Photocrosslinked Co-Assembled Amino Acid Nanoparticles for Controlled Chemo/Photothermal Combined Anticancer Therapy.

Nanostructures formed from the self-assembly of amino acids are promising materials in many fields, especially for biomedical applications. However, their low stability resulting from the weak noncovalent interactions between the amino acid building blocks limits their use. In this work, nanoparticles co-assembled by fluorenylmethoxycarbonyl (Fmoc)-protected tyrosine (Fmoc-Tyr-OH) and tryptophan (Fmoc-Trp-OH) are crosslinked by ultraviolet (UV) light irradiation. Two methods are investigated to induce the dimerization of tyrosine, irradiating at 254 nm or at 365 nm in the presence of riboflavin as a photo-initiator. For the crosslinking performed at 254 nm, both Fmoc-Tyr-OH and Fmoc-Trp-OH generate dimers. In contrast, only Fmoc-Tyr-OH participates in the riboflavin-mediated dimerization under irradiation at 365 nm. The participation of both amino acids in forming the dimers leads to more stable crosslinked nanoparticles, allowing also to perform further chemical modifications for cancer applications. The anticancer drug doxorubicin (Dox) is adsorbed onto the crosslinked nanoparticles, subsequently coated by a tannic acid-iron complex, endowing the nanoparticles with glutathione-responsiveness and photothermal properties, allowing to control the release of Dox. A remarkable anticancer efficiency is obtained in vitro and in vivo in tumor-bearing mice thanks to the combined chemo- and photothermal treatment.

Gastric Leiomyosarcoma in Post-Gastrointestinal Stromal Tumor Era: Revisit.

Primary gastric leiomyosarcoma is an exceptionally rare disease. This review covers 41 post-gastrointestinal stromal tumor (GIST) era gastric leiomyosarcoma cases that are supported by immunohistochemistry markers. Other spindle cell lesions are also excluded through histological and immunohistochemistry evaluations. The patients range from 3 to 82 years old, with an average age of 54.6 years. The male-to-female ratio is 1.4:1, from diverse geographic areas. Patients may experience abdominal symptoms, and tumor sizes vary between 1 cm and 22 cm. Morphologically, tumors originate from the muscularis propria or the muscularis mucosae, well-circumscribed with spindle cells arranged in fascicule. Tumoral cells exhibit positivity for smooth muscle markers while being negative for GIST markers and others. The mitotic index ranges from 2 to 500/50 high power field. Ki-67 index varies from 15% to 70%. Management typically involves gastrectomy and other appropriate treatments, with tumor recurrence being uncommon. 56% of patients are alive, with 5 patients dying from this disease. Statistical analyses conducted on post-GIST era cases reveal that a mitotic index of ≥100/50 high power field, tumor recurrence, metastasis, or positive lymph nodes significantly correlate with prognosis.

Lysine Methyltransferase 5A Promotes the Progression of Growth Hormone Pituitary Neuroendocrine Tumors through the Wnt/ß-Catenin Signaling Pathway.

INTRODUCTION: Growth hormone (GH) secreting pituitary adenoma is considered one of the most harmful types of Pituitary Neuroendocrine Tumors (PitNETs). Our previous research has found that high expression of Lysine methyltransferase 5A (KMT5A) is closely related to the proliferation of PitNETs. The aim of this study was to investigate the role and molecular mechanism of KMT5A in the progression of GH PitNETs. METHODS: Immunohistochemistry, qRT-PCR, and Western blot (WB) were used to assess the expression levels of KMT5A in human normal pituitary and GH PitNETs, as well as in rat normal pituitary and GH3 cells. Additionally, we utilized RNA interference technology and treatment with a selective KMT5A inhibitor to decrease the expression of KMT5A in GH3 cells. CCK-8, EdU, flow cytometry (FCM), clone formation, and WB assay were further employed to evaluate the impact of KMT5A on the proliferation of GH3 cells in vitro. A xenograft model was established to evaluate the role of KMT5A in GH PitNETs progression in vivo. RESULTS: KMT5A was highly expressed in GH PitNETs and GH3 cells. Moreover, the reduction of KMT5A expression led to inhibited growth of GH PitNETs and increased apoptosis of tumor cells, as indicated by the findings from CCK-8, EdU, clone formation, and FCM assays. Additionally, WB analysis identified the Wnt/ß-catenin signaling pathway as a potential mechanism through which KMT5A promotes GH PitNETs progression. CONCLUSION: Our research suggests that KMT5A may facilitate the progression of GH PitNETs via the Wnt/ß-catenin signaling pathway. Therefore, KMT5A may serve as a potential therapeutic target and molecular biomarker for GH PitNETs.

Choledochoscopy combined with double-cannula lavage in the treatment of acute pancreatitis with encapsulated necrosis and the analysis of related inflammatory indexes.

OBJECTIVE: This study aimed to evaluate the application of choledochoscopy combined with double-cannula lavage in the treatment of acute pancreatitis (AP) with encapsulated necrosis and analyzed related inflammatory indexes. METHODS: Thirty patients with AP with encapsulated necrosis were enrolled and treated with choledochoscopy and double-cannula lavage. Serum white blood cell (WBC), procalcitonin (PCT), C-reactive protein (CRP), interleukin 6 (IL-6), IL-8, tumor necrosis factor alpha (TNF-α), and related inflammatory indexes were detected before and after surgery. RESULTS: All of the participants who underwent the surgery recovered well and were discharged without serious complications; no deaths occurred. The serum WBC, PCT, and CRP of patients after surgery decreased compared with before the procedure, and the differences in WBC and CRP were statistically significant (P < 0.05); the difference in PCT was not statistically significant (P > 0.05). Postoperatively, IL-6, IL-8, and TNF-α levels were higher than before surgery, and the differences were statistically significant (P < 0.05). CONCLUSION: The surgical method presented herein effectively controlled and alleviated the infection of patients; it also did not increase the risk of infection and can thus be considered a safe and effective surgical method.

Age-related differences in the removal of information from working memory.

Removal has been assumed to be a core mechanism in working memory. However, it remains unclear whether children can actively remove outdated information from working memory and how this ability develops as children age. The current study aimed to examine age-related differences in removal ability and its relations with cognitive control and working memory capacity. Children aged 7, 9, and 11 years performed a modified working memory updating task assessing removal efficiency. In addition, a battery of cognitive control and working memory capacity tasks was administered. Results indicated that updating response times decreased considerably when a longer time was given for removal, suggesting that children aged 7 to 11 years can actively remove outdated items from working memory prior to encoding the new ones and that removal efficiency increased with age. More important, age-related increases in removal efficiency occurred concurrently with the development of working memory capacity. Proactive control predicted removal efficiency over and beyond age and working memory capacity. The findings shed new light on the mechanisms underlying the development of working memory updating.

The regulatory landscape of multiple brain regions in outbred heterogeneous stock rats.

Heterogeneous Stock (HS) rats are a genetically diverse outbred rat population that is widely used for studying genetics of behavioral and physiological traits. Mapping Quantitative Trait Loci (QTL) associated with transcriptional changes would help to identify mechanisms underlying these traits. We generated genotype and transcriptome data for five brain regions from 88 HS rats. We identified 21 392 cis-QTLs associated with expression and splicing changes across all five brain regions and validated their effects using allele specific expression data. We identified 80 cases where eQTLs were colocalized with genome-wide association study (GWAS) results from nine physiological traits. Comparing our dataset to human data from the Genotype-Tissue Expression (GTEx) project, we found that the HS rat data yields twice as many significant eQTLs as a similarly sized human dataset. We also identified a modest but highly significant correlation between genetic regulatory variation among orthologous genes. Surprisingly, we found less genetic variation in gene regulation in HS rats relative to humans, though we still found eQTLs for the orthologs of many human genes for which eQTLs had not been found. These data are available from the RatGTEx data portal (RatGTEx.org) and will enable new discoveries of the genetic influences of complex traits.

Transcription-coupled donor DNA expression increases homologous recombination for efficient genome editing.

Genomes can be edited by homologous recombination stimulated by CRISPR/Cas9 [clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated peptide 9]-induced DNA double-strand breaks. However, this approach is inefficient for inserting or deleting long fragments in mammalian cells. Here, we describe a simple genome-editing method, termed transcription-coupled Cas9-mediated editing (TEd), that can achieve higher efficiencies than canonical Cas9-mediated editing (CEd) in deleting genomic fragments, inserting/replacing large DNA fragments and introducing point mutations into mammalian cell lines. We also found that the transcription on DNA templates is crucial for the promotion of homology-directed repair, and that tethering transcripts from TEd donors to targeted sites further improves editing efficiency. The superior efficiency of TEd for the insertion and deletion of long DNA fragments expands the applications of CRISPR for editing mammalian genomes.

Extracellular Vesicles from Mycoplasma gallisepticum: Modulators of Macrophage Activation and Virulence.

Extracellular vesicles (EVs) mediate intercellular communication by transporting proteins. To investigate the pathogenesis of Mycoplasma gallisepticum (MG), a major threat to the poultry industry, we isolated and characterized MG-produced EVs. Our study highlights the significant impact of MG-derived EVs on immune function and macrophage apoptosis, setting them apart from other MG metabolites. These EVs dose-dependently enhance MG adhesion and proliferation, simultaneously modulating TLR2 and IFN-γ pathways, thereby inhibiting macrophage activation. A comprehensive protein analysis revealed 117 proteins in MG-derived EVs, including established virulence factors such as GapA, CrmA, VlhA, and CrmB. Crucially, these EV-associated proteins significantly contribute to MG infection. Our findings advance our comprehension of MG pathogenesis, offering insights for preventive strategies, and emphasize the pivotal role of MG-derived EVs and their associated proteins. This research sheds light on the composition and crucial role of MG-derived EVs in MG pathogenesis, aiding our fight against MG infections.

Nickel Phosphonate MOF Derived N-Doped Carbon-Coated Phosphorus-Vacancies-Rich Ni2 P Particles as Efficient Bifunctional Oxygen Electrocatalyst.

The design of non-noble metal bifunctional electrocatalysts with outstanding performance and remarkable stability for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is one of the most essential issues to the realization of rechargeable zinc-air battery, and transition metal phosphides (TMPs) have emerged as robust candidates for oxygen electrocatalysts. Herein, N-doped carbon-coated phosphorus-vacancies-rich Ni2 P particles (Vp -Ni2 P@NC) is proposed via simple carbonization and following Ar plasma treatment from a single nickel phosphonate metal-organic framework (MOF) without extra phosphine and nitrogen sources. The facile and rapid plasma treatment can achieve phosphorus vacancies which could modulate the electronic structure to enhance the inherent active and electrical conductivity. Meanwhile, the pyridine-N and graphitized-N produced during calcination also could provide more active sites and increase the electrical conductivity. The resultant Vp -Ni2 P@NC catalyst shows excellent bifunctional electrocatalytic activity (OER/ORR) based on synergistic effect of introducing P vacancies into Ni2 P and N-doped carbon. Vp -Ni2 P@NC catalyst shows more advantageous ΔE value (0.70 V) compared to Pt/C+RuO2 (0.73 V) and most reported catalysts. Additionally, the zinc-air bbatterie (ZAB) employing Vp -Ni2 P@NC as air cathode shows excellent performance. The maximum power density of 203.48 mW cm-2 , the cycling stability of more than 150 h at 10 mA cm-2 .

Low let-7d microRNA levels in chick embryos enhance innate immunity against Mycoplasma gallisepticum by suppressing the mitogen-activated protein kinase pathway.

Chick embryos are a valuable model for studying immunity and vaccines. Therefore, it is crucial to investigate the molecular mechanism of the Mycoplasma gallisepticum (MG)-induced immune response in chick embryos for the prevention and control of MG. In this study, we screened for downregulated let-7d microRNA in MG-infected chicken embryonic lungs to explore its involvement in the innate immune mechanism against MG. Here, we demonstrated that low levels of let-7d are a protective mechanism for chicken embryo primary type II pneumocytes (CP-II) in the presence of MG. Specifically, we found that depressed levels of let-7 in CP-II cells reduced the adhesion capacity of MG. This suppressive effect was achieved through the activated mitogen-activated protein kinase phosphatase 1 (MKP1) target gene and the inactivated mitogen-activated protein kinase (MAPK) pathway. Furthermore, MG-induced hyperinflammation and cell death were both alleviated by downregulation of let-7d. In conclusion, chick embryos protect themselves against MG infection through the innate immune molecule let-7d, which may result from its function as an inhibitor of the MAPK pathway to effectively mitigate MG adhesion, the inflammatory response and cell apoptosis. This study may provide new insight into the development of vaccines against MG.

Genome-wide association study reveals a genomic region on SSC7 simultaneously associated with backfat thickness, skin thickness and carcass length in a Large White × Tongcheng advanced generation intercross resource population.

In order to identify important genetic markers associated with backfat thickness, skin thickness and carcass length, we first constructed Large White × Tongcheng (Chinese local breed), an advanced generation intercross population, then performed a genome-wide association study (GWAS) to reveal the key genomic region associated with these traits through whole genome sequencing. The GWAS results of backfat thickness, skin thickness and carcass length showed that all the most significant SNPs associated with these three traits were located on SSC7, and that 14.9, 27.0 and 21.1% of phenotypic variances were explained by these three SNPs, respectively. Through linkage disequilibrium analysis, we found that a 66.9 kb (30.23-30.31 Mb) genetic region was overlapped among these three traits, and that NUDT3 and HMGA1 were identified as major candidate genes for backfat thickness and carcass length, and GRM4 as a potential candidate gene for skin thickness. In addition, 13 highly linked SNPs significantly associated with the three traits were also identified in overlapped region, and three completely linked SNPs formed two haplotypes Q and q. The backfat thickness of individuals with the qq genotype was significantly lower than that of individuals with the QQ genotype, but their carcass length and skin thickness were significantly higher than those with the QQ genotype. Our detected candidate genes and SNPs will provide the foundation for genetic improvement of these three traits.

Sulforaphane suppresses paraquat-induced oxidative damage in bovine in vitro-matured oocytes through Nrf2 transduction pathway.

Sulforaphane (SFN), a bioactive phytocompound extracted from cruciferous plants, has received increasing attention due to its vital cytoprotective role in eliminating oxidative free radical through activation of nuclear factor erythroid 2-related factor (Nrf2)-mediated signal transduction pathway. This study aims at a better insight into the protective benefit of SFN in attenuating paraquat (PQ)-caused impairment in bovine in vitro-matured oocytes and the possible mechanisms involved therein. Results showed that addition of 1 µM SFN during oocyte maturation obtained higher proportions of matured oocytes and in vitro-fertilized embryos. SFN application attenuated the toxicological effects of PQ on bovine oocytes, as manifested by enhanced extending capability of cumulus cell and increased extrusion proportion of first polar body. Following incubation with SFN, oocytes exposed to PQ exhibited reduced intracellular ROS and lipid accumulation levels, and elevated T-SOD and GSH contents. SFN also effectively inhibited PQ-mediated increase in BAX and CASPASE-3 protein expressions. Besides, SFN promoted the transcription of NRF2 and its downstream antioxidative-related genes GCLC, GCLM, HO-1, NQO-1, and TXN1 in a PQ-exposed environment, indicating that SFN prevents PQ-caused cytotoxicity through activation of Nrf2 signal transduction pathway. The mechanisms underlying the role of SFN against PQ-induced injury included the inhibition of TXNIP protein and restoration of the global O-GlcNAc level. Collectively, these findings provide novel evidence for the protective role of SFN in alleviating PQ-caused injury, and suggest that SFN application may be an efficacious intervention strategy against PQ cytotoxicity.

Integrated testis transcriptome and whole genome analysis of sexual maturity in Large White and Tongcheng pigs.

Testicular development and spermatogenesis play critical roles in male fertility and sexual maturation. To explore the genetic basis and key genes related to sexual maturity, we measured serum testosterone content and analysed testis tissue sections of Large White (LW) and Tongcheng (TC) boars at an immature age. We then screened differentially expressed genes (DEGs) in testis development in both breeds using RNA-seq. Finally, we analysed the selection signatures of both breeds to investigate which DEGs were subjected to positive selection. Our findings showed that serum testosterone contents in TC pigs (~4 ng/mL) were much higher than those in LW pigs (<0.95 ng/mL). Haematoxylin and eosin staining of testicular sections showed that the cross-sectional areas and perimeters of the seminiferous tubules in TC testes were larger and longer than those in LW pigs. A total of 5068 DEGs were selected by filtering criteria of q value <0.05 and |log2 (fold change)| ≥ 1. Gene Ontology analysis revealed that 250 genes were enriched in 11 biological process categories involved in sexual maturity. Most candidate genes, including TRIP13, NR6A1, STRA8, PCSK4, ACRBP, TSSK1B and TSSK6, were under positive selection. These results provide a better understanding of the genetic basis for testicular maturation and are useful for enhancing boar reproductive traits through molecular breeding.

Self-assembly of amphiphilic amino acid derivatives for biomedical applications.

Amino acids are one of the simplest biomolecules and they play an essential role in many biological processes. They have been extensively used as building blocks for the synthesis of functional nanomaterials, thanks to their self-assembly capacity. In particular, amphiphilic amino acid derivatives can be designed to enrich the diversity of amino acid-based building blocks, endowing them with specific properties and/or promoting self-assembly through hydrophobic interactions, hydrogen bonding, and/or π-stacking. In this review, we focus on the design of various amphiphilic amino acid derivatives able to self-assemble into different types of nanostructures that were exploited for biomedical applications, thanks to their excellent biocompatibility and biodegradability.

Early-Onset Micromorphological Changes of Neuronal Fiber Bundles During Radiotherapy.

BACKGROUND: Patients receiving cranial radiation face the risk of delayed brain dysfunction. However, an early medical imaging marker is not available until irreversible morphological changes emerge. PURPOSE: To explore the micromorphological white matter changes during the radiotherapy session by utilizing an along-tract analysis framework. STUDY TYPE: Prospective. POPULATION: Eighteen nasopharyngeal carcinoma (two female) patients receiving cranial radiation. FIELD STRENGTH/SEQUENCE: 3.0 T; Diffusion tensor imaging (DTI) and T1- and T2-weighted images (T1W, T2W); computed tomography (CT). ASSESSMENT: Patients received three DTI imaging scans during the radiotherapy (RT), namely the baseline scan (1-2 days before RT began), the middle scan (the middle of the RT session), and the end scan (1-2 days after RT ended). Twelve fibers were segmented after whole-brain tractography. Then, the fractional anisotropy (FA) values and the cumulative radiation dose received for each fiber streamline were resampled and projected into their center fiber. STATISTICAL TESTS: The contrast among the three scans (P1: middle scan-baseline scan; P2: end scan-middle scan; P3: end scan-baseline scan) were compared using the linear mixed model for each of the 12 center fibers. Then, a dose-responsiveness relationship was performed using Pearson correlation. P < 0.05 was considered statistically significant. RESULTS: Six of the 12 center fibers showed significant changes of FA values during the RT but with heterogeneous patterns. The significant changes along a specific center fiber were associated with their cumulative dose received (Genu: P1 r = -0.6182, P2 r = -0.5907; Splenium: P1 r = 0.4055, P = 0.1063, P2 r = 0.6742; right uncinate fasciculus: P1 r = -0.3865, P2 r = -0.4912, P = 0.0533; right corticospinal tract: P1 r = 0.4273, P = 0.1122, P2 r = -0.6885). DATA CONCLUSION: The along-tract analysis might provide sensitive measures on the early-onset micromorphological changes. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Effect of empirical antifungal treatment on mortality in non-neutropenic critically ill patients: a propensity-matched retrospective cohort study.

To evaluate the effect of empirical antifungal treatment (EAFT) on mortality in critically ill patients without invasive fungal infections (IFIs). This was a single-center propensity score-matched retrospective cohort study involving non-transplanted, non-neutropenic critically ill patients with risk factors for invasive candidiasis (IC) in the absence of IFIs. We compared all-cause hospital mortality and infection-attributable hospital mortality in patients who was given EAFT for suspected IC as the cohort group and those without any systemic antifungal agents as the control group. Among 640 eligible patients, 177 patients given EAFT and 177 control patients were included in the analyses. As compared with controls, EAFT was not associated with the lower risks of all-cause hospital mortality [odds ratio (OR), 0.911; 95% CI, 0.541-1.531; P = 0.724] or infection-attributable hospital mortality (OR, 1.149; 95% CI, 0.632-2.092; P = 0.648). EAFT showed no benefit of improvement of infection at discharge, duration of mechanical ventilation, and antibiotic-free days. However, the later initiation of EAFT was associated with higher risks of all-cause hospital mortality (OR, 1.039; 95% CI, 1.003 to 1.076; P = 0.034) and infection-attributable hospital mortality (OR, 1.046; 95% CI, 1.009 to 1.085; P = 0.015) in patients with suspected IC. This effect was also found in infection-attributable hospital mortality (OR, 1.042; 95% CI, 1.005 to 1.081; P = 0.027) in septic patients with suspected IC. EAFT failed to decrease hospital mortality in non-neutropenic critically ill patients without IFIs. The timing may be critical for EAFT to improve mortality in these patients with suspected IC. ChiCTR2000038811, registered on Oct 3, 2020.

Broadband and high-efficiency ultrathin wavefront manipulation based on the Pancharatnam-Berry phase principle.

A broadband and high-efficiency metasurface is proposed based on the Pancharatnam-Berry (PB) principle. The PB phase principle is analyzed using the scattering matrix approach and proposed to achieve the abrupt phase with an equal amplitude of the transmission coefficient. The abrupt phase φ has a linear relationship with the rotation angle θ, namely, φ=±2θ. A 1-D gradient metasurface was designed, and the circular polarized waves in the frequency range 8.2-10 GHz were refracted anomalously when left-handed circular polarization or right-handed circular polarization waves were irradiated vertically on the metasurface and the refraction angle of the circular polarized waves, depending on the chirality of the incident wave. Finally, a 2-D parabolic metasurface that not only converts planar circular polarized waves into spherical circular polarized waves, but also converges the parallel wave into a focus point, was designed. The focal distance of the 2-D parabolic metasurface decreases as the frequency of the incident wave decreases, and the half-maximum at full width shows the opposite trend.

Anesthesia inhibited corticospinal excitability and attenuated the modulation of repetitive transcranial magnetic stimulation.

BACKGROUND: Lots of studies have measured motor evoked potential (MEP) induced by transcranial magnetic stimulation (TMS) in anesthetized animals. However, in awake animals, the measurement of TMS-induced MEP is scarce as lack of sufficient restraint. So far, the explicit study of anesthesia effects on corticospinal excitability and repetitive TMS (rTMS) induced modulation is still lacking. This study aimed to: (1) measure TMS-induced MEP in both awake restrained and anesthetized rats, (2) investigate the effect of anesthesia on corticospinal excitability, and (3) on rTMS-induced modulation. METHODS: MEP of eighteen rats were measured under both wakefulness and anesthesia using flexible binding and surface electrodes. Peak-to-peak MEP amplitudes, resting motor threshold (RMT) and the slope of stimulus response (SR) were extracted to investigate anesthesia effects on corticospinal excitability. Thereafter, 5 or 10 Hz rTMS was applied with 600 pulses, and the increase in MEP amplitude and the decrease in RMT were used to quantify rTMS-induced modulation. RESULTS: The RMT in the awake condition was 44.6 ± 1.2% maximum output (MO), the peak-to-peak MEP amplitude was 404.6 ± 48.8 µV at 60% MO. Under anesthesia, higher RMT (55.6 ± 2.9% MO), lower peak-to-peak MEP amplitudes (258.6 ± 32.7 µV) and lower slope of SR indicated that the corticospinal excitability was suppressed. Moreover, under anesthesia, high-frequency rTMS still showed significant modulation of corticospinal excitability, but the modulation of MEP peak-to-peak amplitudes was weaker than that under wakefulness. CONCLUSIONS: This study measured TMS-induced MEP in both awake and anesthetized rats, and provided explicit evidence for the inhibitory effects of anesthesia on corticospinal excitability and on high-frequency rTMS-induced modulation of MEP.

Working memory capacity, mental rotation, and visual perspective taking: A study of the developmental cascade hypothesis.

The present study aimed to investigate the mechanism underlying the development of level 2 visual perspective taking (VPT2). Specifically, we examined the role of working memory capacity (WMC) and mental rotation (MR) in the developmental change of VPT2 among early school-aged children. Children aged between 6 and 8 years (N = 150) completed measures to assess WMC, MR, and VPT2. Results showed that WMC, the ability of MR, and VPT2 developed progressively from 6 to 8 years old. The ability of VPT2 was significantly correlated with WMC and MR, even when age was statistically controlled for. Mediation analyses further revealed that both age-related changes in WMC and MR partially mediated the development of VPT2. Furthermore, age-related development in MR mediated the relationship between changes of WMC and VPT2. Our findings suggest the importance of WMC and MR in the early development of VPT2 and provide preliminary support for the developmental cascade hypothesis. That is, as children grow up, their WMC increases, leading to better capability of MR, which in turn results in the improvement of VPT2.

Fluorescence immunoassay rapid detection of 2019-nCoV antibody based on the fluorescence resonance energy transfer between graphene quantum dots and Ag@Au nanoparticle.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has dramatically changed the world, is a highly contagious virus. The timely and accurate diagnosis of SARS-CoV-2 infections is vital for disease control and prevention. Here in this work, a fluorescence immunoassay was developed to detect 2019 Novel Coronavirus antibodies (2019-nCoV mAb). Fluorescent graphene quantum dots (GQDs) and Ag@Au nanoparticles (Ag@AuNPs) were successfully synthesized and characterized. Fluorescence resonance energy transfer (FRET) enables effective quenching of GQDs fluorescence by Ag@AuNPs. With the presence of 2019-nCoV mAb, a steric hindrance was observed between the Ag@AuNPs-NCP (2019-nCoV antigen) complex and GQDs, which reduced the FRET efficiency and restored the fluorescence of GQDs. The fluorescence enhancement efficiency has a satisfactory linear relationship with the logarithm of the 2019-nCoV mAb in a concentration range of 0.1 pg mL-1-10 ng mL-1, and the limit of detection was 50 fg mL-1. The method has good selectivity. When the serum sample was spiked with 2019-nCoV mAb, the recovery rate was between 90.8% and 103.3%. The fluorescence immunosensor demonstrates the potential to complement the existing serological assays for COVID-19 diagnosis.