Functional Noncentrosymmetric Nanoparticle-Nanofiber Hybrids via Selective Fragmentation.

Noncentrosymmetric nanostructures are an attractive synthetic target as they can exhibit complex interparticle interactions useful for numerous applications. However, generating uniform, colloidally stable, noncentrosymmetric nanoparticles with low aspect ratios is a significant challenge using solution self-assembly approaches. Herein, we outline the synthesis of noncentrosymmetric multiblock co-nanofibers by subsequent living crystallization-driven self-assembly of block co-polymers, spatially confined attachment of nanoparticles, and localized nanofiber fragmentation. Using this strategy, we have fabricated uniform diblock and triblock noncentrosymmetric π-conjugated nanofiber-nanoparticle hybrid structures. Additionally, in contrast to Brownian motion typical of centrosymmetric nanoparticles, we demonstrated that these noncentrosymmetric nanofibers undergo ballistic motion in the presence of H2O2 and thus could be employed as nanomotors in various applications, including drug delivery and environmental remediation.

Carbon dioxide and weak magnetic field enhance iron-carbon micro-electrolysis combined autotrophic denitrification.

Combining iron-carbon micro-electrolysis and autotrophic denitrification is promising for nitrate removal from wastewater. In this study, four continuous reactors were constructed using CO2 and weak magnetic field (WMF) to address challenges like iron passivation and pH stability. In the reactors with CO2 + WMF (10 and 35 mT), the increase in total nitrogen removal efficiency was significantly higher (96.2 ± 1.6 % and 94.1 ± 2.7 %, respectively) than that of the control (51.6 ± 2.7 %), and Fe3O4 converted to low-density FeO(OH) and FeCO3, preventing passivation film formation. The WMF application decreased the N2O emissions flux by 8.7 % and 20.5 %, respectively. With CO2 + WMF, the relative enzyme activity and abundance of denitrifying bacteria, especially unclassified_Rhodocyclaceae and Denitratisoma, increased. Thus, this study demonstrates that CO2 and WMF optimize the nitrate removal process, significantly enhancing removal efficiency, reducing greenhouse gas emissions, and improving process stability.

Enhancing crystal integrity and structural rigidity of CsPbBr3 nanoplatelets to achieve a narrow color-saturated blue emission.

Quantum-confined CsPbBr3 perovskites are promising blue emitters for ultra-high-definition displays, but their soft lattice caused by highly ionic nature has a limited stability. Here, we endow CsPbBr3 nanoplatelets (NPLs) with atomic crystal-like structural rigidity through proper surface engineering, by using strongly bound N-dodecylbenzene sulfonic acid (DBSA). A stable, rigid crystal structure, as well as uniform, orderly-arranged surface of these NPLs is achieved by optimizing intermediate reaction stage, by switching from molecular clusters to mono-octahedra, while interaction with DBSA resulted in formation of a CsxO monolayer shell capping the NPL surface. As a result, both structural and optical stability of the CsPbBr3 NPLs is enhanced by strong covalent bonding of DBSA, which inhibits undesired phase transitions and decomposition of the perovskite phase potentially caused by ligand desorption. Moreover, rather small amount of DBSA ligands at the NPL surface results in a short inter-NPL spacing in their closely-packed films, which facilitates efficient charge injection and transport. Blue photoluminescence of the produced CsPbBr3 NPLs is bright (nearly unity emission quantum yield) and peaks at 457 nm with an extremely narrow bandwidth of 3.7 nm at 80 K, while the bandwidth of the electroluminescence (peaked at 460 nm) also reaches a record-narrow value of 15 nm at room temperature. This value corresponds to the CIE coordinates of (0.141, 0.062), which meets Rec. 2020 standards for ultra-high-definition displays.

Entropy-Driven Strongly Confined Low-Toxicity Pure-Red Perovskite Quantum Dots for Spectrally Stable Light-Emitting Diodes.

Spectrally stable pure-red perovskite quantum dots (QDs) with low lead content are essential for high-definition displays but are difficult to synthesize due to QD self-purification. Here, we make use of entropy-driven quantum-confined pure-red perovskite QDs to fabricate light-emitting diodes (LEDs) that have low toxicity and are efficient and spectrum-stable. Based on experimental data and first-principles calculations, multiple element alloying results in a 60% reduction in lead content while improving QD entropy to promote crystal stability. Entropy-driven QDs exhibit photoluminescence with 100% quantum yields and single-exponential decay lifetimes without alteration of their morphology or crystal structure. The pure-red LEDs utilizing entropy-driven QDs have spectrally stable electroluminescence, achieving a brightness of 4932 cd/m2, a maximum external quantum efficiency of over 20%, and a 15-fold longer operational lifetime than the CsPbI3 QD-based LEDs. These achievements demonstrate that entropy-driven QDs can mitigate local compositional heterogeneity and ion migration.

Triple Ligand Engineered Gold Nanoclusters with Enhanced Fluorescence and Device Compatibility for Efficient Electroluminescence Light-Emitting Diodes.

Gold nanoclusters (Au NCs) are potential emitters for electroluminescent light-emitting diodes (EL-LEDs) but restricted by the limited photoluminescence quantum yield (PLQY) and poor device compatibility. Herein, triple ligand engineered Au NCs enable the fabrication of Au NC-based LEDs with improved EL efficiency. Rigidified triple ligand shells greatly reduce the nonradiative transition and thus increase the PLQY of Au NCs from 2.1 to 73.4%. Most importantly, this strategy significantly improves the compatibility between Au NCs and charge transport materials in EL-LED fabrication. As a result, the EL-LEDs reach a maximum brightness of 1104 cd/m2 and an external quantum efficiency of 5.1%, which is the highest recorded for any reported Au NC-based EL-LEDs.

In vitro models to measure effects on intestinal deconjugation and transport of mixtures of bile acids.

Bile acid metabolism and transport are critical to maintain bile acid homeostasis and host health. In this study, it was investigated if effects on intestinal bile acid deconjugation and transport can be quantified in vitro model systems using mixtures of bile acids instead of studying individual bile acids. To this end deconjugation of mixtures of selected bile acids in anaerobic rat or human fecal incubations and the effect of the antibiotic tobramycin on these reactions was studied. In addition, the effect of tobramycin on the transport of the bile acids in isolation or in a mixture across Caco-2 cell layers was characterized. The results demonstrate that both the reduction of bile acid deconjugation and transport by tobramycin can be adequately detected in vitro systems using a mixture of bile acids, thus eliminating the need to characterize the effects for each bile acid in separate experiments. Subtle differences between the experiments with single or combined bile acids point at mutual competitive interactions and indicate that the use of bile acid mixtures is preferred over use of single bile acid given that also in vivo bile acids occurs in mixtures.

Enhanced fractional order sliding mode control for a class of fractional order uncertain systems with multiple mismatched disturbances.

To improve the control performance of the fractional order uncertain systems with multiple mismatched disturbances, an enhanced fractional order sliding mode control (FOSMC) method is developed in this paper. The multiple disturbances and uncertainties are estimated by the finite-time disturbance observers (FTDO) and a fractional order extended state observer (FOESO), respectively. A fractional order switching law is designed to provide a fast convergence mode for the system states. Then a novel FOSMC law is developed by incorporating the feedforward compensation, the fractional order switching law, and the auxiliary state for input saturation. The proposed method is applied to numerical examples and to a motor speed control problem. The effectiveness of the proposed method is demonstrated by the performance comparisons with some existing control methods.

Mimicking bone matrix through coaxial electrospinning of core-shell nanofibrous scaffold for improving neurogenesis bone regeneration.

There is a significant clinical demand for bone repair materials with high efficacy. This study was designed to fabricate nanofibrous scaffolds to promote bone defect regeneration using magnesium doped mesoporous bioactive glass (MBG), a fusion protein Osteocalcin-Osteopontin-Biglycan (OOB), silk fibroin (SF) and nerve growth factor (NGF) for facilitating accelerated bone formation. We found that MBG adsorbed with OOB (OOB@MBG) as core, and SF adsorbed with NGF (SF@NGF) as shell to fabricate the nanofibrous scaffolds (OOB@MBG/NGF@SF) through coaxial electrospinning. OOB@MBG/NGF@SF scaffolds could effectively mimic the component and structure of bone matrix. Interestingly, we observed that OOB@MBG/NGF@SF scaffolds could substantially promote bone mesenchymal stem cells (BMSCs) osteogenesis through stimulating Erk1/2 activated Runx2 and mTOR pathway, and it could also activate the expression level of various osteogenic marker genes. Intriguingly, OOB@MBG/NGF@SF scaffolds could also enhance BMSCs induced neural differentiation cells differentiated into neuron, and activate the expression of the different neuron specific marker genes. Moreover, it was found that OOB@MBG/NGF@SF scaffolds accelerated bone regeneration with neurogenesis, and new neurons were formed in Haversian canal in vivo. Consistent with these observations, we found that Erk1/2 and mTOR signaling pathways also regulated osteogenesis with the neurogenesis process from RNA sequencing result. Overall, our findings provided novel evidence suggesting that OOB@MBG/NGF@SF scaffolds could function as a potential biomaterial in accelerating bone defect regeneration with neurogenesis, as well as in recovering the motor ability and improving the quality of life of patients.

The Effect of Angiogenesis-Based Scaffold of MesoporousBioactive Glass Nanofiber on Osteogenesis.

There is still an urgent need for more efficient biological scaffolds to promote the healing of bone defects. Vessels can accelerate bone growth and regeneration by transporting nutrients, which is an excellent method to jointly increase osteogenesis and angiogenesis in bone regeneration. Therefore, we aimed to prepare a composite scaffold that could promote osteogenesis with angiogenesis to enhance bone defect repair. Here, we report that scaffolds were prepared by coaxial electrospinning with mesoporous bioactive glass modified with amino (MBG-NH2) adsorbing insulin-like growth factor-1 (IGF-1) as the core and silk fibroin (SF) adsorbing vascular endothelial growth factor (VEGF) as the shell. These scaffolds were named MBG-NH2/IGF@SF/VEGF and might be used as repair materials to promote bone defect repair. Interestingly, we found that the MBG-NH2/IGF@SF/VEGF scaffolds had nano-scale morphology and high porosity, as well as enough mechanical strength to support the tissue. Moreover, MBG-NH2 could sustain the release of IGF-1 to achieve long-term repair. Additionally, the MBG-NH2/IGF@SF/VEGF scaffolds could significantly promote the mRNA expression levels of osteogenic marker genes and the protein expression levels of Bmp2 and Runx2 in bone marrow mesenchymal stem cells (BMSCs). Meanwhile, the MBG-NH2/IGF@SF/VEGF scaffolds promoted osteogenesis by simulating Runx2 transcription activity through the phosphorylated Erk1/2-activated pathway. Intriguingly, the MBG-NH2/IGF@SF/VEGF scaffolds could also significantly promote the mRNA expression level of angiogenesis marker genes and the protein expression level of CD31. Furthermore, RNA sequencing verified that the MBG-NH2/IGF@SF/VEGF scaffolds had excellent performance in promoting bone defect repair and angiogenesis. Consistent with these observations, we found that the MBG-NH2/IGF@SF/VEGF scaffolds demonstrated a good repair effect on a critical skull defect in mice in vivo, which not only promoted the formation of blood vessels in the haversian canal but also accelerated the bone repair process. We concluded that these MBG-NH2/IGF@SF/VEGF scaffolds could promote bone defect repair under accelerating angiogenesis. Our finding provides a new potential biomaterial for bone tissue engineering.

In vitro models to detect in vivo bile acid changes induced by antibiotics.

Bile acid homeostasis plays an important role in many biological activities through the bile-liver-gut axis. In this study, two in vitro models were applied to further elucidate the mode of action underlying reported in vivo bile acid changes induced by antibiotics (colistin sulfate, tobramycin, meropenem trihydrate, and doripenem hydrate). 16S rRNA analysis of rat fecal samples anaerobically incubated with these antibiotics showed that especially tobramycin induced changes in the gut microbiota. Furthermore, tobramycin was shown to inhibit the microbial deconjugation of taurocholic acid (TCA) and the transport of TCA over an in vitro Caco-2 cell layer used as a model to mimic intestinal bile acid reuptake. The effects induced by the antibiotics in the in vitro model systems provide novel and complementary insight explaining the effects of the antibiotics on microbiota and fecal bile acid levels upon 28-day in vivo treatment of rats. In particular, our results provide insight in the mode(s) of action underlying the increased levels of TCA in the feces upon tobramycin exposure. Altogether, the results of the present study provide a proof-of-principle on how in vitro models can be used to elucidate in vivo effects on bile acid homeostasis, and to obtain insight in the mode(s) of action underlying the effect of an antibiotic, in this case tobramycin, on bile acid homeostasis via effects on intestinal bile acid metabolism and reuptake.

Hepatic bile acid synthesis and secretion: Comparison of in vitro methods.

Reliable hepatic in vitro systems are crucial for the safety assessment of xenobiotics. Certain xenobiotics decrease the hepatic bile efflux, which can ultimately result in cholestasis. Preclinical animal models and the currently available in vitro systems poorly predict a xenobiotic's cholestatic potential. Here, we compared the phenotype and capacity of three liver derived in vitro systems to emulate human functionality to synthesize and secrete bile acids (BAs). To this end, basal BA production of sandwich cultured human hepatocytes (SCHHs), HepaRG cells (HepaRGs) and hepatocyte-like intrahepatic cholangiocyte organoids (ICO-heps) were analysed, and the effect of the known BSEP (Bile Salt Export Pump)-inhibitors bosentan and lopinavir on BA disposition in SCHHs and HepaRGs was quantified. RT-qPCR of selected target genes involved in maturation status, synthesis, transport and conjugation of BAs was performed to mechanistically underpin the observed differences in BA homeostasis. ICO-heps produced a (very) low amount of BAs. SCHHs are a powerful tool in cholestasis-testing due to their high basal BA production and high transporter expression compared to the other models tested. HepaRGs were responsive to both selected BSEP-inhibitors and produced a BA profile that is most similar to the human in vivo situation, making them a suitable and practical candidate for cholestasis-testing.

PCL nanofibrous incorporating unique matrix fusion protein adsorbed mesoporous bioactive glass for bone tissue engineering.

Mesoporous bioactive glass (MBG) is a potential biomedical material in bone defect repairment because of its bioactivity, biocompatibility, and osteoinduction properties. Here we report that Mg-doped MBG scaffold with 3:1 Ca/Mg ratio (MBG-Ca/Mg-3) is good for MC3T3-E1 osteoblast differentiation and mineralization. Mimicking bone extracellular matrix structure by electrospinning, we used MBG-Ca/Mg-3 adsorbed with Osteocalcin-Osteopontin-Biglycan (OOB), a new unique matrix fusion protein, to form OOB@MBG-Ca/Mg-3 scaffold, which has multifunctional ability in calvarial bone defect repairment in vivo. Intriguingly, we found that OOB@MBG-Ca/Mg-3 scaffold increases the expression of osteoblastic marker genes, including bone morphogenetic protein (Bmp2), osteopontin (Opn), Osterix, Runx2 through activation of ERK1/2. We concluded that OOB@MBG-Ca/Mg-3 scaffold promotes osteoblast differentiation and mineralization through ERK1/2 pathway and it can also enhance bone formation in vivo, which provides a new biomaterial in bone tissue engineering.

Exposure to the mycotoxin deoxynivalenol reduces the transport of conjugated bile acids by intestinal Caco-2 cells.

Conjugated bile acids are synthesized in liver and subsequently secreted into the intestinal lumen from which they are actively reabsorbed and transported back to liver. The efficient enterohepatic circulation of conjugated bile acids is important to maintain homeostasis. The mycotoxin deoxynivalenol (DON) is a fungal secondary metabolite that contaminates cereal food. Upon human exposure, it can cause intestinal dysfunction. We explored the effects of DON exposure on the intestinal absorption of conjugated bile acids and the expression of bile acid transporters using an in vitro model based on Caco-2 cell layers grown in transwells. Our study shows that the transport rate of taurocholic acid (TCA) is decreased after 48-h pre-exposure of the Caco-2 cells to 2 µM DON, which is a realistic intestinal DON concentration. Exposure to DON downregulates expression of the genes coding for the apical sodium-dependent bile acid transporter (ASBT), the ileal bile acid-binding protein (IBABP) and the organic solute transporter α (OSTα), and it counteracts the agonist activity of Farnesoid X receptor (FXR) agonist GW4064 on these genes. In addition, the transport of ten taurine or glycine-conjugated bile acids in a physiological relevant mixture by the intestinal Caco-2 cell layers was decreased after pre-exposure of the cells to DON, pointing at a potential for DON-mediated accumulation of the conjugated bile acids at the intestinal luminal side. Together the results reveal that DON inhibits intestinal bile acid reabsorption by reducing the expression of bile acid transporters thereby affecting bile acid intestinal kinetics, leading to bile acid malabsorption in the intestine. Our study provides new insights into the hazards of DON exposure.

Design of novel functionalized collagen-chitosan-MBG scaffolds for enhancing osteoblast differentiation in BMSCs.

Collagen and chitosan are two different kinds of natural biodegradable polymers commonly used in the regeneration of bone defects. Mesoporous bioactive glass (MBG) is a type of favorable bone filler which can effectively constitute an enlarged microenvironment to facilitate an exchange of important factors between the cells and scaffolds. Here we prepared a collagen-chitosan-MBG (C-C-MBG) scaffold which displayed significantly increased proliferation, differentiation and mineralization in bone mesenchymal stem cells (BMSCs). Additionally, we found that the scaffold can stimulate extra-cellular signal regulated kinase 1/2 (Erk1/2) activated Runx2 pathway, which is the predominant signaling pathway involved in osteoblast differentiation. Consistently, we observed that the scaffold can markedly enhance the expression ofType I collagen, Osteopontin(Opn), andRunx2, which are important osteoblastic marker genes implicated in the process of osteoblast differentiation. Therefore, we conclude that the composite scaffold can significantly promote the differentiation of BMSCs into osteoblasts by activating Erk1/2-Runx2 pathway. Our finding thereby implies that the C-C-MBG scaffold can possibly act as a potential biomaterial in the bone regeneration.

A sensitive bio-barcode immunoassay based on bimetallic Au@Pt nanozyme for detection of organophosphate pesticides in various agro-products.

Organophosphate pesticides (OPs) are often used as insecticides and acaricides in agriculture, thus improving yields. OP residues may pose a serious threat, duetoinhibitionof the enzymeacetylcholinesterase(AChE). Therefore, a competitive bio-barcode immunoassay was designed for simultaneous quantification of organophosphate pesticide residues using AuNP signal amplification technology and Au@Pt catalysis. The AuNP probes were labelled with antibodies and corresponding bio-barcodes (ssDNAs), MNP probes coated with ovalbumin pesticide haptens and Au@Pt probes functionalized with the complementary ssDNAs were then prepared. Subsequently, pesticides competed with MNP probes to bind the AuNP probes. The recoveries of the developed assay were ranged from 71.26 to 117.47% with RSDs from 2.52 to 14.52%. The LODs were 9.88, 3.91, and 1.47 ng·kg-1, for parathion, triazophos, and chlorpyrifos, respectively. The assay was closely correlated with the data obtained from LC-MS/MS. Therefore, the developed method has the potential to be used as an alternative approach for detection of multiple pesticides.

3D printing silk-gelatin-propanediol scaffold with enhanced osteogenesis properties through p-Smad1/5/8 activated Runx2 pathway.

The application of 3 D printing technology in tissue engineering has become increasingly important. However, due to the limitations of bio-ink, there are still some remaining problems. For example, the major challenge for ideal bio-ink is to maintain stable 3 D structure and good biocompatibility in the meantime while conventional gels are week and nearly unprintable. So, the development of new bio-ink material with improved rheological and mechanical properties is highly demanded to avoid compromising biocompatibility for tissue engineering. Silk fibroin (SF), a natural degradable polymer, is considered to be a proper material for the preparation of bio-inks. We used SF, gelatin, and polyols as raw materials to fabricate bio-inks and scaffolds. We evaluated the rheological properties and printability of bio-inks with a rotational rheometer and a 3 D printer. The scaffolds were prepared by crosslinking and freeze-drying technologies. The biocompatibility and osteoinductive functions of scaffolds were investigated by evaluating proliferation, osteogenic differentiation and related cell signaling of cultured MC3T3-E1 cells. The results showed that the scaffolds using SF, Gel and propanediol (PG) not only had good rheological properties and storage modulus, but also could better enhance osteogenic specific genes expression mediated by Smad1/5/8 and Runx2 pathways. What is more, morphological characterization showed that α-mem incubation could help scaffold form porous structure on its surface, which could shed a light on a new 3 D bio-printed bone repair scaffold with both naturally emerged and CAD-designed porous structure. Our findings provide a potential biomaterial for the treatment of bone tissue regeneration.

A Simplified Fractional Order PID Controller's Optimal Tuning: A Case Study on a PMSM Speed Servo.

A simplified fractional order PID (FOPID) controller is proposed by the suitable definition of the parameter relation with the optimized changeable coefficient. The number of the pending controller parameters is reduced, but all the proportional, integral, and derivative components are kept. The estimation model of the optimal relation coefficient between the controller parameters is established, according to which the optimal FOPID controller parameters can be calculated analytically. A case study is provided, focusing on the practical application of the simplified FOPID controller to a permanent magnet synchronous motor (PMSM) speed servo. The dynamic performance of the simplified FOPID control system is tested by motor speed control simulation and experiments. Comparisons are performed between the control systems using the proposed method and those using some other existing methods. According to the simulation and experimental results, the simplified FOPID control system achieves the optimal dynamic performance. Therefore, the validity of the proposed controller structure and tuning method is demonstrated.

Fractional order active disturbance rejection control with the idea of cascaded fractional order integrator equivalence.

This paper presents a fractional order (FO)-active disturbance rejection control (ADRC) with a FO extended state observer (FOESO) design. Applying this FOESO, a typical second order motion plant can be converted into a cascadedfractionalorderintegrator(1∕s2r;0

Synthesis of fractional order robust controller based on Bode's ideas.

The basic Bode's ideal transfer function (BITF) based controller may not guarantee sufficient disturbance rejection for a class of plants with a cascaded integrator. In this paper, an improved BITF based control method is proposed to enhance the disturbance rejection performance for this class of control systems. A fractional order proportional-integral controller and a Bode's ideal cut-off filter are introduced into the BITF based control strategy, improving the open-loop magnitude characteristics of the control system in the low and high frequency ranges. Therefore, the disturbance rejection performance of the control system can be improved, with small impact on the system's stability. The improved BITF based control method is applied to the speed control problem of a class of permanent magnet synchronous motor servo systems. The robustness and dynamic response performances of the improved BITF based control system are verified by simulation and experiments. Performance comparisons are performed between the system using the improved BITF based control method and those using some existing control methods. Simulation and experimental results both show that the improved BITF based controller can enhance the step response performance and robustness of the PMSM servo system simultaneously and make the system achieve better disturbance rejection performance than the systems using some existing methods.

Promising targets based on pattern recognition receptors for cancer immunotherapy.

Pattern recognition receptors (PRRs) recognize pathogen-associated as well as endogenous damage-associated molecular patterns. Once ligand binding occurs, signaling cascades develop within the cells to activate effector molecules. Thus, PRRs play key roles in immune surveillance and immune tolerance. Due to their differences in cell localization, stage of action, and ligand recognition, PRRs form a defense network from the cell membrane to the cytoplasm, constituting the regulatory networks of the innate and adaptive immune systems in cancer. However, the activation of PRRs cannot only recruit and activate anti-tumor immune cells, but also promote the release of inflammatory cytokines, which may lead to the formation of the local inflammatory microenvironment in tumors, thus promoting the development of cancer. Therefore, the dual regulation of PRRs in the immune system has attracted much attention, with current research being focused on maximizing their anti-tumor immune activity. In addition to their expression in host cells, PRRs are also expressed in tumor cells; this is closely related to the occurrence and development of cancer. This review attempts to clarify the feasibility and directions for the development of PRR-based applications in cancer immunotherapy by elaborating on the mechanisms underlying the action of PRRs and the current status of immunotherapies.