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.

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.

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.

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.

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.

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.

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.

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.

A New Two-Parameter Family of Nonlinear Conjugate Gradient Method Without Line Search for Unconstrained Optimization Problem

This paper puts forward a two-parameter family of nonlinear conjugate gradient(CG)method without line search for solving unconstrained optimization problem.The main feature of this method is that it does not rely on any line search and only requires a simple step size formula to always generate a sufficient descent direction.Under certain assumptions,the proposed method is proved to possess global convergence.Finally,our method is compared with other potential methods.A large number of numerical experiments show that our method is more competitive and effective.

An Adaptive Spectral Conjugate Gradient Method with Restart Strategy

As a generalization of the two-term conjugate gradient method(CGM),the spectral CGM is one of the effective methods for solving unconstrained optimization.In this paper,we enhance the JJSL conjugate parameter,initially proposed by Jiang et al.(Computational and Applied Mathematics,2021,40:174),through the utilization of a convex combination technique.And this improvement allows for an adaptive search direction by integrating a newly constructed spectral gradient-type restart strategy.Then,we develop a new spectral CGM by employing an inexact line search to determine the step size.With the application of the weak Wolfe line search,we establish the sufficient descent property of the proposed search direction.Moreover,under general assumptions,including the employment of the strong Wolfe line search for step size calculation,we demonstrate the global convergence of our new algorithm.Finally,the given unconstrained optimization test results show that the new algorithm is effective.

Cooperative Distributed Beamforming Design for Multi-RIS Aided Cell-Free Systems

Cell-free systems significantly improve network capacity by enabling joint user service without cell boundaries,eliminating intercell interference.However,to satisfy further capacity demands,it leads to high-cost problems of both hardware and power consumption.In this paper,we investigate multiple reconfigurable intelligent surfaces(RISs)aided cell-free systems where RISs are introduced to improve spectrum efficiency in an energy-efficient way.To overcome the centralized high complexity and avoid frequent information exchanges,a cooperative distributed beamforming design is proposed to maximize the weighted sum-rate performance.In particular,the alternating optimization method is utilized with the distributed closed-form solution of active beamforming being derived locally at access points,and phase shifts are obtained centrally based on the Riemannian conjugate gradient(RCG)manifold method.Simulation results verify the effectiveness of the proposed design whose performance is comparable to the centralized scheme and show great superiority of the RISs-aided system over the conventional cellular and cell-free system.

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.

Minor Self-conjugate and Skewpositive Semidefinite Solutions to a System of Matrix Equations over Skew Fields

Minor self conjugate (msc) and skewpositive semidefinite (ssd) solutions to the system of matrix equations over skew fields [A mn X nn =A mn ,B sn X nn =O sn ] are considered. Necessary and sufficient conditions for the existence of and the expressions for the msc solutions and the ssd solutions are obtained for the system.

The Dihedral Angle and Intersection Processes of a Conjugate Strike-Slip Fault System in the Tarim Basin, NW China

Recent studies, focused on dihedral angles and intersection processes, have increased understandings of conjugate fault mechanisms. We present new 3-D seismic data and microstructural core analysis in a case study of a large conjugate strike-slip fault system from the intracratonic Tarim Basin, NW China. Within our study area, ＂X＂ type NE and NW trending faults occur within Cambrian- Ordovician carbonates. The dihedral angles of these conjugate faults have narrow ranges, 19~ to 62~ in the Cambrian and 26~ to 51~ in the Ordovician, and their modes are 42~ and 44~ respectively. These data are significantly different from the ~60~ predicted by the Coulomb fracture criterion. It is concluded that： （1） The dihedral angles of the conjugate faults were not controlled by confining pressure, which was low and associated with shallow burial; （2） As dihedral angles were not controlled by pressure they can be used to determine the shortening direction during faulting; （3） Sequential slip may have played an important role in forming conjugate fault intersections; （4） The conjugate fault system of the Tarim basin initiated as rhombic joints; these subsequently developed into sequentially active ＂X＂ type conjugate faults; followed by preferential development of the NW-trending faults; then reactivation of the NE trending faults. This intact rhombic conjugate fault system presents new insights into mechanisms of dihedral angle development, with particular relevance to intracratonic basins.

Pharmacokinetics of a ternary conjugate based pH-responsive 10-HCPT prodrug nano-micelle delivery system

A pH-responsive conjugate based 10-hydroxycamptothecin-thiosemicarbazide-polyethene glycol 2000 (10-HCPT-hydro-PEG) nano-micelles were prepared in our previous study. In the present study, ultra-performance liquid chromatography (UPLC-MS) method is developed to investigate its pharmacokinetics and biodistribution in tumor bearing mice. The results demonstrated that the conjugate circulated for a much longer time in the blood circulation system than commercial 10-HCPT injection, and bioavailability was significantly improved compared with 10-HCPT. In vivo biodistribution study showed that the conjugate could enhance the targeting and residence time in tumor site.

Conjugate Heat Transfer Analysis of an Ultrasonic Molten Metal Treatment System

In piezoceramic ultrasonic devices,the piezoceramic stacks may fail permanently or function improperly if their working temperatures overstep the Curie temperature of the piezoceramic material.While the end of the horn usually serves near the melting point of the molten metal and is enclosed in an airtight chamber,so that it is difficult to experimentally measure the temperature of the transducer and its variation with time,which bring heavy difficulty to the design of the ultrasonic molten metal treatment system.To find a way out,conjugate heat transfer analysis of an ultrasonic molten metal treatment system is performed with coupled fluid and heat transfer finite element method.In modeling of the system,the RNG model and the SIMPLE algorithm are adopted for turbulence and nonlinear coupling between the momentum equation and the energy equation.Forced air cooling as well as natural air cooling is analyzed to compare the difference of temperature evolution.Numerical results show that,after about 350 s of working time,temperatures in the surface of the ceramic stacks in forced air cooling drop about 7 K compared with that in natural cooling.At 240 s,The molten metal surface emits heat radiation with a maximum rate of about 19 036 W/m2,while the heat insulation disc absorbs heat radiation at a maximum rate of about 7922 W/m2,which indicates the effectiveness of heat insulation of the asbestos pad.Transient heat transfer film coefficient and its distribution,which are difficult to be measured experimentally are also obtained through numerical simulation.At 240 s,the heat transfer film coefficient in the surface of the transducer ranges from–17.86 to 20.17 W/（m2？K）.Compared with the trial and error method based on the test,the proposed research provides a more effective way in the design and analysis of the temperature control of the molten metal treatment system.

Orientation-enhanced nonlinear optical properties and phase-conjugate reflective system of a novel Azobenzene doped polymer film

This paper reports that the nonlinear refractive index of a novel organic optical storage film doped azodiphenylamine polymer is measured by using the Z-scan technique. The nonlinear refractive index up to 3.7× 10^-6 cm^2/W induced by thermo-optical effect is obtained. It indicates that the sample has excellent optical non- linear properties. The physical mechanism of the great nonlinear optical effect is analysed and the optical conjugate characteristic is also discussed with degenerate four-wave-mixing. The phase conjugate wave diffracted from the formative refractive index grating in the sample is acquired and its equivalent reflectivity reaches about 22%. On this basis, the reflective wave phase-conjugated mirror system was designed, and the image aberration experienced in propagation in the storage experiment is corrected by using the system.

Optimization of the Process for Preparing Bivalent Polysaccharide Conjugates to Develop Multivalent Conjugate Vaccines against Streptococcus pneumoniae or Neisseria meningitidis and Comparison with the Corresponding Licensed Vaccines in Animal Models

Objective:This study aimed to describe,optimize and evaluate a method for preparing multivalent conjugate vaccines by simultaneous conjugation of two different bacterial capsular polysaccharides(CPs)with tetanus toxoid(TT)as bivalent conjugates.Methods:Different molecular weights(MWs)of polysaccharides,activating agents and capsular polysaccharide/protein(CP/Pro)ratio that may influence conjugation and immunogenicity were investigated and optimized to prepare the bivalent conjugate bulk.Using the described method and optimized parameters,a 20-valent pneumococcal conjugate vaccine and a bivalent meningococcal vaccine were developed and their effectiveness was compared to that of corresponding licensed vaccines in rabbit or mouse models.Results:The immunogenicity test revealed that polysaccharides with lower MWs were better for Pn1-TT-Pn3 and MenA-TT-MenC,while higher MWs were superior for Pn4-TT-Pn14,Pn6A-TT-Pn6B,Pn7F-TT-Pn23F and Pn8-TT-Pn11A.For activating polysaccharides,1-cyano-4-dimethylaminopyridinium tetrafluoroborate(CDAP)was superior to cyanogen bromide(CNBr),but for Pn1,Pn3 and MenC,N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride(EDAC)was the most suitable option.For Pn6A-TT-Pn6B and Pn8-TT-Pn11A,rabbits immunized with bivalent conjugates with lower CP/Pro ratios showed significantly stronger CP-specific antibody responses,while for Pn4-TT-Pn14,higher CP/Pro ratio was better.Instead of interfering with the respective immunological activity,our bivalent conjugates usually induced higher IgG titers than their monovalent counterparts.Conclusion:The result indicated that the described conjugation technique was feasible and efficacious to prepare glycoconjugate vaccines,laying a solid foundation for developing extended-valent multivalent or combined conjugate vaccines without potentially decreased immune function.

High Level of Ubiquitin Conjugate Enzyme E2O Indicates Poor Prognosis of Patients with Hepatocellular Carcinoma

Objective Ubiquitin conjugate enzyme E2O(UBE2O)is a ubiquitin-conjugating enzyme that has been reported to be involved in tumorigenesis.This study investigated the role of UBE2O in hepatocellular carcinoma(HCC).Methods The expression of UBE2O was detected using qRT-PCR,Western blotting,and immunohistochemical staining.Cell proliferation and Transwell assays were used to detect proliferation,migration,and invasion of HCC cells,respectively.Bioinformatic analysis was performed to analyze the relationship between UBE2O and the clinical features,prognosis,and immune cell infiltration of HCC.Results UBE2O was significantly over-expressed in HCC tissues.High expression of UBE2O was associated with poor tumor grade and poor prognosis.Functional experiments showed that down-regulation of UBE2O inhibited HCC cell proliferation,migration,and invasion.Co-expression gene analysis and gene set enrichment analysis showed that UBE2O was associated with protein hydrolysis,cell cycle,and cancer-related pathways in HCC.The results of immune analysis revealed that the expression of UBE2O was positively correlated with the immune infiltration and expression of immune-related chemokines of HCC.Conclusions UBE2O is significantly correlated with the prognosis of HCC and may be a valuable prognostic biomarker for HCC.