Flavin-containing monooxygenases FMOGS-OXs integrate flowering transition and salt tolerance in Arabidopsis thaliana.

Salt stress substantially leads to flowering delay. The regulation of salt-induced late flowering has been studied at the transcriptional and protein levels; however, the involvement of secondary metabolites has rarely been investigated. Here, we report that FMOGS-OXs (EC 1.14.13.237), the enzymes that catalyze the biosynthesis of glucosinolates (GSLs), promote flowering transition in Arabidopsis thaliana. It has been reported that WRKY75 is a positive regulator, and MAF4 is a negative regulator of flowering transition. The products of FMOGS-OXs, methylsulfinylalkyl GSLs (MS GSLs), facilitate flowering by inducing WRKY75 and repressing the MAS-MAF4 module. We further show that the degradation of MS GSLs is involved in salt-induced late flowering and salt tolerance. Salt stress induces the expression of myrosinase genes, resulting in the degradation of MS GSLs, thereby relieving the promotion of WRKY75 and inhibition of MAF4, leading to delayed flowering. In addition, the degradation products derived from MS GSLs enhance salt tolerance. Previous studies have revealed that FMOGS-OXs exhibit alternative catalytic activity to form trimethylamine N-oxide (TMAO) under salt stress, which activates multiple stress-related genes to promote salt tolerance. Therefore, FMOGS-OXs integrate flowering transition and salt tolerance in various ways. Our study shed light on the functional diversity of GSLs and established a connection between flowering transition, salt resistance, and GSL metabolism.

Transformer based multi-modal MRI fusion for prediction of post-menstrual age and neonatal brain development analysis.

The brain development during the perinatal period is characterized by rapid changes in both structure and function, which have significant impact on the cognitive and behavioral abilities later in life. Accurate assessment of brain age is a crucial indicator for brain development maturity and can help predict the risk of neonatal pathology. However, evaluating neonatal brains using magnetic resonance imaging (MRI) is challenging due to its complexity, multi-dimension, and noise with subtle alterations. In this paper, we propose a multi-modal deep learning framework based on transformers for precise post-menstrual age (PMA) estimation and brain development analysis using T2-weighted structural MRI (T2-sMRI) and diffusion MRI (dMRI) data. First, we build a two-stream dense network to learn modality-specific features from T2-sMRI and dMRI of brain individually. Then, a transformer module based on self-attention mechanism integrates these features for PMA prediction and preterm/term classification. Finally, saliency maps on brain templates are used to enhance the interpretability of results. Our method is evaluated on the multi-modal MRI dataset of the developing Human Connectome Project (dHCP), which contains 592 neonates, including 478 term-born and 114 preterm-born subjects. The results demonstrate that our method achieves a 0.5-week mean absolute error (MAE) in PMA estimation for term-born subjects. Notably, preterm-born subjects exhibit delayed brain development, worsening with increasing prematurity. Our method also achieves 95% accuracy in classification of term-born and preterm-born subjects, revealing significant group differences.

Sensitivity-enhanced strain sensor based on a shape-modulated multimode fiber.

In this Letter, we demonstrate a sensitivity-enhanced strain sensor based on a shape-modulated multimode fiber (MMF). In contrast to conventional single-mode-multimode-single-mode (SMS) fiber structures, which typically contain a single cylindrical homogeneous MMF section, the shape of the MMF section in this investigation is modulated by lateral offset splicing of multiple MMF segments. Simulation results show that the designed shape-modulated MMF has a higher peak mechanical strain than that of a cylindrical MMF. Experimental results demonstrate that the strain sensitivity achieved by the shaped-modulated MMF-formed SMS fiber structure is as high as -55.63 pm/µÎµ, which is 33 times higher than that for a cylindrical MMF-formed conventional SMS fiber structure at -1.65 pm/µÎµ. This high sensitivity and low-fabrication cost SMS fiber sensor has the potential to be a promising candidate in precise strain measurement applications.

Mdpg: a novel multi-disease diagnosis prediction method based on patient knowledge graphs.

Diagnosis prediction, a key factor in enhancing healthcare efficiency, remains a focal point in clinical decision support research. However, the time-series, sparse and multi-noise characteristics of electronic health record (EHR) data make it a great challenge. Existing methods commonly address these issues using RNNs and incorporating medical prior knowledge from medical knowledge bases, but they neglect the local spatial characteristics and spatial-temporal correlation of the data. Consequently, we propose MDPG, a diagnosis prediction model based on patient knowledge graphs. Initially, we represent the electronic visit records of patients as a patient-centered temporal knowledge graph, capturing the local spatial structure and temporal characteristics of the visit information. Subsequently, we design the spatial graph convolution block, temporal self-attention block, and spatial-temporal synchronous graph convolution block to capture the spatial, temporal, and spatial-temporal correlations embedded in them, respectively. Ultimately, we accomplish the prediction of patients' future states through multi-label classification. We conduct comprehensive experiments on two real-world datasets independently and evaluate the results using visit-level precision@k and code-level accuracy@k metrics. The experimental results demonstrate that MDPG outperforms all baseline models, yielding the best performance.

Development of a Mind Map-based Predictive Nursing Protocol and its Impact on the Clarity of Images in Patients Undergoing High-concentration Contrast Three-dimensional Computed Tomography Imaging of Liver Blood Vessels.

OBJECTIVE: To explore the development of a mind map-based predictive nursing protocol and assess its impact on the quality of images in patients undergoing high-concentration contrast three-dimensional computed tomography (CT) imaging of liver blood vessels. METHODS: A total of 600 patients who were admitted to Beijing You an Hospital were chosen for this prospective study and underwent high-concentration contrast three-dimensional CT imaging of liver blood vessels between April 2021 and December 2021. The patients were divided into two groups using the digital table method, with 300 cases. The control group received conventional nursing intervention, while the research group was provided with a mind map-based predictive nursing protocol. We recorded the image quality of three-dimensional CT imaging of liver blood vessels, satisfaction scores regarding nurse examination guidance, and the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) in both groups. RESULTS: The research group achieved a perfect rate of 100.00% for the high-quality three-dimensional CT imaging of liver blood vessels, which was noticeably higher compared to the rate of the control group of 98.67%. Patients in the research group expressed higher satisfaction levels regarding the guidance provided by nurses, including their attitude, timeliness, accuracy, and overall satisfaction, compared to the control group. Initially, the two groups had no notable differences in the SAS and SDS scores. However, after the intervention, both groups experienced a significant decrease in SAS and SDS scores, with the research group showing an even more substantial decline. CONCLUSION: Through the creation of a mind map-based predictive nursing protocol and its implementation on patients undergoing high-concentration contrast three-dimensional CT imaging of liver blood vessels, it is possible to significantly enhance the quality of CT scans, alleviate feelings of anxiety and depression, increase patient satisfaction with examination guidance by nurses, and effectively decrease the occurrences of contrast agent leakage and allergic reactions to iodine.

Distance-specific functional connectivity strength alterations in human immunodeficiency virus asymptomatic neurocognitive impairment patients: a cross-sectional study.

Background: Asymptomatic neurocognitive impairment (ANI) is the mildest form of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HANDs), and functional connectivity strength (FCS) alternations have been observed in the ANI stage. However, it is not clear whether the FCS alterations are influenced by the anatomical distance. This study sought to investigate distance-specific FCS changes in HIV ANI patients. Methods: In total, 29 patients with HAND and 32 healthy controls (HCs) were enrolled in the study. Between-group differences were detected for short, middle and long range anatomical distance FCS. A correlation analysis was performed to examine the relationship between distance-specific FCS and immunological parameters and neuropsychological tests. A receiver operating characteristic (ROC) analysis was conducted to examine the discriminative performance for HIV ANI patients. Results: In comparison to the HCs, the HAND patients showed increased short-range FCS in the left inferior parietal lobule (IPL), middle-range FCS in the superior temporal gyrus (STG), long-range FCS in the left precuneus (PCC), and decreased FCS in the right postcentral gyrus (PCG) (cluster P<0.05, voxel significance P<0.001). Further, the long-range FCS in the right PCG was negatively correlated with the CD4/CD8 ratio (r=-0.479, 95% confidence interval (CI): -0.735 to -0.104, P=0.015), and the distance-specific FCS also showed good classification performance between the HAND patients and HCs. The left IPL, left STG, right PCG, and left PCC had areas under the curve (AUCs) of 0.875 [95% confidence interval (CI): 0.758-0.949, P<0.0001], 0.806 (95% CI: 0.677-0.900, P<0.0001), 0.855 (95% CI: 0.734-0.935, P<0.0001), and 0.852 (95% CI: 0.754-0.950, P<0.0001), respectively. There was no significant relationship between the distance-specific FCS and the neuropsychological tests. Conclusions: Distance-specific FCS could be used to examine subtle alternations in HIV-infected patients in the ANI stage and help to explain the possible neurophysiological mechanism of HAND.

Trimethylamine N-oxide promotes oxidative stress and lipid accumulation in macrophage foam cells via the Nrf2/ABCA1 pathway

Recently, trimethylamine N-oxide (TMAO) has been considered a risk factor for cardiovascular disease and has a proatherogenic effect. Many studies have found that TMAO is involved in plaque oxidative stress and lipid metabolism, but the specific mechanism is still unclear. In our study, meta-analysis and bioinformatic analysis were firstly conducted in the database, and found that the effect of high plasma TMAO levels on promoting atherosclerotic plaque may be related to the expression of key antioxidant genes nuclear factor erytheroid-derived-2-like 2 (NFE2L2/Nrf2) decreased. Next, we assessed the role of Nrf2-mediated signaling pathway in TMAO-treated foam cells. Our results showed that TMAO can inhibit the expression of Nrf2 and its downstream antioxidant response element such as heme oxygenase-1 (HO-1) and glutathione peroxidase4 (GPX4), resulting in increased production of reactive oxygen species and decreased activity of superoxide dismutase, promoting oxidative stress. And TMAO can also promote lipid accumulation in foam cells by inhibiting cholesterol efflux protein expression. In addition, upregulation of Nrf2 expression partially rescues TMAO-induced oxidative stress and reduces ATP-binding cassette A1 (ABCA1)–mediated lipid accumulation. Therefore, TMAO promotes oxidative stress and lipid accumulation in macrophage foam cells through the Nrf2/ABCA1 pathway, which may provide a potential mechanism for the proatherogenic effect of TMAO. (AU)

Trimethylamine N-oxide promotes oxidative stress and lipid accumulation in macrophage foam cells via the Nrf2/ABCA1 pathway

Recently, trimethylamine N-oxide (TMAO) has been considered a risk factor for cardiovascular disease and has a proatherogenic effect. Many studies have found that TMAO is involved in plaque oxidative stress and lipid metabolism, but the specific mechanism is still unclear. In our study, meta-analysis and bioinformatic analysis were firstly conducted in the database, and found that the effect of high plasma TMAO levels on promoting atherosclerotic plaque may be related to the expression of key antioxidant genes nuclear factor erytheroid-derived-2-like 2 (NFE2L2/Nrf2) decreased. Next, we assessed the role of Nrf2-mediated signaling pathway in TMAO-treated foam cells. Our results showed that TMAO can inhibit the expression of Nrf2 and its downstream antioxidant response element such as heme oxygenase-1 (HO-1) and glutathione peroxidase4 (GPX4), resulting in increased production of reactive oxygen species and decreased activity of superoxide dismutase, promoting oxidative stress. And TMAO can also promote lipid accumulation in foam cells by inhibiting cholesterol efflux protein expression. In addition, upregulation of Nrf2 expression partially rescues TMAO-induced oxidative stress and reduces ATP-binding cassette A1 (ABCA1)–mediated lipid accumulation. Therefore, TMAO promotes oxidative stress and lipid accumulation in macrophage foam cells through the Nrf2/ABCA1 pathway, which may provide a potential mechanism for the proatherogenic effect of TMAO. (AU)

An electrochemical biosensor based on DNA tetrahedron nanoprobe for sensitive and selective detection of doxorubicin.

Doxorubicin (DOX) is a clinical chemotherapeutic drug and patients usually suffer from dose-dependent cytotoxic and side effects during chemotherapy process with DOX. Therefore, developing a reliable strategy for DOX analysis in biological samples for dosage guidance during chemotherapy process is of great significance. Herein, a sensitive and selective electrochemical biosensor for DOX detection was designed based on gold nanoparticles (AuNPs) and DNA tetrahedron (TDN) nanoprobe bifunctional glassy carbon electrode that could detect DOX in human serum and cell lysate samples. AuNPs not only could enhance electron transfer efficiency and detection sensitivity, but also could improve the biocompatibility of electrode. TDN nanoprobes were employed as specific DOX bind sites that could bind abundant DOX through intercalative characteristics to contribute to sensitive and selective detection. Under the optimal conditions, the proposed TDN nanoprobes-based DOX biosensor exhibited a wide linear range that ranged from 1.0 nM to 50 µM and a low detection limit that was 0.3 nM. Moreover, the proposed DOX biosensor displayed nice selectivity, reproducibility and stability, and was successfully applied for DOX detection in human serum and cell lysate samples. These promising results maybe pave a way for DOX dosage guidance and therapeutic efficacy optimization in clinic.

Genome Mining Reveals the Biosynthesis of Sativene and Its Oxidative Conversion to seco-Sativene.

Sativene (1) and seco-sativene are an important family of fungal sesquiterpenoids that feature unique tricyclo[4.4.0.01,7]decane and bicyclo[3.2.1]octane skeletons, respectively. Herein, we identify a three-enzyme cassette: SatA cyclizes farnesyl diphosphate (FPP) to form compound 1; CYP450 SatB catalyzes C14-C15 dihydroxylations and subsequent bond cleavage; and reductase SatC regioselectively reduces C14 aldehyde and mediates hemiacetal ring closure to generate prehelminthosporol (2). Our findings clarify the synthetic step of sativene and its oxidative transformation processes into seco-sativene.

Glycosides with galloyl groups from Balakata baccata and their antineuroinflammatory activities.

Seven new glycosides (1 - 7) with galloyl groups and two known kaempferol glycosides (8 and 9) were obtained from the overground parts of Balakata baccata. The structures of the new compounds were determined by comprehensive spectroscopic analyses. The rarely seen allene moiety in compounds 6 and 7 were described by detailed analysis of 1D and 2D NMR data. The antineuroinflammatory effect of all the isolates was assessed through inhibiting nitric oxide (NO) production in lipopolysaccharide (LPS)-induced BV-2 microglial cells. Compounds 1, 2, 6, and 7 showed potent inhibitory activities with IC50 values of 25.7, 17.2, 15.5 and 24.4 µM, respectively, compared with the positive control minocycline (IC50 = 16.1 µM).

Trimethylamine N-oxide promotes oxidative stress and lipid accumulation in macrophage foam cells via the Nrf2/ABCA1 pathway.

Recently, trimethylamine N-oxide (TMAO) has been considered a risk factor for cardiovascular disease and has a proatherogenic effect. Many studies have found that TMAO is involved in plaque oxidative stress and lipid metabolism, but the specific mechanism is still unclear. In our study, meta-analysis and bioinformatic analysis were firstly conducted in the database, and found that the effect of high plasma TMAO levels on promoting atherosclerotic plaque may be related to the expression of key antioxidant genes nuclear factor erytheroid-derived-2-like 2 (NFE2L2/Nrf2) decreased. Next, we assessed the role of Nrf2-mediated signaling pathway in TMAO-treated foam cells. Our results showed that TMAO can inhibit the expression of Nrf2 and its downstream antioxidant response element such as heme oxygenase-1 (HO-1) and glutathione peroxidase4 (GPX4), resulting in increased production of reactive oxygen species and decreased activity of superoxide dismutase, promoting oxidative stress. And TMAO can also promote lipid accumulation in foam cells by inhibiting cholesterol efflux protein expression. In addition, upregulation of Nrf2 expression partially rescues TMAO-induced oxidative stress and reduces ATP-binding cassette A1 (ABCA1)-mediated lipid accumulation. Therefore, TMAO promotes oxidative stress and lipid accumulation in macrophage foam cells through the Nrf2/ABCA1 pathway, which may provide a potential mechanism for the proatherogenic effect of TMAO.

Longitudinal Relation between Harsh Punishment and Psychoticism among Chinese Early Adolescents: Disentangling between­ and within­Family Effects.

This longitudinal study examined bidirectional relations between parental harsh punishment and psychoticism at the between­ and within­family levels in Chinese adolescents. There were 3,307 Chinese youth (43.6% girls, Mage = 11.30 years, SD = 0.24) who participated in a 4-wave longitudinal study, spaced 12 months apart. The results of cross-lagged panel modeling (i.e. CLPM) found the significant bidirectional relations between parental harsh punishment and psychoticism at the between-family level. However, the within-person level analysis of random intercept cross-lagged panel modeling (i.e. RI-CLPM) only revealed parental harsh punishment significantly predicted youth psychoticism, but not vice versa. Moreover, no sex differences were observed in the bidirectional relations between parental harsh punishment and psychoticism at the between- or within-family level. These results suggest parental harsh parenting could exacerbate the psychoticism trait at both the between- and within-family level, whereas the influence of young people's psychoticism on harsh parenting response from parents occurs only at the between-family level. The findings help to understand the nature of the dynamic process of change between psychoticism and harsh parenting among Chinese adolescents.

Microbiome and metabolome dysbiosis analysis in impaired glucose tolerance for the prediction of progression to diabetes mellitus.

Gut microbiota and circulating metabolite dysbiosis predate important pathological changes in glucose metabolic disorders; however, comprehensive studies on impaired glucose tolerance (IGT), a diabetes mellitus (DM) precursor, are lacking. Here, we perform metagenomic sequencing and metabolomics on 47 pairs of individuals with IGT and newly diagnosed DM and 46 controls with normal glucose tolerance (NGT); patients with IGT are followed up after 4 years for progression to DM. Analysis of baseline data reveals significant differences in gut microbiota and serum metabolites among the IGT, DM, and NGT groups. In addition, 13 types of gut microbiota and 17 types of circulating metabolites showed significant differences at baseline before IGT progressed to DM, including higher levels of Eggerthella unclassified, Coprobacillus unclassified, Clostridium ramosum, L-valine, L-norleucine, and L-isoleucine, and lower levels of Eubacterium eligens, Bacteroides faecis, Lachnospiraceae bacterium 3_1_46FAA, Alistipes senegalensis, Megaspaera elsdenii, Clostridium perfringens, α-linolenic acid, 10E,12Z-octadecadienoic acid, and dodecanoic acid. A random forest model based on differential intestinal microbiota and circulating metabolites can predict the progression from IGT to DM (AUC = 0.87). These results suggest that microbiome and metabolome dysbiosis occur in individuals with IGT and have important predictive values and potential for intervention in preventing IGT from progressing to DM.

Effects of combined exposure to polystyrene microplastics and 17α-Methyltestosterone on the reproductive system of zebrafish.

Polystyrene microplastics (PS-MPs) are important carriers of pollutants in water. 17α-Methyltestosterone (MT) is a synthetic environmental endocrine disrupting chemical (EDC) with androgenic effects. To study the effects of PS-MPs and MT on zebrafish reproductive systems, zebrafish were exposed to 0 or 50 ng L-1 MT, 0.5 mg∙L-1 PS-MPs, or 50 ng∙L-1 MT + 0.5 mg∙L-1 PS-MPs for 21 d. The results showed that the different exposure reagents caused varying degrees of damage to the reproductive systems in zebrafish, with the extent of damage increasing as the exposure duration increased. Histological analysis of the gonads revealed that the ratio of mature oocytes and mature spermatozoa in the gonad decreased gradually with increased exposure time, with the ratio being Control > PS-MPs > MT > MT + PS-MPs in decreasing order. The results of quantitative real-time PCR (qRT‒PCR) showed that in female fish treated for 7 d, the expression of cyp11a mRNA was significantly reduced in all three treatment groups(MT, PS-MPs, and MT + PS-MPs), while in the group treated for 14 d with MT + PS-MPs, the expression of cyp19a1a and StAR mRNA was significantly increased. In male fish exposed for 21 d, the expression of cyp11a, cyp17a1, cyp19a1a, StAR, 3ß-HSD, and 17ß-HSD3 mRNA was significantly decreased in MT + PS-MPs. ELISA results showed that after 14 d of exposure, the levels of E2, LH, and FSH in the ovaries of female fish were significantly reduced in all three treatment groups. Similarly, the levels of T, E2, LH, and FSH in the testis of male fish were significantly reduced after 14 d of exposure to PS-MPs and MT + PS-MPs. Offspring of zebrafish exposed to MT and MT + PS-MPs exhibited delayed incubation time and slow development. The cross-generational toxicity of PS-MPs themselves may be negligible, but it can exacerbate the toxicity of MT, making the cross-generational effects more pronounced in the offspring, causing offspring mortality and malformations. Offspring of zebrafish exposed to MT and MT + PS-MPs exhibited delayed incubation time and slow development. In addition, MT caused malformations such as pericardial edema, yolk cysts, and spinal deformities in zebrafish during the incubation period.

The transcription factor MdBPC2 alters apple growth and promotes dwarfing by regulating auxin biosynthesis.

Auxin plays important roles throughout plant growth and development. However, the mechanisms of auxin regulation of plant structure are poorly understood. In this study, we identified a transcription factor (TF) of the BARLEY B RECOMBINANT/BASIC PENTACYSTEINE (BBR/BPC) family in apple (Malus × domestica), MdBPC2. It was highly expressed in dwarfing rootstocks, and it negatively regulated auxin biosynthesis. Overexpression of MdBPC2 in apple decreased plant height, altered leaf morphology, and inhibited root system development. These phenotypes were due to reduced auxin levels and were restored reversed after exogenous indole acetic acid (IAA) treatment. Silencing of MdBPC2 alone had no obvious phenotypic effect, while silencing both Class I and Class II BPCs in apple significantly increased auxin content in plants. Biochemical analysis demonstrated that MdBPC2 directly bound to the GAGA-rich element in the promoters of the auxin synthesis genes MdYUC2a and MdYUC6b, inhibiting their transcription and reducing auxin accumulation in MdBPC2 overexpression lines. Further studies established that MdBPC2 interacted with the polycomb group (PcG) protein LIKE HETEROCHROMATIN PROTEIN 1 (LHP1) to inhibit MdYUC2a and MdYUC6b expression via methylation of histone 3 lysine 27 (H3K27me3). Silencing MdLHP1 reversed the negative effect of MdBPC2 on auxin accumulation. Our results reveal a dwarfing mechanism in perennial woody plants involving control of auxin biosynthesis by a BPC transcription factor, suggesting its use for genetic improvement of apple rootstock.

E3 ubiquitin ligase RNF180 impairs IPO4/SOX2 complex stability and inhibits SOX2-mediated malignancy in ovarian cancer.

RING finger protein 180 (RNF180), an E3 ubiquitin ligase, is thought to be a tumor suppressor gene. However, the detailed mechanism of its effect on ovarian cancer (OV) has not been elucidated. Importin 4 (IPO4) which belongs to transport protein is reported to have cancer-promoting effects on OV. Here, we explored the potential signaling pathways related to RNF180 and IPO4. It was first verified that RNF180 is downregulated and IPO4 is upregulated in OV. By overexpressing or knocking down RNF180 in OV cells, we confirmed that RNF180 inhibited the malignant behaviors of OV cells both in vitro and in vivo. Bioinformatics analysis and proteomics experiments found that RNF180 could interact with IPO4 and promote the degradation of IPO4 through ubiquitination. In addition, overexpression of IPO4 removed the inhibitory effect of RNF180 on OV. We subsequently found that IPO4 could bind to the oncogene Sex determining Region Y-box 2 (SOX2). Knockdown of IPO4 in OV cells decreased SOX2 protein level in nucleus and promoted cyclin-dependent kinase inhibitory protein-1 (p21) expression. Overexpression of RNF180 also inhibited the expression of SOX2 in nucleus. All these results indicated that RNF180 inhibited the nuclear translocation of SOX2 by promoting ubiquitination of IPO4, which ultimately promoted the expression of p21 and then suppressed the progression of OV. This study verified the tumor suppressor effect of RNF180 on OV, elucidated the mechanism of the molecule network related to RNF180 and IPO4 in OV and identified for OV.

Controlling Risk Factors Reduces Cancer Risk in Patients with Atherosclerotic Cardiovascular Disease: A Cohort Study.

BACKGROUND: The association of atherosclerotic cardiovascular disease (ASCVD) with cancer occurrence is not well examined, and the impact of common risk factors on the risk of cancer in ASCVD patients is not known. This study aimed to explore the effect and possible causes of ASCVD on cancer risk through a cohort study. METHODS: A total of 14,665 age- and sex-matched pairs of participants were recruited from the Kailuan cohort (ASCVD vs non-ASCVD). A competing risk model was used to calculate the risk of cancer after ASCVD. RESULTS: A total of 1124 cancers occurred after 5.80 (3.05-9.44) years of follow-up. The ASCVD group had a reduced risk of cancer (hazard ratio 0.74; 95% confidence interval, 0.65-0.85). Also, the risk of cancer in the digestive system, respiratory system, urinary system, and reproductive system was reduced by 17%, 16%, 14%, and 52%, respectively. According to the status of systolic and diastolic blood pressure, fasting blood glucose, high-sensitivity C-reactive protein and body mass index after ASCVD, the risk of overall cancer and digestive system cancer decreased with the increase in the number of ideal indicators (P for trend < .01). With the increase of follow-up time, the risk of cancer and the 5 site-specific cancers gradually decreased. CONCLUSIONS: Cancer risk can be reduced by controlling for common risk factors after ASCVD event. This risk reduction is site-specific-, time-, and the number of ideal indicator-dependent.

A broadly reactive antibody targeting the N-terminal domain of SARS-CoV-2 spike confers Fc-mediated protection.

Most neutralizing anti-SARS-CoV-2 monoclonal antibodies (mAbs) target the receptor binding domain (RBD) of the spike (S) protein. Here, we characterize a panel of mAbs targeting the N-terminal domain (NTD) or other non-RBD epitopes of S. A subset of NTD mAbs inhibits SARS-CoV-2 entry at a post-attachment step and avidly binds the surface of infected cells. One neutralizing NTD mAb, SARS2-57, protects K18-hACE2 mice against SARS-CoV-2 infection in an Fc-dependent manner. Structural analysis demonstrates that SARS2-57 engages an antigenic supersite that is remodeled by deletions common to emerging variants. In neutralization escape studies with SARS2-57, this NTD site accumulates mutations, including a similar deletion, but the addition of an anti-RBD mAb prevents such escape. Thus, our study highlights a common strategy of immune evasion by SARS-CoV-2 variants and how targeting spatially distinct epitopes, including those in the NTD, may limit such escape.

The ratio of lymphocyte/red blood cells and platelets/lymphocytes are predictive biomarkers for lymph node metastasis in patients with breast cancer.

BACKGROUND: Axillary lymph node metastasis (LNM) affects the progression of breast cancer. However, it is difficult to preoperatively diagnose axillary lymph node status with high sensitivity. Therefore, we hypothesized that platelets/lymphocytes ratio (PLR) and lymphocytes/ red blood cells ratio (LRR) might help in the prognosis of lymph node metastasis in T1-T2 breast cancer. METHODS: 166 patients (Chang Ning Maternity & Infant Health Institute) were included in our study, and the associations of PLR and LPR with lymph node metastasis were investigated. Peripheral blood was collected one week before the surgery, and the patients were divided into different categories based on their PLR and LRR. RESULTS: The incidence of LNM was significantly increased in the high PLR group (p= 0.002) compared with the low PLR group; LNM was also significantly increased in the low LRR group (p= 0.036) compared with the high LPR group. Further, our study revealed that high PLR (p< 0.001, OR = 4.397, 95% CI = 2.005-9.645), low LRR (p= 0.017, OR = 0.336, 95%CI = 0.136-0.825) and high clinical T stage (p< 0.001, OR = 3.929, 95%CI = 1.913-8.071) are independent predictors of LNM. CONCLUSIONS: PLR and LRR could be identified as predictors of LNM in patients with T1/T2 breast cancer.