Huntingtin contains an ubiquitin-binding domain and regulates lysosomal targeting of mitochondrial and RNA-binding proteins.

Understanding the normal function of the Huntingtin (HTT) protein is of significance in the design and implementation of therapeutic strategies for Huntington's disease (HD). Expansion of the CAG repeat in the HTT gene, encoding an expanded polyglutamine (polyQ) repeat within the HTT protein, causes HD and may compromise HTT's normal activity contributing to HD pathology. Here, we investigated the previously defined role of HTT in autophagy specifically through studying HTT's association with ubiquitin. We find that HTT interacts directly with ubiquitin in vitro. Tandem affinity purification was used to identify ubiquitinated and ubiquitin-associated proteins that copurify with a HTT N-terminal fragment under basal conditions. Copurification is enhanced by HTT polyQ expansion and reduced by mimicking HTT serine 421 phosphorylation. The identified HTT-interacting proteins include RNA-binding proteins (RBPs) involved in mRNA translation, proteins enriched in stress granules, the nuclear proteome, the defective ribosomal products (DRiPs) proteome and the brain-derived autophagosomal proteome. To determine whether the proteins interacting with HTT are autophagic targets, HTT knockout (KO) cells and immunoprecipitation of lysosomes were used to investigate autophagy in the absence of HTT. HTT KO was associated with reduced abundance of mitochondrial proteins in the lysosome, indicating a potential compromise in basal mitophagy, and increased lysosomal abundance of RBPs which may result from compensatory up-regulation of starvation-induced macroautophagy. We suggest HTT is critical for appropriate basal clearance of mitochondrial proteins and RBPs, hence reduced HTT proteostatic function with mutation may contribute to the neuropathology of HD.

MolFeSCue: enhancing molecular property prediction in data-limited and imbalanced contexts using few-shot and contrastive learning.

MOTIVATION: Predicting molecular properties is a pivotal task in various scientific domains, including drug discovery, material science, and computational chemistry. This problem is often hindered by the lack of annotated data and imbalanced class distributions, which pose significant challenges in developing accurate and robust predictive models. RESULTS: This study tackles these issues by employing pretrained molecular models within a few-shot learning framework. A novel dynamic contrastive loss function is utilized to further improve model performance in the situation of class imbalance. The proposed MolFeSCue framework not only facilitates rapid generalization from minimal samples, but also employs a contrastive loss function to extract meaningful molecular representations from imbalanced datasets. Extensive evaluations and comparisons of MolFeSCue and state-of-the-art algorithms have been conducted on multiple benchmark datasets, and the experimental data demonstrate our algorithm's effectiveness in molecular representations and its broad applicability across various pretrained models. Our findings underscore MolFeSCues potential to accelerate advancements in drug discovery. AVAILABILITY AND IMPLEMENTATION: We have made all the source code utilized in this study publicly accessible via GitHub at http://www.healthinformaticslab.org/supp/ or https://github.com/zhangruochi/MolFeSCue. The code (MolFeSCue-v1-00) is also available as the supplementary file of this paper.

MMGAT: a graph attention network framework for ATAC-seq motifs finding.

BACKGROUND: Motif finding in Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) data is essential to reveal the intricacies of transcription factor binding sites (TFBSs) and their pivotal roles in gene regulation. Deep learning technologies including convolutional neural networks (CNNs) and graph neural networks (GNNs), have achieved success in finding ATAC-seq motifs. However, CNN-based methods are limited by the fixed width of the convolutional kernel, which makes it difficult to find multiple transcription factor binding sites with different lengths. GNN-based methods has the limitation of using the edge weight information directly, makes it difficult to aggregate the neighboring nodes' information more efficiently when representing node embedding. RESULTS: To address this challenge, we developed a novel graph attention network framework named MMGAT, which employs an attention mechanism to adjust the attention coefficients among different nodes. And then MMGAT finds multiple ATAC-seq motifs based on the attention coefficients of sequence nodes and k-mer nodes as well as the coexisting probability of k-mers. Our approach achieved better performance on the human ATAC-seq datasets compared to existing tools, as evidenced the highest scores on the precision, recall, F1_score, ACC, AUC, and PRC metrics, as well as finding 389 higher quality motifs. To validate the performance of MMGAT in predicting TFBSs and finding motifs on more datasets, we enlarged the number of the human ATAC-seq datasets to 180 and newly integrated 80 mouse ATAC-seq datasets for multi-species experimental validation. Specifically on the mouse ATAC-seq dataset, MMGAT also achieved the highest scores on six metrics and found 356 higher-quality motifs. To facilitate researchers in utilizing MMGAT, we have also developed a user-friendly web server named MMGAT-S that hosts the MMGAT method and ATAC-seq motif finding results. CONCLUSIONS: The advanced methodology MMGAT provides a robust tool for finding ATAC-seq motifs, and the comprehensive server MMGAT-S makes a significant contribution to genomics research. The open-source code of MMGAT can be found at https://github.com/xiaotianr/MMGAT , and MMGAT-S is freely available at https://www.mmgraphws.com/MMGAT-S/ .

BEROLECMI: a novel prediction method to infer circRNA-miRNA interaction from the role definition of molecular attributes and biological networks.

Circular RNA (CircRNA)-microRNA (miRNA) interaction (CMI) is an important model for the regulation of biological processes by non-coding RNA (ncRNA), which provides a new perspective for the study of human complex diseases. However, the existing CMI prediction models mainly rely on the nearest neighbor structure in the biological network, ignoring the molecular network topology, so it is difficult to improve the prediction performance. In this paper, we proposed a new CMI prediction method, BEROLECMI, which uses molecular sequence attributes, molecular self-similarity, and biological network topology to define the specific role feature representation for molecules to infer the new CMI. BEROLECMI effectively makes up for the lack of network topology in the CMI prediction model and achieves the highest prediction performance in three commonly used data sets. In the case study, 14 of the 15 pairs of unknown CMIs were correctly predicted.

DSBSO-Based XL-MS Analysis of Breast Cancer PDX Tissues to Delineate Protein Interaction Network in Clinical Samples.

Protein-protein interactions (PPIs) are fundamental to understanding biological systems as protein complexes are the active molecular modules critical for carrying out cellular functions. Dysfunctional PPIs have been associated with various diseases including cancer. Systems-wide PPI analysis not only sheds light on pathological mechanisms, but also represents a paradigm in identifying potential therapeutic targets. In recent years, cross-linking mass spectrometry (XL-MS) has emerged as a powerful tool for defining endogenous PPIs of cellular networks. While proteome-wide studies have been performed in cell lysates, intact cells and tissues, applications of XL-MS in clinical samples have not been reported. In this study, we adopted a DSBSO-based in vivo XL-MS platform to map interaction landscapes from two breast cancer patient-derived xenograft (PDX) models. As a result, we have generated a PDX interaction network comprising 2,557 human proteins and identified interactions unique to breast cancer subtypes. Interestingly, most of the observed differences in PPIs correlated well with protein abundance changes determined by TMT-based proteome quantitation. Collectively, this work has demonstrated the feasibility of XL-MS analysis in clinical samples, and established an analytical workflow for tissue cross-linking that can be generalized for mapping PPIs from patient samples in the future to dissect disease-relevant cellular networks.

Proteomics Platform Reveals Broad-Spectrum Nanobodies for SARS-CoV-2 Variant Neutralization.

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the emergence of different variants of concerns with immune evasion that have been prevalent over the past three years. Nanobodies, the functional variable regions of camelid heavy-chain-only antibodies, have garnered interest in developing neutralizing antibodies due to their smaller size, structural stability, ease of production, high affinity, and low immunogenicity, among other characteristics. In this work, we describe an integrated proteomics platform for the high-throughput screening of nanobodies against different SARS-CoV-2 spike variants. To demonstrate this platform, we immunized a camel with subunit 1 (S1) of the wild-type spike protein and constructed a nanobody phage library. The binding and neutralizing activities of the nanobodies against 72 spike variants were then measured, resulting in the identification of two nanobodies (C-282 and C-39) with broad neutralizing activity against six non-Omicron variants (D614G, Alpha, Beta, Gamma, Delta, Kappa) and five Omicron variants (BA.1-5). Their neutralizing capability was validated using in vitro pseudovirus-based neutralization assays. All these results demonstrate the utility of our proteomics platform to identify new nanobodies with broad neutralizing capability and to develop a treatment for patients with SARS-CoV-2 variant infection in the future.

Research progress on the regulatory mechanism of integrin-mediated mechanical stress in cells involved in bone metabolism.

Mechanical stress is an internal force between various parts of an object that resists external factors and effects that cause an object to deform, and mechanical stress is essential for various tissues that are constantly subjected to mechanical loads to function normally. Integrins are a class of transmembrane heterodimeric glycoprotein receptors that are important target proteins for the action of mechanical stress stimuli on cells and can convert extracellular physical and mechanical signals into intracellular bioelectrical signals, thereby regulating osteogenesis and osteolysis. Integrins play a bidirectional regulatory role in bone metabolism. In this paper, relevant literature published in recent years is reviewed and summarized. The characteristics of integrins and mechanical stress are introduced, as well as the mechanisms underlying responses of integrin to mechanical stress stimulation. The paper focuses on integrin-mediated mechanical stress in different cells involved in bone metabolism and its associated signalling mechanisms. The purpose of this review is to provide a theoretical basis for the application of integrin-mediated mechanical stress to the field of bone tissue repair and regeneration.

Mitochondrial genome provides species-specific targets for the rapid detection of early invasive populations of Hylurgus ligniperda in China.

BACKGROUND: Hylurgus ligniperda, a major international forestry quarantine pest, was recently found to have invaded and posed a serious threat to the Pinus forests of the Jiaodong Peninsula in China. Continuous monitoring and vigilance of the early population is imperative, and rapid molecular detection technology is urgently needed. We focused on developing a single-gene-based species-specific PCR (SS-PCR) method. RESULTS: We sequenced and assembled the mitochondrial genome of H. ligniperda to identify suitable target genes. We identified three closely related species for detecting the specificity of SS-PCR through phylogenetic analysis based on 13 protein-coding genes (PCGs). Subsequently, we analyzed the evolution of 13 PCGs and selected four mitochondrial genes to represent slow-evolving gene (COI) and faster-evolving genes (e.g. ND2, ND4, and ND5), respectively. We developed four species-specific primers targeting COI, ND2, ND4, and ND5 to rapidly identify H. ligniperda. The results showed that the four species-specific primers exhibited excellent specificity and sensitivity in the PCR assays, with consistent performance across a broader range of species. This method demonstrates the ability to identify beetles promptly, even during their larval stage. The entire detection process can be completed within 2-3 h. CONCLUSIONS: This method is suitable for large-scale species detection in laboratory settings. Moreover, the selection of target genes in the SS-PCR method is not affected by the evolutionary rate. SS-PCR can be widely implemented at port and forestry workstations, significantly enhancing early management strategies and quarantine measures against H. ligniperda. This approach will help prevent the spread of the pest and effectively preserve the resources of Chinese pine forests.

Human esophageal cancer stem-like cells escape the cytotoxicity of natural killer cells via down-regulation of ULBP-1.

BACKGROUND: Cancer stem-like cells (CSCs) play an important role in initiation and progression of aggressive cancers, including esophageal cancer. Natural killer (NK) cells are key effector lymphocytes of innate immunity that directly attack a wide variety of cancer cells. NK cell-based therapy may provide a new treatment option for targeting CSCs. In this study, we aimed to investigate the sensitivity of human esophageal CSCs to NK cell-mediated cytotoxicity. METHODS: CSCs were enriched from human esophageal squamous cell carcinoma cell lines via sphere formation culture. Human NK cells were selectively expanded from the peripheral blood of healthy donors. qRT-PCR, flow cytometry and ELISA assays were performed to examine RNA expression and protein levels, respectively. CFSE-labeled target cells were co-cultured with human activated NK cells to detect the cytotoxicity of NK cells by flow cytometry. RESULTS: We observed that esophageal CSCs were more resistant to NK cell-mediated cytotoxicity compared with adherent counterparts. Consistently, esophageal CSCs showed down-regulated expression of ULBP-1, a ligand for NK cells stimulatory receptor NKG2D. Knockdown of ULBP-1 resulted in significant inhibition of NK cell cytotoxicity against esophageal CSCs, whereas ULBP-1 overexpression led to the opposite effect. Finally, the pro-differentiation agent all-trans retinoic acid was found to enhance the sensitivity of esophageal CSCs to NK cell cytotoxicity. CONCLUSIONS: This study reveals that esophageal CSCs are more resistant to NK cells through down-regulation of ULBP-1 and provides a promising approach to promote the activity of NK cells targeting esophageal CSCs.

GANSamples-ac4C: Enhancing ac4C site prediction via generative adversarial networks and transfer learning.

RNA modification, N4-acetylcytidine (ac4C), is enzymatically catalyzed by N-acetyltransferase 10 (NAT10) and plays an essential role across tRNA, rRNA, and mRNA. It influences various cellular functions, including mRNA stability and rRNA biosynthesis. Wet-lab detection of ac4C modification sites is highly resource-intensive and costly. Therefore, various machine learning and deep learning techniques have been employed for computational detection of ac4C modification sites. The known ac4C modification sites are limited for training an accurate and stable prediction model. This study introduces GANSamples-ac4C, a novel framework that synergizes transfer learning and generative adversarial network (GAN) to generate synthetic RNA sequences to train a better ac4C modification site prediction model. Comparative analysis reveals that GANSamples-ac4C outperforms existing state-of-the-art methods in identifying ac4C sites. Moreover, our result underscores the potential of synthetic data in mitigating the issue of data scarcity for biological sequence prediction tasks. Another major advantage of GANSamples-ac4C is its interpretable decision logic. Multi-faceted interpretability analyses detect key regions in the ac4C sequences influencing the discriminating decision between positive and negative samples, a pronounced enrichment of G in this region, and ac4C-associated motifs. These findings may offer novel insights for ac4C research. The GANSamples-ac4C framework and its source code are publicly accessible at http://www.healthinformaticslab.org/supp/.

Adipocyte pyroptosis occurs in omental tumor microenvironment and is associated with chemoresistance of ovarian cancer.

BACKGROUND: Ovarian carcinoma (OC) is a fatal malignancy, with most patients experiencing recurrence and resistance to chemotherapy. In contrast to hematogenous metastasizing tumors, ovarian cancer cells disseminate within the peritoneal cavity, especially the omentum. Previously, we reported omental crown-like structure (CLS) number is associated with poor prognosis of advanced-stage OC. CLS that have pathologic features of a dead or dying adipocyte was surrounded by several macrophages is well known a histologic hallmark for inflammatory adipose tissue. In this study, we attempted to clarify the interaction between metastatic ovarian cancer cells and omental CLS, and to formulate a therapeutic strategy for advanced-stage ovarian cancer. METHODS: A three-cell (including OC cells, adipocytes and macrophages) coculture model was established to mimic the omental tumor microenvironment (TME) of ovarian cancer. Caspase-1 activity, ATP and free fatty acids (FFA) levels were detected by commercial kits. An adipocyte organoid model was established to assess macrophages migration and infiltration. In vitro and in vivo experiments were performed for functional assays and therapeutic effect evaluations. Clinical OC tissue samples were collected for immunochemistry stain and statistics analysis. RESULTS: In three-cell coculture model, OC cells-derived IL-6 and IL-8 could induce the occurrence of pyroptosis in omental adipocytes. The pyroptotic adipocytes release ATP to increase macrophage infiltration, release FFA into TME, uptake by OC cells to increase chemoresistance. From OC tumor samples study, we demonstrated patients with high gasdermin D (GSDMD) expression in omental adipocytes is highly correlated with chemoresistance and poor outcome in advanced-stage OC. In animal model, by pyroptosis inhibitor, DSF, effectively retarded tumor growth and prolonged mice survival. CONCLUSIONS: Omental adipocyte pyroptosis may contribute the chemoresistance in advanced stage OC. Omental adipocytes could release FFA and ATP through the GSDMD-mediate pyroptosis to induce chemoresistance and macrophages infiltration resulting the poor prognosis in advanced-stage OC. Inhibition of adipocyte pyroptosis may be a potential therapeutic modality in advanced-stage OC with omentum metastasis.

SUMOylation of annexin A6 retards cell migration and tumor growth by suppressing RHOU/AKT1-involved EMT in hepatocellular carcinoma.

BACKGROUND: The protein annexin A6 (AnxA6) is involved in numerous membrane-related biological processes including cell migration and invasion by interacting with other proteins. The dysfunction of AnxA6, including protein expression abundance change and imbalance of post-translational modification, is tightly related to multiple cancers. Herein we focus on the biological function of AnxA6 SUMOylation in hepatocellular carcinoma (HCC) progression. METHODS: The modification sites of AnxA6 SUMOylation were identified by LC-MS/MS and amino acid site mutation. AnxA6 expression was assessed by immunohistochemistry and immunofluorescence. HCC cells were induced into the epithelial-mesenchymal transition (EMT)-featured cells by 100 ng/mL 12-O-tetradecanoylphorbol-13-acetate exposure. The ability of cell migration was evaluated under AnxA6 overexpression by transwell assay. The SUMO1 modified AnxA6 proteins were enriched from total cellular proteins by immunoprecipitation with anti-SUMO1 antibody, then the SUMOylated AnxA6 was detected by Western blot using anti-AnxA6 antibody. The nude mouse xenograft and orthotopic hepatoma models were established to determine HCC growth and tumorigenicity in vivo. The HCC patient's overall survival versus AnxA6 expression level was evaluated by the Kaplan-Meier method. RESULTS: Lys579 is a major SUMO1 modification site of AnxA6 in HCC cells, and SUMOylation protects AnxA6 from degradation via the ubiquitin-proteasome pathway. Compared to the wild-type AnxA6, its SUMO site mutant AnxA6K579R leads to disassociation of the binding of AnxA6 with RHOU, subsequently RHOU-mediated p-AKT1ser473 is upregulated to facilitate cell migration and EMT progression in HCC. Moreover, the SENP1 deSUMOylates AnxA6, and AnxA6 expression is negatively correlated with SENP1 protein expression level in HCC tissues, and a high gene expression ratio of ANXA6/SENP1 indicates a poor overall survival of patients. CONCLUSIONS: AnxA6 deSUMOylation contributes to HCC progression and EMT phenotype, and the combination of AnxA6 and SENP1 is a better tumor biomarker for diagnosis of HCC grade malignancy and prognosis.

Visible-Light Induced Radical Addition-Elimination Reaction for Constructing Allylic Sulfones from Sulfonyl Chlorides and Allyl Bromides.

Allyl sulfones are commonly present in bioactive compounds and organic building blocks. This work introduces a photocatalytic radical addition-elimination reaction involving readily accessible sulfonyl chlorides and allyl bromides. It delivers structurally diverse allylic sulfones in moderate to excellent yields, showcasing a high tolerance to functional groups. Notably, this method operates under mild reaction conditions without the need for oxidants, stoichiometric reducing metals, or additives.

Alstomaphylines A-K, monoterpenoid bisindole alkaloids from Alstonia macrophylla with AChE inhibitory activity and cytotoxicity.

Eleven undescribed monoterpenoid bisindole alkaloids, alstomaphyines A-K (1-11), along with three known analogues were isolated from the leaves and stem bark of the Alstonia macrophylla. Compounds 1-3 were unprecedented dimerization alkaloids incorporating a macroline-type motif with an ajmaline-type motif via a C-C linkage. Their structures and absolute configurations were elucidated by extensive spectroscopic analysis, electronic circular dichroism (ECD) calculation, and CD exciton chirality method. Compounds 1-3 displayed potential inhibitory bioactivity against AChE with IC50 values of 4.44 ± 0.35, 3.59 ± 0.18, and 3.71 ± 0.23 µM, respectively. Enzyme kinetic study revealed compounds 1-3 as mixed competitive AChE inhibitors. Besides, compounds 8 and 12-14 exhibited better cytotoxicity against human cancer cell line HT-29 than cisplatin. Flow cytometry data revealed that compounds 8, 13, and 14 significantly induced the HT-29 cells arrest in G0/G1 phase in a concentration-dependent manner.

Neurodevelopmental outcomes of preterm with necrotizing enterocolitis: a systematic review and meta-analysis.

While neonatal necrotising enterocolitis (NEC) is associated with high mortality rates in newborns, survivors can face long-term sequelae. However, the relationship between NEC and neurodevelopmental impairment (NDI) in preterm infants remains unclear. To explore the relationship between neonatal NEC and neurodevelopmental outcomes in preterm infants, we searched PubMed, EMBASE, and the Cochrane Library from their inception to February 2024 for relevant studies. Studies included were cohort or case-control studies reporting neurodevelopmental outcomes of NEC in preterm infants. Two independent investigators extracted data regarding brain damage and neurodevelopmental outcomes in these infants at a corrected age exceeding 12 months. Odds ratios (ORs) were pooled using a random effects model. We included 15 cohort studies and 18 case-control studies, encompassing 60,346 infants. Meta-analysis of unadjusted and adjusted ORs demonstrated a significant association between NEC and increased odds of NDI (OR 2.15, 95% CI 1.9-2.44; aOR 1.89, 95% CI 1.46-2.46). Regarding brain injury, pooled crude ORs indicated an association of NEC with severe intraventricular haemorrhage (IVH) (OR 1.42, 95% CI 1.06-1.92) and periventricular leucomalacia (PVL) (OR 2.55, 95% CI 1.76-3.69). When compared with conservatively treated NEC, surgical NEC potentially carries a higher risk of NDI (OR 1.78, 95% CI 1.09-2.93) and severe IVH (OR 1.57, 95% CI 1.20-2.06). However, the risk of PVL did not show a significant difference (OR 1.60, 95% CI 0.47-5.40). CONCLUSIONS:  Our meta-analysis provides evidence suggesting an association between NEC and NDI. Additionally, the severity of intestinal lesions appears to correlate with a higher risk of NDI. Further high-quality studies with comprehensive adjustments for potential confounding factors are required to definitively establish whether the association with NDI is causal. WHAT IS KNOWN: • NEC is a serious intestinal disease in the neonatal period with a high mortality rate, and surviving children may have digestive system sequelae. • Compared with non-NEC preterm infants, the reported incidences of brain injury and neurodevelopmental disorders in NEC preterm infants are not the same. WHAT IS NEW: • The risk of neonatal brain injury and neurodevelopmental disorders in preterm infants with NEC is higher than that in non-NEC infants, and the risk of NDI in surgical NEC infants is higher than that in the conservative treatment group. • NEC may increase the risk of motor, cognitive, language development delays, and attention deficits in children.

Postsurgical Analgesic Effectiveness of Ultrasound-Guided Parasternal Block After Auricular Reconstruction Using Autologous Costal Cartilage in Pediatric Patients: A Randomized Controlled Trial.

OBJECTIVE: To study the efficacy of ultrasound-guided parasternal block (US-PSI) in pediatric patients undergoing auricular reconstruction surgery. METHODS: For this study, the authors recruited 60 children between the ages of 5 and 12 years who underwent auricular reconstruction with autologous costal cartilage (ACC) to correct microtia. They were randomized to receive either ultrasound-guided modified parasternal block or periprostatic local infiltration anesthesia (PLIA), with 30 cases in each group. Ultrasound-guided parasternal block was administered following anesthesia induction, whereas PLIA was administered after ACC harvest. Lastly, following surgery, all children were provided with patient-controlled intravenous analgesia with sufentanil, and the numeric pain rating scale (NRS) was used to assess the intensity of pain. Our primary outcomes were the resting NRS pain scores and the NRS scores upon coughing at 1, 6, 12, 24, and 48 hours postsurgery. Sufentanil consumption within the first 24 hours of surgery, the mean duration to first ambulation, and the usage of rescue analgesics were our secondary outcomes. The authors also recorded the occurrence of undesirable side effects as well as more serious side effects like pneumothorax. RESULTS: Pediatric patients who were administered US-PSI showed significantly reduced NRS chest pain scores at 6 and 12 hours postsurgery compared to those who received PLIA (P<0.05). In addition, sufentanil consumption within the first 24 hours postsurgery, duration to first ambulation, and use of rescue analgesics were significantly lower among patients in the US-PSI group when compared to those in the PLIA group (P<0.05). CONCLUSIONS: This study found that US-PSI was a highly efficacious and safe technique for postsurgical analgesia following auricular reconstruction with ACC in pediatric patients. LEVEL OF EVIDENCE: Level II, therapeutic study.

What Factors Can Affect the Occurrence of Vertigo in Patients After Craniofacial Surgery in China?

Vertigo is a complication of craniomaxillofacial contour plastic surgery characterized by dizziness from hypovolemia in the cerebral hemispheres and brainstem. The authors analyzed the current status and influencing factors of postoperative vertigo in patients who undergo craniomaxillofacial contouring and discussed improvements in nursing strategies. The authors investigated 418 patients admitted to the authors' hospital who underwent craniomaxillofacial contouring between November 2020 and October 2023 and divided them into asymptomatic and symptomatic groups based on syncopal precursors or vertigo. The authors screened the current status of vertigo in patients after craniomaxillofacial contouring and the factors affecting vertigo and determined nursing improvement strategies. After craniomaxillofacial contouring, 125 patients had vertigo symptoms. Postcraniomaxillofacial contouring syncope or vertigo was associated with age, patient vertigo history, family history, depression, weight loss, blood pressure at admission, feeding before getting out of bed, and the level of intraoperative hemorrhage Multifactorial logistic regression analysis revealed the association between postcraniomaxillofacial contouring syncope or vertigo and vertigo history, depression, weight loss, feeding before getting out of bed, and intraoperative bleeding volume. Vertigo precursor incidence after craniomaxillofacial contouring surgery is 29.90%. Its influencing factors are complex, suggesting that nurses need to improve the perioperative health education of craniomaxillofacial contouring surgery and optimize the nursing care, encourage patients to have a reasonable diet or provide parenteral nutritional support preoperatively, help patients get out of bed early postoperatively, encourage them to have multiple meals in little quantity before getting out of bed, and control the intraoperative bleeding, to ensure patient safety postoperatively.

Comparing the Analgesic Effects Between the Pre- and Post-costal Cartilage Harvest Cohorts Using Ultrasound-Guided Deep Serratus Anterior Plane Block in Children with Microtia Undergoing Auricular Reconstruction: A Randomized Clinical Trial.

PURPOSE: Pain following costal cartilage harvest surgery is the most common complaint of auricular reconstruction (AR). Anesthesiologists are continuously searching for an effective postoperative pain control method. METHODS: This study was conducted from 10 April 2022 to 10 June 2022. Sixty children undergoing AR using costal cartilage were randomly assigned to either a serratus anterior plane block performed before costal cartilage harvest (SAPB-pre-cohort; n = 30) or the SAPB-post-cohort (Post-costal cartilage Harvest Cohort: n = 30). The primary endpoint measures were the Numerical Rating Scale (NRS) scores of the chest and ear pain degrees recorded at 1-, 6-, 12-, 24-, and 48-h after surgery. Intraoperative anesthetic and analgesic dosages, sufentanil consumption and rescue analgesia consumption during the first 24 h post-operation, cough score during extubation, extubation agitation score, length of stay, the extubation time, first ambulatory time, analgesia duration, and opioid-related adverse effects and SAPB-related adverse effects were the secondary endpoints. RESULTS: The rest and coughing NRS scores were significantly reduced in the SAPB-pre-cohort 6 and 12 h post-operation in comparison with the SAPB-post-cohort (rest 6 h p = 0.002, others p < 0.001). No significant difference in the NRS ear scores existed between the two cohorts (p > 0.05). The use of propofol and remifentanil for general anesthesia during the SAPB-pre-procedure was significantly reduced compared to the SAPB-post-group, with statistical significance (p < 0.001). Sufentanil consumption and rescue analgesia consumption were significantly reduced in the SAPB-pre-cohort (p = 0.001, p = 0.033). The extubation time and first ambulatory time were markedly shorter in the SAPB-pre-cohort (all p < 0.001). Analgesia duration was markedly longer in the SAPB-pre-cohort (p < 0.001). No significant differences were noted in the cough score during extubation, extubation agitation score, length of stay between the two cohorts (all p > 0.05). Opioid-related adverse effects occurred more in the SAPB-post-cohort, while there was no statistical significance (16.7 vs. 36.7%; p = 0.082). There were no blockade-related complications observed in either cohort. CONCLUSION: The analgesic effect of the SAPB-pre-cohort was better than the SAPB-post-cohort suggesting both efficacy and feasibility of preemptive analgesia. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Multi-Omics Analysis Reveals That Anthocyanin Degradation and Phytohormone Changes Regulate Red Color Fading in Rapeseed (Brassica napus L.) Petals.

Flower color is an important trait for the ornamental value of colored rapeseed (Brassica napus L.), as the plant is becoming more popular. However, the color fading of red petals of rapeseed is a problem for its utilization. Unfortunately, the mechanism for the process of color fading in rapeseed is unknown. In the current study, a red flower line, Zhehuhong, was used as plant material to analyze the alterations in its morphological and physiological characteristics, including pigment and phytohormone content, 2 d before flowering (T1), at flowering (T2), and 2 d after flowering (T3). Further, metabolomics and transcriptomics analyses were also performed to reveal the molecular regulation of petal fading. The results show that epidermal cells changed from spherical and tightly arranged to totally collapsed from T1 to T3, according to both paraffin section and scanning electron microscope observation. The pH value and all pigment content except flavonoids decreased significantly during petal fading. The anthocyanin content was reduced by 60.3% at T3 compared to T1. The content of three phytohormones, 1-aminocyclopropanecarboxylic acid, melatonin, and salicylic acid, increased significantly by 2.2, 1.1, and 30.3 times, respectively, from T1 to T3. However, auxin, abscisic acid, and jasmonic acid content decreased from T1 to T3. The result of metabolomics analysis shows that the content of six detected anthocyanin components (cyanidin, peonidin, pelargonidin, delphinidin, petunidin, and malvidin) and their derivatives mainly exhibited a decreasing trend, which was in accordance with the trend of decreasing anthocyanin. Transcriptomics analysis showed downregulation of genes involved in flavonol, flavonoid, and anthocyanin biosynthesis. Furthermore, genes regulating anthocyanin biosynthesis were preferentially expressed at early stages, indicating that the degradation of anthocyanin is the main issue during color fading. The corresponding gene-encoding phytohormone biosynthesis and signaling, JASMONATE-ZIM-DOMAIN PROTEIN, was deactivated to repress anthocyanin biosynthesis, resulting in fading petal color. The results clearly suggest that anthocyanin degradation and phytohormone regulation play essential roles in petal color fading in rapeseed, which is a useful insight for the breeding of colored rapeseed.

ESMSec: Prediction of Secreted Proteins in Human Body Fluids Using Protein Language Models and Attention.

The secreted proteins of human body fluid have the potential to be used as biomarkers for diseases. These biomarkers can be used for early diagnosis and risk prediction of diseases, so the study of secreted proteins of human body fluid has great application value. In recent years, the deep-learning-based transformer language model has transferred from the field of natural language processing (NLP) to the field of proteomics, leading to the development of protein language models (PLMs) for protein sequence representation. Here, we propose a deep learning framework called ESM Predict Secreted Proteins (ESMSec) to predict three types of proteins secreted in human body fluid. The ESMSec is based on the ESM2 model and attention architecture. Specifically, the protein sequence data are firstly put into the ESM2 model to extract the feature information from the last hidden layer, and all the input proteins are encoded into a fixed 1000 × 480 matrix. Secondly, multi-head attention with a fully connected neural network is employed as the classifier to perform binary classification according to whether they are secreted into each body fluid. Our experiment utilized three human body fluids that are important and ubiquitous markers. Experimental results show that ESMSec achieved average accuracy of 0.8486, 0.8358, and 0.8325 on the testing datasets for plasma, cerebrospinal fluid (CSF), and seminal fluid, which on average outperform the state-of-the-art (SOTA) methods. The outstanding performance results of ESMSec demonstrate that the ESM can improve the prediction performance of the model and has great potential to screen the secretion information of human body fluid proteins.