Generation and characterization of nanobodies targeting GPCR.

G protein-coupled receptors (GPCRs) are a large family of cell membrane proteins that are important targets for drug discovery. Nanobodies, also known as VHH (variable domains of heavy chain-only antibodies, HcAbs) antibodies, are small antibody fragments derived from camelids that have gained significant attention as potential therapeutics for targeting GPCRs due to their advantages over conventional antibodies. However, there are challenges in developing nanobodies targeting GPCRs, among which epitope accessibility is the most significant because the cell membrane partially shields the GPCR surface. We developed a universal protocol for making nanobodies targeting GPCRs using the cell membrane extract of GPCR-overexpressing HEK293 cells as the llama/alpaca immunization antigen. We constructed an immune VHH library and identified nanobodies by phage display bio-panning. The monoclonal nanobodies were recombinantly expressed in Escherichia coli (E. coli) and purified to characterize their binding potency.

Generation and characterization of nanobodies targeting human pepsinogens.

Human pepsinogens (mainly pepsinogen I and pepsinogen II) are the major inactive precursor forms of the digestive enzyme pepsin which play a crucial role in protein digestion. The levels and ratios of human pepsinogens have demonstrated potential as diagnostic biomarkers for gastrointestinal diseases, particularly gastric cancer. Nanobodies are promising tools for the treatment and diagnosis of diseases, owing to their unique recognition properties. In this study, recombinant human pepsinogens proteins were expressed and purified as immunized antigens. We constructed a VHH phage library and identified several nanobodies via phage display bio-panning. We determined the binding potency and cross-reactivity of these nanobodies. Our study provides technical support for developing immunodiagnostic reagents targeting human pepsinogens.

Serum Cell Division Cycle 42 before and after Programmed Death-1 Inhibitor Therapy in Advanced Melanoma Patients: Correlation with Tumor Features, Clinical Response, and Survival.

Cell division cycle 42 (CDC42) mediates immune escape in cancers. This study aimed to investigate linkages of CDC42 with tumor features, treatment response, and survival in advanced melanoma patients receiving programmed death-1 (PD-1) inhibitors. Pre-treatment and post-treatment (after 2 cycles) serum CDC42 of 35 advanced melanoma patients receiving PD-1 inhibitor was assessed by enzyme-linked immunosorbent assay. Patients with tumor-node-metastasis (TNM) stage IV (vs. III) (P = 0.050) and abnormal (vs. normal) lactate dehydrogenase (LDH) (P = 0.022) had higher pre-treatment CDC42. After 2-cycle therapy, CDC42 was declined (P < 0.001). Objective response and disease control rates were 34.3% and 62.9%, respectively. Additionally, pre-treatment and post-treatment CDC42 was reduced in patients with objective response and disease control than those without (all P < 0.050). Concerning survival, pre-treatment with CDC42 > 700 pg/mL was associated with shorter progression-free survival (PFS) (P = 0.013), but not overall survival (OS) (P = 0.060). Specifically, the 12-month PFS rate was 26.7% and 66.2%, and the 12-month OS rate was 61.1% and 82.5% in patients with pre-treatment with CDC42 > 700 pg/mL and ≤ 700 pg/mL, respectively. Post-treatment with CDC42 > 700 pg/mL was correlated with shortened PFS (P = 0.010) and OS (P = 0.006). The 12-month PFS rate was 12.5% and 62.0%, and the 12-month OS rate was 42.3% and 88.0% in patients with post-treatment with CDC42 > 700 pg/mL and ≤ 700 pg/mL, accordingly. Furthermore, post-treatment with CDC42 > 700 pg/mL was independently related to PFS [hazard ratio (HR): 2.704, P = 0.029 and OS (HR: 7.749, P = 0.005)]. Elevated CDC42 correlates with advanced TNM, abnormal LDH, worse clinical response, and dismal survival in advanced melanoma patients receiving PD-1 inhibitors.

A flexible gradient lateral flow immunochromatographic assay for qualitative, semi-quantitative, and quantitative determination of serum amyloid A.

Serum amyloid A (SAA) is an acute-phase protein produced in response to inflammatory proteins during infections, inflammation, trauma, surgery, cancer, and other conditions. Early and accurate detection of SAA is necessary for diagnosis and monitoring of disease progression. To meet this need, we developed a gradient lateral flow immunoassay test strip using Au nanoparticles as signal reporters. The test strip has three test (T1, T2, and T3) lines with progressively decreasing concentrations of SAA antibody, enabling the determination of high, medium, and low concentrations of SAA in serum. The test strip results were analyzed using three distinct readout methods, each with different sensitivity, accuracy, and precision for SAA concentration measurements. Qualitative judgment is based on the color of the T1 line. Semi-quantitative assessment of SAA concentration is determined by the number of colored T-lines. Specifically, color development in T1 line alone indicates a concentration range of 10-50 µg/mL, while T1 and T2 lines together indicate a range of 50-100 µg/mL, and development in all three lines (T1, T2, and T3) indicates a concentration of >100 µg/mL. Quantitative analysis was performed using either smartphone imaging or image scanning with ImageJ software. By using a five-parameter logistic function, we found a strong correlation (R2 = 0.998) between the ratio of signal intensities of (T1 + T2 + T3) to the control (C) line and SAA concentrations ranging from 5 to 1000 µg/mL. At lower concentrations (0-100 µg/mL), we observed a proportional relationship between the value of (T1 + T2 + T3)/C and SAA concentration. The limit of detection for SAA was 9.33 ng/mL (or 6.53 µg/mL of SAA in undiluted serum samples) for the smartphone method and 3.06 ng/mL (or 2.14 µg/mL of SAA in undiluted serum samples) for the scanner method. The gradient test strip was highly consistent with a commercially available SAA immunochromatographic test strip when tested with real human serum samples. Passing-Bablok regression indicated that results obtained using the smartphone app and scanner methods of the gradient test strip were comparable to those obtained using the commercial test strip. The gradient test strip is flexible and adaptable, providing solutions for qualitative, semi-quantitative, and quantitative SAA measurements.

A Quantitative Detection Algorithm for Multi-Test Line Lateral Flow Immunoassay Applied in Smartphones.

The traditional lateral flow immunoassay (LFIA) detection method suffers from issues such as unstable detection results and low quantitative accuracy. In this study, we propose a novel multi-test line lateral flow immunoassay quantitative detection method using smartphone-based SAA immunoassay strips. Following the utilization of image processing techniques to extract and analyze the pigments on the immunoassay strips, quantitative analysis of the detection results was conducted. Experimental setups with controlled lighting conditions in a dark box were designed to capture samples using smartphones with different specifications for analysis. The algorithm's sensitivity and robustness were validated by introducing noise to the samples, and the detection performance on immunoassay strips using different algorithms was determined. The experimental results demonstrate that the proposed lateral flow immunoassay quantitative detection method based on image processing techniques achieves an accuracy rate of 94.23% on 260 samples, which is comparable to the traditional methods but with higher stability and lower algorithm complexity.

An integrated immunochromatographic device for C-reactive protein detection using hierarchical dendritic gold nanostructure films.

Immunochromatographic test strips typically consist of sample pad, conjugate pad, nitrocellulose membrane, and absorbent pad. Even minute variations in the assembly of these components can lead to inconsistent sample-reagent interactions, thereby reducing reproducibility. In addition, the nitrocellulose membrane is susceptible to damage during assembly and handling. To address this issue, we propose to replace the sample pad, conjugate pad, and nitrocellulose membrane with hierarchical dendritic gold nanostructure (HD-nanoAu) films to develop a compact integrated immunochromatographic strip. The strip uses quantum dots as a background fluorescence signal and employs fluorescence quenching to detect C-reactive protein (CRP) in human serum. A 5.9 µm thick HD-nanoAu film was electrodeposited on an ITO conductive glass by the constant potential method. The wicking kinetics of the HD-nanoAu film was thoroughly investigated, and the results indicated that the film exhibited favorable wicking properties, with a wicking coefficient of 0.72 µm ms-0.5. The immunochromatographic device was fabricated by etching three interconnected rings on HD-nanoAu/ITO to designate sample/conjugate (S/C), test (T), and control (C) regions. The S/C region was immobilized with mouse anti-human CRP antibody (Ab1) labeled with gold nanoparticles (AuNPs), while the T region was preloaded with polystyrene microspheres decorated with CdSe@ZnS quantum dots (QDs) as background fluorescent material, followed by mouse anti-human CRP antibody (Ab2). The C region was immobilized with goat anti-mouse IgG antibody. After the samples were added to the S/C region, the excellent wicking properties of the HD-nanoAu film facilitated the lateral flow of the CRP-containing sample toward the T and C regions after binding to AuNPs labeled with CRP Ab1. In the T region, CRP-AuNPs-Ab1 formed sandwich immunocomplexes with Ab2, and the fluorescence of QDs was quenched by AuNPs. The ratio of fluorescence intensity in the T region to that in the C region was used to quantify CRP. The T/C fluorescence intensity ratio was negatively correlated with the CRP concentration in the range of 26.67-853.33 ng mL-1 (corresponding to 300-fold diluted human serum), with a correlation coefficient (R2) of 0.98. The limit of detection was 15.0 ng mL-1 (corresponding to 300-fold diluted human serum), and the range of relative standard deviation: 4.48-5.31%, with a recovery rate of 98.22-108.33%. Common interfering substances did not cause significant interference, and the range of relative standard deviation: 1.96-5.51%. This device integrates multiple components of conventional immunochromatographic strips onto a single HD-nanoAu film, resulting in a more compact structure that improves the reproducibility and robustness of detection, making it promising for point-of-care testing applications.

An Indoor Fingerprint Positioning Algorithm Based on WKNN and Improved XGBoost.

Considering the low indoor positioning accuracy and poor positioning stability of traditional machine-learning algorithms, an indoor-fingerprint-positioning algorithm based on weighted k-nearest neighbors (WKNN) and extreme gradient boosting (XGBoost) was proposed in this study. Firstly, the outliers in the dataset of established fingerprints were removed by Gaussian filtering to enhance the data reliability. Secondly, the sample set was divided into a training set and a test set, followed by modeling using the XGBoost algorithm with the received signal strength data at each access point (AP) in the training set as the feature, and the coordinates as the label. Meanwhile, such parameters as the learning rate in the XGBoost algorithm were dynamically adjusted via the genetic algorithm (GA), and the optimal value was searched based on a fitness function. Then, the nearest neighbor set searched by the WKNN algorithm was introduced into the XGBoost model, and the final predicted coordinates were acquired after weighted fusion. As indicated in the experimental results, the average positioning error of the proposed algorithm is 1.22 m, which is 20.26-45.58% lower than that of traditional indoor positioning algorithms. In addition, the cumulative distribution function (CDF) curve can converge faster, reflecting better positioning performance.

Screening and characterization estrogen receptor ligands from Arnebia euchroma (Royle) Johnst. via affinity ultrafiltration LC-MS and molecular docking.

Arnebiae Radix (dried root of Arnebia euchroma (Royle) Johnst.) is a traditional Chinese medicine (TCM) used to treat macular eruptions, measles, sore throat, carbuncles, burns, skin ulcers, and inflammations. The Arnebiae Radix extract can exert anti-breast cancer effects through various mechanisms of action. This study aimed to rapidly screen potential estrogen receptor (estrogen receptor α and estrogen receptor ß) ligands from the Arnebiae Radix extract. In this study, an analytical method based on affinity ultrafiltration coupled with UHPLC-Q-Exactive Orbitrap mass spectrometry was established for rapidly screening and identifying estrogen receptor ligands. Then, bindings of the components to the active site of estrogen receptor (estrogen receptor α and estrogen receptor ß) were investigated via molecular docking. Moreover, surface plasmon resonance (SPR) experiments with six compounds were performed to verify the affinity. As a result, a total of 21 ligands were screened from Arnebiae Radix using affinity ultrafiltration. Among them, 14 and 10 compounds from Arnebiae Radix showed affinity with estrogen receptor α and estrogen receptor ß, respectively. All of those ligands could have a good affinity for the multiple amino acid residues of the estrogen receptor based on molecular docking. In addition, six compounds display the great affinity by SPR. The method established in the study could be used to rapidly screen estrogen receptor ligands in Traditional Chinese medicine. The results demonstrated that the affinity ultrafiltration-UHPLC-Q-Exactive Orbitrap mass spectrometry method not only aids in the interpretation of the potential bioactive components and possible mechanisms of action of Arnebiae Radix but also provides a further effective basis for the quality control of this valuable herb medicine.

Factors predicting regression of visual acuity following successful treatment of anisometropic amblyopia.

Objective: To identify factors associated with visual acuity regression following successful treatment of anisometropic amblyopia. Design and method: This was a retrospective cohort study. Database records for 100 and 61 children with anisometropic amblyopia who met at least one criterion for successful treatment proposed by the Pediatric Eye Disease Investigator Group (PEDIG) and had at least 1 year of follow-up data available after the criterion was met were analyzed. The study sample was split into two groups, those who regressed within 1 year of successful treatment (no longer met any of the PEDIG criteria for successful treatment) and those who did not. A two-step analysis involving a least absolute shrinkage and selection operator (LASSO) regression and a logistic regression were used to identify predictor variables for increased risk of regression. A broad range of clinical, perceptual, and demographic variables were included in the analyses. Results: Sixty-eight (42.5%) children regressed within 1 year of successful treatment. Among the 27 predictor variables considered within the statistical modeling process, the three most important for predicting treatment regression were the extent of amblyopic eye visual acuity improvement, age at first hospital visit and sex. Specifically, lower risk of regression was associated with larger amblyopic eye visual acuity improvement with treatment, younger age at initiation of treatment and female sex. Conclusion: Patients who received treatment at a younger age and responded well to treatment had a lower risk of treatment regression. This pattern of results suggests that early detection of amblyopia and strategies that enhance treatment adherence may reduce the risk of treatment regression. The higher risk of regression in boys than girls that we observed may reflect known sex differences in brain development and /or sex differences in environment within our sample of children from South China.

Contrast Sensitivity and Stereoacuity in Successfully Treated Refractive Amblyopia.

Purpose: To assess whether monocular contrast sensitivity and stereoacuity impairments remain when visual acuity is fully recovered in children with refractive amblyopia. Methods: A retrospective review of 487 patients diagnosed with refractive amblyopia whose visual acuity improved to 0.08 logMAR or better in both eyes following optical treatment was conducted. Measurements of monocular contrast sensitivity and stereoacuity had been made when visual acuity normalized. All patients had been treated with refractive correction for approximately 2 years following diagnosis. No other treatments were provided. Monocular contrast sensitivity was measured using the CSV-1000E chart for children 6 years of age or younger and a psychophysical technique called the quick contrast sensitivity function in older children. Stereoacuity was measured using the Random Dot Test that includes monocular cues and the Randot Stereoacuity Test that does not have monocular cues. Results: Statistically significant interocular differences in contrast sensitivity were observed. These differences tended to occur at higher spatial frequencies (12 and 18 cycles per degree). Stereoacuity within the age-specific normal range was achieved by 47.4% of patients for the Random Dot Test and only 23.1% of patients for the Randot Stereoacuity Test. Conclusions: Full recovery of visual acuity following treatment for refractive amblyopia does not equalize interocular contrast sensitivity or restore normal stereopsis. Alternative therapeutic approaches that target contrast sensitivity and/or binocular vision are required.

The Integration of Eye Tracking Responses for the Measurement of Contrast Sensitivity: A Proof of Concept Study.

Contrast sensitivity (CS) is important when assessing functional vision. However, current techniques for assessing CS are not suitable for young children or non-verbal individuals because they require reliable, subjective perceptual reports. This study explored the feasibility of applying eye tracking technology to quantify CS as a first step toward developing a testing paradigm that will not rely on observers' behavioral or language abilities. Using a within-subject design, 27 healthy young adults completed CS measures for three spatial frequencies with best-corrected vision and lens-induced optical blur. Monocular CS was estimated using a five-alternative, forced-choice grating detection task. Thresholds were measured using eye movement responses and conventional key-press responses. CS measured using eye movements compared well with results obtained using key-press responses [Pearson's r best-corrected = 0.966, P < 0.001]. Good test-retest variability was evident for the eye-movement-based measures (Pearson's r = 0.916, P < 0.001) with a coefficient of repeatability of 0.377 log CS across different days. This study provides a proof of concept that eye tracking can be used to automatically record eye gaze positions and accurately quantify human spatial vision. Future work will update this paradigm by incorporating the preferential looking technique into the eye tracking methods, optimizing the CS sampling algorithm and adapting the methodology to broaden its use on infants and non-verbal individuals.

A New Method of Identifying Core Designers and Teams Based on the Importance and Similarity of Networks.

In the process of product collaborative design, the association between designers can be described by a complex network. Exploring the importance of the nodes and the rules of information dissemination in such networks is of great significance for distinguishing its core designers and potential designer teams, as well as for accurate recommendations of collaborative design tasks. Based on the neighborhood similarity model, combined with the idea of network information propagation, and with the help of the ReLU function, this paper proposes a new method for judging the importance of nodes-LLSR. This method not only reflects the local connection characteristics of nodes but also considers the trust degree of network propagation, and the neighbor nodes' information is used to modify the node value. Next, in order to explore potential teams, an LA-LPA algorithm based on node importance and node similarity was proposed. Before the iterative update, all nodes were randomly sorted to get an update sequence which was replaced by the node importance sequence. When there are multiple largest neighbor labels in the propagation process, the label with the highest similarity is selected for update. The experimental results in the related networks show that the LLSR algorithm can better identify the core nodes in the network, and the LA-LPA algorithm has greatly improved the stability of the original LPA algorithm and has stably mined potential teams in the network.

Sensitivity and Stability of Functional Vision Tests in Detecting Subtle Changes Under Multiple Simulated Conditions.

Purpose: To explore whether subtle changes in visual quality can be detected using different measures of visual function against the quick contrast sensitivity function test (quick CSF). Methods: Sixty participants, aged 17 to 34 years, were enrolled. Participants' vision was degraded by 0.25 D undercorrection (0.25 D), 60% neutral density filter brightness reduction (60% ND), and 0.8 Bangerter foil optical diffusion (0.8BAN). Visual function tests including visual acuity and contrast sensitivity (CSV-1000E and quick CSF) were measured with participant's best-corrected vision and under simulated visual degradation conditions. Test sensitivities in detecting differences were compared. Results: Statistically significant visual acuity degradation was observed in the 0.8BAN condition only (Pcorrected < 0.001). With CSV-1000E and outliers removed, significant CS degradation was observed in all spatial frequencies, area under log CSF (AULCSF) in the 0.8BAN condition (Pcorrected < 0.001 for all), medium and high spatial frequencies and AULCSF in the 60%ND condition (Pcorrected,6cpd = 0.002, Pcorrected,12cpd = 0.005, Pcorrected,18cpd = 0.001, Pcorrected,AULCSF < 0.001) and the 0.25 D condition (Pcorrected,6cpd = 0.011, Pcorrected,12cpd = 0.013, Pcorrected,18cpd = 0.015, Pcorrected,AULCSF < 0.001). With the quick CSF, significant CS degradation was observed in all simulated visual conditions in all spatial frequencies, cutoff frequency and AULCSF (Pcorrected < 0.001 for all). Test-retest reliability of the quick CSF method was high; coefficient of repeatability ranged from 0.14 to 0.18 logCS. Conclusions: Compared with visual acuity and chart-based CS tests, the quick CSF method provided more reliable and sensitive measures to detect small visual changes. Translational Relevance: The quick CSF method can provide sensitive and reliable measures to monitor disease progression and assess treatment outcomes.

miR-146b correlates with increased disease activity and psoriatic tissue inflammation and promotes keratinocyte proliferation in psoriasis.

The present study aimed to investigate the expression of microRNA (miR)-146b in psoriatic tissue and its correlation with psoriasis activity and inflammation. The effect of miR-146b overexpression on keratinocyte proliferation and apoptosis was also explored. The expression of miR-146b in the psoriasis-affected tissue and non-affected tissue of 110 patients was determined via reverse transcription-quantitative (RT-q)PCR. The psoriasis-affected body surface area and psoriasis area severity index (PASI) score were recorded for evaluating disease activity. The expression of various inflammatory cytokines in psoriasis-affected tissue was also detected via RT-qPCR. miR-146b overexpression and control plasmids were constructed and transfected into HaCaT cells in vitro. Subsequently, cell proliferation, apoptosis and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced cell apoptosis were determined. The results revealed that the expression of miR-146b was increased in psoriasis-affected tissue compared with that in unaffected tissue. The results obtained from a receiver operating characteristic curve analysis demonstrated that miR-146b levels were able to discriminate between psoriasis-affected tissue and unaffected tissue, with an area under the curve value of 0.781 (95% CI: 0.720-0.843). In addition, miR-146b expression in psoriatic tissue was correlated with an increased PASI score in patients with psoriasis. miR-146b expression in psoriatic tissue was positively correlated with TNF-α, interleukin (IL)-6 and IL-17 mRNA levels. In vitro, miR-146b overexpression enhanced HaCaT cell proliferation and suppressed apoptosis as well as TRAIL-induced apoptosis when compared with that in control-transfected HaCaT cells. In conclusion, miR-146b was positively correlated with disease activity and psoriatic tissue inflammation. Keratinocyte proliferation was also promoted in psoriasis.

Structural basis for distinct quality control mechanisms of GABAB receptor during evolution.

Cell surface trafficking of many G protein-coupled receptors is tightly regulated. Among them, the mandatory heterodimer GABAB receptor for the main inhibitory neurotransmitter, γ-aminobutyric acid (GABA), is a model. In mammals, its cell surface trafficking is highly controlled by an endoplasmic reticulum retention signal in the C-terminal intracellular region of the GB1 subunit that is masked through a coiled-coil interaction with the GB2 subunit. Here, we investigate the molecular basis for the export of its homolog in Drosophila melanogaster that regulates the circadian rhythm and sleep. In contrast to mammals, the endoplasmic retention signal is carried by GB2, while GB1 reaches the cell surface alone. NMR analysis showed that the coiled-coil domain that controls GABAB heterodimer formation is structurally conserved between flies and mammals, despite specific features. These findings show the adaptation of a similar quality control system during evolution for maintaining the subunit composition of a functional heterodimeric receptor.

Cryo-EM structures of inactive and active GABAB receptor.

Metabotropic GABAB G protein-coupled receptor functions as a mandatory heterodimer of GB1 and GB2 subunits and mediates inhibitory neurotransmission in the central nervous system. Each subunit is composed of the extracellular Venus flytrap (VFT) domain and transmembrane (TM) domain. Here we present cryo-EM structures of full-length human heterodimeric GABAB receptor in the antagonist-bound inactive state and in the active state complexed with an agonist and a positive allosteric modulator in the presence of Gi1 protein at a resolution range of 2.8-3.0 Å. Our structures reveal that agonist binding stabilizes the closure of GB1 VFT, which in turn triggers a rearrangement of TM interfaces between the two subunits from TM3-TM5/TM3-TM5 in the inactive state to TM6/TM6 in the active state and finally induces the opening of intracellular loop 3 and synergistic shifting of TM3, 4 and 5 helices in GB2 TM domain to accommodate the α5-helix of Gi1. We also observed that the positive allosteric modulator anchors at the dimeric interface of TM domains. These results provide a structural framework for understanding class C GPCR activation and a rational template for allosteric modulator design targeting the dimeric interface of GABAB receptor.

Bone-like apatite coating on functionalized poly(etheretherketone) surface via tailored silanization layers technique.

Poly(etheretherketone) (PEEK) is a rigid semi-crystalline polymer with outstanding mechanical properties, bone-like stiffness and suitable biocompatibility that has attracted much interest as a biomaterial for orthopedic and dental implants. However, the bio-inert surface of PEEK limits its biomedical applications when direct osteointegration between the implants and the host tissue is desired. In this work, -PO4H2, -COOH and -OH groups were introduced on the PEEK surface by further chemical treatments of the vinyl-terminated silanization layers formed on the hydroxylation-pretreated PEEK surface. Both the surface-functionalized and pristine specimens were characterized by X-ray photoelectron spectroscopy (XPS), attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and water contact angle measurements. When placed in 1.5 strength simulated body fluid (SBF) solution, apatite was observed to form uniformly on the functionalized PEEK surface and firmly attach to the substrate. The characterized results demonstrated that the coating was constituted by poorly crystallized bone-like apatite and the effect of surface functional groups on coating formation was also discussed in detail. In addition, in vitro biocompatibility of PEEK, in terms of pre-osteoblast cell (MC3T3-E1) attachment, spreading and proliferation, was remarkably enhanced by the bone-like apatite coating. Thus, this study provides a method to enhance the bioactivity of PEEK and expand its applications in orthopedic and dental implants.

Carbazole endcapped heterofluorenes as host materials: theoretical study of their structural, electronic, and optical properties.

By mimicking the molecular structure of 4,4'-bis(N-carbazolyl)-2,2'-biphenyl (CBP), which is a widely used host material, a new series of host molecules (carbazole-endcapped heterofluorenes, CzHFs) were designed by linking the hole-transporting carbazole to the core heterofluorene molecules in either meta or para positions of the heterofluorene. The aromatic cores considered in this study are biphenyl, fluorene, silafluorenes, germafluorenes, carbazole, phosphafluorene, oxygafluorene, and sulfurafluorene. To reveal their molecular structures, optoelectronic properties and structure-property relationships of the proposed host materials, an in-depth theoretical investigation was elaborated via quantum chemical calculations. The electronic structures in the ground states, cationic and anionic states, and lowest triplet states of these designed molecules have been studied with emphasis on the highest occupied molecular orbitals (HOMOs), the lowest unoccupied molecular orbitals (LUMOs), energy gaps (E(g)), triplet energy gaps ((3)E(g)), as well as some other electronic properties including ionization potentials (IPs), electron affinities (EAs), reorganization energies (λ), triplet exciton generation fraction (χ(T)), spin density distributions (SD), and absorption spectra. These photoelectronic properties can be tuned by chemical modifications of the heteroatom and the carbazole substitution at different positions. This study provides theoretical insights into the nature of host molecules, and shows that the designed CzHFs can meet the requirements of the host materials for triplet emitters.

Tuning the optoelectronic properties of 4,4'-N,N'-dicarbazole-biphenyl through heteroatom linkage: new host materials for phosphorescent organic light-emitting diodes.

Five carbazole end-capped heterofluorenes (CzHFs) designed by structurally mimicking 4,4'-N,N'-dicarbazole-biphenyl (CBP) via connecting the biphenyl core of CBP with the linking atom of C, P, N, O, and S, respectively, were synthesized successfully, and their optoelectronic properties were investigated. The theoretical calculations and experimental results demonstrate that CzHFs are potential green, red, and even blue hosts for phosphorescent light-emitting diodes (PHOLEDs) with more desirable localization and energy levels of HOMO and LUMO and also higher triplet energy than CBP.