Bioinspired Passive Tactile Sensors Enabled by Reversible Polarization of Conjugated Polymers

Tactile perception plays a vital role for the human body and is also highly desired for smart prosthesis and advanced robots.Compared to active sensing devices,passive piezoelectric and triboelectric tactile sensors consume less power,but lack the capability to resolve static stimuli.Here,we address this issue by utilizing the unique polarization chemistry of conjugated polymers for the first time and propose a new type of bioinspired,passive,and bio-friendly tactile sensors for resolving both static and dynamic stimuli.Specifically,to emulate the polarization process of natural sensory cells,conjugated polymers(including poly(3,4-ethylenedioxythiophen e):poly(styrenesulfonate),polyaniline,or polypyrrole)are controllably polarized into two opposite states to create artificial potential differences.The controllable and reversible polarization process of the conjugated polymers is fully in situ characterized.Then,a micro-structured ionic electrolyte is employed to imitate the natural ion channels and to encode external touch stimulations into the variation in potential difference outputs.Compared with the currently existing tactile sensing devices,the developed tactile sensors feature distinct characteristics including fully organic composition,high sensitivity(up to 773 mV N^(−1)),ultralow power consumption(nW),as well as superior bio-friendliness.As demonstrations,both single point tactile perception(surface texture perception and material property perception)and two-dimensional tactile recognitions(shape or profile perception)with high accuracy are successfully realized using self-defined machine learning algorithms.This tactile sensing concept innovation based on the polarization chemistry of conjugated polymers opens up a new path to create robotic tactile sensors and prosthetic electronic skins.

A Stable Open-Shell Conjugated Diradical Polymer with Ultra-High Photothermal Conversion Efficiency for NIR-Ⅱ Photo-Immunotherapy of Metastatic Tumor

Massive efforts have been concentrated on the advance of eminent near-infrared(NIR) photothermal materials(PTMs) in the NIR-Ⅱ window(1000–1700 nm), especially organic PTMs because of their intrinsic biological safety compared with inorganic PTMs. However, so far, only a few NIR-Ⅱresponsive organic PTMs was explored, and their photothermal conversion efficiencies(PCEs) still remain relatively low. Herein, donor–acceptor conjugated diradical polymers with open-shell characteristics are explored for synergistically photothermal immunotherapy of metastatic tumors in the NIR-Ⅱ window. By employing side-chain regulation, the conjugated diradical polymer TTB-2 with obvious NIR-Ⅱ absorption was developed, and its nanoparticles realize a record-breaking PCE of 87.7% upon NIR-Ⅱ light illustration. In vitro and in vivo experiments demonstrate that TTB-2 nanoparticles show good tumor photoablation with navigation of photoacoustic imaging in the NIR-Ⅱ window, without any side-effect. Moreover, by combining with PD-1 antibody,the pulmonary metastasis of breast cancer is high-effectively prevented by the efficient photo-immunity effect. Thus, this study explores superior PTMs for cancer metastasis theranostics in the NIR-Ⅱ window, offering a new horizon in developing radical-characteristic NIR-Ⅱ photothermal materials.

Recent advances and innovations in the design and fabrication of wearable flexible biosensors and human health monitoring systems based on conjugated polymers

Wearable biosensors have received great interest as patient-friendly diagnostic technologies because of their high flexibility and conformability.The growing research and utilization of novel materials in designing wearable biosensors have accelerated the development of point-of-care sensing platforms and implantable biomedical devices in human health care.Among numerous potential materials,conjugated polymers(CPs)are emerging as ideal choices for constructing high-performance wearable biosensors because of their outstanding conductive and mechanical properties.Recently,CPs have been extensively incorporated into various wearable biosensors to monitor a range of target biomolecules.However,fabricating highly reliable CP-based wearable biosensors for practical applications remains a significant challenge,necessitating novel developmental strategies for enhancing the viability of such biosensors.Accordingly,this review aims to provide consolidated scientific evidence by summarizing and evaluating recent studies focused on designing and fabricating CP-based wearable biosensors,thereby facilitating future research.Emphasizing the superior properties and benefits of CPs,this review aims to clarify their potential applicability within this field.Furthermore,the fundamentals and main components of CP-based wearable biosensors and their sensing mechanisms are discussed in detail.The recent advancements in CP nanostructures and hybridizations for improved sensing performance,along with recent innovations in next-generation wearable biosensors are highlighted.CPbased wearable biosensors have been—and will continue to be—an ideal platform for developing effective and user-friendly diagnostic technologies for human health monitoring.

Hydroxychloroquine and a low antiresorptive activity bisphosphonate conjugate prevent and reverse ovariectomy-induced bone loss in mice through dual antiresorptive and anabolic effects

Osteoporosis remains incurable.The most widely used antiresorptive agents,bisphosphonates(BPs),also inhibit bone formation,while the anabolic agent,teriparatide,does not inhibit bone resorption,and thus they have limited efficacy in preventing osteoporotic fractures and cause some side effects.

Effect of electron-electron interaction on polarization process of exciton and biexciton in conjugated polymer

By using one-dimensional tight-binding model modified to include electron-electric field interaction and electron-electron interaction,we theoretically explore the polarization process of exciton and biexciton in cis-polyacetylene.The dynamical simulation is performed by adopting the non-adiabatic evolution approach.The results show that under the effect of moderate electric field,when the strength of electron-electron interaction is weak,the singlet exciton is stable but its polarization presents obvious oscillation.With the enhancement of interaction,it is dissociated into polaron pairs,the spin-flip of which can be observed through modulating the interaction strength.For the triplet exciton,the strong electron-electron interaction restrains its normal polarization,but it is still stable.In the case of biexciton,the strong electron-electron interaction not only dissociate it,but also flip its charge distribution.The yield of the possible states formed after the dissociation of exciton and biexciton is also calculated.

Conjugated microporous polymers-scaffolded enzyme cascade systems with enhanced catalytic activity

Enhancing catalytic activity of multi-enzyme in vitro through substrate channeling effect is promis-ing yet challenging.Herein,conjugated microporous polymers(CMPs)-scaffolded integrated en-zyme cascade systems(I-ECSs)are constructed through co-entrapping glucose oxidase(GOx)and horseradish peroxidase(HRP),in which hydrogen peroxide(H_(2)O_(2)) is the intermediate product.The interplay of low-resistance mass transfer pathway and appropriate pore wall-H_(2)O_(2) interactions facilitates the directed transfer of H_(2)O_(2),resulting in 2.4-fold and 5.0-fold elevation in catalytic activ-ity compared to free ECSs and separated ECSs,respectively.The substrate channeling effect could be regulated by altering the mass ratio of GOx to HRP.Besides,I-ECSs demonstrate excellent stabili-ties in harsh environments and multiple recycling.

Design of pH-responsive antimicrobial peptide melittin analog-camptothecin conjugates for tumor therapy

Melittin,a classical antimicrobial peptide,is a highly potent antitumor agent.However,its significant toxicity seriously hampers its application in tumor therapy.In this study,we developed novel melittin analogs with pH-responsive,cell-penetrating and membranelytic activities by replacing arginine and lysine with histidine.After conjugation with camptothecin(CPT),CPT-AAM-1 and CPT-AAM-2 were capable of killing tumor cells by releasing CPT at low concentrations and disrupting cell membranes at high concentrations under acidic conditions.Notably,we found that the C-terminus of the melittin analogs was more suitable for drug conjugation than the N-terminus.CPT-AAM-1 significantly suppressed melanoma growth in vivo with relatively low toxicity.Collectively,the present study demonstrates that the development of antitumor drugs based on pH-responsive antimicrobial peptide-drug conjugates is a promising strategy.

Antibody-platinum(IV)prodrugs conjugates for targeted treatment of cutaneous squamous cell carcinoma

Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.

Co and postseismic fault slip models of the 2022 M_(W)6.7 Menyuan earthquake reveal conjugated faulting tectonics at the central section of the Lenglongling fault

The 2022 M_(W)6.7 Menyuan earthquake ruptured the western end of the Tianzhu seismic gap,providing an opportunity to study the regional seismogenic characteristics and seismic hazards.Here we use interferometric synthetic aperture radar(InSAR)and seismic data to study the mainshock rupture,early afterslip and the second largest aftershock of the 2022 Menyuan earthquake sequences.Our modeling results show that the mainshock ruptured the Lenglongling fault and the Tuolaishan fault with a maximum slip of~3 m.Rapid postseismic transient deformation occurred at the center of the Lenglongling fault.Our afterslip modeling reveals that the majority of afterslip occurred in the deeper part of the Lenglongling fault.A high-angle conjugated faulting event is found at the middle section of the Lenglongling fault.We use the stress inversion to investigate the possible triggering mechanism of the conjugated rupture event.The results indicate the maximum principal stress direction is in~222°,forming a~22°angle between the conjugated fault of second largest aftershock and the mainshock.The calculated normal stress changes indicate the region is within a pull-apart stress field,which favors such a conjugated rupturing event.Our study will help understand the rupture behavior of such kind of conjugated fault in other regions.

Magnetohydrodynamic Conjugate Free Convective Heat Transfer Analysis of an Isothermal Horizontal Circular Cylinder with Temperature Dependent Viscosity

Heat transfers due to MHD-conjugate free convection from the isothermal horizontal circular cylinder while viscosity is a function of temperature is investigated. The governing equations of the flow and connected boundary conditions are made dimensionless using a set of non-dimensional parameters. The governing equations are solved numerically using the finite difference method. Numerical results are obtained for various values of viscosity variation parameter, Prandtl number, magnetic parameter, and conjugate conduction parameter for the velocity and the temperature within the boundary layer as well as the skin friction coefficients and heat transfer rate along the surface.

5-year vaccine protection following a single dose of Vi-tetanus toxoid conjugate vaccine in Bangladeshi children(TyVOID):a cluster randomised trial

Background:WHO currently recommends a single dose of typhoid conjugate vaccine(TCV)in high-burden countries based on 2-year vaccine efficacy data from large randomised controlled trials.Given the decay of immunogenicity,the protection beyond 2 years is unknown.We therefore extended the follow-up of the TyVAC trial in Bangladesh to assess waning of vaccine protection to 5 years after vaccination.

Blind Deconvolution Method Based on Precondition Conjugate Gradients

In seismic data processing, blind deconvolution is a key technology. Introduced in this paper is a flow of one kind of blind deconvolution. The optimal precondition conjugate gradients (PCG) in Kyrlov subspace is also used to improve the stability of the algorithm. The computation amount is greatly decreased.

Three-dimensional conjugate gradient inversion of magnetotelluric sounding data

Based on the analysis of the conjugate gradient algorithm, we implement a threedimensional （3D） conjugate gradient inversion algorithm with magnetotelluric impedance data. During the inversion process, the 3D conjugate gradient inversion algorithm doesn＇ t need to compute and store the Jacobian matrix but directly updates the model from the computation of the Jacobian matrix. Requiring only one forward and four pseudo-forward modeling applications per frequency to produce the model update at each iteration, this algorithm efficiently reduces the computation of the inversion. From a trial inversion with synthetic magnetotelluric data, the validity and stability of the 3D conjugate gradient inversion algorithm is verified.

Synthesis of CuAPTPP-TDI-TiO2 Conjugated Microspheres and its Photocatalytic Activity

The metal complex 5-（4-aminophenyl）-10,15,20-triphenylporphyrin copper （CuAPTPP） was covalently linked on the surface of TiO2 microspheres by using toluene disocyanate （TDI） as a bridging bond unit. The hydroxyl group （-OH） of TiO2 microspheres surface and the amino group （-NH2） of CuAPTPP reacted respectively with the active -NCO groups of TDI to form a surface conjugated microsphere CuAPTPP-TDI-TiO2 that was confirmed by FT-IR spectra. The CuAPTPP-TDI-TiO2 microspheres were characterized with UV-visible, elemental analysis, XRD, SEM, and UV-Vis diffuse reflectance spectra. The effect of amounts of linked TDI on the performance of photocatalytic microspheres was discussed, and the optimal molar ratio of TDI：TiO2 was established. The photocatalytic activity of CuAPTPP- TDI-TiO2 was evaluated using the photocatalytic degradation of methylene blue （MB） under visible-light irradiation. The results showed that, TDI, as a bond unit, was used to form a steady chemical brigdging bond linking CuAPTPP and the surface of TiO2 microspheres, and the prepared catalyst exhibited higher photocatalytic activity under visible-light irradiation for MB degradation. The degradation rate of 20 mg/L MB could reach 98.7% under Xe- lamp （150 W） irradiation in 120 rain. The degradation of MB followed the first-order reaction model under visible light irradiation, and the rate constant of 5.1× 10^-2 min-1 and the half- life of 11.3 min were achieved. And the new photocatalyst can be recycled for 4 times, remaining 90.0% MB degradation rate.

Conjugate gradient and cross-correlation based least-square reverse time migration and its application

Although conventional reverse time migration can be perfectly applied to structural imaging it lacks the capability of enabling detailed delineation of a lithological reservoir due to irregular illumination. To obtain reliable reflectivity of the subsurface it is necessary to solve the imaging problem using inversion. The least-square reverse time migration （LSRTM） （also known as linearized refleetivity inversion） aims to obtain relatively high-resolution amplitude preserving imaging by including the inverse of the Hessian matrix. In practice, the conjugate gradient algorithm is proven to be an efficient iterative method for enabling use of LSRTM. The velocity gradient can be derived from a cross-correlation between observed data and simulated data, making LSRTM independent of wavelet signature and thus more robust in practice. Tests on synthetic and marine data show that LSRTM has good potential for use in reservoir description and four-dimensional （4D） seismic images compared to traditional RTM and Fourier finite difference （FFD） migration. This paper investigates the first order approximation of LSRTM, which is also known as the linear Born approximation. However, for more complex geological structures a higher order approximation should be considered to improve imaging quality.

Effect of Liposome Double-Coated with Chitosan and Chitosan-EDTA Conjugates on Oral Absorption of Insulin

Aim To evaluate the gastrointestinal uptake of the insulin liposomes double-coated with chitosan （Ch） and chitosan-EDTA conjugates （CEC）, and verify their efficiencies. Methods Insulin-liposomes were prepared by reversed-phase evaporation. The hypoglycemic effects of the insulin liposomes coated with Ch or/and CEC were investigated using the glucose oxidase method after oral administration in diabetic rats, normal rats, and beagle dogs. Serum insulin concentrations in beagle dogs were determined by radioimmunoassay and were assessed by Pkanalyst computer program. Results The animals fed the insulin liposomes coated with Ch or/and CEC were able to regulate better the glucose load than the animals receiving PBS or uncoated insulin liposome, and the regulative effects of the insulin liposomes double-coated with Ch and CEC were better than those of the insulin liposomes coated with Ch or CEC alone. After oral administration of the insulin-liposomes double-coated with Ch and CEC to animals, a significant （P 〈 0. 05 ） blood glucose reduction was observed. Their relative pharmacological bioavailability was higher than 9 % in comparison with subcutaneous injection of insulin. In addition, in comparison with subcutaneous injection of insulin, the relative bioavailability was 12. 67 % calculated by area under the curve of serum insulin concentration versus time profile after oral administration of the insulin-liposomes double-coated with Ch and CEC to beagle dogs. Conclusion The insulin-liposomes double-coated with Ch and CEC were conducive to improving oral bioavailability of insulin.

CT- B Conjugates顺行示踪显色α-晶状体蛋白对损伤后视神经纤维保护作用的实验研究

目的观察α-晶状体蛋白对损伤后视神经纤维的保护作用。方法将成年Long evens大鼠26只,其中10只用于提取α-晶状体蛋白,另外16只分成4组,分别为正常对照组和伤后2,4,6周组,每组4只。损伤神经后分别右眼经玻璃体腔注射浓度为1×10-5g/L的α-晶体蛋白5μl,左眼牛血清白蛋白5μl,分别于伤后2,4,6周进行视神经取材。取材前48h,在每只眼玻璃体腔中注射CT-B(霍乱毒素B亚单位)Conjugates2.5μl,取材固定脱水并行冰冻切片后进行激光共聚焦照相(488nm波长光)观察。结果CTB Conjugates标记的夹伤视神经中可见线状条索神经纤维染色,并呈现一定扭曲,夹杂点状或者小团块状染色。α-晶状体蛋白组的荧光强度显著高于牛血清白蛋白组。结论CTB Conjugates顺染视神经示踪技术是观察和研究损伤后视神经病理变化的有效和简便的方法,α-晶状体蛋白对损伤后的视神经纤维具有保护作用。

Effect of Chitosan-Cysteine Conjugate on Enzymatic Degradation and Hypoglycemic effect of Insulin

Aim To evaluate the inhibitory effect of chitosan-cysteine conjugate onenzymatic degradation and hypogly-cemic enhancement effect of insulin. Methods Chitosan-cysteineconjugate was synthesized. The protective effect of the conjugate against degradation of insulin byα-chymotrypsin and trypsin was evaluated in vitro. Insulin enteric- microspheres were prepared byusing O_1 /Q_2 emulsion solvent evaporation method. The hypoglycemic enhancement effect of theconjugate was studied by oral administration of insulin solution or enteric-microspheres to rats.Results The thiol group content of the synthesized conjugate was about 200 μmol·g^(-1) polymer,which showed a strong protective effect on insulin from enzymatic degradation in vitro. Almost allthe insulin incubated in a-chymotrypsin solution or trypsin solution without chitosan-cysteineconjugate was degraded entirely within 1 h and 5 h respectively, whereas above 75% of insulinremained in the same content of the enzymatic solution containing 4 mg·mL^(-1) conjugate. The drugloading of insulin enteric-microspheres was about 7% . In vivo experiment, chitosan-cysteineconjugate (85 μg·kg^(-1)) prolonged the hypoglycemic time of insulin solution orenteric-microspheres when administered simultaneously with the absorption enhancer SNAC. ConclusionChitosan-cysteine conjugate has a marked inhibitory effect on the enzymatic degradation of insulinin vitro, and it displays a significant hypoglycemic enhancement effect on insulin oral formulationin vivo.

Folate-conjugated Fe_3O_4 nanoparticles for in vivo tumor labeling

Highly biocompatible superparamagnetic Fe3O4 nanoparticles were synthesized by amide of folic acid （FA） ligands and the NH2-group onto the surface of Fe3O4 nanoparticles. The as-synthesized folate-conjugated Fe3O4 nanoparticles were characterized by X-ray diffraction diffractometer, transmission electron microscope, FT-IR spectrometer, vibrating sample magnetometer, and dynamic light scattering instrument. The in vivo labeling effect of folate-conjugated Fe3O4 nanoparticles on the hepatoma cells was investigated in tumor-bearing rat. The results demonstrate that the as-prepared nanoparticles have cubic structure of Fe3O4 with a particle size of about 8 nm and hydrated diameter of 25.7 nm at a saturation magnetization of 51 A·m2/kg. These nanoparticles possess good physiological stability, low cytotoxicity on human skin fibroblasts and negligible effect on Wistar rats at the concentration as high as 3 mg/kg body mass. The folate-conjugated Fe3O4 nanoparticles could be effectively mediated into the human hepatoma Bel 7402 cells through the binding of folate and folic acid receptor, enhancing the signal contrast of tumor tissue and surrounding normal tissue in MRI imaging. It is in favor of the tumor cells labeling, tracing, magnetic resonance imaging （MRI） target detection and magnetic hyperthermia.

Preparation of Conjugated Linoleic Acid of High Purity and Its Apparent Kinetic Characteristics During Formation

Conjugated linoleic acid (CLA) is a fatty acid with physiological activities and potential application prospect. This paper focuses on the method of synthesis of conjugated linoleic acid of high purity and the process line and conditions for its purification that can be used in large scale production. CLA of more than 95% purity was prepared by means of urea adduct purification and conjugation using safflower oil as material. The total recovery of the product adds up to more than 48%. The reactive kinetics about linoleic acid from sunflower oil converted into CLA was investigated, and its apparent kinetic model was also established, which can be used as a base for industrial designs.