Finite immune imprinting on neutralizing antibody responses to Omicron subvariants by repeated vaccinations.

OBJECTIVE: To investigate the effects of repeated vaccination with ancestral SARS-CoV-2 (Wuhan-hu-1)-based inactivated, recombinant protein subunit or vector-based vaccines on the neutralizing antibody response to Omicron subvariants. METHODS: Individuals who received four-dose vaccinations with the Wuhan-hu-1 strain, individuals who were infected with the BA.5 variant alone without prior vaccination, and individuals who experienced a BA.5 breakthrough infection following receiving 2-4 doses of the Wuhan-hu-1 vaccine were enrolled. Neutralizing antibodies against D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 were detected using a pseudovirus-based neutralization assay. Antigenic cartography was used to analyze cross-reactivity patterns among D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 and sera from individuals. RESULTS: The highest neutralizing antibody titers against D614G were observed in individuals who only received four-dose vaccination and those who experienced BA.5 breakthrough infection, which was also significantly higher than the antibody titers against XBB.1.5, EG.5.1, and BA.2.86. In contrast, only BA.5 infection elicited comparable neutralizing antibody titers against the tested variants. While neutralizing antibody titers against D614G or BA.5 were similar across the cohorts, the neutralizing capacity of antibodies against XBB.1.5, EG.5.1, and BA.2.86 was significantly reduced. BA.5 breakthrough infection following heterologous booster induced significantly higher neutralizing antibody titers against the variants, particularly against XBB.1.5 and EG.5.1, than uninfected vaccinated individuals, only BA.5 infected individuals, or those with BA.5 breakthrough infection after primary vaccination. CONCLUSIONS: Our findings suggest that repeated vaccination with the Wuhan-hu-1 strain imprinted a neutralizing antibody response toward the Wuhan-hu-1 strain with limited effects on the antibody response to the Omicron subvariants.

Coronary Microvascular Function Assessment using the Coronary Angiography-Derived Index of Microcirculatory Resistance in Patients with ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

Background: Studies reporting the status of coronary microvascular function in the infarct-related artery (IRA) after primary percutaneous coronary intervention (PCI) remain limited. This study utilized the coronary angiography-derived index of microcirculatory resistance (caIMR) to assess coronary microvascular function in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI. Methods: We used the FlashAngio system to measure the caIMR after primary PCI in 157 patients with STEMI. The primary endpoint was the occurrence of a major adverse cardiovascular event (MACE), defined as a composite endpoint encompassing cardiac mortality, target vessel revascularization, and rehospitalization due to congestive heart failure (CHF), myocardial infarction (MI), or angina. Results: Approximately 30% of patients diagnosed with STEMI and who experienced successful primary PCI during the study period had a caIMR in the IRA of > 40. The caIMR in the IRA was significantly higher than in the reference vessel (32.9 ± 15.8 vs. 27.4 ± 11.1, p < 0.001). The caIMR in the reference vessel of the caIMR > 40 group was greater than in the caIMR ≤ 40 group (30.9 ± 11.3 vs. 25.9 ± 10.7, p = 0.009). Moreover, the caIMR > 40 group had higher incidence rates of MACEs at 3 months (25.5% vs. 8.3%, p = 0.009) and 1 year (29.8% vs. 13.9%, p = 0.04), than in the caIMR ≤ 40 group, which were mainly driven by a higher rate of rehospitalization due to CHF, MI, or angina. A caIMR in the IRA of > 40 was an independent predictor of a MACE at 3 months (hazard ratio (HR): 3.459, 95% confidence interval (CI): 1.363-8.779, p = 0.009) and 1 year (HR: 2.384, 95% CI: 1.100-5.166, p = 0.03) in patients with STEMI after primary PCI. Conclusions: Patients with STEMI after primary PCI often have coronary microvascular dysfunction, which is indicated by an increased caIMR in the IRA. An elevated caIMR of > 40 in the IRA was associated with an increased risk of adverse outcomes in STEMI patients undergoing primary PCI.

Variant-specific antibody response following repeated SARS-CoV-2 vaccination and infection.

The ongoing emergence of SARS-CoV-2 variants poses challenges to the immunity induced by infections and vaccination. We conduct a 6-month longitudinal evaluation of antibody binding and neutralization of sera from individuals with six different combinations of vaccination and infection against BA.5, XBB.1.5, EG.5.1, and BA.2.86. We find that most individuals produce spike-binding IgG or neutralizing antibodies against BA.5, XBB.1.5, EG.5.1, and BA.2.86 2 months after infection or vaccination. However, compared to ancestral strain and BA.5 variant, XBB.1.5, EG.5.1, and BA.2.86 exhibit comparable but significant immune evasion. The spike-binding IgG and neutralizing antibody titers decrease in individuals without additional antigen exposure, and <50% of individuals neutralize XBB.1.5, EG.5.1, and BA.2.86 during the 6-month follow-up. Approximately 57% of the 107 followed up individuals experienced an additional infection, leading to improved binding IgG and neutralizing antibody levels against these variants. These findings provide insights into the impact of SARS-CoV-2 variants on immunity following repeated exposure.

An electrochemically responsive B-O dynamic bond to switch photoluminescence of boron-nitrogen-doped polyaromatics.

Boron-doped polycyclic aromatic hydrocarbons exhibit excellent optical properties, and regulating their photophysical processes is a powerful strategy to understand the luminescence mechanism and develop new materials and applications. Herein, an electrochemically responsive B-O dynamic coordination bond is proposed, and used to regulate the photophysical processes of boron-nitrogen-doped polyaromatic hydrocarbons. The formation of the B-O coordination bond under a suitable voltage is confirmed by experiments and theoretical calculations, and B-O coordination bond can be broken back to the initial state under opposite voltage. The whole process is accompanied by reversible changes in photophysical properties. Further, electrofluorochromic devices are successfully prepared based on the above electrochemically responsive coordination bond. The success and harvest of this exploration are beneficial to understand the luminescence mechanism of boron-nitrogen-doped polyaromatic hydrocarbons, and provide ideas for design of dynamic covalent bonds and broaden material types and applications.

Multiple Chirality Switching of a Dye-Grafted Helical Polymer Film Driven by Acid & Base.

A stimuli-responsive multiple chirality switching material, which can regulate opposed chiral absorption characteristics, has great application value in the fields of optical modulation, information storage and encryption, etc. However, due to the rareness of effective functional systems and the complexity of material structures, developing this type of material remains an insurmountable challenge. Herein, a smart polymer film with multiple chirality inversion properties was fabricated efficiently based on a newly-designed acid & base-sensitive dye-grafted helical polymer. Benefited from the cooperative effects of various weak interactions (hydrogen bonds, electrostatic interaction, etc.) under the aggregated state, this polymer film exhibited a promising acid & base-driven multiple chirality inversion property containing record switchable chiral states (up to five while the solution showed three-state switching) and good reversibility. The creative exploration of such a multiple chirality switching material can not only promote the application progress of current chiroptical regulation technology, but also provide a significant guidance for the design and synthesis of future smart chiroptical switching materials and devices.

Recent Progress of Quantum Dots Light-Emitting Diodes: Materials, Device Structures, and Display Applications.

Colloidal quantum dots (QDs), as a class of 0D semiconductor materials, have generated widespread interest due to their adjustable band gap, exceptional color purity, near-unity quantum yield, and solution-processability. With decades of dedicated research, the potential applications of quantum dots have garnered significant recognition in both the academic and industrial communities. Furthermore, the related quantum dot light-emitting diodes (QLEDs) stand out as one of the most promising contenders for the next-generation display technologies. Although QD-based color conversion films are applied to improve the color gamut of existing display technologies, the broader application of QLED devices remains in its nascent stages, facing many challenges on the path to commercialization. This review encapsulates the historical discovery and subsequent research advancements in QD materials and their synthesis methods. Additionally, the working mechanisms and architectural design of QLED prototype devices are discussed. Furthermore, the review surveys the latest advancements of QLED devices within the display industry. The narrative concludes with an examination of the challenges and perspectives of QLED technology in the foreseeable future.

Accuracy and Reproducibility of Coronary Angiography-Derived Fractional Flow Reserve in the Assessment of Coronary Lesion Severity.

Purpose: Coronary angiography-derived fractional flow reserve (caFFR) is a novel computational flow dynamics (CFD)-derived assessment of coronary vessel flow with good diagnostic performance. Herein, we performed a retrospective study to evaluate the reproducibility of caFFR findings between observers and investigate the diagnostic performance of caFFR for coronary stenosis defined as FFR ≤0.80, especially in the grey zone (0.75≤caFFR ≤0.80). Patients and Methods: A total of 150 patients (167 coronary vessels) underwent caFFR (with FlashAngio used for calculation of flow variables) and subsequent invasive fractional flow reserve (FFR) measurements. Outcomes, including reproducibility, were compared for vessels in and outside the grey zone. Results: The correlation of caFFR findings was good between the two laboratories (r = 0.723, p<0.001). The AUC of ROC were both high for caFFR-CoreLab1 and caFFR-CoreLab2 (0.975 and 0.883). The diagnostic accuracy, sensitivity, specificity, and negative and positive predictive values were not significantly different between the two laboratories (p>0.05). caFFR had a strong correlation with measures to FFR (r=0.911, p<0.001). There was no systematic difference between caFFR and FFR on Bland-Altman analysis in and outside the grey zone. There was no difference in diagnostic accuracy between the grey and non-grey zones in the prediction of FFR ≤0.80 (p=0.09). Conclusion: The inter-observer reproducibility for caFFR was high, and the diagnostic accuracy of caFFR was good compared to that of FFR.

Proteogenomics of clear cell renal cell carcinoma response to tyrosine kinase inhibitor.

The tyrosine kinase inhibitor (TKI) Sunitinib is one the therapies approved for advanced renal cell carcinoma. Here, we undertake proteogenomic profiling of 115 tumors from patients with clear cell renal cell carcinoma (ccRCC) undergoing Sunitinib treatment and reveal the molecular basis of differential clinical outcomes with TKI therapy. We find that chromosome 7q gain-induced mTOR signaling activation is associated with poor therapeutic outcomes with Sunitinib treatment, whereas the aristolochic acid signature and VHL mutation synergistically caused enhanced glycolysis is correlated with better prognosis. The proteomic and phosphoproteomic analysis further highlights the responsibility of mTOR signaling for non-response to Sunitinib. Immune landscape characterization reveals diverse tumor microenvironment subsets in ccRCC. Finally, we construct a multi-omics classifier that can detect responder and non-responder patients (receiver operating characteristic-area under the curve, 0.98). Our study highlights associations between ccRCC molecular characteristics and the response to TKI, which can facilitate future improvement of therapeutic responses.

Proteogenomic characterization of MiT family translocation renal cell carcinoma.

Microphthalmia transcription factor (MiT) family translocation renal cell carcinoma (tRCC) is a rare type of kidney cancer, which is not well characterized. Here we show the comprehensive proteogenomic analysis of tRCC tumors and normal adjacent tissues to elucidate the molecular landscape of this disease. Our study reveals that defective DNA repair plays an important role in tRCC carcinogenesis and progression. Metabolic processes are markedly dysregulated at both the mRNA and protein levels. Proteomic and phosphoproteome data identify mTOR signaling pathway as a potential therapeutic target. Moreover, molecular subtyping and immune infiltration analysis characterize the inter-tumoral heterogeneity of tRCC. Multi-omic integration reveals the dysregulation of cellular processes affected by genomic alterations, including oxidative phosphorylation, autophagy, transcription factor activity, and proteasome function. This study represents a comprehensive proteogenomic analysis of tRCC, providing valuable insights into its biological mechanisms, disease diagnosis, and prognostication.

Effects of Y2O3 and LiAl5O8 on the Microstructure and Optical Properties of Reactively Sintered AlON Based Transparent Ceramics.

Sintering aid was very crucial to influence the microstructure and thus the optical property of the sintered optical ceramics. The purpose of this work was to explain the difference between the sintering aids of Li+ and Y3+ on Al23O27N5 (AlON) ceramic via reaction sintering method. The effects of LiAl5O8 (LA) and Y2O3 on the sintering of Al2O3-AlN system were carefully compared, in terms of X-ray diffraction (XRD), microstructure, density, X-ray photoelectron spectroscopy (XPS) and optical transmittance. According to the XPS and XRD lattice analysis, the chemical structure of the materials was not obviously affected by different dopants. We firstly reported that, there was obvious volume expansion in the Y3+ dopped AlON ceramics, which was responsible for the low transparency of the ceramics. Obvious enhancements were achieved using Li+ aids from the results that Li: AlONs showing a higher transparency and less optical defects. A higher LA content (20 wt%) was effective to remove pores and thus obtain a higher transmittance (~86.8% at ~3.5 µm). Thus, pores were the main contributions to the property difference between the dopant samples. The importance of sintering aids should be carefully realized for the reaction sintering fabrication of AlON based ceramics towards high transparency.

A Flexible Circularly Polarized Luminescence Switching Device Based on Proton-Coupled Electron Transfer.

Flexible circularly polarized luminescence (CPL) switching devices have been long-awaited due to their promising potential application in wearable optoelectronic devices. However, on account of the few materials and complicated design of manufacturing systems, how to fabricate a flexible electric-field-driven CPL-switching device is still a serious challenge. Herein, a flexible device with multiple optical switching properties (CPL, circular dichroism (CD), fluorescence, color) is designed and prepared efficiently based on proton-coupled electron transfer (PCET) mechanism by optimizing the chiral structure of switching molecule. More importantly, this device can maintain the switching performance even after 300 bending-unbending cycles. It has a remarkable comprehensive performance containing bistable property, low open voltage, and good cycling stability. Then, prototype devices with designed patterns have been fabricated, which opens a new application pattern of CPL-switching materials.

A proteogenomic analysis of clear cell renal cell carcinoma in a Chinese population.

Clear cell renal cell carcinoma (ccRCC) is a common and aggressive subtype of renal cancer. Here we conduct a comprehensive proteogenomic analysis of 232 tumor and adjacent non-tumor tissue pairs from Chinese ccRCC patients. By comparing with tumor adjacent tissues, we find that ccRCC shows extensive metabolic dysregulation and an enhanced immune response. Molecular subtyping classifies ccRCC tumors into three subtypes (GP1-3), among which the most aggressive GP1 exhibits the strongest immune phenotype, increased metastasis, and metabolic imbalance, linking the multi-omics-derived phenotypes to clinical outcomes of ccRCC. Nicotinamide N-methyltransferase (NNMT), a one-carbon metabolic enzyme, is identified as a potential marker of ccRCC and a drug target for GP1. We demonstrate that NNMT induces DNA-dependent protein kinase catalytic subunit (DNA-PKcs) homocysteinylation, increases DNA repair, and promotes ccRCC tumor growth. This study provides insights into the biological underpinnings and prognosis assessment of ccRCC, revealing targetable metabolic vulnerabilities.

Wide-Range and Highly Sensitive Chiral Sensing by Discrete 2D Chirality Transfer on Confined Surfaces of Au(I)-Thiolate Nanosheets.

Circular dichroism (CD) chiral sensing is very promising to meet the ever-increasing demands for high-throughput chiral analysis in asymmetric synthesis. However, it is still very challenging to sensitively quantify the composition of enantiomers in a wide concentration range because the existing sensing systems show either linear CD response resultant from stoichiometric chiral transfer or nonlinear CD response resultant from amplified chiral transfer and thus have the drawbacks of low sensitivity and narrow quantification range, respectively. Herein, we propose a sensing system of two-dimensional (2D) Au(I)-thiolate nanosheets. The disordered interligand interactions on the confined surfaces of nanosheets enable the formation of discrete amplified chiral domains around the adsorbed chiral analytes, resulting in a linearly amplified chiral transfer behavior, which provides a solution for highly sensitive and wide-range quantification of enantiomer compositions. Taking (1R, 2R)-(-)- and (1S, 2S)-(+)-1,2-diamino cyclohexanes as example analytes, the concentration and full-range enantiomeric excess (ee) values have been quickly determined by adsorbing them on the surface of Au(I)-MPA (MPA: 3-mercaptopropionic acid) nanosheets in the concentration range of 1.0 × 10-6 to 4.0 × 10-5 M. By engineering the surface functional groups, Au(I)-thiolate nanosheets can be extended to sense other types of analytes, and several polyols with multiple chiral centers have been sensed by boronic acid functionalized nanosheets at the 10-7 M level. The high performances, good extendibility, and one-pot high-yield aqueous synthesis ensure these Au(I)-thiolate nanosheets can be developed as a practical and powerful chiral sensing platform.

Coronary Microcirculatory Function Indicated by Coronary Angiography-Derived Index of Microvascular Resistance in Patients Undergoing Rotational Atherectomy.

Background: There are scarce published data reporting the effect of rotational atherectomy (RA) on coronary microcirculation function. Objectives: We aimed to evaluate coronary microcirculation function indicated by the coronary angiography-derived index of microvascular resistance (caIMR) in patients undergoing RA. Methods: RA procedures between January 2013 and December 2021 were retrospectively analyzed. We investigated coronary microcirculation function indicated by caIMR as well as peri-procedural adverse events among the study population. All caIMR measurements were performed using a FlashAngio system. The primary outcome was a composite of post-RA thrombolysis in myocardial infarction (TIMI) flow grade < 3 in the target vessel, myocardial injury, procedure-related myocardial infarction, and cardiac death during hospitalization. Results: A total of 155 RA procedures were analyzed. The post-RA caIMRs were significantly higher than pre-RA caIMRs in the target vessels (16.0 ± 7.0 vs. 14.5 ± 7.5, p = 0.029). Patients with post-RA caIMR ≥ 25 accounted for nearly 12% of those with pre-RA caIMR < 25. Patients with post-RA thrombolysis in myocardial infarction (TIMI) flow grade < 3 had a significantly higher pre-RA caIMR (23.5 ± 10.2 vs. 13.7 ± 6.6, p = 0.005), and the proportion of patients with pre-RA caIMR ≥ 25 in the group with TIMI flow grade < 3 was greater (61.5% vs. 38.5%, p < 0.001) than that in the group with TIMI flow grade of 3. Maximum RA time of each pass (odds ratio: 1.127, 95% confidence interval: 1.025-1.239, p = 0.014) and pre-RA caIMR ≥ 25 (odds ratio: 3.254, 95% confidence interval: 1.054-10.048, p = 0.040) were identified to be the independent predictors of the primary outcome for patients who underwent RA. Conclusions: There were significant changes in the coronary microcirculation function of the target vessels after receiving RA as indicated by increased post-RA caIMR compared to pre-RA caIMR. Patients with baseline coronary microcirculatory dysfunction were more likely to have post-RA TIMI flow grade < 3, whereas those with pre-RA caIMR ≥ 25 experienced worse outcomes.

Optical Properties of Bulk Single-Crystal Diamonds at 80-1200 K by Vibrational Spectroscopic Methods.

Bulk diamonds show great potential for optical applications such as for use in infrared (IR) windows and temperature sensors. The development of optical-grade bulk diamond synthesis techniques has facilitated its extreme applications. Here, two kinds of bulk single-crystal diamonds, a high-pressure and high-temperature (HPHT) diamond and a chemical vapor deposition (CVD) diamond, were evaluated by Raman spectroscopy and Fourier Transform Infra-Red (FTIR) spectroscopy at a range of temperatures from 80 to 1200 K. The results showed that there was no obvious difference between the HPHT diamond and the CVD diamond in terms of XRD and Raman spectroscopy at 300-1200 K. The measured nitrogen content was ~270 and ~0.89 ppm for the HPHT diamond and the CVD diamond, respectively. The moderate nitrogen impurities did not significantly affect the temperature dependence of Raman spectra for temperature-sensing applications. However, the nitrogen impurities greatly influence FTIR spectroscopy and optical transmittance. The CVD diamond showed higher transmittance, up to 71% with only a ~6% drop at temperatures as high as 873 K. This study shows that CVD bulk diamonds can be used for IR windows under harsh environments.

Procedural Results and Long-Term Outcomes of Percutaneous Coronary Intervention for in-Stent Restenosis Chronic Total Occlusion Compared with de novo Chronic Total Occlusion.

BACKGROUND: In-stent restenosis (ISR) chronic total occlusion (CTO) represents a challenging subgroup for revascularization of CTO by percutaneous coronary intervention (PCI). There are limited data on the treatment and outcomes of PCI for ISR CTO. OBJECTIVE: We aimed to evaluate the procedural results and 2-year outcomes of PCI for ISR CTO compared with de novo CTO. METHODS: Patients undergoing attempted CTO PCI between January 2017 and December 2019 were prospectively enrolled. We analyzed the procedural results and 2-year major adverse cardiac events (MACE) in patients undergoing ISR CTO and those undergoing de novo CTO PCI. RESULTS: A total of 426 patients undergoing 484 consecutive CTO PCI (ISR CTO PCI, n=84; de novo CTO, n=400) were enrolled during the study period. Patients undergoing de novo CTO PCI had a significantly greater syntax score than those undergoing ISR CTO PCI [23.0 (17.5, 30.5) vs 21.5 (14.5, 27.0), p=0.039]. Technical (73.8% vs 79.0%, p=0.296) and procedural (73.8% vs 78.0, p=0.405) success rates, as well as the incidence of major procedural complications (1.2% vs 2.3%, p=0.842), were comparable between the two groups. After a median follow-up of 20 months, patients who underwent ISR CTO PCI had a significantly higher incidence of MACE (33.3% vs 10.3%, p<0.001), mainly attributed to the higher TVR rates (24.7% vs 7.6%, p<0.001). ISR CTO was the only independent predictor of MACE (hazard ratio, 4.124; 95% confidence interval, 1.951-8.717; p<0.001) during follow-up in patients who underwent CTO PCI. CONCLUSION: ISR CTO PCI shows comparable technical and procedural success, as well as major procedural complications compared with de novo CTO PCI. However, patients who underwent ISR CTO PCI had a significantly worse prognosis than those who underwent de novo CTO PCI, in terms of MACE, driven by TVR. ISR CTO was the only independent predictor of MACE during the follow-up.

Proteome-Wide Profiling of Readers for DNA Modification.

DNA modifications, represented by 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), play important roles in epigenetic regulation of biological processes. The specific recognition of DNA modifications by the transcriptional protein machinery is thought to be a potential mechanism for epigenetic-driven gene regulation, and many modified DNA-specific binding proteins have been uncovered. However, the panoramic view of the roles of DNA modification readers at the proteome level remains largely unclear. Here, a recently developed concatenated tandem array of consensus transcription factor (TF) response elements (catTFREs) approach is employed to profile the binding activity of TFs at DNA modifications. Modified DNA-binding activity is quantified for 1039 TFs, representing 70% of the TFs in the human genome. Additionally, the modified DNA-binding activity of 600 TFs is monitored during the mouse brain development from the embryo to the adult stages. Readers of these DNA modifications are predicted, and the hierarchical networks between the transcriptional protein machinery and modified DNA are described. It is further demonstrated that ZNF24 and ZSCAN21 are potential readers of 5fC-modified DNA. This study provides a landscape of TF-DNA modification interactions that can be used to elucidate the epigenetic-related transcriptional regulation mechanisms under physiological conditions.