Characterization of Cancer Stem Cells in Laryngeal Squamous Cell Carcinoma by Single-cell RNA Sequencing.

Cancer stem cells (CSCs) constitute a pivotal element within the tumor microenvironment (TME), driving the initiation and progression of cancer. However, the identification of CSCs and their underlying molecular mechanisms in laryngeal squamous cell carcinoma (LSCC) remains a formidable challenge. We employed single-cell RNA sequencing of matched primary tumor tissues, paracancerous tissues, and local lymph nodes from three LSCC patients. Two distinct clusters of stem cells originating from epithelial populations were delineated and verified as CSCs and normal stem cells (NSCs), respectively. CSCs were abundant in the paracancerous tissues compared to the tumor tissues. CSCs showed high expression of stem cell marker genes such as PROM1, ALDH1A1, and SOX4, and increased the activity of tumor-related hypoxia, Wnt/ß-catenin, and Notch signaling pathways. We then explored the intricate crosstalk between CSCs and the TME cells and identified targets within the TME that related with CSCs. We also found eight marker genes of CSCs that correlated significantly with the prognosis of LSCC patients. Furthermore, bioinformatics analyses showed that drugs such as erlotinib, OSI-027, and ibrutinib selectively targeted the CSC-specifically expressed genes. In conclusion, our results represent the first comprehensive characterization of CSCs properties in LSCC at the single-cell level.

mTORC2-driven chromatin cGAS mediates chemoresistance through epigenetic reprogramming in colorectal cancer.

Cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor that initiates a STING-dependent innate immune response, binds tightly to chromatin, where its catalytic activity is inhibited; however, mechanisms underlying cGAS recruitment to chromatin and functions of chromatin-bound cGAS (ccGAS) remain unclear. Here we show that mTORC2-mediated phosphorylation of human cGAS serine 37 promotes its chromatin localization in colorectal cancer cells, regulating cell growth and drug resistance independently of STING. We discovered that ccGAS recruits the SWI/SNF complex at specific chromatin regions, modifying expression of genes linked to glutaminolysis and DNA replication. Although ccGAS depletion inhibited cell growth, it induced chemoresistance to fluorouracil treatment in vitro and in vivo. Moreover, blocking kidney-type glutaminase, a downstream ccGAS target, overcame chemoresistance caused by ccGAS loss. Thus, ccGAS coordinates colorectal cancer plasticity and acquired chemoresistance through epigenetic patterning. Targeting both mTORC2-ccGAS and glutaminase provides a promising strategy to eliminate quiescent resistant cancer cells.

Irisin alleviated the reproductive endocrinal disorders of PCOS mice accompanied by changes in gut microbiota and metabolomic characteristics.

Introduction: Folliculogenesis and oligo/anovulation are common pathophysiological characteristics in polycystic ovary syndrome (PCOS) patients, and it is also accompanied by gut microbiota dysbiosis. It is known that physical activity has beneficial effects on improving metabolism and promoting ovulation and menstrual cycle disorder in PCOS patients, and it can also modulate the gastrointestinal microbiota in human beings. However, the mechanism remains vague. Irisin, a novel myokine, plays a positive role in the mediating effects of physical activity. Methods: Mice were randomly divided into the control group, PCOS group and PCOS+irisin group. PCOS model was induced by dehydroepiandrosterone (DHEA) and high-fat diet (HFD). The PCOS+irisin group was given irisin 400µg/kg intraperitoneal injection every other day for 21 days. The serum sex hormones were measured by radioimmunoassay. Hematoxylin and Eosin (H&E) Staining and immunohistochemistry (IHC) were conducted on ovarian tissue. The feces microbiota and metabolomic characteristics were collected by 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS). Results: In this study, we demonstrated that irisin supplementation alleviated reproductive endocrine disorders of PCOS mice, including estrous cycle disturbance, ovarian polycystic degeneration, and hyperandrogenemia. Irisin also improved the PCOS follicles dysplasia and ovulation disorders, while it had no significant effect on the quality of oocytes. Moreover, irisin could mitigate the decreased bacteria of Odoribacter and the increased bacteria of Eisenbergiella and Dubosiella in PCOS mice model. Moreover, irisin could alleviate the increased fecal metabolites: Methallenestril and PS (22:5(4Z,7Z,10Z,13Z,16Z)/ LTE4). Conclusion: These results suggest that irisin may alleviate the status of PCOS mice model by modulating androgen-induced gut microbiota dysbiosis and fecal metabolites. Hence, our study provided evidence that irisin may be considered as a promising strategy for the treatment of PCOS.

Identification of a disulfidptosis-related lncRNA signature for the prognostic and immune landscape prediction in head and neck squamous cell carcinoma.

PURPOSE: Disulfidptosis, a newly identified form of cell death, is triggered by disulfide stress. Herein, a unique signature was developed based on disulfidptosis-related lncRNAs (DRlncRNAs) for the prognostic and immune landscape prediction of head and neck squamous cell carcinoma (HNSCC). METHODS: Transcriptome, somatic mutation, and clinical data were acquired at The Cancer Genome Atlas database. Individuals were partitioned into training and test cohorts at a 1:1 ratio to facilitate the development of a DRlncRNA signature using the least absolute shrinkage and selection operation method. Based on the median risk score, all HNSCC individuals were stratified into the high-risk group (HRG) and low-risk group (LRG). Kaplan-Meier survival and time-dependent receiver operating characteristic (ROC) analyses were used to estimate the prognostic value, and a nomogram was generated for survival prediction. To provide a more comprehensive assessment, the tumor microenvironment, functional enrichment, immune cell infiltration, and immunotherapeutic sensitivity were explored between LRG and HRG. RESULTS: A DRlncRNA signature was established with 10 DRlncRNAs. The corresponding values of areas under the ROC curves for 1-, 3-, and 5-year overall survival were 0.710, 0.692, and 0.640. A more favorable prognosis was noted in the patients with lower risk, along with higher immune scores, increased immune-related functions, and immune cell infiltration, as well as improved response to the immunotherapeutic intervention in comparison with individuals at higher risk. CONCLUSION: These findings demonstrate that the developed DRlncRNA signature holds promise as a reliable prognostic marker and predictor of immunotherapy response in HNSCC patients.

Injuries of Different Surgical Instruments on the Vocal Folds of Dogs.

OBJECTIVE: This study aimed to compare the damage of vocal folds caused by four different surgical instruments: CO2 laser, electrosurgical knife, plasma radiofrequency ablation, and steel knife. STUDY DESIGN: Randomized controlled study. METHODS: The CO2 laser, electrosurgical knife, plasma radiofrequency ablation, steel knife, and other instruments were used to simulate the laryngeal microsurgery on experimental dogs. Both total vocal fold resection and punctate ablation were performed. On the day of surgery and 6 days later, the vocal fold tissue from the surgical site was removed for histological evaluation. The extent of vocal fold damage was assessed using the automatic digital pathological scanning system. RESULTS: We detected varying degrees of damage to the laryngeal tissues. Only the steel knife caused epidermal defects on the vocal fold tissue, while other instruments produced thermal damage of different degrees. Furthermore, the steel knife also showed better and faster healing. The plasma radiofrequency ablation was found to cause more severe thermal burns to vocal folds than other surgical instruments (P < 0.05). Six days postsurgery the inflammatory reaction from the steel knife had basically subsided, with only hyperplasia and tissue repair visible microscopically, showing the best healing degree. On the other hand, the radiofrequency ablation group showed the heaviest inflammatory reaction, indicating relatively poor prognosis (P < 0.05). CONCLUSION: Compared with the CO2 laser, the electrotome and steel knife showed less damage and better healing, while the plasma radiofrequency ablation showed the most obvious thermal burns to laryngeal and vocal tissues during surgery, with relatively poor healing.

Metal-polyphenol networks-modified tantalum plate for craniomaxillofacial reconstruction.

Using three-dimensional (3D) printing technology to make the porous tantalum plate and modify its surface. The physicochemical properties, cytocompatibility, antioxidant capacity, and histocompatibility of the modified materials were evaluated to prepare for the repair of craniomaxillofacial bone defects. The porous tantalum plates were 3D printed by selective laser melting technology. Tantalum plates were surface modified with a metal polyphenol network. The surface-modified plates were analyzed for cytocompatibility using thiazolyl blue tetrazolium bromide and live/dead cell staining. The antioxidant capacity of the surface-modified plates was assessed by measuring the levels of intracellular reactive oxygen species, reduced glutathione, superoxide dismutase, and malondialdehyde. The histocompatibility of the plates was evaluated by animal experiments. The results obtained that the tantalum plates with uniform small pores exhibited a high mechanical strength. The surface-modified plates had much better hydrophilicity. In vitro cell experiments showed that the surface-modified plates had higher cytocompatibility and antioxidant capacity than blank tantalum plates. Through subcutaneous implantation in rabbits, the surface-modified plates demonstrated good histocompatibility. Hence, surface-modified tantalum plates had the potential to be used as an implant material for the treatment of craniomaxillofacial bone defects.

CPFTransformer: transformer fusion context pyramid medical image segmentation network.

Introduction: The application of U-shaped convolutional neural network (CNN) methods in medical image segmentation tasks has yielded impressive results. However, this structure's single-level context information extraction capability can lead to problems such as boundary blurring, so it needs to be improved. Additionally, the convolution operation's inherent locality restricts its ability to capture global and long-distance semantic information interactions effectively. Conversely, the transformer model excels at capturing global information. Methods: Given these considerations, this paper presents a transformer fusion context pyramid medical image segmentation network (CPFTransformer). The CPFTransformer utilizes the Swin Transformer to integrate edge perception for segmentation edges. To effectively fuse global and multi-scale context information, we introduce an Edge-Aware module based on a context pyramid, which specifically emphasizes local features like edges and corners. Our approach employs a layered Swin Transformer with a shifted window mechanism as an encoder to extract contextual features. A decoder based on a symmetric Swin Transformer is employed for upsampling operations, thereby restoring the resolution of feature maps. The encoder and decoder are connected by an Edge-Aware module for the extraction of local features such as edges and corners. Results: Experimental evaluations on the Synapse multi-organ segmentation task and the ACDC dataset demonstrate the effectiveness of our method, yielding a segmentation accuracy of 79.87% (DSC) and 20.83% (HD) in the Synapse multi-organ segmentation task. Discussion: The method proposed in this paper, which combines the context pyramid mechanism and Transformer, enables fast and accurate automatic segmentation of medical images, thereby significantly enhancing the precision and reliability of medical diagnosis. Furthermore, the approach presented in this study can potentially be extended to image segmentation of other organs in the future.

MMGan: a multimodal MR brain tumor image segmentation method.

Computer-aided diagnosis has emerged as a rapidly evolving field, garnering increased attention in recent years. At the forefront of this field is the segmentation of lesions in medical images, which is a critical preliminary stage in subsequent treatment procedures. Among the most challenging tasks in medical image analysis is the accurate and automated segmentation of brain tumors in various modalities of brain tumor MRI. In this article, we present a novel end-to-end network architecture called MMGan, which combines the advantages of residual learning and generative adversarial neural networks inspired by classical generative adversarial networks. The segmenter in the MMGan network, which has a U-Net architecture, is constructed using a deep residual network instead of the conventional convolutional neural network. The dataset used for this study is the BRATS dataset from the Brain Tumor Segmentation Challenge at the Medical Image Computing and Computer Assisted Intervention Society. Our proposed method has been extensively tested, and the results indicate that this MMGan framework is more efficient and stable for segmentation tasks. On BRATS 2019, the segmentation algorithm improved accuracy and sensitivity in whole tumor, tumor core, and enhanced tumor segmentation. Particularly noteworthy is the higher dice score of 0.86 achieved by our proposed method in tumor core segmentation, surpassing those of stateof-the-art models. This study improves the accuracy and sensitivity of the tumor segmentation task, which we believe is significant for medical image analysis. And it should be further improved by replacing different loss functions such as cross-entropy loss function and other methods.

Identification and validation of a novel signature based on T cell marker genes to predict prognosis, immunotherapy response and chemotherapy sensitivity in head and neck squamous carcinoma by integrated analysis of single-cell and bulk RNA-sequencing.

T cells are among the most potent anti-tumor cells that are found in humans. Our study sought to develop a reliable signature incorporating T cell marker genes (TMGs) for predicting the prognosis and therapy responsiveness of head and neck squamous cell carcinoma (HNSCC) patients. We downloaded scRNA-seq data from the GSE181919 to identify TMGs. Subsequently, we devised a 12 TMG signature in the TCGA HNSCC cohort by using LASSO analysis. Patients with high-risk scores were shown to experience unfavorable progression-free survival, disease-specific survival, and overall survival, which was validated in the GSE65858 cohort. Additionally, the nomogram integrated risk score and clinical features are more suitable for clinical application. The enrichment analyses of both pathways and functions showed that high- and low-risk patients had functionally related distinctions. Furthermore, analysis of the immunological landscape confirmed that the low-risk patients had a larger percentage of infiltrating immune cells as well as a higher incidence rate of immune-related events. In the meantime, a greater IPS score and expression of immune checkpoint genes suggested significantly favorable responsiveness to immunotherapy in low-risk patients. On the other hand, the high-risk patients had a greater degree of sensitivity to the chemotherapy agents, which included paclitaxel, gemcitabine, docetaxel, and cisplatin. Our finding revealed that this TMG signature independently functioned as a prognostic marker and guided individualized immunotherapy and chemotherapy selection for patients with HNSCC.

Predicting the prognosis, immune response, and immunotherapy in head and neck squamous cell carcinoma using a novel risk model based on anoikis-related lncRNAs.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is an extremely heterogeneous and metastatic disease. Anoikis, which is a specific type of programmed apoptosis, is involved in tumor metastasis, tissue homeostasis, and development. Herein, we constructed an anoikis-related long non-coding RNA (lncRNA) signature to predict the prognosis, immune responses, and therapeutic effects in HNSCC patients. METHODS: A total of 501 HNSCC samples were acquired from the TCGA database and randomly classified into the training and validation groups (1:1 ratio). Thereafter, the results derived from the training set were analyzed with the LASSO regression analysis, and a novel anoikis-related lncRNA risk model was constructed. Time-dependent ROC curves and Kaplan-Meier analysis were carried out to assess the diagnostic value and survival outcomes. A nomogram was utilized to predict the prognostic accuracy. Furthermore, we studied the tumor microenvironment, tumor mutation burden, enrichment pathways, and the response to chemotherapy and immunotherapy. RESULTS: Seven anoikis-related lncRNAs (AC015878.1, CYTOR, EMSLR, LINC01503, LINC02084, RAB11B-AS1, Z97200.1) were screened to design a novel risk model, which was recognized as the independent prognostic factor for HNSCC patients. The findings implied that low-risk patients showed significantly longer OS, PFS, and DSS compared to those high-risk patients. The two groups that were classified using the risk model showed significant differences in their immune landscape. The risk model also predicted that low-risk HNSCC patients could attain a better response to immunotherapy, while high-risk patients would be more sensitive to gemcitabine, docetaxel, and cisplatin. CONCLUSIONS: We constructed a novel risk model that could be employed for effectively predicting patient prognosis with a good independent prognostic value for HNSCC patients. Furthermore, this model could be used for designing new immunotherapeutic and chemotherapeutic strategies, and it helps clinicians establish personalized and detailed strategies for HNSCC patients.

Biological function and clinical application prospect of tsRNAs in digestive system biology and pathology.

tsRNAs are small non-coding RNAs originating from tRNA that play important roles in a variety of physiological activities such as RNA silencing, ribosome biogenesis, retrotransposition, and epigenetic inheritance, as well as involvement in cellular differentiation, proliferation, and apoptosis. tsRNA-related abnormalities have a significant influence on the onset, development, and progression of numerous human diseases, including malignant tumors through affecting the cell cycle and specific signaling molecules. This review introduced origins together with tsRNAs classification, providing a summary for regulatory mechanism and physiological function while dysfunctional effect of tsRNAs in digestive system diseases, focusing on the clinical prospects of tsRNAs for diagnostic and prognostic biomarkers. Video Abstract.

Biomimetic Polyphenolic Scaffolds with Antioxidative Abilities for Improved Bone Regeneration.

Bone defects have a severe impact on the health and lives of patients due to their long-lasting and difficult-to-treat features. Recent studies have shown that there are complex microenvironments, including excessive production of reactive oxygen species. Herein, a surface functionalization strategy using metal-polyphenolic networks was used, which was found to be beneficial in restoring oxidative balance and enhancing osseointegration. The surface properties, biocompatibility, intracellular ROS scavenging, and osseointegration capacity were evaluated, and the therapeutic effects were confirmed using a skull defect model. This approach has great potential to improve complex microenvironments and enhance the efficiency of bone tissue regeneration.

Neddylation inhibitor MLN4924 sensitizes head and neck squamous carcinoma cells to (S)-10-hydroxycamptothecin.

Head and neck squamous carcinoma (HNSCC) is the seventh most common cancer worldwide. Targeted therapeutic drugs for HNSCC are still being explored. Among them, (S)-10-hydroxycamptothecin (10-HCPT), a specific inhibitor of TOP1, functions by DNA double-strand breaks that can inhibit DNA replication and trigger apoptotic cell death subsequently. Previous studies have reported that MLN4924 exerts potent anti-tumor effects by inhibiting cullin-RING ligases and causing substrate accumulation in a variety of cancers. Here, we show that MLN4924 effectively causes dose-dependent accumulation of topoisomerase I (TOP1) and blocks TOP1 ubiquitination. Importantly, neddylation inhibition with MLN4924 acts synergistically with 10-HCPT to suppress cell growth, migration and apoptosis in HNSCC cells. Mechanistically, transcriptome sequencing shows that the cytotoxic effects of the combination of MLN4924 and 10-HCPT may involve activation of the NFKB1 pathway. Taken together, our results suggest that combined treatment with MLN4924 and 10-HCPT may be an effective strategy in HNSCC.

Identification of a new anoikis-related gene signature for prognostic significance in head and neck squamous carcinomas.

Anoikis, a mode of programmed cell death, is essential for normal development and homeostasis in the organism and plays an important role in the onset and progression of cancers. The authors of this research sought to establish a gene signature associated with anoikis to predict therapy outcomes and patient prognosis for individuals with head and neck squamous cell carcinoma (HNSCC). Transcriptome data of anoikis-related genes (ARGs) in individuals with HNSCC were retrieved from public databases to aid in the formulation of the gene signature. A novel ARG signature was then created using a combination of the Least Absolute Shrinkage and Selection Operator regression and Cox regression analysis. The relationship between ARGs and tumor immune microenvironment in HNSCC was explored using single-cell analysis. HNSCC individuals were classified into high-risk and low-risk groups as per the median value of risk score. The study also investigated the variations in the infiltration status of immune cells, tumor microenvironment, sensitivity to immunotherapy and chemotherapeutics, as well as functional enrichment between the low-risk and high-risk categories. A total of 18 ARGs were incorporated in the formulation of the signature. Our signature's validity as a standalone predictive predictor was validated by multivariate Cox regression analysis and Kaplan-Meier survival analysis. Generally, the prognosis was worse for high-risk individuals. Subjects in the low-risk groups had a better prognosis and responded in a better way to combination immunotherapy, had higher immunological ratings and activity levels, and had more immune cell infiltration. In addition, gene set enrichment analysis findings showed that the low-risk subjects exhibited heightened activity in several immune-related pathways. However, the high-risk patients responded better to chemotherapy. The aim of this research was to develop a new ARG signature to predict the prognosis and sensitivity to immunotherapeutic and chemotherapeutic schemes for HNSCC patient. As a result, this could help spur the creation of new chemotherapeutics and immunotherapeutic approaches for patients with HNSCC.

The influence of embryo stage on obstetric complications and perinatal outcomes following programmed compared to natural frozen-thawed embryo transfer cycles: a systematic review and meta-analysis.

Objective: To investigate the effect of embryo stage at the time of transfer on obstetric and perinatal outcomes in programmed frozen-thawed embryo transfer (FET) versus natural FET cycles. Design: Systematic review and meta-analysis. Setting: Not applicable. Patients: Women with programmed frozen-thawed embryo transfer (FET) and natural FET. Interventions: The PubMed, MEDLINE, and EMBASE databases and the Cochrane Central Register of Controlled Trials (CCRT) were searched from 1983 to October 2022. Twenty-three observational studies were included. Primary outcome measure: The primary outcomes were hypertensive disorders of pregnancy (HDPs), gestational hypertension and preeclampsia (PE). The secondary outcomes were gestational diabetes mellitus (GDM), placenta previa, postpartum haemorrhage (PPH), placental abruption, preterm premature rupture of membranes (PPROM), large for gestational age (LGA), small for gestational age (SGA), macrosomia, and preterm delivery (PTD). Results: The risk of HDP (14 studies, odds ratio (OR) 2.17; 95% confidence interval (CI) 1.95-2.41; P<0.00001; I2 = 43%), gestational hypertension (11 studies, OR 1.38; 95% CI 1.15-1.66; P=0.0006; I2 = 19%), PE (12 studies, OR 2.09; 95% CI 1.88-2.32; P<0.00001; I2 = 0%), GDM (20 studies, OR 1.09; 95% CI 1.02-1.17; P=0.02; I2 = 8%), LGA (18 studies, OR 1.11; 95% CI 1.07-1.15; P<0.00001; I2 = 46%), macrosomia (12 studies, OR 1.15; 95% CI 1.07-1.24; P=0.0002; I2 = 31%), PTD (22 studies, OR 1.21; 95% CI 1.15-1.27; P<0.00001; I2 = 49%), placenta previa (17 studies, OR 1.2; 95% CI 1.02-1.41; P=0.03; I2 = 11%), PPROM (9 studies, OR 1.19; 95% CI 1.02-1.39; P=0.02; I2 = 40%), and PPH (12 studies, OR 2.27; 95% CI 2.02-2.55; P <0.00001; I2 = 55%) were increased in programmed FET cycles versus natural FET cycles with overall embryo transfer. Blastocyst transfer had a higher risk of HDP (6 studies, OR 2.48; 95% CI 2.12-2.91; P<0.00001; I2 = 39%), gestational hypertension (5 studies, OR 1.87; 95% CI 1.27-2.75; P=0.002; I2 = 25%), PE (6 studies, OR 2.23; 95% CI 1.93-2.56; P<0.00001; I2 = 0%), GDM (10 studies, OR 1.13; 95% CI 1.04-1.23; P=0.005; I2 = 39%), LGA (6 studies, OR 1.14; 95% CI 1.07-1.21; P<0.0001; I2 = 9%), macrosomia (4 studies, OR 1.15; 95% CI 1.05-1.26; P<0.002; I2 = 68%), PTD (9 studies, OR 1.43; 95% CI 1.31-1.57; P<0.00001; I2 = 22%), PPH (6 studies, OR 1.92; 95% CI 1.46-2.51; P<0.00001; I2 = 55%), and PPROM (4 studies, OR 1.45; 95% CI 1.14-1.83; P=0.002; I2 = 46%) in programmed FET cycles than in natural FET cycles. Cleavage-stage embryo transfers revealed no difference in HDPs (1 study, OR 0.81; 95% CI 0.32-2.02; P=0.65; I2 not applicable), gestational hypertension (2 studies, OR 0.85; 95% CI 0.48-1.51; P=0.59; I2 = 0%), PE (1 study, OR 1.19; 95% CI 0.58-2.42; P=0.64; I2not applicable), GDM (3 study, OR 0.79; 95% CI 0.52-1.20; P=0.27; I2 = 21%), LGA (1 study, OR 1.15; 95% CI 0.62-2.11; P=0.66; I2not applicable), macrosomia (1 study, OR 1.22; 95% CI 0.54-2.77; P=0.64; I2 not applicable), PTD (2 studies, OR 1.05; 95% CI 0.74-1.49; P=0.79; I2 = 0%), PPH (1 study, OR 1.49; 95% CI 0.85-2.62; P=0.17; I2not applicable), or PPROM (2 studies, OR 0.74; 95% CI 0.46-1.21; P=0.23; I2 = 0%) between programmed FET cycles and natural FET cycles. Conclusions: The risks of HDPs, gestational hypertension, PE, GDM, LGA, macrosomia, SGA, PTD, placenta previa, PPROM, and PPH were increased in programmed FET cycles versus natural FET cycles with overall embryo transfer and blastocyst transfer, but the risks were not clear for cleavage-stage embryo transfer.

Spatial metabolomics in head and neck tumors: a review.

The joint analysis of single-cell transcriptomics, proteomics, lipidomics, metabolomics and spatial metabolomics is continually transforming our understanding of the mechanisms of metabolic reprogramming in tumor cells. Since head and neck tumor is the sixth most common tumor in the world, the study of the metabolic mechanism of its occurrence, development and prognosis is still undeveloped. In the past decade, this field has witnessed tremendous technological revolutions and considerable development that enables major breakthroughs to be made in the study of human tumor metabolism. In this review, a comprehensive comparison of traditional metabolomics and spatial metabolomics has been concluded, and the recent progress and challenges of the application of spatial metabolomics combined multi-omics in the research of metabolic reprogramming in tumors are reviewed. Furthermore, we also highlight the advances of spatial metabolomics in the study of metabolic mechanisms of head and neck tumors, and provide an outlook of its application prospects.

MMDAE-HGSOC: A novel method for high-grade serous ovarian cancer molecular subtypes classification based on multi-modal deep autoencoder.

High-grade serous ovarian cancer (HGSOC) is a type of ovarian cancer developed from serous tubal intraepithelial carcinoma. The intrinsic differences among molecular subtypes are closely associated with prognosis and pathological characteristics. At present, multi-omics data integration methods include early integration and late integration. Most existing HGSOC molecular subtypes classification methods are based on the early integration of multi-omics data. The mutual interference among multi-omics data is ignored, which affects the effectiveness of feature learning. High-dimensional multi-omics data contains genes unassociated with HGSOC molecular subtypes, resulting in redundant information, which is not conducive to model training. In this paper, we propose a multi-modal deep autoencoder learning method, MMDAE-HGSOC. MiRNA expression, DNA methylation, and copy number variation (CNV) are integrated with mRNA expression data to construct a multi-omics feature space. The multi-modal deep autoencoder network is used to learn the high-level feature representation of multi-omics data. The superposition LASSO (S-LASSO) regression algorithm is proposed to fully obtain the associated genes of HGSOC molecular subtypes. The experimental results show that MMDAE-HGSOC is superior to the existing classification methods. Finally, we analyze the enrichment gene ontology (GO) terms and biological pathways of these significant genes, which are discovered during the gene selection process.

Is time-restricted eating (8/16) beneficial for body weight and metabolism of obese and overweight adults? A systematic review and meta-analysis of randomized controlled trials.

Time-restricted eating (TRE) is a new therapeutic strategy for the management of weight loss and dysmetabolic diseases. At present, TRE (8/16, 8 h eating:16 h fasting) is the most common form of TRE. Therefore, this meta-analysis included randomized controlled trials (RCTs) on TRE (8/16) in overweight and obese adults to determine its impact on body weight and metabolism. Articles reviewed from PubMed, Ovid MEDLINE, Embase, and Cochrane Central Register for the relevant RCTs that compared TRE (8/16) to non-TRE in overweight and obese adults. Eight RCTs were included in this meta-analysis. Participants following TRE (8/16) showed significant body weight reduction (mean difference [MD]: -1.48 kg, 95% confidence interval [CI]: -2.53 to -0.44) and fat mass reduction (MD: -1.09 kg, 95% CI: -1.55 to -0.63). There was no significant difference in lean mass change with TRE intervention (MD: -0.48 kg, 95% CI: -1.02 to 0.05, p = .08, I 2 = 41%). The energy restriction and early TRE (eTRE) subgroups resulted in greater weight loss. TRE (8/16) showed beneficial effects on the homeostatic model assessment of insulin resistance (HOMA-IR, MD: -0.32, 95% CI: -0.59 to -0.06), but had no significant effect on other parameters of glucose metabolism and lipid profiles. In conclusion, TRE (8/16), especially eTRE, or in combination with caloric intake restriction, is a potential therapeutic strategy for weight control in overweight and obese adults. TRE (8/16) also reduced HOMA-IR; therefore, it may have a positive effect on glucose metabolism.

Association between long-term exposure to air pollution and the risk of incident laryngeal cancer: a longitudinal UK Biobank-based study.

We assessed the association between long-term joint exposure to ambient air pollutants and the risk of laryngeal cancer and whether this risk was modified by genetic susceptibility. We used a multivariable Cox proportional hazards regression model to analyze data from UK Biobank to determine the relationship between long-term exposure to air pollutants-nitric oxide (NO), nitrogen dioxide (NO2), and 2.5-µm and 10-µm particulate matter (PM2.5 and PM10) and the risk of laryngeal cancer. In multivariable-adjusted models, in model 3 and compared with the participants with lower quintile scores for air pollution, the participants with the highest quintile scores for air pollution had a higher laryngeal cancer risk. The observed association was more pronounced among the participants who were female, were smokers, had a systolic blood pressure equal to or greater than 120 mmHg, and had diabetes. Compared with the participants with a low GRS and the lowest quintile score for air pollution exposure, those with an intermediate GRS and the highest quintile score for air pollution exposure had a higher risk of laryngeal cancer. Long-term exposure to NO2, NO, or PM2.5, individually or jointly, was associated with a risk of incident laryngeal cancer, especially in the participants with an intermediate GRS.