Halogen Bond Unlocks Ultra-High Birefringence.

Anisotropy is crucial for birefringence (Δn) in optical materials, but optimizing it remains a formidable challenge (Δn > 0.3). Supramolecular frameworks incorporating π-conjugated components are promising for achieving enhanced birefringence since their structural diversity and inherent anisotropy. Herein, we first synthesized (C6H6NO2)+Cl- (NAC). And then constructed a halogen bonded supramolecular framework I+(C6H4NO2)- (INA) by halogen aliovalent substitution of Cl- with I+. The organic moieties are protonated and deprotonated nicotinic acid (NA), respectively. The antiparallel arrangement of birefringent-active units in NAC and INA leads to significant differences in bonding characteristics between interlayer and intralayer domains. Moreover, [O···I+···N] halogen bond in 1D [I+(C6H4NO2)-] chain exhibits stronger interactions and stricter directionality, resulting in a more pronounced in-plane anisotropy between the intrachain and interchain directions. Consequently, INA exhibits exceptional birefringent performance, with a value of 0.778 at 550 nm, twice that of NAC (0.363 at 550 nm). This value significantly exceeds those of commercial birefringent crystals, such as CaCO3 (0.172 at 546 nm), and is the highest reported value among ultraviolet birefringent crystals. This work presents a novel design strategy that employs halogen bonds as connection sites and modes for birefringent-active units, opening new avenues for developing high-performance birefringent crystals.

Metal-containing nanoparticles in road dust from a Chinese megacity over the last decade: Spatiotemporal variation and driving factors.

As a crucial sink of metal-containing nanoparticles (MNPs), road dust can record their spatiotemporal variations in urban environments. In this study, taking Shanghai as a representative megacity in China, a total of 272 dust samples were collected in the winter and summer of 2013 and 2021/2022 to understand the spatiotemporal variations and driving factors of MNPs. The number concentrations of Fe-, Ti-, and Zn-containing NPs were 3.8 × 106 - 8.4 × 108, 2.3 × 106-1.4 × 108, and 6.0 × 105-2.3 × 108 particles/mg, respectively, according to single particle (sp)ICP-MS analysis. These MNPs showed significantly higher number concentrations in summer than in winter. Hotspots of Fe-containing NPs were more concentrated in industrial and traffic areas, Zn-containing NPs were mainly distributed in the central urban areas, while Ti-containing NPs were abundant in areas receiving high rainfall. The structural equation model results indicates that substantial rainfall in summer can help remove MNPs from atmospheric PM2.5 into dust, while in winter industrial and traffic activities were the primary contributors for MNPs. Moreover, the contribution of traffic emissions to MNPs has surpassed industrial one over the last decade, highlighting the urgency to control traffic-sourced MNPs, especially those from non-exhaust emissions by electric vehicles.

Polymeric microlens array formed on a discontinuous wetting surface using a self-assembly technique.

In this paper, we demonstrate a facile way to prepare polymeric microlens arrays (MLAs) based on a discontinuous wetting surface using a self-assembly technique. A patterned hydrophobic-octadecyltrichlorosilane (OTS) surface was prepared by U V/O 3 irradiation through a shadow mask. The area exposed to U V/O 3 irradiation turned highly hydrophilic, whereas the area protected by the mask remained highly hydrophobic, generating the patterned OTS surface. The surface energy of the OTS/glass surface changed from 23 to 72.8 mN/m after 17 min of U V/O 3 treatment. The scribing of the optical glue-NOA 81 onto the microhole array enabled one to obtain the MLAs due to the generation of the NOA 81 droplet array via the surface tension. After UV light curing, the cured NOA 81 droplet array with uniform dimensions within a large area exhibited excellent MLA characteristics. Moreover, the method developed in this study is simple in operation, low-cost, and requires neither a clean room nor expensive equipment.

Emergent normal fluid in the superconducting ground state of overdoped cuprates.

The microscopic mechanism for the disappearance of superconductivity in overdoped cuprates is still under heated debate. Here we use scanning tunneling spectroscopy to investigate the evolution of quasiparticle interference phenomenon in Bi2Sr2CuO6+δ over a wide range of hole densities. We find that when the system enters the overdoped regime, a peculiar quasiparticle interference wavevector with arc-like pattern starts to emerge even at zero bias, and its intensity grows with increasing doping level. Its energy dispersion is incompatible with the octet model for d-wave superconductivity, but is highly consistent with the scattering interference of gapless normal carriers. The gapless quasiparticles are mainly located near the antinodes and are independent of temperature, consistent with the disorder scattering mechanism. We propose that a branch of normal fluid emerges from the pair-breaking scattering between flat antinodal bands in the quantum ground state, which is the primary cause for the reduction of superfluid density and suppression of superconductivity in overdoped cuprates.

An ultra-short-acting benzodiazepine in thalamic nucleus reuniens undermines fear extinction via intermediation of hippocamposeptal circuits.

Benzodiazepines, commonly used for anxiolytics, hinder conditioned fear extinction, and the underlying circuit mechanisms are unclear. Utilizing remimazolam, an ultra-short-acting benzodiazepine, here we reveal its impact on the thalamic nucleus reuniens (RE) and interconnected hippocamposeptal circuits during fear extinction. Systemic or RE-specific administration of remimazolam impedes fear extinction by reducing RE activation through A type GABA receptors. Remimazolam enhances long-range GABAergic inhibition from lateral septum (LS) to RE, underlying the compromised fear extinction. RE projects to ventral hippocampus (vHPC), which in turn sends projections characterized by feed-forward inhibition to the GABAergic neurons of the LS. This is coupled with long-range GABAergic projections from the LS to RE, collectively constituting an overall positive feedback circuit construct that promotes fear extinction. RE-specific remimazolam negates the facilitation of fear extinction by disrupting this circuit. Thus, remimazolam in RE disrupts fear extinction caused by hippocamposeptal intermediation, offering mechanistic insights for the dilemma of combining anxiolytics with extinction-based exposure therapy.

Ba2Ga2F6(IO3)(PO4): the first fluoride-containing iodate-phosphate with a 1D [Ga2F6(IO3)(PO4)]4- helix chain.

Herein, the first F-containing iodate-phosphate, namely Ba2Ga2F6(IO3)(PO4), was prepared via a hydrothermal reaction, in which HPF6 (70 wt% solution in water) was used as the source of both fluoride and phosphate anions for the first time. Ba2Ga2F6(IO3)(PO4) features an unprecedented 1D [Ga2F6(IO3)(PO4)]4- helix chain, composed of a 1D Ga(1)(IO3)O4F chain via the bridging of 0D Ga(2)(PO4)F5. The UV-Vis spectrum shows that Ba2Ga2F6(IO3)(PO4) has a wide bandgap with a short-UV absorption edge (4.35 eV; 253 nm). Birefringence measurement under a polarizing microscope shows that Ba2Ga2F6(IO3)(PO4) displays a moderate birefringence of 0.072@550 nm, which is consistent with the value (0.070@550 nm) obtained by DFT calculations, indicating that Ba2Ga2F6(IO3)(PO4) has potential applications as a short-UV birefringent material. This study highlights the crucial role played by the incorporation of specific functional groups into compounds, shedding light on their contribution to promising inorganic functional materials.

Establishment of human post-vaccination SARS-CoV-2 standard reference sera.

There is a critical need to understand the effectiveness of serum elicited by different SARS-CoV-2 vaccines against SARS-CoV-2 variants. We describe the generation of reference reagents comprised of post-vaccination sera from recipients of different primary vaccines with or without different vaccine booster regimens in order to allow standardized characterization of SARS-CoV-2 neutralization in vitro. We prepared and pooled serum obtained from donors who received a either primary vaccine series alone, or a vaccination strategy that included primary and boosted immunization using available SARS-CoV-2 mRNA vaccines (BNT162b2, Pfizer and mRNA-1273, Moderna), replication-incompetent adenovirus type 26 vaccine (Ad26.COV2·S, Johnson and Johnson), or recombinant baculovirus-expressed spike protein in a nanoparticle vaccine plus Matrix-M adjuvant (NVX-CoV2373, Novavax). No subjects had a history of clinical SARS-CoV-2 infection, and sera were screened with confirmation that there were no nucleocapsid antibodies detected to suggest natural infection. Twice frozen sera were aliquoted, and serum antibodies were characterized for SARS-CoV-2 spike protein binding (estimated WHO antibody binding units/ml), spike protein competition for ACE-2 binding, and SARS-CoV-2 spike protein pseudotyped lentivirus transduction. These reagents are available for distribution to the research community (BEI Resources), and should allow the direct comparison of antibody neutralization results between different laboratories. Further, these sera are an important tool to evaluate the functional neutralization activity of vaccine-induced antibodies against emerging SARS-CoV-2 variants of concern. IMPORTANCE: The explosion of COVID-19 demonstrated how novel coronaviruses can rapidly spread and evolve following introduction into human hosts. The extent of vaccine- and infection-induced protection against infection and disease severity is reduced over time due to the fall in concentration, and due to emerging variants that have altered antibody binding regions on the viral envelope spike protein. Here, we pooled sera obtained from individuals who were immunized with different SARS-CoV-2 vaccines and who did not have clinical or serologic evidence of prior infection. The sera pools were characterized for direct spike protein binding, blockade of virus-receptor binding, and neutralization of spike protein pseudotyped lentiviruses. These sera pools were aliquoted and are available to allow inter-laboratory comparison of results and to provide a tool to determine the effectiveness of prior vaccines in recognizing and neutralizing emerging variants of concern.

Complementary to Multiple Labels: A Correlation-Aware Correction Approach.

Complementary label learning (CLL) requires annotators to give irrelevant labels instead of relevant labels for instances. Currently, CLL has shown its promising performance on multi-class data by estimating a transition matrix. However, current multi-class CLL techniques cannot work well on multi-labeled data since they assume each instance is associated with one label while each multi-labeled instance is relevant to multiple labels. Here, we show theoretically how the estimated transition matrix in multi-class CLL could be distorted in multi-labeled cases as they ignore co-existing relevant labels. Moreover, theoretical findings reveal that calculating a transition matrix from label correlations in multi-labeled CLL (ML-CLL) needs multi-labeled data, while this is unavailable for ML-CLL. To solve this issue, we propose a two-step method to estimate the transition matrix from candidate labels. Specifically, we first estimate an initial transition matrix by decomposing the multi-label problem into a series of binary classification problems, then the initial transition matrix is corrected by label correlations to enforce the addition of relationships among labels. We further show that the proposal is classifier-consistent, and additionally introduce an MSE-based regularizer to alleviate the tendency of BCE loss overfitting to noises. Experimental results have demonstrated the effectiveness of the proposed method.

A cocktail nanovaccine targeting key entry glycoproteins elicits high neutralizing antibody levels against EBV infection.

Epstein-Barr virus (EBV) infects more than 95% of adults worldwide and is closely associated with various malignancies. Considering the complex life cycle of EBV, developing vaccines targeting key entry glycoproteins to elicit robust and durable adaptive immune responses may provide better protection. EBV gHgL-, gB- and gp42-specific antibodies in healthy EBV carriers contributed to sera neutralizing abilities in vitro, indicating that they are potential antigen candidates. To enhance the immunogenicity of these antigens, we formulate three nanovaccines by co-delivering molecular adjuvants (CpG and MPLA) and antigens (gHgL, gB or gp42). These nanovaccines induce robust humoral and cellular responses through efficient activation of dendritic cells and germinal center response. Importantly, these nanovaccines generate high levels of neutralizing antibodies recognizing vulnerable sites of all three antigens. IgGs induced by a cocktail vaccine containing three nanovaccines confer superior protection from lethal EBV challenge in female humanized mice compared to IgG elicited by individual NP-gHgL, NP-gB and NP-gp42. Importantly, serum antibodies elicited by cocktail nanovaccine immunization confer durable protection against EBV-associated lymphoma. Overall, the cocktail nanovaccine shows robust immunogenicity and is a promising candidate for further clinical trials.

Postextrasystolic repolarization changes of ventricular premature beats correlate with structural heart disease and suggest prognostic implications.

Ventricular premature beats (VPBs) can potentially lead to life-threatening arrhythmias, especially in patients with structural heart disease (SHD). However, identifying dangerous VPBs has always been a topic and challenge in clinical research. This study aimed to evaluate the relationship of postextrasystolic repolarization changes of VPBs with SHD and its possible additional prognostic value. 125 cases of frequent VPBs with SHD and 156 cases without SHD were included. VPBs were stratified selected from 24 h Holter recording according to the scale of heart rate. Average QTDV (difference value of QT interval between the first beat follow VPB with beats preceding VPB) and max QTDV were significantly longer in SHD group than that in the non-SHD group. For identifying patients with SHD, the best cutoff value were 19 ms for average QTDV (AUC = 0.931) and 29 ms for max QTDV (AUC = 0.910) respectively. For Tu morphology analysis, PT2 (postextrasystolic T wave amplitude change ≥2 mV), reversed T wave, and Pu (postextrasystolic u wave) change were all highly specific, but low sensitive as identification of SHD. Compared with average QTDV < 19 ms patients, average QTDV ≥ 19 ms patients had significantly larger left heart size and wores left cardiac function. The presence of non-persistent ventricular tachycardia runs was higher in average QTDV ≥ 19 ms group and positive Pu change group than that in control groups. The findings indicated that postextrasystolic repolarization changes of VPBs correlated with SHD and suggested potential value in prognosis asssessment.

Macrophage polarization as a novel endpoint for assessing combined risk of phthalate esters.

Combined exposure to phthalate esters (PAEs) has garnered increasing attention due to potential synergistic effects on human health. This study aimed to develop an in vitro model using human macrophages to evaluate the combined toxicity of PAEs and explore the underlying mechanisms. A high-throughput screening system was engineered by expressing a PPRE-eGFP reporter in THP-1 monocytes to monitor macrophage polarization upon PAEs exposure. Individual PAEs exhibited varied inhibitory effects on M2 macrophage polarization, with mono(2-ethylhexyl) phthalate (MEHP) being the most potent. Isobologram analysis revealed additive interactions when MEHP was combined with other PAEs, resulting in more pronounced suppression of M2 markers compared to individual compounds. Mechanistic studies suggested PAEs may exert effects by modulating PPARγ activity to inhibit M2 polarization. Notably, an equimolar mixture of six PAEs showed additive inhibition of M2 markers. In vivo experiments corroborated the combined hepatotoxic effects, with mice exposed to a PAEs mixture exhibiting reduced liver weight, dyslipidemia, and decreased hepatic M2 macrophages compared to DEHP alone. Transcriptome analysis highlighted disruptions in PPAR signaling, and distinct pathway alterations on cholesterol metabolism in the mixture group. Collectively, these findings underscore the importance of evaluating mixture effects and provide a novel approach for hazard assessment of combined PAEs exposure with implications for environmental health risk assessment.

Impact of telomere length and mitochondrial DNA copy number variants on survival of newborn cloned calves.

An established technology to create cloned animals is through the use of somatic cell nuclear transfer (SCNT), in which reprogramming the somatic cell nucleus to a totipotent state by enucleated oocyte cytoplasm is a necessary process, including telomere length reprogramming. The limitation of this technology; however, is that the live birth rate of offspring produced through SCNT is significantly lower than that of IVF. Whether and how telomere length play a role in the development of cloned animals is not well understood. Only a few studies have evaluated this association in cloned mice, and fewer still in cloned cows. In this study, we investigated the difference in telomere length as well as the abundance of some selected molecules between newborn deceased cloned calves and normal cows of different ages either produced by SCNT or via natural conception, in order to evaluate the association between telomere length and abnormal development of cloned cows. The absolute telomere length and relative mitochondrial DNA (mtDNA) copy number were determined by real-time quantitative PCR (qPCR), telomere related gene abundance by reverse-transcription quantitative PCR (RT-qPCR), and senescence-associated ß-galactosidase (SA-ß-gal) expression by SA-ß-gal staining. The results demonstrate that the newborn deceased SCNT calves had significantly shortened telomere lengths compared to newborn naturally conceived calves and newborn normal SCNT calves. Significantly lower mtDNA copy number, and significantly lower relative abundance of LMNB1 and TERT, higher relative abundance of CDKN1A, and aberrant SA-ß-gal expression were observed in the newborn deceased SCNT calves, consistent with the change in telomere length. These results demonstrate that abnormal telomere shortening, lower mtDNA copy number and abnormal abundance of related genes were specific to newborn deceased SCNT calves, suggesting that abnormally short telomere length may be associated with abnormal development in the cloned calves.

Research progress on the quality control of mRNA vaccines.

INTRODUCTION: The mRNA vaccine technologies have progressed rapidly in recent years. The COVID-19 pandemic has accelerated the application of mRNA vaccines, with research and development and clinical trials underway for many vaccines. Application of the quality by design (QbD) framework to mRNA vaccine development and establishing standardized quality control protocols for mRNA vaccines are essential for the continued development of high-quality mRNA vaccines. AREAS COVERED: mRNA vaccines include linear mRNA, self-amplifying mRNA, and circular RNA vaccines. This article summarizes the progress of research on quality control of these three types of vaccines and presents associated challenges and considerations. EXPERT OPINION: Although there has been rapid progress in research on linear mRNA vaccines, their degradation patterns remain unclear. In addition, standardized assays for key impurities, such as residual dsRNA and T7 RNA polymerase, are still lacking. For self-amplifying mRNA vaccines, a key focus should be control of stability in vivo and in vitro. For circular RNA vaccines, standardized assays, and reference standards for determining degree of circularization should be established and optimized.

Generation of an Alagille Syndrome (ALGS) patient-derived induced pluripotent stem cell line (TRNDi036-A) carrying a heterozygous mutation (p.Cys693*) in the JAG1 gene.

Alagille syndrome (ALGS) is an autosomal dominant, multisystemic disorder due to haploinsufficiency in JAG1 or less frequently, mutations in NOTCH2. The disease has been difficult to diagnose and treat due to variable expression. The generation of this iPSC line (TRNDi036-A) carrying a heterozygous mutation (p.Cys693*) in the JAG1 gene provides a means of studying the disease and developing novel therapeutics towards patient treatment.

Multifunctional Integrated Organic-Inorganic-Metal Hybrid Aerogel for Excellent Thermal Insulation and Electromagnetic Shielding Performance.

Vehicles operating in space need to withstand extreme thermal and electromagnetic environments in light of the burgeoning of space science and technology. It is imperatively desired to high insulation materials with lightweight and extensive mechanical properties. Herein, a boron-silica-tantalum ternary hybrid phenolic aerogel (BSiTa-PA) with exceptional thermal stability, extensive mechanical strength, low thermal conductivity (49.6 mW m-1 K-1), and heightened ablative resistance is prepared by an expeditious method. After extremely thermal erosion, the obtained carbon aerogel demonstrates noteworthy electromagnetic interference (EMI) shielding performance with an efficiency of 31.6 dB, accompanied by notable loading property with specific modulus of 272.8 kN·m kg-1. This novel design concept has laid the foundation for the development of insulation materials in more complex extreme environments.

Identification of HLA-A*11:01 and A*02:01-Restricted EBV Peptides Using HLA Peptidomics.

Epstein-Barr Virus (EBV) is closely linked to nasopharyngeal carcinoma (NPC), notably prevalent in southern China. Although type II latency of EBV plays a crucial role in the development of NPC, some lytic genes and intermittent reactivation are also critical for viral propagation and tumor progression. Since T cell-mediated immunity is effective in targeted killing of EBV-positive cells, it is important to identify EBV-derived peptides presented by highly prevalent human leukocyte antigen class I (HLA-I) molecules throughout the EBV life cycle. Here, we constructed an EBV-positive NPC cell model to evaluate the presentation of EBV lytic phase peptides on streptavidin-tagged specific HLA-I molecules. Utilizing a mass spectrometry (LC-MS/MS)-based immunopeptidomic approach, we characterized eleven novel EBV peptides as well as two previously identified peptides. Furthermore, we determined these peptides were immunogenic and could stimulate PBMCs from EBV VCA/NA-IgA positive donors in an NPC endemic southern Chinese population. Overall, this work demonstrates that highly prevalent HLA-I-specific EBV peptides can be captured and functionally presented to elicit immune responses in an in vitro model, which provides insight into the epitopes presented during EBV lytic cycle and reactivation. It expands the range of viral targets for potential NPC early diagnosis and treatment.

dbEBV: A database of Epstein-Barr virus variants and their correlations with human health.

Since Epstein-Barr virus (EBV) was discovered in 1964, it has been reported to be associated with various malignancies as well as benign diseases, and the pathogenicity of EBV has been widely studied. Several databases have been established to provide comprehensive information on the virus and its relation to diseases and introduce convenient analysis tools. Although they have greatly facilitated the analysis of EBV at the genome, gene, protein, or epitope level, they did not provide enough insight into the genomic variants of EBV, which have been suggested as relevant to diseases by multiple studies. Here, we introduce dbEBV, a comprehensive database of EBV genomic variation landscape, which contains 942 EBV genomes with 109,893 variants from different tissues or cell lines in 24 countries. The database enables the visualization of information with varying global frequencies and their relationship with the human health of each variant. It also supports phylogenetic analysis at the genome or gene level in subgroups of different characteristics. Information of interest can easily be reached with functions such as searching, browsing, and filtering. In conclusion, dbEBV is a convenient resource for exploring EBV genomic variants, freely available at http://dbebv.omicsbio.info.

Association of lifestyles and multimorbidity with mortality among individuals aged 60 years or older: Two prospective cohort studies.

Lifestyles are associated with all-cause mortality, yet limited research has explored the association in the elderly population with multimorbidity. We aim to investigate the impact of adopting a healthy lifestyle on reducing the risk of all-cause mortality in older individuals with or without multimorbidity in both China and UK. This prospective study included 29,451 and 173,503 older adults aged 60 and over from Chinese Longitudinal Healthy Longevity Survey (CLHLS) and UK Biobank. Lifestyles and multimorbidity were categorized into three groups, respectively. Cox proportional hazards regression was used to estimate the Hazard Ratios (HRs), 95% confidence intervals (95% CIs), and dose-response for all-cause mortality in relation to lifestyles and multimorbidity, as well as the combination of both factors. During a mean follow-up period of 4.7 years in CLHLS and 12.14 years in UK Biobank, we observed 21,540 and 20,720 deaths, respectively. For participants with two or more conditions, compared to those with an unhealthy lifestyle, adopting a healthy lifestyle was associated with a 27%-41% and 22%-42% reduction in mortality risk in the CLHLS and UK Biobank, respectively; Similarly, for individuals without multimorbidity, this reduction ranged from 18% to 41%. Among participants with multimorbidity, individuals with an unhealthy lifestyle had a higher mortality risk compared to those maintaining a healthy lifestyle, with HRs of 1.15 (95% CI: 1.00, 1.32) and 1.27 (95% CI: 1.16, 1.39) for two conditions, and 1.24 (95% CI: 1.06, 1.45) and 1.73 (95% CI: 1.56, 1.91) for three or more conditions in CLHLS and UK Biobank, respectively. Adherence to a healthy lifestyle can yield comparable mortality benefits for older individuals, regardless of their multimorbidity status. Furthermore, maintaining a healthy lifestyle can alleviate the mortality risks linked to a higher number of diseases.