Nrf2 Signaling Pathway: Focus on Oxidative Stress in Spinal Cord Injury.

Spinal cord injury (SCI) is a serious, disabling injury to the central nervous system that can lead to motor, sensory, and autonomic dysfunction below the injury plane. SCI can be divided into primary injury and secondary injury according to its pathophysiological process. Primary injury is irreversible in most cases, while secondary injury is a dynamic regulatory process. Secondary injury involves a series of pathological events, such as ischemia, oxidative stress, inflammatory events, apoptotic pathways, and motor dysfunction. Among them, oxidative stress is an important pathological event of secondary injury. Oxidative stress causes a series of destructive events such as lipid peroxidation, DNA damage, inflammation, and cell death, which further worsens the microenvironment of the injured site and leads to neurological dysfunction. The nuclear factor erythrocyte 2-associated factor 2 (Nrf2) is considered to be a key pathway of antioxidative stress and is closely related to the pathological process of SCI. Activation of this pathway can effectively inhibit the oxidative stress process and promote the recovery of nerve function after SCI. Therefore, the Nrf2 pathway may be a potential therapeutic target for SCI. This review deeply analyzed the generation of oxidative stress in SCI, the role and mechanism of Nrf2 as the main regulator of antioxidant stress in SCI, and the influence of cross-talk between Nrf2 and related pathways that may be involved in the pathological regulation of SCI on oxidative stress, and summarized the drugs and other treatment methods based on Nrf2 pathway regulation. The objective of this paper is to provide evidence for the role of Nrf2 activation in SCI and to highlight the important role of Nrf2 in alleviating SCI by elucidating the mechanism, so as to provide a theoretical basis for targeting Nrf2 pathway as a therapy for SCI.

Auto-delineation of treatment target volume for radiation therapy using large language model-aided multimodal learning.

PURPOSE: Artificial intelligence (AI)-aided methods have made significant progress in the auto-delineation of normal tissues. However, these approaches struggle with the auto-contouring of radiotherapy target volume. Our goal is to model the delineation of target volume as a clinical decision-making problem, resolved by leveraging large language model-aided multimodal learning approaches. METHODS AND MATERIALS: A vision-language model, termed Medformer, has been developed, employing the hierarchical vision transformer as its backbone, and incorporating large language models to extract text-rich features. The contextually embedded linguistic features are seamlessly integrated into visual features for language-aware visual encoding through the visual language attention module. Metrics, including Dice similarity coefficient (DSC), intersection over union (IOU), and 95th percentile Hausdorff distance (HD95), were used to quantitatively evaluate the performance of our model. The evaluation was conducted on an in-house prostate cancer dataset and a public oropharyngeal carcinoma (OPC) dataset, totaling 668 subjects. RESULTS: Our Medformer achieved a DSC of 0.81 ± 0.10 versus 0.72 ± 0.10, IOU of 0.73 ± 0.12 versus 0.65 ± 0.09, and HD95 of 9.86 ± 9.77 mm versus 19.13 ± 12.96 mm for delineation of gross tumor volume (GTV) on the prostate cancer dataset. Similarly, on the OPC dataset, it achieved a DSC of 0.77 ± 0.11 versus 0.72 ± 0.09, IOU of 0.70 ± 0.09 versus 0.65 ± 0.07, and HD95 of 7.52 ± 4.8 mm versus 13.63 ± 7.13 mm, representing significant improvements (p < 0.05). For delineating the clinical target volume (CTV), Medformer achieved a DSC of 0.91 ± 0.04, IOU of 0.85 ± 0.05, and HD95 of 2.98 ± 1.60 mm, comparable to other state-of-the-art algorithms. CONCLUSIONS: Auto-delineation of the treatment target based on multimodal learning outperforms conventional approaches that rely purely on visual features. Our method could be adopted into routine practice to rapidly contour CTV/GTV.

Synthesis and Biological Evaluation of Novel Chlorogenic Acid-Apigenin Conjugates as Anti-acute Gout Agents.

Gout is the second largest metabolic disease worldwide after diabetes, with acute gouty arthritis as most common symptom. Xanthine oxidase (XOD) and the NOD like receptor-3 (NLRP3) inflammasome are the key targets for acute gout treatment. Chlorogenic acid has been reported with a good anti-inflammatory activity, and Apigenin showed an excellent potential in XOD inhibition. Therefore, a series of chlorogenic acid-apigenin (CA) conjugates with varying linkers were designed and synthesized as dual XOD/NLRP3 inhibitors, and their activities both in XOD and NLRP3 inhibition were evaluated. An in vitro study of XOD inhibitory activity revealed that the majority of CA conjugates exhibited favorable XOD inhibitory activity. Particularly, the effects of compounds 10c and 10d, with an alkyl linker on the apigenin moiety, were stronger than that of allopurinol. The selected CA conjugates also demonstrated a favorable anti-inflammatory activity in RAW264.7 cells. Furthermore, compound 10d, which showed the optimal activity both in XOD inhibition and anti-inflammatory, was chosen and its inhibitory ability on NLRP3 and related proinflammatory cytokines was further tested. Compound 10d effectively reduced NLRP3 expression and the secretion of interluekin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) with an activity stronger than the positive control isoliquiritigenin (ISL). Based on these findings, compound 10d exhibits dual XOD/NLRP3 inhibitory activity and, therefore, the therapeutic effects on acute gout is worthy of further study.

Evaluation of Phenazine Derivatives from the Lichen-Associated Streptomyces flavidovirens as Potent Antineuroinflammatory Agents In Vitro and In Vivo.

Eighteen nitrogen-containing compounds (1-18) were isolated from cultures of the lichen-associated Streptomyces flavidovirens collected from the Qinghai-Tibet Plateau, including seven phenazine derivatives with three new ones, named subphenazines A-C (2-4), two new furan pyrrolidones (8-9), and nine known alkaloids. The structures were elucidated by spectroscopic data analysis, and absolute configurations were determined by single-crystal X-ray diffraction and ECD calculations. The phenazine-type derivatives, in particular compound 3, exhibited significantly better antineuroinflammatory activity than other isolated compounds (8-18). Compound 3 inhibited the release of proinflammatory cytokines including IL-6, TNF-α, and PGE2, and the nuclear translocation of NF-κB; it also reduced the oxidative stress and activated the Nrf2 signaling pathway in LPS-induced BV2 microglia cells. In vivo anti-inflammatory activity in zebrafish indicated that 3 inhibited LPS-stimulated ROS generation. These findings suggested that compound 3 might be a potent antineuroinflammatory agent through the regulation of the NF-κB/Nrf2 signaling pathways.

Identification and experimental validation of KMO as a critical immune-associated mitochondrial gene in unstable atherosclerotic plaque.

BACKGROUND: The heightened risk of cardiovascular and cerebrovascular events is associated with the increased instability of atherosclerotic plaques. However, the lack of effective diagnostic biomarkers has impeded the assessment of plaque instability currently. This study was aimed to investigate and identify hub genes associated with unstable plaques through the integration of various bioinformatics tools, providing novel insights into the detection and treatment of this condition. METHODS: Weighted Gene Co-expression Network Analysis (WGCNA) combined with two machine learning methods were used to identify hub genes strongly associated with plaque instability. The cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) method was utilized to assess immune cell infiltration patterns in atherosclerosis patients. Additionally, Gene Set Variation Analysis (GSVA) was conducted to investigate the potential biological functions, pathways, and mechanisms of hub genes associated with unstable plaques. To further validate the diagnostic efficiency and expression of the hub genes, immunohistochemistry (IHC), quantitative real-time polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA) were performed on collected human carotid plaque and blood samples. Immunofluorescence co-staining was also utilized to confirm the association between hub genes and immune cells, as well as their colocalization with mitochondria. RESULTS: The CIBERSORT analysis demonstrated a significant decrease in the infiltration of CD8 T cells and an obvious increase in the infiltration of M0 macrophages in patients with atherosclerosis. Subsequently, two highly relevant modules (blue and green) strongly associated with atherosclerotic plaque instability were identified. Through intersection with mitochondria-related genes, 50 crucial genes were identified. Further analysis employing least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) algorithms revealed six hub genes significantly associated with plaque instability. Among them, NT5DC3, ACADL, SLC25A4, ALDH1B1, and MAOB exhibited positive correlations with CD8 T cells and negative correlations with M0 macrophages, while kynurenine 3-monooxygenas (KMO) demonstrated a positive correlation with M0 macrophages and a negative correlation with CD8 T cells. IHC and RT-qPCR analyses of human carotid plaque samples, as well as ELISA analyses of blood samples, revealed significant upregulation of KMO and MAOB expression, along with decreased ALDH1B1 expression, in both stable and unstable samples compared to the control samples. However, among the three key genes mentioned above, only KMO showed a significant increase in expression in unstable plaque samples compared to stable plaque samples. Furthermore, the expression patterns of KMO in human carotid unstable plaque tissues and cultured mouse macrophage cell lines were assessed using immunofluorescence co-staining techniques. Finally, lentivirus-mediated KMO silencing was successfully transduced into the aortas of high-fat-fed ApoE-/- mice, with results indicating that KMO silencing attenuated plaque formation and promoted plaque stability in ApoE-/- mice. CONCLUSIONS: The results suggest that KMO, a mitochondria-targeted gene associated with macrophage cells, holds promise as a valuable diagnostic biomarker for assessing the instability of atherosclerotic plaques.

MpANT regulates meristem development in Marchantia polymorpha.

Meristems are crucial for organ formation, but our knowledge of their molecular evolution is limited. Here, we show that AINTEGUMENTA (MpANT) in the euANT branch of the APETALA2-like transcription factor family is essential for meristem development in the nonvascular plant Marchantia polymorpha. MpANT is expressed in the thallus meristem. Mpant mutants show defects to maintain meristem identity and undergo meristem duplication, while MpANT overexpressers show ectopic thallus growth. MpANT directly upregulates MpGRAS9 in the SHORT-ROOT (SHR) branch of the GRAS family. In the vascular plant Arabidopsis thaliana, the euANT-branch genes PLETHORAs (AtPLTs) and AtANT are involved in the formation and maintenance of root/shoot apical meristems and lateral organ primordia, and AtPLTs directly target SHR-branch genes. In addition, euANTs bind through a similar DNA-binding motif to many conserved homologous genes in M. polymorpha and A. thaliana. Overall, the euANT pathway has an evolutionarily conserved role in meristem development.

Clinical efficacy of high-voltage pulsed radiofrequency combined with stellate ganglion block in the acute phase of thoracic and dorsal herpes zoster neuralgia under dual guidance of ultrasound and C-arm.

OBJECTIVES: A single therapeutic approach is not always successful in the treatment of herpes zoster neuralgia, and the appropriate combination of different treatments deserves further exploration. In this study, we investigated the clinical efficacy of high-voltage long-duration pulsed radiofrequency (PRF) combined with stellate ganglion block (SGB) in the acute phase of thoracic and dorsal herpes zoster neuralgia under dual guidance of ultrasound and C-arm. METHODS: 79 cases of acute zoster neuralgia were grouped premised upon differing therapeutic approaches: standard voltage PRF (group S, the temperature, duration, pulse width, frequency and voltage were set to 42 °C, 300 s, 20 ms, 2 Hz, and 45 V), high-voltage long-duration PRF (group H, parameters of PRF were set to 42 °C, 900 s, 20 ms, 2 Hz, and 90 V, respectively), and high-voltage long-duration PRF combined with SGB (group C, parameter settings for PRF are the same as those for group H). The therapeutic outcomes were assessed utilizing the numeric rating scale (NRS), Pittsburgh sleep quality index (PSQI), and Hamilton anxiety rating scale (HAMA). The incidence of clinically significant postherpetic neuralgia post-treatment had been documented. RESULTS: Compared to baseline, scores of NRS, PSQI, and HAMA at each time point post-treatment decreased across all groups, and the decrease was more significant in the C group than in the S group. At the later stage of treatment, the consumption of pregabalin and tramadol and the plasma levels of interleukin-6 and galectin-3 in the C group were significantly lower than those in the S group. The incidence of PHN in the C group was significantly lower than in the S group. CONCLUSIONS: The combination of high-voltage long-duration PRF combined with SGB under dual guidance of ultrasound and C-arm represents a safe, effective, environmentally friendly, and cost-efficient method for treating AZN, significantly improving sleep quality, alleviating anxiety, and reducing the risk of PHN occurrence.

Del Nido cardioplegia versus cold blood cardioplegia in adult cardiac surgery: a meta-analysis of randomized clinical trials.

OBJECTIVE: Systematic evaluation of the safety of del Nido cardioplegia compared to cold blood cardioplegia in adult cardiac surgery. METHODS: We systematically searched PubMed, EMbase, The Cochrane Library and ClinicalTrials.gov for randomized clinical trials (published by 14 January 2024) comparing del Nido cardioplegia to cold blood cardioplegia in adult. Our main endpoints were myocardial injury markers and clinical outcomes. We assessed pooled data by use of a random-effects model or a fixed-effects model. RESULTS: A total of 10 studies were identified, incorporating 889 patients who received del Nido cardioplegia and 907 patients who received cold blood cardioplegia. The meta-analysis results showed that compared with the cold blood cardioplegia, the del Nido cardioplegia had less volume of cardioplegia, higher rate of spontaneous rhythm recovery after cross clamp release, lower levels of postoperative cardiac troponin T and creatinine kinase-myocardial band, all of which were statistically significant. However, there was no statistically significant difference in postoperative troponin I and postoperative left ventricular ejection fraction. The clinical outcomes including mechanical ventilation time, intensive care unit stay time, hospital stay time, postoperative stroke, postoperative new-onset atrial fibrillation, postoperative heart failure requiring intra-aortic balloon pump mechanical circulation support, and in-hospital mortality of both are comparable. CONCLUSION: Existing evidence suggests that del Nido cardioplegia reduced volume of cardioplegia administration and attempts of defibrillation. The superior postoperative results in CTnT and CK-MB may provide a direction for further research on improvement of the composition of cardioplegia.

Inhibiting the self-discharging process of quantum batteries in non-Markovian noises.

One of the main challenges in developing high-performance quantum batteries is the self-discharging process, where energy is dissipated from a quantum battery into the environment. In this work, we investigate the influence of non-Markovian noises on the performance of a quantum battery. Our results demonstrate that adding auxiliary qubits to a quantum battery system can effectively suppress the self-discharging process, leading to an improvement in both the steady-state energy and extractable work. We reveal that the physical mechanism inhibiting the self-discharging process is the formation of system-environment bound states, rather than an increase in non-Markovianity. Our results could be of both theoretical and experimental interest in exploring the ability of quantum batteries to maintain long stored energy in the environment.

Single-Frame Supervision for Spatio-Temporal Video Grounding.

Spatio-Temporal Video Grounding (STVG) aims at localizing the spatio-temporal tube of a specific object in an untrimmed video given a free-form natural language query. As the annotation of tubes is labor intensive, researchers are motivated to explore weakly supervised approaches in recent works, which usually results in significant performance degradation. To achieve a less expensive STVG method with acceptable accuracy, this work investigates the "single-frame supervision" paradigm that requires a single frame labeled with a bounding box within the temporal boundary of the fully supervised counterpart as the supervisory signal. Based on the characteristics of the STVG problem, we propose a Two-Stage Multiple Instance Learning (T-SMILE) method, which creates pseudo labels by expanding the annotated frame to its contextual frames, thereby establishing a fully-supervised problem to facilitate further model training. The innovations of the proposed method are three-folded, including 1) utilizing multiple instance learning to dynamically select instances in positive bags for the recognition of starting and ending timestamps, 2) learning highly discriminative query features by incorporating spatial prior constraints in cross-attention, and 3) designing a curriculum learning-based strategy that iterative assigns dynamic weights to spatial and temporal branches, thereby gradually adapting to the learning branch with larger difficulty. To facilitate future research on this task, we also contribute a large-scale benchmark containing 12,469 videos on complex scenes with single-frame annotation. The extensive experiments on two benchmarks demonstrate that T-SMILE significantly outperforms all weakly-supervised methods. Remarkably, it also performs better than some fully-supervised methods associated with much more annotation labor costs. The dataset and codes are available at https://github.com/qumengxue/T-SMILE.

Bifidobacterium animalis subsp. lactis LPL-RH improves postoperative gastrointestinal symptoms and nutrition indexes by regulating the gut microbiota in patients with valvular heart disease: a randomized controlled trial.

Gastrointestinal symptoms constitute a frequent complication in postoperative patients with valvular heart disease (VHD), impacting their postoperative recovery. Probiotics contribute to regulating human gut microbiota balance and alleviating postoperative gastrointestinal symptoms. Our objective involved assessing the potential of Bifidobacterium animalis subsp. lactis LPL-RH to alleviate postoperative gastrointestinal symptoms and expedite patient recovery. Adult patients diagnosed with VHD scheduled for valve surgery were enrolled. 110 patients were randomly divided into two groups and received LPL-RH or a placebo for 14 days. Gastrointestinal symptoms were evaluated using the Gastrointestinal Symptoms Questionnaire. An analysis of the time to recovery of bowel function and various postoperative variables was conducted in both study groups. Variations in the intestinal microbiota were detected via 16S rRNA sequencing. The study was completed by 105 participants, with 53 in the probiotic group and 52 in the placebo group. Compared to the placebo group, LPL-RH significantly reduced the total gastrointestinal symptom score after surgery (p = 0.004). Additionally, LPL-RH was found to significantly reduce abdominal pain (p = 0.001), bloating (p = 0.018), and constipation (p = 0.022) symptom scores. Furthermore, LPL-RH dramatically shortened the time to recovery of bowel function (p = 0.017). Moreover, LPL-RH administration significantly enhanced patients' postoperative nutrition indexes (red blood cell counts, hemoglobin level, p < 0.05). Microbiome analysis showed that the composition and diversity of the postoperative intestinal microbiota differed between the probiotic and placebo groups. No adverse incidents associated with probiotics were documented, emphasizing their safety. This study initially discovered that oral B. animalis subsp. lactis LPL-RH can assist in regulating intestinal microbiota balance, alleviating gastrointestinal symptoms, promoting intestinal function recovery, and enhancing nutrition indexes in patients with VHD after surgery. Regulating the intestinal microbiota may represent a potential mechanism for LPL-RH to exert clinical benefits.

Identification of Susceptibility Genes Underlying Bovine Respiratory Disease in Xinjiang Brown Cattle Based on DNA Methylation.

DNA methylation is a form of epigenetic regulation, having pivotal parts in controlling cellular expansion and expression levels within genes. Although blood DNA methylation has been studied in humans and other species, its prominence in cattle is largely unknown. This study aimed to methodically probe the genomic methylation map of Xinjiang brown (XJB) cattle suffering from bovine respiratory disease (BRD), consequently widening cattle blood methylome ranges. Genome-wide DNA methylation profiling of the XJB blood was investigated through whole-genome bisulfite sequencing (WGBS). Many differentially methylated regions (DMRs) obtained by comparing the cases and controls groups were found within the CG, CHG, and CHH (where H is A, T, or C) sequences (16,765, 7502, and 2656, respectively), encompassing 4334 differentially methylated genes (DMGs). Furthermore, GO/KEGG analyses showed that some DMGs were involved within immune response pathways. Combining WGBS-Seq data and existing RNA-Seq data, we identified 71 significantly differentially methylated (DMGs) and expressed (DEGs) genes (p < 0.05). Next, complementary analyses identified nine DMGs (LTA, STAT3, IKBKG, IRAK1, NOD2, TLR2, TNFRSF1A, and IKBKB) that might be involved in the immune response of XJB cattle infected with respiratory diseases. Although further investigations are needed to confirm their exact implication in the involved immune processes, these genes could potentially be used for a marker-assisted selection of animals resistant to BRD. This study also provides new knowledge regarding epigenetic control for the bovine respiratory immune process.

Efficacy and safety of trifluridine/tipiracil plus bevacizumab versus trifluridine/tipiracil monotherapy for refractory metastatic colorectal cancer: a retrospective cohort study.

Background: Several studies demonstrated trifluridine/tipiracil (TAS-102) plus bevacizumab (BEV) had better efficacy than the monotherapy of TAS-102 in refractory metastatic colorectal cancer (mCRC). However, it remains unclear whether Chinese population can benefit from this combination or not. Hence, we conducted this retrospective cohort study to compare the efficacy and safety between TAS-102 plus BEV with TAS-102 monotherapy in refractory mCRC. Methods: This retrospective cohort study enrolled patients (any age) with refractory mCRC from Hunan Cancer Hospital. The main inclusion criteria were histopathologically and/or radiographically confirmed refractory mCRC, World Health Organization (WHO) performance status of 0 to 2, adequate organ function, and initial treatment of TAS-102 with or without BEV between November 2020 and October 2022. Previous therapy with fruquintinib or regorafenib was allowed but not mandatory. Baseline demographic and clinical characteristics were collected appropriately. Every 2 or 3 treatment cycles, the patients were assessed by computed tomography (CT) scans and clinical assessments until disease progression or loss to follow-up. The National Cancer Institute Common Terminology Criteria for Adverse Events 5.0 (NCI-CTCAE 5.0) were presented as n (%). The primary endpoint was investigator-evaluated overall survival (OS). As this is a retrospective cohort study, sample size calculation was not performed. Eligible patients would be enrolled as many as possible. Results: A total of 90 patients were enrolled, including 58 patients who received TAS-102 plus BEV and another 32 patients who received TAS-102 monotherapy. The known baseline characteristics were comparable (P<0.05). With a median follow-up of 4.60 months (range, 0.20-22.80), the median OS (mOS) time in the TAS-102 plus BEV group was longer than that in the TAS-102 monotherapy group (10.83 vs. 7.43 months), but the difference was not significant (P=0.79). The median progression-free survival (mPFS) time was comparable between the two groups (4.67 vs. 4.30 months, P=0.96). Multivariate Cox regression analysis demonstrated that undergoing therapy after TAS-102 either with or without BEV was an independent risk factor for OS [hazard ratio (HR) =0.25; 95% confidence interval (CI): 0.09-0.71, P<0.01], and previous treatment with cetuximab was an independent protective factor for PFS (HR =0.17; 95% CI: 0.03-0.91, P=0.04). Of the 70 patients who were evaluated, those receiving TAS-102 plus BEV showed trend of a higher objective response rate (ORR) and disease control rate (DCR) than those who received TAS-102 monotherapy (P=0.16 and P=0.29, respectively). Adverse events (AEs) were similar between the two groups, except that the incidence of platelet count decrease (grade ≥3) was significantly higher in the TAS-102 plus BEV group. Conclusions: There was a trend in favor of the combination of BEV plus TAS-102 regarding OS and DCR, without reaching statistical significance, and it means that there was no clear advantage of one over the other in terms of efficacy. Further prospective studies are still necessary to draw a definite conclusion.

Innovative methods for microplastic characterization and detection: Deep learning supported by photoacoustic imaging and automated pre-processing data.

Plastic products' widespread applications and their non-biodegradable nature have resulted in the continuous accumulation of microplastic waste, emerging as a significant component of ecological environmental issues. In the field of microplastic detection, the intricate morphology poses challenges in achieving rapid visual characterization of microplastics. In this study, photoacoustic imaging technology is initially employed to capture high-resolution images of diverse microplastic samples. To address the limited dataset issue, an automated data processing pipeline is designed to obtain sample masks while effectively expanding the dataset size. Additionally, we propose Vqdp2, a generative deep learning model with multiple proxy tasks, for predicting six forms of microplastics data. By simultaneously constraining model parameters through two training modes, outstanding morphological category representations are achieved. The results demonstrate Vqdp2's excellent performance in classification accuracy and feature extraction by leveraging the advantages of multi-task training. This research is expected to be attractive for the detection classification and visual characterization of microplastics.

Molecular Epidemiology and Clinical Characteristics of an Outbreak on Respiratory Virus Coinfection in Gansu, China.

This study aims to analyze the epidemiological and pathogenic characteristics of an outbreak primarily caused by respiratory syncytial virus (RSV), human rhinovirus (HRV), and human metapneumovirus (HMPV) in a kindergarten and primary school. The outbreak was investigated by field epidemiological investigation, and the common respiratory pathogens were screened by RT-PCR detection technology. The attack rate of this outbreak was 63.95% (110/172). Main symptoms included cough (85.45%), sore throat (60.91%), and sneezing (60.00%). Multifactorial logistic regression analysis revealed that continuous handwashing and mouth and nose covering when sneezing were protective factors. All 15 collected throat swab specimens tested positive for viruses, with HMPV as the predominant pathogen (80.00%), followed by HRV (53.33%), and two cases of positive respiratory syncytial virus (13.33%). Among them, six samples showed coinfections of HMPV and HRV, and one had coinfections of HMPV and RSV, resulting in a coinfection rate of 46.67%. Genetic sequencing indicated that the HMPV genotype in this outbreak was A2c, and the HRV genotype was type A, resulting in a coinfection outbreak of HMPV, HRV, and RSV in schools and kindergartens, suggesting that multi-pathogen surveillance of respiratory tract infections should be strengthened.

Origin of Interfacial Orbital Reconstruction in Perovskite Superlattices.

The competition between on-site electronic correlation and local crystal field stands out as a captivating topic in research. However, its physical ramifications often get overshadowed by influences of strong periodic potential and orbital hybridization. The present study reveals this competition may become more pronounced or even dominant in two-dimensional systems, driven by the combined effects of dimensional confinement and orbital anisotropy. This leads to electronic orbital reconstruction in certain perovskite superlattices or thin films. To explore the emerging physics, we investigate the interfacial orbital disorder-order transition with an effective Hamiltonian and how to modulate this transition through strains.

Advancing microplastic surveillance through photoacoustic imaging and deep learning techniques.

Microplastic contamination presents a significant global environmental threat, yet scientific understanding of its morphological distribution within ecosystems remains limited. This study introduces a pioneering method for comprehensive microplastic assessment and environmental monitoring, integrating photoacoustic imaging and advanced deep learning techniques. Rigorous curation of diverse microplastic datasets enhances model training, yielding a high-resolution imaging dataset focused on shape-based discrimination. The introduction of the Vector-Quantized Variational Auto Encoder (VQVAE2) deep learning model signifies a substantial advancement, demonstrating exceptional proficiency in image dimensionality reduction and clustering. Furthermore, the utilization of Vector Quantization Microplastic Photoacoustic imaging (VQMPA) with a proxy task before decoding enhances feature extraction, enabling simultaneous microplastic analysis and discrimination. Despite inherent limitations, this study lays a robust foundation for future research, suggesting avenues for enhancing microplastic identification precision through expanded sample sizes and complementary methodologies like spectroscopy. In conclusion, this innovative approach not only advances microplastic monitoring but also provides valuable insights for future environmental investigations, highlighting the potential of photoacoustic imaging and deep learning in bolstering sustainable environmental monitoring efforts.

Study on the interaction protein of transcription factor Smad3 based on TurboID proximity labeling technology.

TurboID is a highly efficient biotin-labelling enzyme, which can be used to explore a number of new intercalating proteins due to the very transient binding and catalytic functions of many proteins. TGF-ß/Smad3 signaling pathway is involved in many diseases, especially in diabetic nephropathy and inflammation. In this paper, a stably cell line transfected with Smad3 were constructed by using lentiviral infection. To further investigate the function of TGF-ß/Smad3, the protein labeling experiment was conducted to find the interacting protein with Smad3 gene. Label-free mass spectrometry analysis was performed to obtain 491 interacting proteins, and the interacting protein hnRNPM was selected for IP and immunofluorescence verification, and it was verified that the Smad3 gene had a certain promoting effect on the expression of hnRNPM gene, and then had an inhibitory effect on IL-6. It lays a foundation for further study of the function of Smad3 gene and its involved regulatory network.

Milk fat globule epidermal growth factor 8 alleviates liver injury in severe acute pancreatitis by restoring autophagy flux and inhibiting ferroptosis in hepatocytes.

BACKGROUND: Liver injury is common in severe acute pancreatitis (SAP). Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes, which induces lipid peroxidation and mitochondrial iron deposition and ultimately leads to ferroptosis. Our previous study found that milk fat globule epidermal growth factor 8 (MFG-E8) alleviates acinar cell damage during SAP via binding to αvß3/5 integrins. MFG-E8 also seems to mitigate pancreatic fibrosis via inhibiting chaperone-mediated autophagy. AIM: To speculate whether MFG-E8 could also alleviate SAP induced liver injury by restoring the abnormal autophagy flux. METHODS: SAP was induced in mice by 2 hly intraperitoneal injections of 4.0 g/kg L-arginine or 7 hly injections of 50 µg/kg cerulein plus lipopolysaccharide. mfge8-knockout mice were used to study the effect of MFG-E8 deficiency on SAP-induced liver injury. Cilengitide, a specific αvß3/5 integrin inhibitor, was used to investigate the possible mechanism of MFG-E8. RESULTS: The results showed that MFG-E8 deficiency aggravated SAP-induced liver injury in mice, enhanced autophagy flux in hepatocyte, and worsened the degree of ferroptosis. Exogenous MFG-E8 reduced SAP-induced liver injury in a dose-dependent manner. Mechanistically, MFG-E8 mitigated excessive autophagy and inhibited ferroptosis in liver cells. Cilengitide abolished MFG-E8's beneficial effects in SAP-induced liver injury. CONCLUSION: MFG-E8 acts as an endogenous protective mediator in SAP-induced liver injury. MFG-E8 alleviates the excessive autophagy and inhibits ferroptosis in hepatocytes by binding to integrin αVß3/5.