Fangfei Li

Emerging evidence indicates that osteoclasts direct osteoblastic bone formation. MicroRNAs (miRNAs) have a crucial role in regulating osteoclast and osteoblast function. However, whether miRNAs mediate osteoclast-directed osteoblastic bone formation is mostly unknown. Here, we show that increased osteoclastic miR-214-3p associates with both elevated serum exosomal miR-214-3p and reduced bone formation in elderly women with fractures and in ovariectomized (OVX) mice. Osteoclast-specific miR-214-3p knock-in mice have elevated serum exosomal miR-214-3p and reduced bone formation that is rescued by osteoclast-targeted antagomir-214-3p treatment. We further demonstrate that osteoclast-derived exosomal miR-214-3p is transferred to osteoblasts to inhibit osteoblast activity in vitro and reduce bone formation in vivo. Moreover, osteoclast-targeted miR-214-3p inhibition promotes bone formation in ageing OVX mice. Collectively, our results suggest that osteoclast-derived exosomal miR-214-3p transfers to osteoblasts to inhibit bone formation. Inhibition of miR-214-3p in osteoclasts may be a strategy for treating skeletal disorders involving a reduction in bone formation.

This review surveys the on-going search for ruthenium complexes that are potentially toxic to bacteria but relatively non-toxic to eukaryotic cells.

Aptamers are oligonucleotide sequences with a length of about 25–80 bases which have abilities to bind to specific target molecules that rival those of monoclonal antibodies. They are attracting great attention in diverse clinical translations on account of their various advantages, including prolonged storage life, little batch-to-batch differences, very low immunogenicity, and feasibility of chemical modifications for enhancing stability, prolonging the half-life in serum, and targeted delivery. In this Review, we demonstrate the emerging aptamer discovery technologies in developing advanced techniques for producing aptamers with high performance consistently and efficiently as well as requiring less cost and resources but offering a great chance of success. Further, the diverse modifications of aptamers for therapeutic applications including therapeutic agents, aptamer–drug conjugates, and targeted delivery materials are comprehensively summarized.

This study investigated the effects of multiple freeze-thaw (F-T) cycles on water mobility, microstructure damage and protein structure changes in porcine longissimus muscle. The transverse relaxation time T2 increased significantly when muscles were subjected to multiple F-T cycles (P < 0.05), which means that immobile water shifted to free water and the free water mobility increased. Multiple F-T cycles caused sarcomere shortening, Z line fractures, and I band weakening and also led to microstructural destruction of muscle tissue. The decreased free amino group content and increased dityrosine in myofibrillar protein (MP) revealed that multiple F-T cycles caused protein cross-linking and oxidation. In addition, the results of size exclusion chromatography, circular dichroism spectra, UV absorption spectra, and intrinsic fluorescence spectroscopy indirectly proved that multiple F-T cycles could cause protein aggregation and degradation, α-helix structure disruption, hydrophobic domain exposure, and conformational changes of MP. Overall, repeated F-T cycles changed the protein structure and water distribution within meat.

Paclitaxel (PTX) is among the most commonly used first-line drugs for cancer chemotherapy. However, its poor water solubility and indiscriminate distribution in normal tissues remain clinical challenges. Here we design and synthesize a highly water-soluble nucleolin aptamer-paclitaxel conjugate (NucA-PTX) that selectively delivers PTX to the tumor site. By connecting a tumor-targeting nucleolin aptamer (NucA) to the active hydroxyl group at 2' position of PTX via a cathepsin B sensitive dipeptide bond, NucA-PTX remains stable and inactive in the circulation. NucA facilitates the uptake of the conjugated PTX specifically in tumor cells. Once inside cells, the dipeptide bond linker of NucA-PTX is cleaved by cathepsin B and then the conjugated PTX is released for action. The NucA modification assists the selective accumulation of the conjugated PTX in ovarian tumor tissue rather than normal tissues, and subsequently resulting in notably improved antitumor activity and reduced toxicity.

This study presents a detailed survey on recent development of logical networks and its applications, including the background of logical networks, the theory of a new matrix product called semi-tensor product (STP) of matrices, some fundamental works on logical networks, and some current research works. Particularly, some fundamental works on logical networks are presented for the past years, including controllability, stability and stabilisation, synchronisation, disturbance decoupling and so on. Due to the great potential of STP in dealing with logical networks, a surge of attraction from overseas is paid on the study of STP and its applications. Currently, some new research areas are widely studied including pinning control, function perturbations, system decomposition, trajectory control, output tracking issues, symbolic dynamics and so on. The main concern of this study is to present a comprehensive introduction to logical networks and some other applications under the framework of STP of matrices.

The changes in the gelling property and structural integrity of mirror carp protein that was induced by freeze-thaw (F-T) cycles were discussed. The strength, whiteness and water-holding ability of myofibrillar protein (MP) gel, the solubility and Ca2+-ATPase activity of MP were all significantly reduced after 5 F-T cycles (P < 0.05). The transverse relaxation time peak (T2) of samples under repeated F-T cycles exhibited a significant redshift (P < 0.05). The MP film surface became rough and irregular, as observed using atomic force microscopy (AFM) during the multiple F-T cycles. Additionally, the state and the weight of molecular distribution evidenced that F-T cycles caused protein aggregation and mechanical damage. The alterations in primary, secondary and tertiary protein structure revealed that the protein structure integrity of fish was destroyed under repeated F-T cycles. These findings indicated that repeated F-T cycles should be avoided during the freezing storage of fish to improve gel quality and sustain protein structural integrity.

Osteosarcoma (OS) is a highly aggressive pediatric cancer, characterized by frequent lung metastasis and pathologic bone destruction. Vascular endothelial growth factor A (VEGFA), highly expressed in OS, not only contributes to angiogenesis within the tumor microenvironment via paracrine stimulation of vascular endothelial cells, but also acts as an autocrine survival factor for tumor cell themselves, thus making it a promising therapeutic target for OS. CRISPR/Cas9 is a versatile genome editing technology and holds tremendous promise for cancer treatment. However, a major bottleneck to achieve the therapeutic potential of the CRISPR/Cas9 is the lack of in vivo tumor-targeted delivery systems. Here, we screened an OS cell-specific aptamer (LC09) and developed a LC09-functionalized PEG-PEI-Cholesterol (PPC) lipopolymer encapsulating CRISPR/Cas9 plasmids encoding VEGFA gRNA and Cas9. Our results demonstrated that LC09 facilitated selective distribution of CRISPR/Cas9 in both orthotopic OS and lung metastasis, leading to effective VEGFA genome editing in tumor, decreased VEGFA expression and secretion, inhibited orthotopic OS malignancy and lung metastasis, as well as reduced angiogenesis and bone lesion with no detectable toxicity. The delivery system simultaneously restrained autocrine and paracrine VEGFA signaling in tumor cells and could facilitate translating CRISPR-Cas9 into clinical cancer treatment.

The effects of thawing methods (refrigeration thawing (RT, 4 °C), water immersion thawing (WT, 18 °C), vacuum thawing (VT, 25 °C), ultrasonic thawing (UT, 20 °C) and microwave thawing (MT)) on the conformation and gel qualities of myofibrillar protein (MP) obtained from porcine longissimus muscle were investigated. The results showed that MP conformation and gel qualities of porcine longissimus muscles by VT and UT were insignificantly changed compared to fresh meat (FM). A significant decrease in free amino groups of MP from MT illustrated that MT induced protein aggregation and oxidation (P < 0.05). The results of circular dichroism (CD) spectra analysis and fluorescence spectroscopy indirectly proved that thawing can cause protein cross-linking and degradation, secondary structure destruction, non-hydrophilic domain exposed and conformational change of samples. The largest changes in solubility, surface hydrophobicity and particle size were obtained with MT. The effects on the conformation and gel quality of MP were verified during thawing process.

This study investigated the effects of thawing methods on the thermal stability and structure of myofibrillar protein (MP) from porcine longissimus dorsi. DSC was used to evaluate the thermal stability (Tmax, △H) of MP. FT-IR, Raman, UV absorption, and fluorescence spectra were utilized to assess the secondary and tertiary structures of MP. Changes in the thermal stability and structure of MP after thawing were significant (P < 0.05), except for the vacuum thawing (VT) samples. The lowest Tmax and △H were obtained through microwave thawing (MT). The decreases in α-helices, β-sheets, fluorescence intensity, and total sulfhydryl content, and increases in the intensity of the SS stretching band and Ca2+-ATPase activity illustrated that secondary structure destruction, tertiary structure unfolding, and disulphide bond cross-linking occurred during thawing. The thawing process caused thermal stability degradation and structure destruction; the largest changes in all indexes of MP were obtained through MT.

Changes in quality, protein structure and oxidative reactions of quick-frozen pork patties (after −30 °C, 30 min), which were frozen at −8 °C, −18 °C, −25 °C, −8/−18 °C (stored at −8 °C for 5 days, then stored at −18 °C for 5 days, storage cycle continue until the end of storage period), −18/−25 °C (the same process as −8/−18 °C, temperature is −18 °C and −25 °C) for 0, 1, 2, 3, and 6 months were investigated. The a*-value, pH, water holding capacity and texture properties of pork patties were significantly changed (P < 0.05) at −8 °C, −8/−18 °C, −18/−25 °C after 1 month of frozen storage. The water redistribution within the patties was detected by LF-NMR analyses. After 6 months of frozen storage, the TBARS and carbonyl content of samples frozen at −8/−18 °C increased by 444% and 239%, respectively. Meanwhile, a decrease in fluorescence intensity reflected a decline in protein structure integrity. The association among quality, oxidative reactions and protein structure were elucidated by principal component analysis. The quality deterioration of the pork patties may be induced by the oxidative reaction and destruction of protein structural integrity during frozen storage.

In order to improve the characteristics of uneven melting in the melting process of the horizontal latent heat energy storage system, the triplex-tube latent heat energy storage unit is taken as the research object, and the flip mechanism is applied to its melting process. Numerical simulation is used for the research, and the numerical model is verified by experimental data. The results show that under different dimensionless times, the melting performance of the unit can be significantly improved by a single flip. When the dimensionless time is 0.4576, it is found that the total melting time of the unit is reduced by 16.17 %, the average heat absorption rate is increased by 14.7 %, but the total heat energy absorption is reduced by 3.85 %. The results show that the addition of a flip can effectively shorten the melting time and increase the heat absorption rate, but it has a negative effect on the total heat absorption in one melting cycle. Moreover, through the comparison of dynamic flow rate, dynamic temperature response, and temperature interval, it is shown that the addition of flip effectively reduces the negative influence of the hard-to-melt zone on the melting performance of the unit during the melting process. The flip mechanism reduces the proportion of high-temperature phase change material in the melting process and makes the melting process more uniform.

In this paper, the rotation mechanism is applied to a triplex-tube latent heat thermal energy storage system for the first time. Numerical simulation is used to study the effect of rotation on the solidification performance of this system, and the accuracy of the numerical model is verified experimentally. Firstly, the evolution of the liquid phase, the total amount of heat energy released, and the rate of heat energy released in the solidification process of the thermal energy storage system without rotation and at different rotational speeds are compared and analyzed. It is found that the solidification time of the system at 1 rpm is reduced by 83.85 % and the heat release rate is 4.98 times higher than that at the no-rotation state. It shows that the incorporation of a rotational mechanism can effectively reduce the solidification time and increase the heat release rate of the system. Then, the internal dynamic temperature/flow rate response is used to investigate the change in the heat transfer mode of the solidification process by the addition of rotation and the improvement of the phenomenon of difficult solidification zones, which improved the internal temperature uniformity and thus the solidification behavior. By response surface method, the geometric factors of the heat storage system (fin length, fin width, fin angle) are analyzed by multiple factors. The function of the optimized target (solidification time) on each variable is fitted, and it is found that the fin length had the most significant effect on the optimized target. Finally, the effect of relevant physical parameters on the solidification process and heat release of the thermal energy storage system is investigated. To ensure low solidification time and high heat release rate, this study recommends that the temperature difference between phase change material and tube wall is higher than 25 K. This paper also proves the feasibility and superiority of copper fin/tube wall material.

The melting performance of a rotating triplex-tube latent heat thermal energy storage unit is studied by numerical simulation method. The Taguchi design and response surface method are applied to its optimized design. Firstly, the Taguchi design method is used to quantitatively reveal the specific effects of fin distribution, fin number, and fin material on the melting performance of the unit. Compared with all-inner tube-fin or all-outer tube-fin structures, the melting time of alternating inside and outside fin structures is shortened by 52.64% and 32.42%, the average heat absorption rate is greatly increased by 105.56% and 47.26%, and the total heat is reduced by 2.64% and 2.17%, respectively. Then, the response surface method is applied to the eight alternating fins obtained by the Taguchi design, and the effects of fin length, width, and rotation angle on the melting time and average heat absorption rate of the unit are studied. Compared with the original structure, the optimal structure reduces the total melting time by 7.37% and increases the average heat absorption rate by 7.23%. The geometric parameters’ interaction with the relevant target response is studied, and the corresponding fluid-structure interaction equation is fitted. Finally, the melt growth phenomenon near the wall is found in the initial melting stage of the optimized model by mechanism analysis.

Phase change heat storage is the backbone of energy storage technology, but its storage time is affected by the low thermal conductivity of phase change materials. Therefore, the melting performance of a triplex-tube latent heat thermal energy storage unit (T-LHTESU) in a phase change heat storage system is studied in this paper, and the rotation mechanism is applied to the unit. Firstly, a numerical model of the T-LHTESU considering the rotation mechanism is constructed, and the validity of the rotation unit is verified by comparison with experimental data. In this unit, N-eicosane is used as a phase change material for heat exchange. The effects of different rotational speeds on the liquid phase distribution, temperature distribution, flow velocity distribution, total energy storage, and energy storage efficiency of the T-LHTESU are studied. The results show that the melting time of this unit at 0.1 and 1 rpm is 46.98 and 69.35% lower than that of the stationary model, respectively. The total amount of stored heat is decreased by 0.67 and 2.17%, and the heat storage efficiency is increased by 87.34% and 219.19%, respectively. This indicates that the addition of the rotation mechanism greatly increases the heat storage efficiency of the T-LHTESU and reduces its total melting time, while the reduction of the total energy stored in the melting cycle is small. Then it is proved that rotation improves the single heat transfer mechanism of the stationary model and eliminates the thermal deposition caused by natural convection by studying the internal temperature/velocity response of the stationary model and the speed of 0.1 rpm. The related geometric structure of the model is optimized by response surface optimization design based on 0.1 rpm rotation speed. The influence of each variable on the target response is obtained, and compared with the original model, the melting time of the optimized model is reduced by 12.24%. Finally, based on the geometric optimization design, the influence of element physical factors (temperature and material of fin/tube wall) on the related melting properties is studied. This study is helpful to promote the effective use of rotation mechanism in phase change heat storage systems and has a certain guiding role in the structural design.

Timosaponin AIII (Tim-AIII), a steroid saponin, exhibits strong anticancer activity in a variety of cancers, especially breast cancer and liver cancer. However, the underlying mechanism of the effects of Tim-AIII-mediated anti-lung cancer effects remain obscure. In this study, we showed that Tim-AIII suppressed cell proliferation and migration, induced G2/M phase arrest and ultimately triggered cell death of non-small cell lung cancer (NSCLC) cell lines accompanied by the release of reactive oxygen species (ROS) and iron accumulation, malondialdehyde (MDA) production, and glutathione (GSH) depletion. Interestingly, we found that Tim-AIII-mediated cell death was reversed by ferroptosis inhibitor ferrostatin-1 (Fer-1). Meanwhile, the heat shock protein 90 (HSP90) was predicted and verified as the direct binding target of Tim-AIII by SwissTargetPrediction (STP) and surface plasmon resonance (SPR) assay. Further study showed that Tim-AIII promoted HSP90 expression and Tim-AIII induced cell death was blocked by the HSP90 inhibitor tanespimycin, indicating that HSP90 was the main target of Tim-AIII to further trigger intracellular events. Mechanical analysis revealed that the Tim-AIII-HSP90 complex further targeted and degraded glutathione peroxidase 4 (GPX4), and promoted the ubiquitination of GPX4, as shown by an immunoprecipitation, degradation and in vitro ubiquitination assay. In addition, Tim-AIII inhibited cell proliferation, induced cell death, led to ROS and iron accumulation, MDA production, GSH depletion, as well as GPX4 ubiquitination and degradation, were markedly abrogated when HSP90 was knockdown by HSP90-shRNA transfection. Importantly, Tim-AIII also showed a strong capacity of preventing tumor growth by promoting ferroptosis in a subcutaneous xenograft tumor model, whether C57BL/6J or BALB/c-nu/nu nude mice. Together, HSP90 was identified as a new target of Tim-AIII. Tim-AIII, by binding and forming a complex with HSP90, further targeted and degraded GPX4, ultimately induced ferroptosis in NSCLC. These findings provided solid evidence that Tim-AIII can serve as a potential candidate for NSCLC treatment.

Latent heat storage technology plays an important role in the effective utilization of clean energy such as solar energy in building heating, but the low thermal conductivity of heat storage medium (phase change material) affects its large-scale application. As a new heat storage enhancement technology, rotation mechanism has a good application prospect. In this paper, the solidification performance of a triplex-tube latent heat thermal energy storage unit at constant speed (0.5 rpm) is studied numerically. Different optimization design methods (Taguchi method and response surface method) are used for deep analysis. The influences of fin position, number, and material on solidification properties are explored by the Taguchi method. Then, the unit structure (fin angle, fin length, and fin width) is optimized by the response surface method. Compared with the original structure, the average heat release rate of 8 copper fins with all outer tubes is increased by 108.93%, and the solidification time is reduced by 52.06%. The optimal structure can further shorten the solidification time by 29.14% and increase the average heat release rate by 40.5%. Additionally, the study of wall temperature shows that increasing temperature difference makes solidification speed faster and heat energy release faster. This effect effectively eliminates the adverse effects of slow solidification during the later stages of the process on the system.

This paper investigates the controllability of Boolean networks with time-invariant delays in states. After a brief introduction on converting the logic dynamics to discrete time delay systems, the controllability via two kinds of controls is studied. One kind of control is generated by Boolean control networks, another kind of control is free Boolean sequences. In both cases, necessary and sufficient conditions of the controllability of Boolean control networks are proved. Finally, examples are given to illustrate the efficiency of the obtained results.

In this brief, pinning control design for the stabilization of Boolean network (BN) is addressed. Using the semitensor product of matrices, transition matrix of the BN can be obtained. We achieve global stability to the fixed point or the elementary cycle for the BN by changing the columns of the transition matrix. Then, pinning nodes can be chosen, and pinning control design algorithms are proposed. Finally, an example is employed to show the proposed control design procedure.

Interference of the binding of programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) has become a new inspiring immunotherapy for resisting cancers.To date, the FDA has approved two PD-1 monoclonal antibody drugs against cancer as well as a monoclonal antibody for PD-L1.More PD-1 and PD-L1 monoclonal antibody drugs are on their way in clinical trials.In this review, we focused on the mechanism of the PD-1/PD-L1 signaling pathway and the monoclonal antibodies (mAbs) against PD-1 and PD-L1, which were approved by the FDA or are still in clinical trials.And also presented is the prospect of the PD-1/PD-L1 immune checkpoint blockade in the next generation of immunotherapy.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by intracellular α-synuclein (α-syn) deposition. Alterations in α-syn levels in cerebrospinal fluid (CSF) and plasma of PD patients have been thought to be potential PD biomarkers; however, contamination arising from hemolysis often influences the accuracy of detecting α-syn levels in the CSF and plasma. In this study, α-syn oligomer levels in red blood cells (RBCs) obtained from 100 PD patients, 22 MSA patients, and 102 control subjects were measured by enzyme-linked immunosorbent assay. We showed that the ratio of α-syn oligomer/total RBC protein was higher in PD patients than in controls (29.0±19.8 ng/mg vs. 15.4±7.4 ng/mg, P<0.001). The area under the receiver operating characteristic curve (AUC) indicated a sensitivity of 79.0%, specificity of 64.7% and a positive predictive value of 68.7%, with an AUC of 0.76 for increased α-syn oligomer/total RBC protein ratio. However, there was no correlation between RBC α-syn oligomer levels and age at onset, disease duration, age, UPDRS motor scale score or progression of motor degeneration in PD patients. The ratio of RBC α-syn oligomer/total protein was also higher in MSA patients than in controls (22.9±13.9 ng/mg vs. 15.4±7.4 ng/mg, P<0.001). However, no significant difference was found for α-syn oligomer/total protein ratio between PD and MSA (29.0±19.8 ng/mg vs. 22.9±13.9 ng/mg, P>0.05). The present results suggest that the RBC α-syn oligomer/total protein ratio can be a potential diagnostic biomarker for PD.

This paper studies the set stabilization of switched Boolean control networks, in which a feedback control design algorithm is presented by a constructive method. Necessary and sufficient conditions of the set stabilization of switched Boolean control networks under arbitrary switching signals are presented for the cases of the control input relying on switching signals or not, respectively. Furthermore, the corresponding switching-signal-independent and switching-signal-dependent controllers are provided for these two cases, respectively. It is shown that the condition of the switching-signal-dependent controller is less conservative than the one of the switching-signal-independent controller. Finally, examples are given to illustrate the effectiveness of the proposed results.

The minimum inhibitory concentrations (MIC) of a series of synthetic inert polypyridylruthenium(II) complexes against four strains of bacteria--Gram positive Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA), and Gram negative Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa)--have been determined. The results demonstrate that for the dinuclear ruthenium(II) complexes ΔΔ/ΛΛ-[{Ru(phen)(2)}(2){μ-bb(n)}](4+) {where phen = 1,10-phenanthroline; bb(n) = bis[4(4'-methyl-2,2'-bipyridyl)]-1,n-alkane (n = 2, 5, 7, 10, 12 or 16)} the complexes linked by the bb(12), bb(14) and bb(16) ligands are highly active, with MIC values of 1 μg mL(-1) against both S. aureus and MRSA, and 2-4 and 8-16 μg mL(-1) against E. coli and P. aeruginosa, respectively. The mononuclear complex [Ru(Me(4)phen)(3)](2+) showed equal activity (on a mole basis) against S. aureus compared with the Rubb(12), Rubb(14) and Rubb(16), but was considerably less active against MRSA and the two Gram negative bacteria. For the dinuclear Rubb(n) family of complexes, the antimicrobial activity was related to the octanol-water partition coefficient (logP). However, the highly lipophilic mononuclear complex Δ-[Ru(phen)(2)(bb(16))](2+) was significantly less active than Rubb(16), highlighting the importance of the dinuclear structure. Preliminary toxicity assays were also carried out for the ΔΔ isomers of Rubb(7), Rubb(10), Rubb(12) and Rubb(16) against two human cells lines, fresh red blood cells and THP-1 cells. The results showed that the dinuclear ruthenium complexes are significantly less toxic to human cells compared to bacterial cells, with the HC(50) and IC(50) values 100-fold higher than the MIC for the complex that showed the best potential--ΔΔ-Rubb(12).

This paper deals with the controllability of probabilistic Boolean control networks. First, a survey on the semi-tensor product approach to probabilistic Boolean networks is given. Second, the controllability of probabilistic Boolean control networks via two kinds inputs is studied. Finally, examples are given to show the efficiency of the obtained results.

Abstract A novel sulfur anion-doped NaTaO3 photocatalyst with nanocubic morphology, at an average size of 200–500 nm or so, was synthesized by a simple hydrothermal process. The as-prepared samples were characterized by various techniques, such as X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), UV–vis diffuse reflectance spectra (UV–vis DRS) and photocatalytic degradation evaluation. The results indicate that the as-prepared NaTaO3 is assigned to monoclinic lattice, which is much closer to cubic phase than conventional orthorhombic perovskite structure. And doping of S anions would cause, to some extent at least, expanded unit cell and distorted lattice structure from monoclinic into cubic phase, whose Ta O Ta band angle is much closer to 180°, resulting in the higher mobility of photo induced charge carriers. Narrowed band gap and splitting slopes are observed in S-doped NaTaO3 by UV–vis DRS, confirming the visible-light adsorption capability and the upward shifted valence band edge, which come from the overlapping of S 3p orbitals and Ta 5d orbitals. In virtue of the crystalline and electronic structures, the resultant S-doped NaTaO3 samples, as compared with pure NaTaO3, exhibit remarkably improved visible-light photocatalytic activity and similar UV-light photocatalytic activity, during the photocatalytic degradation of methyl orange. In addition, S-doped NaTaO3 also displays reliable recycling photocatalytic performance and satisfying solar catalytic activity for the organic pollutant. On the basic of above experimental phenomena, a possible mechanism for sulfur anion doping in NaTaO3 perovskite-like structure is also presented.

This study was conducted to evaluate the effects of inoculation with Staphylococcus xylosus, Lactobacillus plantarum, or a mixture of strains (L. plantarum + S. xylosus) on the formation of biogenic amines (BAs) and quality characteristics in Harbin dry sausage. Microbial analysis shows that total aerobic bacteria and lactic acid bacteria (LAB) counts were higher in the inoculated sausages, especially in those inoculated with a mixture of strains, but the growth of enterobacteriaceae was inhibited (P < 0.05). A sharp decrease in the pH value of the sausages was observed, and the moisture content and water activity were significantly decreased during fermentation. Sausages inoculated with a mixture of bacterial strains had the lowest pH, moisture content and water activity (P < 0.05). Inoculation of dry sausages with S. xylosus or L. plantarum, especially a mixture of strains (L. plantarum + S. xylosus), significantly delayed lipid oxidation, improved sensory characteristics, and inhibited BA accumulation. Six types of BAs (cadaverine, putrescine, tryptamine, 2-phenylethylamine, histamine, and tyramine) were inhibited by the presence of L. plantarum and S. xylosus, and a mixture of them had the most inhibitive effect. Correlation analysis showed that the BA concentrations correlated well with enterobacteriaceae counts, and some BAs were negatively correlated with LAB counts. These results demonstrate that S. xylosus and L. plantarum could be used as starter cultures in Harbin dry sausage production to inhibit BA accumulation and improve quality characteristics.

Osteosarcoma (OS) is a bone cancer mostly occurring in pediatric population.Current treatment regime of surgery and intensive chemotherapy could cure about 60%-75% patients with primary osteosarcoma, however only 15% to 30% can be cured when pulmonary metastasis or relapse has taken place.Hence, novel precise OS-targeting therapies are being developed with the hope of addressing this issue.This review summarizes the current development of molecular mechanisms and targets for osteosarcoma.Therapies that target these mechanisms with updated information on clinical trials are also reviewed.Meanwhile, we further discuss novel therapeutic targets and OS-targeting drug delivery systems.In conclusion, a full insight in OS pathogenesis and OS-targeting strategies would help us explore novel targeted therapies for metastatic osteosarcoma.

Titanium dioxide doped with phosphorus was synthesized by the sol–gel method with H3PO4 addition. The samples were calcined at different temperatures under different atmospheres, in order to affect the TiO combination behavior in P-doped TiO2. The physicochemical properties of the prepared samples were investigated using TG-DTA, XRD, FTIR, XPS, TEM and UV–vis. The photocatalytic activity was evaluated by degradation of methyl orange (MO) dye under UV and visible-light irradiation. The results show that P-doped TiO2 calcined in different thermal atmosphere reveals entirely different performances. The XRD and UV–vis analysis reveal that the effect of P species in TiO2 is increased by calcining in reducing atmosphere. Further photocatalytic experiments also display that P-doped TiO2 calcined under carbothermal reduction atmosphere (R-PT) exhibits higher photocatalytic activity than that calcined in air (A-PT). The XPS results confirms that the calcining atmosphere changes the distribution concentration of surface and interface species in P-doped TiO2, such as surface oxygen and Ti3+ sites, resulting in the improved photocatalytic activity and enhanced reutilization performance of R-PT. Further mechanism study illustrates that the promoting photocatalytic activity of P-doped TiO2 are ascribed to the formation of Ti3+ sites rather than exceeding oxygen on the surface. And the carbothermal process helps to reserve these Ti3+ sites during high temperature calcination, resulting in the increased photocatalytic activity of P-doped TiO2, especially when the doping level of P species is relative low.

Effect of new thawing methods (ultrasound thawing (UT), vacuum thawing, (VT), microwave thawing (MT)) on gelling properties of myofibrillar protein (MP) from porcine longissimus dorsi was investigated, compared with traditional thawing methods (water immersion thawing, (WT)) and fresh meat (FM). The results showed that a decrease in MP gelling properties of all thawing samples was observed. The increase in roughness of MP gel from all thawing samples explained that the flatter, smoother, and denser surface morphology of that from FM samples was destroyed based on the observation by atomic force microscopy. There was significant difference (P < 0.05) in all gel indicators (particle size, turbidity, whiteness, water-holding capacity (WHC), moisture distribution, rheological characteristics, surface morphology) of MP from MT samples and there was insignificant difference (P > 0.05) in turbidity, whiteness, WHC of MP from VT samples compared with that from FM samples. There was insignificant difference (P > 0.05) in gel properties between UT and VT. The effect of UT and VT (new thawing methods) on MP gelling properties was significantly lower (P < 0.05) than that of WT (traditional thawing methods), and the effect of that from MT was obviously compared with other thawing methods.

This paper investigates the problem of output feedback adaptive stabilization for a class of nonstrict-feedback stochastic nonlinear systems with both unknown backlashlike hysteresis and unknown control directions. A new linear state transformation is applied to the original system, and then, control design for the new system becomes feasible. By combining the neural network's (NN's) parameterization, variable separation technique, and Nussbaum gain function method, an input-driven observer-based adaptive NN control scheme, which involves only one parameter to be updated, is developed for such systems. All closed-loop signals are bounded in probability and the error signals remain semiglobally bounded in the fourth moment (or mean square). Finally, the effectiveness and the applicability of the proposed control design are verified by two simulation examples.

A sheet-like carbon sandwich, which contains a graphene layer as the conductive filling with N-doped porous carbon layers uniformly coated on both sides, is designed as a sulfur reservoir for lithium–sulfur batteries.

An innovative approach for covalent‐bond‐activated mechanoresponse by complexing rhodamine or spiropyran with cyclodextrin (CD) is reported. This approach endows diverse fluorophores with perfect mechanochromism by introducing a supramolecular system. Unique characteristics such as noncovalent chemical modification and convenient preparation make this approach promising for practical applications. The strong hydrogen bonds provided by CD play a crucial role in triggering the mechanochromic switch. First, the hydrogen bonds seize both sides of the fluorophore's weak chemical bonds and tightly lock the fluorophore in the cavity of CD. Second, the hydrogen bonds prompt the aggregation of complex inclusions in large ordered arrays and strengthen the molecular interactions. In this way, the weak chemical bonds can focus more external force and stretch more easily upon shearing (quantified). This is the first report of supramolecule‐triggered mechanochromic switches. This study opens an avenue to correlate a mechanochemical reaction with a supramolecular system.

<h2>Summary</h2> Gene expression burdens cells by consuming resources and energy. While numerous studies have investigated regulation of expression level, little is known about gene design elements that govern expression costs. Here, we ask how cells minimize production costs while maintaining a given protein expression level and whether there are gene architectures that optimize this process. We measured fitness of ∼14,000 <i>E. coli</i> strains, each expressing a reporter gene with a unique 5′ architecture. By comparing cost-effective and ineffective architectures, we found that cost per protein molecule could be minimized by lowering transcription levels, regulating translation speeds, and utilizing amino acids that are cheap to synthesize and that are less hydrophobic. We then examined natural <i>E. coli</i> genes and found that highly expressed genes have evolved more forcefully to minimize costs associated with their expression. Our study thus elucidates gene design elements that improve the economy of protein expression in natural and heterologous systems.

Although tumor necrosis factor alpha (TNF‑α) is known to serve a critical role in the pathogenesis of inflammatory osteolysis, the exact mechanisms underlying the effects of TNF‑α on osteoclast recruitment and differentiation remain unclear. To investigate the mechanisms by which TNF‑α influences osteoclast differentiation, mouse bone marrow‑derived macrophages (BMMs) were used as osteoclast precursors, and osteoclastogenesis was induced by macrophage colony‑stimulating factor and receptor activator of nuclear factor (NF)‑κB ligand (RANKL) with or without TNF‑α for 4 days. Then, NF‑κB was inhibited using the inhibitor, BAY 11‑7082. The results indicated that treatment with TNF‑α alone did not induce osteoclastogenesis of BMMs. However, TNF‑α in combination with RANKL dramatically stimulated the differentiation of osteoclasts and positively regulated the expression of mRNA markers of osteoclasts. Finally, treatment of BMMs with BAY 11‑7082 prevented the formation of mature osteoclasts by BMMs treated with TNF‑α only or with RANKL, as well as the upregulation of osteoclast marker genes. Therefore, although TNF‑α does not induce osteoclastogenesis alone, it does work with RANKL to induce osteoclastic differentiation, and the NF‑κB pathway may serve an important role in this process.

Hyperspectral image (HSI), with hundreds of narrow and adjacent spectral bands, supplies plentiful information to distinguish various land-cover types. However, these spectral bands ordinarily contain a lot of redundant information, leading to the Hughes phenomenon and an increase in computing time. As a popular dimensionality reduction technology, band/feature selection is indispensable for HSI classification. Based on improved subspace decomposition (ISD) and the artificial bee colony (ABC) algorithm, this paper proposes a band selection technique known as ISD–ABC to address the problem of dimensionality reduction in HSI classification. Subspace decomposition is achieved by calculating the correlation coefficients between adjacent bands and using the visualization result of the HSI spectral curve. The artificial bee colony algorithm is first applied to optimize the combination of selected bands with the guidance of ISD and maximum entropy (ME). Using the selected band subset, support vector machine (SVM) with five-fold cross validation is applied for HSI classification. To evaluate the effectiveness of the proposed method, experiments are conducted on two AVIRIS datasets (Indian Pines and Salinas) and a ROSIS dataset (Pavia University). Three indices, namely, overall accuracy (OA), average accuracy (AA) and kappa coefficient (KC), are used to assess the classification results. The experimental results successfully demonstrate that the proposed method provides good classification accuracy compared with six other state-of-the-art band selection techniques.

Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX), are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems.

Therapeutic genome editing technology has been widely used as a powerful tool for directly correcting genetic mutations in target pathological tissues and cells to cure of diseases.The modification of specific genomic sequences can be achieved by utilizing programmable nucleases, such as Meganucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the clustered regularly-interspaced short palindromic repeat-associated nuclease Cas9 (CRISPR/Cas9).However, given the properties, such as large size, negative charge, low membrane penetrating ability, as well as weak tolerance for serum, and low endosomal escape, of these nucleases genome editing cannot be successfully applied unless in vivo delivery of related programmable nucleases into target organisms or cells is achieved.Here, we look back at delivery strategies having been used in the in vivo delivery of three main genome editing nucleases, followed by methodologies currently undergoing testing in clinical trials, and potential delivery strategies provided by analyzing characteristics of nucleases and commonly used vectors.

Cyber-security is of the fundamental importance for cyber-physical systems (CPSs), since CPSs are vulnerable to cyber attack. In order to make the defensive measures better, one needs to understand the behavior from the view of an attacker. In this paper, the problem of false data injection attack on remote state estimation with resource constraints is studied in two cases, where the first case is that the attacker adds a Gaussian noise to the innovation, while the other is that the attacker employs a Gaussian noise to replace the innovation. In addition, the attacker is assumed to has a resource constraint, i.e., he/she cannot attack all the sensors, at the same time should decide which sensors to attack. By using the matrix theory, the optimal attack strategy problem, which aims to maximize the trace of the remote estimation error covariance, is converted into a convex optimization problem that can be solved. Thus, an optimal attack strategy is given to illustrate which sensors should be attacked. An example is given to show the effectiveness of the theoretical results.

The search for high-temperature superconductivity is one of the research frontiers in physics. In the sulfur hydride system, an extremely high Tc (∼200 K) has been recently developed at pressure. However, the Meissner effect measurement above megabar pressures is still a great challenge. Here, we report the superconductivity identification of sulfur hydride at pressure, employing an in situ alternating-current magnetic susceptibility technique. We determine the superconducting phase diagram, finding that superconductivity suddenly appears at 117 GPa and Tc reaches 183 K at 149 GPa before decreasing monotonically with increasing pressure. By means of theoretical calculations, we elucidate the variation of Tc in the low-pressure region in terms of the changing stoichiometry of sulfur hydride and the further decrease in Tc owing to a drop in the electron-phonon interaction parameter λ. This work provides a new insight into clarifying superconducting phenomena and anchoring the superconducting phase diagram in the hydrides.

Breast cancer remains one of the most life-threatening tumors affecting women. Most patients with advanced breast cancer eventually develop metastatic diseases, which cause significant morbidity and mortality. Approximately two-thirds of patients with advanced breast cancer exhibit osteolytic-type bone metastasis, which seriously reduce the quality of life. Therefore, development of novel therapeutic strategies for treating breast cancer patients with bone metastasis is urgently required. The "seed and soil" theory, which describes the interaction between the circulating breast cancer cells (seeds) and bone microenvironment (soil), is widely accepted as the mechanism underlying metastasis. Disruption of any step in this cycle might have promising anti-metastasis implications. The interaction of receptor activator of nuclear factor-κB ligand (RANKL) and its receptor RANK is fundamental in this vicious cycle and has been shown to be a novel effective therapeutic target. A series of therapeutic strategies have been developed to intervene in this cross-talk. Therefore, in this review, we have systematically introduced the functions of the RANKL/RANK signaling system in breast cancer and discussed related therapeutic strategies.

The effects of edible chitosan (CTS) coatings (0, 1, 2, and 3%) on Harbin red sausage storage stability at room temperature compared to vacuum packaging are discussed. The pH, moisture and L* of sausages decreased gradually, while the a*, TBARS, total aerobic bacteria (TAB) and lactic acid bacteria (LAB) increased significantly (P < 0.05) with the prolongation of storage time. In the same storage time, the storage stability was improved with the increase in the concentration of edible CTS coating, but there was no significant difference between 2% and 3% (P > 0.05). Although vacuum packaging can effectively maintain colour, moisture and reduce lipid oxidation, 2% CTS is outstanding in sustaining storage stability (pH and water distribution) and inhibition of microbial growth (TAB and LAB). In addition, no significant difference was observed between CTS coating and vacuum packaging on aroma and flavour (P > 0.05). In conclusion, CTS coating as edible packaging material can be used in meat products preservation.

The inhibitory effect of ice structuring protein (ISP) on the quality deterioration of quick-frozen pork patties subjected to multiple freeze-thaw (F-T) cycles was investigated. The inhibitory effect of ISP on patty quality deterioration was obvious after five F-T cycles (P < 0.05). The hardness and springiness of patties with 0.20% ISP were 3.84% and 10.61% higher than those of patties without ISP, and the thawing loss of patties with 0.20% ISP was 43.64% lower than that of patties without ISP (P < 0.05). In addition, ISP effectively restrained moisture migration and destruction of pork patty microstructure during F-T cycles. More importantly, thiobarbituric acid reactive substance levels and carbonyl contents in the patties with 0.20% ISP were 25% and 32% lower than those in the control group (no significant difference with patties with 0.30% ISP) after five F-T cycles. Therefore, these results illustrated the potential benefits of ISP in meat products.

In this paper, an attack defense method is proposed to address the secure remote state estimation problem caused by linear man-in-the-middle attacks in cyber–physical systems (CPS). We utilize the pseudo-random number as a watermarking to encrypt and decrypt the data transmitted through the wireless network. Via the proposed method, the transmitted data in the normal operation can be recovered. Since the data modified by the attacker can be marked with the watermarking, the χ2 detector is capable of detecting the attack. For three different attack scenarios, we analyze the evolution of the remote estimation error covariances and the detection performance, respectively. In the sense of minimizing the estimation error covariance, the optimal parameter set of the watermarking is derived. Furthermore, the proposed method can even be extended to detect the false data injection attack and the replay attack. Finally, several examples are provided to illustrate the derived results.

The goal of this study was to explore the cryoprotective effect of ice structuring protein (ISP) on the aggregation behaviour and structural changes of myofibrillar protein (MP) from quick-frozen pork patties during frozen storage. Frozen storage causes the formation of large protein aggregates and weakens MP structures. After adding ISP into patties, MP had a more stable aggregation system, which was manifested by a uniform particle size distribution and significantly higher absolute zeta potential (11.71 mV) than the control (9.56 mV) (P < 0.05). Atomic force microscopy results showed that the surface roughness of MP aggregation decreased by 9.78% with ISP after freezing for 180 d. Additionally, compared to patties without ISP, the MP carbonyl content from the ISP-treated patty decreased by 32%, and the free amino content increased by 14.99% during frozen storage. Results from circular dichroism spectroscopy and fluorescence spectroscopy showed that MP secondary and tertiary structure stability in patties improved with ISP. Overall, ISP has the potential to improve MP aggregation and structural stability during frozen storage.

Biochar has attracted considerable attentions for its potential in many environmental and industrial applications. Here, a novel facile and efficient one-step acidic ball milling approach was designed to fabricate a porous biochar directly from hickory wood without any external heat treatment. After characterization, the biochar was tested for its ability to remove Titan Yellow (TY) organic dye from aqueous solution. Compared to the pristine ball milled biomass (BMB), the acidic ball milled biochar (ABMB) had a greater degree of carbonization and a larger diversity of oxygen-containing functional groups. As a result, the ABMB sorbed 23 times more TY dye than BMB (maximum sorption capacities of 182.3 and 8.1 mg g−1, respectively). Freundlich isotherm and intraparticle diffusion kinetic models best described the TY adsorption by ABMB and BMB. The results suggest that the one-step acidic ball milling method has great potential as a convenient and efficient approach to convert biomass to biochar with excellent characteristics for environmental remediation and perhaps water treatment applications.

The physicochemical properties and antioxidant activity of sea cucumber gonadal polysaccharide extracted by enzymatic, ultrasound and ultrasound-assisted enzymatic methods were investigated. The results showed that the total sugar and sulphate group content (69.1 g/100 g, 14.7 g/100 g) of SCGP-UAE were higher than those of SCGP-E (58.8 g/100 g, 10.6 g/100 g) and SCGP-U (62.9 g/100 g, 13.3 g/100 g). The zeta potential, molecular weight and particle size of SCGP-UAE were significantly lower than those of SCGP-E and SCGP-U (P < 0.05). Their molar ratios of monosaccharide composition were different. With the concentration of SCGP-E, SCGP-U and SCGP-UAE from 0.25 increased to 4.00 mg/mL, the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH∙), hydroxyl radical (∙OH) scavenging ability and reducing power of them were improved. In the concentration range of 0.50–4.00 mg/mL, the antioxidant ability of SCGP-UAE was higher than SCGP-E and SCGP-U. At 4.00 mg/mL, the DPPH∙, ∙OH scavenging ability and reducing power of SCGP-UAE were 12.8%, 14.6% and 9.42% higher than those of SCGP-U and 38.1%, 29.9% and 29.3% higher than those of SCGP-E, respectively. The strongest antioxidant activity of SCGP-UAE was due to the UAE method degraded SCGP chains and exposed more sulphate groups by breaking glycosidic bonds within SCGP.

The electrochemical oxygen evolution reaction (OER) is a fundamental anodic semi-reaction used in the hydrogen energy industry. Herein, we report a novel NiFe-layered double hydroxide (NiFe-LDH)-based hybrid catalyst for the OER, which is promoted by the two-step hydrothermal loading of carbon sphere (CS) onto NiFe-LDH sheets, named as [email protected] The effects of hydrothermal carbonization (HTC) parameters (such as hydrothermal time and glucose concentration) and the loading ratio of CSs on [email protected] were investigated. The results showed that the two-step hydrothermal synthesis significantly inhibited the interference of the carbonized substances on the lattice formation of NiFe-LDH and successfully achieved a firm combination. By adjusting the HTC process, the surface characteristics and graphitization degree of the carbonized microspheres can be effectively controlled, leading to increased OER performance of [email protected] Thus, under the optimal process parameters (5 h, 0.6 M, and 5 mL), [email protected] exhibited an excellent overpotential of 292 mV at 50 mA cm-2 and 372 mV at 100 mA cm-2 for the OER. The outstanding OER performance of [email protected] is attributed to the excellent morphology control of the composite, abundant functional groups, and suitable graphitization degree of the hydrothermally carbonized CS, as well as the synergistic effect between the CSs and NiFe-LDH.

As one of the most efficient, low-cost, and readily available electrocatalysts for oxygen evolution reaction (OER) in alkaline environments, the nickel-iron electrocatalyst is of great significance to commercial water splitting. In this study, NiFe-layered double hydroxide loaded on nickel foam (NiFe-LDH/NF) was synthesized via a simple one-step hydrothermal method, whose OER catalytic performance could be successfully optimized by further electrochemical reconstruction. The results show that NF is an effective precursor to loading crystallized Ni(OH)2 nanoparticles during hydrothermal synthesis, leading to the generation of high-performance NiOOH during OER reconstruction. Under the optimal Ni:Fe feeding ratio, Ni2Fe1-LDH/NF requires an ultra-low OER overpotential of 239 mV at 50 mA cm−2 and 260 mV at 100 mA cm−2, whose Tafel slope is only 64.1 mV dec−1. Impressively, Ni2Fe1-LDH/NF also achieves an ultra-low voltage of 1.44 V at 10 mA cm−2 with excellent long-term stability for overall water splitting. Unlike the previous viewpoint that only Ni species dominate surface reconstruction of NiFe-LDH, in this article the decisive influence related to Fe species on the reconstruction layers’ activity and stability is confirmed by electrochemistry, Raman, and XPS analysis during reconstruction process. During OER reconstruction, the surface Ni:Fe ratios can be "self-adaptively" regulated to an appropriate region, thus the stable reconstruction layers rich in NiOOH can be formed as the protective shells for NiFe-LDH. Furthermore, such "self-adaptive" reconstruction, assisted with appropriate initial Ni:Fe feeding ratios, can also stimulate more Ni3+ active sites for OER, benefitting the outstanding catalytic performance of NiFe-LDH/NF for overall water splitting and prospective large-scale application.

Thermal energy storage technology is of great significance for the efficient utilization of solar energy. In this paper, the melting process of a horizontal latent heat energy storage unit is studied by numerical method. Taguchi design method and response surface method are exploited to optimize its melting performance. The effects of inner tube eccentricity, fin deflection angle, and fin width upon the melting performance are investigated. The contribution of each parameter to the melting performance is processed by Taguchi method, and the interactions of each parameter are obtained by response surface method. The fluid-structure coupling equation of target response is fitted to obtain the optimal structure, and the influence of different structural parameters on the melting performance is discussed. The results reveal that compared with the initial structure, the melting time of the optimal structure is reduced by 64.16% and the average heat absorption rate is increased by 168.38%, respectively. It is evaluated that the structure optimization greatly increases the heat absorption rate and reduces the melting time, but it has a negative effect on the heat absorption in one melting cycle. Finally, the single flip mechanism is introduced innovatively, and the influence of flip time on the related melting properties is discussed. The single flip is the best to increase the average thermal energy absorption rate by 6.30% and reduce the melting time of the unit by 10.57%.

The combination of latent heat storage (LHS) technology with the Organic Rankine Cycle represents a widely recognized solar thermoelectric conversion means. However, this technology is hindered by the instability of solar energy and the poor thermal conductivity of thermal storage materials. This study addresses the challenges posed by solar energy fluctuations by implementing a sinusoidal heat source condition during the heat release process of LHS system. Furthermore, a comprehensive approach is taken to enhance heat transfer, incorporating both active methods such as rotational conditions, and passive methods using metal nanoparticles and high-performance fins. The Taguchi method is employed to optimize rotation speed, heat source amplitude, and half-period of the latent heat storage unit, and the resulting heat release performance is compared between different structures and the optimized structures. The findings from optimal design analysis reveal that rotation speed has the most significant influence on mean heat discharging rate and solidification time, followed by the heat source amplitude and half-cycle period. There is a notable interaction between heat source amplitude and half-cycle period. Compared to the initial structure, the optimal structure identified through the optimal design shortens the solidification time by 11.18%, increases the mean heat discharging rate by 13.04% and raises the average temperature response by 18.82%. Furthermore, the addition of Al2O3 nanoparticles further enhances heat discharging properties. Specifically, the presence of 2.5% and 5% Al2O3 nanoparticles shortens unit solidification time by 9.52% and 18.83% and increases the mean heat release rate by 7.69% and 17.26%. It is noted that the incorporation of rotating-fit nanoparticles partly compensates for the limitations of increased viscosity and particle settlement associated with metal nanoparticles, although it does not fully address the challenges related to reduced heat storage/release.

Ca2Nb2O7 is a promising material for high-temperature piezoelectric applications due to its ultra-high Curie temperature, which makes it a suitable candidate for use in harsh environments. However, their piezoelectric performance needs improvement. Here, through chemical engineering methods, we have successfully grown Bi3+ doped Ca2Nb2O7 single crystals using the optical floating zone technique. The Ca1.94Bi0.06Nb2O7 single crystals achieved better high-temperature stability, transparency and a higher piezoelectric constant of 12.8 pC/N at 298 K and 20.0 pC/N at 660 K. In addition to the dopant effects, mechanisms for enhancing the piezoelectric properties of perovskite-like layer structure (PLS) materials have been identified, highlighting the significant contribution of the NbO6 octahedron and interlayer ions. These findings offers valuable insights into improving the performance of PLS materials, which is crucial for promoting their practical applications as high-temperature lead-free piezoelectric materials.

New blood vessels are formed through the assembly or sprouting of endothelial cells (ECs) and become stabilized by the formation of perivascular matrix and the association with supporting mural cells. To investigate the role of endothelial Smad4 in vascular development, we deleted the Smad4 gene specifically in ECs using the Cre-LoxP system. EC-specific Smad4 mutant mice died at embryonic day 10.5 due to cardiovascular defects, including attenuated vessels sprouting and remodeling, collapsed dorsal aortas, enlarged hearts with reduced trabeculae, and failed endocardial cushion formation. Noticeably, Smad4-deficient ECs demonstrated an intrinsic defect in tube formation in vitro. Furthermore, the mutant vascular ECs dissociated away from the surrounding cells and suffered from impaired development of vascular smooth muscle cells. The disturbed vascular integrity and maturation was associated with aberrant expression of angiopoietins and a gap junction component, connexin43. Collectively, we have provided direct functional evidence that Smad4 activity in the developing ECs is essential for blood vessel remodeling, maturation, and integrity.

We show that R-Ras, a small GTPase of the Ras family, is essential for the establishment of mature, functional blood vessels in tumors. The genetic disruption of R-Ras severely impaired the maturation processes of tumor vessels in mice. Conversely, the gain of function of R-Ras improved vessel structure and blood perfusion and blocked plasma leakage by enhanced endothelial barrier function and pericyte association with nascent blood vessels. Thus, R-Ras promotes normalization of the tumor vasculature. These findings identify R-Ras as a critical regulator of vessel integrity and function during tumor vascularization.

This paper investigates the stability and stabilization of Boolean networks with impulsive effects. After giving a survey on semi-tensor product of matrices, we convert a Boolean network with impulsive effects into impulsive discrete-time dynamics. Then, some necessary and sufficient conditions are given for the stability and stabilization of Boolean networks with impulsive effects. Finally, examples are provided to illustrate the efficiency of the obtained results.

Natural mordenite, replacing the synthetic zeolites, has been employed as the support of TiO2, and its photocatalytic activity has been examined in methyl orange (MO) aqueous under UV light. AFM, TEM, XRD, FTIR and fluorescence spectra have been used to reveal the loading effects of TiO2 on mordenite. The results show that the photocatalytic degradation (PCD) reaction rates are sharply increased by natural zeolite supports. Since mordenite is photo-inert, the PCD-enhancement is mostly caused by the bonding effects of Ti-O-Si and Ti-O-Al. Moreover, another two distinct natural zeolites have been employed as the supports of TiO2, in order to check the universality of PCD-enhancement effect of natural zeolites on TiO2. And the factors of PCD reaction on TiO2-zeolite, such as pH and catalyst dose, have been investigated.

This brief deals with the problem of the observability for the Boolean control networks with time delays in states. First, using semi-tensor product of matrices and the matrix expression of logic, the Boolean control networks with state delays can be converted into discrete time delay dynamics. Then, the observability of the Boolean control networks via two kinds of inputs is investigated by giving necessary and sufficient conditions. Finally, examples are given to illustrate the efficiency of the obtained results.

P-doped TiO2 nanoparticles were synthesized by the sol−gel method with various H3PO4 amounts. The samples were calcinated at different temperature and charactered by XPS, ICP, XRD, SEM, Raman, FTIR, and UV−vis methods, so that the formation process of phosphate species could be inspected. The XRD results show that P species hinder the particle growth of anatase and increase the anatase-to-rutile phase transformation temperature to more than 900 °C, and a new titanyl phosphate, Ti5O4(PO4)4, was observed in P-doped TiO2 when calcined at 1000 °C. The UV−vis results indicate that the P species is likely to have two different states, leading to the variety of visible-light photocatalytic activity and band gap energy of P-doped TiO2. One state is the “separated phase”. In this state, the P/Ti ratio is very low so that the P species is surrounded by TiO2. The “separated phase” of P species introduces oxygen into TiO2 lattice and hence causes a red-shift of the adsorption band edge of anatase, leading to the increased visible-light photocatalytic activity of P-doped TiO2. The other state is the “congregated phase”. It appears at the micro region where the ratio of P/Ti is high enough to make the TiO2 clusters isolated by P species. The “congregated phase” of P species acts as the interface phase between TiO2 clusters and strongly retards the crystal growth of anatase, resulting in the widened band gap of P-doped TiO2. Furthermore, a possible mechanism was also proposed to explain the formation of the two phases during the sol−gel process. The results indicate that in order to improve the visible-light photocatalytic activity of P-doped TiO2 the percentage of “separated phase” in P species needs to be enhanced.

TiO2-diatomite photocatalysts were prepared by sol–gel process with various pre-modified diatomite. In order to obtain diatomite with different surface characteristics, two modification approaches including calcination and phosphoric acid treatment on the micro-structure of diatomite are introduced. The photocatalysts were characterized by XRD, XPS, nitrogen adsorption–desorption isotherms and micromorphology analysis. The results indicate that, compared with pure TiO2, the anatase-to-rutile phase transition temperature of TiO2 loaded on diatomite carrier is significantly increased to nearly 900 °C, depending on the different pretreatment method of diatomite. The photocatalytic activities of different samples were evaluated by their degradation rate of methyl orange (MO) dye under UV and visible-light irradiation. The samples prepared by phosphoric acid pretreatment method exhibit the highest photocatalytic activity. After 90 min of UV irradiation, about 90% of MO is decomposed by the best effective photocatalyst. And after 8 h visible-light irradiation, nearly 60% of MO is decomposed by the same sample. Further mechanism investigation reveals that the H3PO4 pretreatment process can obviously change the surface features of diatomite carrier, cause the formation of Si–O–Ti bond, increase the binding strength between TiO2 and diatomite, restrain crystal growth of loaded TiO2, and thus form thermal-stable mesoporous structure at the granular spaces. It helps to build micro-, meso- and macro-porous hierarchical porous structure in TiO2-diatomite, and improves the charge and mass transfer efficiency during catalyzing process, resulting in the significantly increased photocatalytic activity of TiO2-diatomite pretreated by phosphoric acid.

The stabilization and set stabilization of a multivalued logical system are investigated in this paper by using pinning control. First, new algorithms are presented to redesign the transition matrix of the multivalued logical system such that the system is stable or set stable. Then, by using reconstruction theory of a k-valued logical system, the pinning nodes are selected. In addition, the transition matrix of the pinning control is given by solving some logical matrix equations. Then, a pinning control design algorithm is provided. Finally, an example is employed to illustrate the proposed control design procedure.

The high dimensionality of hyperspectral images (HSIs) brings great difficulty for their later data processing. Band selection, as a commonly used dimension reduction technique, is the selection of optimal band combinations from the original bands, while attempting to remove the redundancy between bands and maintain a good classification ability. In this study, a novel hybrid filter-wrapper band selection method is proposed by a three-step strategy, i.e., band subset decomposition, band selection and band optimization. Based on the information gain (IG) and the spectral curve of the hyperspectral dataset, the band subset decomposition technique is improved, and a random selection strategy is suggested. The implementation of the first two steps addresses the problem of reducing inter-band redundancy. An optimization strategy based on a gray wolf optimizer (GWO) ensures that the selected band combination has a good classification ability. The classification performance of the selected band combination is verified on the Indian Pines, Pavia University and Salinas hyperspectral datasets with the aid of support vector machine (SVM) with a five-fold cross-validation. By comparing the proposed IG-GWO method with five state-of-the-art band selection approaches, the superiority of the proposed method for HSIs classification is experimentally demonstrated on three well-known hyperspectral datasets.

Abstract The role of osteoclastic miRNAs in regulating osteolytic bone metastasis (OBM) of breast cancer is still underexplored. Here, we examined the expression profiles of osteoclastogenic miRNAs in human bone specimens and identified that miR-214-3p was significantly upregulated in breast cancer patients with OBM. Consistently, we found increased miR-214-3p within osteoclasts, which was associated with the elevated bone resorption, during the development of OBM in human breast cancer xenografted nude mice (BCX). Furthermore, genetic ablation of osteoclastic miR-214-3p in nude mice prevent the development of OBM. Conditioned medium from MDA-MB-231 cells dramatically stimulated miR-214-3p expression to promote osteoclast differentiation. Mechanistically, a series of in vitro study showed that miR-214-3p directly targeted Traf3 to promote osteoclast activity and bone-resorbing activity. In addition, osteoclast-specific miR-214-3p knock-in mice showed remarkably increased bone resorption when compared to the littermate controls, which was attenuated after osteoclast-targeted treatment with Traf3 3′UTR-containing plasmid. In BCX nude mice, osteoclast-targeted antagomir-214-3p delivery could recover the TRAF3 protein expression and attenuate the development of OBM, respectively. Collectively, inhibition of osteoclastic miR-214-3p may be a potential therapeutic strategy for breast cancer patients with OBM. Meanwhile, the intraosseous TRAF3 could be a promising biomarker for evaluation of the treatment response of antagomir-214-3p.

A series of polypyridyl-ruthenium(II) and -iridium(III) complexes that contain labile chlorido ligands, [{M(tpy)Cl}2{μ-bbn}]2/4+ {Cl-Mbbn; where M = Ru or Ir; tpy = 2,2′:6′,2′′-terpyridine; and bbn = bis[4(4′-methyl-2,2′-bipyridyl)]-1,n-alkane (n = 7, 12 or 16)} have been synthesised and their potential as antimicrobial agents examined. The minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of the series of metal complexes against four strains of bacteria – Gram positive Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA), and Gram negative Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) – have been determined. All the ruthenium complexes were highly active and bactericidal. In particular, the Cl-Rubb12 complex showed excellent activity against all bacterial cell lines with MIC values of 1 μg mL−1 against the Gram positive bacteria and 2 and 8 μg mL−1 against E. coli and P. aeruginosa, respectively. The corresponding iridium(III) complexes also showed significant antimicrobial activity in terms of MIC values; however and surprisingly, the iridium complexes were bacteriostatic rather than bactericidal. The inert iridium(III) complex, [{Ir(phen)2}2{μ-bb12}]6+ {where phen = 1,10-phenanthroline) exhibited no antimicrobial activity, suggesting that it could not cross the bacterial membrane. The mononuclear model complex, [Ir(tpy)(Me2bpy)Cl]Cl2 (where Me2bpy = 4,4′-dimethyl-2,2′-bipyridine), was found to aquate very rapidly, with the pKa of the iridium-bound water in the corresponding aqua complex determined to be 6.0. This suggests the dinuclear complexes [Ir(tpy)Cl}2{μ-bbn}]4+ aquate and deprotonate rapidly and enter the bacterial cells as 4+ charged hydroxo species.

Abstract Pressure‐induced electronic structure transition from insulating phase to metal state is a potential new paradigm for halide perovskites. The metallization based on these materials may afford a novel motif toward realizing new electronic properties even superconductivity phenomenon. Herein, how static compression modulates the crystal and electronic structure of typical perovskite semiconductors cesium lead iodine (CsPbI 3 ) by both experimental and theoretical studies is reported. The comprehensive studies discover the insulator–metal transition of CsPbI 3 at 39.3 GPa, and reveal the key information behind the electronic transition. The perovskite's precise structural evolution is tracked upon compression, from orthorhombic Pnma phase to monoclinic C2/m structure before the metallic transition. More interestingly, the C2/m phase has the most distorted octahedra and the shortest Pb–I bond length relative to the average bond length that is ever reported in a halide perovskite structure. The electronic transition stems from the structural changes accompanied by the anomalously self‐distorted octahedra. These studies show that pressure can significantly alter the structural and electronic properties of these technologically important perovskites.

With ever increasing interest in layered materials, molybdenum disulfide has been widely investigated due to its unique optoelectronic properties. Pressure is an effective technique to tune the lattice and electronic structure of materials such that high pressure studies can disclose new structural and optical phenomena. In this study, taking MoS2 as an example, we investigate the pressure confinement effect on monolayer MoS2 by in situ high pressure Raman and photoluminescence (PL) measurements. Our results reveal a structural deformation of monolayer MoS2 starting from 0.84 GPa, which is evidenced by the splitting of E(1)2g and A1g modes. A further compression leads to a transition from the 1H-MoS2 phase to a novel structure evidenced by the appearance of two new peaks located at 200 and 240 cm(-1). This is a distinct feature of monolayer MoS2 compared with bulk MoS2. The new structure is supposed to have a distorted unit with the S atoms slided within a single layer like that of metastable 1T'-MoS2. However, unlike the non-photoluminescent 1T'-MoS2 structure, our monolayer shows a remarkable PL peak and a pressure-induced blue shift up to 13.1 GPa. This pressure-dependent behavior might enable the development of novel devices with multiple phenomena involving the strong coupling of the mechanical, electrical and optical properties of layered nanomaterials.

Poly (ADP-ribose) polymerase 1 (PARP1), the best-studied isoform of the nuclear enzyme PARP family, plays a pivotal role in cellular biological processes, such as DNA repair, gene transcription, and so on. PARP1 has been found to be overexpressed in various carcinomas. These all indicate the clinical potential of PARP1 as a therapeutic target of human malignancies. Additionally, multiple preclinical research studies and clinical trials demonstrate that inhibition of PARP1 can repress tumor growth and metastasis. Up until now, PARP1 inhibitors are clinically used not only for monotherapy to suppress various tumors, but also for adjuvant therapy, to maintain or enhance therapeutic effects of mature antineoplastic drugs, as well as protect patients from chemotherapy and surgery-induced injury. To supply a framework for understanding recent research progress of PARP1 in carcinomas, we review the structure, expression, functions, and mechanisms of PARP1, and summarize the clinically mature PARP1-related anticancer agents, to provide some ideas for the development of other promising PARP1 inhibitors in antineoplastic therapy.

This paper focuses on the problem of adaptive tracking control for a class of switched strict-feedback nonlinear systems with unknown time-varying delays and asymmetric saturation actuators under arbitrary switching. Especially, the considered time-varying delays absolutely depend on the subsystem number. The main technical difficulties lie in finding an appropriate common Lyapunov function (CLF) for all subsystems and designing a common adaptive control scheme in the presence of unknown time-varying delays and asymmetric saturation nonlinearities. Based on a novel combination of Lyapunov–Razumikhin method, dynamic surface control (DSC) technique, variable separation approach and neural network (NN) approximation, a simple quadratical CLF is constructed and a common adaptive control scheme involving only one adaptive parameter is developed. The proposed controller guarantees that all signals of closed-loop system are semi-globally uniformly ultimately bounded (SGUUB) while the tracking error converges to an adjustable neighborhood of the origin. Finally, the effectiveness of the design methodology is illustrated with two simulation examples.

Probabilistic Boolean network (PBN) is a kind of stochastic logical system in which update functions are randomly selected from a set of candidate Boolean functions according to a prescribed probability distribution at each time step. In this brief, a pinning controller design algorithm is proposed to set stabilize any PBN with probability one. First, an algorithm is given to change the columns of its transition matrix. Then, according to the newly obtained transition matrix, a fraction of nodes can be selected as pinning nodes to inject control inputs to achieve set stabilization. The problem is challenging since the Boolean functions in a PBN are not deterministic but are randomly chosen among several Boolean functions. Furthermore, the structure matrices of the pinning controllers are given by solving some logical matrices equations based on which a pinning controller design algorithm is provided to set stabilize the PBN with probability one. Finally, the theoretical results are validated using several examples.

Biological macromolecules are the basis of life activities. There is a separation of spatial dimension between DNA replication and RNA biogenesis, and protein synthesis, which is an interesting phenomenon. The former occurs in the cell nucleus, while the latter in the cytoplasm. The separation requires protein to transport across the nuclear envelope to realize a variety of biological functions. Nucleocytoplasmic transport of protein including import to the nucleus and export to the cytoplasm is a complicated process that requires involvement and interaction of many proteins. In recent years, many studies have found that proteins constantly shuttle between the cytoplasm and the nucleus. These shuttling proteins play a crucial role as transport carriers and signal transduction regulators within cells. In this review, we describe the mechanism of nucleocytoplasmic transport of shuttling proteins and summarize some important diseases related shuttling proteins.

The composite catalysts of TiO2/SiO2 were prepared though a sol-gel process followed by the calcination crystallization process. The inexpensive precursors, titanium sulfate and fly ash acid sludge, were used as providing titania and silica sources, respectively. The decomposition of fly ash acid sludge was digested with NaOH to extract silica, and the obtained sodium silicate was used to prepare TiO2/SiO2 composite. The effect of calcination temperature on the structure of TiO2/SiO2 composites was studied by means of XRD, BET, FTIR, SEM, photocatalysis and adsorption test. It was found that the anatase-to-rutile phase transition temperature of TiO2/SiO2 composite powders was significantly higher than that of pure TiO2. The presence of the TiOSi bond was confirmed in the final products when the incorporation of titania into silica were performed. The photocatalytic performance of TiO2/SiO2 composite annealed at different temperatures was evaluated by Rhodamine B (RhB) as the target pollutant under visible-light irradiation. Results indicated that the sample exhibited the highest photocatalytic activity when the calcination temperature is up to 600 °C. After 4 h visible-light irradiation, about 90% of RhB was removed by this type of photocatalysts.

This study aimed to analyze the impact of baseline posterior circulation Acute Stroke Prognosis Early Computed Tomography Score (pc-ASPECTS) on the efficacy and safety of endovascular therapy (EVT) for patients with acute basilar artery occlusion.The BASILAR was a nationwide prospective registry of consecutive patients with a symptomatic and radiologically confirmed acute basilar artery occlusion within 24 hours of symptom onset. We estimated the effect of standard medical therapy alone (SMT group) versus SMT plus EVT (EVT group) for patients with documented pc-ASPECTS on noncontrast CT, both as a categorical (0-4 versus 5-7 versus 8-10) and as a continuous variable. The primary outcomes included favorable functional outcomes (modified Rankin Scale ≤3) at 90 days and mortality within 90 days.In total, 823 cases were included: 468 with pc-ASPECTS 8 to 10 (SMT: 71; EVT: 397), 317 with pc-ASPECTS 5 to 7 (SMT: 85; EVT: 232), and 38 with pc-ASPECTS 0 to 4 (SMT: 13; EVT: 25). EVT was associated with higher rate of favorable outcomes (adjusted relative risk with 95% CI, 4.35 [1.30-14.48] and 3.20 [1.68-6.09]; respectively) and lower mortality (60.8% versus 77.6%, P=0.005 and 35.0% versus 66.2%, P<0.001; respectively) than SMT in the pc-ASPECTS 5 to 7 and 8 to 10 subgroups. Continuous benefit curves also showed the superior efficacy and safety of EVT over SMT in patients with pc-ASPECTS ≥5. Furthermore, the prognostic effect of onset to puncture time on favorable outcome with EVT was not significant after adjustment for pc-ASPECTS (adjusted odds ratio, 0.98 [95% CI, 0.94-1.02]).Patients of basilar artery occlusion with pc-ASPECTS ≥5 could benefit from EVT. The baseline pc-ASPECTS appears more important for decision making and predicting prognosis than time to EVT. Registration: URL: http://www.chictr.org.cn. Unique identifier: ChiCTR1800014759.

Osteoarthritis (OA) is a prevalent aging-related joint disease lacking disease-modifying therapies. Here, we identified an upregulation of circulating exosomal osteoclast (OC)-derived microRNAs (OC-miRNAs) during the progression of surgery-induced OA in mice. We found that reducing OC-miRNAs by Cre-mediated excision of the key miRNA-processing enzyme Dicer or blocking the secretion of OC-originated exosomes by short interfering RNA-mediated silencing of Rab27a substantially delayed the progression of surgery-induced OA in mice. Mechanistically, the exosomal transfer of OC-miRNAs to chondrocytes reduced the resistance of cartilage to matrix degeneration, osteochondral angiogenesis and sensory innervation during OA progression by suppressing tissue inhibitor of metalloproteinase-2 (TIMP-2) and TIMP-3. Furthermore, systemic administration of a new OC-targeted exosome inhibitor (OCExoInhib) blunted the progression of surgery-induced OA in mice. We suggest that targeting the exosomal transfer of OC-miRNAs to chondrocytes represents a potential therapeutic avenue to tackle OA progression.

T cells display significant phenotypical changes and play multiple roles in promoting the immune response in SLE. The frequencies of T cell subpopulations in SLE are still not well understood. To better understanding the phenotypic abnormalities of T cells in SLE will help us to clarify disease immunopathology and to find promising biomarkers for disease monitoring and control.Peripheral blood CD4+ and CD8+ T cells and their subsets were determined by flow cytometry. Forty-one active SLE patients were selected, including 28 new-onset patients and 13 relapsing patients. One hundred healthy controls (HCs) were enrolled as the control group. The percentages of these cell subsets between patients with SLE and HCs and their relationships with disease activity and autoantibody titers were analysed. Thirteen of 28 new-onset SLE patients were assessed before and after treatment. The changes in the frequencies of these cell subsets and their relationships with renal response were analysed.There was a broad range of anomalies in the proportion of T cell subsets in patients with SLE compared with that of the HCs. Compared with the HCs, a higher frequency of memory T cells and a lower frequency of naïve T cells were noted in patients with SLE. In addition, an imbalance of CD28+ and CD28- cells in CD4+ T cells was observed in patients with SLE. We found that the expanded CD4+CD28- T cells did not decrease after treatment in patients who had impaired renal responses. It was very interesting to exhibit a negative correlation in the frequency between the CD4+CD28- T cells and T regulatory (Treg) cells and a positive correlation between the frequency of CD4+CD28+ T cells and Treg cells in this study. Increased CD8+HLADR+ T cell and CD8+CD38+HLADR+ T cell counts were observed in patients with SLE, suggesting an impaired cytotoxic capacity of CD8+ T cells in SLE. Additionally, we found that CD8+CD38+HLADR+ T cells were closely associated with disease activity, autoantibody titres and renal prognosis. CD4+ CXCR5-PD1+ T cells were expanded in patients with SLE in this study and were associated with disease activity in SLE. Th1 (T helper type 1) cells and Treg cells were decreased, but frequencies of T follicular helper (Tfh) cells, Th2 cells, Th17 cells and Tfh17 cells were increased. A strong correlation between Th17 cells and Tregs with renal involvement was observed in this study.The proportions of CD4+CD28- T cells, CD4+CXCR5-PD1+ T cells, CD8+HLADR+ T cells and CD8+CD38+HLADR+ T cells increased in patients with SLE and could be associated with disease activity and renal prognosis.

The rate of adaptive evolution depends on the rate at which beneficial mutations are introduced into a population and the fitness effects of those mutations. The rate of beneficial mutations and their expected fitness effects is often difficult to empirically quantify. As these 2 parameters determine the pace of evolutionary change in a population, the dynamics of adaptive evolution may enable inference of their values. Copy number variants (CNVs) are a pervasive source of heritable variation that can facilitate rapid adaptive evolution. Previously, we developed a locus-specific fluorescent CNV reporter to quantify CNV dynamics in evolving populations maintained in nutrient-limiting conditions using chemostats. Here, we use CNV adaptation dynamics to estimate the rate at which beneficial CNVs are introduced through de novo mutation and their fitness effects using simulation-based likelihood–free inference approaches. We tested the suitability of 2 evolutionary models: a standard Wright–Fisher model and a chemostat model. We evaluated 2 likelihood-free inference algorithms: the well-established Approximate Bayesian Computation with Sequential Monte Carlo (ABC-SMC) algorithm, and the recently developed Neural Posterior Estimation (NPE) algorithm, which applies an artificial neural network to directly estimate the posterior distribution. By systematically evaluating the suitability of different inference methods and models, we show that NPE has several advantages over ABC-SMC and that a Wright–Fisher evolutionary model suffices in most cases. Using our validated inference framework, we estimate the CNV formation rate at the GAP1 locus in the yeast Saccharomyces cerevisiae to be 10 −4.7 to 10 −4 CNVs per cell division and a fitness coefficient of 0.04 to 0.1 per generation for GAP1 CNVs in glutamine-limited chemostats. We experimentally validated our inference-based estimates using 2 distinct experimental methods—barcode lineage tracking and pairwise fitness assays—which provide independent confirmation of the accuracy of our approach. Our results are consistent with a beneficial CNV supply rate that is 10-fold greater than the estimated rates of beneficial single-nucleotide mutations, explaining the outsized importance of CNVs in rapid adaptive evolution. More generally, our study demonstrates the utility of novel neural network–based likelihood–free inference methods for inferring the rates and effects of evolutionary processes from empirical data with possible applications ranging from tumor to viral evolution.

This study evaluated the synergistic effects and disinfection mechanism of ultrasound (US, 200 W and 30 kHz) and slightly acidic electrolysed water (SAEW, 60 mg/L and pH of 6.2) treatment and the associated preservation of mirror carp during refrigeration storage (4 °C). US and SAEW alone and US combined with SAEW (US + SAEW) showed the lower water loss of fish. Fish treated with US + SAEW exhibited significantly lower degrees of lipid oxidation and protein degradation (P < 0.05). Microbiological results showed that US + SAEW inhibited the growth of Pseudomonas and activity of endogenous enzymes; also, US + SAEW decreased the relative activities of 2,3,5-triphenyl tetrazolium chloride-dehydrogenase (TTC-dehydrogenase) and ATP-ase in Pseudomonas by 65.89% and 10.26%, respectively. The combination of US + SAEW destroyed the cellular membrane and aggravated the leakage of nucleic acid and protein of Pseudomonas, and effectively inhibited the activity of antioxidant enzyme. This study reports a new industrial method for preserving refrigerated fish.

The aim of the study was to evaluate the positive effect of ultrasound-assisted saline thawing (UST) on the technological properties (water mobility, water holding capacity, colour, pH, shear force, TVB-N, oxidation reaction and microstructure) of mirror carp (Cyprinus carpio L.). The results present in the study showed that different thawing methods had negative impacts on the quality of mirror carp to varying degrees. Among them, UST samples had significant lower thawing loss, centrifugal loss and cooking loss than ultrasound thawing (UT) and air thawing (AT) samples (P < 0.05). The analysis result of low-field nuclear magnetic resonance illustrated that UST inhibited the mobility and distribution of water effectively. Decrease in shear force and TVBN values were observed in all thawing samples, and the UST samples maintained the significant better texture property and freshness than UT and AT samples did (P < 0.05). In addition, the treatment of UST obtained 1% salt concentration inhibited the oxidation reactions effectively. Investigation of the microstructure of samples demonstrated that the treatment of UST kept the relatively complete structure of tissue than other thawing methods. Therefore, UST can be an alternative strategy to the traditional thawing of meat.

Stochastic Boolean networks (SBNs) take process noise into account, so it is better to fit the actual situation and has a wider application background than Boolean networks (BNs). However, the presence of noise influences us to estimate the real state of the system. To minimize the inaccuracies caused by the presence of noise, an optimal state estimation problem is studied in this article. The multi-sensor fusion Boolean Bayesian filtering is proposed and a recursive algorithm is provided to calculate the prior and posterior belief of system state by fusing multi-sensor measurements based on the algebraic form of the SBN and Bayesian law. Then, the optimal state estimator is obtained, which minimizes the mean-square estimation error. Finally, a simulation example is carried out to demonstrate the performance of the proposed methodology. It has been shown through the simulation experiment that it increases the confidence level of the state estimation and improves the estimation performance using multi-sensor fusion compared with using single sensor.

Abstract The fitness of a genotype is defined as its lifetime reproductive success, with fitness itself being a composite trait likely dependent on many underlying phenotypes. Measuring fitness is important for understanding how alteration of different cellular components affects a cell’s ability to reproduce. Here, we describe an improved approach, implemented in Python, for estimating fitness in high throughput via pooled competition assays.

Fish gelatin nanoparticles (FGNPs) of different sizes (∼155–410 nm) were successfully obtained by adjusting the ratio of gelatin and glutaraldehyde (Gel/Glu ratio), and their possible generation mechanisms were revealed by Fourier transform infrared (FTIR) analysis and transmission electron microscopy images. The FGNPs were then used to fabricate collagen composite films. Compared to a pure collagen film, the tensile strength, elongation at break, and Young's modulus of composite films increased by 37.1%, 34.4%, and 79.2%, respectively, while the water vapor permeability decreased by 51.5%. Meanwhile, scanning electron microscopy images, FTIR, and X-ray diffraction analysis suggested that small-sized and uniformly distributed FGNPs maintained the original crystal structure and well-arranged super helical structure of collagen, while large-sized and cross-linked FGNPs destabilized the collagen structure. A Gel/Glu ratio of 12:4 afforded FGNPs with a size of ∼155 nm, which was the best collagen composite film-forming size. Moreover, the FGNPs could bind to collagen through weak but countless non-covalent bonds (hydrogen bonds and ionic bonds), thereby improving the mechanical properties of the films. Overall, the FGNPs improved the performances characteristic of collagen films by influencing their structure, including hydrogen bonding interaction, crystalline structure, and superhelix structure, which would advance the understanding of collagen-based films.

The surface interaction between TiO2 and natural zeolite, clinoptilolite, has been investigated by means of transmission electron microscope (TEM), atom force microscope (AFM), X-ray diffractometer (XRD), diffuse reflectance infrared Fourier transform (DRIFT) and far Fourier transform infrared ray (FTIR) spectroscopy. And the photocatalytic degradation (PCD) rate of methyl orange (MO), a model of recalcitrant azo dye, in aqueous system has been measured to compare the photocatalytic activities of different photocatalysts. A model has been carried out to explain the incorporation between TiO2 particles and natural zeolite. The results show that the TiO2 particles loaded on zeolite are 50 nm or so, smaller than the pure one, and combine with zeolite via chemical force. Since the reserved adsorption ability and the existence of electron trapper, the TiO2–zeolite performed more efficient at low initial concentration and in the later period of PCD process, as compared with pure TiO2 nanopowders.

To develop a new practical method of purifying and recycling ionic liquids, we performed direct microscopic observations and in situ crystallization of low-melting ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF(6)]), in detail by high pressure Raman spectroscopy. Compression of [BMIM][PF(6)] was measured under pressures up to about 2.0 GPa at temperatures 293-353 K by using a high pressure diamond anvil cell (DAC). At room temperature, with pressure increasing, the characteristic bands of [BMIM][PF(6)] displayed nonmonotonic pressure-induced frequency shifts, and [BMIM][PF(6)] experienced the liquid-solid phase transition at about 0.50 GPa. In separate experiments, in situ crystallization of low-melting ionic liquid [BMIM][PF(6)] were also measured at various P-T regions, in order to improve the understanding of its stability limits. Finally, the T versus P phase diagram of [BMIM][PF(6)] was constructed, and it showed that the melting point was an increase function of pressure. It was also indicated that the structure changes in the crystalline and liquid states under high pressure might also be associated with conformational changes in the butyl chain. Pressure-released Raman spectra also showed that the phase transition of [BMIM][PF(6)] was reversible.

The effect of human serum on the minimum inhibitory/bactericidal concentrations of the potential antimicrobial agents ΔΔ-[{Ru(phen)2}2(μ-bbn)]4+ {ΔΔ-Rubbn; where phen = 1,10-phenanthroline, bbn = 1,n-bis[4(4′-methyl-2,2′-bipyridyl)]-alkane for n = 12 and 16} against four strains of bacteria – Gram positive Staphylococcus aureus and methicillin-resistant S. aureus (MRSA), and Gram negative Escherichia coli and Pseudomonas aeruginosa – has been determined. The results demonstrated that the ruthenium(II) complexes have significantly decreased in vitro activity in serum. Fluorescence spectroscopy was used to confirm that the decrease in antimicrobial activity was due to the strong binding of the ruthenium complexes with the serum proteins human serum albumin (HSA) and transferrin. A series of ruthenium complexes showed stronger binding to HSA than apo-transferrin but comparable or less than with holo-transferrin, with the binding affinity to all three proteins decreasing in the order trinuclear > dinuclear > mononuclear. The dinuclear complex ΔΔ-Rubb12 displaced warfarin from HSA, tentatively suggesting that the ruthenium complexes bind at or near the warfarin-binding site, Sudlow's site 1. The binding of ΔΔ-Rubb12 and ΔΔ-Rubb16 to the macrocyclic host molecule cucurbit[10]uril (Q[10]) was examined by NMR spectroscopy. The large upfield 1H NMR chemical shift changes observed for the methylene protons in the bridging ligands upon addition of Q[10], coupled with the observation of a range of intermolecular ROEs in ROESY spectra, indicated that the dinuclear complexes bound Q[10] with the bridging ligand within the cavity and the metal centres positioned outside the portals. NMR and fluorescence spectroscopy demonstrated that the Q[10]-encapsulated ruthenium complexes directly bound HSA, and with similar affinity to the corresponding free metal complexes.

Vanadium sesquioxide, V2O3, is a prototypical metal-to-insulator system where, in temperature-dependent studies, the transition always coincides with a corundum-to-monoclinic structural transition. As a function of pressure, V2O3 follows the expected behavior of increased metallicity due to a larger bandwidth for pressures up to 12.5 GPa. Surprisingly, for higher pressures when the structure becomes unstable, the resistance starts to increase. Around 32.5 GPa at 300 K, we observe a novel pressure-induced corundum-to-monoclinic transition between two metallic phases, showing that the structural phase transition can be decoupled from the metal-insulator transition. Using x-ray Raman scattering, we find that screening effects, which are strong in the corundum phase, become weakened at high pressures. Theoretical calculations indicate that this can be related to a decrease in coherent quasiparticle strength, suggesting that the high-pressure phase is likely a critical correlated metal, on the verge of Mott-insulating behavior.

Using the semi-tensor product method, this paper investigates the controllability of a μth order Boolean control network. After a brief introduction on semi-tensor product of matrices to μth order Boolean control networks, the controllability issue is studied. First, a systematic procedure to reconstruct the logical dynamic of a μth order Boolean control network from its network transition matrix is presented for design purpose. Then, the controllability via two types of controls is considered. Necessary and sufficient conditions are provided for each case. The application of input-state incidence matrix to the controllability of μth order Boolean control networks is studied. Finally, as an application, examples are given to illustrate the effectiveness of the obtained results.

In order to investigate the influences of modification on industrial-grade cathode materials, layered Ti-doped Li(Ni0.5Co0.2Mn0.3)1−xTixO2 cathode materials have been synthesized via a simple solid state method using industrial raw materials in bulk scale (>10 kg) in this work. X-ray diffraction (XRD), Rietveld refinement, scanning electron microscopy (SEM), energy dispersive spectrometer (EDS) mapping, particle size distribution and electrochemical tests including cyclic voltammetry (CV) and electrical impedance spectroscopy (EIS) have been used to characterize electrochemical performance of industrial-grade cathode materials. The results of XRD, SEM and EDS mapping characterization indicate that all the modified cathode materials with their Ni, Co and Mn components doped by titanium keep a typical α-NaFeO2 layered structure with R-3m space group and titanium atoms are uniformly distributed in all series of Ti-doped materials as prepared. Electrochemical characterization confirms that the material of 0.2% Ti doping has the best cycling performance and the least capacity loss because of its best cation ordering figured by Rietveld refinement of XRD. The initial discharge capacity of 0.2% Ti doping material achieves 185.0 mA h/g at 1 C between 2.8 and 4.6 V. Additionally, the capacity retention maintains at 93.4% after 200 charge–discharge cycles.

Synchronization of complex networks is an important issue in the study of complex networks. Many existing works reveal that complex networks can reach synchronization under the condition of connected topology; however, by introducing the concept of joint connectivity and sequential connectivity, this brief shows us that complex networks can synchronize even if the topology is not connected at any time instant. Strict technical analysis demonstrates the feasibility of this brief.

This letter studies complete synchronization of two temporal Boolean networks coupled in the drive-response configuration. Necessary and sufficient conditions are provided based on the algebraic representation of Boolean networks. Moreover, the upper bound to check the criterion is given. Finally, an illustrative example shows the efficiency of the proposed results.

Wide-field fluorescence microscopy at high magnification was used to study the intracellular binding site of Rubb16 in Escherichia coli. Upon incubation of E. coli cells at the minimum inhibitory concentration, Rubb16 localised at ribosomes with no significant DNA binding observed. Furthermore, Rubb16 condensed the ribosomes when they existed as polysomes. It is postulated that the condensation of polysomes would halt protein production, and thereby inhibit bacterial growth. The results of this study indicate that the family of inert dinuclear ruthenium complexes Rubbn selectively target RNA over DNA in vivo. Selective RNA targeting could be advantageous for the development of therapeutic agents, and because of differences in ribosome structure between bacteria and eukaryotic cells, the Rubbn complexes could be selectively toxic to bacteria. In support of this hypothesis, the toxicity of Rubb16 was found to be significantly less to liver and kidney cell lines than against a range of bacteria.

Multiple stimuli-responsive fluorescent materials have gained increasing attention for their fundamental investigation and intelligent applications. In this work, we report design and synthesis of a novel polyamic acid bearing oligoaniline, triphenylamine, and fluorene groups, which served as sensitive units and fluorescence emission unit, respectively. The resulting polymer exhibits multiple stimuli-responsive fluorescence switching behavior triggered by redox species, pH, electrochemical, and pressure stimuli. Every fluorescence switching mechanism upon each stimulus was studied in detail. The interactions and energy transfer between sensitive units and emission unit are largely responsible for this fascinating fluorescent switching behavior. This work provides a deep understanding of the optical switching essence upon these stimuli, opening the way for the development of new fluorescent sensing applications.

This brief investigates a pinning control design for the synchronization of two Boolean networks (BNs) coupled in the drive-response configuration. A complete synchronization for BNs can be achieved by changing the columns of the transition matrix of the response BN. Then, pinning nodes can be chosen, and a pinning control design algorithm is proposed. Finally, examples are given to show the effectiveness of the design procedure.

Biomass derived amorphous carbon has received considerable attention in recent years for its great potential applications. In this work, the cellulosic biomass carbon based montmorillonite composite is synthesized by using carbon-bed pyrolysis method. The micro-structure and properties of samples are characterized by Raman, XRD, FT-IR, SEM, TEM and adsorption analyses. The results demonstrates that the montmorillonite components used to enhance the surface performance (granule-layer structure) also has strengthened the Methylene Blue adsorption capacity of biomass carbon in composite, the adsorption capacity is enhanced as the MT concentration increases, the maximum equilibrium value is obtained for 15 wt% montmorillonite mixed biomass carbon composite (93.5 mg/g), which confirms the effects of clay mineral (montmorillonite) on the biomass carbon in carbon-clay composite system. The isotherm data fits the Freundlich isotherm model (R2 = 0.927) corresponding to the physical adsorption (n = 1.214, favorable adsorption). The kinetic data is well described by the intraparticle diffusion model (R2 = 0.939), indicating the intraparticle diffusion controlled adsorption process.

Spinel LiMn2O4 has been synthesized by solid state reaction with industrial grade Mn3O4 and Li2CO3 as precursors without purification, and its electrochemical performance for lithium ion battery has been investigated by CR2025 coin cell. The results of X-ray diffraction (XRD) patterns and scanning electron microscope (SEM) images show that the size of LiMn2O4 particles grow up with increasing temperature of calcination, and the sample synthesized at 800 °C for 12 h has the best crystallinity with a submicron size. It can deliver initial capacity of 112.9 mA h/g with capacity retention ratio of 89.1% after 200 cycles at charge/discharge rate of 1 C. The results of cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) also show that it has the highest electrochemical activity and lowest charge transfer impedance.

Abnormalities in the integral components of bone, including bone matrix, bone mineral and bone cells, give rise to complex disturbances of skeletal development, growth and homeostasis. Non-specific drug delivery using high-dose systemic administration may decrease therapeutic efficacy of drugs and increase the risk of toxic effects in non-skeletal tissues, which remain clinical challenges in the treatment of skeletal disorders. Thus, targeted delivery systems are urgently needed to achieve higher drug delivery efficiency, improve therapeutic efficacy in the targeted cells/tissues, and minimize toxicities in non-targeted cells/tissues. In this review, we summarize recent progress in the application of different targeting moieties and nanoparticles for targeted drug delivery in skeletal disorders, and also discuss the advantages, challenges and perspectives in their clinical translation.

The formation of endothelial lumen is fundamental to angiogenesis and essential to the oxygenation of hypoxic tissues. The molecular mechanism underlying this important process remains obscure. Here, we show that Akt activation by a Ras homolog, R-Ras, stabilizes the microtubule cytoskeleton in endothelial cells leading to endothelial lumenogenesis. The activation of Akt by the potent angiogenic factor VEGF-A does not strongly stabilize microtubules or sufficiently promote lumen formation, hence demonstrating a distinct role for the R-Ras-Akt axis. We show in mice that this pathway is important for the lumenization of new capillaries and microvessels developing in ischemic muscles to allow sufficient tissue reperfusion after ischemic injury. Our work identifies a role for Akt in lumenogenesis and the significance of the R-Ras-Akt signaling for the patency of regenerating blood vessels.

Abstract Bone morphogenetic protein (BMP) signaling is essential for osteogenesis. However, recombinant human BMPs (rhBMPs) exhibit large inter-individual variations in local bone formation during clinical spinal fusion. Smurf1 ubiquitinates BMP downstream molecules for degradation. Here, we classify age-related osteoporosis based on distinct intraosseous BMP-2 levels and Smurf1 activity. One major subgroup with a normal BMP-2 level and elevated Smurf1 activity (BMP-2 n /Smurf1 e ) shows poor response to rhBMP-2 during spinal fusion, when compared to another major subgroup with a decreased BMP-2 level and normal Smurf1 activity (BMP-2 d /Smurf1 n ). We screen a chalcone derivative, i.e., 2-(4-cinnamoylphenoxy)acetic acid, which effectively inhibits Smurf1 activity and increases BMP signaling. For BMP-2 n /Smurf1 e mice, the chalcone derivative enhances local bone formation during spinal fusion. After conjugating to an osteoblast-targeting and penetrating oligopeptide (DSS) 6 , the chalcone derivative promotes systemic bone formation in BMP-2 n /Smurf1 e mice. This study demonstrates a precision medicine-based bone anabolic strategy for age-related osteoporosis.

In this paper, the composite membranes based on poly(vinylidene fluoride) (PVDF) with different amounts of halloysite (HNT) nano-filler were prepared by phase inversion method for the application of lithium ion batteries. The effect of the content of HNT on the crystallinity and morphology of the composite membranes were investigated. The results showed that the crystallization behaviors of the HNT/PVDF composite membranes were reduced with the increase of HNT filler content. Furthermore, the introduction of HNT into PVDF matrix remarkably affected the formation rate of nuclei which could evolve into pores to change surface morphology. The HNT/PVDF composite membranes showed the sufficient porosity and good affinity between the eletrolyte as well as the electrode, which led to superb electrolyte uptake and low interfacial impedance. Among HNT/PVDF composite membranes, in particular, the 4-HNT/PVDF composite membrane with 4 wt% HNT content had a great electrolyte uptake (430.2%), superior electrochemical stability window (4.5 V), high ionic conductivity (2.4 mS/cm), and low interfacial impedance (63Ω). The cells assembled with the 4-HNT/PVDF composite membranes obtain discharge capacities of 164.72 mAh/g (0.1C) and 134.88 mAh/g (2C), corresponding to 96.89% and 79.34% of the theoretical capacity of LiFePO4 (170 mAh/g), respectively, better cycle performance (with capacity retention 89.12% after 100 cycles) at 0.5C and excellent rate performance. It is concluded that the content of HNT deeply affects membrane performance. Therefore, the 4-HNT/PVDF composite membranes could be a good option of high performance lithium ion batteries.

Since calcium and phosphorus play vital roles in a multitude of physiologic systems, disorders of calcium and phosphorus metabolism always lead to severe consequences such as skeletal-related and cardiovascular morbidity, or even life-threatening. Physiologically, the maintenance of calcium and phosphorus homeostasis is achieved via a variety of concerted actions of hormones such as parathyroid hormone (PTH), vitamin D, and fibroblast growth factor (FGF23), which could be regulated mainly at three organs, the intestine, kidney, and bone. Disruption of any organ or factor might lead to disorders of calcium and phosphorus metabolism. Currently, lacking of accurate diagnostic approaches and unknown molecular basis of pathophysiology will result in patients being unable to receive a precise diagnosis and personalized treatment timely. Therefore, it is urgent to identify early diagnostic biomarkers and develop therapeutic strategies. Fortunately, proteomics and metabolomics offer promising tools to discover novel indicators and further understanding of pathological mechanisms. Therefore, in this review, we will give a systematic introduction on PTH-1,25(OH)2D-FGF23 axis in the disorders of calcium and phosphorus metabolism, diagnostic biomarkers identified, and potential altered metabolic pathways involved.

In this paper, pinning controllability for a Boolean network (BN) under arbitrary disturbance inputs is considered. By selecting a fraction of nodes as the pinning nodes and injecting controllers that depend on the values of the disturbance inputs of the previous time instant, the controllability can be guaranteed for any BNs under arbitrary disturbance inputs. First, based on the necessary and sufficient conditions for the controllability of a BN with arbitrary disturbance inputs obtained in this paper, a constructive method for designing the transition matrix of the BN is presented, which further provides a method for selecting the pinning nodes. Second, a logical relationship between the control input nodes and system nodes is provided through solving logical matrix equations. Third, the control input sequence algorithm is also given. Finally, an example is presented to show the effectiveness of the proposed results.

The combination of electride state and superconductivity within the same compound, e.g., [Ca_{24}Al_{28}O_{6}]^{4+}(4e^{-}), opens up a new category of conventional superconductors. However, neither the underlying causations to explain superconducting behaviors nor effects of interstitial quasiatoms (ISQs) on superconductivity remain unclear. Here we have designed an efficient and resource-saving method to identify superconducting electrides only by chemical compositions and bonding characteristics. A representative superconducting electride Li_{6}C with a noteworthy T_{c} of 10 K below 1 Mbar among the known binary electrides has been revealed. Our first-principles studies unveil that the anomalous sp-hybridized cage-state ISQs, as a guest in Li_{6}C, exhibit unexpected ionic and covalent bonds, which act as a chemical precompression to lower dynamically stable pressure. More importantly, we uncover that, contrary to common expectations, the high T_{c} is attributed to the strong electron-phonon coupling derived from the synergy of interatomic coupling effect, phonon softening caused by Fermi surface nesting, and phonon-coupled bands, which are mainly dominated by host sp-hybridized electrons, rather than the ISQs. Our present results elucidate a new superconducting mechanism of electrides and shed light on the way for seeking a high-T_{c} superconductor at lower pressures in cage-state electrides.

In this article, a defense method with watermarking to detect linear deception attack under Kullback-Leibler (K-L) divergence detector in cyber-physical system (CPS) is proposed. It is known that linear deception attacks can reduce the performance of remote estimator without being detected by the K-L divergence detector. In order to detect this kind of attack, we use watermarking to encrypt and decrypt data transmitted through wireless networks. When the attack does not exist, the transmitted data can be restored to ensure the remote estimation performance. In the presence of linear deception attacks, these data are marked with a watermarking so that they can assist the K-L divergence detector to discover the attack. The watermarking encryption method is proved to be helpful for K-L divergence detector to discover attack, or weaken the impact of the attack in different situations. Finally, numerical simulations are provided to further illustrate the results.

The effect of ice structuring protein (ISP) on the gelling properties of myofibrillar protein from quick-frozen pork patty during frozen storage was investigated by determining and comparing protein solubility, turbidity and gel properties. Protein solubility was increased by 10.23% and turbidity was decreased after ISP treated. The gel whiteness and strength of myofibrillar protein from patty with ISP were 8.38% and 13.70% higher than that of the control after frozen for 180 days. And the addition of ISP could weaken the influence of frozen storage on water mobility and reduce the water loss. Furthermore, ISP retrained the decrease in the maximum elastic (G′) value and loss factor (tan δ) value of samples. Through observing by scanning electron microscope (SEM), ISP retarded the destruction of gel microstructure and maintained the relatively complete tissue of gel. These findings confirmed the importance of ISP in myofibrillar protein gel quality assurance of pork patty during frozen storage.