown potential in improving the prognosis of hepatocellular carcinoma (HCC) patients after curative resection. However, whether an individual could obtain survival benefit from CIK cell treatment remains unknown. In the present study, we focused on the characteristics of CIK cells and aimed to identify the best predictive biomarker for adjuvant CIK cell treatment in patients with HCC after surgery. This study included 48 patients with HCC treated with postoperative adjuvant CIK cell immunotherapy. The phenotype activity and cytotoxic activity of CIK cells were determined by flow cytometry and xCELLigence™ Real-Time Cell Analysis (RTCA) system, respectively. Correlation analysis revealed that the cytotoxic activity of CIK cells was significantly negative correlated with the percentage of CD3+ CD4+ cell subsets, but significantly positive correlated with CD3-CD56+ and CD3+ CD56+ cell subsets. Survival analysis showed that there were no significant associations between patients' prognosis and the phenotype of CIK cells. By contrast, there was statistically significant improvement in recurrence-free survival (RFS) and overall survival (OS) for patients with high cytotoxic activity of CIK cells as compared with those with low cytotoxic activity of CIK cells. Univariate and multivariate analyses indicated that CIK cell cytotoxicity was an independent prognostic factor for RFS and OS. In conclusion, a high cytotoxic activity of CIK cells can serve as a valuable biomarker for adjuvant CIK cell immunotherapy of HCC patients after surgery.

A systematic understanding of interactions at the nano-bio interface is critical for the development of bio-functional nanomaterials and nano-agents for medical applications, which essentially require high safety, biocompatibility and therapeutic efficiency. As a new member of the two-dimensional material family, α-phase phosphorene carbide (α-PC) has attracted significant research interest in recent years. Benefitting from the unique buckled structure and its rich physical and chemical features, the future applications of α-PC in biological and medical areas are intriguing. Using molecular dynamics simulations (MDs), herein, we theoretically explore the interactions of α-PC nanoribbons with the cell lipid membrane to evaluate the potential biological toxicity to lipids. Our results clearly demonstrate that the α-PC sheet can only penetrate the membrane along its zigzag direction by attracting the lipids to the groove regions. The membrane undergoes slight structural distortion, but quickly recovers after the penetration. Only localized impacts are detected on the membrane after the penetration. In contrast, the intrusion along armchair direction is highly blocked by lipids. Free energy analysis by the umbrella sampling method revealed that the fatty acid tails of lipids prefer to bind along the groove regions of α-PC rather than across the grooves, resulting in a high anisotropic penetration behavior. The overall attraction of α-PC to lipid is weaker than graphene, and the binding lipids cannot be fully extracted from the membrane environment. The self-equilibration of the membrane is fast enough to prevent lipids from escaping, leading to the well-preserved membrane integrity. Our present findings suggest that α-PC might offer new potential as bio-agents with high membrane-penetrating efficiency and lower cytotoxicity. The unique anisotropic behaviors can be further utilized for the design and fabrication of specialized nanomaterials with the capability of efficient and template-directed molecule delivery.

Sensitive diagnosis and elimination of multidrug-resistant bacterial infections at an early stage remain paramount challenges. Herein, we present a gelatinase-responsive turn-on nanoprobe for in situ near-infrared (NIR) fluorescence imaging and localized photothermal treatment (PTT) of in vivo methicillin-resistant Staphylococcus aureus (MRSA) infections. The designed nanoprobe (named AuNS-Apt-Cy) is based on gold nanostars functionalized with MRSA-identifiable aptamer and gelatinase-responsive heptapeptide linker (CPLGVRG)-cypate complexes. The AuNS-Apt-Cy nanoprobe is non-fluorescent in aqueous environments due to the fluorescence resonance energy transfer between the gold nanostar core and cypate dye. We demonstrate that the AuNS-Apt-Cy nanoprobe can achieve MRSA targeting and accumulation as well as gelatinase (overexpressed in MRSA environments)-responsive turn-on NIR fluorescence due to the cleavage of the CPLGVRG linker and localized in vitro PTT via a mechanism involving bacterial cell wall and membrane disruption. In vivo experiments show that the AuNS-Apt-Cy nanoprobe can enable rapid (1 h post-administration) and in situ turn-on NIR fluorescence imaging with high sensitivity (105 colony-forming units) in diabetic wound and implanted bone plate mouse models. Remarkably, the AuNS-Apt-Cy nanoprobe can afford efficient localized PTT of diabetic wound and implanted bone plate-associated MRSA infections under the guidance of turn-on NIR fluorescence imaging, showing robust capability for early diagnosis and treatment of in vivo MRSA infections. In addition, the nanoprobe exhibits negligible damage to surrounding healthy tissues during PTT due to its targeted accumulation in the MRSA-infected site, guaranteeing its excellent in vivo biocompatibility and solving the main bottlenecks that hinder the clinical application of PTT-based antibacterial strategies.

The unique puckered structure of α-phase phosphorene carbide (α-PC) results in anisotropic electronic and thermal transporting properties. In the present work, the interactions between a model protein, villin headpiece sub-domain (HP35), and the surface of α-PC and monolayer black phosphorus (MBP, another puckered nanostructure) were explored by molecular dynamic (MD) simulations. It is found that HP35 diffuses quickly only along the zigzag direction of the α-PC surface. On the MBP surface, HP35 migrates mainly along the zigzag direction but can also easily stride over the ridges and grooves along the armchair direction. Moreover, the mild binding strength between α-PC and HP35 does not cause distortion in the protein structure. The intrinsic biocompatibility of α-PC, which is distinct from several other widely studied nanomaterials, such as carbon nanotubes, graphene and MoS2, makes it a promising candidate in functional biomedical applications. This work is supported by the National Natural Science Foundation of China (Grant No. 11874238), the Natural Science Foundation of Shandong Province (Grant No. ZR2018MA034) and Fundamental Research Funds of Shandong University.

Biofilm infections can induce chronic inflammation and stall the normal orchestrated course of wound-healing cascades. Herein, pH-switchable antimicrobial hydrogel with nanofiber networks for biofilm eradication and rescuing stalled healing in chronic wounds is reported on the basis of the self-assembly of a designed octapeptide (IKFQFHFD) at neutral pH. This hydrogel is biocompatible and exhibits an acidic pH (pathological environment of infected chronic wounds)-switchable broad-spectrum antimicrobial effect via a mechanism involving cell wall and membrane disruption. The antimicrobial activity of hydrogel is derived from its acidic pH-dependent nanofiber network destabilization and activated release of IKFQFHFD, which is antimicrobial only at acidic pH due to the antimicrobial peptide-like molecular structure. In addition, supramolecular nanofiber networks loaded with drugs of cypate (photothermal agent) and proline (procollagen component) are further developed. In vitro experiments show that loaded drugs exhibit acidic pH (pH ∼ 5.5)-responsive release profiles, and synergistic biofilm eradication and subsequent healing cascade activation of cells proliferation are achieved on the basis of the supramolecular nanofiber networks. Remarkably, the nanofiber networks of hydrogel enable in vivo complete healing of MRSA biofilm infected wound in diabetic mice within 20 days, showing great potential as promising chronic wound dressings. The proposed synergistic strategy for eradicating biofilm and activating subsequent healing cascades may offer a powerful modality for the management of clinical chronic wounds.

We investigate the effects of spin squeezing interaction, external magnetic field and temperature on dense coding capacity properties in two kinds of two-qubit spin squeezing model: one-axis twisting model (OATM) and two-axis countertwisting model (TACM). To the OATM, it is found that the value of dense coding capacity χ is larger than 1 in the region of larger values of Ω(external magnetic filed) and μ(squeezing interaction) parameters space, while in the region of lower values of Ω and μ parameters space, χ is always less than 1 and not valid for dense coding. With increasing temperature T the dense coding capacity is decayed, and one can carry out the valid dense coding in the lower T region through tuning Ω. To the TACM, it is found that the value of χ is promoted with increasing the squeezing parameter γ. Through increasing γ, χ finally reached to one stable value, which is always larger than 1 whatever value of Ω is. The valid dense coding capacity χ can be enhanced through tuning the parameter Ω or γ, but it is decreased with increasing T. Our results show that with proper enhancing the parameter Ω or γ it is easy to carry out the valid dense coding (χ > 1) and the optimal dense coding (χ = 2) when the system in TACM.

Bacterial infections pose mounting public health concerns and cause an enormous medical and financial burden today. Rapid and sensitive detection of pathogenic bacteria at the point of care (POC) remains a paramount challenge. Here, we report a novel concept of bacteria-instructed click chemistry and employ it for POC microbial sensing. In this concept of bacteria-instructed click chemistry, we demonstrate for the first time that pathogenic bacteria can capture and reduce exogenous Cu2+ to Cu+ by leveraging their unique metabolic processes. The produced Cu+ subsequently acts as a catalyst to trigger the click reaction between gold nanoparticles (AuNPs) modified with azide and alkyne functional molecules, resulting in the aggregation of nanoparticles with a color change of the solution from red to blue. In this process, signal amplification from click chemistry is complied with the aggregation of functionalized AuNPs, thus presenting a robust colorimetric strategy for sensitive POC sensing of pathogenic bacteria. Notably, this colorimetric strategy is easily integrated in a smartphone app as a portable platform to achieve one-click detection in a mobile way. Moreover, with the help of the magnetic preseparation process, this smartphone app-assisted platform enables rapid (within 1 h) detection of Escherichia coli with high sensitivity (40 colony-forming units/mL) in the complex artificial sepsis blood samples, showing great potential for clinical early diagnosis of bacterial infections.

In this study, the chemical composition of cement pastes, exposed to accelerated carbonation using different concentration of CO2 (3%, 10%, 20%, 50%,100%), have been determined and compared with those of natural carbonation (0.03%). Quantitative X-ray diffraction (QXRD) and( 29)Si Magic Angle Spinning Nuclear Magnetic Resonance (MAS NMR) were used for characterisation and quantitative analysis of the carbonated phases. The obtained QXRD results revealed that the complete carbonation was hardly attained. Calcite, aragonite and vaterite were in co-existence after accelerated carbonation, while vaterite was dominant. The preferential polymorphic precipitation of the three crystal forms of calcium carbonate was affected by the carbonation degree of C-S-H and the duration of the carbonation process, but not by the concentration of CO2. The NMR results indicated that C-S-H gel was strongly decalcified, and calcium modified silica gel was formed after carbonation. The C-S-H decalcification, under all the accelerated carbonation conditions, was clearly more pronounced than that under the natural carbonation conditions. When the concentration of CO2 was in the range of 3%-20%, the ratio of decalcified to remaining C-S-H was similar, in a range of 5-6, while under the higher concentration of CO2 this ratio was increased to > 8. Therefore, in consideration of both acceleration rate and measurement uncertainty, the higher concentration, up to 20%, of CO2 in an accelerated carbonation should be applicable.

One key task in virtual screening is to accurately predict the binding affinity ($\triangle$$G$) of protein-ligand complexes. Recently, deep learning (DL) has significantly increased the predicting accuracy of scoring functions due to the extraordinary ability of DL to extract useful features from raw data. Nevertheless, more efforts still need to be paid in many aspects, for the aim of increasing prediction accuracy and decreasing computational cost. In this study, we proposed a simple scoring function (called OnionNet-2) based on convolutional neural network to predict $\triangle$$G$. The protein-ligand interactions are characterized by the number of contacts between protein residues and ligand atoms in multiple distance shells. Compared to published models, the efficacy of OnionNet-2 is demonstrated to be the best for two widely used datasets CASF-2016 and CASF-2013 benchmarks. The OnionNet-2 model was further verified by non-experimental decoy structures from docking program and the CSAR NRC-HiQ data set (a high-quality data set provided by CSAR), which showed great success. Thus, our study provides a simple but efficient scoring function for predicting protein-ligand binding free energy., 7 pages, 4 figures, 1 table

Carboxylesterases (CarEs) usually play critical roles in the detoxification of toxic chemicals and therefore may be involved in insecticide resistance in agricultural pests. Previous work has shown that CarE 001C from Helicoverpa armigera was able to metabolize the isomers of cypermethrin and fenvalerate. In this study, seven mutants of CarE 001C with single amino acid substitution were produced and expressed in the Escherichia coli. Enzyme kinetic analysis indicated that all seven mutations dramatically reduced enzymatic activities toward the generic substrate α-naphthyl acetate, but in vitro metabolism assay showed that two of the mutations, H423I and R322L, significantly improved hydrolase activities toward fenvalerate, with their recorded specific activities being 3.5 and 5.1 nM·s−1·mg −1 proteins, respectively. Further, thermostability assay showed that the stability of one mutant enzyme was enhanced. This study will help us better understand the potential of CarEs in insecticide detoxification and resistance in H. armigera.

Although nanomaterials are widely studied in biomedical applications, the major concern of nanotoxicity still exists. Therefore, numerous works have been conducted on the interactions of various biomolecules with various types of nanomaterials, including carbon nanotube, graphene, fullerene and etc. However, the size effect of nanomaterials is poorly documented, especially the ultra-small particles. Here, the interactions of the smallest carbon nanoparticle (NP), C28, with cell membrane were studied using molecular dynamics (MD) simulations. The results show that similar to fullerene C60, the C28 NPs can self-assemble into stable clusters in water. Inside membrane, the C28 NPs are more prone to aggregate to form clusters than C60 NPs. The reason of the C28 aggregation is characterized by potential of mean force (PMF) and can be explained by the polarized nature of C28 NPs while the acyl chains of lipids are nonpolar. At the C28 cluster regions, the thickness of the membrane is significantly reduced by the C28 aggregation. Accordingly, the membrane losses its structural integrity and translocation of water molecules through it were observed. Thus, these results predict a stronger cytotoxicity to cells than C60 NPs. The present findings might shed light on the understanding of the cytotoxicity of NPs with different size and would be helpful for the potential biomedical applications of carbon NPs, especially as antibacterial agents.

Solid-state nanopore detection and sequencing of a single molecule offers a new paradigm because of its several well-recognized features such as long reads, high throughput, high precision and direct analyses. However, several key technical challenges are yet to be addressed, especially the abilities to control the speed and direct the translocation of the target molecules. In this work, using molecular dynamics (MD) simulations, we found a spontaneous translocation of single-stranded DNA (ssDNA) through a van der Waals (vdW) heterostructure nanopore formed by stacking two graphenic materials, namely those of BC3 and C3N. Our results showed that, without using an external stimulus, ssDNA can be spontaneously transported through such a vdW nanopore from its BC3 side to its C3N side, with the C3N surface demonstrating a stronger capability than the BC3 surface to attract DNA bases. Thus, the distinct binding strengths of BC3 and C3N were concluded to drive the ssDNA translocation. The results indicated the vdW forces playing a leading role during the translocation process. Our simulations also showed, at the edges of the nanopore, a clear energy barrier for nucleotides, resulting in a translocation speed slowed to a value of 0.2 μs per base, i.e., twice as slow as that indicated for the latest published methods. The present findings provide a new architecture for biomolecule detection and sequencing, which may be considered some of the most important functions of nanomaterials in biological and chemical analyses.

Staphylococcus aureus (S. aureus) related staphylococcal infection is one of the most common types of hospital-acquired infections, which requires selective and effective treatment in clinical practice. Considering gelatinase as a characteristic feature of S. aureus, gelatinase-responsive release of the antibiotic reagent thereby can target the pathogenic S. aureus while sparing beneficial bacteria in the microflora. In this work, we design a hybrid antibacterial photodynamic peptide (APP, Ce6-GKRWWKWWRRPLGVRGC) based on the polycationic antimicrobial peptide GKRWWKWWRR by introducing a photosensitizer chlorin e6 (Ce6) at the N-terminus, a cysteine residue at the C-terminus, and a gelatinase cleavage site (PLGVRG) inserted between the C-terminal cysteine and the polycationic peptide. This multi-motif peptide assembles with gold nanoclusters (AuNc) via Au-thiol bonding and affords a gelatinase-responsive antibacterial photodynamic nanocomposite (GRAPN). In vitro results show that the gelatinase secreted by S. aureus can cleave and release APP from AuNc, thereby resulting in preferential killing of S. aureus over E. coli. In a mouse model of staphylococcal skin wound infection, by integrating gelatinase-responsive drug release and the synergistic effect of a photodynamic agent and APP, GRAPN exhibits a marked photodynamic antibacterial activity, effectively eradicates S. aureus infection, and promotes rapid healing of the infected wounds.

Due to nature abundant and low-cost of sodium reserves with broad distribution in the earth's crust, sodium-ion batteries (SIBs) have attracted widespread attention for their great potential application in low-speed electric vehicles and large-scale energy storage system. However, their practical application is still hampered by the lack of decent anode materials. In this work, we develop an effective strategy to fabricate a nanohybrid of Sn4P3 and graphene oxide and demonstrate its outstanding sodium-storage behavior as an anode material for SIBs. By directly grinding tin(IV) chloride pentahydrate, sodium hydroxide, graphene oxide (GO) and surfactant PEG-200 at ambient temperature, an effective solid state reaction occurred to give rise to a precursor (named as SnO2/GO-PEG200), i.e. a nanocomposite of SnO2 encapsulated within GO matrix. After subsequent phosphorization at 280 °C using sodium hypophosphite monohydrate as phosphorous source, a nanohybrid of Sn4P3 and graphene oxide (designated as Sn4P3/GO-PEG200) was acquired. The coexistence of Sn4P3 nanoparticles and GO nanosheets endows the nanohybrid with improved electronic conductivity, highly structural integrity and superior electrochemical performance. When employed as anode material for SIBs, the nanohybrid anode demonstrates a good cycling stability (419 mA h g−1 after 100 cycles at 0.1 A g−1), with a remarkable rate capabilities (325 mA h g−1 at a current density of 1 A g−1 and 187 mA h g−1 at a current density of 5 A g−1, respectively).

Nano-radiosensitizers provide a powerful tool for cancer radiation therapy. However, their limited tumor retention/penetration and the inherent or adaptive radiation resistance of tumor cells hamper the clinical success of radiation therapy. Herein, we report a synergistic strategy for potentiated cancer radiation/gene therapy based on transformable gold nanocluster aggregates loaded with antisense oligonucleotide-targeting survivin mRNA (named AuNC-ASON). AuNC-ASON exhibited acidic pH-triggered structure splitting from a gold nanocluster aggregate (around 80 nm) to gold nanocluster (

BackgroundUnderstanding the associations of axial length (AL) with retinal thickness (RT) and choroidal thickness (CT) at different subgrids among diabetic participants are of great important in exploring potential protective mechanism and pathogenesis of diabetic retinopathy (DR) in myopic eyes. Therefore, this study aimed to investigate the associations of AL with RT and CT among participants with type-2 diabetes mellitus (T2DM).MethodsParticipants with T2DM and registered with the government-monitored diabetes communities near Zhongshan Ophthalmic Center, Guangzhou, China, were consecutively invited to participate in the current study from October 2017 to April 2019. High-definition retina and choroid images of the macular area were obtained using swept-source optical coherence tomography.AL and other ocular biometrics were measured using Lenstar900. Linear regression models were used to assess relationships between AL and RT as well as CT.ResultsA total of 1378 participants with a mean age of 63.8±7.75 years and mean AL of 23.6±1.15 mm were included in the current study. In the multivariate linear regression models, AL was positively associated with the central RT (β=4.11 per mm increased in AL, 95%confidence interval (CI)=2.66 to 5.56, PConclusionsMyopic ocular elongation is accompanied by retinal thinning of the outer ring and retinal thickening of the foveal area. The CT of the macular area tended to become thinner with elongated AL among the diabetic subjects.

Sensitive diagnosis and elimination of multidrug-resistant bacterial infections at an early stage remain paramount challenges. Herein, we present a gelatinase-responsive turn-on nanoprobe for in situ near-infrared (NIR) fluorescence imaging and localized photothermal treatment (PTT) of in vivo methicillin-resistant Staphylococcus aureus (MRSA) infections. The designed nanoprobe (named AuNS-Apt-Cy) is based on gold nanostars functionalized with MRSA-identifiable aptamer and gelatinase-responsive heptapeptide linker (CPLGVRG)-cypate complexes. The AuNS-Apt-Cy nanoprobe is non-fluorescent in aqueous environments due to the fluorescence resonance energy transfer between the gold nanostar core and cypate dye. We demonstrate that the AuNS-Apt-Cy nanoprobe can achieve MRSA targeting and accumulation as well as gelatinase (overexpressed in MRSA environments)-responsive turn-on NIR fluorescence due to the cleavage of the CPLGVRG linker and localized in vitro PTT via a mechanism involving bacterial cell wall and membrane disruption. In vivo experiments show that the AuNS-Apt-Cy nanoprobe can enable rapid (1 h post-administration) and in situ turn-on NIR fluorescence imaging with high sensitivity (105 colony-forming units) in diabetic wound and implanted bone plate mouse models. Remarkably, the AuNS-Apt-Cy nanoprobe can afford efficient localized PTT of diabetic wound and implanted bone plate-associated MRSA infections under the guidance of turn-on NIR fluorescence imaging, showing robust capability for early diagnosis and treatment of in vivo MRSA infections. In addition, the nanoprobe exhibits negligible damage to surrounding healthy tissues during PTT due to its targeted accumulation in the MRSA-infected site, guaranteeing its excellent in vivo biocompatibility and solving the main bottlenecks that hinder the clinical application of PTT-based antibacterial strategies.

Background The Cucurbita genus contains important economic crops in the world, while limited molecular markers have been developed in the past years. Simple sequence repeats (SSR) markers are powerful tools for the study of genetic mapping construction, genetic diversity analysis and genome wide association. The availability of pumpkin genome information has made it possible to analyze SSRs in genome wide across three Cucurbita species. Results In this paper, based on the whole genome sequences, 34,375 SSR loci were found in C. moschata, 30,577 SSR loci were found in C. maxima and 38,104 SSR loci were found in C. pepo. C. pepo has the maximum density of SSRs with an average of 145 SSR/Mb. In general, the frequency in total SSR loci decreased with the increase of the motif length, dinucleotide motifs were the most common motifs in the three species, and for the same repeat types, the SSR frequency decreased sharply with the increase of the repeat number. Most of those SSR loci were suitable for marker development (84.75% in C. moscata, 94.53% in C. maxima and 95.09% in C. pepo). Based on those markers, we compared and analyzed the cross-species SSR markers between C. pepo and other Cucurbitaceae species by silico-PCR. Using these cross-species primers, the high collinear relationships between C. pepo and the other two species were detected, respectively. Furthermore, the application of SSR markers in genetic diversity analysis was tested in C. pepo, the results showed that they were good tools to be used in genetic diversity analysis. Conclusion In this study, the genome wide SSR markers were detected from three Cucurbita species, and some of their applications were proved by comparative genomics and genetic diversity analysis. The large number of genome-wide SSR markers and crossspecies markers would promote the basic and applied studies of Cucurbita species, such as gene mapping, QTLs mapping, comparative genomics and marker-assisted breeding.

BACKGROUND Separation of the pubic symphysis can occur during the peripartum period. Relaxin (RLX) is a hormone primarily secreted by the corpus luteum that can mediate hemodynamic changes during pregnancy as well as loosen the pelvic ligaments. However, it is unknown whether RLX is associated with peripartum pubic symphysis separation and if the association is affected by other factors. AIM To study the association between RLX and peripartum pubic symphysis separation and evaluate other factors that might affect this association. METHODS We performed a cross-sectional study of pregnant women between April 2019 and January 2020. Baseline demographic characteristics, including gestational age, weight, neonatal weight, delivery mode and duration of the first and second stages of labor, were recorded. The clinical symptoms were used as a screening index during pregnancy, and the patients with pubic symphysis and inguinal pain were examined by color Doppler ultrasonography to determine whether there was pubic symphysis separation. Serum RLX concentrations were evaluated 1 d after delivery using an enzyme-linked immunosorbent assay, and pubic symphysis separation was diagnosed based on postpartum X-ray examination. We used an independent-sample t test to analyze the association between serum RLX levels and peripartum pubic symphysis separation. Multivariate regression analysis was used to evaluate whether the association between RLX and peripartum pubic symphysis separation was confounded by other factors, and the association between RLX and the severity of pubic symphysis separation was also assessed. We used Pearson correlation analysis to determine the factors related to RLX levels as well as the correlation between the degree of pubic symphysis separation and activities of daily living (ADL) and pain. RESULTS A total of 54 women were enrolled in the study, with 15 exhibiting (observational group) and 39 not exhibiting (control group) peripartum pubic symphysis separation. There were no statistically significant differences in terms of maternal age, gestational age, pre-pregnancy weight, weight gain during pregnancy, delivery modes, or duration of the first or second stages of labor between the 2 groups. We did, however, note a statistically significant difference in serum RLX concentrations and neonatal weight between the observational and control groups (122.3 ± 0.7 µg/mL vs 170.4 ± 42.3 µg/mL, P < 0.05; 3676.000 ± 521.725 g vs 3379.487 ± 402.420 g, P < 0.05, respectively). Multivariate regression analyses showed that serum RLX level [odds ratio (OR): 1.022) and neonatal weight (OR: 1.002) were associated with pubic symphysis separation peripartum. The degree of separation of the pubic symphysis was negatively correlated with ADL and positively correlated with pain. There was no statistically significant association between serum RLX levels and the severity of pubic symphysis separation after adjusting for confounding factors. CONCLUSION Serum RLX levels and neonatal weight were associated with the occurrence, but not the severity, of peripartum pubic symphysis separation.

In recent years, nanomaterials have attracted considerable research attention for biological and medical related applications due to their well-recognized physical and chemical properties. However, the deep understanding of the binding process at the protein–nanomaterial interface is essential to solve the concern of nano-toxicity. Here, we study the interactions between the recently reported graphenic nano-sheets, BC3 and C3N, and a prototypical protein (YAP65WW domain) via atomistic molecular dynamics simulations. Our simulations reveal that elemental doping is an effective way to tune the binding characteristics of YAP65WW with two nanomaterials. While YAP65WW can be attracted by two nanomaterials, the BC3 sheet is less able to disrupt the protein structure than C3N. From the energy point of view, this is because protein residues demonstrate a binding preference with the trend from electron rich nitrogen to electron deficient boron. Structural analyses of the bio-nano interface revealed the formation of an ordered water shell on the BC3 surface, which was compatible to the crystal pattern of BC3. When a protein binds with BC3, these interfacial water molecules protect the protein from being disrupted. We suggest that elemental doping is efficient to produce fruitful biological-effects of graphenic nanomaterials, which make it a prospective solution for the future design and fabrication of advanced nanomaterials with desired function.

Clean with power for oil-immersed transformer by robotic arm is investigated. We establish kinematic model of IRB4600 Robotic Arm, coordinate transfer is analyzed. Space near inline and outline of transformer is treated as obstacle, surface to be sprayed is departed into several areas, and RRT algorithm is modified in form of point to multi-points to search optimal path for cleansing. Simulation and test by virtual robot platform show that scheme proposed in this paper is valid.

In this study, we present a novel and robust strategy to develop a bacteria-activated photodynamic nanosystem based on polyelectrolyte-coated silica nanoparticles modified with chlorin e6 photosensitizer. Due to the aggregation of chlorin e6 on silica nanoparticles to induce excited-state quenching, the fluorescence and singlet oxygen generation of the obtained nanosystem are quenched. We demonstrate that polyelectrolyte–chlorin e6 complexes can be effectively extracted, by bacteria, from silica nanoparticles and form stable binding on the bacterial surface, changing the aggregation state of chlorin e6 and leading to the recovery of fluorescence and singlet oxygen generation. Based on this activatable photodynamic nanosystem, complete elimination of methicillin-resistant Staphylococcus aureus (MRSA) is achieved via a mechanism involving cell wall and membrane disruption, showing great potential to combat drug-resistant bacterial infections in clinical settings. Different from the bacterial enzyme-activated photodynamic systems responsive to specific bacterial strains, our activatable nanosystem exerts a broad-spectrum bacteria-triggered photodynamic effect by exploiting the unique charge characteristics of the cell envelope structure of bacteria. More importantly, we believe that the mechanism of bacteria-triggered polyelectrolyte dissociation from nanoparticles proposed in this work could be further used as a general strategy for the fabrication of bacteria-responsive multifunctional nanomaterials.