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.

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.

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.

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.

Localization of stationary pronuclei during conjugation of Paramecium as indicated by immunofluorescence staining

After the third prezygotic division during conjugation of Paramecium caudatum,migratory and stationary pronuclei are produced.The migratory pronuclei remain in the paroral region tightly against the conjugating boundaries;while the stationary pronuclei are located beside the migratory pronuclei.To date,however,it is not clear what causes this close side-by-side localization between migratory and stationary pronuclei.In the current study,immunofluorescence staining with monoclonal antibody of anti-α tubulin indicated that ＂U＂ or ＂V＂ shaped spindles connected the migratory and stationary pronuclei during the third prezygotic division.This observation accounts for the close localization between these two types of pronuclei.

New details indicated by different stainings during conjugation of ciliated protozoa Paramecium

During conjugation of Paramecium caudatum, nuclear events occur in a scheduled program. Morphological studies on nuclear behavior during conjugation of P. caudatum have been performed since the end of the 19th century. Here we report on new details concerning the conjugation of P. caudatum through the staining of conjugating ceils with protargol, carbol fuchsin solution, Hoechst 33342 and immunofluorescence labeling with monoclonal antibody of anti-a tubulin. 1） The crescent nucleus is a characteristic of the meiotic prophase of P. caudatum, has an unstained area. We stained this area with protargol, which was separated from the chromatin area and was not detected by the other stainings. 2） In regards to the four meiotic products, it has long been considered that only one product enters the paroral cone region （PC） and survives after meiosis. However, our protargol and immunofluorescence labeling results indicated that PC entrance of the meiotic product happened before the completion of meiosis instead of after. 3） In our previous study, protargol staining indicated the presence of a swollen structure around the central part of the ＂U＂ and ＂V＂ shaped spindles connecting the two types of prospective pronuclei. However, immunofluorescence labeling with anti-a tubulin antibodies gave a different image from protargol. All these observations form the basis for further studies of their molecular mechanisms.

Characterization and Comparison of Ochratoxin A-Ovalbumin(OTA-OVA) Conjugation by Three Methods

In order to generate an antibody against a small hapten molecule, the hapten is cross-linked with carrier protein to make it immunogenic. In this study, the hapten （ochratoxin A, OTA） was coupled to ovalbumin （OVA） by an active ester reaction. To develop a technique for detecting the conjugation, the hapten-protein conjugate （OTA-OVA） was characterized thoroughly by immunoarray technology, ultraviolet （UV） spectroscopy and matrix-assisted laser desorption ionization time-of-flight mass spectrometry （MALDI-TOF-MS）, respectively. The molecular weight of OTA-OVA was 50 350.141 Da, and the molecular weight of OVA was 44 887.506 Da, which were determined by MALDI-TOF-MS, respectively. In OTA-OVA, the molecular coupling ratio was 13：1 by MALDI-TOF-MS while the molecular coupling ratio was 10：1 by UV. In this experiment, UV and MALDI-TOF-MS were selected as the efficient methods to evaluate the cross-linking effect and calculate the molecular coupling ratio.

Wavefront correction of Ti:sapphire terawatt laser with varying precision of phase conjugation between deformable mirror and wavefront sensor

The phase conjugation between the deformable mirror and the wavefront sensor in the aberration correction of a terawatt Ti：sapphire laser is studied experimentally and theoretically in this paper. At varying values of phase- conjugation precision, we focus the corresponding beams into spots of the same size of 5.1 μm × 5.3 μm with a f/4 parabola in the 32 TW/36 fs Ti：sapphire laser system. The results show that the precision of conjugation can induce an intensity modulation but does not significantly affect the wavefront correction.

OPTICAL PHASE CONJUGATION RESPONSE OF PHOTOINDUCED POLYMER FILMS CONTAINING AZOBENZENE MOIETIES WITH CHIRAL GROUP

An optically active monomer containing azobenzene moieties with chiral group (s-2-methyl-butyl), 4-[2-(methacryloyloxy)ethyloxy] -4'-(s-2-methyl-1-butyloxycarbonyl) azobenzene (M1) was synthesized. Polymer (PM1) possessing optical phase conjugated response was obtained by homopolymerization of the optically active monomer (M1) using free radical polymerization. The polymer was very soluble in common solvents and good optical quality films could be easily fabricated by spin coating. The optical phase conjugated responses of the polymer PM1 were measured by degenerate four-wave mixing (DFWM). In comparison with polymer containing no chiral group, it was found from the preliminary measurement of photoisomeric change that optical phase conjugated response of the PM1 in the long-range order hexagonal symmetry microstructure could be easily controlled by choosing the appropriate polarization direction of the irradiating beams (514.5 nm) and the irradiating number, presumably due to the chiral group in the PM1 molecular structure. For the case of the polymer investigated here, a chiral group side chain was introduced to increase optical phase conjugated response intensity with different polarization directions of the irradiating beams, which aims originally at searching for a new photoactive material.

Transposon mutagenesis of Psychrobacter cryohalolentis PAMC 21807 by tri-parental conjugation

Random mutagenesis is commonly used to study gene function. The screening of mutants exhibiting specific pheno- types assists in the identification of phenotype-related genes. In the current study, we isolated Antarctic bacteria, and developed a transposon Tn5 mutagenesis system. A total of 26 strains were isolated from seawater and freshwater near Antarctic King Sejong Research Station, King George Island. Six Psychrobacter strains were identified as psychrophilic, with optimal growth tempera- tures of 10~C or 15~C Psychrobacter cryohalolentis PAMC 21807 with a high growth rate at 4~C was selected for transposon mutagenesis. Tri-parental conjugation with a plasmid containing Tn5 produced 13 putative recombinants containing the selectable marker. Genomic Southern hybridization confirmed Tn5 existed as episomes for seven recombinants, and for a single recombinant, Tn5 was integrated into the genome of Psychrobacter cryohalolentis PAMC 21807. The result indicates that the mutagenesis method, although successful, has a relatively low rate. The psychrophilic bacteria isolated in this study may be a useful resource for studying cold adaptation mechanisms, and the mutagenesis method can be applied to genetic analysis.

Strategies for Precise Engineering and Conjugation of Antibody Targeted-nanoparticles for Cancer Therapy

Improvements in the diagnosis and treatment of cancer are urgently needed for use in nanotechnology.Nanoparticles(NPs)can reduce the side effects of traditional chemotherapy by sustained release of loaded drugs and increase therapeutic efficiency.NPs can also enhance endothelial permeation retention by size effect and its accumulation in tumor cells through passive targeting.Furthermore,it is critical to treat cancer with a controlled targeted drug which can be specifically delivered into tumor cells and released there,resulting in a targeted therapy to eradicate tumor cells while sparing normal cells.To this end,antibody-mediated targeting therapy has been developed,but imperfections in antibodies(Abs)limit this therapy.Therefore,the combination of NPs and Abs has been highly valued in recent years,because conjugating special Abs on the surface of NPs can increase targeting efficiency,enabling selective delivery of anti-cancer drugs to tumor cells.In this mini-review,we would like to enumerate the strategies for the conjugation of Abs to the surface of the NPs as well as the precise engineering of targeted NPs.The application of targeting antibody fragments in this drug delivery system will also be discussed.

Conjugation of a zwitterionic polymer with dimethyl chains to lipase significantly increases the enzyme activity and stability

Enzyme-polymer conjugates are complex molecules with great practical significance.This work was designed to develop a novel enzyme-polymer conjugate by covalently coupling a zwitterionic polymer with side dimethyl chains(pID)to Candida rugosa lipase(CRL)via the reaction between the anhydrides of polymer chains with the amino groups of the enzyme.The resulting two CRL-pID conjugates with different pID grafting densities were investigated in term of the catalytic activity,stability and structural changes.In comparison with native CRL,both the CRL conjugates displayed 2.2 times higher activity than the native enzyme,and showed an increase in the maximum reaction rate(V_(max))and a decrease in the Michaelis constant(K_(m)),thus resulting in about three-fold increases in the catalytic efficiency(k_(cat)/K_(m)).These are mainly attributed to the activation of lipase by the hydrophobic alky side chains.Moreover,the thermostability and pH tolerance of the lipase conjugates were significantly enhanced due to the stabilizing effect of the zwitterion moieties.For instance,a five-fold increase of the enzyme half-life at 50℃ for the high-pID conjugated CRL was observed.Spectroscopic studies reveal that the pID conjugation protected the enzyme in the changes in its microenvironment and conformation,well correlating with enhanced activity and stability of lipase conjugates.The findings indicate that enzyme conjugation to the zwitterionic polymer is promising for improving enzyme performance and deserves further development.

Boundary Control for 2 ×2 Elliptic Systems with Conjugation Conditions

In this paper, we consider 2 × 2 non-cooperative elliptic system involving Laplace operator defined on bounded, continuous and strictly Lipschitz domain of Rn. First we prove the existence and uniqueness for the state of the system under conjugation conditions;then we discuss the existence of the optimal control of boundary type with Neumann conditions, and we find the set of equations and inequalities that characterize it.

Novel insights into conjugation of antitumor-active unsymmetrical bisacridine C-2028 with glutathione:Characteristics of non-enzymatic and glutathione S-transferase-mediated reactions

Unsymmetrical bisacridines(UAs) are a novel potent class of antitumor-active therapeutics.A significant route of phase II drug metabolism is conjugation with glutathione(GSH),which can be non-enzymatic and/or catalyzed by GSH-dependent enzymes.The aim of this work was to investigate the GSHmediated metabolic pathway of a representative UA,C-2028.GSH-supplemented incubations of C-2028 with rat,but not with human,liver cytosol led to the formation of a single GSH-related metabolite.Interestingly,it was also revealed with rat liver microsomes.Its formation was NADPH-independent and was not inhibited by co-incubation with the cytochrome P450(CYP450) inhibitor 1-aminobenzotriazole.Therefore,the direct conjugation pathway occurred without the prior CYP450-catalyzed bioactivation of the substrate.In turn,incubations of C-2028 and GSH with human recombinant glutathione S-transferase(GST) P1-1 or with heat-/ethacrynic acid-inactivated liver cytosolic enzymes resulted in the presence or lack of GSH conjugated form,respectively.These findings proved the necessary participation of GST in the initial activation of the GSH thiol group to enable a nucleophilic attack on the substrate molecule.Another C-2028-GSH S-conjugate was also formed during non-enzymatic reaction.Both GSH S-conjugates were characterized by combined liquid chromatography/tandem mass spectrometry.Mechanisms for their formation were proposed.The ability of C-2028 to GST-mediated and/or direct GSH conjugation is suspected to be clinically important.This may affect the patient’s drug clearance due to GST activity,loss of GSH,or the interactions with GSH-conjugated drugs.Moreover,GST-mediated depletion of cellular GSH may increase tumor cell exposure to reactive products of UA metabolic transformations.

Theoretical study on phase conjugation in weakly injected vertical-cavity surface-emitting lasers

This paper gives a detailed theoretical investigation on phase conjugation induced by nearly degenerate fourwave mixing in single mode vertical-cavity surface-emitting lasers （VCSELs） with weak optical injection. Considering VCSELs that can work in linearly polarized or elliptically polarized states, it derives the theoretical expression of the conjugated field by small signal analysis based on the vectoral rate equations-the spin-flip model. For linearly polarized state, VCSELs show similar conjugate spectra to edge-emitting semiconductor lasers. For the elliptically polarized state, dichroism and birefringence parameters as well as the spin-flip rate can change the conjugate spectra. Especially, when frequency detuning of the probe and pump waves is between the positive and negative relaxation oscillation frequency, changes are evident. For specific values of parameters, conjugate efficiency between 20 dB to 40 dB are obtained.

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.

Improving the performance of arylamine-based hole transporting materials in perovskite solar cells： Extending π-conjugation length or increasing the number of side groups？

In this work, we prepared three simple arylamine-based hole transporting materials from commercially available starting materials. The effect of extending z-conjugation length or increasing the number of side groups compared with reference compound on the photophysical, electrochemical, hole mobility properties and performance in perovskite solar cells were further studied. It is noted that these two kinds of molecular modifications can significantly lower the HOMO level and improve the hole mobility, thus improving the hole injection from valence band of perovskite. On the other hand, the compound with more side groups showed higher hole injection efficiency due to lower HOMO level and higher hole mo- bility compared with the compound with extending π-conjugation length. The perovskite solar cells with the modified molecules as hole transporting materials showed a higher efficiency of 15.40% and 16.95%, respectively, which is better than that of the reference compound （13.18%）. Moreover, the compound with increasing number of side groups based devices showed comparable photovoltaic performance with that of conventional spiro-OMeTAD （16.87%）.