Boosting Circularly Polarized Luminescence from Alkyl-Locked Axial Chirality Scaffold by Restriction of Molecular Motions.

Boosting the circularly polarized luminescence of small organic molecules has been a stubborn challenge because of weak structure rigidity and dynamic molecular motions. To investigate and eliminate these factors, here, we carried out the structure-property relationship studies on a newly-developed axial chiral scaffold of bidibenzo[b,d]furan. The molecular rigidity was finely tuned by gradually reducing the alkyl-chain length. The environmental factors were considered in solution, crystal, and polymer matrix at different temperatures. As a result, a significant amplification of the dissymmetry factor glum from 10-4 to 10-1 was achieved, corresponding to the situation from (R)-4C in solution to (R)-1C in polymer film at room temperature. A synergistic strategy of increasing the intramolecular rigidity and enhancing the intermolecular interaction to restrict the molecular motions was thus proposed to improve circularly polarized luminescence. The though-out demonstrated relationship will be of great importance for the development of high-performance small organic chiroptical systems in the future.

Comparative visual outcomes of the first versus second eye following small-incision lenticule extraction (SMILE).

BACKGROUND: This study aimed to compare the visual outcomes of the first operated eyes with those of the second operated eyes following small-incision lenticule extraction (SMILE). METHODS: A total of 202 patients (404 eyes) underwent SMILE using the tear film mark centration method for myopia and myopic astigmatism correction. Baseline characteristics, objective optical quality, decentered displacement, induced corneal aberrations, and modulation transfer function (MTF) values were assessed. Linear regression analyzed the relationship between decentration and visual quality parameters, including corneal aberrations and MTF values. RESULTS: No significant difference was observed in objective visual quality, efficacy, and safety indexes between the two groups (all P > 0.05). The average decentered displacement for the first and second surgical eyes was 0.278 ± 0.17 mm and 0.315 ± 0.15 mm, respectively (P = 0.002). The horizontal coma in the first surgical eyes were notably lower than in the second (P = 0.000). MTF values at spatial frequencies of 5, 10, 15, and 20 cycles/degree (c/d) were higher in the first surgical eyes compared to the second (all P < 0.05). Linear regression indicated that high-order aberrations (HOAs), root mean square (RMS) coma, spherical aberration, horizontal coma, vertical coma, and eccentric displacement were all linearly correlated. Furthermore, MTF values exhibited a linear relationship with eccentric displacement across these spatial frequencies. CONCLUSIONS: There was no discernible difference in visual acuity, efficacy, or safety between the two operated eyes. Nonetheless, the first operated eyes exhibited reduced decentered displacement and demonstrated superior outcomes in terms of horizontal coma and MTF values compared to the second operated eyes following SMILE. The variations in visual quality parameters were linearly correlated with decentered displacement.

Bibliometric analysis and systematic review of electrochemical methods for environmental remediation.

Electrochemical methods are increasingly favored for remediating polluted environments due to their environmental compatibility and reagent-saving features. However, a comprehensive understanding of recent progress, mechanisms, and trends in these methods is currently lacking. Web of Science (WoS) databases were utilized for searching the primary data to understand the knowledge structure and research trends of publications on electrochemical methods and to unveil certain hotspots and future trends of electrochemical methods research. The original data were sampled from 9080 publications in those databases with the search deadline of June 1st, 2022. CiteSpace and VOSviewer software facilitated data visualization and analysis of document quantities, source journals, institutions, authors, and keywords. We discussed principles, influencing factors, and progress related to seven major electrochemical methods. Notably, publications on this subject have experienced significant growth since 2007. The most frequently-investigated areas in electrochemical methods included novel materials development, heavy metal remediation, organic pollutant degradation, and removal mechanism identification. "Advanced oxidation process" and "Nanocomposite" are currently trending topics. The major remediation mechanisms are adsorption, oxidation, and reduction. The efficiency of electrochemical systems is influenced by material properties, system configuration, electron transfer efficiency, and power density. Electro-Fenton exhibits significant advantages in achieving synergistic effects of anodic oxidation and electro-adsorption among the seven techniques. Future research should prioritize the improvement of electron transfer efficiency, the optimization of electrode materials, the exploration of emerging technology coupling, and the reduction in system operation and maintenance costs.

Increased Expression of TMPRSS11E Is Involved in LPS- or Poly(I:C)-mediated Inflammation.

Transmembrane serine proteases are a group of enzymes that are implicated in diverse biological processes. Transmembrane serine protease 11E (TMPRSS11E) is expressed in epithelial cells. Previous studies on TMPRSS11E mainly focused on its function in tumor progression. In this study, we investigated the association of TMPRSS11E with the inflammatory response. We found that TMPRSS11E levels were upregulated in the BAL fluid of patients with acute respiratory distress syndrome and LPS-stimulated cultured epithelial cells. In an LPS-induced acute lung injury mouse model and a cercal ligation and puncture-induced sepsis model, increased expression levels of TMPRSS11E were also observed in the lung tissues. Knockdown of TMPRSS11E suppressed the proinflammatory cytokine release and alleviated lung injury. In addition, increased TMPRSS11E expression was detected in lung tissues of poly(I:C)-challenged mice, and overexpression of TMPRSS11E aggregated the lung injury. Unexpectedly, ectopic TMPRSS11E expression in macrophages was observed. Protease-activated receptor-1 was proteolytically activated by TMPRSS11E and enhanced the levels of proinflammatory cytokines. Taken together, our results indicate that TMPRSS11E can be induced during inflammatory response triggered by infection. Therefore, interventions with TMPRSS11E can aid in the treatment of pulmonary inflammation.

PAX5 and circ1857 affected DLBCL progression and B-cell proliferation through regulating GINS1.

PAX5, a member of the paired box gene family of transcription factors, is a B-cell-specific activator protein that plays important roles during B lymphopoiesis. Two putative PAX5 binding sites in the human GINS1 promoter region were identified. EMSA, ChIP and luciferase assay showed that PAX5 functions as a positive transcription factor for GINS1 expression. Furthermore, coordinated expression of PAX5 and GINS1 was observed in mice B cells under physiological conditions and LPS stimulation situations. A similar pattern was also observed in human DLBCL cell lines under differentiation-inducing conditions. In addition, both PAX5 and GINS1 were highly expressed and significantly correlated in DLBCL specimens and cell lines. These findings suggested that dysregulation of PAX5 played an extremely important role in controlling the universal phenomenon of tumor progression through increased expression of GINS1 in DLBCL. In addition, circ1857 that was generated using back splicing of PAX5 pre-mRNA could further stabilize GINS1 mRNA, modulate GINS1 expression and promote lymphoma progression. To the best of our knowledge, this report is the first to demonstrate the role of GINS1 in DLBCL progression, and the mechanism of GINS1 upregulation using both circ1857 and PAX5 in DLBCL was revealed. Our results suggested that GINS1 may be a possible therapeutic target for DLBCL.

Immune-related biomarkers predict the prognosis and immune response of breast cancer based on bioinformatic analysis and machine learning.

Breast cancer (BC) is the malignancy with the highest mortality rate among women, identification of immune-related biomarkers facilitates precise diagnosis and improvement of the survival rate in early-stage BC patients. 38 hub genes significantly positively correlated with tumor grade were identified based on weighted gene coexpression network analysis (WGCNA) by integrating the clinical traits and transcriptome analysis. Six candidate genes were screened from 38 hub genes basing on least absolute shrinkage and selection operator (LASSO)-Cox and random forest. Four upregulated genes (CDC20, CDCA5, TTK and UBE2C) were identified as biomarkers with the log-rank p < 0.05, in which high expression levels of them showed a poor overall survival (OS) and recurrence-free survival (RFS). A risk model was finally constructed using LASSO-Cox regression coefficients and it possessed superior capability to identify high risk patients and predict OS (p < 0.0001, AUC at 1-, 3- and 5-years are 0.81, 0.73 and 0.79, respectively). Decision curve analysis demonstrated risk score was the best prognostic predictor, and low risk represented a longer survival time and lower tumor grade. Importantly, multiple immune cell types and immunotherapy targets were observed increase in expression levels in high-risk group, most of which were significantly correlated with four genes. In summary, the immune-related biomarkers could accurately predict the prognosis and character the immune responses in BC patients. In addition, the risk model is conducive to the tiered diagnosis and treatment of BC patients.

Large aperture and defect-free liquid crystal planar optics enabled by high-throughput pulsed polarization patterning.

The liquid crystal (LC) geometrical phase optics, which is realized by the high-resolution control of the optical axis orientation in transparent micrometer-thin polymer films, is emerging as a next generation of planar optics. It features pronounced optical properties and stimuli-responsive behaviors, which could introduce appealing and new possibilities for photonic purposes. The development of fabrication techniques producing elements with large aperture sizes and arbitrarily varying molecular orientation is of significance in terms of practical utility. Here, we propose the pulsed polarization patterning technique to create large-aperture and defect-free LC geometrical phase elements. We investigated the capability of the azo photo-alignment material responding to nanosecond laser pulses and the corresponding anchoring behaviors to LCs. The threshold was reduced to one fourth of that under the continuous wave recording. The patterning resolution was found to be enhanced to around 0.71 µm, due to the ultra-fast interaction nature of the photo-alignment material with the polarized light field. We proposed the flying exposure mode to deliver high frequency modulated polarized laser pulses (8 kHz), with the precision stage moving in a uniform velocity for light-field stitching and the servo auto-focusing in the sample normal, enabling the stable and reliable polarization patterning for large aperture sizes. We further report on representative fabrication of LC polarization gratings with an aperture of 4 inch and 99.2% average diffraction efficiency.

Base-mediated carboxylation of C-nucleophiles with CO2.

Carbon dioxide (CO2) is an available, abundant, and renewable C1 resource, which could be converted into value-added chemicals. Due to its inherent thermodynamic stability and kinetic inertness, it is difficult to realize its efficient utilization. Nevertheless, many elegant strategies for the utilization of CO2 have been developed using Lewis bases, frustrated Lewis pairs, hydroxyl-containing compounds, amino-group-containing compounds or transition metal catalysis. Among them, base-mediated carboxylation of C-nucleophiles is an environmentally friendly strategy for CO2 conversion, which is operationally simple, using low-toxicity bases and economical available promoters, without the use of complex ligands or cocatalysts. This review summarizes related work on the base-mediated carboxylation of C-nucleophiles with CO2, based on the effects of nucleophiles, promoters, additives, and solvents. The types of pronucleophile are categorized as follows: hydrocarbon with C(sp3)-H, C(sp2)-H or C(sp)-H bonds, organosilanes, organotin, organoboron, and N-tosylhydrazones. Typical mechanisms and applications of these carboxylation reactions are also depicted. Moreover, mechanistic comprehension of CO2 activation and conversion at a molecular level aims to further expand the repertoire of carboxylation transformations mediated by bases.

Interactive effects of vitamin D and serum uric acid concentration on protein-energy wasting in maintenance hemodialysis patients.

This study aimed to explore the influence of the interaction between vitamin D level and blood uric acid level on protein-energy wasting (PEW) in patients with Maintenance hemodialysis (MHD), in order to provide a solution for disease prevention. For this aim, a total of 150 patients with maintenance hemodialysis aged 30-79 years in a hospital were included in the study. The logistic regression model was used to analyze the relationship between vitamin D level, blood uric acid level and PEW, and the additive interaction was evaluated by calculating the relative excess risk ratio (RERI) attributive ratio (AP) and synergy index (S) of the interaction. Finally, the ROC curve was drawn to evaluate the diagnostic value of vitamin D level and blood uric acid level for PEW. In this study, the detection rate of PEW was 68%, low vitamin D level was 57.33%, and high blood uric acid level was 64.67%. Compared with non-low vitamin D levels, the PEW risk was OR=16.794, 95%CI: 4.973-60.356; Compared with those without high uric acid levels, the PEW risk was OR=7.599, 95%CI: 2.460-23.468. However, there was no multiplicative interaction between the two on PEW risk (OR=0.345, 95%CI: 0.060-1.983, P=0.233). In the additive interaction analysis, the PEW risk OR=43.992,95%CI: 12.795-151.253, higher than those with only high uric acid levels or only low vitamin D levels, the combination of the two had a summative interaction with PEW risk, with a RERI of 20.599 (95%CI: -26.158-67.356) API was 0.468 (-0.159-1.095) and S was 1.920 (0.569-6.483). In conclusion, both vitamin D deficiency and high uric acid levels were associated with an increased risk of PEW in MHD patients, and low vitamin D and high uric acid levels had a summative interaction with protein-energy expenditure risk.

Remission effect of Canagliflozin in patients with newly diagnosed type 2 diabetes mellitus: a protocol for a multicenter, parallel-group, randomized, controlled, open-label trial.

BACKGROUND: Studies reporting the effects of metabolic surgery, lifestyle intervention, and intensive insulin therapy for the remission of type 2 diabetes (T2DM) has been increasing, with fruitful results better conducted and yielded. However, there are only a few studies on the remission of T2DM using oral hypoglycemic drugs. Therefore, this study aims to investigate the remission effect of canagliflozin and metformin on participants with newly diagnosed T2DM and its possible underlying mechanism(s) through which these two medications elicit diabetes remission. METHOD: To this end, we performed a multicenter, parallel-group, randomized, controlled, and open-label trial. A total of 184 participants with a ≤ 3-year course of T2DM will be enrolled and randomly assigned to the canagliflozin or metformin treatment group in a ratio of 1:1. Participants in each group will maintain their medication for 3 months after achieving the target blood glucose level and then stop it. These participants will be followed up for one year to determine remission rates in both groups. DISCUSSION: In this study, we will establish that whether canagliflozin is superior to metformin in terms of remission rate in participants with newly diagnosed T2DM. The results of this trial may provide robust evidence regarding the efficacy and mechanisms of the action of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in T2DM remission. TRIAL REGISTRATION: ChiCTR2100043770(February 28, 2021).

Time-series expression profiles of mRNAs and lncRNAs during mammalian palatogenesis.

OBJECTIVES: Mammalian palatogenesis is a highly regulated morphogenetic process to form the intact roof of the oral cavity. Long noncoding RNAs (lncRNAs) and mRNAs participate in numerous biological and pathological processes, but their roles in palatal development and causing orofacial clefts (OFC) remain to be clarified. METHODS: Palatal tissues were separated from ICR mouse embryos at four stages (E10.5, E13.5, E15, and E17). Then, RNA sequencing (RNA-seq) was used. Various analyses were performed to explore the results. Finally, hub genes were validated via qPCR and in situ hybridization. RESULTS: Starting from E10.5, the expression of cell adhesion genes escalated in the following stages. Cilium assembly and ossification genes were both upregulated at E15 compared with E13.5. Besides, the expression of cilium assembly genes was also increased at E17 compared with E15. Expression patterns of three lncRNAs (H19, Malat1, and Miat) and four mRNAs (Cdh1, Irf6, Grhl3, Efnb1) detected in RNA-seq were validated. CONCLUSIONS: This study provides a time-series expression landscape of mRNAs and lncRNAs during palatogenesis, which highlights the importance of processes such as cell adhesion and ossification. Our results will facilitate a deeper understanding of the complexity of gene expression and regulation during palatogenesis.

Two rare variants reveal the significance of Grainyhead-like 3 Arginine 391 underlying non-syndromic cleft palate only.

OBJECTIVES: Non-syndromic cleft palate only (NSCPO) is one of the most common craniofacial birth defects with largely undetermined genetic etiology. It has been established that Grainyhead-like 3 (GRHL3) plays an essential role in the pathogenesis of NSCPO. This study aimed to identify and verify the first-reported GRHL3 variant underlying NSCPO among the Chinese cohort. METHODS: We performed whole-exome sequencing (WES) on a Chinese NSCPO patient and identified a rare variant of GRHL3 (p.Arg391His). A validated deleterious variant p.Arg391Cys was introduced as a positive control. Zebrafish embryos injection, reporter assays, live-cell imaging, and RNA sequencing were conducted to test the pathogenicity of the variants. RESULTS: Zebrafish embryos microinjection demonstrated that overexpression of the variants could disrupt the normal development of zebrafish embryos. Reporter assays showed that Arg391His disturbed transcriptional activity of GRHL3 and exerted a dominant-negative effect. Interestingly, Arg391His and Arg391Cys displayed distinct nuclear localization patterns from that of wild-type GRHL3 in live-cell imaging. Bulk RNA sequencing suggested that the two variants changed the pattern of gene expression. CONCLUSIONS: In aggregate, this study identified and characterized a rare GRHL3 variant in NSCPO, revealing the critical role of Arginine 391 in GRHL3. Our findings will help facilitate understanding and genetic counseling of NSCPO.

Spatiotemporal variations and influential factors affecting reproductive dynamics of Pacific saury in the Northwest Pacific during fishing season.

This study examined the spatial and monthly variations in reproductive dynamics of Pacific saury collected in the high sea (40°N-49°N, 149°E-168°E) of the northwestern Pacific during the fishing season of the Taiwanese stick-held dip-net fisheries (July-November) from 2018 to 2019. Generalized additive mixed-effects models (GAMMs) were applied to explore the relationship between the probability of maturing and spawning occurrence (PMOS ) and the explanatory variables (month, body length, sea-surface temperature [SST] as fixed effects, and fishing set as a random effect) for the age 0 and age 1 fish, respectively. In addition, the impact of the geographical difference in growth rates of age 0 fish, quantified as the radius of the otolith annual ring, on the PMOS of age 1 fish was explored in the GAMMs. Results showed that the mean values of the condition factor (CF) varied by months, and higher mean CFs were observed north of 45°N. However, the mean values of the gonado-somatic index did not show a clear spatiotemporal pattern. The spatial distribution of the ovarian maturation states revealed that the spawning ground of Pacific saury during July-November was broader than that previously known and had partly overlapped with the high-sea fishing ground. The best GAMM showed that the predicted PMOS of the age 0 fish were generally low (mean = 19%, standard deviation [SD] = 10%) and tended to increase with increasing body length. In contrast, the predicted PMOS were relatively higher (mean = 37%, SD = 10%) for the age 1 fish and increased with increasing SST and decreasing latitude. Two candidate GAMMs, which are equally supported as the best model (ΔAIC < 2), provide evidence that a higher growth rate of age 0 fish may result in higher reproductive activity in age 1 fish. This is one of few studies focusing on the reproductive dynamics of Pacific saury during the fishing season; current limitations, future directions, and conservation implications were discussed.

Efficient Visible-Light-Activated Ultra-Long Room-Temperature Phosphorescence Triggered by Multi-Esterification.

The development of ultra-long room-temperature phosphorescence (UL-RTP) in processable amorphous organic materials is highly desirable for applications in flexible displays, anti-counterfeiting, and bio-imaging. However, achieving efficient UL-RTP from amorphous materials remains a challenging task, especially with activation by visible light and a bright afterglow. Here we report a general and rational molecular-design strategy to enable efficient visible-light-excited UL-RTP by multi-esterification of a rigid large-plane phosphorescence core. Notably, multi-esterification minimizes the aggregation-induced quenching and accomplishes a 'four birds with one stone' possibility in the generation and radiation process of UL-RTP: i) shifting the excitation from ultraviolet light to blue-light through enhancing the transition dipole moment of low-lying singlet-states, ii) facilitating the intersystem crossing process through the incorporation of lone-pair electrons, iii) boosting the decay process of long-lived triplet excitons resulting from a significantly increased transition dipole moment, and iv) reducing the intrinsic triplet nonradiative decay by substitution of high-frequency vibrating hydrogen atoms. All these factors synergistically contribute to the most efficient and stable visible-light-stimulated UL-RTP (lifetime up to 2.01 s and efficiency up to 35.4 % upon excitation at 450 nm) in flexible films using multi-esterified coronene, which allows high-tech applications in single-component time-delayed white light-emitting diodes and information technology based on flashlight-activated afterglow encryption.

High-throughput and controllable manufacturing of liquid crystal polymer planar microlens array for compact fingerprint imaging.

The microlens array (MLA) with a small geometric footprint and unique performances, is the key enabler to push the development of photonic devices toward miniaturization, multi-function and large-scale integration. However, the realization of 100% fill-factor (FF) MLAs with high controllability and its mass manufacturing without complex steps has always been a difficult issue. Here, we propose an efficient, highly flexible and low-cost manufacturing approach for MLAs with a high FF via snapshot polarization patterning. The digitalized linear polarization pattern was distributed across the photo-alignment layer with both high efficiency and accuracy, enabling large-area liquid crystal MLA with parameter controllability from element to element. The MLA manufacturing process does not involve developing, etching and deposition steps and is suitable for industry up-scaling. We further proposed a novel compact compound-eye imaging system for biometrics with the obtained MLAs. The 100% FF MLA enables high light utilization efficiency and low background crosstalk, yielding compact biometrics indentation with high recognition accuracy. The realization of such planar optics would lead to a plethora of different miniaturized multiaperture imaging systems in the future.

Wide field of view chiral imaging with a liquid crystal planar lens enabled by digitalized nanogratings.

To compensate for the inability for polarization imaging by conventional methods, metasurface optics with compactness and multi-function emerge as an approach to provide images with different linear and circular polarizations. Here, we propose a liquid crystal (LC) geometric phase-based chiral imaging lens (CIL) that simultaneously forms images of objects with opposite helicity. The CIL (Diameter 2.3 cm) was optimized by a spatial multiplexing algorithm and realized using the digital holography technique, where the LC domains were regulated by pixelated nanogratings with varied orientation. We investigated the potential of the patterning technique toward high order LC alignment by balancing the periodicity and depth of the nanogratings. The CIL exhibited a wide field of view of ±20°, which is attributed to the self- assembling effects of LC molecules. The compactness, lightness, and ability to produce chiral images of the LC CIL even at large angles have significant potential for practical polarization imaging.

Combined assessment of tumour cell nest size and desmoplastic reaction as an excellent prognostic predictor in oesophageal squamous cell carcinoma.

AIMS: Tumour budding (TB) activity, cell nest size (CNS), and desmoplastic reaction (DR) have been confirmed to be significantly correlated with prognosis in oesophageal squamous cell cancer (ESCC) recently. However, there are limited data on the prognostic significance of combined assessment of cellular dissociation and tumour stroma in ESCC. METHODS: In all, 265 cases with resected ESCCs diagnosed between January 2018 and August 2019 were retrospectively reviewed. All slides were reviewed for assessing TB, CNS, and DR. The Cellular Dissociation Grading and our Combined CNS and DR (CNS/DR) Grading systems were adopted to re-grade ESCCs. RESULTS: High TB activity, small CNS, and immature DR had a strong association with shorter overall survival (OS) and progression-free survival (PFS) (P < 0.001, respectively) in ESCC. Combined assessment of CNS and DR in a 4-tiered grading system displayed a prognostic excellence for survival (P < 0.001), and outperformed the Cellular Dissociation Grading for both OS (area under the curve [AUC], 0.728 versus 0.644, P = 0.043) and PFS (AUC, 0.763 versus 0.667, P = 0.018) by receiver operator characteristic curves. Also, Combined CNS/DR Grading showed superiority in recognizing a G4 subgroup with the worst outcome in our cohort, to whom the most urgent attention needs to be called. CONCLUSIONS: This is the first study to propose a novel Combined Grading system based on CNS and DR in ESCC, which has been demonstrated to be relatively superior to Cellular Dissociation Grading in predicting prognosis. The findings shed new light on the histopathological grading of ESCC and facilitates identifying biologically aggressive ESCCs.

Metal-Free Hydroxymethylation of Indole Derivatives with Formic Acid as an Alternative Way to Indirect Utilization of CO2.

The selective N-alkylation of indole substrates remains an ongoing research challenge for the relative attenuated nucleophilicity toward nitrogen. Herein, we developed the hydroxymethylation of indole derivatives to afford N-alkylated indole products with formic acid. This metal-free process was promoted by the organic base 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) using phenylsilane as the reductant under mild conditions. Besides, this strategy represents an alternative way for indirect utilization of CO2, considering the facile hydrogenation of CO2 to produce HCOOH.

Strong Circularly-Polarized Room-Temperature Phosphorescence from a Feasibly Separable Scaffold of Bidibenzo[b,d]furan with Locked Axial Chirality.

Novel accessible scaffold featuring circularly-polarized room-temperature phosphorescence (RTP) is attractive but challenging. Herein, we report a new feasibly separable bidibenzo[b,d]furan compound with strong circularly-polarized RTP when doping into the rigid polymer matrix. The simple silica-gel column can separate the absolute chiral R-isomer with excellent chiroptical properties. The experimental data reveal that the treated films exhibit an RTP efficiency of 14.8 %, a largest dissymmetric factor of 0.12, and a longest lifetime of 0.56 s under ambient conditions. It is found that reducing the nonradiative decays boosts the intrinsic circularly-polarized RTP emission. The impressive results indicate that the locked axial chirality skeleton endows the potential of achieving superior circularly-polarized emission for the small organic optoelectronic molecules.

A novel intracellular nanobody against HPV16 E6 oncoprotein.

Cervical cancer occurs as a result of the persistent infection of high-risk human papillomavirus (HPV). HPV16 oncoproteins E6 and E7 exert different and concerted pro-tumor actions in cell transformation and malignance maintenance in various m echanisms. Nanobody expressed as "intracellular antibodies" (intrabodies) can target intracellular antigens to hamper their function efficaciously and specifically. In this work, phage-display approach was employed to select the high affinity HPV16 E6-specific nanobody, nanobody Nb9 against HPV16 E6 was selected. Nb9 has high affinity (Kaff =6.3 × 108 M-) and can specifically bind endogenous HPV16 E6 protein in HPV16 positive CaSki and SiHa cells. In Nb9 overexpressed SiHa and CaSki cells, nucleus localization of HPV16 E6 was inhibited, p53 inactivation was prevented and increased apoptosis was observed. Moreover, tumor growth was inhibited in mouse xenograft model. Taken together, our results suggested that nanobody Nb9 could be a useful inhibitor for HPV16 E6 function and particularly appropriate for the treatment of HPV-associated disease.