[Cryoprotective effects of deicing micro/nanomaterials with different sizes and shapes on cells].

Extensive studies have been conducted on deicing nanomaterials to improve the cryoprotective effects on cells, tissues, and organs. The nanomaterials with different composition, sizes, and shapes can inhibit the formation and growth of ice crystals, thereby reducing the damage to the cryopreserved samples. In this study, the carbon composite particles (CCPs) with different sizes and shapes were prepared by the hydrothermal method. The results demonstrated that the cryoprotective effect of CCPs enhanced with the decrease in particle size. Compared with spherical CCPs, Janus nanoparticles and WSP nanoflower with special shapes demonstrated improved protective effects on cryopreserved cells. In addition, the combination of deicing micro/nanomaterials at appropriate concentrations with commercial cryoprotectants exerted improved cryoprotective effects on cells. The prepared deicing micro/nanomaterials can improve cell cryopreservation, demonstrating great application potential in biomedical research and cryopreservation.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

RNA-sequencing expression profile and functional analysis of retinal pigment epithelium in atrophic age-related macular degeneration.

The retinal pigment epithelium (RPE) is fundamental to sustaining retinal homeostasis. RPE abnormality leads to visual defects and blindness, including age-related macular degeneration (AMD). Although breakthroughs have been made in the treatment of neovascular AMD, effective intervention for atrophic AMD is largely absent. The inadequate knowledge of RPE pathology is hindered by a lack of patient RPE datasets, especially at the single-cell resolution. In this study, we delved into a large-scale single-cell resource of AMD donors in which RPE cells were occupied in a substantial proportion. Bulk RNA-seq datasets of atrophic AMD were integrated to extract molecular characteristics of RPE in the pathogenesis of atrophic AMD. Both in vivo and in vitro models revealed that carboxypeptidase X, M14 family member 2 (CPXM2) was specifically expressed in the RPE cells of atrophic AMD, which might be induced by oxidative stress and involved in the epithelial-mesenchymal transition of RPE cells. Additionally, silencing of CPXM2 inhibited the mesenchymal phenotype of RPE cells in an oxidative stress cell model. Thus, our results demonstrate that CPXM2 plays a crucial role in regulating atrophic AMD and may serve as a potential therapeutic target for atrophic AMD.

Cardiorespiratory fitness attenuates the association between fatness and cardiometabolic risk in Chinese children.

Background: Childhood obesity tends to persist into adulthood, predisposing individuals to cardiometabolic risk (CMR). This study aims to investigate the mediating role of cardiorespiratory fitness (CRF) in the associations between multiple fatness indicators and individual CMR markers and clustered CMR-score, and explore sex differences. Methods: We recruited 1,557 children (age: 8 to 10, male/female: 52.7%/47.3%) in September 2022 in Ningbo, China. Physical examinations, overnight fasting blood test, and CRF was evaluated. The CMR-score was calculated by summing age- and sex-specific z scores of four CMR markers, including mean arterial blood pressure, triglycerides, the total cholesterol to high-density lipoprotein cholesterol ratio, and homeostatic model assessment for insulin resistance. Generalized linear mixed models were used to identify the associations, mediation analyses were performed to dissect the function of CRF. Results: Partial correlation analyses revealed positive associations between high fatness indicators (including body mass index [BMI], BMI z score, body fat mass index [BFMI] and waist-to-height ratio [WHtR]) and increased CMR markers, whereas high CRF was associated with decreased CMR markers (all P < 0.05). In the mediation analyses, CRF emerged as a partial mediator, attenuating the relationship between four fatness indicators and CMR-score. Specifically, CRF mediated 6.5%, 7.7%, 5.3%, and 12.5% of the association between BMI, BMI z score, BFMI, WHtR and CMR-score (all P < 0.001). And the mediating effects of CRF between WHtR and four individual CMR markers was particularly robust, ranging from 10.4% to 21.1% (all P < 0.05). What's more, CRF mediates the associations between WHtR and CMR-score more pronounced in girls than boys with a mediation effect size of 17.3% (P < 0.001). Conclusion: In Chinese children, CRF partially mitigates the adverse effects of fatness on CMR, underscoring the significance of enhancing CRF in children.