Exposure to polycyclic aromatic hydrocarbons promotes the progression of low-grade cervical intraepithelial neoplasia: A population-based cohort study in China.

Low-grade cervical intraepithelial neoplasia (CIN1) is an early stage of cervical cancer development. Previously, we reported that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of cervical precancerous lesions, especially in females with a high-risk human papillomavirus (HR-HPV) infection. However, the effects of PAHs on CIN1 progression remain unclear. A community-based prospective cohort study was conducted to evaluate the role of exposure to PAHs in the progression of CIN1. A total of 564 patients diagnosed with CIN1 were followed-up at 6, 12, and 24 months, post-diagnosis, to determine CIN1 reversion, persistence, and progression. Exposure to PAHs was determined by the urine 1-hydroxipayrene (1-OHP) level. Our results showed that the 1-OHP level was significantly higher in patients with CIN1 persistence/progression than in those with reversion (P < .05). High exposure to PAHs increased the risk of CIN1 persistence/progression, with hazard ratios (HR), 95% confidence intervals (CI) of (1.62, 1.24-2.67), (1.98, 1.42-2.75), and (2.37, 1.61-3.49) at 6, 12, and 24 months, post-diagnosis, respectively. The effect was enhanced with HR-HPV positivity, as determined at 6 (1.82, 1.24-2.67), 12 (3.02, 1.74-5.23), and 24 (2.51, 1.48-4.26) months, post-diagnosis. Moreover, the predictive value of exposure to PAHs for CIN1 persistence/progression was higher in HR-HPV-positive patients than in HR-HPV-negative patients. The results revealed that exposure to PAHs facilitated the malignant progression of CIN1 and hindered its reversal, particularly in patients with HR-HPV infection. Our findings provide novel insights into early prevention and intervention targeting the initiation and progression of cervical neoplasia.

Impact of cesarean section on metabolic syndrome components in offspring rats.

INTRODUCTION: Epidemiological evidence suggests an association between CS and offspring metabolic syndrome (MetS), but whether a causal relationship exists is unknown. METHODS: In this study, timed-mated Wistar rat dams were randomly assigned to cesarean section (CS), vaginal delivery (VD), and surrogate groups. The offspring from both CS and VD groups were reared by surrogate dams until weaning, and weaned male offspring from both groups were randomly assigned to receive normal diet (ND) or high-fat/high-fructose diet (HFF) ad libitum for 39 weeks. RESULTS: By the end of study, CS-ND offspring gained 17.8% more weight than VD-ND offspring, while CS-HFF offspring gained 36.4% more weight than VD-HFF offspring. Compared with VD-ND offspring, CS-ND offspring tended to have increased triglycerides (0.27 mmol/l, 95% CI, 0.05 to 0.50), total cholesterol (0.30 mmol/l, -0.08 to 0.68), and fasting plasma glucose (FPG) (0.30 mmol/l, -0.01 to 0.60); more pronounced differences were observed between CS-HFF and VD-HFF offspring in these indicators (triglyceride, 0.66 mmol/l, 0.35 to 0.97; total cholesterol, 0.46 mmol/l, 0.13 to 0.79; and FPG, 0.55 mmol/l, 0.13 to 0.98). CONCLUSIONS: CS offspring were more prone to adverse metabolic profile and HFF might exacerbate this condition, indicating the association between CS and MetS is likely to be causal. IMPACT: Whether the observed associations between CS and MetS in non-randomized human studies are causally relevant remains undetermined. Compared with vaginally born offspring rats, CS born offspring gained more body weight and tended to have compromised lipid profiles and abnormal insulin sensitivity, suggesting a causal relationship between CS and MetS that may be further amplified by a high-fat/high-fructose diet. Due to the high prevalence of CS births globally, greater clinical consideration must be given to the potential adverse effects of CS, and whether these risks should be made known to patients in clinical practice merits evaluation.

The Clinical Significance and Expression Level of miR-411-5p in Colorectal Cancer.

Background: MicroRNAs (miRNAs) have been widely recognized as crucial regulators in the development and progression of various cancers, including colorectal cancer (CRC). Previous studies have highlighted the involvement of several miRNAs in CRC, such as miR-145, miR-29a-3p, and miR-196. However, the specific role and clinical significance of miR-411-5p in CRC have not been thoroughly investigated, representing a significant gap in the current understanding of CRC biology. While miR-411-5p has been implicated in the pathogenesis of other human malignancies, its precise mechanisms and impact on CRC development and prognosis remain largely unexplored. Understanding the functional relevance of miR-411-5p in CRC and elucidating its molecular interactions can provide valuable insights into the underlying mechanisms of CRC progression and potentially identify novel therapeutic targets. Therefore, this study aims to investigate the clinical value and level of miR-411-5p in colorectal cancer, shedding light on its potential as a diagnostic and prognostic biomarker. Additionally, we aim to explore the molecular mechanisms underlying the effects of miR-411-5p on CRC cells, particularly its interaction with the target gene NFE2L3. By filling this knowledge gap, our research contributes to a deeper understanding of the role of miR-411-5p in CRC and opens avenues for developing targeted therapies for this prevalent malignancy. Methods: Colorectal cancer (CRC) tissue samples and corresponding normal paracancerous tissue samples were collected from 60 CRC patients treated at the Affiliated Hospital of Hebei University. Normal paracancerous tissue refers to the healthy tissue adjacent to the cancerous region. These tissue samples were obtained through biopsies, and the patients provided informed consent for their use in the study. To investigate the expression levels of miR-411-5p and NFE2L3, we employed quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. This technique allowed us to measure the levels of miR-411-5p and NFE2L3 mRNA in both CRC and normal tissue samples. Additionally, we validated the protein levels of NFE2L3 using Western blot analysis. Furthermore, we assessed the functional impact of miR-411-5p on CRC cells through various assays. The MTT assay determined cell viability, the transwell migration assay evaluated cell migration and invasion abilities, and flow cytometry measured the rate of apoptosis in CRC cells. To confirm the molecular interaction between miR-411-5p and its target gene NFE2L3, we conducted dual-luciferase reporter assays. These assays enabled us to validate the binding between miR-411-5p and the 3' untranslated region (3'UTR) of the NFE2L3 mRNA. To investigate the potential therapeutic role of NFE2L3 in CRC, we transfected CRC cells with pcDNA3.0-NFE2L3, a plasmid overexpressing NFE2L3. This allowed us to assess the impact of NFE2L3 restoration on the behavior of CRC cells. Results: Overexpression of miR-411-5p in CRC cells significantly reduced cell viability, inhibited migration and invasion, and increased the rate of apoptosis. Conversely, inhibition of miR-411-5p expression exerted the opposite effects on the biological behavior of CRC cells. Furthermore, our study revealed that NFE2L3 is a downstream target of miR-411-5p. Dual-luciferase reporter assays confirmed the binding between miR-411-5p and the 3'UTR of NFE2L3 mRNA, indicating a direct interaction between them. To investigate the therapeutic potential of targeting NFE2L3 in CRC, we transfected CRC cells with pcDNA3.0-NFE2L3, resulting in the restoration of NFE2L3 levels. This restoration effectively reversed the effects induced by miR-411-5p mimics on the behavior of CRC cells. Conclusion: Our study provides compelling evidence for the tumor-suppressive role of miR-411-5p in CRC. The overexpression of miR-411-5p resulted in reduced cell viability, inhibited migration and invasion, and increased apoptosis in CRC cells. Importantly, we identified NFE2L3 as a downstream target of miR-411-5p and demonstrated its involvement in mediating the effects of miR-411-5p on CRC cell behavior. These findings not only confirm the tumor-suppressive role of miR-411-5p in CRC but also highlight NFE2L3 as a promising target for novel therapeutic strategies. Targeting NFE2L3 to modulate the biological function of CRC cells may hold therapeutic potential and serve as a basis for the development of targeted drugs. Further investigations are warranted to fully elucidate the underlying molecular mechanisms of miR-411-5p-NFE2L3 interaction and its impact on CRC progression. Additionally, future studies could explore the clinical implications of miR-411-5p as a diagnostic or prognostic biomarker in CRC patients. By advancing our understanding of the intricate regulatory networks involved in CRC, we can pave the way for personalized therapeutic approaches and improve patient outcomes.

A Doped Lanthanide-Based Coordination Polymer Exhibiting High Relative Sensitivity to Ratiometric Luminescent Thermometers at 440 K.

Ratiometric luminescent thermometers with excellent performance often require the luminescent materials to possess high thermal stability and relative sensitivity (Sr). However, such luminescent materials are very rare, especially in physiological (298-323 K) and high-temperature (>373 K) regions. Here we report the synthesis and luminescent property of [Tb0.995Eu0.005(pfbz)2(phen)Cl] (3), which not only exhibits high Sr in physiological temperature but also has a Sr up to 7.47% K-1 at 440 K, the largest Sr at 440 K in known lanthanide-based coordination compound luminescent materials.

Activation of cDCs and iNKT cells contributes to triptolide-induced hepatotoxicity via STING signaling pathway and endoplasmic reticulum stress.

Triptolide (TP) exhibits therapeutic potential against multiple diseases. However, its application in clinics is limited by TP-induced hepatoxicity. TP can activate invariant natural killer T (iNKT) cells in the liver, shifting Th1 cytokine bias to Th2 cytokine bias. The damaging role of iNKT cells in TP-induced hepatoxicity has been established, and iNKT cell deficiency can mitigate hepatotoxicity. However, the activation of iNKT cells in vitro by TP requires the presence of antigen-presenting cells. Therefore, we hypothesized that TP could induce dendritic cells (DCs) to activate iNKT cells, thereby leading to hepatotoxicity. The hepatic conventional DCs (cDCs) exhibited immunogenic activities after TP administration, upregulating the expression of CD1d, co-stimulatory molecules, and IL-12. Neutralization with IL-12p40 antibody extenuated TP-induced hepatotoxicity and reduced iNKT cell activation, suggesting that IL-12 could cause liver injury by activating iNKT cells. TP triggered the activation and upregulation of STING signaling pathway and increased endoplasmic reticulum (ER) stress. Downregulation of STING reduced cDC immunogenicity, inhibiting the activation of iNKT cells and hepatic damage. These indicated the regulatory effects of STING pathway on cDCs and iNKT cells, and the important roles it plays in hepatoxicity. ER stress inhibitor, 4-phenylbutyrate (4-PBA), also suppressed iNKT cell activation and liver injury, which might be regulated by the STING signaling pathway. Our results demonstrated the possible mechanisms underlying TP-induced hepatoxicity, where the activation of cDCs and iNKT cells was stimulated by upregulated STING signaling and increased ER stress as a result of TP administration.

Cross-View Gait Recognition Method Based on Multi-Teacher Joint Knowledge Distillation.

Aiming at challenges such as the high complexity of the network model, the large number of parameters, and the slow speed of training and testing in cross-view gait recognition, this paper proposes a solution: Multi-teacher Joint Knowledge Distillation (MJKD). The algorithm employs multiple complex teacher models to train gait images from a single view, extracting inter-class relationships that are then weighted and integrated into the set of inter-class relationships. These relationships guide the training of a lightweight student model, improving its gait feature extraction capability and recognition accuracy. To validate the effectiveness of the proposed Multi-teacher Joint Knowledge Distillation (MJKD), the paper performs experiments on the CASIA_B dataset using the ResNet network as the benchmark. The experimental results show that the student model trained by Multi-teacher Joint Knowledge Distillation (MJKD) achieves 98.24% recognition accuracy while significantly reducing the number of parameters and computational cost.

Identification of Genes Associated with Prognosis and Immunotherapy Prediction in Triple-Negative Breast Cancer via M1/M2 Macrophage Ratio.

Background and Objectives: Triple-negative breast cancer (TNBC), a highly aggressive and heterogeneous subtype of breast cancer, accounts for ap-proximately 10-15% of all breast cancer cases. Currently, there is no effective therapeutic target for TNBC. Tu-mor-associated macrophages (TAMs), which can be phenotypically classified into M1 and M2 subtypes, have been shown to influence the prognosis of various cancers, including ovarian cancer. This study aimed to investigate the role of M1/M2 macrophages in the TNBC tumor microenvironment (TME), with a focus on identifying prognostic genes and predicting immunotherapy response. Materials and Methods: The study employed the CIBERSORT algorithm to analyze immune cell expression in the TME. Genes associated with the M1/M2 macrophage ratio were identified using Pearson correlation analysis and used to classify patients into dis-tinct clusters. Dimensionality reduction techniques, including univariate Cox regression and Lasso, were applied to these genes. The expression of prognostic genes was validated through immunohistochemistry. Results: The study found a high prevalence of TAMs in the TME. Among the patient clusters, 109 differentially expressed genes (DEGs) were identified. Three significant DEGs (LAMP3, GZMB, and CXCL13) were used to construct the riskScores. The riskScore model effectively stratified patients based on mortality risk. Gene Set Enrichment Analysis (GSEA) associated the riskScore with several significant pathways, including mismatch repair, JAK/STAT3 signaling, VEGF signaling, antigen processing presentation, ERBB signaling, and P53 signaling. The study also predicted patient sensitivity to im-munotherapy using the riskScores. The expression of the three significant DEGs was validated through immunohisto-chemistry. Conclusions: The study concluded that the riskScore model, based on the M1/M2 macrophage ratio, is a valid prognostic tool for TNBC. The findings underscore the importance of the TME in TNBC progression and prognosis and highlight the po-tential of the riskScore model in predicting immunotherapy response in TNBC patients.

Locating Hydrogen Positions for COF-300 by Cryo-3D Electron Diffraction.

Covalent organic frameworks (COFs) have wide-ranging applications, and their host-guest interactions play an essential role in the achievement of COF functions. To investigate these host-guest interactions, it is necessary to locate all atoms, especially hydrogen atoms. However, it is difficult to determine the hydrogen atomic positions in COFs because of the complexities in synthesizing high-quality large single crystals. Three-dimensional electron diffraction (3D ED) has unique advantages for the structural determination of nanocrystals and identification of light atoms. In this study, it was demonstrated for the first time that the hydrogen atoms of a COF, not only on the framework but also on the guest molecule, can be located by 3D ED using continuous precession electron diffraction tomography (cPEDT) under cryogenic conditions. The host-guest interactions were clarified with the location of the hydrogen atoms. These findings provide novel insights into the investigation of COFs.

Histone acetylation recruits the SWR1 complex to regulate active DNA demethylation in Arabidopsis.

Active DNA demethylation is critical for controlling the DNA methylomes in plants and mammals. However, little is known about how DNA demethylases are recruited to target loci, and the involvement of chromatin marks in this process. Here, we identify 2 components of the SWR1 chromatin-remodeling complex, PIE1 and ARP6, as required for ROS1-mediated DNA demethylation, and discover 2 SWR1-associated bromodomain-containing proteins, AtMBD9 and nuclear protein X1 (NPX1). AtMBD9 and NPX1 recognize histone acetylation marks established by increased DNA methylation 1 (IDM1), a known regulator of DNA demethylation, redundantly facilitating H2A.Z deposition at IDM1 target loci. We show that at some genomic regions, H2A.Z and DNA methylation marks coexist, and H2A.Z physically interacts with ROS1 to regulate DNA demethylation and antisilencing. Our results unveil a mechanism through which DNA demethylases can be recruited to specific target loci exhibiting particular histone marks, providing a conceptual framework to understand how chromatin marks regulate DNA demethylation.

Synergistic protective effects of folic acid and resveratrol against fine particulate matter-induced heart malformations in zebrafish embryos.

Ambient fine particulate matter (PM2.5) is a major environmental health problem worldwide, and recent studies indicate that maternal PM2.5 exposure is closely associated with congenital heart diseases (CHDs) in offspring. We previously found that supplementation with folic acid (FA) or Resveratrol (RSV) could protect against heart defects in zebrafish embryos exposed to extractable organic matter (EOM) from PM2.5 by targeting aryl hydrocarbon receptor (AHR) signaling and reactive oxygen species (ROS) production respectively. Thus, we hypothesized that FA combined with RSV may have a synergistic protective effect against PM2.5-induced heart defects. To test our hypothesis, we treated zebrafish embryos with EOM in the presence or absence of FA, RSV or a combination of both. We found that RSV and FA showed a clear synergistic protection against EOM-induced heart defects in zebrafish embryos. Further studies showed that FA and RSV suppressed EOM-induced AHR activity and ROS generation respectively. Although only RSV inhibited EOM-induced apoptosis, FA enhanced the inhibitory effect of RSV. Moreover, vitamin C (VC), a typical antioxidant, also exhibits a synergistic inhibitory effect with FA on EOM-induced apoptosis and heart defects. In conclusion, supplementation with FA and RSV have a synergistic protective effect against PM2.5-induced heart defects in zebrafish embryos by targeting AHR activity and ROS production respectively. Our results indicate that, in the presence of antioxidants, FA even at a low concentration level could protect against the high risk of CHDs caused by air pollution.

Pyrogallate-Based Metal-Organic Framework with a Two-Dimensional Secondary Building Unit.

We report a metal-organic framework (MOF) with a rare two-dimensional (2D) secondary building unit (SBU). The SBU comprises mixed-valent Fe2+ and Fe3+ metal ions bridged by oxygen atoms pertaining to the polytopic ligand 3,3',4,4',5,5'-hexahydroxybiphenyl, which also define the iron-oxide 2D layers. Overall, the anionic framework exhibits rare topology and evidences strong electronic communication between the mixed-valence iron sites. These results highlight the importance of dimensionality control of MOF SBUs for discovering new topologies in reticular chemistry, and especially for improving electronic communication within the MOF skeleton.

DeepAntigen: a novel method for neoantigen prioritization via 3D genome and deep sparse learning.

MOTIVATION: The mutations of cancers can encode the seeds of their own destruction, in the form of T-cell recognizable immunogenic peptides, also known as neoantigens. It is computationally challenging, however, to accurately prioritize the potential neoantigen candidates according to their ability of activating the T-cell immunoresponse, especially when the somatic mutations are abundant. Although a few neoantigen prioritization methods have been proposed to address this issue, advanced machine learning model that is specifically designed to tackle this problem is still lacking. Moreover, none of the existing methods considers the original DNA loci of the neoantigens in the perspective of 3D genome which may provide key information for inferring neoantigens' immunogenicity. RESULTS: In this study, we discovered that DNA loci of the immunopositive and immunonegative MHC-I neoantigens have distinct spatial distribution patterns across the genome. We therefore used the 3D genome information along with an ensemble pMHC-I coding strategy, and developed a group feature selection-based deep sparse neural network model (DNN-GFS) that is optimized for neoantigen prioritization. DNN-GFS demonstrated increased neoantigen prioritization power comparing to existing sequence-based approaches. We also developed a webserver named deepAntigen (http://yishi.sjtu.edu.cn/deepAntigen) that implements the DNN-GFS as well as other machine learning methods. We believe that this work provides a new perspective toward more accurate neoantigen prediction which eventually contribute to personalized cancer immunotherapy. AVAILABILITY AND IMPLEMENTATION: Data and implementation are available on webserver: http://yishi.sjtu.edu.cn/deepAntigen. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Integration of histopathological images and multi-dimensional omics analyses predicts molecular features and prognosis in high-grade serous ovarian cancer.

OBJECTIVE: This study used histopathological image features to predict molecular features, and combined with multi-dimensional omics data to predict overall survival (OS) in high-grade serous ovarian cancer (HGSOC). METHODS: Patients from The Cancer Genome Atlas (TCGA) were distributed into training set (n = 115) and test set (n = 114). In addition, we collected tissue microarrays of 92 patients as an external validation set. Quantitative features were extracted from histopathological images using CellProfiler, and utilized to establish prediction models by machine learning methods in training set. The prediction performance was assessed in test set and validation set. RESULTS: The prediction models were able to identify BRCA1 mutation (AUC = 0.952), BRCA2 mutation (AUC = 0.912), microsatellite instability-high (AUC = 0.919), microsatellite stable (AUC = 0.924), and molecular subtypes: proliferative (AUC = 0.961), differentiated (AUC = 0.952), immunoreactive (AUC = 0.941), mesenchymal (AUC = 0.918) in test set. The prognostic model based on histopathological image features could predict OS in test set (5-year AUC = 0.825) and validation set (5-year AUC = 0.703). We next explored the integrative prognostic models of image features, genomics, transcriptomics and proteomics. In test set, the models combining two omics had higher prediction accuracy, such as image features and genomics (5-year AUC = 0.834). The multi-omics model including all features showed the best prediction performance (5-year AUC = 0.911). According to risk score of multi-omics model, the high-risk and low-risk groups had significant survival differences (HR = 18.23, p < 0.001). CONCLUSIONS: These results indicated the potential ability of histopathological image features to predict above molecular features and survival risk of HGSOC patients. The integration of image features and multi-omics data may improve prognosis prediction in HGSOC patients.

Trimodal Ratiometric Luminescent Thermometer Covering Three Near-Infrared Transparency Windows.

Near-infrared (NIR) transparency windows have evoked considerable interest in biomedical thermal imaging owing to the superior tissue penetration and the high signal-to-noise ratio, allowing in vivo real-time temperature reading with nanometric spatial resolution. Here, we develop a multimode nonintrusive luminescent thermometer based on the Y3Al5O12 (YAG):Cr3+/Ln3+ (Ln = Ho, Er, Yb) phosphor, which covers three NIR biological transparency windows, enabling cross-checking readings with high sensitivity and a high penetration depth. Utilizing the energy transfer between lanthanide ions and transition-metal ions, the Cr3+/Ln3+-activated upconversion emissions provide ideal signals for ratiometric luminescent thermometry of the NIR-I mode. The phonon-assisted downshifting emissions of Er3+/Ho3+ are used to construct the NIR-III/II mode, and the NIR-III mode is based on the thermal coupling between stark levels of 4I13/2 (Er3+). Three independent modes show distinct thermometric performance in different NIR transparency windows and temperature ranges, and the combination of the three modes is conducive to obtain more accurate temperature readings in a broad temperature range, which paves the way toward versatile luminescent thermometers.

Fetal Right Aortic Arch: A Quantitative Method of Outcome Prediction.

OBJECTIVE: To investigate right aortic arches (RAA) quantitatively and risk-stratify fetuses with RAA prenatally. METHOD: A total of 143 singleton fetuses were enrolled. Four measurements were studied, including the angle and distance between the aortic arch (AO) and ductal arch (DA), the diameters of the AO and DA, and the distance growth rate (DGR). RESULT: A significant increase in mean distance was observed in the study group (4.89 ± 1.07 mm) compared to the control group (1.62 ± 0.33 mm, p<.01). The distance increased from the second (1.52 ± 0.35 mm, p<.01, 4.06 ± 0.78 mm, p<.01) to third trimester (1.71 ± 0.29 mm, p<.01, 5.13 ± 1.10 mm, p<.01) in the normal and study groups. Fetuses with abnormalities in addition to RAAs had significantly lower growth rates (12.4 ± 5.2%) than those with an isolated RAA (33.7 ± 12.0%). CONCLUSION: Parameters, especially DGR, may be clinically significant. DGR may be restricted when an RAA exists with other malformations. Decreasing DGR in fetuses with RAAs suggests the presence of other malformations.

The Effect of End Group and Molecular Weight on the Yellowness of Polyetherimide.

The effects of end group and molecular weight on the yellowness of telechelic polyetherimide (PEI) are investigated. Electron-withdrawing dianhydride end groups reduce the yellowness and increase the transparency of PEI regardless of the molecular weight. Electron-donating phenyl, amine, and phthalic end groups increase the yellowness of PEI but the effect depends on the molecular weight. As the molecular weight is increased, the yellowness of PEIs with electron-donating end groups initially decreases due to a decreasing end-group density and then increases due to an increasing probability of charge-transfer complex formation. The systematic study reveals the correlations among yellowness, end group, and molecular weight of PEIs. The correlations can be used for designing highly transparent PEIs and other high-performance polymers.

Switched voltammetric determination of ractopamine by using a temperature-responsive sensing film.

This study describes an electrochemical sensor for the animal growth promoter ractopamine. The method is based on the use of a glassy carbon electrode (GCE) modified with a temperature-responsive sensing film composed of reduced graphene oxide, C60 fullerene, and the temperature-sensitive polymer poly(2-(2-methoxyethoxy)ethyl methacrylate) (PMEO2MA). The modified GCE was characterized by scanning electron microscopy and electrochemical impedance spectroscopy. A large oxidation peak current can be observed (maximum typically at 0.57 V vs. Ag/AgCl) when the temperature is raised to above the lower critical solution temperature of PMEO2MA. This peak disappears at lower temperature. Under optimum conditions, the sensor has a detection range for ractopamine from 0.1 to 3.1 µM, with an 82 nM detection limit. The method was successfully applied to the determination of ractopamine in spiked pork samples. Graphical abstract Schematic presentation of the reversible, temperature-controlled "on/off" electrochemical behavior of ractopamine at a glassy carbon electrode modified with a film composed of reduced graphene oxide (rGO), C60 fullerene and the poly(2-(2-methoxyethoxy)ethyl methacrylate) (PMEO2MA).

Manufacturing process used to produce long-acting recombinant factor VIII Fc fusion protein.

Recombinant factor VIII Fc fusion protein (rFVIIIFc) is a long-acting coagulation factor approved for the treatment of hemophilia A. Here, the rFVIIIFc manufacturing process and results of studies evaluating product quality and the capacity of the process to remove potential impurities and viruses are described. This manufacturing process utilized readily transferable and scalable unit operations and employed multi-step purification and viral clearance processing, including a novel affinity chromatography adsorbent and a 15 nm pore size virus removal nanofilter. A cell line derived from human embryonic kidney (HEK) 293H cells was used to produce rFVIIIFc. Validation studies evaluated identity, purity, activity, and safety. Process-related impurity clearance and viral clearance spiking studies demonstrate robust and reproducible removal of impurities and viruses, with total viral clearance >8-15 log10 for four model viruses (xenotropic murine leukemia virus, mice minute virus, reovirus type 3, and suid herpes virus 1). Terminal galactose-α-1,3-galactose and N-glycolylneuraminic acid, two non-human glycans, were undetectable in rFVIIIFc. Biochemical and in vitro biological analyses confirmed the purity, activity, and consistency of rFVIIIFc. In conclusion, this manufacturing process produces a highly pure product free of viruses, impurities, and non-human glycan structures, with scale capabilities to ensure a consistent and adequate supply of rFVIIIFc.

Postoperative delayed massive bleeding in gastric cancer: a case report.

BACKGROUND: Postoperative delayed bleeding of gastric cancer is a complication of radical gastrectomy with low incidence rate and high mortality. CASE PRESENTATION: This case report presents the case of a 63-year-old female patient of Mongolian ethnicity who was diagnosed with gastric malignancy during a routine medical examination and underwent Billroth's I gastric resection in our department. However, on the 24th day after the surgery, she was readmitted due to sudden onset of hematemesis. Gastroscopy, abdominal CT, and digital subtraction angiography revealed postoperative anastomotic fistula, rupture of the duodenal artery, and bleeding from the abdominal aorta. The patient underwent three surgical interventions and two arterial embolizations. The patient's condition stabilized, and she was discharged successfully. CONCLUSION: Currently, there are no specific guidelines for the diagnosis and treatment of pseudoaneurysms in the abdominal cavity resulting from gastric cancer surgery. Early digital subtraction angiography examination should be performed to assist in formulating treatment plans. Early diagnosis and treatment contribute to an improved overall success rate of rescue interventions.

The Effects of Breastfeeding on Childhood Behavioral and Emotional Development: A Prospective Cohort Study in China.

BACKGROUND: Breastfeeding could improve a child's health early on, but its long-term effects on childhood behavioral and emotional development remain inconclusive. We aimed to estimate the associations of feeding practice with childhood behavioral and emotional development. METHODS: In this population-based birth cohort study, data on feeding patterns for the first 6 mo of life, the duration of breastfeeding, and children's emotional and behavioral outcomes were prospectively collected from 2489 mother-child dyads. Feeding patterns for the first 6 mo included exclusive breastfeeding (EBF) and non-exclusive breastfeeding (non-EBF, including mixed feeding or formula feeding), and the duration of breastfeeding (EBF or mixed feeding) was categorized into ≤6 mo, 7-12 mo, 13-18 mo, and >18 mo. Externalizing problems and internalizing problems were assessed with the Child Behavior Checklist (CBCL) and operationalized according to recommended clinical cutoffs, corresponding to T scores ≥64. Multivariable linear regression and logistic regression were used to evaluate the association of feeding practice with CBCL outcomes. RESULTS: The median (interquartile range) age of children at the outcome measurement was 32.0 (17.0) mo. Compared with non-EBF for the first 6 mo, EBF was associated with a lower T score of internalizing problems [adjusted mean difference (aMD): -1.31; 95% confidence interval (95% CI): -2.53, -0.10], and it was marginally associated with T scores of externalizing problems (aMD: -0.88; 95% CI: -1.92, 0.15). When dichotomized, EBF versus non-EBF was associated with a lower risk of externalizing problems (aOR: 0.54, 95% CI: 0.34, 0.87), and it was marginally associated with internalizing problems (aOR: 0.75, 95% CI: 0.54, 1.06). Regarding the duration of breastfeeding, breastfeeding for 13-18 mo versus ≤6 mo was associated with lower T scores of internalizing problems (aMD: -2.50; 95% CI: -4.43, -0.56) and externalizing problems (aMD: -2.75; 95% CI: -4.40, -1.10), and breastfeeding for >18 mo versus ≤6 mo was associated with lower T scores of externalizing problems (aMD: -1.88; 95% CI: -3.68, -0.08). When dichotomized, breastfeeding for periods of 7-12 mo, 13-18 mo, and >18 mo was associated with lower risks of externalizing problems [aOR (95% CI): 0.96 (0.92, 0.99), 0.94 (0.91, 0.98), 0.96 (0.92, 0.99), respectively]. CONCLUSIONS: Exclusive breastfeeding for the first 6 mo and a longer duration of breastfeeding, exclusively or partially, are beneficial for childhood behavioral and emotional development.