Submerged plant-biochar composite system exhibits effective control over residual organic pollutants in the benthic organisms of aquaculture ponds.

As of now, submerged plants and biochar have demonstrated significant benefits in aquaculture pond sediment remediation. However, there is limited research on the synergistic effects of biochar and submerged plants in mitigating hydrophobic organic contaminant (HOC) accumulation in aquaculture benthic organisms and in controlling the nutrient (nitrogen and phosphorus) levels in aquaculture water. This study assesses a submerged plant-biochar system's efficacy in removing HOCs from simulated freshwater aquaculture ponds. Vallisneria natans was planted in sediment with varying levels of wheat straw biochar, while Corbicula fluminea served as the targeted benthic organism. The bioaccumulation experiment identified the optimal biochar ratio for the Vallisneria natans-biochar system in controlling HOCs in aquaculture products. Analyses included final accumulation concentrations in benthic organisms, changes in freely-dissolved concentrations in aquaculture sediment, and a mass balance calculation to explore key factors in their removal from the system. Results indicated that the Vallisneria natans-1.5% biochar composite system achieved optimal control of HOCs in sediment and aquaculture products. Biochar addition to the sediment in the composite system demonstrated a "promotion with low addition, inhibition with high addition" effect on Vallisneria natans growth. Notably, the addition of 1.5% biochar (VN1.5 group) significantly promoted the growth of Vallisneria natans leaves and roots. Comparing the final pollutant proportions in different environmental media, concentrations in water (0.20%-1.8%), clam accumulation (0.032%-0.11%), and plant absorption (0.10%-0.44%) constituted a minimal portion of the overall pollutant load in the system. The majority of pollutants (24%-65%) were degraded in the aquaculture environment, with microbial degradation likely playing a predominant role. Bacterial phyla, particularly Proteobacteria and Firmicutes, were identified as potential direct contributors to pollutant degradation in the Vallisneria natans-biochar system.

Nomograms for Predicting Risk and Survival of Esophageal Cancer Lung Metastases: a SEER Analysis.

Background: The overall survival rate is notably low for esophageal cancer patients with lung metastases (LM), presenting significant challenges in their treatment. Methods: Through the Surveillance, Epidemiology, and End Results (SEER) program, individuals diagnosed with esophageal cancer between 2010 and 2015 were enrolled. Based on whether esophageal cancer metastasized to the lungs, we used propensity score matching (PSM) to balance correlated variables. Propensity score matching was a critical step in our study that helped to minimize the impact of possible confounders on the study results. We balanced variables related to lung metastases using the PSM method to ensure more accurate comparisons between the study and control groups. Specifically, we performed PSM in the following steps. First, we performed a univariate logistic regression analysis to screen for variables associated with lung metastasis. For each patient, we calculated their propensity scores using a logistic regression model, taking into account several factors, including gender, T-stage, N-stage, surgical history, radiotherapy history, chemotherapy history, and bone/brain/liver metastases. We used a 1:1 matching ratio based on the propensity score to ensure more balanced baseline characteristics between the study and control groups after matching. After matching, we validated the balance of baseline characteristics to ensure that the effect of confounders was minimized. We used logistic regression to identify risk variables for LM, while Cox regression was used to find independent prognostic factors. We then created nomograms and assessed their accuracy using the calibration curve, receiver operating curves (ROC), and C index. Results: In the post-PSM cohort, individuals diagnosed with LM experienced a median overall survival (OS) of 5.0 months (95% confidence interval [CI] 4.3-5.7), which was significantly lower than those without LM (P<0.001). LM has been associated to sex, T stage, N stage, surgery, radiation, chemotherapy, and bone/brain/liver metastases. LM survival was affected by radiation, chemotherapy, and bone/liver metastases. The nomograms' predictive power was proved using the ROC curve, C-index, and validation curve. Conclusion: Patients with LM have a worse chance of surviving esophageal cancer. The nomograms can effectively predict the risk and prognosis of lung metastases from esophageal cancer.

Steering Sulfur Reduction Pathways via Cisplatin Enables High Performance in Lithium-Sulfur Batteries.

The sulfur reduction reaction (SRR) is an attractive 16-electron transfer process that endows Li-S batteries with a theoretical capacity of 1,672 mAh g-1. However, the slow kinetics and complex pathways of the SRR cause the shuttling of soluble polysulfides (PSs), thus fast capacity fading. Here, we report using cisplatin (cis-Pt) as a novel mediator to improve the SRR kinetics and a molecular probe to identify the SRR pathways. We show that cis-Pt with a reductive Pt2+ center can directly slice the S-S bonds of PSs, leading to enhanced charge transfer kinetics, guided SRR pathways, and depth conversion of PSs to Li2S. With cis-Pt added, Li-S coin cells deliver a maximum specific capacity of 1,437 mAh g-1 and a capacity decay of 0.017% per cycle after 1000 cycles, while a pouch cell with a practical electrolyte-sulfur ratio (2.5 µl mg-1) exhibits a high energy density of 318.8 Wh kg-1. Our mechanistic studies reveal that cis-Pt steers the cathodic SRR pathways by generating redox active cis-Pt/PSs complexes, enabling the replacement of the sluggish SRR with a faster redox cycling of Pt4+/Pt2+ pairs. These findings provide insights into the rational design of functional mediators for tackling the cathodic challenges inside Li-S batteries.

Microplastics in different tissues of historical and live samples of endangered mega-fish (Acipenser sinensis) and their potential relevance to exposure pathways.

The Chinese sturgeon (Acipenser sinensis) is an endangered freshwater mega-fish (IUCN-red listed) that survives in the Yangtze River Basin, but the population of which has declined significantly in response to environmental pressures generated by human activities. In order to evaluate the interaction between Chinese sturgeon and microplastics (MPs) for the first time, we examined the gut and gills of historical samples (n = 27), in conjunction with the blood and mucus of live samples (n = 10), to explore the potential pathways involved in MP uptake. We detected MPs in 62.9 % of the field fish, with no significant difference between guts (mean=0.9 items/individual) and gills (mean=0.8 items/individual). The abundance of MPs in fish from 2017 was significantly higher than that from 2015 to 2016 with regards to both gills and gut samples. The size of MPs in gills was significantly smaller than those in guts, yet both contained mostly fibers (90.2 %). No MPs were confirmed in blood, however 62.5 % of mucus samples contained MPs. The MPs in mucus indicated the possibility of MPs entering Chinese sturgeons if their skins were damaged. The body size of Chinese sturgeons affected their MPs uptake by ingestion and inhalation, as less MPs were detected in the gut and gills of smaller individuals. Combining the evidence from historical and live samples, we revealed the presence of MPs in different tissues of Chinese sturgeon and their potential relevance to exposure pathways. Our work expands the understanding of multiple exposure pathways between MPs and long-lived mega-fish, while emphasizing the potential risks of long-term exposure in the field.

De-nitrosylation Coordinates Appressorium Function for Infection of the Rice Blast Fungus.

As a signaling molecule, nitric oxide (NO) regulates the development and stress response in different organisms. The major biological activity of NO is protein S-nitrosylation, whose function in fungi remains largely unclear. Here, it is found in the rice blast fungus Magnaporthe oryzae, de-nitrosylation process is essential for functional appressorium formation during infection. Nitrosative stress caused by excessive accumulation of NO is harmful for fungal infection. While the S-nitrosoglutathione reductase GSNOR-mediated de-nitrosylation removes excess NO toxicity during appressorium formation to promote infection. Through an indoTMT switch labeling proteomics technique, 741 S-nitrosylation sites in 483 proteins are identified. Key appressorial proteins, such as Mgb1, MagB, Sps1, Cdc42, and septins, are activated by GSNOR through de-nitrosylation. Removing S-nitrosylation sites of above proteins is essential for proper protein structure and appressorial function. Therefore, GSNOR-mediated de-nitrosylation is an essential regulator for appressorium formation. It is also shown that breaking NO homeostasis by NO donors, NO scavengers, as well as chemical inhibitor of GSNOR, shall be effective methods for fungal disease control.

FOXO1 reshapes neutrophils to aggravate acute brain damage and promote late depression after traumatic brain injury.

BACKGROUND: Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury (TBI). However, the heterogeneity, multifunctionality, and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood. METHODS: Using the combined single-cell transcriptomics, metabolomics, and proteomics analysis from TBI patients and the TBI mouse model, we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests. We also characterized the underlying mechanisms both in vitro and in vivo through molecular simulations, signaling detections, gene expression regulation assessments [including dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays], primary cultures or co-cultures of neutrophils and oligodendrocytes, intracellular iron, and lipid hydroperoxide concentration measurements, as well as forkhead box protein O1 (FOXO1) conditional knockout mice. RESULTS: We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model. Infiltration of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI, aggravating acute brain inflammatory damage and promoting late TBI-induced depression. In the acute stage, FOXO1 upregulated cytoplasmic Versican (VCAN) to interact with the apoptosis regulator B-cell lymphoma-2 (BCL-2)-associated X protein (BAX), suppressing the mitochondrial translocation of BAX, which mediated the antiapoptotic effect companied with enhancing interleukin-6 (IL-6) production of FOXO1high neutrophils. In the chronic stage, the "FOXO1-transferrin receptor (TFRC)" mechanism contributes to FOXO1high neutrophil ferroptosis, disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein, which contributes to the progression of late depression after TBI. CONCLUSIONS: FOXO1high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI, which provides insight into the heterogeneity, reprogramming activity, and versatility of neutrophils in TBI.

Potential diagnostic markers shared between non-alcoholic fatty liver disease and atherosclerosis determined by machine learning and bioinformatic analysis.

Background: Evidence indicates that chronic non-alcoholic fatty liver disease (NAFLD) can increase the risk of atherosclerosis (AS), but the underlying mechanism remains unclear. Objective: This study is intended for confirming key genes shared between NAFLD and AS, and their clinical diagnostic value to establish a foundation for searching novel therapeutic targets. Methods: We downloaded the Gene Expression Omnibus (GEO) datasets, GSE48452 and GSE89632 for NAFLD and GSE100927, GSE40231 and GSE28829 for AS. The progression of NAFLD co-expression gene modules were recognized via weighted gene co-expression network analysis (WGCNA). We screened for differentially expressed genes (DEGs) associated with AS and identified common genes associated with NAFLD and AS using Venn diagrams. We investigated the most significant core genes between NAFLD and AS using machine learning algorithms. We then constructed a diagnostic model by creating a nomogram and evaluating its performance using ROC curves. Furthermore, the CIBERSORT algorithm was utilized to explore the immune cell infiltration between the two diseases, and evaluate the relationship between diagnostic genes and immune cells. Results: The WGCNA findings associated 1,129 key genes with NAFLD, and the difference analysis results identified 625 DEGs in AS, and 47 genes that were common to both diseases. We screened the core RPS6KA1 and SERPINA3 genes associated with NAFLD and AS using three machine learning algorithms. A nomogram and ROC curves demonstrated that these genes had great clinical meaning. We found differential expression of RPS6KA1 in patients with steatosis and NASH, and of SERPINA3 only in those with NASH compared with normal individuals. Immune infiltration findings revealed that macrophage and mast cell infiltration play important roles in the development of NAFLD and AS. Notably, SERPINA3 correlated negatively, whereas RPS6KA1 correlated positively with macrophages and mast cells. Conclusion: We identified RPS6KA1 and SERPINA3 as potential diagnostic markers for NAFLD and AS. The most promising marker for a diagnosis of NAFLD and AS might be RPS6KA1, whereas SERPINA3 is the most closely related gene for NASH and AS. We believe that further exploration of these core genes will reveal the etiology and a pathological relationship between NAFLD and AS.

Dietary factors and hypertension: A Mendelian randomization analysis.

This research explores the causal link between dietary habits and hypertension through Mendelian randomization, providing distinct perspectives on the role of diet in addressing this worldwide health issue. Utilizing instrumental variables, we applied advanced statistical methods, including the weighted median, inverse variance weighted, and MR-Egger, to evaluate the impact of 17 dietary elements on hypertension. These elements ranged across various food groups, such as fruits, meats, vegetables, and beverages, both alcoholic and nonalcoholic. Our results identified a significant positive association of hypertension with weekly alcohol consumption (OR 1.340 [95%CI 1.0001 to 1.794], p = .0499) and poultry intake (OR 2.569 [95%CI 1.305 to 5.057], p = .00631). Conversely, a negative association was observed with lamb/mutton (OR 0.550 [95%CI 0.343 to 0.881], p = .0129), cheese (OR 0.650 [95%CI 0.519 to 0.813], p = .000159), tea (OR 0.797 [95%CI 0.640 to 0.993], p = .0433), cereal (OR 0.684 [95%CI 0.494 to 0.948], p = .0227), and dried fruit consumption (OR 0.492 [95%CI 0.343 to 0.707], p = .000127). These findings suggest that dietary modifications, such as increasing consumption of specific foods like cheese, lamb/mutton, tea, cereals, and dried fruits, could potentially reduce hypertension risk while reducing intake of alcoholic beverages and poultry might mitigate its increase. No direct causal relationships were established between other dietary factors and hypertension. The study highlights the importance of specific dietary modifications for the prevention and control of hypertension, making a substantial contribution to public health tactics and recommendations.

In vivo affinity maturation of mouse B cells reprogrammed to express human antibodies.

Mice adoptively transferred with mouse B cells edited via CRISPR to express human antibody variable chains could help evaluate candidate vaccines and develop better antibody therapies. However, current editing strategies disrupt the heavy-chain locus, resulting in inefficient somatic hypermutation without functional affinity maturation. Here we show that these key B-cell functions can be preserved by directly and simultaneously replacing recombined mouse heavy and kappa chains with those of human antibodies, using a single Cas12a-mediated cut at each locus and 5' homology arms complementary to distal V segments. Cells edited in this way to express the human immunodeficiency virus type 1 (HIV-1) broadly neutralizing antibody 10-1074 or VRC26.25-y robustly hypermutated and generated potent neutralizing plasma in vaccinated mice. The 10-1074 variants isolated from the mice neutralized a global panel of HIV-1 isolates more efficiently than wild-type 10-1074 while maintaining its low polyreactivity and long half-life. We also used the approach to improve the potency of anti-SARS-CoV-2 antibodies against recent Omicron strains. In vivo affinity maturation of B cells edited at their native loci may facilitate the development of broad, potent and bioavailable antibodies.

Association between red cell distribution width-to-albumin ratio and prognostic outcomes in pediatric intensive care unit patients: a retrospective cohort study.

Objective: This study aimed to assess the association between Red Cell Distribution Width-to-Albumin Ratio (RAR) and the clinical outcomes in Pediatric Intensive Care Unit (PICU) patients. Design: This is a retrospective cohort study. Methods: We conducted a retrospective cohort study based on the Pediatric Intensive Care database. The primary outcome was the 28-day mortality rate. Secondary outcomes included the 90-day mortality rate, in-hospital mortality rate, and length of hospital stay. We explored the relationship between RAR and the prognosis of patients in the PICU using multivariate regression and subgroup analysis. Results: A total of 7,075 participants were included in this study. The mean age of the participants was 3.4 ± 3.8 years. Kaplan-Meier survival curves demonstrated that patients with a higher RAR had a higher mortality rate. After adjusting for potential confounding factors, we found that for each unit increase in RAR, the 28-day mortality rate increased by 6% (HR = 1.06, 95% CI: 1.01-1.11, P = 0.015). The high-RAR group (RAR ≥ 4.0) had a significantly increased 28-day mortality rate compared to the low-RAR group (RAR ≤ 3.36) (HR = 1.7, 95% CI: 1.23-2.37, P < 0.001). Similar results were observed for the 90-day and in-hospital mortality rate. No significant interactions were observed in the subgroup analysis. Conclusion: Our study suggests a significant association between RAR and adverse outcomes in PICU patients. A higher RAR is associated with higher 28-day, 90-day, and in-hospital mortality rates.

Overwintering and summer survival of Ulva prolifera in sediments: Indoor simulation of temperature impacts.

Green tides, a globally prevalent marine ecological anomaly observed in coastal regions, have received substantial attention. However, there is limited research on the burial of Ulva prolifera in sediments during the late stages of green tide outbreaks. This study investigates the effect of temperature on U. prolifera buried in sediment over 30 days. The measurements included the length, biomass, relative growth rate, chlorophyll composition and maximum quantum yield (Fv/Fm) of PS II at different stages. The results indicate that at -20 °C, numerous seedlings emerged after 14 days of recovery culture, suggesting the release of spores or gametes; survival was possible from -2 °C to 15 °C; but at 20 °C and 30 °C, all U. prolifera died. The U. prolifera buried in sediment during the late stage of green tide outbreaks may serve as one of the sources for the subsequent year's green tide eruption. This research provides insights into the origins of green tide outbreaks in the southern Yellow Sea.

In vivo affinity maturation of the HIV-1 Env-binding domain of CD4.

Many human proteins have been repurposed as biologics for clinical use. These proteins have been engineered with in vitro techniques that improve affinity for their ligands. However, these approaches do not select against properties that impair efficacy such as protease sensitivity or self-reactivity. Here we engineer the B-cell receptor of primary murine B cells to express a human protein biologic without disrupting their ability to affinity mature. Specifically, CD4 domains 1 and 2 (D1D2) of a half-life enhanced-HIV-1 entry inhibitor CD4-Ig (CD4-Ig-v0) were introduced into the heavy-chain loci of murine B cells, which were then adoptively transferred to wild-type mice. After immunization, transferred B cells proliferated, class switched, affinity matured, and efficiently produced D1D2-presenting antibodies. Somatic hypermutations found in the D1D2-encoding region of engrafted B cells improved binding affinity of CD4-Ig-v0 for the HIV-1 envelope glycoprotein (Env) and the neutralization potency of CD4-Ig-v0 by more than ten-fold across a global panel of HIV-1 isolates, without impairing its pharmacokinetic properties. Thus, affinity maturation of non-antibody protein biologics in vivo can guide development of more effective therapeutics.

In vivo affinity maturation of the HIV-1 Env-binding domain of CD4.

Many human proteins have been repurposed as biologics for clinical use. These proteins have been engineered with in vitro techniques that improve affinity for their ligands. However, these approaches do not select against properties that impair efficacy such as protease sensitivity or self-reactivity. Here we engineer the B-cell receptor of primary murine B cells to express a human protein biologic without disrupting their ability to affinity mature. Specifically, CD4 domains 1 and 2 (D1D2) of a half-life enhanced-HIV-1 entry inhibitor CD4-Ig (CD4-Ig-v0) were introduced into the heavy-chain loci of murine B cells, which were then adoptively transferred to wild-type mice. After immunization, transferred B cells proliferated, class switched, affinity matured, and efficiently produced D1D2-presenting antibodies. Somatic hypermutations found in the D1D2-encoding region of engrafted B cells improved binding affinity of CD4-Ig-v0 for the HIV-1 envelope glycoprotein (Env) and the neutralization potency of CD4-Ig-v0 by more than ten-fold across a global panel of HIV-1 isolates, without impairing its pharmacokinetic properties. Thus, affinity maturation of non-antibody protein biologics in vivo can guide development of more effective therapeutics.

Metabotropic glutamate receptor 5 promotes blood-brain barrier recovery after traumatic brain injury.

Blood-brain barrier (BBB) impairment and glutamate release are two pathophysiological features of traumatic brain injury (TBI), contributing to secondary brain damage and neuroinflammation. However, our knowledge of BBB integrity damage and dysfunction are still limited due to the diverse and fluctuating expression of glutamate receptors after trauma. Here, we confirmed the downregulation of metabotropic glutamate receptor 5 (mGluR5) on microvascular endothelial cell within the acute phase of TBI, and the recovered mGluR5 levels on BBB was positively associated with blood perfusion and neurological recovery. In whole body mGluR5-knockout mice, BBB dysfunction and neurological deficiency were exacerbated after TBI compared with wild type mice. In terms of mechanism, the amino acid sequence 201-259 of cytoskeletal protein Alpha-actinin-1 (ACTN1) interacted with mGluR5, facilitating mGluR5 translocation from cytoplasmic compartment to plasma membrane in endothelial cells. Activation of plasma membrane mGluR5 triggers the PLC/PKCµ/c-Jun signaling pathway, leading to increased expression of the tight junction-actin cytoskeleton connecting protein zonula occludens-1 (ZO-1). Our findings uncover a novel mechanism mediated by membrane and cytoplasmic mGluR5 in endothelial cell integrity maintenance and repair, providing the potential therapeutic target for TBI treatment targeting at mGluR5 and mGluR5/ACTN1 complex in BBB.

Boosting Electrochemical CO2 Reduction on Copper-Based Metal-Organic Frameworks via Valence and Coordination Environment Modulation.

Cu-based metal-organic frameworks (MOFs) have attracted much attention for electrocatalytic CO2 reduction to high value-added chemicals, but they still suffer from low selectivity and instability. Here, an associative design strategy for the valence and coordination environment of the metal node in Cu-based MOFs is employed to regulate the CO2 electroreduction to ethylene. A novel "reduction-cleavage-recrystallization" method is developed to modulate the Cu(II)-Trimesic acid (BTC) framework to form a Cu(I)-BTC structure enriched with free carboxyl groups in the secondary coordination environment (SCE). In contrast to Cu(II)-BTC, the Cu(I)-BTC shows higher catalytic activity and better ethylene selectivity (≈2.2-fold) for CO2 electroreduction, which is further enhanced by increasing the content of free carboxyl groups, resulting in ethylene Faraday efficiency of up to 57% and the durability of the catalyst could last for 38 h without performance decline. It indicates that the synergistic effect between Cu(I)-O coordinated structure and free carboxyl groups considerably enhances the dimerization of *CO intermediates and hinders the hydrogenation of *CO intermediates in these competitive pathways. This work unravels the strong dependence of CO2 electroreduction on the Cu valence state and coordination environment in MOFs and provides a platform for designing highly selective electrocatalytic CO2 reduction catalysts.

Characteristics and driving factors of antibiotic resistance genes in aquaculture products from freshwater ponds in China Yangtze River Delta.

Antibiotic resistance genes (ARGs) are widespread in aquaculture and pose a huge threat to aquaculture organisms and human health. In this study, occurrences and relative abundances of ARGs were analysed in the guts of products cultured in freshwater ponds in the Yangtze River Delta region in China. A total of 29 ARGs were found in the gut samples, with detection frequencies ranging from 4.8% to 81%, and the relative abundances (ARGs/16S rRNA) ranging from 10-7 to 1. In addition, the human dietary intake of ARGs via aquaculture products was assessed, where the daily intake of most ARGs via aquaculture products was higher than those via PM2.5 and drinking water, but lower than that via vegetables. The relative abundances of MGE (IS613, Tp614, tnpA and int1) were significantly correlated with those of multiple ARGs, indicating the horizontal gene transfer (HGT) of ARGs among gut microorganisms. Proteobacteria, Firmicutes and Actinobacteria were the dominated microbial communities found in the guts of aquaculture products. In addition, significant correlations were found between Cyanobacteria and int1, between Nitrospira and tetE, and between sul2 and aadA2, indicating potential same hosts of these genes. In addition, results from co-correlation indicated both HGT (dominated by MGEs) of ARGs and the enrichment of ARGs in bacteria. MGEs, mostly int1, were more effective than bacteria in increasing the ARG abundance. This study could provide a better understanding of the transmission of ARGs in the aquaculture environment and improve the quality of aquaculture products and the ecology.

The phonological congruency modulated long-term form priming of Chinese characters.

Elucidating the interaction between lexical processing and word learning is essential for a complete understanding of the underlying mechanisms of each of them. Long-term priming for words reflects an interplay between lexical processing and word learning. Although robust long-term priming effects have been found between two occurrences of the same word and between semantically similar words, it remains unclear whether long-term priming between orthographically similar words (i.e., long-term form priming) is a reliable effect. Following the theoretical analysis based on the connectionist framework, we articulated the possibility that long-term form priming might be modulated by the phonological congruency between the prime and target words, and that if this modulator was under control, reliable effects of long-term form priming would emerge. However, this hypothesis has not been adequately tested empirically. The present study tested this hypothesis by using Chinese phonograms and the phonetic radicals embedded in them as the prime and target items. In three experiments that varied in the types of stimuli and testing tasks, we consistently found that when the prime and target had the same phonology, naming the prime facilitated later processing of the target, while when they had different phonologies, the priming effect was inhibitory. These observations were consistent with the connectionist account of long-term priming for words. Our findings help confirm the reliability, generalizability, and robustness of long-term form priming and elucidate its underlying mechanisms, and suggesting promising future directions on the interactions between lexical processing and word learning.

Unlabelled LRET biosensor based on double-stranded DNA for the detection of anthraquinone anticancer drugs.

Based on upconversion nanoparticles (UCNPs) as energy donor and herring sperm DNA (hsDNA) as molecular recognition element, an unlabelled upconversion luminescence (UCL) affinity biosensor was constructed for the detection of anthraquinone (AQ) anticancer drugs in biological fluids. AQ anticancer drugs can insert into the double helix structure of hsDNA on the surface of UCNPs, thereby shortening the distance from UCNPs. Therefore, the luminescence resonance energy transfer (LRET) phenomenon is effectively triggered between UCNPs and AQ anticancer drugs. Hence, AQ anticancer drugs can be quantitatively detected according to the UCL quenching rate. The biosensor showed good sensitivity and stability for the detection of daunorubicin (DNR) and doxorubicin (ADM). For the detection of DNR, the linear range is 1-100 µg·mL-1 with a limit of detection (LOD) of 0.60 µg·mL-1, and for ADM, the linear range is 0.5-100 µg·mL-1 with a LOD of 0.38 µg·mL-1. The proposed biosensor provides a convenient method for monitoring AQ anticancer drugs in clinical biological fluids in the future.

Independent and Interactive Roles of Immunity and Metabolism in Aortic Dissection.

Aortic dissection (AD) is a cardiovascular disease that seriously endangers the lives of patients. The mortality rate of this disease is high, and the incidence is increasing annually, but the pathogenesis of AD is complicated. In recent years, an increasing number of studies have shown that immune cell infiltration in the media and adventitia of the aorta is a novel hallmark of AD. These cells contribute to changes in the immune microenvironment, which can affect their own metabolism and that of parenchymal cells in the aortic wall, which are essential factors that induce degeneration and remodeling of the vascular wall and play important roles in the formation and development of AD. Accordingly, this review focuses on the independent and interactive roles of immunity and metabolism in AD to provide further insights into the pathogenesis, novel ideas for diagnosis and new strategies for treatment or early prevention of AD.

In vivo affinity maturation of murine B cells reprogrammed to express human antibodies.

CRISPR-edited murine B cells engineered to express human antibody variable chains proliferate, class switch, and secrete these antibodies in vaccinated mice. However, current strategies disrupt the heavy-chain locus, resulting in inefficient somatic hypermutation without functional affinity maturation. Here we show that recombined murine heavy- and kappa-variable genes can be directly and simultaneously overwritten, using Cas12a-mediated cuts at their 3'-most J segments and 5' homology arms complementary to distal V segments. Cells edited in this way to express the HIV-1 broadly neutralizing antibodies 10-1074 or VRC26.25-y robustly hypermutated and generated potent neutralizing plasma in vaccinated recipient mice. 10-1074 variants isolated from these mice bound and neutralized HIV-1 envelope glycoprotein more efficiently than wild-type 10-1074 while maintaining or improving its already low polyreactivity and long in vivo half-life. We further validated this approach by generating substantially broader and more potent variants of the anti-SARS-CoV-2 antibodies ZCB11 and S309. Thus, B cells edited at their native loci affinity mature, facilitating development of broad, potent, and bioavailable antibodies and expanding the potential applications of engineered B cells.